Overview and Risk Factors
Osteoporosis is a metabolic disease characterized by progressive thinning of the bone matrix and cortex. Fractures may result from decreased bone strength, and hip fractures are a significant cause of morbidity and mortality for aging adults. Primary osteoporosis reflects an imbalance in the coupling of osteoblasts and osteoclasts and commonly reflects natural hormonal and metabolic changes. Secondary osteoporosis makes up 5% of cases and can be caused by hyperparathyroidism, hyperthyroidism, diabetes mellitus, chronic kidney disease, hepatic disease, malabsorption syndromes, pancreatic insufficiency, malignancy, and certain medications, such as corticosteroids, aluminum-containing antacids, and heparin.
In general, whites are at greater risk than persons of Latin American or African heritage. African Americans have greater bone densities and a lower risk of fracture, compared with white Americans. African American women, however, have higher morbidity and mortality associated with fracture.1 This example shows the importance of screening at-risk individuals independent of race, ethnic background, and gender.
Many risk factors are associated with osteoporosis. The following are among the most common:
Age. In postmenopausal women, fracture risk increases with age. Both men and women aged 70 and older have an increased risk of fracture.
Female gender. Primary osteoporosis is 6 times more common in women than in men. Also, osteoporosis begins earlier and tends to be more severe in women.
Body habitus. Persons with lower body mass have lower bone mineral density. Obesity reduces the risk of developing osteoporosis.
- Sedentary lifestyle.
- Genetic factors.
- Previous fracture.
- Glucocorticoid, cyclosporine, and methotrexate treatment.
- Vitamin A, heparin, aluminum-containing antacids, and medroxyprogesterone increase risk, whereas thiazide diuretics, estrogen, and androgens are protective.
- High alcohol consumption. However, a moderate-to-low alcohol intake could be protective.2
- Elevated blood homocysteine concentration is associated with elevated risk.
- Early onset of menopause.
- Calcium or vitamin D deficiency.
- Low peak bone density achieved in young adulthood.
- Dietary factors (see Nutritional Considerations).
Diagnosis and Treatment
Vertebral fracture is the most common clinical manifestation of osteoporosis or osteopenia (a diagnosis of less severe bone loss), typically presenting as an asymptomatic incidental finding on x-ray. Fracture of the vertebrae usually occurs in the lower thoracic or upper lumbar region, and may occur after simple movements like bending over and lifting. Multiple fractures may result in pronounced thoracic kyphosis, sometimes called "dowager's hump."3 In the absence of fracture, pain is unlikely to be due to osteoporosis, but it could be due to osteomalacia or other bone disease.
In the absence of fragility fracture, radiological bone densitometry establishes the diagnosis of osteoporosis. Bone biopsy, which can ensure histologic diagnosis, is rarely performed. A history of fracture is not necessary for diagnosis.
Laboratory tests, particularly thyroid-stimulating hormone, complete blood count (CBC), 25-hydroxy vitamin D, serum protein electrophoresis, urine calcium, and a comprehensive metabolic panel (including calcium and phosphate), can help determine if osteoporosis is due to another disease process. Because many disease processes can contribute to osteoporosis, disease-specific diagnostic evaluations are necessary, based on results of clinical presentation and screening tests.
The clinical focus should be on prevention, symptomatic therapy, and inhibition of disease progression. Lifestyle modification is an important component of therapy. Modifications include making dietary changes and reducing caffeine consumption (see Nutritional Considerations), as well as avoiding falls. Other important lifestyle changes include weight-bearing exercise at least 3 times a week and smoking cessation (see below for more information).
Medications used to decrease bone resorption include bisphosphonates, raloxifene, calcitonin, and estrogens. Teriparatide is used to increase bone mass. All these medications must be given with adequate amounts of calcium and vitamin D.
Bisphosphonates (alendronate, pamidronate, risedronate, and ibandronate) decrease bone resorption and are useful for prevention and treatment.
Raloxifene, a selective estrogen receptor modulator (SERM), inhibits bone resorption and is useful for prevention. Like tamoxifen, it reduces the risk of breast cancer, but, unlike tamoxifen, it does not increase the risk of endometrial cancer.
Calcitonin decreases bone resorption and may help decrease associated pain.
Estrogen use, with or without progesterone, reduces bone resorption and slows progression of osteoporosis. However, the benefits of estrogens must be weighed against the many possible adverse effects of estrogen therapy, particularly the increased risk of breast cancer, cardiac events, and strokes.
Testosterone may increase bone mass for men with osteoporosis and low testosterone levels. However, the effect of testosterone on cancer risk should be considered. If it is used, prostate-specific antigen (PSA) level should be monitored.
Thiazides decrease renal calcium loss, and are associated with increased bone mass density. However, they may increase the risk for electrolyte disturbances and postural hypotension.
Teriparatide, a recombinant human parathyroid hormone, stimulates bone formation and is administered subcutaneously.
Exercise reduces osteoporosis risk. Expert reviews have confirmed that regular weight-bearing and resistance exercise is helpful for increasing the bone mineral density (BMD) of the spine in postmenopausal women and for treating osteoporosis.4,5
Smoking cessation has been associated with decreased risk of hip fracture. Smoking has an independent, dose-dependent effect on bone loss, which increases fracture risk in both sexes. Smoking increases the lifetime risk of developing a hip fracture by an estimated 31% in women and 40% in men, and increases the lifetime risk for vertebral fracture by an estimated 13% in women and 32% in men. Risk declines among former smokers, but the benefit is not observed until 10 years after smoking cessation.6,7
Osteoporosis is a common disease in areas where Western diets prevail. The common belief that this complex disease is preventable or treatable by a high intake of calcium supplements or dairy products has not withstood scrutiny.8 The Nurses' Health Study, following more than 72,000 women for 18 years, found no effect of either dairy products or a high-calcium diet on fracture risk.9 Skeletal health involves dietary habits that support bone formation and retard bone resorption, in addition to regular exercise. For some, a combination of drug therapy and supplemental approaches may be required as well. The topic of daily calcium intake and its impact on bone metabolism remains highly controversial.
The following factors are under investigation for their role in preventing or slowing osteoporosis:
Reduced animal protein intake. Cross-cultural studies have found strong, positive relationships between animal protein intake and risk for hip fracture.10 Higher meat intake (> 5 servings per week) significantly increased the risk for forearm fracture in women, compared with eating meat less than once per week.11 Elderly women whose diets contain a high ratio of animal to vegetable protein have more rapid bone loss and greater risk for hip fracture than those with a low ratio.12 Bone health appears to benefit from replacing animal protein with vegetable sources of protein, particularly soy. In clinical studies with postmenopausal women, soy foods have been found to prevent bone loss.13 Other research has found a dose-response relationship between soy protein and bone mineral density in postmenopausal women.14 The relatively high concentrations of isoflavones in plant-based proteins may be one of the many proposed reasons for their beneficial effect on bone metabolism.15
Increased fruit and vegetable intakes. Studies have shown that fruit and vegetable intakes are associated with bone mineral density in both women and men. These associations may be due to the buffering effect of potassium and magnesium in fruits and vegetables on the acid-base balance that partly determines bone resorption.16,17 These foods also provide vitamin K, low intakes of which may contribute to osteoporosis and risk of hip fracture by causing undercarboxylation of osteocalcin.18,19
Reduced sodium intake. Some studies have found that habitually high sodium intake increases urinary calcium loss20 and markers of bone resorption.21 Although restricting dietary sodium reduces calcium loss and markers of bone resorption in post- (not pre-) menopausal women,22 the effect of sodium restriction on long-term bone integrity and fracture risk remains unclear.
Low-fat diets. Studies have found that higher intake of fat is associated with a greater loss of bone2 and greater fracture risk.23 Possible mechanisms include the tendency of excess fat intake to reduce calcium absorption and to affect eicosanoid production. Specifically, the omega-6 polyunsaturated fatty acids linoleic acid and arachidonic acid act as precursors to prostaglandin E2 (PGE2), which favors osteoclast-induced bone resorption at the expense of osteoblast-induced bone formation.24
Moderation in caffeine use. Studies have found that women consuming the most caffeine have accelerated spinal bone loss25 and almost triple the risk for hip fracture.26 The risk for bone loss appears to be greatest in women who consume > 18 ounces of coffee per day, or 300 mg caffeine from other sources.
Limiting supplemental vitamin A. Studies have shown that the declines in bone density and risk for hip fracture are increased at as little as twice the recommended intake for retinol.27 Risk for fracture also appears to be significantly higher in women consuming more food sources of retinol.28 Vitamin A adequacy can instead be ensured with beta carotene from plant sources, particularly orange and yellow vegetables.
Combined supplemental vitamin D and calcium. The effect of a combination of these 2 nutrients appears to be of significant benefit in reducing bone loss in patients with corticosteroid-induced osteoporosis.29 Supplements of vitamin D (500-800 IU/day) and calcium (1200-1300 mg/day) have also been found to increase bone density and decrease bone turnover and fracture risk in older adult women.30
Low sodium diet.
Restrict caffeine and alcohol consumption.
Female patients with osteoporosis should aim for a total calcium intake from diet and supplements of about 1500 mg/day in 3 or more divided doses, plus at least 100% of the dietary reference intake (DRI) for vitamin D (400-800 IU/day). While supplemental calcium and vitamin D may benefit selected adult patients without osteoporosis, no theoretical basis exists for population wide recommendations for high calcium intakes, particularly in males, due to associations between calcium or dairy intake and prostate cancer (see Prostate Cancer).
Exercise prescription with patient-appropriate, weight-bearing exercises. Physical therapy or exercise physiology consultation as needed.
What to Tell the Family
Osteoporosis is a preventable and treatable disorder. Proper dietary and exercise habits help maintain bone integrity and reduce bone loss later in life. The osteoporosis patient should limit alcohol and caffeine to <1 serving per day and restrict salt intake in order to limit the calcium losses these substances may cause. Medications may help adjunctively to reduce bone loss, improve bone density, and reduce fracture risk.
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