INTRODUCTION — The Pap smear is a common test used to screen women for cervical precancer or cancer. However, most abnormal Pap smears are not due to cancer, but rather caused by infection or low estrogen levels.
This topic reviews the anatomy of the cervix, factors that increase a woman's risk of having cervical precancer or cancer, tests to detect cervical abnormalities, and a description of both normal and abnormal Pap smear results. A separate topic is available that discusses treatment of abnormal Pap smears. (See "Patient information: Treatment of abnormal Pap smears").
ANATOMY OF THE CERVIX — The cervix is located at the lower end of the uterus (show figure 1). The surface of the cervix includes several layers of cells. Squamous cells make up the outer layer of the cervix and vagina.
The cervix also includes glandular (also called columnar) cells, which line the opening in the cervix. The region where the two cell types meet is called the "transformation" zone (show picture 1). The transformation zone is the region most likely to contain abnormal cells.
If more than one third of the layers contain abnormal cells, this is called high grade squamous intraepithelial lesion (HSIL or HGSIL) (show figure 2).
What is a Pap smear? — A Pap smear is a method of examining cells from the cervix. The traditional Pap smear (named after Dr. Papanicolaou) involved smearing the cervical cells onto a glass slide. More recently, liquid-based tests (eg, ThinPrep, SurePath) have become available; these tests place the sample of cervical cells into a vial containing a liquid preservative. In both types of test, the cells are viewed with a microscope to detect abnormalities.
Cervical cells may appear abnormal for a variety of reasons. For example, a woman may have low estrogen levels or a cervical infection, or she may have a precancerous area or even cervical cancer. If the Pap smear is abnormal, further testing is needed to determine what the abnormality is and if treatment is needed.
Who should have a Pap smear? — The first Pap smear should be done by age 21 years. For most women, a Pap smear is recommended every one to three years. For women who have a past history of abnormal Pap smears or who have risk factors for cervical cancer, testing is recommended once per year (see "Risk factors for cervical cancer" below).
Women who are older than 30 years who have no risk factors, a negative Pap smear three years in a row, and a negative HPV test may choose to have a Pap smear and HPV testing every three years rather than every year (see "HPV testing" below). Most experts feel that women who are at low risk for cervical cancer (eg, no past history of an abnormal Pap) can discontinue Pap smears by age 65 to 70 years.
How are Pap smears obtained? — Pap smears are performed during a pelvic examination. To perform the test, a healthcare provider uses an instrument (speculum) to view the cervix, which is located at the lower end of the uterus (show figure 1). The provider sweeps the surface of the cervix and inner cervix (called the endocervical canal) with a soft brush or small spatula to collect cervical cells. This is not painful.
Pap smear accuracy — Most Pap smears can accurately identify women with abnormal cervical cells. However, the test is not perfect, and it misses between 5 and 25 percent of women with abnormalities. These women are said to have a false negative result. There are several important points to consider when discussing false negative results: Many false negative results are due to difficulty in collecting a sufficient number of cervical cells, not errors in reading the smear. It may be difficult to collect cervical cells if the cervix is hard to find during a pelvic examination, if the abnormal area is very small or high up inside the cervix, if only a few cervical cells are obtained, if the specimen dries too quickly, if the patient douches or has sexual intercourse before the examination, or if the woman is bleeding or has an infection at the time of the Pap smear. If a woman has a normal result three years in a row, then it is unlikely that an abnormality has been missed. The frequency of screening for cervical cancer can then be spread out (see "Who should have a Pap smear?" above). If a new lesion develops in a woman who is only tested every three years, it will be found before it becomes serious because it takes years for a new abnormality to develop into a high-grade precancer or cervical cancer. It usually takes many years for precancerous cervical cells to progress to cancer, and progression to cancer does not always occur.
RISK FACTORS FOR CERVICAL CANCER — The most important risk factor for cervical cancer is infection with the human papillomavirus (HPV). Other factors that increase the risk of cervical cancer include sexual intercourse, use of tobacco (eg, cigarettes), use of birth control pills, and a weakened immune system (eg, due to HIV infection or certain medications) (show table 1).
Human papillomavirus — Infection of the cervix with certain types of human papillomavirus (HPV) is the most significant risk factor for cervical abnormalities and cancer. Over 100 different types of HPV have been identified, however not all types infect the cervix or cause cancer. Researchers have labeled the HPV types as being high or low risk for causing cervical cancer. HPV types 6 and 11 can cause warts and are low-risk types because they rarely cause cervical cancer; types 16 and 18 are considered high-risk types because they may cause cervical cancer in some women. (See "Patient information: Condyloma (genital warts) in women").
HPV is spread by direct skin-to-skin contact, including sexual intercourse, oral sex, anal sex, or any other contact involving the genital area (eg, hand to genital contact). It is not possible to become infected with HPV by touching an object, such as a toilet seat.
Most persons who are infected with HPV have no signs or symptoms. Most HPV infections are temporary and resolve within two years. When the virus persists (in 10 to 20 percent of cases), there is a higher likelihood of developing cervical cell abnormalities and cancer. However, it usually takes several years for HPV infection to cause cervical cancer (see "HPV testing" below).
Sexual history — Cervical cancer is rare in women who have never had sexual intercourse. Cervical cancer is more common in women who have had more than one sexual partner or whose partners have more than one sexual partner. Other risk factors include: HIV infection, sexual intercourse before age 17, or a history of sexually transmitted diseases (eg, genital herpes or Chlamydia).
Tobacco use — Smoking cigarettes increases the risk of cervical cancer and precancer by up to seven times that of women who do not smoke. This is believed to occur because cancer-causing products from tobacco are secreted into the cervical mucous. Stopping smoking can decrease this risk. (See "Patient information: Smoking cessation").
Birth control with estrogen — Woman who use a birth control method that contain estrogen (eg, pills, patch) have a slightly higher risk of cervical precancers and cancers compared to women who do not take them (show table 1). The risk of cervical cancer related to birth control is small, and is related to infection with HPV. Thus, women who take a birth control with estrogen but are not infected with HPV have no increased risk of cervical cancer or precancer.
The reason that oral contraceptives increase the risk of cervical cancer is not clear. Higher levels of estrogen may causes changes in the cervix that increase the growth of cells that develop as a result of the HPV infection.
However, birth control with estrogen has a number of benefits, including a reduced risk of ovarian and uterine cancer and decreased pain and bleeding with menstrual periods. Women should discuss all the risks and benefits of this type of birth control with a healthcare provider. (See "Patient information: Hormonal methods of birth control").
Weakened immune system — Normally, the immune system works to protect the body from illness and infection, including the infection caused by human papillomavirus. Women with a weakened immune system have a significantly increased risk of cancers and precancers of the cervix.
A number of factors can weaken the immune system, including HIV infection, prolonged use of glucocorticoids (eg, prednisone), and use of medications to prevent rejection after organ transplantation.
PAP SMEAR RESULTS — The information reported in a Pap smear is described in table 2 (show table 2A-B). Pap smear results may be reported as:
Negative — Pap smears that have no abnormal, precancerous, or cancerous cells are labeled as "Negative for intraepithelial lesion or malignancy".
Smears that are negative can show other conditions, such as a vaginal infection (Trichomoniasis, yeast, herpes, or bacterial vaginosis) or cellular changes related to vaginal dryness, radiation therapy, or an intrauterine device (IUD) string. In some situations, further testing and/or treatment are needed.
Abnormal results — A number of medical terms are used to describe abnormalities of the cervix, including dysplasia, squamous intraepithelial lesion, and intraepithelial neoplasia. These terms all mean that the abnormality is confined to the surface or glandular lining of the cervix.
Follow up testing — Further testing is often needed after an abnormal Pap smear. The most common tests include HPV testing and colposcopy.
HPV testing — HPV testing is recommended only in particular circumstances: If the Pap smear shows a specific abnormality (for example, atypical squamous cells of uncertain significance, or ASC-US), HPV testing is then performed. This is called reflex testing.
Testing every woman for HPV is not recommended because of the risk of false positive results (when the HPV test was falsely positive and the Pap smear was negative). It is likely that many women develop HPV infections that resolve spontaneously. Having a false positive result would lead to unnecessary follow-up testing and anxiety for many women.
Colposcopy — Colposcopy is an office procedure that allows a clinician to closely examine the cervix. It is commonly performed after an abnormal Pap smear. Colposcopy is performed similar to a pelvic examination, while the woman lies on an exam table. A speculum is used to view the cervix, and the viewing device (called a colposcope) remains outside the woman's body (show picture 2).
The colposcope magnifies the appearance of the cervix 10 times. This allows the clinician to better see the location and size of any abnormalities, and also to see any changes in the capillaries (small blood vessels) on the surface of the cervix. Capillary changes are not detected by cervical cytology or HPV tests, but are important signs of the severity of cervical abnormalities.
Using the colposcope, a small piece of the abnormal area can be removed (biopsied). Anesthesia (numbing medicine) is not needed because the biopsy causes only mild discomfort or cramping. The biopsy is then examined with a microscope by a physician (called a pathologist). The results of the biopsy are usually available within one to two weeks.
Some women also need to have a biopsy of the inner cervix during colposcopy; this is called endocervical curettage. Endocervix refers to the inner cervix and curettage means scraping.
ATYPICAL SQUAMOUS CELLS (ASC) — A Pap smear may be read as atypical when cervical cells are not completely normal but are not thought to be precancerous. Further testing of ASC is suggested because some women (5 to 17 percent) have a precancerous lesion that is seen when colposcopy is performed. ASC is subdivided into ASC-US and ASC-H; ASC-H is more likely than ASC-US to be caused by a precancerous change.
ASC-US — There are three options for follow up of a single ASC-US result: Perform HPV testing. This is the preferred follow up for ASC-US. HPV testing can often be done at the same time as the Pap smear. This is convenient because a woman does not have to return for a second visit (see "HPV testing" above).
Women who test positive for high-risk HPV types are referred for colposcopy because they are at greater risk of having a precancerous lesion.
Women who test negative for HPV are not likely to have cervical precancer. These women should have a repeat Pap smear in one year. In most cases, the ASC-US resolves on its own. Repeat the Pap smear in four to six months. If this Pap is normal, it is repeated every four to six months until there have been two normal tests in a row. If the woman has two ASC-US results, she should have colposcopy.
For postmenopausal women, use of an estrogen treatment in the vagina for one month may be recommended after one ASC-US result; low estrogen levels in the vaginal and cervical tissues can cause mild cellular abnormalities that often revert to normal after estrogen treatment. Colposcopy should be performed if the woman has a second ASC-US result after use of estrogen therapy. Have colposcopy. This approach is preferred for women who are HIV positive or who have a weakened immune system because of the higher risk of a precancerous lesion (see "Colposcopy" above).
ASC-H — This finding requires further testing with colposcopy (see "Colposcopy" above).
LOW-GRADE SQUAMOUS LESION (LSIL) — These are mild cellular changes. Further testing is almost always recommended for women with LSIL because 15 percent of women with LSIL have a precancerous lesion that was not detected by the Pap smear.
A small number of women with low-grade changes will develop cancer over a period of several years if no treatment is performed. A large percentage (50 to 90 percent) of women with low-grade changes do not require treatment because the abnormality resolves on its own.
Low-grade abnormalities may be described with other names, including low-grade squamous intraepithelial lesions (LSIL), cervical intraepithelial neoplasia, grade 1 (CIN 1), and mild dysplasia.
Follow up of LSIL — Colposcopy is recommended for women with low-grade lesions (LSIL) (see "Colposcopy" above). Determining the size and location of the lesion with colposcopy can help to decide whether to treat the lesion or follow it over time. Large lesions are less likely to heal without treatment. Observing the extent and severity of the lesion with colposcopy is useful for establishing a baseline in women who are not treated.
However, LSIL in postmenopausal or adolescent women may be approached differently. A repeat Pap smear or HPV test may be recommended for adolescents; if the HPV is positive or the Pap smear continues to be abnormal, the adolescent is usually referred for colposcopy. Postmenopausal women may be treated with a course of estrogen cream, as described above (see "Atypical squamous cells (ASC)" above).
Treatment of LSIL — There are three options for management of LSIL: Close follow-up with HPV testing after 12 months or repeat Pap smear at six and 12 months. Colposcopy is performed if abnormalities persist or worsen (see "Follow up testing" abovesee "Follow up testing" above). HPV testing is preferred because it is as effective as Pap smear but requires fewer visits and less need for colposcopy. Treatment to remove or destroy the abnormal cells (See "Patient information: Treatment of abnormal Pap smears"). Repeat colposcopy and Pap smear at 12 months.
Since many of these lesions will heal without treatment, some women prefer to delay treatment and have close monitoring. Treatment is the best option if LSIL persists, if the woman would have difficulty remembering to follow-up every six months, if the lesion is large (large lesions usually persist), if the lesion extends into the inner cervix (where it is difficult to see), or if the patient prefers treatment.
HIGH-GRADE SQUAMOUS LESION (HSIL) — These are moderate to severe changes in the cells of the cervix that may be precancerous (show picture 1). Approximately 20 percent of women will develop cervical cancer over a period of several years if no treatment is given.
A number of terms are used to describe high grade lesions, including CIN 2 and 3, moderate and severe dysplasia, and carcinoma in situ (CIS).
Follow up of HSIL — All women with high-grade lesions (HSIL) should have a colposcopy and biopsy. If colposcopy does not detect a high grade abnormality, close follow-up, further testing, and/or treatment may be recommended.
Treatment of HSIL — Women with high grade abnormalities should be treated because approximately 20 percent of untreated abnormalities will develop into invasive cancer. The most common treatment involves removal (excision) of the abnormal area of the cervix. (See "Patient information: Treatment of abnormal Pap smears").
Adolescent patients may be able to delay treatment of HSIL because, in this age group, there is a good chance that the abnormal area will heal without treatment. Close follow up is required, including colposcopy and Pap smear every four to six months. To delay treatment, the provider must be able to see the entire cervix during colposcopy and a test of the inner cervix (called endocervical curettage) must be negative.
Likewise, for pregnant women with HSIL, treatment is often delayed until after delivery. Colposcopy and Pap smear are generally performed several times during the pregnancy.
SQUAMOUS CELL CARCINOMA — Squamous cell carcinoma is the medical term for cervical cancer. Women with this result require a biopsy, which is usually performed with colposcopy. If biopsy confirms that cancerous cells are present, treatment is strongly recommended. The diagnosis and treatment of early stage cervical cancer is discussed in a separate topic review. (See "Patient information: Treatment of early stage cervical cancer").
GLANDULAR CELL ABNORMALITIES — Glandular cells develop from the inside the cervix (called the endocervical canal). Glandular cells can also come from the endometrium (lining of the uterus), the fallopian tube, or the ovary. Women with abnormal glandular cells need to have further testing to determine the source of the abnormality, if cancer or precancer is present, and to determine if treatment is needed.
Follow up testing — All women with atypical glandular cells (AGC) require further testing (colposcopy, biopsy, endometrial biopsy). This is because 10 to 40 percent of women with atypical glandular cells have precancerous or cancerous cells when evaluated by colposcopy and biopsy.
Treatment — Treatment of AGC depends upon the underlying abnormality and may involve monitoring, removal of a large part of the inner cervix, or less commonly, hysterectomy. (See "Patient information: Treatment of abnormal Pap smears").
PREVENTING CERVICAL CANCER
HPV vaccine — A vaccine (Gardasil®) is now available to help prevent infection with some types of HPV (types 6, 11, 16, and 18). Approximately 70 percent of cervical cancers result from infection with HPV 16 and 18, and approximately 90 percent of cases of genital warts result from infection with HPV 6 and 11. The vaccine was proven to be safe and effective in several large clinical trials [1,2].
The vaccine is currently recommended for all females who are between ages 9 and 26 years. Decisions about the age at which to start HPV immunization have been guided by the age at which the greatest number of women is infected with HPV and estimates regarding how long the vaccine continues to prevent infection. While it is not known exactly how long the vaccine protects against HPV infection, clinical trials prove protection for at least four years [3]. Further study is underway to determine if a booster shot is needed after this time.
The vaccine has not been studied in women over 26 years old and thus its effectiveness is uncertain. Women over this age are more likely to have been exposed to the four types of HPV in the vaccine (6, 11, 16, and 18); the vaccine does not protect against HPV infection if the woman has previously been exposed.
The vaccine is given by injection and requires three doses; the first injection is followed by a second and third dose two and six months later.
It is not known if vaccination of men could help to reduce the incidence of cervical cancer in women. Studies are currently underway to address this question. The vaccine is not currently recommended during pregnancy.
Sexual contact — Avoiding sex or sexual contact is not a practical way to prevent infection with HPV. Condoms provide partial protection, but not complete protection because they do not cover all areas of the genitals. Having a limited number of sexual partners may reduce the risk of HPV infection.
Smoking cessation — Women who smoke cigarettes are at increased risk of developing cervical cancer [4]. Cigarette smoking and HPV infection increase the risk of developing high-grade squamous lesions. The risk of cervical cancer is increased two- to four-fold among cigarette smokers compared to nonsmokers.
Women who smoke and have an abnormal Pap smear can reduce their risk of cervical cancer by quitting smoking. (See "Patient information: Smoking cessation").
WHERE TO GET MORE INFORMATION — Your healthcare provider is the best source of information for questions and concerns related to your medical problem. Because no two patients are exactly alike and recommendations can vary from one person to another, it is important to seek guidance from a provider who is familiar with your individual situation.
This discussion will be updated as needed every four months on our web site (www.patients.uptodate.com). Additional topics as well as selected discussions written for healthcare professionals are also available for those who would like more detailed information.
A number of web sites have information about medical problems and treatments, although it can be difficult to know which sites are reputable. Information provided by the National Institutes of Health, national medical societies and some other well-established organizations are often reliable sources of information, although the frequency with which they are updated is variable. National Library of Medicine
(www.nlm.nih.gov/medlineplus/healthtopics.html)
National Cancer Institute
(www.nci.nih.gov)
American Society of Cytopathology
(www.cytopathology.org)
American Society for Colposcopy and Cervical Pathology
(www.asccp.org)
American Cancer Society
(www.cancer.org, search for HPV)
National HPV and Cervical Cancer Public Education Campaign
Telephone: 1-866-280-6605
(www.cervicalcancercampaign.org)
National Institute of Allergy and Infectious Diseases
(www.niaid.nih.gov/factsheets/stdhpv.htm)
Center for Disease Control and Prevention
(www.cdc.gov/)
American Social Health Association
(http://www.ashastd.org/)
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Use of UpToDate is subject to the Subscription and License Agreement. REFERENCES 1. Koutsky, LA, Ault, KA, Wheeler, CM, et al. A controlled trial of a human papillomavirus type 16 vaccine. N Engl J Med 2002; 347:1645.
2. Harper, DM, Franco, EL, Wheeler, C, et al. Efficacy of a bivalent L1 virus-like particle vaccine in prevention of infection with human papillomavirus types 16 and 18 in young women: a randomised controlled trial. Lancet 2004; 364:1757.
3. Harper, DM, Franco, EL, Wheeler, CM, et al. Sustained efficacy up to 4.5 years of a bivalent L1 virus-like particle vaccine against human papillomavirus types 16 and 18: follow-up from a randomised control trial. Lancet 2006; 367:1247.
4. Carcinoma of the cervix and tobacco smoking: Collaborative reanalysis of individual data on 13,541 women with carcinoma of the cervix and 23,017 women without carcinoma of the cervix from 23 epidemiological studies. Int J Cancer 2006; 118:1481.
5. Solomon, D, Davey, D, Kurman, R, et al. The 2001 bethesda system: terminology for reporting results of cervical cytology. JAMA 2002; 287:2114.
6. Wright, TC Jr, Cox, JT, Massad, LS, et al. 2001 consensus guidelines for the management of women with cervical cytological abnormalities. JAMA 2002; 287:2120.
7. Human PAP illomavirus testing for triage of women with cytologic evidence of low-grade squamous intraepithelial lesions: baseline data from a randomized trial. The Atypical Squamous Cells of Undetermined Significance/Low-Grade Squamous Intraepithelial Lesions Triage Study (ALTS) Group. J Natl Cancer Inst 2000; 92:397.
8. ACOG Practice Bulletin #66: Management of Abnormal Cervical Cytology and Histology. Obstet Gynecol 2005; 106:645.
9. ACOG Committee Opinion No. 344: Human papillomavirus vaccination. Obstet Gynecol 2006; 108:699.
Monday, October 15, 2007
Osteoporosis prevention and treatment
INTRODUCTION — Osteoporosis is a common skeletal disorder that causes a decrease in bone mass and density, causing bones to become abnormally thin (osteopenic), weakened, and easily broken (fractured). Women are at a higher risk for osteoporosis after menopause due to lower levels of estrogen, a female hormone that helps to maintain bone mass.
Fortunately, preventive treatments are available that can help to maintain or increase bone density. For those already affected by osteoporosis, prompt diagnosis of bone loss and fracture risk are essential because therapies are available that can slow further loss of bone or increase bone density.
This topic review discusses the therapies available for the prevention and treatment of osteoporosis. A separate topic review is available about the causes, diagnosis, and screening measures for osteoporosis. (See "Patient information: Osteoporosis causes, diagnosis, and screening").
NON-DRUG PREVENTION AND TREATMENT — The non-drug therapy of osteoporosis includes three major components: diet, exercise, and smoking cessation. These recommendations apply to men and women.
Diet — An optimal diet for the prevention or treatment of osteoporosis includes an adequate intake of calories as well as calcium and vitamin D, both of which are essential in helping to maintain proper bone formation and density.
Calcium intake — Experts recommend that daily elemental calcium intake (total of diet plus supplement) be at least 1000 mg for premenopausal women and men, and 1500 mg in postmenopausal women who do not take estrogen. However, the total daily calcium intake should not routinely exceed 2000 mg due to the possibility of adverse effects. (See "Patient information: Calcium for bone health").
The main dietary sources of calcium include milk and other dairy products, such as cottage cheese, yogurt, or hard cheese, and green vegetables, such as spinach and broccoli (show table 1). A rough method of estimating dietary calcium intake is to multiply the number of dairy servings consumed each day by 300 mg. One serving is 8 oz of milk or yogurt, 1 oz of hard cheese, or 16 oz of cottage cheese.
Calcium supplements (calcium carbonate or calcium citrate) may be suggested if a person cannot get enough calcium in their diet (show figure 1). Calcium doses greater than 500 mg/day should be taken in divided doses (eg, once in morning and evening). The daily intake recommendations given above always apply to "elemental calcium". Use caution when reading the labels of calcium supplements and be sure to note the amount of elemental calcium contained per serving, as many products give the calcium content per two pills.
Vitamin D intake — Experts also recommend 800 International Units (IU) of vitamin D each day. This dose appears to reduce bone loss and fracture rate in older women and men when there is adequate calcium intake (described above).
Milk is the primary dietary source of dietary vitamin D, containing approximately 100 IU per cup. Experts recommend vitamin D supplementation for all patients with osteoporosis whose intake of vitamin D is below 400 IU per day. This can be found in a daily multivitamin or a calcium/vitamin D supplement. Vitamin D is available separately in 400 IU supplements.
Protein supplements — Protein supplements may also be recommended for some patients to ensure sufficient protein intake. This may be particularly important for those who have already had osteoporotic fractures.
Alcohol, caffeine, and salt intake — A healthcare provider may also recommend limiting alcohol consumption, since high alcohol intake may increase the risk of fracture due to an increased risk of falling, poor nutrition, etc. It is not clear if restricting caffeine or salt is helpful; these measures have not been proven to prevent bone loss in those who have a sufficient intake of calcium.
Exercise — A person who has or wants to prevent osteoporosis should exercise for at least 30 minutes three times per week. Any weight-bearing exercise regimen is appropriate (eg, walking). However, exercises that could increase the risk of falling should be avoided.
Weight-bearing exercises can improve bone mass in premenopausal women and help to maintain bone density for women after menopause. Physical activity reduces the risk of hip fracture in older women as a result of increased muscle strength.
The benefits of exercise are quickly lost if a person stop exercising. A regular, weight-bearing exercise regimen that a person genuinely enjoys improves the chances of continuing to follow the routine over the long term. (See "Patient information: Exercise").
Smoking cessation — Smoking cessation is strongly recommended for patients at risk for osteoporosis because smoking cigarettes is known to accelerate bone loss. One study suggested that women who smoke one pack per day throughout adulthood have a 5 to 10 percent reduction in bone density by menopause, resulting in an increased risk of fracture. (See "Patient information: Smoking cessation").
Preventing falls — Repeated falling may significantly increase the risk of osteoporotic fractures in the elderly. Taking measures to prevent falls can decrease the risk of fractures. Such measures may include the following: Remove loose rugs and electrical cords or any other loose items in your home that could lead to tripping, slipping, and falling. Ensure that there is adequate lighting in all areas inside and around the home, including stairwells and entrance ways. Avoid walking on ice, wet or polished floors, or other potentially slippery surfaces. Avoid walking in unfamiliar areas outside.
Because certain drugs may increase the risk of falls, drug regimens should be reviewed on a regular basis. In some cases, the healthcare provider may decide to substitute one medication with an alternative that has a lower risk of causing falls. In addition, people with poor vision should see an eye specialist (eg, optomotrist or ophthamologist) for corrective lenses (glasses).
Hip pads — A person with osteoporosis who falls on their hip but has a substantial amount of muscle or fat padding over the hips has a lower risk of fracture than a person who has little padding. Hip pads (external hip protectors) are designed to reduce the risk of fracture when an elderly person falls. Results of studies that used hip pads have shown mixed results. For people who are willing to wear them on a consistent basis, hip pads may be of benefit in preventing fractures related to an accidental fall.
Medication monitoring — Prolonged therapy with and/or high doses of certain medications that increase bone loss should be monitored closely by a healthcare provider and decreased or discontinued when possible. Such medications include the following: Glucocorticoid medications (eg, prednisone) Heparin, a medication used to prevent and treat abnormal blood clotting (ie, anticoagulant) Vitamin A and certain synthetic retinoids (eg, etretinate) Certain antiepileptic drugs (eg, phenytoin, carbamazepine, primidone, phenobarbital, and valproate)
MEDICATIONS — The non-drug measures discussed above can help to reduce bone loss. For certain men and for premenopausal women who have or who are at risk for osteoporosis, drug or hormonal therapies may also be recommended.
However, the relationship between bone density and fracture risk in premenopausal women is not well defined. A premenopausal woman with low bone density may have no increased risk of fracture. Thus, bone density alone should not be used to define osteoporosis in a premenopausal woman, but instead indicates the need for further evaluation. (See "Patient information: Osteoporosis causes, diagnosis, and screening").
Bisphosphonates — Bisphosphonates inhibit the breakdown and removal of bone (ie, resorption). They are widely used for the prevention and treatment of osteoporosis in postmenopausal women.
These drugs need to be taken first thing in the morning on an empty stomach with a full 8 oz glass of water. The person must then wait at least half an hour (with alendronate (Fosamax®) and risedronate (Actonel®)) or one hour (with ibandronate (Boniva®)) before eating or taking any other medications. These dosing instructions help to reduce the risk of side effects and potential complications.
Side effects of bisphosphonates — Most people who take bisphosphonates for prevention or treatment of osteoporosis do not have any serious side effects related to the medication. However, it is important to closely follow the instructions for taking the medication; lying down or eating sooner than 30 minutes after a dose increases the risk of stomach upset.
There has been concern about a risk of bisphosphonates in people who require invasive dental work. A problem known as avascular necrosis or osteonecrosis of the jaw has rarely developed in a small number of people who used bisphosphonates. The risk of this problem is small in people who take bisphosphonates for osteoporosis prevention and treatment. However, there is a slightly higher risk of this problem when higher doses of bisphosphonates are given into vein during cancer treatment.
Most experts do not think that it is necessary to stop bisphosphonates before invasive dental work (eg, tooth extraction or implant) unless the treatment has been given into a vein. In this case, the patient should consult their healthcare provider for a specific recommendation.
Bisphosphonates are not recommended for premenopausal women who could become pregnant because of the unknown effects on a developing fetus.
Alendronate — Alendronate (Fosamax®) reduces vertebral and nonvertebral fractures, and decreases the loss of height associated with vertebral fractures. The dose for treatment is 10 mg per day, and the dose for prevention is 5 mg per day. Alendronate is usually taken as a weekly 70 or 35 mg pill.
Risedronate — Risedronate (Actonel®) is also approved for both prevention and treatment of osteoporosis at a dose of 5 mg/day (or as a single 35 mg once-weekly pill). Like alendronate, it reduces the risk of both vertebral and hip fractures.
Ibandronate — Ibandronate (Boniva®) can be used for prevention and treatment of osteoporosis at a dose of 150 mg once monthly. A monthly reminder can be sent by phone, mail, or email from the manufacturer. Although Boniva reduces the risk of bone loss and spine fractures, there is no proof that it reduces the risk of hip fractures.
Other new bisphosphonates are being studied, including single yearly intravenous infusions of zoledronic acid, which might be an effective treatment for postmenopausal osteoporosis.
"Estrogen-like" medications — Certain medications, known as selective estrogen receptor modulators (SERMs) produce some estrogen-like effects in the bone that provides protection against postmenopausal bone loss. In addition, SERMS also decrease the risk of breast cancer in women who are at high risk. Currently available SERMs include raloxifene (Evista®) and tamoxifen. Raloxifene (Evista) can be used for the prevention and treatment of osteoporosis in postmenopausal women, although it may be less effective in preventing bone loss than bisphosphonates or estrogen. (See "Patient information: Tamoxifen and raloxifene for the prevention of breast cancer").
SERMs are not recommended for premenopausal women.
Estrogen/progestin therapy — In the past, estrogen or estrogen-progestin therapy was considered the best way to prevent postmenopausal osteoporosis and was often used for treatment. Data from the Women's Health Initiative (WHI), a large clinical trial, found that combined estrogen-progestin treatment reduced hip and vertebral fracture risk by 34 percent. A similar reduction in fracture risk was seen in the WHI trial of estrogen alone.
Estrogen had the additional advantages of controlling menopausal symptoms. However, the WHI found that estrogen plus progestin does not reduce the risk of coronary heart disease, and slightly increases the risk of breast cancer, stroke, and blood clots. The details of the WHI are discussed elsewhere. (See "Patient information: Postmenopausal hormone therapy").
Thus, estrogen is not recommended for the treatment or prevention of osteoporosis in postmenopausal women. However, some postmenopausal women continue to use estrogen, including women with persistent menopausal symptoms and those who cannot tolerate other types of osteoporosis treatment.
Estrogen may be an appropriate treatment for prevention of osteoporosis in young women with amenorrhea (absence of menses). This is often accomplished with a birth control pill. (See "Patient information: Menstrual cycle disorders (Absent and irregular periods)").
Calcitonin — Calcitonin is a hormone produced by the thyroid gland that, together with parathyroid hormone, helps to regulate calcium concentrations in the body. Synthetic calcitonin is sometimes recommended as a treatment for osteoporosis. Calcitonin may be administered via nasal spray or injection (subcutaneous salmon calcitonin). Nasal administration is typically preferred due to ease of use and because the injections tend to cause more nausea and flushing.
Other drugs are usually recommended before calcitonin because it is not clear if calcitonin increases bone density and decreases the fracture rate outside the spine. However, due to its pain-relieving (analgesic) effects, calcitonin may be suggested as a first-line therapy for those who have a sudden, intense (acute) onset of pain due to vertebral fractures. The treatment regimen is typically changed once the acute pain subsides or if the pain fails to subside over a prolonged period (eg, four weeks).
Parathyroid hormone (PTH) — PTH is produced by the parathyroid glands and stimulates both bone resorption and new bone formation. Intermittent administration stimulates formation more than resorption. Clinical trials suggest that PTH therapy is effective in both the prevention and treatment of osteoporosis in postmenopausal women and in men.
A PTH preparation called Forteo®, given by daily injection for two years, is approved for the treatment of severe osteoporosis. It is more effective at building spine bone density than any other treatment, although it is unclear if it also prevents fracture better than other treatments (specifically, the bisphosphonates). Because it requires daily injection and is expensive, it is usually reserved for patients with very severe hip or spine osteoporosis. It is not recommended for premenopausal women.
Monitoring response to hormonal or drug therapy — Testing may be recommended to monitor a patient's response to osteoporosis therapy. This may include measurement of bone mineral density or laboratory tests that indicate bone turnover (ie, rate of new bone formation and breakdown).
Testing is typically done before treatment begins to get a baseline measurement. Laboratory testing may be repeated three months after treatment begins, while bone density testing may be repeated after two years.
SUMMARY Osteoporosis causes bones to become abnormally thin (osteopenic), weakened, and easily broken. This condition can be treated and prevented with diet, exercise, and stopping smoking. Calcium and vitamin D can prevent and treat thinning bones. The main dietary sources of calcium include milk and other dairy products, such as cottage cheese, yogurt, or hard cheese, and green vegetables, such as spinach and broccoli (show table 1). Milk is the primary source of dietary vitamin D, containing approximately 100 IU per cup. Calcium and vitamin D can also be taken as a supplement (eg, in a pill, show figure 1). A total of at least 1000 mg of calcium per day is recommended for premenopausal women and men. Women after menopause should consume 1500 mg calcium per day if they do not take estrogen. Experts also recommend 800 International Units (IU) of vitamin D each day. Exercise can help to prevent and treat thinning bones. Exercise should be done for at least 30 minutes three times per week. Any weight-bearing exercise regimen is appropriate (eg, walking). Smoking cigarettes can cause bones to become thinner and weaker. Stopping smoking can reduce this risk. Falling can cause fractures in the elderly. Preventing falls can lower the risk of fractures. Some medications can cause bone thinning. Such medications include glucocorticoid medications (eg, prednisone), heparin, vitamin A and certain synthetic retinoids (eg, etretinate), and certain antiepileptic drugs (eg, phenytoin, carbamazepine, primidone, phenobarbital, and valproate). You should talk to your provider about the risk of bone thinning if you take one of these medications (see "Medication monitoring" above). There are several medications that help prevent osteoporosis in women after menopause. We think alendronate (Fosamax®), risedronate (Actonel®), or raloxifene (Evista) are the best medications for prevention (see "Bisphosphonates" above). Alendronate (Fosamax®) or risedronate (Actonel®) are recommended to treat women after menopause who have osteoporosis (see "Bisphosphonates" above). Parathyroid hormone (Forteo®) is another medication that can be used to treat osteoporosis. We recommend this medication for men or postmenopausal women with severe hip or spine osteoporosis (see "Parathyroid hormone (PTH)" above). Hormone replacement (eg, estrogen, progesterone) is not usually recommended to prevent osteoporosis in women after menopause. Hormone therapy is recommended for some young women who do not have a monthly menstrual period (see "Estrogen/progestin therapy" above). A bone density test may be recommend to monitor how the bones respond to osteoporosis treatment. For postmenopausal women, a bone density test is usually done two years after treatment starts.
WHERE TO GET MORE INFORMATION — Your healthcare provider is the best source of information for questions and concerns related to your medical problem. Because no two patients are exactly alike and recommendations can vary from one person to another, it is important to seek guidance from a provider who is familiar with your individual situation.
This discussion will be updated as needed every four months on our web site (www.patients.uptodate.com). Additional topics as well as selected discussions written for healthcare professionals are also available for those who would like more detailed information.
A number of web sites have information about medical problems and treatments, although it can be difficult to know which sites are reputable. Information provided by the National Institutes of Health, national medical societies and some other well-established organizations are often reliable sources of information, although the frequency with which they are updated is variable. National Library of Medicine
(www.nlm.nih.gov/medlineplus/healthtopics.html)
Osteoporosis and Related Bone Diseases National Resource Center (ORBD-NRC)
Toll-free: (800) 624-BONE (2663)
TTY: (202) 466-4315
E-mail: orbdnrc@nof.org
(www.osteo.org)
National Osteoporosis Foundation
Phone: (202) 223-2226
E-mail: patientinfo@nof.org
(www.nof.org)
National Women's Health Resource Center (NWHRC)
Toll-free: (877) 986-9472
E-mail: ddiamant@healthywomen.org
(www.healthywomen.org)
Osteoporosis Society of Canada
Phone: (416) 696-2663 x 294
(www.osteoporosis.ca/)
The Hormone Foundation
(www.hormone.org/public/osteoporosis.cfm, available in English, Spanish, French, Italian, German, and Portuguese)
[1-5]
Use of UpToDate is subject to the Subscription and License Agreement. REFERENCES 1. Delmas, PD, Bjarnason, NH, Mitlak, BH, et al. Effects of raloxifene on bone mineral density, serum cholesterol concentrations, and uterine endometrium in postmenopausal women. N Engl J Med 1997; 337:1641.
2. Rossouw, JE, Anderson, GL, Prentice, RL, et al. Risks and benefits of estrogen plus progestin in healthy postmenopausal women: principal results From the Women's Health Initiative randomized controlled trial. JAMA 2002; 288:321.
3. Fulton, JP. New guidelines for the prevention and treatment of osteoporosis. National Osteoporosis Foundation. Med Health R I 1999; 82:110.
4. Gregg, EW, Cauley, JA, Seeley, DG, et al. Physical activity and osteoporotic fracture risk in older women. Ann Intern Med 1998; 129:81.
5. NIH Consensus Development Panel on Optimal Calcium Intake. Optimal calcium intake. JAMA 1994; 272:1942.
Fortunately, preventive treatments are available that can help to maintain or increase bone density. For those already affected by osteoporosis, prompt diagnosis of bone loss and fracture risk are essential because therapies are available that can slow further loss of bone or increase bone density.
This topic review discusses the therapies available for the prevention and treatment of osteoporosis. A separate topic review is available about the causes, diagnosis, and screening measures for osteoporosis. (See "Patient information: Osteoporosis causes, diagnosis, and screening").
NON-DRUG PREVENTION AND TREATMENT — The non-drug therapy of osteoporosis includes three major components: diet, exercise, and smoking cessation. These recommendations apply to men and women.
Diet — An optimal diet for the prevention or treatment of osteoporosis includes an adequate intake of calories as well as calcium and vitamin D, both of which are essential in helping to maintain proper bone formation and density.
Calcium intake — Experts recommend that daily elemental calcium intake (total of diet plus supplement) be at least 1000 mg for premenopausal women and men, and 1500 mg in postmenopausal women who do not take estrogen. However, the total daily calcium intake should not routinely exceed 2000 mg due to the possibility of adverse effects. (See "Patient information: Calcium for bone health").
The main dietary sources of calcium include milk and other dairy products, such as cottage cheese, yogurt, or hard cheese, and green vegetables, such as spinach and broccoli (show table 1). A rough method of estimating dietary calcium intake is to multiply the number of dairy servings consumed each day by 300 mg. One serving is 8 oz of milk or yogurt, 1 oz of hard cheese, or 16 oz of cottage cheese.
Calcium supplements (calcium carbonate or calcium citrate) may be suggested if a person cannot get enough calcium in their diet (show figure 1). Calcium doses greater than 500 mg/day should be taken in divided doses (eg, once in morning and evening). The daily intake recommendations given above always apply to "elemental calcium". Use caution when reading the labels of calcium supplements and be sure to note the amount of elemental calcium contained per serving, as many products give the calcium content per two pills.
Vitamin D intake — Experts also recommend 800 International Units (IU) of vitamin D each day. This dose appears to reduce bone loss and fracture rate in older women and men when there is adequate calcium intake (described above).
Milk is the primary dietary source of dietary vitamin D, containing approximately 100 IU per cup. Experts recommend vitamin D supplementation for all patients with osteoporosis whose intake of vitamin D is below 400 IU per day. This can be found in a daily multivitamin or a calcium/vitamin D supplement. Vitamin D is available separately in 400 IU supplements.
Protein supplements — Protein supplements may also be recommended for some patients to ensure sufficient protein intake. This may be particularly important for those who have already had osteoporotic fractures.
Alcohol, caffeine, and salt intake — A healthcare provider may also recommend limiting alcohol consumption, since high alcohol intake may increase the risk of fracture due to an increased risk of falling, poor nutrition, etc. It is not clear if restricting caffeine or salt is helpful; these measures have not been proven to prevent bone loss in those who have a sufficient intake of calcium.
Exercise — A person who has or wants to prevent osteoporosis should exercise for at least 30 minutes three times per week. Any weight-bearing exercise regimen is appropriate (eg, walking). However, exercises that could increase the risk of falling should be avoided.
Weight-bearing exercises can improve bone mass in premenopausal women and help to maintain bone density for women after menopause. Physical activity reduces the risk of hip fracture in older women as a result of increased muscle strength.
The benefits of exercise are quickly lost if a person stop exercising. A regular, weight-bearing exercise regimen that a person genuinely enjoys improves the chances of continuing to follow the routine over the long term. (See "Patient information: Exercise").
Smoking cessation — Smoking cessation is strongly recommended for patients at risk for osteoporosis because smoking cigarettes is known to accelerate bone loss. One study suggested that women who smoke one pack per day throughout adulthood have a 5 to 10 percent reduction in bone density by menopause, resulting in an increased risk of fracture. (See "Patient information: Smoking cessation").
Preventing falls — Repeated falling may significantly increase the risk of osteoporotic fractures in the elderly. Taking measures to prevent falls can decrease the risk of fractures. Such measures may include the following: Remove loose rugs and electrical cords or any other loose items in your home that could lead to tripping, slipping, and falling. Ensure that there is adequate lighting in all areas inside and around the home, including stairwells and entrance ways. Avoid walking on ice, wet or polished floors, or other potentially slippery surfaces. Avoid walking in unfamiliar areas outside.
Because certain drugs may increase the risk of falls, drug regimens should be reviewed on a regular basis. In some cases, the healthcare provider may decide to substitute one medication with an alternative that has a lower risk of causing falls. In addition, people with poor vision should see an eye specialist (eg, optomotrist or ophthamologist) for corrective lenses (glasses).
Hip pads — A person with osteoporosis who falls on their hip but has a substantial amount of muscle or fat padding over the hips has a lower risk of fracture than a person who has little padding. Hip pads (external hip protectors) are designed to reduce the risk of fracture when an elderly person falls. Results of studies that used hip pads have shown mixed results. For people who are willing to wear them on a consistent basis, hip pads may be of benefit in preventing fractures related to an accidental fall.
Medication monitoring — Prolonged therapy with and/or high doses of certain medications that increase bone loss should be monitored closely by a healthcare provider and decreased or discontinued when possible. Such medications include the following: Glucocorticoid medications (eg, prednisone) Heparin, a medication used to prevent and treat abnormal blood clotting (ie, anticoagulant) Vitamin A and certain synthetic retinoids (eg, etretinate) Certain antiepileptic drugs (eg, phenytoin, carbamazepine, primidone, phenobarbital, and valproate)
MEDICATIONS — The non-drug measures discussed above can help to reduce bone loss. For certain men and for premenopausal women who have or who are at risk for osteoporosis, drug or hormonal therapies may also be recommended.
However, the relationship between bone density and fracture risk in premenopausal women is not well defined. A premenopausal woman with low bone density may have no increased risk of fracture. Thus, bone density alone should not be used to define osteoporosis in a premenopausal woman, but instead indicates the need for further evaluation. (See "Patient information: Osteoporosis causes, diagnosis, and screening").
Bisphosphonates — Bisphosphonates inhibit the breakdown and removal of bone (ie, resorption). They are widely used for the prevention and treatment of osteoporosis in postmenopausal women.
These drugs need to be taken first thing in the morning on an empty stomach with a full 8 oz glass of water. The person must then wait at least half an hour (with alendronate (Fosamax®) and risedronate (Actonel®)) or one hour (with ibandronate (Boniva®)) before eating or taking any other medications. These dosing instructions help to reduce the risk of side effects and potential complications.
Side effects of bisphosphonates — Most people who take bisphosphonates for prevention or treatment of osteoporosis do not have any serious side effects related to the medication. However, it is important to closely follow the instructions for taking the medication; lying down or eating sooner than 30 minutes after a dose increases the risk of stomach upset.
There has been concern about a risk of bisphosphonates in people who require invasive dental work. A problem known as avascular necrosis or osteonecrosis of the jaw has rarely developed in a small number of people who used bisphosphonates. The risk of this problem is small in people who take bisphosphonates for osteoporosis prevention and treatment. However, there is a slightly higher risk of this problem when higher doses of bisphosphonates are given into vein during cancer treatment.
Most experts do not think that it is necessary to stop bisphosphonates before invasive dental work (eg, tooth extraction or implant) unless the treatment has been given into a vein. In this case, the patient should consult their healthcare provider for a specific recommendation.
Bisphosphonates are not recommended for premenopausal women who could become pregnant because of the unknown effects on a developing fetus.
Alendronate — Alendronate (Fosamax®) reduces vertebral and nonvertebral fractures, and decreases the loss of height associated with vertebral fractures. The dose for treatment is 10 mg per day, and the dose for prevention is 5 mg per day. Alendronate is usually taken as a weekly 70 or 35 mg pill.
Risedronate — Risedronate (Actonel®) is also approved for both prevention and treatment of osteoporosis at a dose of 5 mg/day (or as a single 35 mg once-weekly pill). Like alendronate, it reduces the risk of both vertebral and hip fractures.
Ibandronate — Ibandronate (Boniva®) can be used for prevention and treatment of osteoporosis at a dose of 150 mg once monthly. A monthly reminder can be sent by phone, mail, or email from the manufacturer. Although Boniva reduces the risk of bone loss and spine fractures, there is no proof that it reduces the risk of hip fractures.
Other new bisphosphonates are being studied, including single yearly intravenous infusions of zoledronic acid, which might be an effective treatment for postmenopausal osteoporosis.
"Estrogen-like" medications — Certain medications, known as selective estrogen receptor modulators (SERMs) produce some estrogen-like effects in the bone that provides protection against postmenopausal bone loss. In addition, SERMS also decrease the risk of breast cancer in women who are at high risk. Currently available SERMs include raloxifene (Evista®) and tamoxifen. Raloxifene (Evista) can be used for the prevention and treatment of osteoporosis in postmenopausal women, although it may be less effective in preventing bone loss than bisphosphonates or estrogen. (See "Patient information: Tamoxifen and raloxifene for the prevention of breast cancer").
SERMs are not recommended for premenopausal women.
Estrogen/progestin therapy — In the past, estrogen or estrogen-progestin therapy was considered the best way to prevent postmenopausal osteoporosis and was often used for treatment. Data from the Women's Health Initiative (WHI), a large clinical trial, found that combined estrogen-progestin treatment reduced hip and vertebral fracture risk by 34 percent. A similar reduction in fracture risk was seen in the WHI trial of estrogen alone.
Estrogen had the additional advantages of controlling menopausal symptoms. However, the WHI found that estrogen plus progestin does not reduce the risk of coronary heart disease, and slightly increases the risk of breast cancer, stroke, and blood clots. The details of the WHI are discussed elsewhere. (See "Patient information: Postmenopausal hormone therapy").
Thus, estrogen is not recommended for the treatment or prevention of osteoporosis in postmenopausal women. However, some postmenopausal women continue to use estrogen, including women with persistent menopausal symptoms and those who cannot tolerate other types of osteoporosis treatment.
Estrogen may be an appropriate treatment for prevention of osteoporosis in young women with amenorrhea (absence of menses). This is often accomplished with a birth control pill. (See "Patient information: Menstrual cycle disorders (Absent and irregular periods)").
Calcitonin — Calcitonin is a hormone produced by the thyroid gland that, together with parathyroid hormone, helps to regulate calcium concentrations in the body. Synthetic calcitonin is sometimes recommended as a treatment for osteoporosis. Calcitonin may be administered via nasal spray or injection (subcutaneous salmon calcitonin). Nasal administration is typically preferred due to ease of use and because the injections tend to cause more nausea and flushing.
Other drugs are usually recommended before calcitonin because it is not clear if calcitonin increases bone density and decreases the fracture rate outside the spine. However, due to its pain-relieving (analgesic) effects, calcitonin may be suggested as a first-line therapy for those who have a sudden, intense (acute) onset of pain due to vertebral fractures. The treatment regimen is typically changed once the acute pain subsides or if the pain fails to subside over a prolonged period (eg, four weeks).
Parathyroid hormone (PTH) — PTH is produced by the parathyroid glands and stimulates both bone resorption and new bone formation. Intermittent administration stimulates formation more than resorption. Clinical trials suggest that PTH therapy is effective in both the prevention and treatment of osteoporosis in postmenopausal women and in men.
A PTH preparation called Forteo®, given by daily injection for two years, is approved for the treatment of severe osteoporosis. It is more effective at building spine bone density than any other treatment, although it is unclear if it also prevents fracture better than other treatments (specifically, the bisphosphonates). Because it requires daily injection and is expensive, it is usually reserved for patients with very severe hip or spine osteoporosis. It is not recommended for premenopausal women.
Monitoring response to hormonal or drug therapy — Testing may be recommended to monitor a patient's response to osteoporosis therapy. This may include measurement of bone mineral density or laboratory tests that indicate bone turnover (ie, rate of new bone formation and breakdown).
Testing is typically done before treatment begins to get a baseline measurement. Laboratory testing may be repeated three months after treatment begins, while bone density testing may be repeated after two years.
SUMMARY Osteoporosis causes bones to become abnormally thin (osteopenic), weakened, and easily broken. This condition can be treated and prevented with diet, exercise, and stopping smoking. Calcium and vitamin D can prevent and treat thinning bones. The main dietary sources of calcium include milk and other dairy products, such as cottage cheese, yogurt, or hard cheese, and green vegetables, such as spinach and broccoli (show table 1). Milk is the primary source of dietary vitamin D, containing approximately 100 IU per cup. Calcium and vitamin D can also be taken as a supplement (eg, in a pill, show figure 1). A total of at least 1000 mg of calcium per day is recommended for premenopausal women and men. Women after menopause should consume 1500 mg calcium per day if they do not take estrogen. Experts also recommend 800 International Units (IU) of vitamin D each day. Exercise can help to prevent and treat thinning bones. Exercise should be done for at least 30 minutes three times per week. Any weight-bearing exercise regimen is appropriate (eg, walking). Smoking cigarettes can cause bones to become thinner and weaker. Stopping smoking can reduce this risk. Falling can cause fractures in the elderly. Preventing falls can lower the risk of fractures. Some medications can cause bone thinning. Such medications include glucocorticoid medications (eg, prednisone), heparin, vitamin A and certain synthetic retinoids (eg, etretinate), and certain antiepileptic drugs (eg, phenytoin, carbamazepine, primidone, phenobarbital, and valproate). You should talk to your provider about the risk of bone thinning if you take one of these medications (see "Medication monitoring" above). There are several medications that help prevent osteoporosis in women after menopause. We think alendronate (Fosamax®), risedronate (Actonel®), or raloxifene (Evista) are the best medications for prevention (see "Bisphosphonates" above). Alendronate (Fosamax®) or risedronate (Actonel®) are recommended to treat women after menopause who have osteoporosis (see "Bisphosphonates" above). Parathyroid hormone (Forteo®) is another medication that can be used to treat osteoporosis. We recommend this medication for men or postmenopausal women with severe hip or spine osteoporosis (see "Parathyroid hormone (PTH)" above). Hormone replacement (eg, estrogen, progesterone) is not usually recommended to prevent osteoporosis in women after menopause. Hormone therapy is recommended for some young women who do not have a monthly menstrual period (see "Estrogen/progestin therapy" above). A bone density test may be recommend to monitor how the bones respond to osteoporosis treatment. For postmenopausal women, a bone density test is usually done two years after treatment starts.
WHERE TO GET MORE INFORMATION — Your healthcare provider is the best source of information for questions and concerns related to your medical problem. Because no two patients are exactly alike and recommendations can vary from one person to another, it is important to seek guidance from a provider who is familiar with your individual situation.
This discussion will be updated as needed every four months on our web site (www.patients.uptodate.com). Additional topics as well as selected discussions written for healthcare professionals are also available for those who would like more detailed information.
A number of web sites have information about medical problems and treatments, although it can be difficult to know which sites are reputable. Information provided by the National Institutes of Health, national medical societies and some other well-established organizations are often reliable sources of information, although the frequency with which they are updated is variable. National Library of Medicine
(www.nlm.nih.gov/medlineplus/healthtopics.html)
Osteoporosis and Related Bone Diseases National Resource Center (ORBD-NRC)
Toll-free: (800) 624-BONE (2663)
TTY: (202) 466-4315
E-mail: orbdnrc@nof.org
(www.osteo.org)
National Osteoporosis Foundation
Phone: (202) 223-2226
E-mail: patientinfo@nof.org
(www.nof.org)
National Women's Health Resource Center (NWHRC)
Toll-free: (877) 986-9472
E-mail: ddiamant@healthywomen.org
(www.healthywomen.org)
Osteoporosis Society of Canada
Phone: (416) 696-2663 x 294
(www.osteoporosis.ca/)
The Hormone Foundation
(www.hormone.org/public/osteoporosis.cfm, available in English, Spanish, French, Italian, German, and Portuguese)
[1-5]
Use of UpToDate is subject to the Subscription and License Agreement. REFERENCES 1. Delmas, PD, Bjarnason, NH, Mitlak, BH, et al. Effects of raloxifene on bone mineral density, serum cholesterol concentrations, and uterine endometrium in postmenopausal women. N Engl J Med 1997; 337:1641.
2. Rossouw, JE, Anderson, GL, Prentice, RL, et al. Risks and benefits of estrogen plus progestin in healthy postmenopausal women: principal results From the Women's Health Initiative randomized controlled trial. JAMA 2002; 288:321.
3. Fulton, JP. New guidelines for the prevention and treatment of osteoporosis. National Osteoporosis Foundation. Med Health R I 1999; 82:110.
4. Gregg, EW, Cauley, JA, Seeley, DG, et al. Physical activity and osteoporotic fracture risk in older women. Ann Intern Med 1998; 129:81.
5. NIH Consensus Development Panel on Optimal Calcium Intake. Optimal calcium intake. JAMA 1994; 272:1942.
Osteoporosis prevention and treatment
INTRODUCTION — Osteoporosis is a common skeletal disorder that causes a decrease in bone mass and density, causing bones to become abnormally thin (osteopenic), weakened, and easily broken (fractured). Women are at a higher risk for osteoporosis after menopause due to lower levels of estrogen, a female hormone that helps to maintain bone mass.
Fortunately, preventive treatments are available that can help to maintain or increase bone density. For those already affected by osteoporosis, prompt diagnosis of bone loss and fracture risk are essential because therapies are available that can slow further loss of bone or increase bone density.
This topic review discusses the therapies available for the prevention and treatment of osteoporosis. A separate topic review is available about the causes, diagnosis, and screening measures for osteoporosis. (See "Patient information: Osteoporosis causes, diagnosis, and screening").
NON-DRUG PREVENTION AND TREATMENT — The non-drug therapy of osteoporosis includes three major components: diet, exercise, and smoking cessation. These recommendations apply to men and women.
Diet — An optimal diet for the prevention or treatment of osteoporosis includes an adequate intake of calories as well as calcium and vitamin D, both of which are essential in helping to maintain proper bone formation and density.
Calcium intake — Experts recommend that daily elemental calcium intake (total of diet plus supplement) be at least 1000 mg for premenopausal women and men, and 1500 mg in postmenopausal women who do not take estrogen. However, the total daily calcium intake should not routinely exceed 2000 mg due to the possibility of adverse effects. (See "Patient information: Calcium for bone health").
The main dietary sources of calcium include milk and other dairy products, such as cottage cheese, yogurt, or hard cheese, and green vegetables, such as spinach and broccoli (show table 1). A rough method of estimating dietary calcium intake is to multiply the number of dairy servings consumed each day by 300 mg. One serving is 8 oz of milk or yogurt, 1 oz of hard cheese, or 16 oz of cottage cheese.
Calcium supplements (calcium carbonate or calcium citrate) may be suggested if a person cannot get enough calcium in their diet (show figure 1). Calcium doses greater than 500 mg/day should be taken in divided doses (eg, once in morning and evening). The daily intake recommendations given above always apply to "elemental calcium". Use caution when reading the labels of calcium supplements and be sure to note the amount of elemental calcium contained per serving, as many products give the calcium content per two pills.
Vitamin D intake — Experts also recommend 800 International Units (IU) of vitamin D each day. This dose appears to reduce bone loss and fracture rate in older women and men when there is adequate calcium intake (described above).
Milk is the primary dietary source of dietary vitamin D, containing approximately 100 IU per cup. Experts recommend vitamin D supplementation for all patients with osteoporosis whose intake of vitamin D is below 400 IU per day. This can be found in a daily multivitamin or a calcium/vitamin D supplement. Vitamin D is available separately in 400 IU supplements.
Protein supplements — Protein supplements may also be recommended for some patients to ensure sufficient protein intake. This may be particularly important for those who have already had osteoporotic fractures.
Alcohol, caffeine, and salt intake — A healthcare provider may also recommend limiting alcohol consumption, since high alcohol intake may increase the risk of fracture due to an increased risk of falling, poor nutrition, etc. It is not clear if restricting caffeine or salt is helpful; these measures have not been proven to prevent bone loss in those who have a sufficient intake of calcium.
Exercise — A person who has or wants to prevent osteoporosis should exercise for at least 30 minutes three times per week. Any weight-bearing exercise regimen is appropriate (eg, walking). However, exercises that could increase the risk of falling should be avoided.
Weight-bearing exercises can improve bone mass in premenopausal women and help to maintain bone density for women after menopause. Physical activity reduces the risk of hip fracture in older women as a result of increased muscle strength.
The benefits of exercise are quickly lost if a person stop exercising. A regular, weight-bearing exercise regimen that a person genuinely enjoys improves the chances of continuing to follow the routine over the long term. (See "Patient information: Exercise").
Smoking cessation — Smoking cessation is strongly recommended for patients at risk for osteoporosis because smoking cigarettes is known to accelerate bone loss. One study suggested that women who smoke one pack per day throughout adulthood have a 5 to 10 percent reduction in bone density by menopause, resulting in an increased risk of fracture. (See "Patient information: Smoking cessation").
Preventing falls — Repeated falling may significantly increase the risk of osteoporotic fractures in the elderly. Taking measures to prevent falls can decrease the risk of fractures. Such measures may include the following: Remove loose rugs and electrical cords or any other loose items in your home that could lead to tripping, slipping, and falling. Ensure that there is adequate lighting in all areas inside and around the home, including stairwells and entrance ways. Avoid walking on ice, wet or polished floors, or other potentially slippery surfaces. Avoid walking in unfamiliar areas outside.
Because certain drugs may increase the risk of falls, drug regimens should be reviewed on a regular basis. In some cases, the healthcare provider may decide to substitute one medication with an alternative that has a lower risk of causing falls. In addition, people with poor vision should see an eye specialist (eg, optomotrist or ophthamologist) for corrective lenses (glasses).
Hip pads — A person with osteoporosis who falls on their hip but has a substantial amount of muscle or fat padding over the hips has a lower risk of fracture than a person who has little padding. Hip pads (external hip protectors) are designed to reduce the risk of fracture when an elderly person falls. Results of studies that used hip pads have shown mixed results. For people who are willing to wear them on a consistent basis, hip pads may be of benefit in preventing fractures related to an accidental fall.
Medication monitoring — Prolonged therapy with and/or high doses of certain medications that increase bone loss should be monitored closely by a healthcare provider and decreased or discontinued when possible. Such medications include the following: Glucocorticoid medications (eg, prednisone) Heparin, a medication used to prevent and treat abnormal blood clotting (ie, anticoagulant) Vitamin A and certain synthetic retinoids (eg, etretinate) Certain antiepileptic drugs (eg, phenytoin, carbamazepine, primidone, phenobarbital, and valproate)
MEDICATIONS — The non-drug measures discussed above can help to reduce bone loss. For certain men and for premenopausal women who have or who are at risk for osteoporosis, drug or hormonal therapies may also be recommended.
However, the relationship between bone density and fracture risk in premenopausal women is not well defined. A premenopausal woman with low bone density may have no increased risk of fracture. Thus, bone density alone should not be used to define osteoporosis in a premenopausal woman, but instead indicates the need for further evaluation. (See "Patient information: Osteoporosis causes, diagnosis, and screening").
Bisphosphonates — Bisphosphonates inhibit the breakdown and removal of bone (ie, resorption). They are widely used for the prevention and treatment of osteoporosis in postmenopausal women.
These drugs need to be taken first thing in the morning on an empty stomach with a full 8 oz glass of water. The person must then wait at least half an hour (with alendronate (Fosamax®) and risedronate (Actonel®)) or one hour (with ibandronate (Boniva®)) before eating or taking any other medications. These dosing instructions help to reduce the risk of side effects and potential complications.
Side effects of bisphosphonates — Most people who take bisphosphonates for prevention or treatment of osteoporosis do not have any serious side effects related to the medication. However, it is important to closely follow the instructions for taking the medication; lying down or eating sooner than 30 minutes after a dose increases the risk of stomach upset.
There has been concern about a risk of bisphosphonates in people who require invasive dental work. A problem known as avascular necrosis or osteonecrosis of the jaw has rarely developed in a small number of people who used bisphosphonates. The risk of this problem is small in people who take bisphosphonates for osteoporosis prevention and treatment. However, there is a slightly higher risk of this problem when higher doses of bisphosphonates are given into vein during cancer treatment.
Most experts do not think that it is necessary to stop bisphosphonates before invasive dental work (eg, tooth extraction or implant) unless the treatment has been given into a vein. In this case, the patient should consult their healthcare provider for a specific recommendation.
Bisphosphonates are not recommended for premenopausal women who could become pregnant because of the unknown effects on a developing fetus.
Alendronate — Alendronate (Fosamax®) reduces vertebral and nonvertebral fractures, and decreases the loss of height associated with vertebral fractures. The dose for treatment is 10 mg per day, and the dose for prevention is 5 mg per day. Alendronate is usually taken as a weekly 70 or 35 mg pill.
Risedronate — Risedronate (Actonel®) is also approved for both prevention and treatment of osteoporosis at a dose of 5 mg/day (or as a single 35 mg once-weekly pill). Like alendronate, it reduces the risk of both vertebral and hip fractures.
Ibandronate — Ibandronate (Boniva®) can be used for prevention and treatment of osteoporosis at a dose of 150 mg once monthly. A monthly reminder can be sent by phone, mail, or email from the manufacturer. Although Boniva reduces the risk of bone loss and spine fractures, there is no proof that it reduces the risk of hip fractures.
Other new bisphosphonates are being studied, including single yearly intravenous infusions of zoledronic acid, which might be an effective treatment for postmenopausal osteoporosis.
"Estrogen-like" medications — Certain medications, known as selective estrogen receptor modulators (SERMs) produce some estrogen-like effects in the bone that provides protection against postmenopausal bone loss. In addition, SERMS also decrease the risk of breast cancer in women who are at high risk. Currently available SERMs include raloxifene (Evista®) and tamoxifen. Raloxifene (Evista) can be used for the prevention and treatment of osteoporosis in postmenopausal women, although it may be less effective in preventing bone loss than bisphosphonates or estrogen. (See "Patient information: Tamoxifen and raloxifene for the prevention of breast cancer").
SERMs are not recommended for premenopausal women.
Estrogen/progestin therapy — In the past, estrogen or estrogen-progestin therapy was considered the best way to prevent postmenopausal osteoporosis and was often used for treatment. Data from the Women's Health Initiative (WHI), a large clinical trial, found that combined estrogen-progestin treatment reduced hip and vertebral fracture risk by 34 percent. A similar reduction in fracture risk was seen in the WHI trial of estrogen alone.
Estrogen had the additional advantages of controlling menopausal symptoms. However, the WHI found that estrogen plus progestin does not reduce the risk of coronary heart disease, and slightly increases the risk of breast cancer, stroke, and blood clots. The details of the WHI are discussed elsewhere. (See "Patient information: Postmenopausal hormone therapy").
Thus, estrogen is not recommended for the treatment or prevention of osteoporosis in postmenopausal women. However, some postmenopausal women continue to use estrogen, including women with persistent menopausal symptoms and those who cannot tolerate other types of osteoporosis treatment.
Estrogen may be an appropriate treatment for prevention of osteoporosis in young women with amenorrhea (absence of menses). This is often accomplished with a birth control pill. (See "Patient information: Menstrual cycle disorders (Absent and irregular periods)").
Calcitonin — Calcitonin is a hormone produced by the thyroid gland that, together with parathyroid hormone, helps to regulate calcium concentrations in the body. Synthetic calcitonin is sometimes recommended as a treatment for osteoporosis. Calcitonin may be administered via nasal spray or injection (subcutaneous salmon calcitonin). Nasal administration is typically preferred due to ease of use and because the injections tend to cause more nausea and flushing.
Other drugs are usually recommended before calcitonin because it is not clear if calcitonin increases bone density and decreases the fracture rate outside the spine. However, due to its pain-relieving (analgesic) effects, calcitonin may be suggested as a first-line therapy for those who have a sudden, intense (acute) onset of pain due to vertebral fractures. The treatment regimen is typically changed once the acute pain subsides or if the pain fails to subside over a prolonged period (eg, four weeks).
Parathyroid hormone (PTH) — PTH is produced by the parathyroid glands and stimulates both bone resorption and new bone formation. Intermittent administration stimulates formation more than resorption. Clinical trials suggest that PTH therapy is effective in both the prevention and treatment of osteoporosis in postmenopausal women and in men.
A PTH preparation called Forteo®, given by daily injection for two years, is approved for the treatment of severe osteoporosis. It is more effective at building spine bone density than any other treatment, although it is unclear if it also prevents fracture better than other treatments (specifically, the bisphosphonates). Because it requires daily injection and is expensive, it is usually reserved for patients with very severe hip or spine osteoporosis. It is not recommended for premenopausal women.
Monitoring response to hormonal or drug therapy — Testing may be recommended to monitor a patient's response to osteoporosis therapy. This may include measurement of bone mineral density or laboratory tests that indicate bone turnover (ie, rate of new bone formation and breakdown).
Testing is typically done before treatment begins to get a baseline measurement. Laboratory testing may be repeated three months after treatment begins, while bone density testing may be repeated after two years.
SUMMARY Osteoporosis causes bones to become abnormally thin (osteopenic), weakened, and easily broken. This condition can be treated and prevented with diet, exercise, and stopping smoking. Calcium and vitamin D can prevent and treat thinning bones. The main dietary sources of calcium include milk and other dairy products, such as cottage cheese, yogurt, or hard cheese, and green vegetables, such as spinach and broccoli (show table 1). Milk is the primary source of dietary vitamin D, containing approximately 100 IU per cup. Calcium and vitamin D can also be taken as a supplement (eg, in a pill, show figure 1). A total of at least 1000 mg of calcium per day is recommended for premenopausal women and men. Women after menopause should consume 1500 mg calcium per day if they do not take estrogen. Experts also recommend 800 International Units (IU) of vitamin D each day. Exercise can help to prevent and treat thinning bones. Exercise should be done for at least 30 minutes three times per week. Any weight-bearing exercise regimen is appropriate (eg, walking). Smoking cigarettes can cause bones to become thinner and weaker. Stopping smoking can reduce this risk. Falling can cause fractures in the elderly. Preventing falls can lower the risk of fractures. Some medications can cause bone thinning. Such medications include glucocorticoid medications (eg, prednisone), heparin, vitamin A and certain synthetic retinoids (eg, etretinate), and certain antiepileptic drugs (eg, phenytoin, carbamazepine, primidone, phenobarbital, and valproate). You should talk to your provider about the risk of bone thinning if you take one of these medications (see "Medication monitoring" above). There are several medications that help prevent osteoporosis in women after menopause. We think alendronate (Fosamax®), risedronate (Actonel®), or raloxifene (Evista) are the best medications for prevention (see "Bisphosphonates" above). Alendronate (Fosamax®) or risedronate (Actonel®) are recommended to treat women after menopause who have osteoporosis (see "Bisphosphonates" above). Parathyroid hormone (Forteo®) is another medication that can be used to treat osteoporosis. We recommend this medication for men or postmenopausal women with severe hip or spine osteoporosis (see "Parathyroid hormone (PTH)" above). Hormone replacement (eg, estrogen, progesterone) is not usually recommended to prevent osteoporosis in women after menopause. Hormone therapy is recommended for some young women who do not have a monthly menstrual period (see "Estrogen/progestin therapy" above). A bone density test may be recommend to monitor how the bones respond to osteoporosis treatment. For postmenopausal women, a bone density test is usually done two years after treatment starts.
WHERE TO GET MORE INFORMATION — Your healthcare provider is the best source of information for questions and concerns related to your medical problem. Because no two patients are exactly alike and recommendations can vary from one person to another, it is important to seek guidance from a provider who is familiar with your individual situation.
This discussion will be updated as needed every four months on our web site (www.patients.uptodate.com). Additional topics as well as selected discussions written for healthcare professionals are also available for those who would like more detailed information.
A number of web sites have information about medical problems and treatments, although it can be difficult to know which sites are reputable. Information provided by the National Institutes of Health, national medical societies and some other well-established organizations are often reliable sources of information, although the frequency with which they are updated is variable. National Library of Medicine
(www.nlm.nih.gov/medlineplus/healthtopics.html)
Osteoporosis and Related Bone Diseases National Resource Center (ORBD-NRC)
Toll-free: (800) 624-BONE (2663)
TTY: (202) 466-4315
E-mail: orbdnrc@nof.org
(www.osteo.org)
National Osteoporosis Foundation
Phone: (202) 223-2226
E-mail: patientinfo@nof.org
(www.nof.org)
National Women's Health Resource Center (NWHRC)
Toll-free: (877) 986-9472
E-mail: ddiamant@healthywomen.org
(www.healthywomen.org)
Osteoporosis Society of Canada
Phone: (416) 696-2663 x 294
(www.osteoporosis.ca/)
The Hormone Foundation
(www.hormone.org/public/osteoporosis.cfm, available in English, Spanish, French, Italian, German, and Portuguese)
[1-5]
Use of UpToDate is subject to the Subscription and License Agreement. REFERENCES 1. Delmas, PD, Bjarnason, NH, Mitlak, BH, et al. Effects of raloxifene on bone mineral density, serum cholesterol concentrations, and uterine endometrium in postmenopausal women. N Engl J Med 1997; 337:1641.
2. Rossouw, JE, Anderson, GL, Prentice, RL, et al. Risks and benefits of estrogen plus progestin in healthy postmenopausal women: principal results From the Women's Health Initiative randomized controlled trial. JAMA 2002; 288:321.
3. Fulton, JP. New guidelines for the prevention and treatment of osteoporosis. National Osteoporosis Foundation. Med Health R I 1999; 82:110.
4. Gregg, EW, Cauley, JA, Seeley, DG, et al. Physical activity and osteoporotic fracture risk in older women. Ann Intern Med 1998; 129:81.
5. NIH Consensus Development Panel on Optimal Calcium Intake. Optimal calcium intake. JAMA 1994; 272:1942.
Fortunately, preventive treatments are available that can help to maintain or increase bone density. For those already affected by osteoporosis, prompt diagnosis of bone loss and fracture risk are essential because therapies are available that can slow further loss of bone or increase bone density.
This topic review discusses the therapies available for the prevention and treatment of osteoporosis. A separate topic review is available about the causes, diagnosis, and screening measures for osteoporosis. (See "Patient information: Osteoporosis causes, diagnosis, and screening").
NON-DRUG PREVENTION AND TREATMENT — The non-drug therapy of osteoporosis includes three major components: diet, exercise, and smoking cessation. These recommendations apply to men and women.
Diet — An optimal diet for the prevention or treatment of osteoporosis includes an adequate intake of calories as well as calcium and vitamin D, both of which are essential in helping to maintain proper bone formation and density.
Calcium intake — Experts recommend that daily elemental calcium intake (total of diet plus supplement) be at least 1000 mg for premenopausal women and men, and 1500 mg in postmenopausal women who do not take estrogen. However, the total daily calcium intake should not routinely exceed 2000 mg due to the possibility of adverse effects. (See "Patient information: Calcium for bone health").
The main dietary sources of calcium include milk and other dairy products, such as cottage cheese, yogurt, or hard cheese, and green vegetables, such as spinach and broccoli (show table 1). A rough method of estimating dietary calcium intake is to multiply the number of dairy servings consumed each day by 300 mg. One serving is 8 oz of milk or yogurt, 1 oz of hard cheese, or 16 oz of cottage cheese.
Calcium supplements (calcium carbonate or calcium citrate) may be suggested if a person cannot get enough calcium in their diet (show figure 1). Calcium doses greater than 500 mg/day should be taken in divided doses (eg, once in morning and evening). The daily intake recommendations given above always apply to "elemental calcium". Use caution when reading the labels of calcium supplements and be sure to note the amount of elemental calcium contained per serving, as many products give the calcium content per two pills.
Vitamin D intake — Experts also recommend 800 International Units (IU) of vitamin D each day. This dose appears to reduce bone loss and fracture rate in older women and men when there is adequate calcium intake (described above).
Milk is the primary dietary source of dietary vitamin D, containing approximately 100 IU per cup. Experts recommend vitamin D supplementation for all patients with osteoporosis whose intake of vitamin D is below 400 IU per day. This can be found in a daily multivitamin or a calcium/vitamin D supplement. Vitamin D is available separately in 400 IU supplements.
Protein supplements — Protein supplements may also be recommended for some patients to ensure sufficient protein intake. This may be particularly important for those who have already had osteoporotic fractures.
Alcohol, caffeine, and salt intake — A healthcare provider may also recommend limiting alcohol consumption, since high alcohol intake may increase the risk of fracture due to an increased risk of falling, poor nutrition, etc. It is not clear if restricting caffeine or salt is helpful; these measures have not been proven to prevent bone loss in those who have a sufficient intake of calcium.
Exercise — A person who has or wants to prevent osteoporosis should exercise for at least 30 minutes three times per week. Any weight-bearing exercise regimen is appropriate (eg, walking). However, exercises that could increase the risk of falling should be avoided.
Weight-bearing exercises can improve bone mass in premenopausal women and help to maintain bone density for women after menopause. Physical activity reduces the risk of hip fracture in older women as a result of increased muscle strength.
The benefits of exercise are quickly lost if a person stop exercising. A regular, weight-bearing exercise regimen that a person genuinely enjoys improves the chances of continuing to follow the routine over the long term. (See "Patient information: Exercise").
Smoking cessation — Smoking cessation is strongly recommended for patients at risk for osteoporosis because smoking cigarettes is known to accelerate bone loss. One study suggested that women who smoke one pack per day throughout adulthood have a 5 to 10 percent reduction in bone density by menopause, resulting in an increased risk of fracture. (See "Patient information: Smoking cessation").
Preventing falls — Repeated falling may significantly increase the risk of osteoporotic fractures in the elderly. Taking measures to prevent falls can decrease the risk of fractures. Such measures may include the following: Remove loose rugs and electrical cords or any other loose items in your home that could lead to tripping, slipping, and falling. Ensure that there is adequate lighting in all areas inside and around the home, including stairwells and entrance ways. Avoid walking on ice, wet or polished floors, or other potentially slippery surfaces. Avoid walking in unfamiliar areas outside.
Because certain drugs may increase the risk of falls, drug regimens should be reviewed on a regular basis. In some cases, the healthcare provider may decide to substitute one medication with an alternative that has a lower risk of causing falls. In addition, people with poor vision should see an eye specialist (eg, optomotrist or ophthamologist) for corrective lenses (glasses).
Hip pads — A person with osteoporosis who falls on their hip but has a substantial amount of muscle or fat padding over the hips has a lower risk of fracture than a person who has little padding. Hip pads (external hip protectors) are designed to reduce the risk of fracture when an elderly person falls. Results of studies that used hip pads have shown mixed results. For people who are willing to wear them on a consistent basis, hip pads may be of benefit in preventing fractures related to an accidental fall.
Medication monitoring — Prolonged therapy with and/or high doses of certain medications that increase bone loss should be monitored closely by a healthcare provider and decreased or discontinued when possible. Such medications include the following: Glucocorticoid medications (eg, prednisone) Heparin, a medication used to prevent and treat abnormal blood clotting (ie, anticoagulant) Vitamin A and certain synthetic retinoids (eg, etretinate) Certain antiepileptic drugs (eg, phenytoin, carbamazepine, primidone, phenobarbital, and valproate)
MEDICATIONS — The non-drug measures discussed above can help to reduce bone loss. For certain men and for premenopausal women who have or who are at risk for osteoporosis, drug or hormonal therapies may also be recommended.
However, the relationship between bone density and fracture risk in premenopausal women is not well defined. A premenopausal woman with low bone density may have no increased risk of fracture. Thus, bone density alone should not be used to define osteoporosis in a premenopausal woman, but instead indicates the need for further evaluation. (See "Patient information: Osteoporosis causes, diagnosis, and screening").
Bisphosphonates — Bisphosphonates inhibit the breakdown and removal of bone (ie, resorption). They are widely used for the prevention and treatment of osteoporosis in postmenopausal women.
These drugs need to be taken first thing in the morning on an empty stomach with a full 8 oz glass of water. The person must then wait at least half an hour (with alendronate (Fosamax®) and risedronate (Actonel®)) or one hour (with ibandronate (Boniva®)) before eating or taking any other medications. These dosing instructions help to reduce the risk of side effects and potential complications.
Side effects of bisphosphonates — Most people who take bisphosphonates for prevention or treatment of osteoporosis do not have any serious side effects related to the medication. However, it is important to closely follow the instructions for taking the medication; lying down or eating sooner than 30 minutes after a dose increases the risk of stomach upset.
There has been concern about a risk of bisphosphonates in people who require invasive dental work. A problem known as avascular necrosis or osteonecrosis of the jaw has rarely developed in a small number of people who used bisphosphonates. The risk of this problem is small in people who take bisphosphonates for osteoporosis prevention and treatment. However, there is a slightly higher risk of this problem when higher doses of bisphosphonates are given into vein during cancer treatment.
Most experts do not think that it is necessary to stop bisphosphonates before invasive dental work (eg, tooth extraction or implant) unless the treatment has been given into a vein. In this case, the patient should consult their healthcare provider for a specific recommendation.
Bisphosphonates are not recommended for premenopausal women who could become pregnant because of the unknown effects on a developing fetus.
Alendronate — Alendronate (Fosamax®) reduces vertebral and nonvertebral fractures, and decreases the loss of height associated with vertebral fractures. The dose for treatment is 10 mg per day, and the dose for prevention is 5 mg per day. Alendronate is usually taken as a weekly 70 or 35 mg pill.
Risedronate — Risedronate (Actonel®) is also approved for both prevention and treatment of osteoporosis at a dose of 5 mg/day (or as a single 35 mg once-weekly pill). Like alendronate, it reduces the risk of both vertebral and hip fractures.
Ibandronate — Ibandronate (Boniva®) can be used for prevention and treatment of osteoporosis at a dose of 150 mg once monthly. A monthly reminder can be sent by phone, mail, or email from the manufacturer. Although Boniva reduces the risk of bone loss and spine fractures, there is no proof that it reduces the risk of hip fractures.
Other new bisphosphonates are being studied, including single yearly intravenous infusions of zoledronic acid, which might be an effective treatment for postmenopausal osteoporosis.
"Estrogen-like" medications — Certain medications, known as selective estrogen receptor modulators (SERMs) produce some estrogen-like effects in the bone that provides protection against postmenopausal bone loss. In addition, SERMS also decrease the risk of breast cancer in women who are at high risk. Currently available SERMs include raloxifene (Evista®) and tamoxifen. Raloxifene (Evista) can be used for the prevention and treatment of osteoporosis in postmenopausal women, although it may be less effective in preventing bone loss than bisphosphonates or estrogen. (See "Patient information: Tamoxifen and raloxifene for the prevention of breast cancer").
SERMs are not recommended for premenopausal women.
Estrogen/progestin therapy — In the past, estrogen or estrogen-progestin therapy was considered the best way to prevent postmenopausal osteoporosis and was often used for treatment. Data from the Women's Health Initiative (WHI), a large clinical trial, found that combined estrogen-progestin treatment reduced hip and vertebral fracture risk by 34 percent. A similar reduction in fracture risk was seen in the WHI trial of estrogen alone.
Estrogen had the additional advantages of controlling menopausal symptoms. However, the WHI found that estrogen plus progestin does not reduce the risk of coronary heart disease, and slightly increases the risk of breast cancer, stroke, and blood clots. The details of the WHI are discussed elsewhere. (See "Patient information: Postmenopausal hormone therapy").
Thus, estrogen is not recommended for the treatment or prevention of osteoporosis in postmenopausal women. However, some postmenopausal women continue to use estrogen, including women with persistent menopausal symptoms and those who cannot tolerate other types of osteoporosis treatment.
Estrogen may be an appropriate treatment for prevention of osteoporosis in young women with amenorrhea (absence of menses). This is often accomplished with a birth control pill. (See "Patient information: Menstrual cycle disorders (Absent and irregular periods)").
Calcitonin — Calcitonin is a hormone produced by the thyroid gland that, together with parathyroid hormone, helps to regulate calcium concentrations in the body. Synthetic calcitonin is sometimes recommended as a treatment for osteoporosis. Calcitonin may be administered via nasal spray or injection (subcutaneous salmon calcitonin). Nasal administration is typically preferred due to ease of use and because the injections tend to cause more nausea and flushing.
Other drugs are usually recommended before calcitonin because it is not clear if calcitonin increases bone density and decreases the fracture rate outside the spine. However, due to its pain-relieving (analgesic) effects, calcitonin may be suggested as a first-line therapy for those who have a sudden, intense (acute) onset of pain due to vertebral fractures. The treatment regimen is typically changed once the acute pain subsides or if the pain fails to subside over a prolonged period (eg, four weeks).
Parathyroid hormone (PTH) — PTH is produced by the parathyroid glands and stimulates both bone resorption and new bone formation. Intermittent administration stimulates formation more than resorption. Clinical trials suggest that PTH therapy is effective in both the prevention and treatment of osteoporosis in postmenopausal women and in men.
A PTH preparation called Forteo®, given by daily injection for two years, is approved for the treatment of severe osteoporosis. It is more effective at building spine bone density than any other treatment, although it is unclear if it also prevents fracture better than other treatments (specifically, the bisphosphonates). Because it requires daily injection and is expensive, it is usually reserved for patients with very severe hip or spine osteoporosis. It is not recommended for premenopausal women.
Monitoring response to hormonal or drug therapy — Testing may be recommended to monitor a patient's response to osteoporosis therapy. This may include measurement of bone mineral density or laboratory tests that indicate bone turnover (ie, rate of new bone formation and breakdown).
Testing is typically done before treatment begins to get a baseline measurement. Laboratory testing may be repeated three months after treatment begins, while bone density testing may be repeated after two years.
SUMMARY Osteoporosis causes bones to become abnormally thin (osteopenic), weakened, and easily broken. This condition can be treated and prevented with diet, exercise, and stopping smoking. Calcium and vitamin D can prevent and treat thinning bones. The main dietary sources of calcium include milk and other dairy products, such as cottage cheese, yogurt, or hard cheese, and green vegetables, such as spinach and broccoli (show table 1). Milk is the primary source of dietary vitamin D, containing approximately 100 IU per cup. Calcium and vitamin D can also be taken as a supplement (eg, in a pill, show figure 1). A total of at least 1000 mg of calcium per day is recommended for premenopausal women and men. Women after menopause should consume 1500 mg calcium per day if they do not take estrogen. Experts also recommend 800 International Units (IU) of vitamin D each day. Exercise can help to prevent and treat thinning bones. Exercise should be done for at least 30 minutes three times per week. Any weight-bearing exercise regimen is appropriate (eg, walking). Smoking cigarettes can cause bones to become thinner and weaker. Stopping smoking can reduce this risk. Falling can cause fractures in the elderly. Preventing falls can lower the risk of fractures. Some medications can cause bone thinning. Such medications include glucocorticoid medications (eg, prednisone), heparin, vitamin A and certain synthetic retinoids (eg, etretinate), and certain antiepileptic drugs (eg, phenytoin, carbamazepine, primidone, phenobarbital, and valproate). You should talk to your provider about the risk of bone thinning if you take one of these medications (see "Medication monitoring" above). There are several medications that help prevent osteoporosis in women after menopause. We think alendronate (Fosamax®), risedronate (Actonel®), or raloxifene (Evista) are the best medications for prevention (see "Bisphosphonates" above). Alendronate (Fosamax®) or risedronate (Actonel®) are recommended to treat women after menopause who have osteoporosis (see "Bisphosphonates" above). Parathyroid hormone (Forteo®) is another medication that can be used to treat osteoporosis. We recommend this medication for men or postmenopausal women with severe hip or spine osteoporosis (see "Parathyroid hormone (PTH)" above). Hormone replacement (eg, estrogen, progesterone) is not usually recommended to prevent osteoporosis in women after menopause. Hormone therapy is recommended for some young women who do not have a monthly menstrual period (see "Estrogen/progestin therapy" above). A bone density test may be recommend to monitor how the bones respond to osteoporosis treatment. For postmenopausal women, a bone density test is usually done two years after treatment starts.
WHERE TO GET MORE INFORMATION — Your healthcare provider is the best source of information for questions and concerns related to your medical problem. Because no two patients are exactly alike and recommendations can vary from one person to another, it is important to seek guidance from a provider who is familiar with your individual situation.
This discussion will be updated as needed every four months on our web site (www.patients.uptodate.com). Additional topics as well as selected discussions written for healthcare professionals are also available for those who would like more detailed information.
A number of web sites have information about medical problems and treatments, although it can be difficult to know which sites are reputable. Information provided by the National Institutes of Health, national medical societies and some other well-established organizations are often reliable sources of information, although the frequency with which they are updated is variable. National Library of Medicine
(www.nlm.nih.gov/medlineplus/healthtopics.html)
Osteoporosis and Related Bone Diseases National Resource Center (ORBD-NRC)
Toll-free: (800) 624-BONE (2663)
TTY: (202) 466-4315
E-mail: orbdnrc@nof.org
(www.osteo.org)
National Osteoporosis Foundation
Phone: (202) 223-2226
E-mail: patientinfo@nof.org
(www.nof.org)
National Women's Health Resource Center (NWHRC)
Toll-free: (877) 986-9472
E-mail: ddiamant@healthywomen.org
(www.healthywomen.org)
Osteoporosis Society of Canada
Phone: (416) 696-2663 x 294
(www.osteoporosis.ca/)
The Hormone Foundation
(www.hormone.org/public/osteoporosis.cfm, available in English, Spanish, French, Italian, German, and Portuguese)
[1-5]
Use of UpToDate is subject to the Subscription and License Agreement. REFERENCES 1. Delmas, PD, Bjarnason, NH, Mitlak, BH, et al. Effects of raloxifene on bone mineral density, serum cholesterol concentrations, and uterine endometrium in postmenopausal women. N Engl J Med 1997; 337:1641.
2. Rossouw, JE, Anderson, GL, Prentice, RL, et al. Risks and benefits of estrogen plus progestin in healthy postmenopausal women: principal results From the Women's Health Initiative randomized controlled trial. JAMA 2002; 288:321.
3. Fulton, JP. New guidelines for the prevention and treatment of osteoporosis. National Osteoporosis Foundation. Med Health R I 1999; 82:110.
4. Gregg, EW, Cauley, JA, Seeley, DG, et al. Physical activity and osteoporotic fracture risk in older women. Ann Intern Med 1998; 129:81.
5. NIH Consensus Development Panel on Optimal Calcium Intake. Optimal calcium intake. JAMA 1994; 272:1942.
Osteoporosis causes, diagnosis, and screening
INTRODUCTION — Osteoporosis is characterized by a progressive decrease in bone density, causing bones to become brittle, weakened, and fracture easily. Osteoporosis and the fractures that result are a major public health concern; more than 1.3 million osteoporotic fractures occur annually in the United States. Early diagnosis of bone loss can reduce or eliminate the risk of fractures.
This topic review discusses the causes, risk factors, signs, and symptoms of osteoporosis, as well as the ways that it can be diagnosed. For information about ways to prevent and treat osteoporosis, see "Patient information: Osteoporosis prevention and treatment".
BONE METABOLISM — To maintain bone density and strength, the body needs a sufficient supply of calcium and phosphorus, normal production of hormones that help to regulate bone cell function (eg, the calcium-regulating hormones, parathyroid hormone, calcitriol, and calcitonin; thyroid hormone; glucocorticoids; the sex hormones estrogen and testosterone), and an adequate supply of vitamin D, which is essential for normal bone formation and calcium absorption.
Bone is constantly being turned over and replaced as a result of cells that break down and remove bone (osteoclasts) and cells that replace and rebuild bone (osteoblasts). The resorption and formation of bone are essential to repair tiny breaks (microfractures) and to "remodel" bone (ie, remove and replace bone) in response to stress, including injury.
Osteoporosis is the result of years of bone loss, due to a "mismatch" between bone formation and resorption. Osteoporosis may also be related to years of inadequate bone formation, especially during the teens and 20s, which are the most important years of bone building. When bone becomes abnormally thin (known as osteopenia) and porous, the risk of fracture increases. Osteopenia is
Cortical bone, the normally dense, compact bone that forms the outer part of skeletal structures, provides strength and protection. Trabecular bone is found inside the long bones, particularly at the ends, and helps to provide mechanical support, particularly within the vertebrae. In patients with osteoporosis, both cortical and trabecular bone may be affected (show figure 1).
The processes of bone resorption and formation vary with age. Although 95 to 100 percent of expected peak bone mass develops by the late teen years, the body continues to form more bone than it breaks down until approximately 30 years of age. Maximum bone density is attained between 20 years (hip) and 30 years of age (spine and forearm). Thereafter, bone mass is slowly lost in the spine and hip; the loss occurs more rapidly during perimenopause.
SIGNS AND SYMPTOMS — Osteoporosis usually causes no symptoms until a fracture occurs, but it can cause back pain or loss of height.
Vertebral fractures — Vertebrae are the bones that make up the spine, and vertebral fractures are the most common sign of osteoporosis. About two-thirds of these fractures occur without symptoms. In these cases, the fracture is found during a chest or abdominal x-ray done for other reasons. In some patients, vertebral fractures may lead to a sudden onset of back pain, usually when performing routine activities, such as bending or lifting. This pain usually resolves over several weeks and is replaced by a chronic dull ache or pain. However, the pain may sometimes persist for many months. Successive compression or crush fractures, in which there is collapse of affected bone, may lead to increased curvature of the spine (thoracic kyphosis). As a result, there is typically an abnormal rounding of the upper back, known as a "dowager's hump," and loss of height (show figure 2). Due to vertebral fractures and associated height loss, the abdomen may be compressed, causing it to bulge forward. Such patients may note that their abdomens appear larger than before, their clothes no longer fit, and their waists seem to have "disappeared" even though they have not gained weight. Patients with multiple vertebral compression fractures may also have hip discomfort. The pain may be due to a decrease in the distance between the bottom of the rib cage and the uppermost portion of the pelvis. This change may also result in difficulty breathing or digestive abnormalities, such as constipation or an early feeling of fullness while eating.
Other fractures — Hip fractures are relatively common in patients with osteoporosis, affecting 15 percent of women and 5 percent of men by age 80. Such fractures are a major cause of disability in the elderly and increase the risk of death, although conditions other than the fracture (such as surgical complications) may be responsible for this increase.
Osteoporosis may also lead to fractures near the wrist in the lower end of the radius (the bone on the thumb side of the forearm), causing backward displacement of the wrist and hand. This type of break is known as a Colles' fracture, and often results when the hand is outstretched to stop a fall.
CAUSES — As mentioned above, osteoporosis results from either accelerated bone loss or inadequate bone formation. The imbalance between the rate of new bone formation and breakdown may occur due to several underlying conditions, including the following:
Menopause-related loss of estrogen — Estrogen is a hormone that plays an important role in regulating bone formation. The rate of bone loss increases soon after the menopause, particularly in trabecular bone; this increased rate of loss lasts for approximately 10 years. At this point, the rate of bone loss slows to near the premenopausal rate, but the premenopausal rate of bone formation is absent.
Hyperthyroidism — Hyperthyroidism is a condition in which the thyroid gland is overactive in its production of thyroid hormones. It is associated with increased bone turnover, potentially leading to bone loss. (See "Patient information: Hyperthyroidism").
Hyperparathyroidism — Hyperparathyroidism refers to overactivity of the parathyroid glands. These glands produce parathyroid hormone, which helps to regulate calcium concentrations in the body. Increased secretion of parathyroid hormone increases the removal of calcium from bone, raising blood calcium levels (hypercalcemia) and potentially leading to osteoporosis. (See "Patient information: Primary hyperparathyroidism").
Age-related bone loss — This may result from decreased calcium absorption, which typically begins in the fourth or fifth decade of life. It is associated with a slow loss of cortical and trabecular bone in both women and men.
Hypogonadism — Hypogonadism is a decrease in activity of the ovaries or testes resulting in low amounts of estrogen or testosterone, respectively. This may be a result of aging, but it can also occur in younger men and women due to medications that cause hypogonadism (eg, chemotherapy agents), block estrogen synthesis (aromatase inhibitors), or induce testosterone/estrogen deficiency (GnRH agonists). It may also occur as a result of low body weight, excessive exercise, or pituitary abnormalities.
Men who have low or absent levels of the hormone testosterone are at increased risk of osteoporosis, and women who have a low level of estrogen are also at risk. Symptoms of hypogonadism in men include a decreased sexual drive (libido) or impotence. In young women, signs of hypogonadism include loss of menstrual periods, which may or may not be associated with hot flashes, night sweats, or vaginal dryness.
Medications — Prolonged therapy with certain medications, including glucocorticoids (also called corticosteroids), heparin, certain medications for seizure disorders (eg, phenytoin, carbamazepine, primidone, and phenobarbital), cyclosporine, medroxyprogesterone acetate and vitamin A may result in accelerated bone resorption as well as slowed bone formation, leading to bone loss.
Pregnancy and breastfeeding — Bone loss occurs during pregnancy and breastfeeding, although the loss is temporary and has no long term effect on a woman's bone density. In women who become pregnant and breastfeed, there is no increased risk of fracture after menopause. Using a calcium supplement while breastfeeding has no effect on the amount of bone lost.
Vitamin B12 deficiency — Vitamin B12 deficiency (also known as pernicious anemia) appears to increase the risk of osteoporosis, which can lead to an increased risk of hip and spine fractures.
RISK FACTORS FOR FRACTURE — Several factors are associated with an increased risk of osteoporotic fractures, including the following:
Age — In people aged 90 years or more, approximately one-third of women and 15 percent of men will have a hip fracture.
Sex — Osteoporosis is a serious problem in men, although women are affected more commonly. Women have a lower average peak bone mass and lose more bone after menopause. About 30 percent of women over age 50 have osteoporosis, and this percentage increases with age.
Race — Whites have a considerably higher risk of hip fractures than blacks. Blacks generally have a higher peak bone mass and a lower rate of bone loss after menopause.
Falls — Repeated falling can be a significant problem for older people with osteoporosis. Over 90 percent of hip fractures occur after a fall. Certain factors contribute to the risk of falls, including poor vision, certain medications (eg, tranquilizers, some anxiety medications, sleeping pills), and neurologic disorders such as dementia (confusion).
Other factors — A number of other factors increase the risk of fractures, some of which include the following: Previous fracture between the ages of 20 and 50 years History of fracture in a first degree relative Cigarette smoking (men and women) Inflammatory bowel disease Celiac disease Cystic fibrosis Sedentary life style Drinking large amounts of caffeine Medications for anxiety or seizures Low body weight or weight loss Above average height Type 1 or 2 diabetes mellitus
DIAGNOSIS — Osteoporosis is diagnosed based upon the patient and family history, physical examination, laboratory studies, and bone mineral density (BMD) testing. It is important to exclude other conditions that can cause bone thinning (osteopenia), such as osteomalacia (softening and weakening of bone) as well as other potentially treatable conditions (eg, hyperparathyroidism, hyperthyroidism, kidney disease).
History and physical examination — During a medical history, a healthcare provider will ask about life events (pregnancies, age at first menstrual period and menopause), past or present medical conditions, medications, calcium intake, exercise, and alcohol/tobacco use.
The physical examination will include measurement of height and weight and may include laboratory tests. Such studies may include a complete blood count, measurement of calcium, phosphorus, vitamin D, bicarbonate, creatinine, and hormones such as thyroid-stimulating hormone (TSH). The testosterone level may be measured in men, particularly if the man has decreased libido or impotence. (See "Patient information: Sexual problems in men").
Bone density measurement — Measurement of bone mineral density is the most common method to determine if a person is at risk for or already has osteoporosis. The goal is to recognize people who are at risk before a fracture occurs. Several methods are available to measure bone density.
Dual x-ray absorptiometry (DXA) — DXA testing is the most popular method for measuring BMD because it provides precise measurements at important bone sites (eg, spine, hip, forearm) with minimal radiation.
During DXA, the patient lies on an examination table. An x-ray detector scans a bone region, and the amount of x-rays that pass through bone are measured and displayed as an image that is interpreted by a radiologist. The test causes no discomfort, and usually takes only 5 to 10 minutes. The bone mineral density is then compared with the normal range for the patient's sex and race.
Other Quantitative computerized tomography — This is a type of CT that provides accurate measures of bone density in the spine. Although this test may be a good alternative to DXA, it is seldom used because it is expensive, less precise for following measurements over time, and requires a higher radiation dose. Ultrasonography — Ultrasound can be used to measure the bone density of the heel. This may be useful to determine a person's fracture risk. However, it is used less frequently than DXA because there are no guidelines that use ultrasound measurements to diagnose osteoporosis or predict fracture risk. In areas that do not have access to DXA, ultrasound is an acceptable way to measure bone density.
We recommend DXA of the hip and spine because measurements at these sites are effective for predicting osteoporotic fracture at any site.
Interpreting BMD results — The World Health Organization (WHO) has defined normal bone density as a value within one standard deviation (SD) from average peak bone mass. Standard deviation is a statistical measure that defines how much a patient's result vary from the "average" young adult. Normal bone density — Bone density that is between 0 and 1 standard deviation below the mean is considered to be normal. This may be reported as a T-score of 0 to -1. Treatment is not usually recommended for people with normal bone density, although preventive measures (eg, calcium supplementation, weight-bearing exercise) are recommended to prevent osteopenia and osteoporosis. (See "Patient information: Osteoporosis prevention and treatment"). Osteopenia — Bone density that is between 1 and 2.5 standard deviations below the mean is called osteopenia. This may be reported as a T-score of -1 to -2.4. A person with osteopenia does not yet have osteoporosis, but is at risk to develop it if not treated. Osteoporosis — Osteoporosis is defined as BMD more than 2.5 standard deviations (SD) below the mean of normal young women. This is reported as a T-score of -2.5 or less. The lower the bone density, the greater the risk of fracture.
When to measure BMD — Bone density testing can be used to diagnose osteoporosis, as well as to screen for it. The National Osteoporosis Foundation has issued recommendations for bone density testing that primarily apply to white women after menopause. Bone density should be measured in women: Greater than 65 years of age Under age 65 who have one or more risk factors for osteoporotic fracture in addition to menopause.
In addition to the recommendations above, the International Society for Clinical Densitometry (ISCD) recommends bone density testing for men over 70 years of age and for adults (including premenopausal women): With fragility fracture (a bone fracture that occurs after a fall from standing height or less) With disease associated with low bone mass (Cushing's syndrome, hyperthyroidism, hyperparathyroidism, rheumatoid arthritis, gastrointestinal diseases associated with malabsorption) Taking drugs associated with low bone mass (glucocorticoids, GnRH agonists, some chemotherapy drugs)
PREVENTION AND TREATMENT — All women should be educated about the risk factors for osteoporotic fractures. A provider may recommend certain lifestyle changes that can help to reduce fracture risk, such as stopping smoking, limiting alcohol consumption, and participating in regular weight-bearing and muscle-strengthening exercises. A full discussion of osteoporosis prevention and treatment is available separately. (See "Patient information: Osteoporosis prevention and treatment").
WHERE TO GET MORE INFORMATION — Your healthcare provider is the best source of information for questions and concerns related to your medical problem. Because no two patients are exactly alike and recommendations can vary from one person to another, it is important to seek guidance from a provider who is familiar with your individual situation.
This discussion will be updated as needed every four months on our web site (www.patients.uptodate.com). Additional topics as well as selected discussions written for healthcare professionals are also available for those who would like more detailed information.
A number of web sites have information about medical problems and treatments, although it can be difficult to know which sites are reputable. Information provided by the National Institutes of Health, national medical societies and some other well-established organizations are often reliable sources of information, although the frequency with which they are updated is variable. National Library of Medicine
(www.nlm.nih.gov/medlineplus/healthtopics.html)
Osteoporosis and Related Bone Diseases National Resource Center (ORBD-NRC)
Toll-free: (800) 624-BONE (2663)
TTY: (202) 466-4315
(www.osteo.org)
National Osteoporosis Foundation
Phone: (202) 223-2226
(www.nof.org)
International Society for Clinical Densitometry (ISCD)
(www.ISCD.org)
National Women's Health Resource Center (NWHRC)
Toll-free: (877) 986-9472
(www.healthywomen.org)
Osteoporosis Society of Canada
Phone: (416) 696-2663 x 294
(www.osteoporosis.ca/)
The Hormone Foundation
(www.hormone.org/public/osteoporosis.cfm, available in English, Spanish, French, Italian, German, and Portuguese)
[1-4]
Use of UpToDate is subject to the Subscription and License Agreement. REFERENCES 1. Johnell, O, Kanis, JA, Black, DM, et al. Associations between baseline risk factors and vertebral fracture risk in the Multiple Outcomes of Raloxifene Evaluation (MORE) Study. J Bone Miner Res 2004; 19:764.
2. Raisz, LG. Clinical practice. Screening for osteoporosis. N Engl J Med 2005; 353:164.
3. Marshall, D, Johnell, O, Wedel, H. Meta-analysis of how well measures of bone mineral density predict occurrence of osteoporotic fractures. BMJ 1996; 312:1254.
4. Bainbridge, KE, Sowers, MF, Crutchfield, M, et al. Natural history of bone loss over 6 years among premenopausal and early postmenopausal women. Am J Epidemiol 2002; 156:410.
This topic review discusses the causes, risk factors, signs, and symptoms of osteoporosis, as well as the ways that it can be diagnosed. For information about ways to prevent and treat osteoporosis, see "Patient information: Osteoporosis prevention and treatment".
BONE METABOLISM — To maintain bone density and strength, the body needs a sufficient supply of calcium and phosphorus, normal production of hormones that help to regulate bone cell function (eg, the calcium-regulating hormones, parathyroid hormone, calcitriol, and calcitonin; thyroid hormone; glucocorticoids; the sex hormones estrogen and testosterone), and an adequate supply of vitamin D, which is essential for normal bone formation and calcium absorption.
Bone is constantly being turned over and replaced as a result of cells that break down and remove bone (osteoclasts) and cells that replace and rebuild bone (osteoblasts). The resorption and formation of bone are essential to repair tiny breaks (microfractures) and to "remodel" bone (ie, remove and replace bone) in response to stress, including injury.
Osteoporosis is the result of years of bone loss, due to a "mismatch" between bone formation and resorption. Osteoporosis may also be related to years of inadequate bone formation, especially during the teens and 20s, which are the most important years of bone building. When bone becomes abnormally thin (known as osteopenia) and porous, the risk of fracture increases. Osteopenia is
Cortical bone, the normally dense, compact bone that forms the outer part of skeletal structures, provides strength and protection. Trabecular bone is found inside the long bones, particularly at the ends, and helps to provide mechanical support, particularly within the vertebrae. In patients with osteoporosis, both cortical and trabecular bone may be affected (show figure 1).
The processes of bone resorption and formation vary with age. Although 95 to 100 percent of expected peak bone mass develops by the late teen years, the body continues to form more bone than it breaks down until approximately 30 years of age. Maximum bone density is attained between 20 years (hip) and 30 years of age (spine and forearm). Thereafter, bone mass is slowly lost in the spine and hip; the loss occurs more rapidly during perimenopause.
SIGNS AND SYMPTOMS — Osteoporosis usually causes no symptoms until a fracture occurs, but it can cause back pain or loss of height.
Vertebral fractures — Vertebrae are the bones that make up the spine, and vertebral fractures are the most common sign of osteoporosis. About two-thirds of these fractures occur without symptoms. In these cases, the fracture is found during a chest or abdominal x-ray done for other reasons. In some patients, vertebral fractures may lead to a sudden onset of back pain, usually when performing routine activities, such as bending or lifting. This pain usually resolves over several weeks and is replaced by a chronic dull ache or pain. However, the pain may sometimes persist for many months. Successive compression or crush fractures, in which there is collapse of affected bone, may lead to increased curvature of the spine (thoracic kyphosis). As a result, there is typically an abnormal rounding of the upper back, known as a "dowager's hump," and loss of height (show figure 2). Due to vertebral fractures and associated height loss, the abdomen may be compressed, causing it to bulge forward. Such patients may note that their abdomens appear larger than before, their clothes no longer fit, and their waists seem to have "disappeared" even though they have not gained weight. Patients with multiple vertebral compression fractures may also have hip discomfort. The pain may be due to a decrease in the distance between the bottom of the rib cage and the uppermost portion of the pelvis. This change may also result in difficulty breathing or digestive abnormalities, such as constipation or an early feeling of fullness while eating.
Other fractures — Hip fractures are relatively common in patients with osteoporosis, affecting 15 percent of women and 5 percent of men by age 80. Such fractures are a major cause of disability in the elderly and increase the risk of death, although conditions other than the fracture (such as surgical complications) may be responsible for this increase.
Osteoporosis may also lead to fractures near the wrist in the lower end of the radius (the bone on the thumb side of the forearm), causing backward displacement of the wrist and hand. This type of break is known as a Colles' fracture, and often results when the hand is outstretched to stop a fall.
CAUSES — As mentioned above, osteoporosis results from either accelerated bone loss or inadequate bone formation. The imbalance between the rate of new bone formation and breakdown may occur due to several underlying conditions, including the following:
Menopause-related loss of estrogen — Estrogen is a hormone that plays an important role in regulating bone formation. The rate of bone loss increases soon after the menopause, particularly in trabecular bone; this increased rate of loss lasts for approximately 10 years. At this point, the rate of bone loss slows to near the premenopausal rate, but the premenopausal rate of bone formation is absent.
Hyperthyroidism — Hyperthyroidism is a condition in which the thyroid gland is overactive in its production of thyroid hormones. It is associated with increased bone turnover, potentially leading to bone loss. (See "Patient information: Hyperthyroidism").
Hyperparathyroidism — Hyperparathyroidism refers to overactivity of the parathyroid glands. These glands produce parathyroid hormone, which helps to regulate calcium concentrations in the body. Increased secretion of parathyroid hormone increases the removal of calcium from bone, raising blood calcium levels (hypercalcemia) and potentially leading to osteoporosis. (See "Patient information: Primary hyperparathyroidism").
Age-related bone loss — This may result from decreased calcium absorption, which typically begins in the fourth or fifth decade of life. It is associated with a slow loss of cortical and trabecular bone in both women and men.
Hypogonadism — Hypogonadism is a decrease in activity of the ovaries or testes resulting in low amounts of estrogen or testosterone, respectively. This may be a result of aging, but it can also occur in younger men and women due to medications that cause hypogonadism (eg, chemotherapy agents), block estrogen synthesis (aromatase inhibitors), or induce testosterone/estrogen deficiency (GnRH agonists). It may also occur as a result of low body weight, excessive exercise, or pituitary abnormalities.
Men who have low or absent levels of the hormone testosterone are at increased risk of osteoporosis, and women who have a low level of estrogen are also at risk. Symptoms of hypogonadism in men include a decreased sexual drive (libido) or impotence. In young women, signs of hypogonadism include loss of menstrual periods, which may or may not be associated with hot flashes, night sweats, or vaginal dryness.
Medications — Prolonged therapy with certain medications, including glucocorticoids (also called corticosteroids), heparin, certain medications for seizure disorders (eg, phenytoin, carbamazepine, primidone, and phenobarbital), cyclosporine, medroxyprogesterone acetate and vitamin A may result in accelerated bone resorption as well as slowed bone formation, leading to bone loss.
Pregnancy and breastfeeding — Bone loss occurs during pregnancy and breastfeeding, although the loss is temporary and has no long term effect on a woman's bone density. In women who become pregnant and breastfeed, there is no increased risk of fracture after menopause. Using a calcium supplement while breastfeeding has no effect on the amount of bone lost.
Vitamin B12 deficiency — Vitamin B12 deficiency (also known as pernicious anemia) appears to increase the risk of osteoporosis, which can lead to an increased risk of hip and spine fractures.
RISK FACTORS FOR FRACTURE — Several factors are associated with an increased risk of osteoporotic fractures, including the following:
Age — In people aged 90 years or more, approximately one-third of women and 15 percent of men will have a hip fracture.
Sex — Osteoporosis is a serious problem in men, although women are affected more commonly. Women have a lower average peak bone mass and lose more bone after menopause. About 30 percent of women over age 50 have osteoporosis, and this percentage increases with age.
Race — Whites have a considerably higher risk of hip fractures than blacks. Blacks generally have a higher peak bone mass and a lower rate of bone loss after menopause.
Falls — Repeated falling can be a significant problem for older people with osteoporosis. Over 90 percent of hip fractures occur after a fall. Certain factors contribute to the risk of falls, including poor vision, certain medications (eg, tranquilizers, some anxiety medications, sleeping pills), and neurologic disorders such as dementia (confusion).
Other factors — A number of other factors increase the risk of fractures, some of which include the following: Previous fracture between the ages of 20 and 50 years History of fracture in a first degree relative Cigarette smoking (men and women) Inflammatory bowel disease Celiac disease Cystic fibrosis Sedentary life style Drinking large amounts of caffeine Medications for anxiety or seizures Low body weight or weight loss Above average height Type 1 or 2 diabetes mellitus
DIAGNOSIS — Osteoporosis is diagnosed based upon the patient and family history, physical examination, laboratory studies, and bone mineral density (BMD) testing. It is important to exclude other conditions that can cause bone thinning (osteopenia), such as osteomalacia (softening and weakening of bone) as well as other potentially treatable conditions (eg, hyperparathyroidism, hyperthyroidism, kidney disease).
History and physical examination — During a medical history, a healthcare provider will ask about life events (pregnancies, age at first menstrual period and menopause), past or present medical conditions, medications, calcium intake, exercise, and alcohol/tobacco use.
The physical examination will include measurement of height and weight and may include laboratory tests. Such studies may include a complete blood count, measurement of calcium, phosphorus, vitamin D, bicarbonate, creatinine, and hormones such as thyroid-stimulating hormone (TSH). The testosterone level may be measured in men, particularly if the man has decreased libido or impotence. (See "Patient information: Sexual problems in men").
Bone density measurement — Measurement of bone mineral density is the most common method to determine if a person is at risk for or already has osteoporosis. The goal is to recognize people who are at risk before a fracture occurs. Several methods are available to measure bone density.
Dual x-ray absorptiometry (DXA) — DXA testing is the most popular method for measuring BMD because it provides precise measurements at important bone sites (eg, spine, hip, forearm) with minimal radiation.
During DXA, the patient lies on an examination table. An x-ray detector scans a bone region, and the amount of x-rays that pass through bone are measured and displayed as an image that is interpreted by a radiologist. The test causes no discomfort, and usually takes only 5 to 10 minutes. The bone mineral density is then compared with the normal range for the patient's sex and race.
Other Quantitative computerized tomography — This is a type of CT that provides accurate measures of bone density in the spine. Although this test may be a good alternative to DXA, it is seldom used because it is expensive, less precise for following measurements over time, and requires a higher radiation dose. Ultrasonography — Ultrasound can be used to measure the bone density of the heel. This may be useful to determine a person's fracture risk. However, it is used less frequently than DXA because there are no guidelines that use ultrasound measurements to diagnose osteoporosis or predict fracture risk. In areas that do not have access to DXA, ultrasound is an acceptable way to measure bone density.
We recommend DXA of the hip and spine because measurements at these sites are effective for predicting osteoporotic fracture at any site.
Interpreting BMD results — The World Health Organization (WHO) has defined normal bone density as a value within one standard deviation (SD) from average peak bone mass. Standard deviation is a statistical measure that defines how much a patient's result vary from the "average" young adult. Normal bone density — Bone density that is between 0 and 1 standard deviation below the mean is considered to be normal. This may be reported as a T-score of 0 to -1. Treatment is not usually recommended for people with normal bone density, although preventive measures (eg, calcium supplementation, weight-bearing exercise) are recommended to prevent osteopenia and osteoporosis. (See "Patient information: Osteoporosis prevention and treatment"). Osteopenia — Bone density that is between 1 and 2.5 standard deviations below the mean is called osteopenia. This may be reported as a T-score of -1 to -2.4. A person with osteopenia does not yet have osteoporosis, but is at risk to develop it if not treated. Osteoporosis — Osteoporosis is defined as BMD more than 2.5 standard deviations (SD) below the mean of normal young women. This is reported as a T-score of -2.5 or less. The lower the bone density, the greater the risk of fracture.
When to measure BMD — Bone density testing can be used to diagnose osteoporosis, as well as to screen for it. The National Osteoporosis Foundation has issued recommendations for bone density testing that primarily apply to white women after menopause. Bone density should be measured in women: Greater than 65 years of age Under age 65 who have one or more risk factors for osteoporotic fracture in addition to menopause.
In addition to the recommendations above, the International Society for Clinical Densitometry (ISCD) recommends bone density testing for men over 70 years of age and for adults (including premenopausal women): With fragility fracture (a bone fracture that occurs after a fall from standing height or less) With disease associated with low bone mass (Cushing's syndrome, hyperthyroidism, hyperparathyroidism, rheumatoid arthritis, gastrointestinal diseases associated with malabsorption) Taking drugs associated with low bone mass (glucocorticoids, GnRH agonists, some chemotherapy drugs)
PREVENTION AND TREATMENT — All women should be educated about the risk factors for osteoporotic fractures. A provider may recommend certain lifestyle changes that can help to reduce fracture risk, such as stopping smoking, limiting alcohol consumption, and participating in regular weight-bearing and muscle-strengthening exercises. A full discussion of osteoporosis prevention and treatment is available separately. (See "Patient information: Osteoporosis prevention and treatment").
WHERE TO GET MORE INFORMATION — Your healthcare provider is the best source of information for questions and concerns related to your medical problem. Because no two patients are exactly alike and recommendations can vary from one person to another, it is important to seek guidance from a provider who is familiar with your individual situation.
This discussion will be updated as needed every four months on our web site (www.patients.uptodate.com). Additional topics as well as selected discussions written for healthcare professionals are also available for those who would like more detailed information.
A number of web sites have information about medical problems and treatments, although it can be difficult to know which sites are reputable. Information provided by the National Institutes of Health, national medical societies and some other well-established organizations are often reliable sources of information, although the frequency with which they are updated is variable. National Library of Medicine
(www.nlm.nih.gov/medlineplus/healthtopics.html)
Osteoporosis and Related Bone Diseases National Resource Center (ORBD-NRC)
Toll-free: (800) 624-BONE (2663)
TTY: (202) 466-4315
(www.osteo.org)
National Osteoporosis Foundation
Phone: (202) 223-2226
(www.nof.org)
International Society for Clinical Densitometry (ISCD)
(www.ISCD.org)
National Women's Health Resource Center (NWHRC)
Toll-free: (877) 986-9472
(www.healthywomen.org)
Osteoporosis Society of Canada
Phone: (416) 696-2663 x 294
(www.osteoporosis.ca/)
The Hormone Foundation
(www.hormone.org/public/osteoporosis.cfm, available in English, Spanish, French, Italian, German, and Portuguese)
[1-4]
Use of UpToDate is subject to the Subscription and License Agreement. REFERENCES 1. Johnell, O, Kanis, JA, Black, DM, et al. Associations between baseline risk factors and vertebral fracture risk in the Multiple Outcomes of Raloxifene Evaluation (MORE) Study. J Bone Miner Res 2004; 19:764.
2. Raisz, LG. Clinical practice. Screening for osteoporosis. N Engl J Med 2005; 353:164.
3. Marshall, D, Johnell, O, Wedel, H. Meta-analysis of how well measures of bone mineral density predict occurrence of osteoporotic fractures. BMJ 1996; 312:1254.
4. Bainbridge, KE, Sowers, MF, Crutchfield, M, et al. Natural history of bone loss over 6 years among premenopausal and early postmenopausal women. Am J Epidemiol 2002; 156:410.
Osteoporosis causes, diagnosis, and screening
INTRODUCTION — Osteoporosis is characterized by a progressive decrease in bone density, causing bones to become brittle, weakened, and fracture easily. Osteoporosis and the fractures that result are a major public health concern; more than 1.3 million osteoporotic fractures occur annually in the United States. Early diagnosis of bone loss can reduce or eliminate the risk of fractures.
This topic review discusses the causes, risk factors, signs, and symptoms of osteoporosis, as well as the ways that it can be diagnosed. For information about ways to prevent and treat osteoporosis, see "Patient information: Osteoporosis prevention and treatment".
BONE METABOLISM — To maintain bone density and strength, the body needs a sufficient supply of calcium and phosphorus, normal production of hormones that help to regulate bone cell function (eg, the calcium-regulating hormones, parathyroid hormone, calcitriol, and calcitonin; thyroid hormone; glucocorticoids; the sex hormones estrogen and testosterone), and an adequate supply of vitamin D, which is essential for normal bone formation and calcium absorption.
Bone is constantly being turned over and replaced as a result of cells that break down and remove bone (osteoclasts) and cells that replace and rebuild bone (osteoblasts). The resorption and formation of bone are essential to repair tiny breaks (microfractures) and to "remodel" bone (ie, remove and replace bone) in response to stress, including injury.
Osteoporosis is the result of years of bone loss, due to a "mismatch" between bone formation and resorption. Osteoporosis may also be related to years of inadequate bone formation, especially during the teens and 20s, which are the most important years of bone building. When bone becomes abnormally thin (known as osteopenia) and porous, the risk of fracture increases. Osteopenia is
Cortical bone, the normally dense, compact bone that forms the outer part of skeletal structures, provides strength and protection. Trabecular bone is found inside the long bones, particularly at the ends, and helps to provide mechanical support, particularly within the vertebrae. In patients with osteoporosis, both cortical and trabecular bone may be affected (show figure 1).
The processes of bone resorption and formation vary with age. Although 95 to 100 percent of expected peak bone mass develops by the late teen years, the body continues to form more bone than it breaks down until approximately 30 years of age. Maximum bone density is attained between 20 years (hip) and 30 years of age (spine and forearm). Thereafter, bone mass is slowly lost in the spine and hip; the loss occurs more rapidly during perimenopause.
SIGNS AND SYMPTOMS — Osteoporosis usually causes no symptoms until a fracture occurs, but it can cause back pain or loss of height.
Vertebral fractures — Vertebrae are the bones that make up the spine, and vertebral fractures are the most common sign of osteoporosis. About two-thirds of these fractures occur without symptoms. In these cases, the fracture is found during a chest or abdominal x-ray done for other reasons. In some patients, vertebral fractures may lead to a sudden onset of back pain, usually when performing routine activities, such as bending or lifting. This pain usually resolves over several weeks and is replaced by a chronic dull ache or pain. However, the pain may sometimes persist for many months. Successive compression or crush fractures, in which there is collapse of affected bone, may lead to increased curvature of the spine (thoracic kyphosis). As a result, there is typically an abnormal rounding of the upper back, known as a "dowager's hump," and loss of height (show figure 2). Due to vertebral fractures and associated height loss, the abdomen may be compressed, causing it to bulge forward. Such patients may note that their abdomens appear larger than before, their clothes no longer fit, and their waists seem to have "disappeared" even though they have not gained weight. Patients with multiple vertebral compression fractures may also have hip discomfort. The pain may be due to a decrease in the distance between the bottom of the rib cage and the uppermost portion of the pelvis. This change may also result in difficulty breathing or digestive abnormalities, such as constipation or an early feeling of fullness while eating.
Other fractures — Hip fractures are relatively common in patients with osteoporosis, affecting 15 percent of women and 5 percent of men by age 80. Such fractures are a major cause of disability in the elderly and increase the risk of death, although conditions other than the fracture (such as surgical complications) may be responsible for this increase.
Osteoporosis may also lead to fractures near the wrist in the lower end of the radius (the bone on the thumb side of the forearm), causing backward displacement of the wrist and hand. This type of break is known as a Colles' fracture, and often results when the hand is outstretched to stop a fall.
CAUSES — As mentioned above, osteoporosis results from either accelerated bone loss or inadequate bone formation. The imbalance between the rate of new bone formation and breakdown may occur due to several underlying conditions, including the following:
Menopause-related loss of estrogen — Estrogen is a hormone that plays an important role in regulating bone formation. The rate of bone loss increases soon after the menopause, particularly in trabecular bone; this increased rate of loss lasts for approximately 10 years. At this point, the rate of bone loss slows to near the premenopausal rate, but the premenopausal rate of bone formation is absent.
Hyperthyroidism — Hyperthyroidism is a condition in which the thyroid gland is overactive in its production of thyroid hormones. It is associated with increased bone turnover, potentially leading to bone loss. (See "Patient information: Hyperthyroidism").
Hyperparathyroidism — Hyperparathyroidism refers to overactivity of the parathyroid glands. These glands produce parathyroid hormone, which helps to regulate calcium concentrations in the body. Increased secretion of parathyroid hormone increases the removal of calcium from bone, raising blood calcium levels (hypercalcemia) and potentially leading to osteoporosis. (See "Patient information: Primary hyperparathyroidism").
Age-related bone loss — This may result from decreased calcium absorption, which typically begins in the fourth or fifth decade of life. It is associated with a slow loss of cortical and trabecular bone in both women and men.
Hypogonadism — Hypogonadism is a decrease in activity of the ovaries or testes resulting in low amounts of estrogen or testosterone, respectively. This may be a result of aging, but it can also occur in younger men and women due to medications that cause hypogonadism (eg, chemotherapy agents), block estrogen synthesis (aromatase inhibitors), or induce testosterone/estrogen deficiency (GnRH agonists). It may also occur as a result of low body weight, excessive exercise, or pituitary abnormalities.
Men who have low or absent levels of the hormone testosterone are at increased risk of osteoporosis, and women who have a low level of estrogen are also at risk. Symptoms of hypogonadism in men include a decreased sexual drive (libido) or impotence. In young women, signs of hypogonadism include loss of menstrual periods, which may or may not be associated with hot flashes, night sweats, or vaginal dryness.
Medications — Prolonged therapy with certain medications, including glucocorticoids (also called corticosteroids), heparin, certain medications for seizure disorders (eg, phenytoin, carbamazepine, primidone, and phenobarbital), cyclosporine, medroxyprogesterone acetate and vitamin A may result in accelerated bone resorption as well as slowed bone formation, leading to bone loss.
Pregnancy and breastfeeding — Bone loss occurs during pregnancy and breastfeeding, although the loss is temporary and has no long term effect on a woman's bone density. In women who become pregnant and breastfeed, there is no increased risk of fracture after menopause. Using a calcium supplement while breastfeeding has no effect on the amount of bone lost.
Vitamin B12 deficiency — Vitamin B12 deficiency (also known as pernicious anemia) appears to increase the risk of osteoporosis, which can lead to an increased risk of hip and spine fractures.
RISK FACTORS FOR FRACTURE — Several factors are associated with an increased risk of osteoporotic fractures, including the following:
Age — In people aged 90 years or more, approximately one-third of women and 15 percent of men will have a hip fracture.
Sex — Osteoporosis is a serious problem in men, although women are affected more commonly. Women have a lower average peak bone mass and lose more bone after menopause. About 30 percent of women over age 50 have osteoporosis, and this percentage increases with age.
Race — Whites have a considerably higher risk of hip fractures than blacks. Blacks generally have a higher peak bone mass and a lower rate of bone loss after menopause.
Falls — Repeated falling can be a significant problem for older people with osteoporosis. Over 90 percent of hip fractures occur after a fall. Certain factors contribute to the risk of falls, including poor vision, certain medications (eg, tranquilizers, some anxiety medications, sleeping pills), and neurologic disorders such as dementia (confusion).
Other factors — A number of other factors increase the risk of fractures, some of which include the following: Previous fracture between the ages of 20 and 50 years History of fracture in a first degree relative Cigarette smoking (men and women) Inflammatory bowel disease Celiac disease Cystic fibrosis Sedentary life style Drinking large amounts of caffeine Medications for anxiety or seizures Low body weight or weight loss Above average height Type 1 or 2 diabetes mellitus
DIAGNOSIS — Osteoporosis is diagnosed based upon the patient and family history, physical examination, laboratory studies, and bone mineral density (BMD) testing. It is important to exclude other conditions that can cause bone thinning (osteopenia), such as osteomalacia (softening and weakening of bone) as well as other potentially treatable conditions (eg, hyperparathyroidism, hyperthyroidism, kidney disease).
History and physical examination — During a medical history, a healthcare provider will ask about life events (pregnancies, age at first menstrual period and menopause), past or present medical conditions, medications, calcium intake, exercise, and alcohol/tobacco use.
The physical examination will include measurement of height and weight and may include laboratory tests. Such studies may include a complete blood count, measurement of calcium, phosphorus, vitamin D, bicarbonate, creatinine, and hormones such as thyroid-stimulating hormone (TSH). The testosterone level may be measured in men, particularly if the man has decreased libido or impotence. (See "Patient information: Sexual problems in men").
Bone density measurement — Measurement of bone mineral density is the most common method to determine if a person is at risk for or already has osteoporosis. The goal is to recognize people who are at risk before a fracture occurs. Several methods are available to measure bone density.
Dual x-ray absorptiometry (DXA) — DXA testing is the most popular method for measuring BMD because it provides precise measurements at important bone sites (eg, spine, hip, forearm) with minimal radiation.
During DXA, the patient lies on an examination table. An x-ray detector scans a bone region, and the amount of x-rays that pass through bone are measured and displayed as an image that is interpreted by a radiologist. The test causes no discomfort, and usually takes only 5 to 10 minutes. The bone mineral density is then compared with the normal range for the patient's sex and race.
Other Quantitative computerized tomography — This is a type of CT that provides accurate measures of bone density in the spine. Although this test may be a good alternative to DXA, it is seldom used because it is expensive, less precise for following measurements over time, and requires a higher radiation dose. Ultrasonography — Ultrasound can be used to measure the bone density of the heel. This may be useful to determine a person's fracture risk. However, it is used less frequently than DXA because there are no guidelines that use ultrasound measurements to diagnose osteoporosis or predict fracture risk. In areas that do not have access to DXA, ultrasound is an acceptable way to measure bone density.
We recommend DXA of the hip and spine because measurements at these sites are effective for predicting osteoporotic fracture at any site.
Interpreting BMD results — The World Health Organization (WHO) has defined normal bone density as a value within one standard deviation (SD) from average peak bone mass. Standard deviation is a statistical measure that defines how much a patient's result vary from the "average" young adult. Normal bone density — Bone density that is between 0 and 1 standard deviation below the mean is considered to be normal. This may be reported as a T-score of 0 to -1. Treatment is not usually recommended for people with normal bone density, although preventive measures (eg, calcium supplementation, weight-bearing exercise) are recommended to prevent osteopenia and osteoporosis. (See "Patient information: Osteoporosis prevention and treatment"). Osteopenia — Bone density that is between 1 and 2.5 standard deviations below the mean is called osteopenia. This may be reported as a T-score of -1 to -2.4. A person with osteopenia does not yet have osteoporosis, but is at risk to develop it if not treated. Osteoporosis — Osteoporosis is defined as BMD more than 2.5 standard deviations (SD) below the mean of normal young women. This is reported as a T-score of -2.5 or less. The lower the bone density, the greater the risk of fracture.
When to measure BMD — Bone density testing can be used to diagnose osteoporosis, as well as to screen for it. The National Osteoporosis Foundation has issued recommendations for bone density testing that primarily apply to white women after menopause. Bone density should be measured in women: Greater than 65 years of age Under age 65 who have one or more risk factors for osteoporotic fracture in addition to menopause.
In addition to the recommendations above, the International Society for Clinical Densitometry (ISCD) recommends bone density testing for men over 70 years of age and for adults (including premenopausal women): With fragility fracture (a bone fracture that occurs after a fall from standing height or less) With disease associated with low bone mass (Cushing's syndrome, hyperthyroidism, hyperparathyroidism, rheumatoid arthritis, gastrointestinal diseases associated with malabsorption) Taking drugs associated with low bone mass (glucocorticoids, GnRH agonists, some chemotherapy drugs)
PREVENTION AND TREATMENT — All women should be educated about the risk factors for osteoporotic fractures. A provider may recommend certain lifestyle changes that can help to reduce fracture risk, such as stopping smoking, limiting alcohol consumption, and participating in regular weight-bearing and muscle-strengthening exercises. A full discussion of osteoporosis prevention and treatment is available separately. (See "Patient information: Osteoporosis prevention and treatment").
WHERE TO GET MORE INFORMATION — Your healthcare provider is the best source of information for questions and concerns related to your medical problem. Because no two patients are exactly alike and recommendations can vary from one person to another, it is important to seek guidance from a provider who is familiar with your individual situation.
This discussion will be updated as needed every four months on our web site (www.patients.uptodate.com). Additional topics as well as selected discussions written for healthcare professionals are also available for those who would like more detailed information.
A number of web sites have information about medical problems and treatments, although it can be difficult to know which sites are reputable. Information provided by the National Institutes of Health, national medical societies and some other well-established organizations are often reliable sources of information, although the frequency with which they are updated is variable. National Library of Medicine
(www.nlm.nih.gov/medlineplus/healthtopics.html)
Osteoporosis and Related Bone Diseases National Resource Center (ORBD-NRC)
Toll-free: (800) 624-BONE (2663)
TTY: (202) 466-4315
(www.osteo.org)
National Osteoporosis Foundation
Phone: (202) 223-2226
(www.nof.org)
International Society for Clinical Densitometry (ISCD)
(www.ISCD.org)
National Women's Health Resource Center (NWHRC)
Toll-free: (877) 986-9472
(www.healthywomen.org)
Osteoporosis Society of Canada
Phone: (416) 696-2663 x 294
(www.osteoporosis.ca/)
The Hormone Foundation
(www.hormone.org/public/osteoporosis.cfm, available in English, Spanish, French, Italian, German, and Portuguese)
[1-4]
Use of UpToDate is subject to the Subscription and License Agreement. REFERENCES 1. Johnell, O, Kanis, JA, Black, DM, et al. Associations between baseline risk factors and vertebral fracture risk in the Multiple Outcomes of Raloxifene Evaluation (MORE) Study. J Bone Miner Res 2004; 19:764.
2. Raisz, LG. Clinical practice. Screening for osteoporosis. N Engl J Med 2005; 353:164.
3. Marshall, D, Johnell, O, Wedel, H. Meta-analysis of how well measures of bone mineral density predict occurrence of osteoporotic fractures. BMJ 1996; 312:1254.
4. Bainbridge, KE, Sowers, MF, Crutchfield, M, et al. Natural history of bone loss over 6 years among premenopausal and early postmenopausal women. Am J Epidemiol 2002; 156:410.
This topic review discusses the causes, risk factors, signs, and symptoms of osteoporosis, as well as the ways that it can be diagnosed. For information about ways to prevent and treat osteoporosis, see "Patient information: Osteoporosis prevention and treatment".
BONE METABOLISM — To maintain bone density and strength, the body needs a sufficient supply of calcium and phosphorus, normal production of hormones that help to regulate bone cell function (eg, the calcium-regulating hormones, parathyroid hormone, calcitriol, and calcitonin; thyroid hormone; glucocorticoids; the sex hormones estrogen and testosterone), and an adequate supply of vitamin D, which is essential for normal bone formation and calcium absorption.
Bone is constantly being turned over and replaced as a result of cells that break down and remove bone (osteoclasts) and cells that replace and rebuild bone (osteoblasts). The resorption and formation of bone are essential to repair tiny breaks (microfractures) and to "remodel" bone (ie, remove and replace bone) in response to stress, including injury.
Osteoporosis is the result of years of bone loss, due to a "mismatch" between bone formation and resorption. Osteoporosis may also be related to years of inadequate bone formation, especially during the teens and 20s, which are the most important years of bone building. When bone becomes abnormally thin (known as osteopenia) and porous, the risk of fracture increases. Osteopenia is
Cortical bone, the normally dense, compact bone that forms the outer part of skeletal structures, provides strength and protection. Trabecular bone is found inside the long bones, particularly at the ends, and helps to provide mechanical support, particularly within the vertebrae. In patients with osteoporosis, both cortical and trabecular bone may be affected (show figure 1).
The processes of bone resorption and formation vary with age. Although 95 to 100 percent of expected peak bone mass develops by the late teen years, the body continues to form more bone than it breaks down until approximately 30 years of age. Maximum bone density is attained between 20 years (hip) and 30 years of age (spine and forearm). Thereafter, bone mass is slowly lost in the spine and hip; the loss occurs more rapidly during perimenopause.
SIGNS AND SYMPTOMS — Osteoporosis usually causes no symptoms until a fracture occurs, but it can cause back pain or loss of height.
Vertebral fractures — Vertebrae are the bones that make up the spine, and vertebral fractures are the most common sign of osteoporosis. About two-thirds of these fractures occur without symptoms. In these cases, the fracture is found during a chest or abdominal x-ray done for other reasons. In some patients, vertebral fractures may lead to a sudden onset of back pain, usually when performing routine activities, such as bending or lifting. This pain usually resolves over several weeks and is replaced by a chronic dull ache or pain. However, the pain may sometimes persist for many months. Successive compression or crush fractures, in which there is collapse of affected bone, may lead to increased curvature of the spine (thoracic kyphosis). As a result, there is typically an abnormal rounding of the upper back, known as a "dowager's hump," and loss of height (show figure 2). Due to vertebral fractures and associated height loss, the abdomen may be compressed, causing it to bulge forward. Such patients may note that their abdomens appear larger than before, their clothes no longer fit, and their waists seem to have "disappeared" even though they have not gained weight. Patients with multiple vertebral compression fractures may also have hip discomfort. The pain may be due to a decrease in the distance between the bottom of the rib cage and the uppermost portion of the pelvis. This change may also result in difficulty breathing or digestive abnormalities, such as constipation or an early feeling of fullness while eating.
Other fractures — Hip fractures are relatively common in patients with osteoporosis, affecting 15 percent of women and 5 percent of men by age 80. Such fractures are a major cause of disability in the elderly and increase the risk of death, although conditions other than the fracture (such as surgical complications) may be responsible for this increase.
Osteoporosis may also lead to fractures near the wrist in the lower end of the radius (the bone on the thumb side of the forearm), causing backward displacement of the wrist and hand. This type of break is known as a Colles' fracture, and often results when the hand is outstretched to stop a fall.
CAUSES — As mentioned above, osteoporosis results from either accelerated bone loss or inadequate bone formation. The imbalance between the rate of new bone formation and breakdown may occur due to several underlying conditions, including the following:
Menopause-related loss of estrogen — Estrogen is a hormone that plays an important role in regulating bone formation. The rate of bone loss increases soon after the menopause, particularly in trabecular bone; this increased rate of loss lasts for approximately 10 years. At this point, the rate of bone loss slows to near the premenopausal rate, but the premenopausal rate of bone formation is absent.
Hyperthyroidism — Hyperthyroidism is a condition in which the thyroid gland is overactive in its production of thyroid hormones. It is associated with increased bone turnover, potentially leading to bone loss. (See "Patient information: Hyperthyroidism").
Hyperparathyroidism — Hyperparathyroidism refers to overactivity of the parathyroid glands. These glands produce parathyroid hormone, which helps to regulate calcium concentrations in the body. Increased secretion of parathyroid hormone increases the removal of calcium from bone, raising blood calcium levels (hypercalcemia) and potentially leading to osteoporosis. (See "Patient information: Primary hyperparathyroidism").
Age-related bone loss — This may result from decreased calcium absorption, which typically begins in the fourth or fifth decade of life. It is associated with a slow loss of cortical and trabecular bone in both women and men.
Hypogonadism — Hypogonadism is a decrease in activity of the ovaries or testes resulting in low amounts of estrogen or testosterone, respectively. This may be a result of aging, but it can also occur in younger men and women due to medications that cause hypogonadism (eg, chemotherapy agents), block estrogen synthesis (aromatase inhibitors), or induce testosterone/estrogen deficiency (GnRH agonists). It may also occur as a result of low body weight, excessive exercise, or pituitary abnormalities.
Men who have low or absent levels of the hormone testosterone are at increased risk of osteoporosis, and women who have a low level of estrogen are also at risk. Symptoms of hypogonadism in men include a decreased sexual drive (libido) or impotence. In young women, signs of hypogonadism include loss of menstrual periods, which may or may not be associated with hot flashes, night sweats, or vaginal dryness.
Medications — Prolonged therapy with certain medications, including glucocorticoids (also called corticosteroids), heparin, certain medications for seizure disorders (eg, phenytoin, carbamazepine, primidone, and phenobarbital), cyclosporine, medroxyprogesterone acetate and vitamin A may result in accelerated bone resorption as well as slowed bone formation, leading to bone loss.
Pregnancy and breastfeeding — Bone loss occurs during pregnancy and breastfeeding, although the loss is temporary and has no long term effect on a woman's bone density. In women who become pregnant and breastfeed, there is no increased risk of fracture after menopause. Using a calcium supplement while breastfeeding has no effect on the amount of bone lost.
Vitamin B12 deficiency — Vitamin B12 deficiency (also known as pernicious anemia) appears to increase the risk of osteoporosis, which can lead to an increased risk of hip and spine fractures.
RISK FACTORS FOR FRACTURE — Several factors are associated with an increased risk of osteoporotic fractures, including the following:
Age — In people aged 90 years or more, approximately one-third of women and 15 percent of men will have a hip fracture.
Sex — Osteoporosis is a serious problem in men, although women are affected more commonly. Women have a lower average peak bone mass and lose more bone after menopause. About 30 percent of women over age 50 have osteoporosis, and this percentage increases with age.
Race — Whites have a considerably higher risk of hip fractures than blacks. Blacks generally have a higher peak bone mass and a lower rate of bone loss after menopause.
Falls — Repeated falling can be a significant problem for older people with osteoporosis. Over 90 percent of hip fractures occur after a fall. Certain factors contribute to the risk of falls, including poor vision, certain medications (eg, tranquilizers, some anxiety medications, sleeping pills), and neurologic disorders such as dementia (confusion).
Other factors — A number of other factors increase the risk of fractures, some of which include the following: Previous fracture between the ages of 20 and 50 years History of fracture in a first degree relative Cigarette smoking (men and women) Inflammatory bowel disease Celiac disease Cystic fibrosis Sedentary life style Drinking large amounts of caffeine Medications for anxiety or seizures Low body weight or weight loss Above average height Type 1 or 2 diabetes mellitus
DIAGNOSIS — Osteoporosis is diagnosed based upon the patient and family history, physical examination, laboratory studies, and bone mineral density (BMD) testing. It is important to exclude other conditions that can cause bone thinning (osteopenia), such as osteomalacia (softening and weakening of bone) as well as other potentially treatable conditions (eg, hyperparathyroidism, hyperthyroidism, kidney disease).
History and physical examination — During a medical history, a healthcare provider will ask about life events (pregnancies, age at first menstrual period and menopause), past or present medical conditions, medications, calcium intake, exercise, and alcohol/tobacco use.
The physical examination will include measurement of height and weight and may include laboratory tests. Such studies may include a complete blood count, measurement of calcium, phosphorus, vitamin D, bicarbonate, creatinine, and hormones such as thyroid-stimulating hormone (TSH). The testosterone level may be measured in men, particularly if the man has decreased libido or impotence. (See "Patient information: Sexual problems in men").
Bone density measurement — Measurement of bone mineral density is the most common method to determine if a person is at risk for or already has osteoporosis. The goal is to recognize people who are at risk before a fracture occurs. Several methods are available to measure bone density.
Dual x-ray absorptiometry (DXA) — DXA testing is the most popular method for measuring BMD because it provides precise measurements at important bone sites (eg, spine, hip, forearm) with minimal radiation.
During DXA, the patient lies on an examination table. An x-ray detector scans a bone region, and the amount of x-rays that pass through bone are measured and displayed as an image that is interpreted by a radiologist. The test causes no discomfort, and usually takes only 5 to 10 minutes. The bone mineral density is then compared with the normal range for the patient's sex and race.
Other Quantitative computerized tomography — This is a type of CT that provides accurate measures of bone density in the spine. Although this test may be a good alternative to DXA, it is seldom used because it is expensive, less precise for following measurements over time, and requires a higher radiation dose. Ultrasonography — Ultrasound can be used to measure the bone density of the heel. This may be useful to determine a person's fracture risk. However, it is used less frequently than DXA because there are no guidelines that use ultrasound measurements to diagnose osteoporosis or predict fracture risk. In areas that do not have access to DXA, ultrasound is an acceptable way to measure bone density.
We recommend DXA of the hip and spine because measurements at these sites are effective for predicting osteoporotic fracture at any site.
Interpreting BMD results — The World Health Organization (WHO) has defined normal bone density as a value within one standard deviation (SD) from average peak bone mass. Standard deviation is a statistical measure that defines how much a patient's result vary from the "average" young adult. Normal bone density — Bone density that is between 0 and 1 standard deviation below the mean is considered to be normal. This may be reported as a T-score of 0 to -1. Treatment is not usually recommended for people with normal bone density, although preventive measures (eg, calcium supplementation, weight-bearing exercise) are recommended to prevent osteopenia and osteoporosis. (See "Patient information: Osteoporosis prevention and treatment"). Osteopenia — Bone density that is between 1 and 2.5 standard deviations below the mean is called osteopenia. This may be reported as a T-score of -1 to -2.4. A person with osteopenia does not yet have osteoporosis, but is at risk to develop it if not treated. Osteoporosis — Osteoporosis is defined as BMD more than 2.5 standard deviations (SD) below the mean of normal young women. This is reported as a T-score of -2.5 or less. The lower the bone density, the greater the risk of fracture.
When to measure BMD — Bone density testing can be used to diagnose osteoporosis, as well as to screen for it. The National Osteoporosis Foundation has issued recommendations for bone density testing that primarily apply to white women after menopause. Bone density should be measured in women: Greater than 65 years of age Under age 65 who have one or more risk factors for osteoporotic fracture in addition to menopause.
In addition to the recommendations above, the International Society for Clinical Densitometry (ISCD) recommends bone density testing for men over 70 years of age and for adults (including premenopausal women): With fragility fracture (a bone fracture that occurs after a fall from standing height or less) With disease associated with low bone mass (Cushing's syndrome, hyperthyroidism, hyperparathyroidism, rheumatoid arthritis, gastrointestinal diseases associated with malabsorption) Taking drugs associated with low bone mass (glucocorticoids, GnRH agonists, some chemotherapy drugs)
PREVENTION AND TREATMENT — All women should be educated about the risk factors for osteoporotic fractures. A provider may recommend certain lifestyle changes that can help to reduce fracture risk, such as stopping smoking, limiting alcohol consumption, and participating in regular weight-bearing and muscle-strengthening exercises. A full discussion of osteoporosis prevention and treatment is available separately. (See "Patient information: Osteoporosis prevention and treatment").
WHERE TO GET MORE INFORMATION — Your healthcare provider is the best source of information for questions and concerns related to your medical problem. Because no two patients are exactly alike and recommendations can vary from one person to another, it is important to seek guidance from a provider who is familiar with your individual situation.
This discussion will be updated as needed every four months on our web site (www.patients.uptodate.com). Additional topics as well as selected discussions written for healthcare professionals are also available for those who would like more detailed information.
A number of web sites have information about medical problems and treatments, although it can be difficult to know which sites are reputable. Information provided by the National Institutes of Health, national medical societies and some other well-established organizations are often reliable sources of information, although the frequency with which they are updated is variable. National Library of Medicine
(www.nlm.nih.gov/medlineplus/healthtopics.html)
Osteoporosis and Related Bone Diseases National Resource Center (ORBD-NRC)
Toll-free: (800) 624-BONE (2663)
TTY: (202) 466-4315
(www.osteo.org)
National Osteoporosis Foundation
Phone: (202) 223-2226
(www.nof.org)
International Society for Clinical Densitometry (ISCD)
(www.ISCD.org)
National Women's Health Resource Center (NWHRC)
Toll-free: (877) 986-9472
(www.healthywomen.org)
Osteoporosis Society of Canada
Phone: (416) 696-2663 x 294
(www.osteoporosis.ca/)
The Hormone Foundation
(www.hormone.org/public/osteoporosis.cfm, available in English, Spanish, French, Italian, German, and Portuguese)
[1-4]
Use of UpToDate is subject to the Subscription and License Agreement. REFERENCES 1. Johnell, O, Kanis, JA, Black, DM, et al. Associations between baseline risk factors and vertebral fracture risk in the Multiple Outcomes of Raloxifene Evaluation (MORE) Study. J Bone Miner Res 2004; 19:764.
2. Raisz, LG. Clinical practice. Screening for osteoporosis. N Engl J Med 2005; 353:164.
3. Marshall, D, Johnell, O, Wedel, H. Meta-analysis of how well measures of bone mineral density predict occurrence of osteoporotic fractures. BMJ 1996; 312:1254.
4. Bainbridge, KE, Sowers, MF, Crutchfield, M, et al. Natural history of bone loss over 6 years among premenopausal and early postmenopausal women. Am J Epidemiol 2002; 156:410.
Calcium for bone health
INTRODUCTION — Osteoporosis is a common bone disorder characterized by a progressive decrease in bone density and mass. As a result, bones become thin, weakened, and easily fractured. It is estimated that more than 1.3 million osteoporosis-associated (or "osteoporotic") fractures occur every year in the United States, primarily of bone within the vertebral column, the hip, and the forearm near the wrist. (See "Patient information: Osteoporosis causes, diagnosis, and screening").
Osteoporosis is the result of accelerated bone loss due to an imbalance between the normal breakdown (resorption) and replacement (formation) of bone. In most patients, such bone loss is largely menopause- and/or age-related. Bone mass naturally declines as people age (ie, beginning at about age 35 years); in addition, women are particularly at risk for osteoporosis following menopause due to declining production of the female hormone estrogen, which helps to maintain bone mass.
Multiple therapies are available that may prevent bone loss and treat low bone mass. However, the first step in preventing or treating osteoporosis is to eat the right foods, particularly those that provide calcium, a mineral essential for bone strength, and vitamin D, which aids in calcium break down and absorption. (See "Patient information: Osteoporosis prevention and treatment").
BENEFITS — Good nutrition is important at all ages, from infants to the elderly, to keep the bones healthy. In some studies in postmenopausal women, taking calcium reduced bone loss and decreased the risk of recurrent vertebral fractures.
In addition, consuming calcium during childhood (eg, in milk) can lead to higher bone mass in adulthood. The increase in bone mineral density is important in modifying future fracture risk. The risk for most osteoporotic fractures increases as the bone density decreases. This means, the lower the bone mass, the greater the tendency to fracture. Calcium also has benefits in other body systems by reducing blood pressure and cholesterol levels.
Calcium balance in the body refers to the balance between calcium that is taken in (eaten) and calcium that is excreted (eg, in urine). Not surprisingly, the less calcium an individual takes in, the more negative the calcium balance. By increasing one's calcium intake, calcium balance can become more positive.
Multiple investigations have supported the importance of calcium intake, demonstrating that adequate calcium reduces bone loss in adults. As examples: Two studies demonstrated that postmenopausal women whose calcium intake was less than 400 or 750 mg/day had significant reductions in bone loss when supplemented with calcium as opposed to placebo (an inactive substance). In women over age 60 years with a low calcium intake who had preexisting spinal (vertebral) fractures, calcium supplementation reduced the incidence of additional vertebral fractures compared to placebo and stopped detectable bone loss within the forearm (over four years of follow-up). One study demonstrated that calcium supplementation in postmenopausal women was associated with a small but significant increase in bone density.
Calcium and vitamin D supplements have been shown to help prevent tooth loss in the elderly.
RECOMMENDATIONS — As mentioned above, adequate calcium intake can result in positive calcium balance and a reduction in the rate of bone loss; it is less clear if adequate calcium intake decreases the risk of bone fractures. However, most clinicians recommend calcium supplementation for patients with a low calcium intake since it appears to reduce bone loss.
Daily calcium intake should be at least 1000 mg in premenopausal women and men, and 1500 mg in postmenopausal women who do not take estrogen. The total daily calcium intake should not routinely exceed 2000 mg due to the possibility of adverse effects.
Persons who cannot get enough calcium from dietary sources should speak with their clinician for specific recommendations about the type, dose, and timing of calcium supplementation (show figure 1). The following are general guidelines Calcium carbonate is an effective and inexpensive form of calcium. It is best absorbed with a low-iron meal (such as breakfast). Calcium citrate (eg, Citracal®) may be recommended for elderly people who absorb calcium carbonate less readily (because of less acid in the stomach). Chewable preparations of calcium carbonate (eg, Viactiv®, Tums®) or calcium citrate (Citracal®) are preferred since many natural calcium carbonate preparations (eg, bone meal, oyster shells) do not dissolve well. In addition, these preparations can be contaminated with lead and/or mercury. Calcium supplements should be taken in divided doses. Doses above 500 mg are not absorbed as well as smaller doses. Calcium supplementation is not an alternative to other osteoporosis treatments. Calcium is less effective than other treatments, including hormone replacement, bisphosphonates (eg, risedronate [Actonel®] and alendronate [Fosamax®]), and raloxifene (Evista®) in slowing bone loss in postmenopausal women. Hormone therapy is recommended only for women with certain menopausal symptoms. However, calcium had additive benefits when used along with other treatments. (See "Patient information: Osteoporosis prevention and treatment").
Underlying gastrointestinal diseases — Patients with impaired absorption of nutrients from the gastrointestinal tract (malabsorption) may have higher than normal calcium requirements due to reduced calcium absorption. In such cases, a healthcare provider can help to determine the appropriate level of calcium supplementation.
Medications — Administration of certain medications may influence calcium balance, such as drugs that promote the excretion of urine (diuretics). As an example, so-called "loop diuretics" increase the excretion of calcium; however, thiazide diuretics may lead to reduced levels of calcium in the urine, potentially helping to protect against possible bone loss and kidney stones (see below). Therefore, it is important for patients to tell their physicians and pharmacists about all medications they are taking so that any possible interactions with calcium can be identified.
DETERMINING CURRENT CALCIUM INTAKE — The primary sources of calcium within the diet include milk and other dairy products, such as hard cheese, cottage cheese, or yogurt, as well as green vegetables, such as spinach (show table 1). A simple way to estimate one's daily intake of dietary calcium is to multiply the number of dairy servings consumed each day by 300 mg. One serving equals 8 oz of milk or yogurt, 1 oz of hard cheese, 16 oz of cottage cheese, or 2 cups of broccoli.
Many experts recommend calcium supplementation rather than dietary changes for individuals with inadequate calcium intake. Evidence suggests that calcium is as well absorbed from supplements as from whole milk. In addition, calcium supplements were used in the studies cited above that demonstrated benefits from increased calcium intake. Therefore, it is likely that calcium supplements are just as effective as calcium in dairy products. However, calcium absorption from vegetables (eg, spinach) is less than that from dairy products.
IMPORTANCE OF VITAMIN D — In addition to calcium, vitamin D is important in the prevention and treatment of osteoporosis. Vitamin D is normally synthesized in the skin after exposure to sunlight. It can also be ingested from dietary sources. Vitamin D deficiency occurs as a result of decreased intake or absorption or from reduced exposure to the sun. Vitamin D levels decline with age and with decreased sun exposure, especially in the winter. In temperate areas such as Boston and Edmonton, for example, production of vitamin D by the skin virtually ceases in winter.
Multiple clinical trials have proven that vitamin D decreases bone loss and lowers fracture rates, especially in older men and women. The current recommendation for daily intake of vitamin D in adults is at least 800 International Units (IU). Lower levels of vitamin D are not as effective while doses higher than 2000 IU per day can be toxic. Milk is the best source of dietary vitamin D, with approximately 100 IU per cup.
A vitamin D supplement is recommended for all patients with osteoporosis whose dietary intake of vitamin D is below 400 IU/day. A daily multivitamin is both convenient and economical, and has the added advantage of providing other vitamins. Alternately, patients may take a calcium supplement that contains Vitamin D.
SIDE EFFECTS — Side effects related to calcium include constipation and indigestion (dyspepsia).
Previous data suggested that calcium supplementation might be associated with weight loss, though two large, randomized trials reported no significant effect of calcium supplements (1000 mg/day) on body weight.
Concern that high dietary calcium increases the risk of kidney stones in otherwise healthy patients appears to be unfounded since the incidence of stone formation appears to be reduced in both men and women who consume high amounts of dietary calcium.
WHERE TO GET MORE INFORMATION — Your healthcare provider is the best source of information for questions and concerns related to your medical problem. Because no two patients are exactly alike and recommendations can vary from one person to another, it is important to seek guidance from a provider who is familiar with your individual situation.
This discussion will be updated as needed every four months on our web site (www.patients.uptodate.com). Additional topics as well as selected discussions written for healthcare professionals are also available for those who would like more detailed information.
A number of web sites have information about medical problems and treatments, although it can be difficult to know which sites are reputable. Information provided by the National Institutes of Health, national medical societies and some other well-established organizations are often reliable sources of information, although the frequency with which they are updated is variable. National Library of Medicine
(www.nlm.nih.gov/medlineplus/healthtopics.html)
Osteoporosis and Related Bone Diseases National Resource Center (ORBD-NRC)
1232 22nd Street, NW
Washington, DC 20037-1292
Phone: (202) 223-0344
Toll-free: (800) 624-BONE (2663)
TTY: (202) 466-4315
E-mail: orbdnrc@nof.org
(www.osteo.org)
National Osteoporosis Foundation
1232 22nd Street NW
Washington, DC 20037-1292
Phone: (202) 223-2226
E-mail: patientinfo@nof.org
(www.nof.org)
Osteoporosis Society of Canada
33 Laird Drive
Toronto, Ontario M4G 3S9
Phone: (800) 463-6842
(www.osteoporosis.ca/)
The Hormone Foundation
(www.hormone.org/public/osteoporosis.cfm, available in English and Spanish)
[1-7]
Use of UpToDate is subject to the Subscription and License Agreement. REFERENCES 1. NIH Consensus Development Panel on Optimal Calcium Intake. Optimal calcium intake. JAMA 1994; 272:1942.
2. Aloia, JF, Vaswani, A, Yeh, JK, et al. Calcium supplementation with and without hormone replacement therapy to prevent postmenopausal bone loss. Ann Intern Med 1994; 120:97.
3. Cook, JD, Dassenko, SA, Whittaker, P. Calcium supplementation: Effect on iron absorption. Am J Clin Nutr 1991; 53:106.
4. Curhan, GC, Willett, WC, Speizer, FE, et al. Comparison of dietary calcium with supplemental calcium and other nutrients as factors affecting the risk for kidney stones in women. Ann Intern Med 1997; 126:497.
5. Dawson-Hughes, B, Harris, SS, Krall, EA, Dallal, GE. Effect of calcium and vitamin D supplementation on bone density in men and women 65 years of age or older. N Engl J Med 1997; 337:670.
6. Ross, EA, Szabo, NJ, Tebbett, IR. Lead content of calcium supplements. JAMA 2000; 284:1425.
7. Heaney, RP. Lead in calcium supplements: cause for alarm or celebration?. JAMA 2000; 284:1432.
Osteoporosis is the result of accelerated bone loss due to an imbalance between the normal breakdown (resorption) and replacement (formation) of bone. In most patients, such bone loss is largely menopause- and/or age-related. Bone mass naturally declines as people age (ie, beginning at about age 35 years); in addition, women are particularly at risk for osteoporosis following menopause due to declining production of the female hormone estrogen, which helps to maintain bone mass.
Multiple therapies are available that may prevent bone loss and treat low bone mass. However, the first step in preventing or treating osteoporosis is to eat the right foods, particularly those that provide calcium, a mineral essential for bone strength, and vitamin D, which aids in calcium break down and absorption. (See "Patient information: Osteoporosis prevention and treatment").
BENEFITS — Good nutrition is important at all ages, from infants to the elderly, to keep the bones healthy. In some studies in postmenopausal women, taking calcium reduced bone loss and decreased the risk of recurrent vertebral fractures.
In addition, consuming calcium during childhood (eg, in milk) can lead to higher bone mass in adulthood. The increase in bone mineral density is important in modifying future fracture risk. The risk for most osteoporotic fractures increases as the bone density decreases. This means, the lower the bone mass, the greater the tendency to fracture. Calcium also has benefits in other body systems by reducing blood pressure and cholesterol levels.
Calcium balance in the body refers to the balance between calcium that is taken in (eaten) and calcium that is excreted (eg, in urine). Not surprisingly, the less calcium an individual takes in, the more negative the calcium balance. By increasing one's calcium intake, calcium balance can become more positive.
Multiple investigations have supported the importance of calcium intake, demonstrating that adequate calcium reduces bone loss in adults. As examples: Two studies demonstrated that postmenopausal women whose calcium intake was less than 400 or 750 mg/day had significant reductions in bone loss when supplemented with calcium as opposed to placebo (an inactive substance). In women over age 60 years with a low calcium intake who had preexisting spinal (vertebral) fractures, calcium supplementation reduced the incidence of additional vertebral fractures compared to placebo and stopped detectable bone loss within the forearm (over four years of follow-up). One study demonstrated that calcium supplementation in postmenopausal women was associated with a small but significant increase in bone density.
Calcium and vitamin D supplements have been shown to help prevent tooth loss in the elderly.
RECOMMENDATIONS — As mentioned above, adequate calcium intake can result in positive calcium balance and a reduction in the rate of bone loss; it is less clear if adequate calcium intake decreases the risk of bone fractures. However, most clinicians recommend calcium supplementation for patients with a low calcium intake since it appears to reduce bone loss.
Daily calcium intake should be at least 1000 mg in premenopausal women and men, and 1500 mg in postmenopausal women who do not take estrogen. The total daily calcium intake should not routinely exceed 2000 mg due to the possibility of adverse effects.
Persons who cannot get enough calcium from dietary sources should speak with their clinician for specific recommendations about the type, dose, and timing of calcium supplementation (show figure 1). The following are general guidelines Calcium carbonate is an effective and inexpensive form of calcium. It is best absorbed with a low-iron meal (such as breakfast). Calcium citrate (eg, Citracal®) may be recommended for elderly people who absorb calcium carbonate less readily (because of less acid in the stomach). Chewable preparations of calcium carbonate (eg, Viactiv®, Tums®) or calcium citrate (Citracal®) are preferred since many natural calcium carbonate preparations (eg, bone meal, oyster shells) do not dissolve well. In addition, these preparations can be contaminated with lead and/or mercury. Calcium supplements should be taken in divided doses. Doses above 500 mg are not absorbed as well as smaller doses. Calcium supplementation is not an alternative to other osteoporosis treatments. Calcium is less effective than other treatments, including hormone replacement, bisphosphonates (eg, risedronate [Actonel®] and alendronate [Fosamax®]), and raloxifene (Evista®) in slowing bone loss in postmenopausal women. Hormone therapy is recommended only for women with certain menopausal symptoms. However, calcium had additive benefits when used along with other treatments. (See "Patient information: Osteoporosis prevention and treatment").
Underlying gastrointestinal diseases — Patients with impaired absorption of nutrients from the gastrointestinal tract (malabsorption) may have higher than normal calcium requirements due to reduced calcium absorption. In such cases, a healthcare provider can help to determine the appropriate level of calcium supplementation.
Medications — Administration of certain medications may influence calcium balance, such as drugs that promote the excretion of urine (diuretics). As an example, so-called "loop diuretics" increase the excretion of calcium; however, thiazide diuretics may lead to reduced levels of calcium in the urine, potentially helping to protect against possible bone loss and kidney stones (see below). Therefore, it is important for patients to tell their physicians and pharmacists about all medications they are taking so that any possible interactions with calcium can be identified.
DETERMINING CURRENT CALCIUM INTAKE — The primary sources of calcium within the diet include milk and other dairy products, such as hard cheese, cottage cheese, or yogurt, as well as green vegetables, such as spinach (show table 1). A simple way to estimate one's daily intake of dietary calcium is to multiply the number of dairy servings consumed each day by 300 mg. One serving equals 8 oz of milk or yogurt, 1 oz of hard cheese, 16 oz of cottage cheese, or 2 cups of broccoli.
Many experts recommend calcium supplementation rather than dietary changes for individuals with inadequate calcium intake. Evidence suggests that calcium is as well absorbed from supplements as from whole milk. In addition, calcium supplements were used in the studies cited above that demonstrated benefits from increased calcium intake. Therefore, it is likely that calcium supplements are just as effective as calcium in dairy products. However, calcium absorption from vegetables (eg, spinach) is less than that from dairy products.
IMPORTANCE OF VITAMIN D — In addition to calcium, vitamin D is important in the prevention and treatment of osteoporosis. Vitamin D is normally synthesized in the skin after exposure to sunlight. It can also be ingested from dietary sources. Vitamin D deficiency occurs as a result of decreased intake or absorption or from reduced exposure to the sun. Vitamin D levels decline with age and with decreased sun exposure, especially in the winter. In temperate areas such as Boston and Edmonton, for example, production of vitamin D by the skin virtually ceases in winter.
Multiple clinical trials have proven that vitamin D decreases bone loss and lowers fracture rates, especially in older men and women. The current recommendation for daily intake of vitamin D in adults is at least 800 International Units (IU). Lower levels of vitamin D are not as effective while doses higher than 2000 IU per day can be toxic. Milk is the best source of dietary vitamin D, with approximately 100 IU per cup.
A vitamin D supplement is recommended for all patients with osteoporosis whose dietary intake of vitamin D is below 400 IU/day. A daily multivitamin is both convenient and economical, and has the added advantage of providing other vitamins. Alternately, patients may take a calcium supplement that contains Vitamin D.
SIDE EFFECTS — Side effects related to calcium include constipation and indigestion (dyspepsia).
Previous data suggested that calcium supplementation might be associated with weight loss, though two large, randomized trials reported no significant effect of calcium supplements (1000 mg/day) on body weight.
Concern that high dietary calcium increases the risk of kidney stones in otherwise healthy patients appears to be unfounded since the incidence of stone formation appears to be reduced in both men and women who consume high amounts of dietary calcium.
WHERE TO GET MORE INFORMATION — Your healthcare provider is the best source of information for questions and concerns related to your medical problem. Because no two patients are exactly alike and recommendations can vary from one person to another, it is important to seek guidance from a provider who is familiar with your individual situation.
This discussion will be updated as needed every four months on our web site (www.patients.uptodate.com). Additional topics as well as selected discussions written for healthcare professionals are also available for those who would like more detailed information.
A number of web sites have information about medical problems and treatments, although it can be difficult to know which sites are reputable. Information provided by the National Institutes of Health, national medical societies and some other well-established organizations are often reliable sources of information, although the frequency with which they are updated is variable. National Library of Medicine
(www.nlm.nih.gov/medlineplus/healthtopics.html)
Osteoporosis and Related Bone Diseases National Resource Center (ORBD-NRC)
1232 22nd Street, NW
Washington, DC 20037-1292
Phone: (202) 223-0344
Toll-free: (800) 624-BONE (2663)
TTY: (202) 466-4315
E-mail: orbdnrc@nof.org
(www.osteo.org)
National Osteoporosis Foundation
1232 22nd Street NW
Washington, DC 20037-1292
Phone: (202) 223-2226
E-mail: patientinfo@nof.org
(www.nof.org)
Osteoporosis Society of Canada
33 Laird Drive
Toronto, Ontario M4G 3S9
Phone: (800) 463-6842
(www.osteoporosis.ca/)
The Hormone Foundation
(www.hormone.org/public/osteoporosis.cfm, available in English and Spanish)
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Use of UpToDate is subject to the Subscription and License Agreement. REFERENCES 1. NIH Consensus Development Panel on Optimal Calcium Intake. Optimal calcium intake. JAMA 1994; 272:1942.
2. Aloia, JF, Vaswani, A, Yeh, JK, et al. Calcium supplementation with and without hormone replacement therapy to prevent postmenopausal bone loss. Ann Intern Med 1994; 120:97.
3. Cook, JD, Dassenko, SA, Whittaker, P. Calcium supplementation: Effect on iron absorption. Am J Clin Nutr 1991; 53:106.
4. Curhan, GC, Willett, WC, Speizer, FE, et al. Comparison of dietary calcium with supplemental calcium and other nutrients as factors affecting the risk for kidney stones in women. Ann Intern Med 1997; 126:497.
5. Dawson-Hughes, B, Harris, SS, Krall, EA, Dallal, GE. Effect of calcium and vitamin D supplementation on bone density in men and women 65 years of age or older. N Engl J Med 1997; 337:670.
6. Ross, EA, Szabo, NJ, Tebbett, IR. Lead content of calcium supplements. JAMA 2000; 284:1425.
7. Heaney, RP. Lead in calcium supplements: cause for alarm or celebration?. JAMA 2000; 284:1432.
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