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Harrison’s Manual of Medicine




Osteoporosis is defined as a reduction in bone mass (or density) or the presence of fragility fracture. It is defined operationally as a bone density that falls 2.5 SD below the mean for a young normal individual (a T-score of <–2.5). Those with a T-score of <1.0 have low bone density and are at increased risk for osteoporosis. The most common sites for osteoporosis-related fractures are the vertebrae, hip, and distal radius.
Etiology   Low bone density may result from low peak bone mass or increased bone loss. Risk factors for an osteoporotic fracture are listed in Table 177-1, and diseases associated with osteoporosis are listed in Table 177-2. Certain drugs, primarily glucocorticoids, cyclosporine, cytotoxic drugs, anticonvulsants, aluminum, and heparin, also have detrimental effects on the skeleton.

Table 177-1 Risk Factors for Osteoporosis Fracture

Table 177-2 Diseases Associated with an Increased Risk of Generalized Osteoporosis in Adults

Clinical Features   Pts with multiple vertebral crush fractures may have height loss, kyphosis, and secondary pain from altered biomechanics of the back. Thoracic fractures can be associated with restrictive lung disease, whereas lumbar fractures are sometimes associated with abdominal symptoms. Dual- energy x-ray absorptiometry has become the standard for measuring bone density in most centers. Criteria approved for Medicare reimbursement of bone mass measurement are summarized in Table 177-3. A general laboratory evaluation includes complete blood count, serum calcium, and urine calcium. Further testing is based on clinical suspicion and may include thyroid-stimulating hormone (TSH), urinary free cortisol, parathyroid hormone (PTH), serum and urine electrophoresis, and testosterone levels (in men). Markers of bone resorption (e.g., urine cross-linked N-telopeptide) may be helpful in detecting an early response to antiresorptive therapy if measured prior to and 4 to 6 months after initiating therapy.

Table 177-3 FDA-Approved Indications for BMD Testsa

Treatment involves the management of acute fractures, modifying risk factors, and treating any underlying disorders that lead to reduced bone mass. Treatment decisions are based on an individual’s risk factors, but active treatment is generally recommended if the T-score is <–2.5. Oral calcium (1–1.5 g/d of elemental calcium in divided doses), vitamin D (400–800 IU qd), exercise, and smoking cessation should be initiated in all patients with osteoporosis. Estrogen (0.625 mg/d for conjugated estrogens) in postmenopausal women decreases the rate of bone reabsorption and should be given with a progestin in women with an intact uterus. Bisphosphonates (alendronate 10 mg PO qAM, risedronate 5 mg PO qAM) augment bone density and decrease fracture rates. Alendronate can also be administered as a single weekly 70- mg dose. Bisphosphonates are poorly absorbed and should be taken in the morning on an empty stomach with 0.25 L (8 oz) of tap water. Raloxifene (60 mg PO qd), a selective estrogen receptor modulator, increases bone density and decreases total and LDL cholesterol without stimulating endometrial hyperplasia, though it may precipitate hot flashes.

Etiology   Defective mineralization of the organic matrix of bone results in osteomalacia. Osteomalacia is caused by inadequate intake or malabsorption of vitamin D (chronic pancreatic insufficiency, gastrectomy, malabsorption), acquired or inherited disorders of vitamin D metabolism (anticonvulsant therapy, chronic renal failure), chronic acidosis (renal tubular acidosis, acetazolamide ingestion), renal tubular defects that produce hypophosphatemia (Fanconi’s syndrome), and chronic administration of aluminum-containing antacids.
Clinical Features   Skeletal deformities may be overlooked until fractures occur after minimal trauma. Symptoms include diffuse skeletal pain and bony tenderness and may be subtle. Pain in the hips may result in an altered gait. Proximal muscle weakness may mimic primary muscle disorders. A decrease in bone density is usually associated with loss of trabeculae and thinning of the cortices. Characteristic x-ray findings are radiolucent bands (Looser’s zones or pseudofractures) ranging from a few millimeters to several centimeters in length, usually perpendicular to the surface of the femur, pelvis, scapula, upper fibula, or metatarsals. Changes in serum calcium, phosphorus, 25(OH)D, and 1,25(OH)2D levels vary depending on the cause. However, modest vitamin D deficiency leads to compensatory secondary hyperparathyroidism characterized by increased levels of PTH and alkaline phosphatase and lower levels of ionized calcium. 1,25 dihydroxyvitamin D levels may be preserved, reflecting upregulation of 1a hydroxylase activity.

In osteomalacia due to vitamin D deficiency, vitamin D2 (ergocalciferol) or D3 (cholecalciferol) is given orally in doses of 800–4000 IU daily for 6–12 weeks, followed by daily supplements of 200–600 IU. Elderly persons may require 50,000 IU weekly for 8 weeks to treat vitamin D deficiency. Osteomalacia due to malabsorption requires still larger doses of vitamin D (up to 100,000 IU/d) and calcium (calcium carbonate 4 g/d). In pts taking anticonvulsants, concurrent vitamin D should be administered in doses that maintain the serum calcium and 25(OH)D levels in the normal range. Calcitriol (0.25–1 µg PO qd or 1.0–2.5 µg IV thrice weekly) is effective in treating hypocalcemia or osteodystrophy caused by chronic renal failure.


For a more detailed discussion, see Holick MF, Krane SM: Introduction to Bone and Mineral Metabolism, Chap. 340, p. 2192; and Lindsay R, Cosman F: Osteoporosis, Chap. 342, p. 2226, in HPIM-15.


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