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Osteoporosis
is a progressive metabolic bone disease that decreases bone density
(bone mass per unit volume), with deterioration of bone structure.
Skeletal weakness leads to fractures with minor or inapparent trauma,
particularly in the thoracic and lumbar spine, wrist, and hip. Acute
or chronic back pain is common. Diagnosis is by dual-energy x‑ray
absorptiometry. Prevention and treatment involve Ca and vitamin
D supplements, exercises to maximize bone and muscle strength and
minimize the risk of falls, and drug therapy to preserve bone mass or
stimulate new bone formation.
Pathophysiology
Normally, bone formation and resorption are closely coupled. Osteoblasts (cells that make the organic matrix of bone and then mineralize bone) and osteoclasts (cells that resorb bone) are regulated by parathyroid hormone (PTH), calcitonin, estrogen, vitamin D, various cytokines, and other local factors such as prostaglandins.
Peak bone mass in men and women occurs by the mid 20s. Blacks reach higher bone mass than whites and Asians, whereas Hispanics have intermediate values. Men have higher bone mass than women. Bone mass plateaus for about 10 yr, during which time bone formation approximately equals bone resorption. After this, bone loss occurs at a rate of about 0.3 to 0.5%/yr. Beginning with menopause, bone loss accelerates in women to about 3 to 5%/yr for about 5 to 7 yr.
Osteoporotic bone loss affects cortical and trabecular (cancellous) bone. Cortical thickness and the number and size of trabeculae decrease, resulting in increased porosity. Trabeculae may be disrupted or entirely absent.
Classification
Osteoporosis can develop as a primary disorder or secondarily due to some other factor.
Primary osteoporosis:
More than 95% of osteoporosis in women and probably about 80% in men is primary. Most cases occur in postmenopausal women and older men. The terms postmenopausal, involutional, senile, and age-related osteoporosis have been used to describe primary osteoporosis in elderly patients. Estrogen deficiency is an important factor in men as well as women. Other contributing factors may include decreased Ca intake, low vitamin D levels, and secondary hyperparathyroidism.
The major mechanism is increased bone resorption, which results in decreased bone mass and microarchitectural deterioration, but other mechanisms also contribute not only in primary osteoporosis but also in the various secondary forms of osteoporosis. The mechanisms of bone loss may involve the following:
Trabecular bone loss occurs more rapidly than cortical bone loss because trabecular bone is more porous and bone turnover is high. However, loss of both types contributes to skeletal fragility.
The most common sites for fragility fractures are the distal radius (dorsally displaced fractures), spine (vertebral compression fractures), femoral neck, and greater trochanter. Other sites include the proximal humerus and pelvis. Fragility fractures rarely occur in children or young adults with normal gonadal function and no detectable secondary cause. This condition is called idiopathic osteoporosis.
Secondary
osteoporosis:
Secondary osteoporosis accounts for < 5% of osteoporosis cases in women but probably more in men. The causes (see Table 1: Osteoporosis: Causes of Secondary Osteoporosis ) may also aggravate bone loss and increase fracture risk in patients with primary osteoporosis.
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Table 1
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Causes of
Secondary Osteoporosis
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Cancer
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COPD
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Chronic renal failure
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Drugs (eg, corticosteroids, ethanol, phenytoin , tobacco, barbiturates, heparin )
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Endocrine disease (eg, glucocorticoid excess, hyperparathyroidism, hyperthyroidism, hypogonadism, hyperprolactinemia, diabetes mellitus)
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Hypervitaminosis A
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Immobilization
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Liver disease
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Malabsorption syndromes
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Prolonged weightlessness (as occurs in space flight)
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RA
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Sarcoidosis and the drugs used to treat sarcoidosis
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Risk Factors
Because stress, including weight bearing, is necessary for bone growth, immobilization or extended sedentary periods result in bone loss. Being thin predisposes to decreased bone mass. Insufficient dietary intake of Ca, P, and vitamin D predisposes to bone loss, as does endogenous acidosis (eg, high-protein diets). Cigarette smoking and excessive caffeine or alcohol use also adversely affect bone mass. Whites and Asians are at higher risk. A family history of osteoporosis also increases risk. Other risk factors (eg, decreasing amounts of sex hormones) predispose to specific types of osteoporosis. Patients who have had one fragility fracture are at increased risk of having other clinical (symptomatic) fractures as well as clinically asymptomatic vertebral compression fractures.
Symptoms and Signs
Most of the chronic pain typical of osteoporosis results from fractures, which may develop after minimal, inapparent, or no trauma. Patients may be asymptomatic for years, until fractures begin to occur. Eventually, patients often develop pain in the bones or muscles, particularly of the back. Vertebral compression fractures are common, usually in weight-bearing vertebrae (T6 and below). The pain begins acutely, usually does not radiate, is aggravated by weight bearing, may cause local tenderness, and generally begins to subside in 1 wk. However, residual pain may last for months or be constant.
Multiple thoracic compression fractures eventually cause dorsal kyphosis, with exaggerated cervical lordosis (dowager's hump). Abnormal stress on the spinal muscles and ligaments may cause chronic, dull, aching pain, particularly in the lower back. Fractures can develop at other sites, commonly the hip or wrist, usually from falls.
Diagnosis
Osteoporosis should be suspected in patients who sustain fractures after only mild or trivial trauma; older adults, particularly those with risk factors and unexplained back pain; patients with decreased bone density that is incidentally noted on imaging studies; and patients at risk of secondary osteoporosis. If imaging studies have been done or are necessary to evaluate symptoms (eg, back pain), osteoporosis may be obvious. However, imaging studies are often equivocal, and the diagnosis should be established by bone density measurement.
Plain x‑rays:
Bones show decreased radiodensity and loss of trabecular structure, but not until about 30% of bone has been lost. A loss of horizontally oriented trabeculae increases the prominence of the cortical end plates and of vertically oriented, weight-bearing trabeculae. Loss of height and increased biconcavity characterize vertebral compression fractures. Thoracic vertebral fractures may cause anterior wedging. In long bones, although the cortices may be thin, the periosteal surface remains smooth. Vertebral fractures at T4 or above suggest cancer rather than osteoporosis.
Corticosteroid-induced osteoporosis is likely to cause rib fractures and exuberant callus formation at sites of healing fractures. Osteomalacia may cause abnormalities on imaging tests similar to those of osteoporosis (
see Sidebar 1: Osteoporosis: Osteopenia: Differentiating Osteoporosis and Osteomalacia ). Hyperparathyroidism can be differentiated when it causes subperiosteal resorption or cystic bone lesions, but these are uncommon.
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Sidebar 1
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Bone
density measurement:
Dual-energy x-ray absorptiometry (DEXA) is used to measure bone density. DEXA is diagnostic for osteoporosis, predicts the risk of fracture, and can be used to follow treatment response. Bone density of the lumbar spine, hip, distal radius or ulna, or the entire body can be measured. (Quantitative CT scanning can produce similar measurements in the spine or hip.) Usually, the lumbar spine, total proximal femur, or femoral neck is measured. DEXA results are reported as T scores. A T score corresponds to the number of standard deviations by which bone density differs from a healthy, young person of the same sex and race. A DEXA result of > 1 is defined as osteopenia and suggests an increased risk of osteoporosis; > 2.5 is diagnostic for osteoporosis.
If DEXA scanning of the central skeleton is unavailable, portable, less expensive systems such as peripheral DEXA or quantitative ultrasound of the heel can be used. However, monitoring the response to treatment with serial measurements of bone density should be done only with central DEXA scanning.
Current central DEXA systems can also assess vertebral deformities in the lower thoracic and lumbar spine, a procedure termed vertebral fracture analysis (VFA). Vertebral deformities, even those clinically silent, may indicate increased risk of future fractures. VFA is more likely to be useful in patients with loss of
≥
3 cm in height.
Other
testing:
Once osteoporosis is diagnosed, patients should be checked for causes of secondary osteoporosis. Serum Ca should be measured to rule out asymptomatic hyperparathyroidism. PTH levels may be increased in patients with decreased Ca absorption or hypercalciuria. Other tests such as thyroid-stimulating hormone or free thyroxine to check for hyperthyroidism, vitamin D levels, measurements of urinary free cortisol, and blood counts and other tests to rule out cancer, especially myeloma (eg, serum protein electrophoresis), should be considered depending on the clinical findings. Serum alkaline phosphatase is usually normal but may be elevated by recent fracture.
Patients with weight loss should be screened for GI disorders as well as cancer. Bone biopsy is reserved for unusual cases (eg, young patients with pathologic fractures and no apparent cause). Levels of serum or urine N-telopeptide crosslinks (NTX) or free deoxypyridinoline (DPYR) may reflect increased breakdown of collagen. These tests are not sufficiently accurate for routine clinical use but may be used to assess the effectiveness of therapy.
Screening
DEXA screening is recommended for all women > 65. Bone density should also be measured in women between 50 and 65 who have risk factors, including a family history of osteoporosis, a history of fragility fractures, and low body weight. Screening is also recommended for both men and women who have had fragility fractures, even at younger ages.
Treatment
The goals of treatment are to preserve bone mass, prevent fractures, decrease pain, and maintain function.
Preserving bone mass:
The rate of bone loss can be slowed with drugs and, when possible, modification of risk factors. Ca and vitamin D intake and physical activity must be adequate for drug treatment to be effective.
Risk factor modification can include maintaining adequate body weight, increasing weight-bearing exercise, minimizing caffeine and alcohol intake, and stopping smoking. The optimal amount of weight-bearing exercise is not established, but an average of 30 min/day is recommended. A physical therapist can develop a safe exercise program.
All men and women should consume at least 1000 mg of elemental Ca daily. An intake of 1200 to 1500 mg/day is recommended for postmenopausal women and older men and for periods of increased requirements, such as pubertal growth, pregnancy, and lactation. Diet alone is rarely adequate; Ca supplements are needed, most commonly as Ca carbonate or Ca citrate. Supplements differ in their elemental Ca concentration. Ca citrate is better absorbed in patients with achlorhydria, but both are well absorbed when taken with meals. Ca should be taken in divided doses of 500 to 600 mg bid or tid.
Vitamin D in doses of 800 U once/day is generally recommended, but up to 2000 U/day is safe and may be helpful in osteoporotic patients. Patients with vitamin D deficiency may need even higher doses. Supplemental vitamin D is usually given as cholecalciferol, the natural form of vitamin D, although ergocalciferol , the synthetic plant derived form, is probably also acceptable.
Bisphosphonates are first-line drug therapy. By inhibiting bone resorption, bisphosphonates preserve bone mass and can decrease vertebral and hip fractures by 50%. To treat osteoporosis, bisphosphonates can be given orally. Alendronate can be given at doses of 10 mg po once/day or 70 mg po once/wk, ibandronate 2.5 mg po once/day or 150 mg once/mo, or risedronate at 5 mg po once/day or 35 mg once/wk. All increase bone mineral density and decrease risk of at least vertebral fractures. Oral bisphosphonates must be taken on an empty stomach with a full glass of water, and the patient must remain upright for ≥ 30 min. They can cause esophageal irritation. Esophageal disorders that delay transit time and symptoms of upper GI disorders are relative contraindications to oral bisphosphonates. Weekly or monthly therapy is generally preferred for its greater convenience and probably fewer adverse effects. Parenteral zoledronic acid is an alternative to oral bisphosphonates. Doses of 5 mg IV once/year increase bone mass and decreases risk of vertebral and nonvertebral fractures. Pamidronate can also be given IV but has not yet been shown to prevent fractures. Osteonecrosis of the jaw has been associated with use of bisphosphonates; however, this is rare in patients taking oral bisphosphonates. Risk factors include IV bisphosphonate use and cancer. Bisphosphonates may also be associated with atrial fibrillation, but the mechanism is not clear and there has been no association with increased cardiovascular mortality.
Salmon calcitonin is less effective than bisphosphonates for treating osteoporosis. The subcutaneous dose is 100 IU/day or every other day; the nasal spray dose is 200 U/day in alternating nostrils (1 spray). Salmon calcitonin may provide short-term analgesia after an acute fracture.
Estrogen can preserve bone density and prevent fractures. Most effective if started within 4 to 6 yr of menopause, estrogen may slow bone loss and possibly reduce fractures even when started much later. It 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. Use of estrogen increases the risk of thromboembolism and endometrial cancer and may increase the risk of breast cancer. The risk of endometrial cancer can be reduced in women with an intact uterus by taking a progestin with estrogen (see Menopause: Hormone therapy). However, taking a combination of a progestin and estrogen increases the risk of breast cancer, coronary artery disease, stroke, and biliary disease.
Raloxifene is a selective estrogen receptor modulator (SERM) that may be appropriate for treatment of osteoporosis in women who cannot take bisphosphonates. It reduces vertebral fractures by about 50% but has not been shown to reduce nonvertebral fractures. Raloxifene does not stimulate the uterus and antagonizes estrogen effects in the breast, probably reducing the risk of breast cancer.
PTH, which stimulates new bone formation, is generally reserved for patients who have the following characteristics:
When given daily by injection for an average of 20 mo, synthetic PTH (PTH 1-34; teriparatide ) increased bone mass and reduced fractures.
Preventing
fractures:
Many elderly patients are at risk of falls 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 exercises may increase stability. Hip pads can reduce the incidence of hip fracture despite continued falls.
Treating
pain and maintaining function:
Acute back pain from a vertebral compression fracture should be treated with orthopedic support, analgesics, and (when muscle spasm is prominent) heat and massage (see Rehabilitation: Treatment of Pain and Inflammation). Chronic backache may be relieved by an orthopedic garment and exercises to strengthen paravertebral muscles. Avoiding heavy lifting can help. Bed rest should be minimized, and consistent, carefully designed weight-bearing exercise should be encouraged.
In some cases, vertebroplasty, sometimes preceded by kyphoplasty, can relieve severe pain. In vertebroplasty, methyl methacrylate is injected into the vertebral body. In kyphoplasty, the vertebral body is expanded with a balloon. These procedures may reduce deformity in the injected vertebrae but do not reduce and may even increase the risk of fractures in adjacent vertebrae. Other risks may include rib fractures, cement leakage, and pulmonary edema or MI.
Prevention
The goals of prevention are to preserve bone mass and prevent fractures. Preventive measures are indicated in postmenopausal women and older men, patients taking long-term systemic corticosteroids, and patients at high risk (eg, osteopenia with multiple risk factors or secondary causes).
Preventive measures are similar to treatment measures, including those aimed at preserving bone mass. Bisphosphonates and other drugs can be given as for treatment of osteoporosis, but alendronate is given at a reduced dose (5 mg po once/day or 35 mg once/wk). Measures to prevent fractures are also indicated.
Last full review/revision February 2008 by Lawrence G. Raisz, MD
Content last modified February 2008
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