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.
Monday, October 15, 2007
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)
[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.
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)
[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.
Miscarriage
INTRODUCTION — A miscarriage is a pregnancy that ends before the fetus is able to live outside the uterus. A brief review of the events of early pregnancy will help in the understanding of miscarriage.
A woman's reproductive system includes the uterus (including the cervix), two ovaries, two fallopian tubes, and the vagina. The fallopian tubes are a pair of hollowed tubes that run from each side of the uterus to the ovaries (show figure 1). Once a month, an egg is released by one of the ovaries and travels down the fallopian tube. If the egg is fertilized in the tube by the male's sperm, pregnancy begins.
Once the egg and sperm join, they rapidly develop new cells. This bundle of cells, called the embryo, normally implants on the inner wall of the uterus. Once implanted, the embryo continues to grow inside a sac of amniotic fluid, sometimes called the "bag of water." After several weeks, the embryo is called a fetus.
INCIDENCE — Miscarriage in early pregnancy is very common. Studies show that about 10 to 20 percent of women who know they are pregnant have a miscarriage some time before 20 weeks of pregnancy; 80 percent of these occur in the first 12 weeks. But the actual rate of miscarriage is even higher since many women have very early miscarriages without ever realizing that they are pregnant. One study that followed women's hormone levels every day in order to detect very early pregnancy found a total pregnancy loss rate of 31 percent.
CAUSES — Many different factors can lead to miscarriage, and it is difficult to say with certainty what causes a particular miscarriage to occur. One or more problems with the pregnancy can be found in a significant percentage of early miscarriages.
As an example, in 1/3 of miscarriages occurring before 8 weeks, there is a pregnancy sac but no embryo inside. This means the egg was fertilized and the cells began to divide, but an embryo did not develop. In other cases, the embryo develops but it is abnormal. Chromosomal abnormalities, in particular, are common. One study found that of 8841 miscarriages, 41 percent had chromosomal abnormalities.
In some cases, medical conditions in the mother, such as uncontrolled diabetes, or structural problems in the reproductive tract, such as uterine fibroids, can lead to miscarriage. (See "Patient information: Care during pregnancy for women with type 1 or 2 diabetes" and see "Patient information: Fibroids").
RISK FACTORS — Several risk factors are associated with a higher rate of miscarriage. Age — Older women are more likely to have a miscarriage than younger women. Number of pregnancies — The risk of miscarriage increases in women who have had been pregnant previously. That is, women who have been pregnant two or more times have an increased risk of miscarriage. Previous miscarriage — Having a miscarriage in the past may increase the risk for a future miscarriage. As an example, the risk of miscarriage in future pregnancy is about 20 percent after one miscarriage, 28 percent after two, and 43 percent after three or more miscarriages. By comparison, only 5 percent of women whose previous pregnancy was successful miscarried in the next pregnancy. Smoking — There is evidence that smoking more than 10 cigarettes a day increases the risk of miscarriage. Alcohol — Drinking more than 30 ounces of alcohol per month doubled the risk of miscarriage in one study. In another, there was an increased risk of miscarriage in women who drank more than 3 drinks per week in the first 12 weeks of pregnancy. No amount of alcohol is known to be safe during pregnancy. Fever — Pregnant women who develop fevers of 100ºF (37.5ºC) or more appear to have an increased risk of miscarriage. Trauma — Trauma to the uterus can increase the risk of miscarriage. This includes some forms of prenatal testing, such as amniocentesis or chorionic villus sampling. (See "Patient information: Amniocentesis" and see "Patient information: Chorionic villus sampling"). Caffeine — In one study, some women who ingested 500 mg of caffeine per day had a significantly increased risk of miscarriage (8 ounces of coffee contains 100 to 135 mg of caffeine). Other causes — Women who are exposed to certain substances or conditions may have an increased risk of congenital abnormalities and miscarriage. This includes exposure to certain infections, medications, radiation, physical stresses, and environmental chemicals.
SIGNS AND SYMPTOMS — The most common signs of miscarriage are vaginal bleeding and abdominal pain early in pregnancy. These problems should always be evaluated by a clinician. However, bleeding and discomfort can occur in normal pregnancies. In many cases, bleeding resolves on its own and the pregnancy continues normally without further problems.
Based on particular signs and symptoms, a woman may be diagnosed as follows:
Threatened miscarriage — A woman who has vaginal bleeding early in pregnancy but no other signs of problems is said to have a threatened miscarriage. The cervix, or opening to the uterus, is closed, and the uterus is the right size for the woman's particular stage of pregnancy. If the pregnancy is far enough along, a fetal heart beat may be noted. In many women with threatened miscarriage, the bleeding subsides and the pregnancy continues to term. In others, the bleeding becomes heavier and miscarriage occurs.
Inevitable miscarriage — This means a miscarriage cannot be avoided. The cervix is open, bleeding is heavy or increasing, and abdominal cramping is present.
Incomplete miscarriage — An incomplete miscarriage means that the woman has passed much of the pregnancy tissue, but some remains in the uterus. Typically, the fetus has been passed, but bits of the placenta remain. The cervix remains open, and bleeding may be heavy.
Complete miscarriage — A woman who passes all of the pregnancy tissue is said to have had a complete miscarriage. This is common in miscarriages that occur before 12 weeks of pregnancy. After the miscarriage there is a period of bleeding and cramping, which resolves without medical intervention. On examination, the clinician typically finds that the cervix is closed, and there is no sign of a pregnancy sac in the uterus. Ultrasound examination confirms the diagnosis.
Septic miscarriage — Some women who have miscarriage develop an infection in the uterus. This is known as a septic miscarriage. Symptoms include fever, chills, malaise, abdominal pain, vaginal bleeding, and vaginal discharge, which may be thick and may have an unpleasant odor.
DIAGNOSIS — In some cases, miscarriage is evident based on the woman's symptoms and the physical exam. As an example, with inevitable miscarriage, the cervix is open and pregnancy tissue may be seen in the cervix.
However, in many cases of vaginal bleeding in early pregnancy, ultrasound is used to establish a diagnosis, and/or to help determine if the pregnancy is "viable", that is, whether it is capable of progressing to term. Ultrasound uses sound waves to visualize the structures inside the uterus. In early pregnancy, the exam is often done through the vagina.
Ultrasound — In a woman who has had a complete miscarriage, no pregnancy sac or embryo will be seen on ultrasound. In other women, a pregnancy sac will be seen but it will be abnormal or an embryo will not be present, indicating that the pregnancy is not viable.
If an embryo is present, its size is measured and compared to the size that is expected at the woman's stage of pregnancy. The sac and other materials surrounding the embryo are also examined to look for abnormalities in these structures.
Fetal heart beat — At about 6 weeks after the last menstrual period, the motion of the fetal heart should be visible on ultrasound. If the pregnancy has progressed to the stage where a heart beat should be present, the failure to detect a heart beat during an ultrasound exam indicates that the pregnancy has likely ended.
On the other hand, the presence of a fetal heart beat (in the absence of other abnormalities in the pregnancy) indicates the pregnancy may still be viable and that miscarriage may not occur.
Doctors will also evaluate the rate of the fetal heart. A fetal heart beat that is slower than normal (120 to 170 beats per minute) can indicate that a miscarriage is likely.
TREATMENT OPTIONS — Once it has been determined that a miscarriage is inevitable or is already occurring , several options are available depending on the stage of the miscarriage, the condition of the mother, and other factors. The three main options are: observation, medical treatment, or surgical treatment.
Observation — In some situations, women having a miscarriage require little treatment. Many women with complete miscarriage fall into this group. In addition, women who miscarry at less than 13 weeks of pregnancy and have stable vital signs and no signs of infection can often be managed without medical or surgical treatment. In time, the contents of the uterus will pass, usually within two weeks of diagnosis, but sometimes as long as 3 to 4 weeks later. Once the contents have been passed, an ultrasound is done to ensure that the miscarriage is complete.
Medical treatment — In some cases, medications can be given to stimulate the uterus to pass the pregnancy tissue. The medicine can be given by mouth or vaginally, and works over several days.
Surgical treatment — The conventional treatment for early miscarriage is a surgical procedure called dilation and curettage, or D and C. The cervix (the opening to the uterus) is dilated, and an instrument is inserted that uses suction and/or a gentle scraping motion to remove the contents of the uterus.
As with any surgical procedure, there are risks of complications. The risks associated with D and C are small, and include perforation of the uterus, formation of scar tissue in the uterus, trauma to the cervix, and infection, which could lead to future fertility problems. The procedure is done in women who do not want to wait for spontaneous passage of the pregnancy, and in women with heavy bleeding or infection.
AFTER MISCARRIAGE — Following miscarriage, a woman is advised to avoid having sex or putting anything into the vagina, such as a douche or tampon. Women have traditionally been told to wait two to three months before trying to become pregnant again, although several studies have shown no increased risks with a shorter interval. Any type of contraception, including an intrauterine device, may be started immediately.
Medications may be given to help decrease bleeding and reduce infection. In addition, women who have an Rh negative blood type (ie, A, B, AB, or O negative) need to receive a drug called Rh(D) immune globulin (RhoGam®). This medicine helps protect future fetuses against problems that can occur if an Rh negative mother is carrying a baby who is Rh positive.
Emotional health — Women experience a range of emotions following miscarriage; there is no right or wrong way to feel. The loss of a pregnancy can cause significant grief. Sometimes these reactions are strong and long-lasting. A woman should let her healthcare provider know if she is feeling profound sadness or depression following pregnancy loss, especially if it continues for greater than two weeks. Referral for grief counseling or other treatment may be beneficial. (See "Patient information: Depression in adults").
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)
The March of Dimes
(www.marchofdimes.com)
Pregnancy & Infant Loss Support, Inc.
(www.nationalshareoffice.com)
[1-4]
Use of UpToDate is subject to the Subscription and License Agreement. REFERENCES 1. Regan, L, Rai, R. Epidemiology and the medical causes of miscarriage. Baillieres Best Pract Res Clin Obstet Gynaecol 2000; 14:839.
2. Wilcox, AJ, Weinberg, CR, O'Connor, JF, et al. Incidence of early loss of pregnancy. N Engl J Med 1988; 319:189.
3. Ankum, WM, Wieringa-De Waard, M, Bindels, PJ. Management of spontaneous miscarriage in the first trimester: an example of putting informed shared decision making into practice. BMJ 2001; 322:1343.
4. Demetroulis, C, Saridogan, E, Kunde, D, Naftalin, AA. A prospective randomized control trial comparing medical and surgical treatment for early pregnancy failure. Hum Reprod 2001; 16:365.
A woman's reproductive system includes the uterus (including the cervix), two ovaries, two fallopian tubes, and the vagina. The fallopian tubes are a pair of hollowed tubes that run from each side of the uterus to the ovaries (show figure 1). Once a month, an egg is released by one of the ovaries and travels down the fallopian tube. If the egg is fertilized in the tube by the male's sperm, pregnancy begins.
Once the egg and sperm join, they rapidly develop new cells. This bundle of cells, called the embryo, normally implants on the inner wall of the uterus. Once implanted, the embryo continues to grow inside a sac of amniotic fluid, sometimes called the "bag of water." After several weeks, the embryo is called a fetus.
INCIDENCE — Miscarriage in early pregnancy is very common. Studies show that about 10 to 20 percent of women who know they are pregnant have a miscarriage some time before 20 weeks of pregnancy; 80 percent of these occur in the first 12 weeks. But the actual rate of miscarriage is even higher since many women have very early miscarriages without ever realizing that they are pregnant. One study that followed women's hormone levels every day in order to detect very early pregnancy found a total pregnancy loss rate of 31 percent.
CAUSES — Many different factors can lead to miscarriage, and it is difficult to say with certainty what causes a particular miscarriage to occur. One or more problems with the pregnancy can be found in a significant percentage of early miscarriages.
As an example, in 1/3 of miscarriages occurring before 8 weeks, there is a pregnancy sac but no embryo inside. This means the egg was fertilized and the cells began to divide, but an embryo did not develop. In other cases, the embryo develops but it is abnormal. Chromosomal abnormalities, in particular, are common. One study found that of 8841 miscarriages, 41 percent had chromosomal abnormalities.
In some cases, medical conditions in the mother, such as uncontrolled diabetes, or structural problems in the reproductive tract, such as uterine fibroids, can lead to miscarriage. (See "Patient information: Care during pregnancy for women with type 1 or 2 diabetes" and see "Patient information: Fibroids").
RISK FACTORS — Several risk factors are associated with a higher rate of miscarriage. Age — Older women are more likely to have a miscarriage than younger women. Number of pregnancies — The risk of miscarriage increases in women who have had been pregnant previously. That is, women who have been pregnant two or more times have an increased risk of miscarriage. Previous miscarriage — Having a miscarriage in the past may increase the risk for a future miscarriage. As an example, the risk of miscarriage in future pregnancy is about 20 percent after one miscarriage, 28 percent after two, and 43 percent after three or more miscarriages. By comparison, only 5 percent of women whose previous pregnancy was successful miscarried in the next pregnancy. Smoking — There is evidence that smoking more than 10 cigarettes a day increases the risk of miscarriage. Alcohol — Drinking more than 30 ounces of alcohol per month doubled the risk of miscarriage in one study. In another, there was an increased risk of miscarriage in women who drank more than 3 drinks per week in the first 12 weeks of pregnancy. No amount of alcohol is known to be safe during pregnancy. Fever — Pregnant women who develop fevers of 100ºF (37.5ºC) or more appear to have an increased risk of miscarriage. Trauma — Trauma to the uterus can increase the risk of miscarriage. This includes some forms of prenatal testing, such as amniocentesis or chorionic villus sampling. (See "Patient information: Amniocentesis" and see "Patient information: Chorionic villus sampling"). Caffeine — In one study, some women who ingested 500 mg of caffeine per day had a significantly increased risk of miscarriage (8 ounces of coffee contains 100 to 135 mg of caffeine). Other causes — Women who are exposed to certain substances or conditions may have an increased risk of congenital abnormalities and miscarriage. This includes exposure to certain infections, medications, radiation, physical stresses, and environmental chemicals.
SIGNS AND SYMPTOMS — The most common signs of miscarriage are vaginal bleeding and abdominal pain early in pregnancy. These problems should always be evaluated by a clinician. However, bleeding and discomfort can occur in normal pregnancies. In many cases, bleeding resolves on its own and the pregnancy continues normally without further problems.
Based on particular signs and symptoms, a woman may be diagnosed as follows:
Threatened miscarriage — A woman who has vaginal bleeding early in pregnancy but no other signs of problems is said to have a threatened miscarriage. The cervix, or opening to the uterus, is closed, and the uterus is the right size for the woman's particular stage of pregnancy. If the pregnancy is far enough along, a fetal heart beat may be noted. In many women with threatened miscarriage, the bleeding subsides and the pregnancy continues to term. In others, the bleeding becomes heavier and miscarriage occurs.
Inevitable miscarriage — This means a miscarriage cannot be avoided. The cervix is open, bleeding is heavy or increasing, and abdominal cramping is present.
Incomplete miscarriage — An incomplete miscarriage means that the woman has passed much of the pregnancy tissue, but some remains in the uterus. Typically, the fetus has been passed, but bits of the placenta remain. The cervix remains open, and bleeding may be heavy.
Complete miscarriage — A woman who passes all of the pregnancy tissue is said to have had a complete miscarriage. This is common in miscarriages that occur before 12 weeks of pregnancy. After the miscarriage there is a period of bleeding and cramping, which resolves without medical intervention. On examination, the clinician typically finds that the cervix is closed, and there is no sign of a pregnancy sac in the uterus. Ultrasound examination confirms the diagnosis.
Septic miscarriage — Some women who have miscarriage develop an infection in the uterus. This is known as a septic miscarriage. Symptoms include fever, chills, malaise, abdominal pain, vaginal bleeding, and vaginal discharge, which may be thick and may have an unpleasant odor.
DIAGNOSIS — In some cases, miscarriage is evident based on the woman's symptoms and the physical exam. As an example, with inevitable miscarriage, the cervix is open and pregnancy tissue may be seen in the cervix.
However, in many cases of vaginal bleeding in early pregnancy, ultrasound is used to establish a diagnosis, and/or to help determine if the pregnancy is "viable", that is, whether it is capable of progressing to term. Ultrasound uses sound waves to visualize the structures inside the uterus. In early pregnancy, the exam is often done through the vagina.
Ultrasound — In a woman who has had a complete miscarriage, no pregnancy sac or embryo will be seen on ultrasound. In other women, a pregnancy sac will be seen but it will be abnormal or an embryo will not be present, indicating that the pregnancy is not viable.
If an embryo is present, its size is measured and compared to the size that is expected at the woman's stage of pregnancy. The sac and other materials surrounding the embryo are also examined to look for abnormalities in these structures.
Fetal heart beat — At about 6 weeks after the last menstrual period, the motion of the fetal heart should be visible on ultrasound. If the pregnancy has progressed to the stage where a heart beat should be present, the failure to detect a heart beat during an ultrasound exam indicates that the pregnancy has likely ended.
On the other hand, the presence of a fetal heart beat (in the absence of other abnormalities in the pregnancy) indicates the pregnancy may still be viable and that miscarriage may not occur.
Doctors will also evaluate the rate of the fetal heart. A fetal heart beat that is slower than normal (120 to 170 beats per minute) can indicate that a miscarriage is likely.
TREATMENT OPTIONS — Once it has been determined that a miscarriage is inevitable or is already occurring , several options are available depending on the stage of the miscarriage, the condition of the mother, and other factors. The three main options are: observation, medical treatment, or surgical treatment.
Observation — In some situations, women having a miscarriage require little treatment. Many women with complete miscarriage fall into this group. In addition, women who miscarry at less than 13 weeks of pregnancy and have stable vital signs and no signs of infection can often be managed without medical or surgical treatment. In time, the contents of the uterus will pass, usually within two weeks of diagnosis, but sometimes as long as 3 to 4 weeks later. Once the contents have been passed, an ultrasound is done to ensure that the miscarriage is complete.
Medical treatment — In some cases, medications can be given to stimulate the uterus to pass the pregnancy tissue. The medicine can be given by mouth or vaginally, and works over several days.
Surgical treatment — The conventional treatment for early miscarriage is a surgical procedure called dilation and curettage, or D and C. The cervix (the opening to the uterus) is dilated, and an instrument is inserted that uses suction and/or a gentle scraping motion to remove the contents of the uterus.
As with any surgical procedure, there are risks of complications. The risks associated with D and C are small, and include perforation of the uterus, formation of scar tissue in the uterus, trauma to the cervix, and infection, which could lead to future fertility problems. The procedure is done in women who do not want to wait for spontaneous passage of the pregnancy, and in women with heavy bleeding or infection.
AFTER MISCARRIAGE — Following miscarriage, a woman is advised to avoid having sex or putting anything into the vagina, such as a douche or tampon. Women have traditionally been told to wait two to three months before trying to become pregnant again, although several studies have shown no increased risks with a shorter interval. Any type of contraception, including an intrauterine device, may be started immediately.
Medications may be given to help decrease bleeding and reduce infection. In addition, women who have an Rh negative blood type (ie, A, B, AB, or O negative) need to receive a drug called Rh(D) immune globulin (RhoGam®). This medicine helps protect future fetuses against problems that can occur if an Rh negative mother is carrying a baby who is Rh positive.
Emotional health — Women experience a range of emotions following miscarriage; there is no right or wrong way to feel. The loss of a pregnancy can cause significant grief. Sometimes these reactions are strong and long-lasting. A woman should let her healthcare provider know if she is feeling profound sadness or depression following pregnancy loss, especially if it continues for greater than two weeks. Referral for grief counseling or other treatment may be beneficial. (See "Patient information: Depression in adults").
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)
The March of Dimes
(www.marchofdimes.com)
Pregnancy & Infant Loss Support, Inc.
(www.nationalshareoffice.com)
[1-4]
Use of UpToDate is subject to the Subscription and License Agreement. REFERENCES 1. Regan, L, Rai, R. Epidemiology and the medical causes of miscarriage. Baillieres Best Pract Res Clin Obstet Gynaecol 2000; 14:839.
2. Wilcox, AJ, Weinberg, CR, O'Connor, JF, et al. Incidence of early loss of pregnancy. N Engl J Med 1988; 319:189.
3. Ankum, WM, Wieringa-De Waard, M, Bindels, PJ. Management of spontaneous miscarriage in the first trimester: an example of putting informed shared decision making into practice. BMJ 2001; 322:1343.
4. Demetroulis, C, Saridogan, E, Kunde, D, Naftalin, AA. A prospective randomized control trial comparing medical and surgical treatment for early pregnancy failure. Hum Reprod 2001; 16:365.
Miscarriage
INTRODUCTION — A miscarriage is a pregnancy that ends before the fetus is able to live outside the uterus. A brief review of the events of early pregnancy will help in the understanding of miscarriage.
A woman's reproductive system includes the uterus (including the cervix), two ovaries, two fallopian tubes, and the vagina. The fallopian tubes are a pair of hollowed tubes that run from each side of the uterus to the ovaries (show figure 1). Once a month, an egg is released by one of the ovaries and travels down the fallopian tube. If the egg is fertilized in the tube by the male's sperm, pregnancy begins.
Once the egg and sperm join, they rapidly develop new cells. This bundle of cells, called the embryo, normally implants on the inner wall of the uterus. Once implanted, the embryo continues to grow inside a sac of amniotic fluid, sometimes called the "bag of water." After several weeks, the embryo is called a fetus.
INCIDENCE — Miscarriage in early pregnancy is very common. Studies show that about 10 to 20 percent of women who know they are pregnant have a miscarriage some time before 20 weeks of pregnancy; 80 percent of these occur in the first 12 weeks. But the actual rate of miscarriage is even higher since many women have very early miscarriages without ever realizing that they are pregnant. One study that followed women's hormone levels every day in order to detect very early pregnancy found a total pregnancy loss rate of 31 percent.
CAUSES — Many different factors can lead to miscarriage, and it is difficult to say with certainty what causes a particular miscarriage to occur. One or more problems with the pregnancy can be found in a significant percentage of early miscarriages.
As an example, in 1/3 of miscarriages occurring before 8 weeks, there is a pregnancy sac but no embryo inside. This means the egg was fertilized and the cells began to divide, but an embryo did not develop. In other cases, the embryo develops but it is abnormal. Chromosomal abnormalities, in particular, are common. One study found that of 8841 miscarriages, 41 percent had chromosomal abnormalities.
In some cases, medical conditions in the mother, such as uncontrolled diabetes, or structural problems in the reproductive tract, such as uterine fibroids, can lead to miscarriage. (See "Patient information: Care during pregnancy for women with type 1 or 2 diabetes" and see "Patient information: Fibroids").
RISK FACTORS — Several risk factors are associated with a higher rate of miscarriage. Age — Older women are more likely to have a miscarriage than younger women. Number of pregnancies — The risk of miscarriage increases in women who have had been pregnant previously. That is, women who have been pregnant two or more times have an increased risk of miscarriage. Previous miscarriage — Having a miscarriage in the past may increase the risk for a future miscarriage. As an example, the risk of miscarriage in future pregnancy is about 20 percent after one miscarriage, 28 percent after two, and 43 percent after three or more miscarriages. By comparison, only 5 percent of women whose previous pregnancy was successful miscarried in the next pregnancy. Smoking — There is evidence that smoking more than 10 cigarettes a day increases the risk of miscarriage. Alcohol — Drinking more than 30 ounces of alcohol per month doubled the risk of miscarriage in one study. In another, there was an increased risk of miscarriage in women who drank more than 3 drinks per week in the first 12 weeks of pregnancy. No amount of alcohol is known to be safe during pregnancy. Fever — Pregnant women who develop fevers of 100ºF (37.5ºC) or more appear to have an increased risk of miscarriage. Trauma — Trauma to the uterus can increase the risk of miscarriage. This includes some forms of prenatal testing, such as amniocentesis or chorionic villus sampling. (See "Patient information: Amniocentesis" and see "Patient information: Chorionic villus sampling"). Caffeine — In one study, some women who ingested 500 mg of caffeine per day had a significantly increased risk of miscarriage (8 ounces of coffee contains 100 to 135 mg of caffeine). Other causes — Women who are exposed to certain substances or conditions may have an increased risk of congenital abnormalities and miscarriage. This includes exposure to certain infections, medications, radiation, physical stresses, and environmental chemicals.
SIGNS AND SYMPTOMS — The most common signs of miscarriage are vaginal bleeding and abdominal pain early in pregnancy. These problems should always be evaluated by a clinician. However, bleeding and discomfort can occur in normal pregnancies. In many cases, bleeding resolves on its own and the pregnancy continues normally without further problems.
Based on particular signs and symptoms, a woman may be diagnosed as follows:
Threatened miscarriage — A woman who has vaginal bleeding early in pregnancy but no other signs of problems is said to have a threatened miscarriage. The cervix, or opening to the uterus, is closed, and the uterus is the right size for the woman's particular stage of pregnancy. If the pregnancy is far enough along, a fetal heart beat may be noted. In many women with threatened miscarriage, the bleeding subsides and the pregnancy continues to term. In others, the bleeding becomes heavier and miscarriage occurs.
Inevitable miscarriage — This means a miscarriage cannot be avoided. The cervix is open, bleeding is heavy or increasing, and abdominal cramping is present.
Incomplete miscarriage — An incomplete miscarriage means that the woman has passed much of the pregnancy tissue, but some remains in the uterus. Typically, the fetus has been passed, but bits of the placenta remain. The cervix remains open, and bleeding may be heavy.
Complete miscarriage — A woman who passes all of the pregnancy tissue is said to have had a complete miscarriage. This is common in miscarriages that occur before 12 weeks of pregnancy. After the miscarriage there is a period of bleeding and cramping, which resolves without medical intervention. On examination, the clinician typically finds that the cervix is closed, and there is no sign of a pregnancy sac in the uterus. Ultrasound examination confirms the diagnosis.
Septic miscarriage — Some women who have miscarriage develop an infection in the uterus. This is known as a septic miscarriage. Symptoms include fever, chills, malaise, abdominal pain, vaginal bleeding, and vaginal discharge, which may be thick and may have an unpleasant odor.
DIAGNOSIS — In some cases, miscarriage is evident based on the woman's symptoms and the physical exam. As an example, with inevitable miscarriage, the cervix is open and pregnancy tissue may be seen in the cervix.
However, in many cases of vaginal bleeding in early pregnancy, ultrasound is used to establish a diagnosis, and/or to help determine if the pregnancy is "viable", that is, whether it is capable of progressing to term. Ultrasound uses sound waves to visualize the structures inside the uterus. In early pregnancy, the exam is often done through the vagina.
Ultrasound — In a woman who has had a complete miscarriage, no pregnancy sac or embryo will be seen on ultrasound. In other women, a pregnancy sac will be seen but it will be abnormal or an embryo will not be present, indicating that the pregnancy is not viable.
If an embryo is present, its size is measured and compared to the size that is expected at the woman's stage of pregnancy. The sac and other materials surrounding the embryo are also examined to look for abnormalities in these structures.
Fetal heart beat — At about 6 weeks after the last menstrual period, the motion of the fetal heart should be visible on ultrasound. If the pregnancy has progressed to the stage where a heart beat should be present, the failure to detect a heart beat during an ultrasound exam indicates that the pregnancy has likely ended.
On the other hand, the presence of a fetal heart beat (in the absence of other abnormalities in the pregnancy) indicates the pregnancy may still be viable and that miscarriage may not occur.
Doctors will also evaluate the rate of the fetal heart. A fetal heart beat that is slower than normal (120 to 170 beats per minute) can indicate that a miscarriage is likely.
TREATMENT OPTIONS — Once it has been determined that a miscarriage is inevitable or is already occurring , several options are available depending on the stage of the miscarriage, the condition of the mother, and other factors. The three main options are: observation, medical treatment, or surgical treatment.
Observation — In some situations, women having a miscarriage require little treatment. Many women with complete miscarriage fall into this group. In addition, women who miscarry at less than 13 weeks of pregnancy and have stable vital signs and no signs of infection can often be managed without medical or surgical treatment. In time, the contents of the uterus will pass, usually within two weeks of diagnosis, but sometimes as long as 3 to 4 weeks later. Once the contents have been passed, an ultrasound is done to ensure that the miscarriage is complete.
Medical treatment — In some cases, medications can be given to stimulate the uterus to pass the pregnancy tissue. The medicine can be given by mouth or vaginally, and works over several days.
Surgical treatment — The conventional treatment for early miscarriage is a surgical procedure called dilation and curettage, or D and C. The cervix (the opening to the uterus) is dilated, and an instrument is inserted that uses suction and/or a gentle scraping motion to remove the contents of the uterus.
As with any surgical procedure, there are risks of complications. The risks associated with D and C are small, and include perforation of the uterus, formation of scar tissue in the uterus, trauma to the cervix, and infection, which could lead to future fertility problems. The procedure is done in women who do not want to wait for spontaneous passage of the pregnancy, and in women with heavy bleeding or infection.
AFTER MISCARRIAGE — Following miscarriage, a woman is advised to avoid having sex or putting anything into the vagina, such as a douche or tampon. Women have traditionally been told to wait two to three months before trying to become pregnant again, although several studies have shown no increased risks with a shorter interval. Any type of contraception, including an intrauterine device, may be started immediately.
Medications may be given to help decrease bleeding and reduce infection. In addition, women who have an Rh negative blood type (ie, A, B, AB, or O negative) need to receive a drug called Rh(D) immune globulin (RhoGam®). This medicine helps protect future fetuses against problems that can occur if an Rh negative mother is carrying a baby who is Rh positive.
Emotional health — Women experience a range of emotions following miscarriage; there is no right or wrong way to feel. The loss of a pregnancy can cause significant grief. Sometimes these reactions are strong and long-lasting. A woman should let her healthcare provider know if she is feeling profound sadness or depression following pregnancy loss, especially if it continues for greater than two weeks. Referral for grief counseling or other treatment may be beneficial. (See "Patient information: Depression in adults").
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)
The March of Dimes
(www.marchofdimes.com)
Pregnancy & Infant Loss Support, Inc.
(www.nationalshareoffice.com)
[1-4]
Use of UpToDate is subject to the Subscription and License Agreement. REFERENCES 1. Regan, L, Rai, R. Epidemiology and the medical causes of miscarriage. Baillieres Best Pract Res Clin Obstet Gynaecol 2000; 14:839.
2. Wilcox, AJ, Weinberg, CR, O'Connor, JF, et al. Incidence of early loss of pregnancy. N Engl J Med 1988; 319:189.
3. Ankum, WM, Wieringa-De Waard, M, Bindels, PJ. Management of spontaneous miscarriage in the first trimester: an example of putting informed shared decision making into practice. BMJ 2001; 322:1343.
4. Demetroulis, C, Saridogan, E, Kunde, D, Naftalin, AA. A prospective randomized control trial comparing medical and surgical treatment for early pregnancy failure. Hum Reprod 2001; 16:365.
A woman's reproductive system includes the uterus (including the cervix), two ovaries, two fallopian tubes, and the vagina. The fallopian tubes are a pair of hollowed tubes that run from each side of the uterus to the ovaries (show figure 1). Once a month, an egg is released by one of the ovaries and travels down the fallopian tube. If the egg is fertilized in the tube by the male's sperm, pregnancy begins.
Once the egg and sperm join, they rapidly develop new cells. This bundle of cells, called the embryo, normally implants on the inner wall of the uterus. Once implanted, the embryo continues to grow inside a sac of amniotic fluid, sometimes called the "bag of water." After several weeks, the embryo is called a fetus.
INCIDENCE — Miscarriage in early pregnancy is very common. Studies show that about 10 to 20 percent of women who know they are pregnant have a miscarriage some time before 20 weeks of pregnancy; 80 percent of these occur in the first 12 weeks. But the actual rate of miscarriage is even higher since many women have very early miscarriages without ever realizing that they are pregnant. One study that followed women's hormone levels every day in order to detect very early pregnancy found a total pregnancy loss rate of 31 percent.
CAUSES — Many different factors can lead to miscarriage, and it is difficult to say with certainty what causes a particular miscarriage to occur. One or more problems with the pregnancy can be found in a significant percentage of early miscarriages.
As an example, in 1/3 of miscarriages occurring before 8 weeks, there is a pregnancy sac but no embryo inside. This means the egg was fertilized and the cells began to divide, but an embryo did not develop. In other cases, the embryo develops but it is abnormal. Chromosomal abnormalities, in particular, are common. One study found that of 8841 miscarriages, 41 percent had chromosomal abnormalities.
In some cases, medical conditions in the mother, such as uncontrolled diabetes, or structural problems in the reproductive tract, such as uterine fibroids, can lead to miscarriage. (See "Patient information: Care during pregnancy for women with type 1 or 2 diabetes" and see "Patient information: Fibroids").
RISK FACTORS — Several risk factors are associated with a higher rate of miscarriage. Age — Older women are more likely to have a miscarriage than younger women. Number of pregnancies — The risk of miscarriage increases in women who have had been pregnant previously. That is, women who have been pregnant two or more times have an increased risk of miscarriage. Previous miscarriage — Having a miscarriage in the past may increase the risk for a future miscarriage. As an example, the risk of miscarriage in future pregnancy is about 20 percent after one miscarriage, 28 percent after two, and 43 percent after three or more miscarriages. By comparison, only 5 percent of women whose previous pregnancy was successful miscarried in the next pregnancy. Smoking — There is evidence that smoking more than 10 cigarettes a day increases the risk of miscarriage. Alcohol — Drinking more than 30 ounces of alcohol per month doubled the risk of miscarriage in one study. In another, there was an increased risk of miscarriage in women who drank more than 3 drinks per week in the first 12 weeks of pregnancy. No amount of alcohol is known to be safe during pregnancy. Fever — Pregnant women who develop fevers of 100ºF (37.5ºC) or more appear to have an increased risk of miscarriage. Trauma — Trauma to the uterus can increase the risk of miscarriage. This includes some forms of prenatal testing, such as amniocentesis or chorionic villus sampling. (See "Patient information: Amniocentesis" and see "Patient information: Chorionic villus sampling"). Caffeine — In one study, some women who ingested 500 mg of caffeine per day had a significantly increased risk of miscarriage (8 ounces of coffee contains 100 to 135 mg of caffeine). Other causes — Women who are exposed to certain substances or conditions may have an increased risk of congenital abnormalities and miscarriage. This includes exposure to certain infections, medications, radiation, physical stresses, and environmental chemicals.
SIGNS AND SYMPTOMS — The most common signs of miscarriage are vaginal bleeding and abdominal pain early in pregnancy. These problems should always be evaluated by a clinician. However, bleeding and discomfort can occur in normal pregnancies. In many cases, bleeding resolves on its own and the pregnancy continues normally without further problems.
Based on particular signs and symptoms, a woman may be diagnosed as follows:
Threatened miscarriage — A woman who has vaginal bleeding early in pregnancy but no other signs of problems is said to have a threatened miscarriage. The cervix, or opening to the uterus, is closed, and the uterus is the right size for the woman's particular stage of pregnancy. If the pregnancy is far enough along, a fetal heart beat may be noted. In many women with threatened miscarriage, the bleeding subsides and the pregnancy continues to term. In others, the bleeding becomes heavier and miscarriage occurs.
Inevitable miscarriage — This means a miscarriage cannot be avoided. The cervix is open, bleeding is heavy or increasing, and abdominal cramping is present.
Incomplete miscarriage — An incomplete miscarriage means that the woman has passed much of the pregnancy tissue, but some remains in the uterus. Typically, the fetus has been passed, but bits of the placenta remain. The cervix remains open, and bleeding may be heavy.
Complete miscarriage — A woman who passes all of the pregnancy tissue is said to have had a complete miscarriage. This is common in miscarriages that occur before 12 weeks of pregnancy. After the miscarriage there is a period of bleeding and cramping, which resolves without medical intervention. On examination, the clinician typically finds that the cervix is closed, and there is no sign of a pregnancy sac in the uterus. Ultrasound examination confirms the diagnosis.
Septic miscarriage — Some women who have miscarriage develop an infection in the uterus. This is known as a septic miscarriage. Symptoms include fever, chills, malaise, abdominal pain, vaginal bleeding, and vaginal discharge, which may be thick and may have an unpleasant odor.
DIAGNOSIS — In some cases, miscarriage is evident based on the woman's symptoms and the physical exam. As an example, with inevitable miscarriage, the cervix is open and pregnancy tissue may be seen in the cervix.
However, in many cases of vaginal bleeding in early pregnancy, ultrasound is used to establish a diagnosis, and/or to help determine if the pregnancy is "viable", that is, whether it is capable of progressing to term. Ultrasound uses sound waves to visualize the structures inside the uterus. In early pregnancy, the exam is often done through the vagina.
Ultrasound — In a woman who has had a complete miscarriage, no pregnancy sac or embryo will be seen on ultrasound. In other women, a pregnancy sac will be seen but it will be abnormal or an embryo will not be present, indicating that the pregnancy is not viable.
If an embryo is present, its size is measured and compared to the size that is expected at the woman's stage of pregnancy. The sac and other materials surrounding the embryo are also examined to look for abnormalities in these structures.
Fetal heart beat — At about 6 weeks after the last menstrual period, the motion of the fetal heart should be visible on ultrasound. If the pregnancy has progressed to the stage where a heart beat should be present, the failure to detect a heart beat during an ultrasound exam indicates that the pregnancy has likely ended.
On the other hand, the presence of a fetal heart beat (in the absence of other abnormalities in the pregnancy) indicates the pregnancy may still be viable and that miscarriage may not occur.
Doctors will also evaluate the rate of the fetal heart. A fetal heart beat that is slower than normal (120 to 170 beats per minute) can indicate that a miscarriage is likely.
TREATMENT OPTIONS — Once it has been determined that a miscarriage is inevitable or is already occurring , several options are available depending on the stage of the miscarriage, the condition of the mother, and other factors. The three main options are: observation, medical treatment, or surgical treatment.
Observation — In some situations, women having a miscarriage require little treatment. Many women with complete miscarriage fall into this group. In addition, women who miscarry at less than 13 weeks of pregnancy and have stable vital signs and no signs of infection can often be managed without medical or surgical treatment. In time, the contents of the uterus will pass, usually within two weeks of diagnosis, but sometimes as long as 3 to 4 weeks later. Once the contents have been passed, an ultrasound is done to ensure that the miscarriage is complete.
Medical treatment — In some cases, medications can be given to stimulate the uterus to pass the pregnancy tissue. The medicine can be given by mouth or vaginally, and works over several days.
Surgical treatment — The conventional treatment for early miscarriage is a surgical procedure called dilation and curettage, or D and C. The cervix (the opening to the uterus) is dilated, and an instrument is inserted that uses suction and/or a gentle scraping motion to remove the contents of the uterus.
As with any surgical procedure, there are risks of complications. The risks associated with D and C are small, and include perforation of the uterus, formation of scar tissue in the uterus, trauma to the cervix, and infection, which could lead to future fertility problems. The procedure is done in women who do not want to wait for spontaneous passage of the pregnancy, and in women with heavy bleeding or infection.
AFTER MISCARRIAGE — Following miscarriage, a woman is advised to avoid having sex or putting anything into the vagina, such as a douche or tampon. Women have traditionally been told to wait two to three months before trying to become pregnant again, although several studies have shown no increased risks with a shorter interval. Any type of contraception, including an intrauterine device, may be started immediately.
Medications may be given to help decrease bleeding and reduce infection. In addition, women who have an Rh negative blood type (ie, A, B, AB, or O negative) need to receive a drug called Rh(D) immune globulin (RhoGam®). This medicine helps protect future fetuses against problems that can occur if an Rh negative mother is carrying a baby who is Rh positive.
Emotional health — Women experience a range of emotions following miscarriage; there is no right or wrong way to feel. The loss of a pregnancy can cause significant grief. Sometimes these reactions are strong and long-lasting. A woman should let her healthcare provider know if she is feeling profound sadness or depression following pregnancy loss, especially if it continues for greater than two weeks. Referral for grief counseling or other treatment may be beneficial. (See "Patient information: Depression in adults").
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)
The March of Dimes
(www.marchofdimes.com)
Pregnancy & Infant Loss Support, Inc.
(www.nationalshareoffice.com)
[1-4]
Use of UpToDate is subject to the Subscription and License Agreement. REFERENCES 1. Regan, L, Rai, R. Epidemiology and the medical causes of miscarriage. Baillieres Best Pract Res Clin Obstet Gynaecol 2000; 14:839.
2. Wilcox, AJ, Weinberg, CR, O'Connor, JF, et al. Incidence of early loss of pregnancy. N Engl J Med 1988; 319:189.
3. Ankum, WM, Wieringa-De Waard, M, Bindels, PJ. Management of spontaneous miscarriage in the first trimester: an example of putting informed shared decision making into practice. BMJ 2001; 322:1343.
4. Demetroulis, C, Saridogan, E, Kunde, D, Naftalin, AA. A prospective randomized control trial comparing medical and surgical treatment for early pregnancy failure. Hum Reprod 2001; 16:365.
Ectopic (tubal) pregnancy
DEFINITION — Ectopic pregnancy occurs when a developing embryo implants at a site other than the inside wall of the uterus. A brief overview of early pregnancy may be helpful in understanding ectopic pregnancy.
Normal pregnancy — A woman's reproductive system includes the uterus, two ovaries, two fallopian tubes, and the vagina. The fallopian tubes are narrow tubes that link the ovaries and uterus (show figure 1). Once a month, an egg is released by one of the ovaries (ovulation) and travels down the fallopian tube to the uterine cavity. In women undergoing treatment for infertility, more than one egg may be released by the ovary. If the egg is fertilized in the fallopian tube by the male's sperm, pregnancy begins.
Once joined, the egg and sperm begin to rapidly develop new cells. This group of cells, called the embryo, normally implants on the inner wall of the uterus, called the endometrium. Once implanted, the embryo continues to grow and also forms the placenta, the organ that provides a blood supply for the developing embryo.
Ectopic pregnancy — In an ectopic pregnancy, the developing embryo does not implant on the endometrial wall, but instead attaches to some other surface. Ninety eight percent of the time, that surface is within fallopian tubes. An ectopic pregnancy in a fallopian tube is sometimes called a tubal pregnancy.
Very rarely, the developing embryo will attach to another site such as the cervix or an ovary. It can also implant at the site where the fallopian tube and uterus join; this is called an interstitial pregnancy, or on the abdominal wall. Rarely in twin pregnancies, one embryo implants in the uterus and the other implants at an ectopic location. This rare event is called a heterotopic pregnancy and occurs more commonly in women undergoing infertility treatments.
Embryos that do not implant in the uterine wall are generally unable to develop normally. In addition, an ectopic pregnancy can cause rupture of the organ on which they are implanted, typically the fallopian tube. Rupture can result in severe internal bleeding, shock, and possibly death of the mother. Fortunately, the ability to diagnose, monitor, and treat ectopic pregnancy reduces the risk of life-threatening complications.
RISK FACTORS — A number of factors increase the risk for ectopic pregnancy. They can be divided into strong, moderate, and weak risk factors.
Strong risk factors Abnormalities of the fallopian tubes — If the fallopian tubes are damaged or abnormal as a result of previous infection or surgery, tumors, or rarely, due to malformations present since birth, there is an increased risk of ectopic pregnancy. Surgery to reconstruct the fallopian tube (to improve a woman's chances of becoming pregnant) can increase the risk of ectopic pregnancy, although preexisting tubal damage poses an even greater risk. Previous ectopic pregnancy — Women who have had one ectopic pregnancy have an increased risk for having another. The underlying tubal disorder that led to the first ectopic, and the effects of treating the first episode increase the risk for another ectopic pregnancy. In-utero diethylstilbestrol (DES) exposure — Women whose mothers took DES while pregnant are more likely to have abnormalities of the fallopian tubes and are at increased risk for an ectopic pregnancy.
Moderate risk factors Previous genital infections — Pelvic infection with gonorrhea or chlamydia is a major cause of tubal problems and increases the risk of ectopic pregnancy. Infertility — The incidence of ectopic pregnancy is higher in the infertility population, mostly due to the increased incidence of tubal abnormalities in these women. Fertility drugs also appear to alter tubal function by their effects on hormones and may be associated with the increased risk in this population. Multiple sexual partners — Having more than one sexual partner is associated with an increased risk of pelvic infection, and therefore an increased risk of ectopic pregnancy.
Weak risk factors Smoking — Cigarette smoking around the time of conception increases the risk of ectopic pregnancy; the risk increases with the number of cigarettes smoked. This risk may be the result of impaired immunity in smokers, which predisposes them to pelvic infection or impaired functioning of the fallopian tubes. Vaginal douching — Regular vaginal douching is associated with increased risk of both pelvic infections and ectopic pregnancy. Douching is never recommended under any circumstance. Age — Having a first sexual encounter at a young age (less than 18) slightly increases the risk of ectopic pregnancy.
Other risk factors In vitro fertilization (IVF) — IVF, a fertility treatment in which a woman's egg is fertilized outside the body and then placed in her uterus, is associated with an increased risk of both ectopic and heterotopic pregnancy. Tubal sterilization — Tubal sterilization is a surgical procedure in which the fallopian tubes are either cut, ligated, or coagulated. It is commonly known as having the "tubes tied," and is performed to prevent future pregnancies. Rarely, tubal sterilization fails and pregnancy can result. Women who become pregnant after tubal sterilization have a higher risk for ectopic pregnancy. Intrauterine contraceptive devices — Women who become pregnant while using an intrauterine contraceptive device (IUD) are at higher risk for ectopic pregnancy than women using other forms of contraception or no contraception.
SYMPTOMS — Symptoms, when they occur, appear early in pregnancy and often before the woman realizes she is pregnant. They include abdominal pain, amenorrhea (absence of a period), and vaginal bleeding, which may be minimal. Symptoms of pregnancy (such as breast tenderness, frequent urination, or nausea) may also be present.
However, over 50 percent of women have no symptoms until rupture occurs. Following rupture of the tube, the woman may experience severe pain and profound hemorrhage (bleeding). Lightheadedness or dizziness may occur first, followed by a drop in blood pressure, fainting, and shock. If there is severe bleeding, shock can progress to death.
Sometimes, the embryo is expelled by the fallopian tube before rupture occurs. This is called a "tubal abortion." Once expelled, the embryonic tissue may degenerate, or it may reimplant in the abdominal cavity or on the ovary. Tubal abortion can be accompanied by severe intra-abdominal bleeding requiring surgical intervention, or by minimal bleeding that does not require treatment.
Ectopic pregnancies can sometimes resolve on their own, but the incidence of spontaneous resolution is not known. Because an ectopic pregnancy poses such great risk to the mother, it should be treated as soon as possible after it is diagnosed.
DIAGNOSIS — Transvaginal ultrasound and a blood test that measures the pregnancy hormone, hCG (human chorionic gonadotropin), are used to diagnose ectopic pregnancy. Ultrasound technology uses sound waves to visualize structures within the body. In a transvaginal ultrasound, the ultrasound transducer is inserted into the woman's vagina allowing clearer visualization of the uterus and other pelvic organs. It can generally detect intrauterine pregnancies that are 5 to 6 weeks along. Ultrasound is most useful for identifying an intrauterine gestation. An extrauterine pregnancy will be visualized in only 16 to 32 percent of women, therefore a negative pelvic ultrasound (that is, no intrauterine or extrauterine gestation is seen) does not exclude the possibility of an ectopic pregnancy. hCG (human chorionic gonadotropin) is a substance secreted by the developing embryo/placenta. The hCG blood level is measured to confirm a pregnancy and can be used to monitor the progress of the early pregnant state.
Ectopic pregnancy is diagnosed if the ultrasound detects a fetal heart beat or an embryo that is outside of the uterus. Since ectopic pregnancies may not be detected by ultrasound, the hCG level is also measured. If the hCG is above a threshold level (usually 1500 mIU/mL), but no pregnancy is seen with ultrasound, an ectopic pregnancy is suspected. A value below this level may indicate either an ectopic pregnancy or early intrauterine pregnancy. When this happens, the ultrasound and hCG are repeated every few days until an ectopic pregnancy can be either confirmed or ruled out.
Women with moderate or strong risk factors for ectopic pregnancy, and those who conceived after IVF, are often monitored with ultrasound and blood testing after their first missed period to ensure early detection and treatment of a potential ectopic pregnancy.
TREATMENT — An ectopic pregnancy must be treated to stop its growth; observation or "watch and wait" treatment is never recommended as the life of the mother is at risk if treatment is delayed. Treatment is started as soon as a diagnosis of ectopic pregnancy is confirmed. Ectopic pregnancy may be treated with medication or surgery.
Medical management — The majority of unruptured ectopic pregnancies are treated with methotrexate, which inhibits the production of new cells and halts further growth of the embryo. It is given in an intramuscular injection. After the injection, the woman may experience abdominal pain or cramps, which can usually be controlled with acetaminophen (Tylenol®). Nonsteroidal antiinflammatory drugs should be avoided due to the risk of an interaction between NSAIDs and methotrexate.
hCG levels are monitored once weekly until the level has fallen to less than 10 mIU/mL. In 20 percent of women, a second dose of methotrexate is necessary; this is recommended if the day 7 hCG level has not fallen by at least 25 percent. In some cases, multiple doses of methotrexate are required.
Methotrexate is most successful in women who have an ectopic pregnancy without symptoms (eg, pain), and whose hCG level and ultrasound results fall within specified limits. When used in appropriate situations, treatment with methotrexate is successful 92 to 98 percent of the time (show table 1). If treatment with methotrexate is unsuccessful, tubal rupture can occur. This complication can be avoided with close monitoring and surgical management, if needed.
Surgical management — Surgery is sometimes recommended as treatment for ectopic pregnancy. Indications include: Ruptured ectopic pregnancy, especially when the woman's blood pressure has fallen and she is unstable. A woman who is unable or unwilling to return for monitoring after methotrexate therapy. A woman who would normally be a candidate for medical treatment, but who could not reach a hospital (due to lack of transportation or distance to an appropriate healthcare facility) in the event of tubal rupture during medical therapy.
Surgery may be performed using a laparoscopic approach or through an abdominal incision. In laparoscopy, special instruments are inserted into the abdomen through a few small incisions. These instruments are used to visualize and remove the ectopic pregnancy and control bleeding. In an abdominal procedure, the surgeon opens the abdomen using a single larger incision and then directly visualizes and removes the ectopic pregnancy.
Surgical management may include removal of the fallopian tube (called total or partial salpingectomy) or may remove the ectopic pregnancy and repair the tube (called salpingostomy). Leaving the tube in place is an option for some women and is preferred if the woman would like to become pregnant in the future. Some conditions require removal of the tube, including uncontrolled bleeding, recurrent ectopic pregnancy in the same tube, a severely damaged tube, or a large tubal pregnancy. It may also be performed in women who have completed childbearing.
In a small number of women treated surgically, embryonic tissue may still be present after surgery and cause the hCG level to remain elevated. A dose of methotrexate may be given if this occurs.
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)
The Nemours Foundation
(http://kidshealth.org)
Planned Parenthood Federation of America
(www.plannedparenthood.org)
Mayo Clinic
(www.mayoclinic.com)
[1-4]
Use of UpToDate is subject to the Subscription and License Agreement. REFERENCES 1. Ankum, WM, Mol, BWJ, Van Der Veen, F, Bossuyt, PMM. Risk factors for ectopic pregnancy: a meta-analysis. Fertil Steril 1996; 65:1093.
2. Yao, M, Tulandi, T. Current status of surgical and non-surgical treatment of ectopic pregnancy. Fertil Steril 1997; 67:421.
3. Tulandi, T. Current protocol for ectopic pregnancy. Contemp Obstet Gynecol 1999; 44:42.
4. Practical and current management of tubal and nontubal ectopic pregnancy. Curr Probl Obstet Gynecol Fertil 2000; 23:94.
Normal pregnancy — A woman's reproductive system includes the uterus, two ovaries, two fallopian tubes, and the vagina. The fallopian tubes are narrow tubes that link the ovaries and uterus (show figure 1). Once a month, an egg is released by one of the ovaries (ovulation) and travels down the fallopian tube to the uterine cavity. In women undergoing treatment for infertility, more than one egg may be released by the ovary. If the egg is fertilized in the fallopian tube by the male's sperm, pregnancy begins.
Once joined, the egg and sperm begin to rapidly develop new cells. This group of cells, called the embryo, normally implants on the inner wall of the uterus, called the endometrium. Once implanted, the embryo continues to grow and also forms the placenta, the organ that provides a blood supply for the developing embryo.
Ectopic pregnancy — In an ectopic pregnancy, the developing embryo does not implant on the endometrial wall, but instead attaches to some other surface. Ninety eight percent of the time, that surface is within fallopian tubes. An ectopic pregnancy in a fallopian tube is sometimes called a tubal pregnancy.
Very rarely, the developing embryo will attach to another site such as the cervix or an ovary. It can also implant at the site where the fallopian tube and uterus join; this is called an interstitial pregnancy, or on the abdominal wall. Rarely in twin pregnancies, one embryo implants in the uterus and the other implants at an ectopic location. This rare event is called a heterotopic pregnancy and occurs more commonly in women undergoing infertility treatments.
Embryos that do not implant in the uterine wall are generally unable to develop normally. In addition, an ectopic pregnancy can cause rupture of the organ on which they are implanted, typically the fallopian tube. Rupture can result in severe internal bleeding, shock, and possibly death of the mother. Fortunately, the ability to diagnose, monitor, and treat ectopic pregnancy reduces the risk of life-threatening complications.
RISK FACTORS — A number of factors increase the risk for ectopic pregnancy. They can be divided into strong, moderate, and weak risk factors.
Strong risk factors Abnormalities of the fallopian tubes — If the fallopian tubes are damaged or abnormal as a result of previous infection or surgery, tumors, or rarely, due to malformations present since birth, there is an increased risk of ectopic pregnancy. Surgery to reconstruct the fallopian tube (to improve a woman's chances of becoming pregnant) can increase the risk of ectopic pregnancy, although preexisting tubal damage poses an even greater risk. Previous ectopic pregnancy — Women who have had one ectopic pregnancy have an increased risk for having another. The underlying tubal disorder that led to the first ectopic, and the effects of treating the first episode increase the risk for another ectopic pregnancy. In-utero diethylstilbestrol (DES) exposure — Women whose mothers took DES while pregnant are more likely to have abnormalities of the fallopian tubes and are at increased risk for an ectopic pregnancy.
Moderate risk factors Previous genital infections — Pelvic infection with gonorrhea or chlamydia is a major cause of tubal problems and increases the risk of ectopic pregnancy. Infertility — The incidence of ectopic pregnancy is higher in the infertility population, mostly due to the increased incidence of tubal abnormalities in these women. Fertility drugs also appear to alter tubal function by their effects on hormones and may be associated with the increased risk in this population. Multiple sexual partners — Having more than one sexual partner is associated with an increased risk of pelvic infection, and therefore an increased risk of ectopic pregnancy.
Weak risk factors Smoking — Cigarette smoking around the time of conception increases the risk of ectopic pregnancy; the risk increases with the number of cigarettes smoked. This risk may be the result of impaired immunity in smokers, which predisposes them to pelvic infection or impaired functioning of the fallopian tubes. Vaginal douching — Regular vaginal douching is associated with increased risk of both pelvic infections and ectopic pregnancy. Douching is never recommended under any circumstance. Age — Having a first sexual encounter at a young age (less than 18) slightly increases the risk of ectopic pregnancy.
Other risk factors In vitro fertilization (IVF) — IVF, a fertility treatment in which a woman's egg is fertilized outside the body and then placed in her uterus, is associated with an increased risk of both ectopic and heterotopic pregnancy. Tubal sterilization — Tubal sterilization is a surgical procedure in which the fallopian tubes are either cut, ligated, or coagulated. It is commonly known as having the "tubes tied," and is performed to prevent future pregnancies. Rarely, tubal sterilization fails and pregnancy can result. Women who become pregnant after tubal sterilization have a higher risk for ectopic pregnancy. Intrauterine contraceptive devices — Women who become pregnant while using an intrauterine contraceptive device (IUD) are at higher risk for ectopic pregnancy than women using other forms of contraception or no contraception.
SYMPTOMS — Symptoms, when they occur, appear early in pregnancy and often before the woman realizes she is pregnant. They include abdominal pain, amenorrhea (absence of a period), and vaginal bleeding, which may be minimal. Symptoms of pregnancy (such as breast tenderness, frequent urination, or nausea) may also be present.
However, over 50 percent of women have no symptoms until rupture occurs. Following rupture of the tube, the woman may experience severe pain and profound hemorrhage (bleeding). Lightheadedness or dizziness may occur first, followed by a drop in blood pressure, fainting, and shock. If there is severe bleeding, shock can progress to death.
Sometimes, the embryo is expelled by the fallopian tube before rupture occurs. This is called a "tubal abortion." Once expelled, the embryonic tissue may degenerate, or it may reimplant in the abdominal cavity or on the ovary. Tubal abortion can be accompanied by severe intra-abdominal bleeding requiring surgical intervention, or by minimal bleeding that does not require treatment.
Ectopic pregnancies can sometimes resolve on their own, but the incidence of spontaneous resolution is not known. Because an ectopic pregnancy poses such great risk to the mother, it should be treated as soon as possible after it is diagnosed.
DIAGNOSIS — Transvaginal ultrasound and a blood test that measures the pregnancy hormone, hCG (human chorionic gonadotropin), are used to diagnose ectopic pregnancy. Ultrasound technology uses sound waves to visualize structures within the body. In a transvaginal ultrasound, the ultrasound transducer is inserted into the woman's vagina allowing clearer visualization of the uterus and other pelvic organs. It can generally detect intrauterine pregnancies that are 5 to 6 weeks along. Ultrasound is most useful for identifying an intrauterine gestation. An extrauterine pregnancy will be visualized in only 16 to 32 percent of women, therefore a negative pelvic ultrasound (that is, no intrauterine or extrauterine gestation is seen) does not exclude the possibility of an ectopic pregnancy. hCG (human chorionic gonadotropin) is a substance secreted by the developing embryo/placenta. The hCG blood level is measured to confirm a pregnancy and can be used to monitor the progress of the early pregnant state.
Ectopic pregnancy is diagnosed if the ultrasound detects a fetal heart beat or an embryo that is outside of the uterus. Since ectopic pregnancies may not be detected by ultrasound, the hCG level is also measured. If the hCG is above a threshold level (usually 1500 mIU/mL), but no pregnancy is seen with ultrasound, an ectopic pregnancy is suspected. A value below this level may indicate either an ectopic pregnancy or early intrauterine pregnancy. When this happens, the ultrasound and hCG are repeated every few days until an ectopic pregnancy can be either confirmed or ruled out.
Women with moderate or strong risk factors for ectopic pregnancy, and those who conceived after IVF, are often monitored with ultrasound and blood testing after their first missed period to ensure early detection and treatment of a potential ectopic pregnancy.
TREATMENT — An ectopic pregnancy must be treated to stop its growth; observation or "watch and wait" treatment is never recommended as the life of the mother is at risk if treatment is delayed. Treatment is started as soon as a diagnosis of ectopic pregnancy is confirmed. Ectopic pregnancy may be treated with medication or surgery.
Medical management — The majority of unruptured ectopic pregnancies are treated with methotrexate, which inhibits the production of new cells and halts further growth of the embryo. It is given in an intramuscular injection. After the injection, the woman may experience abdominal pain or cramps, which can usually be controlled with acetaminophen (Tylenol®). Nonsteroidal antiinflammatory drugs should be avoided due to the risk of an interaction between NSAIDs and methotrexate.
hCG levels are monitored once weekly until the level has fallen to less than 10 mIU/mL. In 20 percent of women, a second dose of methotrexate is necessary; this is recommended if the day 7 hCG level has not fallen by at least 25 percent. In some cases, multiple doses of methotrexate are required.
Methotrexate is most successful in women who have an ectopic pregnancy without symptoms (eg, pain), and whose hCG level and ultrasound results fall within specified limits. When used in appropriate situations, treatment with methotrexate is successful 92 to 98 percent of the time (show table 1). If treatment with methotrexate is unsuccessful, tubal rupture can occur. This complication can be avoided with close monitoring and surgical management, if needed.
Surgical management — Surgery is sometimes recommended as treatment for ectopic pregnancy. Indications include: Ruptured ectopic pregnancy, especially when the woman's blood pressure has fallen and she is unstable. A woman who is unable or unwilling to return for monitoring after methotrexate therapy. A woman who would normally be a candidate for medical treatment, but who could not reach a hospital (due to lack of transportation or distance to an appropriate healthcare facility) in the event of tubal rupture during medical therapy.
Surgery may be performed using a laparoscopic approach or through an abdominal incision. In laparoscopy, special instruments are inserted into the abdomen through a few small incisions. These instruments are used to visualize and remove the ectopic pregnancy and control bleeding. In an abdominal procedure, the surgeon opens the abdomen using a single larger incision and then directly visualizes and removes the ectopic pregnancy.
Surgical management may include removal of the fallopian tube (called total or partial salpingectomy) or may remove the ectopic pregnancy and repair the tube (called salpingostomy). Leaving the tube in place is an option for some women and is preferred if the woman would like to become pregnant in the future. Some conditions require removal of the tube, including uncontrolled bleeding, recurrent ectopic pregnancy in the same tube, a severely damaged tube, or a large tubal pregnancy. It may also be performed in women who have completed childbearing.
In a small number of women treated surgically, embryonic tissue may still be present after surgery and cause the hCG level to remain elevated. A dose of methotrexate may be given if this occurs.
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)
The Nemours Foundation
(http://kidshealth.org)
Planned Parenthood Federation of America
(www.plannedparenthood.org)
Mayo Clinic
(www.mayoclinic.com)
[1-4]
Use of UpToDate is subject to the Subscription and License Agreement. REFERENCES 1. Ankum, WM, Mol, BWJ, Van Der Veen, F, Bossuyt, PMM. Risk factors for ectopic pregnancy: a meta-analysis. Fertil Steril 1996; 65:1093.
2. Yao, M, Tulandi, T. Current status of surgical and non-surgical treatment of ectopic pregnancy. Fertil Steril 1997; 67:421.
3. Tulandi, T. Current protocol for ectopic pregnancy. Contemp Obstet Gynecol 1999; 44:42.
4. Practical and current management of tubal and nontubal ectopic pregnancy. Curr Probl Obstet Gynecol Fertil 2000; 23:94.
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