Management of Osteoporosis in Postmenopausal Women: 2010 Position Statement
Management of Osteoporosis in Postmenopausal Women: 2010 Position Statement
All postmenopausal women should be assessed for risk factors associated with osteoporosis and fracture. This assessment requires a history, physical examination, and any necessary diagnostic tests. The goals of this evaluation are to evaluate fracture risk, to rule out secondary causes of osteoporosis, to identify modifiable risk factors, and to determine appropriate candidates for pharmacologic therapy.
The medical history and physical examination should solicit clinical risk factors for osteoporosis and fracture and also evaluate for secondary causes of osteoporosis and fragility fracture. This includes the WHO's FRAX risk factors (personal history of fracture after age 40, history of hip fracture in a parent, cigarette smoking, excess alcohol consumption, glucocorticoid use, RA, or other secondary causes of osteoporosis. See Table 1). Risk factors must be accurately collected, often with the aid of a simple questionnaire. Risk factors may help identify contributing causes of osteoporosis and are essential in the determination of FRAX. This tool, used with guidelines for treatment thresholds, is very helpful in identifying candidates for pharmacotherapy. Osteoporosis can be diagnosed by bone density testing in postmenopausal women over age 50. A fragility fracture can also indicate a clinical diagnosis of osteoporosis.
Loss of height and kyphosis may be signs of vertebral fracture. After achieving maximal height, women can lose up to 1.0 to 1.5 inches (2.0–3.8 cm) of height as part of the normal aging process, primarily as a result of degenerative arthritis and shrinkage of intervertebral disks. Height loss greater than 1.5 inches (3.8 cm) increases the likelihood that a vertebral fracture is present. Height should be measured annually with an accurate method, such as a wall-mounted ruler or a stadiometer. Loss of 1.5 inches (3.8 cm) or more calls for evaluation by a lateral thoracolumbar radiograph or vertebral fracture assessment (VFA) by DXA to identify vertebral fractures.
Weight should also be recorded to identify those women with low BMI and to be aware of weight changes, which may interfere with the interpretation of changes in BMD over time.
The evaluation should include eliciting symptoms of acute or chronic back pain, which may indicate the presence of vertebral fractures. Signs of percussion tenderness may indicate acute fracture or bony infiltrative disease. The midback vertebrae T11-T12 and L1 are the most common fracture sites, followed by T6 through T9. Vertebral compression fractures may result in kyphosis, the most obvious sign of osteoporosis.
Because back pain, height loss, and kyphosis can occur without osteoporosis, and because two thirds of vertebral fractures are asymptomatic, vertebral fracture must be confirmed by lateral spine radiographs or VFA visualization of fracture at the time of BMD testing. Vertebral height loss of more than 20%—more than 2 mm (measured) or 4 mm (historical)—of the anterior, mid, or posterior dimension of a vertebra on imaging is indicative of vertebral fracture. Grading of vertebral fractures and percentage of height reduction (grade 1, mild, 20%–25%; grade 2, moderate, 25%–40%; grade 3, severe, over 40%) by a Genant semiquantitative methodology or equivalent is most important in the evaluation of the patient with severe osteoporosis. Both the number and the severity of existing vertebral fractures predict the risk of future fracture.
After menopause, a woman's risk for falls should be assessed. Clinical factors related to an increased risk of falls include the following:
The risk of falls is also increased by use of medications that affect balance and coordination (eg, sedatives, narcotic analgesics, anticholinergics, antihypertensives) or by use of multiple medications.
The greater the number of risk factors, the greater the risk of falling. In one study, having four or more of these risk factors increased the risk of falls by nearly 80%. Several studies have indicated that exercise and gait/balance training may decrease the risk of falls.
Safety hazards in the home and work environment, such as obstacles and poor lighting, also contribute to the risk of falls. These hazards can be assessed by questioning the woman or through a home or workplace visit (or both) by an occupational therapist or other healthcare professional knowledgeable about fall prevention.
BMD testing of hip (femoral neck, total hip), spine (at least two vertebral bodies), or radius (one-third radius site) is required for a densitometric diagnosis of osteoporosis. Measurements of bone strength other than bone density at these sites may predict fracture risk but cannot be used to diagnose osteoporosis. A clinical diagnosis of osteoporosis can be made if fragility fractures are present, regardless of the BMD.
Indications for BMD Testing The decision to test BMD in a postmenopausal woman should be based on the woman's risk profile. Testing is not indicated unless the results will influence a management decision. Although perimenopausal women can be classified by WHO criteria and may be candidates for FRAX risk assessment, care must be taken to appropriately interpret DXA tests and to make correct recommendations for risk factor reduction and sometimes pharmacotherapy. Other factors, such as availability of BMD testing equipment and reimbursement by insurance, also affect the decision to measure BMD.
NAMS recommends that BMD be measured in the following populations:
Testing should be considered for postmenopausal women age 50 and over when one or more of the following risk factors for fracture have been identified:
Bone-testing Options Fracture risk can be estimated by a variety of technologies at numerous skeletal sites. BMD measured by DXA is the only diagnostic technology by which measurements are made at hip, spine, and radius. These are also important sites of osteoporotic fracture.
When BMD testing is indicated, NAMS recommends measuring the total hip, femoral neck, and posterior-anterior lumbar spine, using the lowest of the three BMD scores for diagnosis. In some patients, degenerative or other artifacts at the spine site make measurements unreliable. In such cases, the one-third radius should be measured and used as a second site valid for diagnosis. The spine may be a useful site for BMD measurement in early postmenopausal women because decreases in BMD can be faster at the spine than at the hip.
Although bone tests at peripheral sites (eg, tibia, finger, calcaneus) can identify women at risk of fracture, they are not useful for the diagnosis of osteoporosis and have limited or no value in the follow-up of patients. Peripheral site measurements may be useful to raise awareness about bone health and have been utilized as a prescreen for DXA testing where DXA availability is limited.
Follow-up BMD Testing In most cases, repeat DXA testing in untreated postmenopausal women is not useful until 2 to 5 years have passed, given the rate of bone loss of 1% to 1.5% per year. Postmenopausal women, after substantial BMD losses in early postmenopause, generally lose about 0.5 T-score units in BMD every 5 years.
For women receiving osteoporosis therapy, BMD monitoring may not provide clinically useful information until after 1 to 2 years of treatment. Stable BMD (within the precision error of the instrument) indicates successful therapy; fracture risk reductions for patients on antiresorptive therapy are similar with stable bone density or with increases in BMD. Marked declines in BMD predict greater fracture risk and should trigger a reevaluation for secondary causes of osteoporosis or treatment nonadherence.
Each DXA testing center should perform precision testing to determine the least significant change that can be detected in their patient population. Statistically insignificant decreases in BMD should be reported as stable bone density within the precision error of the instrument. Statistically significant changes in BMD (equal to or greater than the least significant change) should be reported as such.
Biochemical markers of bone turnover can be measured in serum or urine. They can indicate either osteoclastic bone resorption (breakdown products of type I collagen in bone: N-telopeptides, C-telopeptides, deoxypyridinoline) or osteoblast functioning (bone matrix synthesis: bone-specific alkaline phosphatase, procollagen type I N-terminal propeptide, osteocalcin). Bone turnover markers cannot diagnose osteoporosis and have varying ability to predict fracture risk when studied in groups of patients in clinical trials. They also have varying value in predicting individual patient response to therapy. Nevertheless, these tests may show an individual patient's response to therapy earlier than BMD changes, sometimes within 2 to 3 months as opposed to the 1 to 3 years required with BMD. Most bone turnover markers vary greatly from day to day, are affected by food intake and time of day, and lack assay standardization, limiting their clinical utility. In some cases, persistently elevated bone turnover markers in the face of antiresorptive therapy may alert the clinician to nonadherence to therapy, poor absorption of medication, or other secondary causes of osteoporosis.
The value of bone turnover markers in encouraging adherence to therapy has been debated. Several trials have found no difference in adherence when marker values are communicated to women.
Low BMD in postmenopausal women is most often the result of low peak bone mass, postmenopausal declines in bone density (related to estrogen deficiency), or both. There are, however, important secondary causes of bone loss, which should be identified clinically and through appropriate laboratory testing. Laboratory tests that may be useful in some circumstances are listed in Table 3. Routine tests for patients with low bone mass include a complete blood cell count, serum calcium, phosphate, creatinine, thyroid-stimulating hormone, alkaline phosphatase, and albumin. Tests for serum 25-hydroxyvitamin D [25(OH)D] and 24-hour urinary calcium excretion may be useful to detect patients with poor calcium and vitamin D nutrition as well as those with hypercalciuria. Special tests that may be appropriate in some clinical circumstances include 24-hour urine free cortisol, serum protein electrophoresis, tissue transglutaminase antibody, and intact parathyroid hormone (PTH).
Evaluation
All postmenopausal women should be assessed for risk factors associated with osteoporosis and fracture. This assessment requires a history, physical examination, and any necessary diagnostic tests. The goals of this evaluation are to evaluate fracture risk, to rule out secondary causes of osteoporosis, to identify modifiable risk factors, and to determine appropriate candidates for pharmacologic therapy.
History and Physical Examination
The medical history and physical examination should solicit clinical risk factors for osteoporosis and fracture and also evaluate for secondary causes of osteoporosis and fragility fracture. This includes the WHO's FRAX risk factors (personal history of fracture after age 40, history of hip fracture in a parent, cigarette smoking, excess alcohol consumption, glucocorticoid use, RA, or other secondary causes of osteoporosis. See Table 1). Risk factors must be accurately collected, often with the aid of a simple questionnaire. Risk factors may help identify contributing causes of osteoporosis and are essential in the determination of FRAX. This tool, used with guidelines for treatment thresholds, is very helpful in identifying candidates for pharmacotherapy. Osteoporosis can be diagnosed by bone density testing in postmenopausal women over age 50. A fragility fracture can also indicate a clinical diagnosis of osteoporosis.
Loss of height and kyphosis may be signs of vertebral fracture. After achieving maximal height, women can lose up to 1.0 to 1.5 inches (2.0–3.8 cm) of height as part of the normal aging process, primarily as a result of degenerative arthritis and shrinkage of intervertebral disks. Height loss greater than 1.5 inches (3.8 cm) increases the likelihood that a vertebral fracture is present. Height should be measured annually with an accurate method, such as a wall-mounted ruler or a stadiometer. Loss of 1.5 inches (3.8 cm) or more calls for evaluation by a lateral thoracolumbar radiograph or vertebral fracture assessment (VFA) by DXA to identify vertebral fractures.
Weight should also be recorded to identify those women with low BMI and to be aware of weight changes, which may interfere with the interpretation of changes in BMD over time.
The evaluation should include eliciting symptoms of acute or chronic back pain, which may indicate the presence of vertebral fractures. Signs of percussion tenderness may indicate acute fracture or bony infiltrative disease. The midback vertebrae T11-T12 and L1 are the most common fracture sites, followed by T6 through T9. Vertebral compression fractures may result in kyphosis, the most obvious sign of osteoporosis.
Because back pain, height loss, and kyphosis can occur without osteoporosis, and because two thirds of vertebral fractures are asymptomatic, vertebral fracture must be confirmed by lateral spine radiographs or VFA visualization of fracture at the time of BMD testing. Vertebral height loss of more than 20%—more than 2 mm (measured) or 4 mm (historical)—of the anterior, mid, or posterior dimension of a vertebra on imaging is indicative of vertebral fracture. Grading of vertebral fractures and percentage of height reduction (grade 1, mild, 20%–25%; grade 2, moderate, 25%–40%; grade 3, severe, over 40%) by a Genant semiquantitative methodology or equivalent is most important in the evaluation of the patient with severe osteoporosis. Both the number and the severity of existing vertebral fractures predict the risk of future fracture.
After menopause, a woman's risk for falls should be assessed. Clinical factors related to an increased risk of falls include the following:
A history of falls, fainting, or loss of consciousness
Muscle weakness
Dizziness, coordination, or balance problems
Difficulty standing or walking
Arthritis of the lower extremities
Neuropathy of the lower extremities
Impaired vision
The risk of falls is also increased by use of medications that affect balance and coordination (eg, sedatives, narcotic analgesics, anticholinergics, antihypertensives) or by use of multiple medications.
The greater the number of risk factors, the greater the risk of falling. In one study, having four or more of these risk factors increased the risk of falls by nearly 80%. Several studies have indicated that exercise and gait/balance training may decrease the risk of falls.
Safety hazards in the home and work environment, such as obstacles and poor lighting, also contribute to the risk of falls. These hazards can be assessed by questioning the woman or through a home or workplace visit (or both) by an occupational therapist or other healthcare professional knowledgeable about fall prevention.
BMD Measurement
BMD testing of hip (femoral neck, total hip), spine (at least two vertebral bodies), or radius (one-third radius site) is required for a densitometric diagnosis of osteoporosis. Measurements of bone strength other than bone density at these sites may predict fracture risk but cannot be used to diagnose osteoporosis. A clinical diagnosis of osteoporosis can be made if fragility fractures are present, regardless of the BMD.
Indications for BMD Testing The decision to test BMD in a postmenopausal woman should be based on the woman's risk profile. Testing is not indicated unless the results will influence a management decision. Although perimenopausal women can be classified by WHO criteria and may be candidates for FRAX risk assessment, care must be taken to appropriately interpret DXA tests and to make correct recommendations for risk factor reduction and sometimes pharmacotherapy. Other factors, such as availability of BMD testing equipment and reimbursement by insurance, also affect the decision to measure BMD.
NAMS recommends that BMD be measured in the following populations:
All women age 65 and over, regardless of clinical risk factors
Postmenopausal women with medical causes of bone loss (eg, steroid use, hyperparathyroidism), regardless of age
Postmenopausal women age 50 and over with additional risk factors (see below)
Postmenopausal women with a fragility fracture (eg, fracture from a fall from standing height)
Testing should be considered for postmenopausal women age 50 and over when one or more of the following risk factors for fracture have been identified:
Fracture (other than skull, facial bone, ankle, finger, and toe) after menopause
Thinness (body weight < 127 lb [57.7 kg] or BMI < 21 kg/m)
History of hip fracture in a parent
Current smoker
Rheumatoid arthritis
Alcohol intake of more than two units per day (one unit is 12 oz of beer, 4 oz of wine, or 1 oz of liquor)
Bone-testing Options Fracture risk can be estimated by a variety of technologies at numerous skeletal sites. BMD measured by DXA is the only diagnostic technology by which measurements are made at hip, spine, and radius. These are also important sites of osteoporotic fracture.
When BMD testing is indicated, NAMS recommends measuring the total hip, femoral neck, and posterior-anterior lumbar spine, using the lowest of the three BMD scores for diagnosis. In some patients, degenerative or other artifacts at the spine site make measurements unreliable. In such cases, the one-third radius should be measured and used as a second site valid for diagnosis. The spine may be a useful site for BMD measurement in early postmenopausal women because decreases in BMD can be faster at the spine than at the hip.
Although bone tests at peripheral sites (eg, tibia, finger, calcaneus) can identify women at risk of fracture, they are not useful for the diagnosis of osteoporosis and have limited or no value in the follow-up of patients. Peripheral site measurements may be useful to raise awareness about bone health and have been utilized as a prescreen for DXA testing where DXA availability is limited.
Follow-up BMD Testing In most cases, repeat DXA testing in untreated postmenopausal women is not useful until 2 to 5 years have passed, given the rate of bone loss of 1% to 1.5% per year. Postmenopausal women, after substantial BMD losses in early postmenopause, generally lose about 0.5 T-score units in BMD every 5 years.
For women receiving osteoporosis therapy, BMD monitoring may not provide clinically useful information until after 1 to 2 years of treatment. Stable BMD (within the precision error of the instrument) indicates successful therapy; fracture risk reductions for patients on antiresorptive therapy are similar with stable bone density or with increases in BMD. Marked declines in BMD predict greater fracture risk and should trigger a reevaluation for secondary causes of osteoporosis or treatment nonadherence.
Each DXA testing center should perform precision testing to determine the least significant change that can be detected in their patient population. Statistically insignificant decreases in BMD should be reported as stable bone density within the precision error of the instrument. Statistically significant changes in BMD (equal to or greater than the least significant change) should be reported as such.
Bone Turnover Markers
Biochemical markers of bone turnover can be measured in serum or urine. They can indicate either osteoclastic bone resorption (breakdown products of type I collagen in bone: N-telopeptides, C-telopeptides, deoxypyridinoline) or osteoblast functioning (bone matrix synthesis: bone-specific alkaline phosphatase, procollagen type I N-terminal propeptide, osteocalcin). Bone turnover markers cannot diagnose osteoporosis and have varying ability to predict fracture risk when studied in groups of patients in clinical trials. They also have varying value in predicting individual patient response to therapy. Nevertheless, these tests may show an individual patient's response to therapy earlier than BMD changes, sometimes within 2 to 3 months as opposed to the 1 to 3 years required with BMD. Most bone turnover markers vary greatly from day to day, are affected by food intake and time of day, and lack assay standardization, limiting their clinical utility. In some cases, persistently elevated bone turnover markers in the face of antiresorptive therapy may alert the clinician to nonadherence to therapy, poor absorption of medication, or other secondary causes of osteoporosis.
The value of bone turnover markers in encouraging adherence to therapy has been debated. Several trials have found no difference in adherence when marker values are communicated to women.
Tests for Secondary Causes
Low BMD in postmenopausal women is most often the result of low peak bone mass, postmenopausal declines in bone density (related to estrogen deficiency), or both. There are, however, important secondary causes of bone loss, which should be identified clinically and through appropriate laboratory testing. Laboratory tests that may be useful in some circumstances are listed in Table 3. Routine tests for patients with low bone mass include a complete blood cell count, serum calcium, phosphate, creatinine, thyroid-stimulating hormone, alkaline phosphatase, and albumin. Tests for serum 25-hydroxyvitamin D [25(OH)D] and 24-hour urinary calcium excretion may be useful to detect patients with poor calcium and vitamin D nutrition as well as those with hypercalciuria. Special tests that may be appropriate in some clinical circumstances include 24-hour urine free cortisol, serum protein electrophoresis, tissue transglutaminase antibody, and intact parathyroid hormone (PTH).