Osteoporosis, the most common bone disorder, has no warning signs and is a serious health threat for aging postmenopausal women. Osteoporotic fractures are associated with significant morbidity and mortality rates in older women, many of whom have lost an average of 30 percent of their peak bone mass by 80 years of age. To address the need for standards of care as they relate to menopause-associated health conditions, the North American Menopause Society (NAMS) has updated its evidence-based guidelines on the diagnosis, prevention, and treatment of osteoporosis in postmenopausal women. The full report was published in the May/June 2006 issue ofMenopause.

The World Health Organization defines osteoporosis in postmenopausal women as a bone mineral density (BMD) T-score of −2.5 or less at the total hip, femoral neck, or lumbar spine (posterior-anterior). Other measures of bone quality (e.g., degree of mineralization, hydroxyapatite crystal size, collagen structure, heterogeneity of bone microstructure, connectivity of trabeculae, microdamage) are difficult or impossible to measure in clinical practice.

Osteoporosis is categorized as primary or secondary. Primary osteoporosis usually is the result of the bone loss that occurs with aging. Secondary osteoporosis is caused by medications (e.g., glucocorticoids), certain medical conditions (e.g., hypogonadism), and diseases (e.g., gastrointestinal malabsorption) that adversely affect skeletal health (Table 1).

Risk Factors

Risk factors for osteoporosis include older age, genetics, lifestyle factors (e.g., smoking, low calcium and vitamin D intake), low body weight or body mass index (BMI), and menopause. Risk factors for osteoporotic fracture are listed in Table 2.

In general, the risk of osteoporotic fracture in women doubles every seven to eight years after 50 years of age; the median age for hip fracture is 82 years. In women 65 years and older, bone density is an important determinant of fracture risk. In general, lower BMD scores indicate more severe osteoporosis and a higher risk of fracture. A decrease of one standard deviation in BMD represents a 10 to 12 percent decrease in BMD and a 1.5- to 2.6-fold increased risk of fracture.

The greatest influence on a woman’s peak bone mass is heredity. Studies have suggested that up to 80 percent of variability in peak bone density may be attributable to genetic factors. First-degree relatives of women with osteoporosis tend to have lower bone density than those with no family history. A history of fracture in a first-degree relative also significantly increases fracture risk. Hip fracture risk is 50 percent greater in persons with a family history of fracture and 127 percent greater if the hip fracture occurred in a parent.

Adequate intake of calcium and vitamin D is required throughout life for a woman to achieve her genetically determined peak bone mass and to maintain optimal bone mass and strength. Low intake of vitamin D is associated with reduced muscle strength, increased rates of bone loss, and increased risk of falls and fractures. Low dietary calcium intake is associated with an increased risk of hip fracture in older postmenopausal women.

Weight-bearing exercises provide significant osteogenic stimulus, and regular exercise has been associated with reduced fracture risk. Exercise also reduces the risk of falls by increasing muscle mass, strength, and balance.

Evidence suggests that cigarette smokers may have impaired calcium absorption and lower 17β-estradiol levels. Compared with nonsmokers, women who smoke lose bone more rapidly, have lower bone mass, and reach menopause an average of two years earlier. Postmenopausal women who smoke have significantly higher fracture rates than nonsmokers. The risk imparted by smoking remains significant even after adjusting for BMD.

Heavy alcohol consumption (i.e., 7 oz or more per week) increases the risk of falls and hip fracture. However, moderate alcohol consumption (i.e., 1 to 2 oz per week) in women 65 years and older is associated with higher BMD and a decreased risk of hip fracture.

Having a BMI of less than 21 kg per m² or a body weight of less than 127 lb (57.6 kg) is a risk factor for low BMD and has been associated with increased fracture risk, especially in older women. Women with a BMI of 20 kg per m² have nearly a twofold increased risk of fracture compared with women who have a BMI in the upper range of normal (i.e., at least 25 kg per m²).

Bone loss begins to accelerate approximately two to three years before the last menses, and this acceleration ends three to four years after menopause. For a few years around menopause, women lose 2 percent of bone annually; this loss later slows to about 1 to 1.5 percent annually. Although some of the decrease in BMD can be attributed to age-related factors, lower estrogen levels seem to account for about two thirds of bone loss. Lower estrogen levels also have been associated with increased fracture risk in older women. Women who experience menopause at or before 40 years of age (either spontaneously or induced) are at greater risk of low BMD than other women of the same age who have not reached menopause. However, by 70 years of age, these women have the same risk for low BMD and fracture as women who reached menopause at the average age.

Diagnosis

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 identify risk factors for fractures and modifiable risk factors for falls and injuries. If osteoporosis is present, its severity must be assessed and secondary causes of osteoporosis must be ruled out.

Loss of height may be a sign of vertebral fracture. After achieving maximal height, women can lose up to 1.5 inches (3.8 cm) of height as part of the normal aging process, primarily as a result of shrinkage of intervertebral disks. Height loss of more than 1.5 inches 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 stadiometer. Patients with a height loss of at least 1.5 inches should be evaluated with lateral thoracolumbar radiography to identify vertebral fractures.

The examination should include assessment for acute or chronic back pain, especially in the middle back, which may indicate the presence of vertebral fractures. The midback vertebrae T11, T12, and L1 are the most common fracture sites, followed by T6 through T9. Multiple severe vertebral compression fractures ultimately result in kyphosis (i.e., abnormal curvature of the thoracic spine), the most obvious sign of osteoporosis.

Back pain, height loss, and kyphosis can occur without osteoporosis, and two thirds of vertebral fractures are asymptomatic. For these reasons, vertebral fracture must be confirmed, usually by lateral spine radiography. Some dual energy x-ray absorptiometry (DEXA) techniques allow assessment of vertebral fractures and may be used to visualize a fracture at the same time that BMD is being measured.

Testing of BMD should be performed based on the individual patient’s risk profile. Testing is not indicated unless the results will influence a treatment decision. NAMS recommends that BMD be measured in all postmenopausal women with medical causes of bone loss and in postmenopausal women 65 years and older. Testing should be considered in healthy postmenopausal women younger than 65 years who have at least one of the following risk factors:

• Current smoker

• History of fracture after menopause (other than skull, facial bone, ankle, finger, and toe fractures)

• BMI of less than 21 kg per m² or body weight of less than 127 lb

• History of hip fracture in a parent.

Several tests to measure BMD are available. DEXA is the preferred technique for measuring central BMD and for diagnosing osteoporosis. When BMD testing is indicated, NAMS recommends measuring the total hip, femoral neck, and posterior-anterior lumbar spine, using the lowest of the three scores. Although testing at peripheral sites (e.g., wrist, calcaneus) can identify women with low bone mass, it is not as useful as central-site testing.

Once osteoporosis is diagnosed, laboratory testing may help to identify any secondary causes (Table 3).

Management

The primary clinical goal of osteoporosis management is to reduce fracture risk. This is accomplished by slowing or stopping bone loss, increasing bone mass or improving bone architecture, maintaining or increasing bone strength, and minimizing factors that contribute to falls. Management strategies include general preventive health measures and pharmacologic interventions.

All postmenopausal women, regardless of their osteoporosis risk factors, should be encouraged to take steps to prevent bone loss and fractures, such as eating a balanced diet, obtaining adequate amounts of calcium and vitamin D, participating in appropriate exercise, avoiding excessive alcohol consumption and tobacco use, and taking measures to prevent falls.

Although a management strategy focused on lifestyle approaches may be all that is needed for postmenopausal women at low risk of osteoporotic fracture, NAMS recommends the addition of drug therapy in the following populations:

• All postmenopausal women who have had an osteoporotic vertebral fracture

• All postmenopausal women with BMD values consistent with osteoporosis (i.e., T-scores of −2.5 or less)

• Postmenopausal women with T-scores of −2.0 to −2.5 and at least one of the following risk factors for fracture: body weight of less than 127 lb; BMI less than 21 kg per m², history of fragility fracture since menopause, or history of hip fracture in a parent.

Several pharmacologic options are available for osteoporosis therapy, including bisphosphonates, raloxifene (Evista), parathyroid hormone, estrogens, and calcitonin. None of these therapies has been studied for preventing fractures. Adherence is poor, ranging from 25 to 81 percent at six months to one year after initiation of therapy. Therefore, ensuring adherence to therapy may be the most important follow-up measure for physicians.

BISPHOSPHONATES

Bisphosphonates inhibit the activity of osteoclasts and shorten their life span, thereby reducing bone resorption. Bisphosphonates significantly increase BMD at the spine and hip in a dose-dependent manner. In women with osteoporosis, bisphosphonates reduce the risk of vertebral fractures by 40 to 50 percent and reduce the risk of nonvertebral fractures by approximately one half this amount.

All of the bisphosphonates approved for osteoporosis therapy in the United States (i.e., alendronate [Fosamax], ibandronate [Boniva], etidronate [Didronel], and risedronate [Actonel]) are available in oral formulations for daily or intermittent dosing. Weekly oral dosing of alendronate and risedronate and monthly oral or intravenous dosing of ibandronate have been approved based on clinical trials that showed BMD responses equivalent to those achieved with daily treatment. The most common adverse effect of bisphosphonate therapy is esophageal and gastric irritation.

RALOXIFENE

Raloxifene is the only selective estrogen receptor modulator approved for the treatment of osteoporosis. It has beneficial effects on BMD at the lumbar spine and femoral neck and decreases bone turnover as assessed by biochemical markers. Raloxifene also has been proven to reduce osteoporotic vertebral fracture risk, although no effect has been reported on the risk of hip or other nonvertebral fractures. Bone loss often resumes when raloxifene therapy is stopped.

In addition to its effects on bone, raloxifene has been associated with a reduced risk of invasive breast cancer in postmenopausal women with osteoporosis. This agent may increase the risk of cardiovascular events in select women and may be associated with an increase in vasomotor symptoms.

PARATHYROID HORMONE

The various chemical structures of parathyroid hormone are anabolic agents that stimulate osteoblastic bone formation, resulting in substantial increases in trabecular bone density and connectivity in women with post-menopausal osteoporosis. Teriparatide (For-teo) is approved in the United States for the treatment of postmenopausal women with osteoporosis who are at high risk of fracture. Randomized controlled trials have shown that daily subcutaneous injections of teriparatide stimulate bone formation and improve bone density in postmenopausal women, regardless of whether they are receiving estrogen therapy. In postmenopausal women with previous vertebral fracture, treatment with teriparatide for 19 months significantly increased BMD in the spine and femoral neck and reduced the incidence of new vertebral and nonvertebral fragility fractures.

Adverse effects associated with teriparatide include muscle cramps and infrequent hypercalcemia, nausea, and dizziness.

ESTROGENS

Systemic estrogens are approved in the United States for the prevention—but not treatment—of postmenopausal osteoporosis. The beneficial effects of standard doses of systemic oral or transdermal estrogen and estrogen plus progestogen on BMD preservation are well established. The use of even substandard doses is associated with significant increases in spine and hip BMD.

Evidence supports the use of standard doses of estrogen or estrogen plus progestogen in reducing fracture risk in post-menopausal women. However, the primary indication for systemic estrogen and estrogen plus progestogen is moderate to severe menopause symptoms. The use of systemic estrogen/plus progestogen at standard doses for more than five years is associated with a significantly increased risk of breast cancer, stroke, coronary heart disease, and thromboembolic events. In women without a uterus, the use of estrogen alone for more than six years is associated with a significantly increased risk of stroke and deep venous thrombosis. NAMS recommends the use of estrogen, with or without progestogen, at the lowest effective dose for the shortest time consistent with the goals of therapy.

CALCITONIN

Salmon calcitonin (Miacalcin) is approved in the United States for the treatment—but not prevention—of postmenopausal osteoporosis. It is available as a nasal spray and subcutaneous injection. Calcitonin is an inhibitor of bone resorption, but in clinical use, the reduction in bone turnover is much less than that associated with other antiresorptive agents. Significant increases in spinal BMD were found in a small study of intranasal calcitonin in postmenopausal women. The use of intranasal calcitonin (200 IU per day) for five years significantly reduces the risk of new vertebral fractures in postmenopausal women with osteoporosis. After five years of therapy, significant increases in spinal BMD are associated only with higher dosages of calcitonin (400 IU per day).

Calcitonin has been proven to reduce bone pain from osteoporotic vertebral compression fractures more quickly than placebo immediately after a fracture. Adverse effects associated with calcitonin include nausea, local inflammation, and flushing of the face and hands when given as an injection.

COMBINATION THERAPIES

Combining potent antiresorptive agents results in only small additional increments in BMD. It is unknown whether increases in BMD result in better fracture protection, and the long-term safety of combination therapies has not been evaluated. One concern is that combining two antiresorptive agents may oversuppress bone turnover, adversely affect bone quality, and thereby increase the likelihood of fracture. Therefore, combining antiresorptive agents generally is not recommended. Although the combination of an anabolic agent with an antiresorptive agent has been considered, NAMS could not make recommendations for or against such a combination.