Osteoporosis

Osteoporosis is characterized by low bone mass and microarchitectural deterioration of bone tissue leading to enhanced bone fragility and a consequent increase in fracture risk. Symptoms occur only if there is a fracture. Diagnosis is by dual-energy x-ray absorptiometry. Prevention and treatment involve Ca and vitamin D supplements, drug therapy to decrease bone resorption, exercise, and measures that minimize the risk of falls.

Geriatric Essentials

• Osteoporosis causes substantial morbidity and mortality among the elderly.
• Major risk factors for osteoporosis in the elderly include older age, female sex, white or Asian race, family history of osteoporosis, thin body habitus, chronic deficiency of sex hormones, vitamin D deficiency, inadequate weight-bearing exercise, and glucocorticoid use.
• Osteoporosis should be considered in all elderly women and in elderly men who have thoracic kyphosis plus cervical lordosis or who have fractures.
• Screening and diagnosis in the elderly are usually by dual-energy x-ray absorptiometry of the hip.
• Most elderly patients benefit from supplemental Ca and vitamin D.
• Measures that decrease the risk of falls or injury from falls are particularly important in elderly patients with osteoporosis.

Bone loss in the elderly is considered normal if bone density (also called bone mineral density or BMD) is within 1 standard deviation (SD) of the mean density in young adults of the same gender and race; osteopenic if bone density is between 1 SD and 2.5 SD below the young adult mean; or osteoporotic if bone density is > 2.5 SD below the young adult mean.

In 2002, the estimated prevalence of osteopenia (decreased bone radiodensity and loss of trabecular structure) in the US among people > age 50 was 21.8% in women and 11.8% in men. The estimated prevalence of osteoporosis was 7.8% in women and 2.3% in men. Because prevalence increases with aging and the percentage of the population that is >= 65 continues to increase, the number of people who have osteoporosis is expected to increase by at least 50% by 2020. Thus, osteopenia and osteoporosis are major public health problems, resulting in substantial morbidity and health costs.

Classification

Primary osteoporosis: Primary osteoporosis can be classified as type I or II. Type I (menopausal) osteoporosis occurs mainly in people age 51 to 75, is 6 times more common in women, and predisposes to vertebral and Colles' fractures. Type II (senescent) osteoporosis occurs in people > 60, is 2 times more common in women, and predisposes to vertebral and hip fractures. Overlap between types I and II is substantial, so this classification is of limited clinical use. Primary osteoporosis is thought to result mainly from the hormonal changes that occur with aging, particularly decreasing levels of estrogen in women and decreasing levels of both testosterone and estrogen in men.

Secondary osteoporosis: Secondary osteoporosis accounts for only a small proportion of osteoporosis cases among the elderly, in whom primary and secondary osteoporosis often occur together. It accounts for a much greater proportion of cases among premenopausal women and younger men.

Secondary osteoporosis may be due to many causes, including hyperparathyroidism, hyperthyroidism, cancer, immobilization, GI disease, renal abnormality (eg, idiopathic hypercalciuria), and use of drugs that cause bone loss (eg, anticonvulsants). Mild to moderate vitamin D deficiency, which is common in elderly people, may give rise to osteoporosis rather than to osteomalacia. Glucocorticoid-induced osteoporosis is of particular concern in the elderly, who may already have Ca deficiency and impaired bone formation, both of which are worsened by glucocorticoids. Screening for secondary osteoporosis is important in patients of all ages, because many of the causes are treatable or have an important effect on prognosis (see Figure 49-1).

Pathophysiology

Diminished bone mass can result from failure to reach an optimal peak bone mass in early adulthood, from increased bone resorption, or from decreased bone formation after peak bone mass has been achieved. All 3 of these factors probably play a role in diminished bone mass in most elderly people. Low bone mass, rapid bone loss, and increased fracture risk correlate with high bone turnover rates (ie, resorption and formation). Presumably, in osteoporosis, the formation rate is inadequate to offset the resorption rate and maintain the structural integrity of the skeleton.

Risk Factors

Major risk factors for osteoporosis are history of fracture as an adult, older age, female sex, white or Asian race, family history (specifically, in a first-degree relative) of osteoporosis or a fragility fracture, and thin body habitus. Other risk factors include decreased lifelong exposure to estrogen or testosterone, low Ca or vitamin D intake, inadequate weight-bearing exercise, current cigarette smoking, use of certain drugs (eg, glucocorticoids for >= 3 mo), and excessive caffeine or alcohol intake.

Age: Age has a complex effect on the skeleton. Bone resorption rates seem to be maintained or even increase with aging; bone formation rates tend to decrease. Deterioration of bone architecture due to complete resorption of trabecular elements or to endosteal removal of cortical bone produces irreversible bone loss. Age-related microdamage and death of osteocytes may also increase skeletal fragility. However, osteoporosis is not an inevitable consequence of aging; many people maintain good bone mass and structural integrity into their 80s and 90s.

Sex: Women are prone to osteoporotic fractures because they have lower peak bone mass and lower muscle mass (and thus less ongoing bone stress) than men. In addition to an age-related decline in bone mass that occurs in both sexes, women experience accelerated bone loss at menopause and may also lose bone during the reproductive years, particularly with prolonged lactation. Women's smaller periosteal bone diameter also increases skeletal fragility.

Race: Although osteoporosis is more prevalent among whites and Asians than among blacks, the reasons are not well understood; prevalence also varies among ethnic groups. Whites have lower peak bone mass than do blacks, but the difference in fracture risk seems to be independent of the difference in bone density. Differences in body composition, skeletal structure, and bone turnover may play a role.

Heredity: Genetic factors are more important determinants of peak bone mass than any other factor, explaining about 50 to 80% of the variance. A family history of osteoporosis increases fracture risk, independent of bone density. Genetic studies comparing patients with osteoporosis to healthy people have shown several differences in specific genes for collagen, hormone receptors, and local factors. Many genes probably play a role.

Body habitus: The increased risk of fracture associated with a thin body habitus is probably multifactorial. Thin women produce less estrogen from androgens (this conversion occurs in fat tissue), especially after menopause. Obesity may be associated with increased muscle mass, greater weight-bearing impact on the skeleton, and greater protection of the skeleton, particularly of the hip, by subcutaneous fat.

Systemic hormones: Age-related decreases in estrogen levels increase fracture risk. In addition, increased levels of parathyroid hormone, usually in patients with decreased Ca intake and vitamin D deficiency, can decrease bone mass and increase fracture risk. Although excess glucocorticoids and thyroid hormone can contribute to secondary osteoporosis, they have not been shown to play a role in primary osteoporosis.

Local factors: Animal studies suggest that the interaction of systemic hormones with local regulators of bone remodeling, including cytokines and prostaglandins, plays a critical role in the increase in bone resorption and relative impairment of bone formation that occurs after oophorectomy. However, evidence implicating these local factors in human osteoporosis is limited. IL-1 activity may be increased in osteoporosis; although IL-6 activity seems to increase with aging, no correlation with osteoporosis has been shown. Other important cytokines and local regulators may include receptor activator of nuclear factor B (RANK) ligand, which is produced by osteoblasts and interacts with the RANK receptor to activate osteoclasts. RANK ligand inhibition can markedly reduce bone breakdown. Other cytokines that have been implicated include tumor necrosis factor- and macrophage colony-stimulating factor, which can increase osteoclast formation. Inhibiting prostaglandin production with NSAIDs results in a small increase in bone mass.

Symptoms and Signs

Osteoporosis has been termed a silent disease because, until a fracture occurs, symptoms are absent. Osteoporotic fractures may occur after minor or even inapparent trauma (ie, fragility fractures).

A loss of height may indicate a vertebral compression fracture, which occurs in many patients without trauma or other acute precipitant; these fractures are most common at T6 and below. Dorsal kyphosis with exaggerated cervical lordosis (dowager's hump) may result from multiple thoracic compression fractures. In some patients with fracture, pain may be acute and severe and aggravated by weight bearing. Pain usually subsides slowly over several weeks but may last longer. Chronic back pain in the elderly can be caused by vertebral compression from osteoporosis but is as likely to be caused by joint or disk disease.

Osteoporotic fractures commonly affect the hip because the elderly tend to fall sideways or backwards, landing on the joint. Osteoporosis also predisposes to fractures of the extremities (eg, the wrist) and pelvis, but not to fractures of the head and face.

Diagnosis

Screening with dual-energy x-ray absorptiometry is recommended for all women > 65 and for men who sustain fragility fractures. US Preventive Services Task Force recommendations for screening for osteoporosis are available from the task force.

Osteoporosis should be considered in all elderly people, but should be suspected particularly in elderly people who have sustained fragility fractures, who have risk factors and unexplained back pain, who have decreased bone density that is incidentally noted on radiographic studies, or who have risk factors for secondary osteoporosis.

History should focus on primary risk factors and causes of secondary osteoporosis. A complete history of menstrual function, pregnancy, and lactation should be obtained in women, and a complete history of sexual function should be obtained in men, in whom decreased libido and erectile dysfunction may be due to low testosterone levels. Neurologic deficits and drugs that might increase the risk of falls should be analyzed. Family history should include fragility fractures, evidence of endocrinopathy, and renal calculi. One of the most important predictors of osteoporotic fractures is history of fracture after age 40 due to minimal or moderate trauma. In people with such a history, the fracture risk may be increased severalfold.

The physical examination is often unremarkable. Spinal deformity and tenderness over the lower back should be sought.

Plain x-ray findings are generally insufficient for the diagnosis of primary osteoporosis; x-rays may show signs of osteopenia, but only when bone loss is > 30%. Vertebral compression fractures can be seen on x-ray, but anterior wedging may have been present since adolescence (Scheuermann's disease), and some degree of age-related wedging can occur in the absence of marked bone loss. Plain x-rays can also show findings that suggest other causes of metabolic bone disease, such as lytic lesions in multiple myeloma, pseudofractures typical of osteomalacia, subperiosteal resorption or cystic bone lesions typical of hyperparathyroidism, or vertebral fractures at T4 or above typical of cancer.

Dual energy x-ray absorptiometry (DXA), a method of measuring bone density (bone densitometry), can be used for screening, diagnosing, predicting fracture risk, and monitoring response to treatment. DXA can measure bone density in the lumbar spine, hip, wrist, or total body. (Quantitative CT scanning can produce similar measurements in the spine or hip.) The relationship between bone density and fracture risk is continuous and graded; with densitometry, diagnostic cutoffs are arbitrary and must be considered in light of other risk factors. Usually, a difference of 1 SD from the young adult mean equals a 10 to 12% difference in bone density. There is a 2.7-fold increase in the relative risk of hip fracture for a 1-SD decrease in femoral neck bone density from the young adult mean; the increase in relative risk is somewhat less (about 1.5- to 2.0-fold increase for a 1-SD decrease) when density is measured at sites other than the femoral neck. In women > 75, a measurement even 1 SD below the age-adjusted norm is highly predictive of fractures. Furthermore, peripheral densitometry measurement may not reflect central measurement and is subject to artifacts. In the elderly, measurement of the lumbar spine is often complicated by osteoarthritic changes, disk disease, and calcification of the underlying aorta. Other limitations of densitometry are that current criteria are based on data from white postmenopausal women and that appropriate diagnostic criteria for other populations have not been established. In addition, bone density values vary with the technique used and the position of the patient.

Other testing is done for patients with diagnosed osteoporosis with the aim of detecting causes of secondary osteoporosis (see Figure 49-1).

Markers such as collagen cross-links (eg, levels of serum or urine N-telopeptide cross-links [NTX] or free deoxypyridinoline [DPYR]) and bone-specific alkaline phosphatase levels can be used to assess the response to therapy.

Prognosis

Osteoporosis does not directly cause death. However, an excess mortality of 10 to 20% occurs in patients with established osteoporosis, particularly those with hip fractures.

Treatment

In the elderly, there is considerable overlap between what might be considered treatment and prevention. Although there are several different published criteria regarding indications for antiresorptive drugs, a general rule is to prescribe such drugs for patients who have osteoporosis, as defined by a bone density > 2.5 SD below the young adult mean, as well as for patients who have a bone density > 1.5 SD below the young adult mean and who have additional risk factors. Some measures are recommended for all elderly patients, regardless of their degree of bone loss, to maximize bone density and bone health (ie, for treatment or prevention of osteoporosis), including adequate intake of Ca and vitamin D, regular weight-bearing exercise and other efforts to minimize the risk of falls, smoking cessation, minimizing caffeine and alcohol intake, and good general nutrition. The Physician's Guide to Prevention and Treatment of Osteoporosis is available from the National Osteoporosis Foundation.

Ca and vitamin D: An elderly American's typical diet provides only about 600 mg/day of Ca and < 200 IU of vitamin D. Supplemental Ca and vitamin D can reduce the risk of fracture by as much as 30% in elderly people who have relatively low intakes and limited sun exposure, particularly nursing home residents. Supplementation can be achieved through increased dietary intake of dairy products and other nutrients rich in Ca and vitamin D or through supplement use. Some Ca supplements and most multivitamins contain vitamin D. The recommended intake for elderly Americans is 1200 mg/day of elemental Ca and 400 IU/day of vitamin D; a somewhat larger intake of Ca (eg, up to 1500 mg/day of elemental Ca) and vitamin D (eg, up to 800 IU/day) may be beneficial and is usually considered safe. However, vitamin D intoxication can occur if intake is >= 2000 IU/day. Ca carbonate supplements (eg, 500 to 600 mg po bid or tid) are usually well tolerated in the elderly; if Ca carbonate causes achlorhydria or GI symptoms (particularly constipation), Ca citrate and efforts to increase dietary Ca are preferred. A good diet should include an adequate amount of vitamin K, because vitamin K deficiency increases fracture risk. Limiting Na intake may also be helpful, because a high Na intake can increase urinary Ca losses.

Antiresorptive therapy: Antiresorptive drugs include bisphosphonates, calcitonin, estrogen, and selective estrogen receptor modulators (SERMs).

Bisphosphonates are first-line antiresorptive drug therapy. These potent antiresorptive drugs directly inhibit osteoclast activity and increase bone mass. Oral bisphosphonates decrease the risk of fractures, particularly in patients taking glucocorticoids, and decrease the incidence of vertebral and nonvertebral fractures by 50%. Alendronate is used to prevent (5 mg po once/day or 35 mg po once/wk) and treat (10 mg po once/day or 70 mg po once/wk) osteoporosis. Ibandronate can be used for prevention or treatment (150 mg po once/mo), as can risedronate (5 mg po once/day or 35 mg po once/wk). Usually, < 1% of bisphosphonates is absorbed when taken orally. To achieve optimal absorption, patients must take bisphosphonates with a full glass of water but without food or other drugs; the patient must then remain upright for > 30 min. Oral use causes adverse GI effects, particularly esophageal irritation. Weekly or monthly therapy is usually preferred for greater convenience and the likelihood of fewer adverse effects. Because of GI effects, bisphosphonates are often avoided in patients with gastroesophageal reflux disease; however, a cautious trial of these drugs may be justified. Pamidronate and zoledronic acid are available IV for patients who cannot tolerate oral bisphosphonates, but neither drug has been shown to prevent fractures. These drugs can cause transient fever, usually not higher than 40° C, and flu-like symptoms.

Salmon calcitonin is less effective than bisphosphonates and probably also less effective than estrogen and raloxifene. Salmon calcitonin is available as a nasal spray (200 IU/day, alternating nostrils daily) or as a rarely used sc injection (100 IU/day). It can provide short-term pain relief after an acute fracture. The major adverse effect of nasal salmon calcitonin is local irritation.

Estrogen can prevent menopausal bone loss and fractures in most women. Other antiresorptive drugs may have an additive effect when given with estrogen. Relative deficiency of estrogen may occur in postmenopausal women who had an early menopause or an oophorectomy (usually with a hysterectomy). Estrogen therapy is particularly effective during the first few years after menopause when bone loss is most rapid. Therapy is usually given as conjugated estrogen 0.625 to 1.25 mg po once/day; however, 0.3 mg po once/day may be as effective. Estrogen use increases the risk of thromboembolism and endometrial cancer and may increase the risk of breast cancer. Progestin is added to estrogen in women who have a uterus to reduce the increased risk of endometrial cancer. However, using the estrogen-progestin combination increases the risk of coronary artery disease, stroke, breast cancer, and biliary disease. Because of the breadth and potential severity of adverse effects caused by estrogen, it is no longer recommended solely to treat osteoporosis.

Raloxifene is a SERM that is antiestrogenic in typical target organs (eg, breast, uterus) but has antiresorptive effects on bone. It is less effective as an antiresorptive drug than are estrogens or bisphosphonates but can prevent bone loss and decrease the incidence of vertebral fractures. SERMs have relatively few adverse effects. However, like estrogens, they increase the risk of thromboembolism. A possible advantage of SERMs is an apparent ability to reduce the risk of breast cancer.

Parathyroid hormone (PTH): PTH, which stimulates new bone formation, is usually reserved for patients who do not respond to antiresorptive drugs, as well as Ca, vitamin D, and exercise. When it is injected daily for an average of 20 mo, synthetic PTH (1-34, teriparatide) increases bone mass and reduces fractures. It is recommended that use should not exceed 2 yr. Patients should be told that high-dose, long-term use of synthetic PTH can cause osteosarcoma in rats; however, there is no evidence that this occurs in humans.

Monitoring response to treatment: Response should be monitored by repeating bone density measurement with DXA 1 to 2 yr after initiating antiresorptive treatment. An interval of 2 yr is consistent with guidelines issued by the Centers for Medicare and Medicaid Services. Bone density measurement should also be repeated 1 to 2 yr after stopping one antiresorptive drug and starting another; such a change in drugs is sometimes needed due to adverse effects.

Preventing fractures: Many elderly patients are at risk of falling because of poor coordination, poor vision, muscle weakness, confusion, and use of drugs that cause postural hypotension or alter the sensorium. Educating patients about the risks of falls and fractures and developing individualized programs to increase physical stability and attenuate risk can help. Strengthening and weight-bearing exercises may increase stability. However, the effects of these exercises on bone density are relatively small. Wearing undergarments with hip-protective pads may reduce the incidence of hip fracture despite continued falls; however, clinical trials of their use have yielded disappointing results.

Treating pain and maintaining function: Acute back pain from a vertebral compression fracture should be treated with analgesics; when muscle spasm is prominent, heat and massage help. Chronic backache may be relieved by an orthopedic garment and exercises to strengthen paravertebral muscles. Avoiding heavy lifting can help. For ambulatory patients, bed rest should be minimized, and consistent, carefully designed weight-bearing exercise should be encouraged.

This topic was last updated February 2006.