Current Geriatric Diagnosis & Treatment, 1st Edition

Section III - Common Disorders in the Elderly

27. Osteoporosis & Hip Fractures

Manish Srivastava MD

Chad Deal MD

ESSENTIALS OF DIAGNOSIS

  • In 1994, the World Health Organization established bone mineral density measurement criteria for the diagnosis of osteoporosis (Table 27-1).
  • Osteoporosis is a systemic skeletal disease characterized by low bone mass and microarchitectural deterioration of the bone tissue, with a consequent increase in bone fragility and susceptibility to fracture.
  • Osteoporosis is more common in women than in men, although the incidence among men is increasing.
  • The prevalence of osteoporosis and osteoporotic fractures increases with age.

General Considerations

According to the National Osteoporosis Foundation, in the United States in 2002, 32 million women and 12 million men older than 50 have either osteoporosis or low bone mass (defined as T ≤ 2.0 and ≤ 1.0, respectively). This number is expected to increase to 52 million by 2010. Of these, it is estimated that > 10 million people have osteoporosis, a figure that will rise to almost 12 million by 2010 and approximately 14 million by 2020 if additional measures are not taken to stem this disease. The prevalence of osteoporosis increases with age from 15% in women 50–59 years old to 70% in women 80 years old. The lifetime risk for fracture for a 50-year-old woman is 40–50%. A fracture is considered to be osteoporotic (fragility fracture) if it is due to relatively low trauma such as a fall from standing height or less, a force that in a young healthy adult would not be expected to cause a fracture. There is overwhelming evidence that the incidence of fracture in specific settings is closely linked to the prevalence of osteoporosis or low bone mass. In most populations, hip fracture incidence increases with age and typically peaks after age 85. With increasing life expectancy worldwide, the number of elderly individuals is increasing in every geographic region. Because hip fracture incidence rates rise exponentially with age, this will result in increasing numbers of hip fractures. In 1990, there were an estimated 1.65 million hip fractures (1.2 million in women and 450,000 in men) worldwide, which is projected to increase to 6.3 million by the year 2050.

  1. OSTEOPOROSIS IN WOMEN

Radiographic population surveys find that ~5% of 50- to 54-year-old white women have at least 1 prevalent radiographic vertebral fracture, and the proportion with a prevalent fracture rises to > 35% among women aged 80–85 years. The risk of an incident vertebral fracture on x-ray film is only about 0.5% in the next year in a 50-year-old white woman but increases to 2–3% per year by 80–85 years. Pelvic fractures and fractures of the proximal humerus and shaft–distal femur have an occurrence pattern that resembles that of hip fractures.

  1. OSTEOPOROSIS IN MEN

There is growing awareness that osteoporosis in men is not rare, although its incidence is lower than in women. Thirty-three percent of all hip fractures worldwide occur in men. The risk factors for osteoporosis in men age 60 and older are low femoral neck bone mineral density (BMD), quadriceps weakness, low body weight, falls in the preceding year, and a history of fractures in the last 5 years. The Framingham Osteoporosis Study identified low baseline weight, weight loss, and cigarette smoking as risk factors for osteoporosis. In addition, low estradiol levels have been associated with vertebral fractures, whereas low testosterone level consistent with hypogonadism poses no significant increased risk for fracture. Age-related decline in testosterone level has been thought to play a role in decreased bone formation in elderly men.

Currently, there is no validated guideline for prevention or treatment of osteoporosis in men. Men with a history of fractures and those with known risk factors for low bone density should be targeted for prevention of osteoporosis and can be offered BMD measurement. However, the BMD threshold at which therapy should be started is unclear.

Lifestyle modifications, including increasing physical activity and cessation of smoking and alcohol, should be recommended to all men. Calcium and vitamin D supplementation

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should be recommended for older men, although evidence is limited and conflicting.

Table 27-1. Diagnostic categories for osteoporosis in postmenopausal women based on World Health Organization Criteria.

Category

Definition by bone density

Normal

A value for BMD that is not >1 SD below the young adult mean value.

Osteopenia

A value of BMD that lies between 1 and 2.5 SD below the young adult mean value.

Osteoporosis

A value for BMD that is >2.5 SD below the young adult mean value.

Severe osteoporosis

A value for BMD >2.5 SD or below the young adult mean in the presence of 1 or more fragility fractures.

BMD, bone mineral density.

The use of testosterone therapy in eugonadal men is controversial, and current data do not support any benefit associated with it. Testosterone replacement is appropriate only in the setting of proven hypogonadism in men with markedly low total testosterone levels. Currently, the roles of PTH, growth hormone, and raloxifene are being evaluated.

Clinical Findings

  1. SIGNS & SYMPTOMS

Osteoporosis has no clinical manifestations until there is a fracture. Osteoporosis-associated fracture occurs most likely at sites of low bone mass. Vertebral spine and hip are the 2 common sites of fracture. Others include wrist, pelvic, proximal humerus, and shaft–distal femur.

  1. Vertebral fracture—About 66% of vertebral fractures are asymptomatic; they are diagnosed as an incidental finding on chest or abdominal x-ray film. The most common sites for fractures are the lower thoracic area and upper lumbar spine. Osteoporotic fracture can lead to the acute onset of pain, typically occurring suddenly during routine activities, such as lifting or bending. The acute pain usually subsides in several weeks to months and is replaced by a chronic dull pain that usually resolves but can persist for a prolonged period.

Multiple vertebral fractures can lead to

  • Increased thoracic kyphosis with height loss and development of “dowager's hump.”
  • Crowding of internal organs (patients note that their abdomens have become larger, that their clothes do not fit, or that they no longer have a waist).
  • Complaints of pain in the muscles of the neck because patients must extend the neck to look forward.
  • Reduction in the distance between the bottom of the rib cage and the top of the iliac crests, which may be associated with dyspnea and gastrointestinal complaints (eg, early satiety and constipation).
  • Functional and physical limitation because of chronic pain, which leads to anxiety, depression, and loss of self-esteem and self-image.
  1. Hip fracture—Hip fractures are relatively common in osteoporosis. The incidence increases with increasing age, affecting 15% of women and 5% of men by age 80. They are usually associated with a fall. Most hip fracture patients have difficulty standing, and the involved leg appears shorter and externally rotated. A patient with an impacted hip fracture may occasionally be able to walk. Intertrochanteric fractures are usually unstable and may be associated with substantial blood loss and hemodynamic compromise in the elderly. Hip fracture mortality is higher for men than for women, increases with age, and is greater for those with coexisting illnesses and poor prefracture functional status.
  2. RISK FACTORS

Low bone density is an important risk factor for osteoporosis. Predictors of low bone mass include female sex, increased age, estrogen deficiency, white race, low body weight (<127 lbs), family history of osteoporosis, and history of fracture. Cigarette smoking, alcohol abuse, and calcium or vitamin D deficiencies are also associated with osteoporosis. Residents of nursing homes and other long-term care facilities are at high risk for fractures. Most have low BMD and a high prevalence of other risk factors for fracture, including advanced age, poor physical function, low muscle strength, decreased cognition and high rates of dementia, poor nutrition, and multiple-drug regimen.

Although low BMD has been established as an important predictor of future fracture risks in women, other clinical risk factors have also been identified, among them historical factors, such as previous fracture, self-rated poor health, use of long-acting benzodiazepines, and sedentary lifestyle, and physical examination findings, such as inability to rise from a chair, poor visual performance, and resting tachycardia. The presence of 5 or more of these factors increased the rate of hip fracture in the highest tertile of BMD from 1.1/1000 woman-years to 9.9/1000 woman-years and in the lowest tertile of BMD to 27.1/1000 woman years.

Approximately 95% of hip fractures are caused by falls. Falls risk increases with advancing age for persons older than 65. Risk factors for falls include lack of physical activity, muscle weakness or balance problems,

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functional limitations, cognitive impairment or dementia, use of psychoactive medications, and environmental factors, including home hazards. Frequently, a fall is the result of an interaction between personal and environmental factors.

  1. IMAGING STUDIES

Because 66% of vertebral fractures are asymptomatic, radiographs of the thoracic and lumbar spine are necessary to detect existing fractures. However, osteoporosis cannot be reliably diagnosed using x-ray films alone because a loss of up to 30% of bone mass is often not detected. Bone density measurement is needed to quantify osteoporosis.

  1. BONE MINERAL DENSITY MEASUREMENT

BMD measurement can be used to establish the diagnosis of osteoporosis, estimate fracture risk, and identify candidates for intervention. It is also used to assess changes in bone mass over time in treated and untreated patients.

  1. Indications—The National Osteoporosis Foundation (NOF) has recommended BMD testing for all white women age 65 and older and for postmenopausal women younger than 65 who have clinical risk factors (Table 27-2).
  2. Measurement techniques—Several different methods are used to measure BMD (Table 27-3). Dual energy x-ray absorptiometry (DEXA) is the most common because it gives very precise measurements at clinically important sites with minimal radiation. It is the gold standard against which all other technologies are compared. The cost of DEXA is approximately $150–$250. Medicare covers the cost in all elderly women (> 65 years) for initial diagnosis and for follow-up after 23 mo.

Table 27-2. National Osteoporosis Foundation recommendations for BMD testing.

Postmenopausal women (age 50–65) with risk factors for osteoporosis (besides menopause)
      Family history of osteoporosis
      Personal history of low trauma fracture at age >45 years
      Current smoking
      Low body weight (<127 lb)
Women age 65 years and older regardless of additional risk factors
Postmenopausal women with fractures
Women considering therapy for osteoporosis if BMD testing would facilitate such a decision
Women who have been on HT for prolonged periods

BMD, bone mineral density; HT, hormone replacement therapy.

  1. Measurement sites—The routine DEXA examination should include scans of the hip and spine. BMD measurement at central sites (spine and hip) provides reproducible values at important sites of osteoporosis-associated fractures and also is more likely than measurement at peripheral sites to show a response to treatment in serial measurements. Peripheral sites can identify patients with low bone mass and predict fracture risk. However, peripheral sites are not as predictive for hip and spine fractures as site-specific measurement.
  2. Bone density reports—Bone density data are reported as T scores and Z scores. T scores represent the number of standard deviations above or below young adult mean bone density values, whereas Z scores represent the standard deviations above or below age- and sex-matched control women. T scores are used by the World Health Organization (WHO) for establishing the diagnosis of osteopenia and osteoporosis (see Table 27-1). Each standard deviation change in the BMD increases fracture risk by 2–2.5 times. Patients with Z scores lower than -1.5 or -2.0 often have a secondary cause of osteoporosis.
  3. Follow-up scans—Because annual losses of bone mass normally seen with aging are in the range of 1% per year, the precision error of current instruments (approximately 1–2% with DEXA) means that the usual interval between scans should be at least 2 years. Because high-dose steroid therapy can result in rapid bone loss in a shorter interval (6–12 mo), more frequent scans should be obtained in these patients.
  4. LABORATORY EVALUATION

Despite the lack of definitive guidelines on the use of biochemical markers, such markers have the potential to provide independent or adjunctive information on decision making. The resorption markers are measured in the urine. However, blood measurements have become available (Table 27-4). Resorption markers must be measured in the morning on the second void urine because there is a large diurnal variation. The resorption markers are also independent risk factors for fracture. Women who have elevated markers are at increased risk of bone loss in the near future, and those with low bone mass may be candidates for pharmacological intervention.

Secondary causes of osteoporosis should be excluded in individuals with very low bone densities before rendering a diagnosis of idiopathic or primary osteoporosis. The common secondary causes are listed in Table 27-5 along with laboratory tests required to evaluate each disease. Men are more likely to have a secondary cause of osteoporosis than women. The most commonly

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reported secondary causes of osteoporosis in men are hypogonadism, alcoholism, hypercalciuria, and malabsorption syndromes.

Table 27-3. Bone mineral density measurement techniques.

Technique

Sites measured

Advantages

Disadvantages

DEXA

Central and peripheral

Precise measurements
Minimal radiation
Rapid
Noninvasive

Machine is large (not portable)
Expensive

QCT

Central and peripheral

Selectively measures trabecular bone
Volumetric density
Not influenced by degenerative disease

Poor precision
Less reproducible
High radiation
Expensive

QUS

Peripheral

Portability
Lack of radiation exposure
Lower expense

Lack of precision
Not useful in monitoring

RA

Peripheral

Uses conventional x-ray machinery

Measures bone density in a largely cortical site

DEXA, dual energy x-ray absorptiometry; QCT, quantitative computed tomography; QUS, quantitative ultrasonometry; RA, radiographic absorptiometry.

Prevention & Treatment

Effective therapies for prevention and treatment of osteoporosis are now available. The goal of therapy is to decrease osteoporosis-related morbidity and mortality by reducing the risk of fracture through maintaining or increasing bone strength.

  1. NONPHARMACOLOGICAL THERAPY

Nonpharmacological therapy is an important adjunct to pharmacological management of osteoporosis. This includes elimination or reduction of potentially modifiable risk factors along with exercise and calcium and vitamin D supplementation.

  1. Reduction of modifiable risk factors—Alcohol and tobacco use can be decreased and physical activity increased in most elderly patients. Physical activity such as resistance training and weight-bearing exercises may have a 2-fold contribution to reducing fracture risk. First, it may enhance bone strength by optimizing BMD and improving bone quality. Second, it has the potential to reduce the risk of falling. Low-impact exercises, such as walking, have beneficial effects on other aspects of health and function, although their effects on BMD have been minimal. The emphasis of physical exercise programs in elderly patients with osteoporosis should not be on increasing bone mass but on improving muscle strength and balance. Older patients should be encouraged to participate safely in any activity in a frequent, regular, and sustained manner. The exercise should be weight bearing and easy to complete and should fit into their daily routine. A program of walking, sitting and standing exercises, and low-impact or water aerobics can be recommended initially and then gradually increased to more rigorous activity.

Table 27-4. Serum markers.

Bone formation

Bone resorption

Serum bone-specific alkaline phosphatase

Urinary hydroxyproline

Serum osteocalcin

Urinary total deoxypyridinoline

Serum procollagen type I carboxyterminal pro-peptide

Urinary collagen type I cross-linked N-telopeptide

Serum procollagen type I N-terminal propeptide

Urinary collagen type I cross-linked C-telopeptide

  1. Reducing the use of medications that increase the risk of falls and making adjustments to the home environment can decrease the incidence of falls leading to fracture. Hip protectors can reduce the risk of hip fractures in nursing home residents. Hip protectors consist of a hard or soft shell with a soft padding that covers the area over the greater trochanter of the hip. Their use should be encouraged for patients at increased risk (ie, those with osteoporosis and high risk of falling), particularly those in nursing homes. However, compliance may be a problem.
  2. Calcium & vitamin D—Bone loss in the elderly may be accelerated by calcium deficiency leading to secondary hyperparathyroidism. Deficiency of calcium and vitamin D contributes to alterations of bone remodeling

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and bone integrity. Low calcium intake and vitamin D deficiency have been repeatedly observed in the elderly population. Vitamin D or calcium supplementation alone have little effect on bone mass in the early menopausal years but can have substantial effects on bone mass and fragility fractures in the elderly population.

Table 27-5. Laboratory evaluation for secondary causes of osteoporosis.

Disease

Laboratory tests

Hypogonadism (men only)

Serum testosterone, prolactin

Malabsorption syndrome

Potential tests such as stool for fat or xylose breath test

Primary hyperparathyroidism

Ionized calcium, intact PTH (if calcium elevated)

Multiple myeloma

Serum and urine protein electrophoresis

Hyperthyroidism or excess thyroid hormone replacement

T4, TSH

Osteomalacia

Alkaline phosphatase, 25(OH)D, 24-h urine calcium

PTH, parathyroid hormone; T4, levothyroxine; TSH, thyroid-stimulating hormone; 25(OH)D, 25-hydroxyvitamin D.

  1. Side effects—Risks of calcium supplementation are minimal. Older patients may suffer from constipation, rebound gastric hyperacidity, and dyspepsia, especially with calcium carbonate. Persons with personal or family histories of kidney stones must be screened with 24-h urinary calcium. Because most stones are calcium oxalate, and because calcium binds oxalate in the gastrointestinal (GI) tract, in most cases calcium is not contraindicated in stone disease. Calcium citrate is the preferred calcium supplementation in these patients because it decreases urine pH.
  2. Recommended dose—The optimal effective dose of vitamin D is 400–800 IU/day. The recommended dose of calcium for elderly women and men is 1500 mg/day; women on hormone replacement therapy (HT) need 1000 mg/day. Dairy products are a good source of calcium, but they may not be tolerated in individuals with lactose intolerance, which is common in the elderly. Because the recommended dose of calcium and vitamin D usually is not obtained through diet alone, calcium supplementation is recommended. There is little evidence that one form of calcium supplementation is better than another. However, calcium citrate may be better tolerated in persons unable to tolerate other forms of calcium supplement and is better absorbed in the achlorhydric stomach.
  3. PHARMACOLOGICAL TREATMENT
  4. Bisphosphonates—These compounds bind avidly to hydroxyapatite crystals on bone surfaces and are potent inhibitors of bone resorption. Bisphosphonates significantly reduce vertebral fracture rates after only 1 year of treatment, making them ideal for patients with high short-term fracture risk.
  5. Alendronate—
  6. Efficacy—Alendronate has been shown to prevent bone loss and increase BMD at the spine and hip by 5–10%. Also, alendronate therapy has been well tolerated. Elderly women with osteoporosis were shown to have significant gains in BMD at the lumbar spine and trochanter. It has been found that the magnitude of the fracture reductions with alendronate are similar in women who meet the WHO BMD criterion for osteoporosis without vertebral fracture and in those who have existing vertebral fracture with low BMD.

Treatment with alendronate also has significant effects on the physical disability resulting from osteoporotic fractures.

  1. Intermittent dosing—The efficacy of once-weekly compared with daily dosing of alendronate has been validated. The incidence of clinical and laboratory adverse effects, including GI intolerance, between the 2 regimens is also similar. However, rare but serious GI adverse events (perforation, ulcers, and bleeds) might be less with the once-weekly regimen. In addition, it is more convenient and has been approved by the Food and Drug Administration (FDA) for treatment of osteoporosis.
  2. Adverse effects—GI side effects (eg, heartburn, indigestion, pain while swallowing, and substernal discomfort) have been described, and a small number of patients have been reported to have experienced erosive esophagitis with alendronate. Because of this potential problem, it is important that patients take the medication in the morning with a full glass of water (6–8 oz) and remain upright (sitting or standing) for at least 30 min after the dose. An interval of 30 min before taking any liquid other than water is necessary to ensure absorption.
  3. Contraindications—Alendronate is contraindicated in patients with esophageal stricture or motility disorders and in those who are unable to remain upright for at least 30 min after ingestion of the drug. Alendronate should also be used with caution in patients with severe renal insufficiency (creatinine clearance <35 mL/min).

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  1. Recommended dose—The approved dose of alendronate for prevention of osteoporosis in recently menopausal women is 5 mg daily or 35 mg weekly. For treatment of postmenopausal osteoporosis, 10 mg daily or 70 mg weekly is the approved dose.
  2. Duration of use—The duration of alendronate therapy is not yet clear. One of the major determinants is what happens when therapy is discontinued. Seven-year follow-up of patients using alendronate showed that spinal BMD continued to increase through 7 years of alendronate treatment and BMD remained stable at other sites after rising during the first few years. After the withdrawal of treatment, there was a small increase in biochemical markers of bone turnover, but this was well below pretreatment levels 2 years after discontinuation. It appears that skeletal benefits may be preserved for at least 1–2 years after cessation, but long-term follow-up studies are needed.
  3. Risedronate—
  4. Efficacy—Risedronate (5 mg/day) has been shown to increase lumbar spine BMD.
  5. Adverse effects—It is not known whether the GI side effects are different from alendronate.
  6. Contraindications—Contraindications to risedronate include esophageal stricture and motility disorders, hypocalcemia, and hypersensitivity to risedronate.
  7. Recommended dose—The approved dose for prevention and treatment of osteoporosis is 5 mg daily. BMD increases are equivalent with 5 mg once-daily and 35 mg once-weekly dosages.
  8. Other bisphosphonates—Intermittent cyclical etidronate has been shown to significantly increase spinal bone mass and decrease the risk of vertebral fractures, especially among high-risk individuals. Cyclical etidronate is approved for treatment of osteoporosis in many countries. Although not approved by the FDA for treatment of osteoporosis, etidronate is often used off-label for patients who would benefit from a bisphosphonate but cannot tolerate other oral bisphosphonates. It is less expensive than alendronate or risedronate.

Zoledronic acid has also been shown to increase BMD at the spine and hip. The medication had similar effects on bone turnover and BMD when given as 1 mg every 3 mo or 4 mg every 12 mo. These increases were similar to those seen with risedronate and alendronate. Pamidronate has also been used, but no fracture data are available.

  1. Hormone Therapy
  2. Efficacy—The beneficial effects of HT on BMD at different skeletal sites have been documented. Conjugated estrogens have been shown to increase BMD by almost 6% in the spine and 2.8% in the hip after 3 years. The addition of progesterone did not alter the effect of estrogen. Estrogen and medroxyprogesterone acetate have produced a 1.4–3.9% increase in BMD at skeletal sites.
  3. Duration & timing—The timing of initiation and duration of HT is the topic of much debate. It is suggested that women be started on estrogen within 2–7 years of menopause, but this guideline is being disputed. Several studies have shown that HT begun before 60 years of age prevents nonvertebral, hip, and wrist fractures, but there is insufficient evidence that fracture risk is reduced when HT is begun after age 60. Estrogen may have a positive effect on BMD even when started ~20 years after menopause. Estrogen begun and continued after age 60 years appears to maintain and in some cases increase BMD. There is growing evidence, however, for an attenuation of the beneficial skeletal effects of HT after the withdrawal of treatment. The duration of therapy necessary to protect women against fragility fractures is indefinite.
  4. Side effects—Compliance with HT is typically poor because of common side effects and concern about increased incidence of breast or endometrial cancer. Women who have not undergone hysterectomy should have progestins added to the estrogen regimen to prevent endometrial neoplasia. HT also increases the risk of venous thromboembolism and cholelithiasis. One major reason why elderly women discontinue therapy is irregular uterine bleeding. Low-dose HT can reduce the amount of uterine bleeding as well as the incidence of fluid retention, mastalgia, and headaches, making estrogen therapy much easier to tolerate. Concerns about cardiovascular risks (stroke and myocardial infarction) will limit the use of HT for treatment of osteoporosis in older women. See Chapter 36 for recommended doses of HT and contraindications to use.
  5. Raloxifene—Selective estrogen receptor modulators (SERMs) are compounds that bind to and activate estrogen receptors but cause differential estrogenic or antiestrogenic responses in different tissues. Raloxifene was the first SERM approved by the FDA for the prevention and treatment of osteoporosis.
  6. Efficacy—Raloxifene has been shown to reduce the incidence of new vertebral fracture in women with low BMD and no prevalent vertebral fracture by 55%. Among women with prevalent vertebral fractures, raloxifene reduced the incidence of new vertebral fracture by 30%.
  7. Side effects—Women receiving raloxifene may be at increased risk of venous thromboembolism (~3/1000), a risk similar to estrogen. Hot flashes and leg cramps may also occur.

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  1. Extraskeletal effects—Raloxifene is associated with a 76% overall reduction of breast cancer and a 90% reduction in estrogen receptor-positive breast cancer. In addition, a post hoc analysis suggested that women may be at a significantly lower risk of cardiovascular events. A randomized controlled trial is ongoing to answer this question.
  2. Contraindications—Raloxifene is contraindicated in patients with history of venous thromboembolic disease.
  3. Recommended dose—The dosage for prevention of osteoporosis in recently menopausal women and treatment of established osteoporosis is 60 mg daily.
  4. Calcitonin—Calcitonin, an endogenous hormone secreted by the parafollicular C cells of the thyroid gland, helps to maintain normal calcium homeostasis. Calcitonin acts directly on osteoclasts, with inhibitory effects on bone resorption.
  5. Efficacy—Salmon calcitonin nasal spray (200 IU/day) has been shown to significantly reduce the risk of new vertebral fractures by 33–36% in women with prevalent vertebral fractures. It does not appear to reduce the risk of nonvertebral fractures.
  6. Side effects—Common side effects of injectable calcitonin include nausea, local inflammatory reactions at the site of injection, and generalized flushing. Nasal calcitonin is well tolerated; the major side effect is nasal discomfort, including rhinitis and occasional epistaxis.
  7. Contraindications—The major contraindication to the use of both forms of calcitonin is hypersensitivity.
  8. Recommended dose—Injectable calcitonin is administered subcutaneously or intramuscularly at a dose of 50–100 IU daily; the recommended dose of nasal calcitonin is 200 IU daily, administered in alternate nostrils. In some patients, calcitonin has an analgesic effect, making it suitable for patients with acute vertebral fracture who are bedridden and may need to avoid bisphosphonates because of risk of esophageal injury or avoid estrogen because of risk of venous thromboembolism.
  9. Alternative therapies—Phytoestrogens are a diverse group of compounds found in a wide variety of plant foods believed to have both estrogenic and antiestrogenic activity. Phytoestrogens may have a role in preventing osteoporosis. However, ipriflavone has not been shown to prevent bone loss or affect biochemical markers of bone metabolism.
  10. Anabolic agents—In contrast to the currently available drugs that slow bone turnover, thereby allowing bone formation to exceed bone resorption, anabolic agents, like parathyroid hormone (PTH), actually stimulate remodeling, preferentially increasing formation over resorption.

PTH (20 µg subcutaneously once daily) has been shown to achieve a 65% reduction in vertebral fractures. New nonvertebral fragility fractures were reduced by 54%. Nausea and headache are the most common, but infrequent, side effects. PTH injection is now available for treatment of osteoporosis.

  1. Combination therapy—More than 5% of women continue to lose bone density while receiving HT alone and require additional therapy for osteoporosis. Some nonresponse may be due to noncompliance or underdosing. Estrogen and bisphosphonates together have produced greater gains in BMD than either agent used alone, but no data on fracture reduction exist with combination therapy.

Patients treated with PTH who had previously been treated with alendronate for 18–36 mo had a blunted bone density response. Previous treatment with raloxifene and estrogen do not appear to blunt the BMD response. Sequential therapy with PTH first followed by an antiresorptive agent seems to be preferable, giving an additive effect on BMD. No fracture data are available.

  1. FOLLOW-UP

Once patients have been identified and treatment is initiated, they should be monitored to evaluate the response to treatment and assess compliance. The response may be monitored by use of biochemical markers such as serum NTx 3–4 mo after initiating treatment with antiresorptive drugs. In most patients, these markers decrease by at least 40–70% compared with pretreatment levels. BMD should be repeated after 2 years of therapy. If BMD is stable at 2 years, it need not be repeated every 2 years as long as the patient continues the treatment and the medical condition is stable. Early follow-up may be required in patients who have a fracture while on drug treatment or if there is a change in the patient's medical condition or steroid dose.

EVIDENCE-BASED POINTS

  • Osteoporosis is a major health problem in the elderly. The prevalence of osteoporosis increases with age from 15% in 50- to 59-year-olds to 70% in women aged 80 years.
  • Osteoporosis has no clinical manifestations until there is a fracture. Vertebral spine and hip are the most common sites of fracture.

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  • Low bone density is a major risk factor for fracture.
  • BMD can be assessed by noninvasive techniques. DEXA is the most commonly used method to diagnose osteoporosis and identify candidates for intervention.
  • Secondary causes of osteoporosis should be excluded in individuals with very low bone mineral density (Z scores ≤ 1.5).
  • Physical exercise helps to maintain bone density; slow rate of bone loss; improve muscle coordination, mobility, and balance; and reduce incidence of falls.
  • The combination of calcium and vitamin D reduces the risk of fractures.
  • Supplementation with calcium and vitamin D is often required in the elderly.
  • The bisphosphonates, alendronate and risedronate, inhibit bone resorption, increase spine and hip density, and significantly decrease the incidence of vertebral and hip fractures in postmenopausal women with osteoporosis.
  • The evidence for antifracture efficacy of HT comes primarily from observational studies. The WHI (a randomized controlled trial) demonstrated a 34% reduction in hip and fractures.
  • Raloxifene, a selective estrogen receptor modulator, mimics the beneficial effects of estrogen on bone while avoiding the adverse effects on the uterus and breast. It reduces the risk of vertebral fractures but not nonvertebral fractures.
  • Calcitonin has weak antifracture efficacy at the vertebral spine.
  • PTH has been demonstrated to reduce both vertebral and nonvertebral fractures.

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