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Chapter 46 Osteoporosis

Manual of Rheumatology and Outpatient Orthopedic Disorders


Chapter 46 Osteoporosis

Joseph M. Lane and John H. Healey

Pathogenesis
Clinical presentation
Differential diagnosis
Treatment
Prognosis

Osteoporosis (OP) is a condition in which bone mass is below normal for an person's age, sex, and race. OP implies low quantities of mineralized bone, unmineralized matrix, microarchitectural defects, and susceptibility to low-energy, fragility fractures. A fracture is the result of a combination of bone mass, bone geometry, and the level and vector of trauma. Osteomalacia (OM) refers to an increase in unmineralized matrix, independent of the amount of bone mass. In practice, some patients have a mixture of OP and OM. Osteopenia refers to the radiographic finding of decreased bone density, which may be found in OP, OM, or other conditions.

Reduced bone mass is the most significant factor contributing to fractures. Normal, age-dependent bone loss is accelerated at menopause. Cancellous bone (also called trabecular bone) is lost more rapidly than cortical bone. Fractures usually occur earlier in principally cancellous bones (vertebrae) than in cortical bones (femoral neck). OP is the most common metabolic bone disease, contributing to fractures in 25% of women and 17% of men over age 70. It is important to appreciate the fact that we now have available excellent measurement and treatment tools which, in combination, can prevent or retard the development of OP.

I. Pathogenesis. Low initial levels of adult bone mass or an acceleration in bone loss can reduce bone mass and strength to below the fracture threshold (the bone mass below which the propensity to fracture is increased). Inadequate calcium intake and postmenopausal estrogen deficiency account for 90% of OP cases. Factors affecting primary and secondary OP are the following:

  1. Nutritional abnormalities and social practices
    1. Inadequate calcium intake.
    2. Malabsorption.
    3. Alcoholism.
    4. Smoking.
    5. Vitamin D deficiency.
    6. Vitamin C deficiency.
  2. Endocrine conditions
    1. Menopause.
    2. Hyperthyroidism.
    3. Hyperparathyroidism.
    4. Cushing's disease.
    5. Diabetes mellitus.
  3. Immobilization
    1. Illness.
    2. Weightlessness.
  4. Iatrogenic causes
    1. Corticosteroid therapy .
    2. Long- term heparin therapy.
    3. Long-term phenytoin (Dilantin) therapy.
    4. Castration (oophorectomy, radiation, chemotherapy).
    5. Excessive thyroid therapy.
  5. Risk factors
    1. Female sex. (Female maximal bone mass is lower than male maximal bone mass.)
    2. White race. (Blacks have a greater bone mass; that of other races is probably intermediate but not as well-defined .)
    3. Northwest European extraction. Other ethnic groups are less susceptible.
    4. Lactation contributes to a cumulative negative calcium balance if calcium supplementation is inadequate.
    5. Smoking.
    6. Scoliosis.
    7. Ectomorphic habitus.
    8. Sedentary life-style.
    9. Amenorrhea (marathon runners, ballerinas).
    10. Family history (one-third have strong inheritance).
    11. Collagen disorders: osteogenesis imperfecta, Ehlers-Danlos syndrome, Marfan syndrome.
    12. History of low-energy fracture.
    13. Systemic inflammatory disorders, such as rheumatoid arthritis and ankylosing spondylitis.

II. Clinical presentation. Back pain and fractures are the most characteristic presenting symptoms. Loss of height is a cardinal sign of vertebral OP. More than 60% of vertebral fractures are not symptomatic. Compression fractures are often multiple and most commonly occur in the T-11 to L-2 distribution. Fractures of the wrist (Colles' fracture), hip (femoral neck and intertrochanteric), and pelvis may be the first manifestation of OP. High- turnover OP results from increased bone resorption and occurs at the onset of menopause. Low-turnover OP is caused by decreased osteoblastic bone formation as a consequence of genetics , senility, and antimetabolites.

  1. History. Multiple risk factors and at least one other pathologic factor are usually present.
  2. Physical examination findings. Thin appearance, kyphosis, scoliosis, height loss, and percussion tenderness of spine.
  3. Laboratory studies. Serum levels of calcium, phosphorus, and alkaline phosphatase are normal. Urinary calcium may be high in early postmenopausal period but is normal or low in chronic OP. Collagen breakdown products (N-telopeptide, pyridinoline cross-links) are elevated in high-turnover osteoporosis.
  4. Radiographs
    1. Osteopenia, loss of horizontal vertebral trabeculation.
    2. Compression fractures: wedge , crush, or biconcave. Intact posterior elements.
    3. Pedicles preserved. No lytic or blastic lesions.
  5. Bone densitometry. Bone mass can be measured by noninvasive means (spinal and femoral dual-energy x-ray densitometry, radial single-photon densitometry, quantitative spinal computed tomography or ultrasound ). Bone mass measurements correlate well with fracture risk. Values (called the T score) between 1 and 2.5 standard deviations (SD) below those for young, normal, peak bone mass indicate diminished bone mass or osteopenia, and values of 2.5 SD below normal represent full osteoporosis. Severe osteoporosis is defined as values of 2.5 SD below normal in the setting of a fragility fracture (World Health Organization). Serial measurements of bone density may identify patients losing bone rapidly and help monitor therapy.
  6. Bone biopsy. Iliac crest biopsy reveals reduced bone mass and excludes concomitant OM, excessive osteoclastic bone resorption, and marrow disorders such as malignancies. This is the only method to assess bone quality and gives the most precise measure of bone turnover. It is not, however, a routine test.

III. Differential diagnosis. Treatable causes of secondary OP should be identified.

  1. Multiple myeloma. An elevated erythrocyte sedimentation rate, proteinuria, monoclonal gammopathy, and radiographic lytic lesions suggest the diagnosis.
  2. Metastatic malignancy may be associated with increased alkaline phosphatase, hypercalcemia, blastic bone lesions, and radiographic evidence of destructive lesions of a vertebral pedicle.
  3. Osteomalacia. Low serum calcium and phosphorus levels, high levels of alkaline phosphatase, low levels of 25(OH)-vitamin D, and radiographic pseudofractures. Biopsy shows wide osteoid seams and delayed mineralization.
  4. Hyperthyroidism is suggested by weight loss, heat intolerance, palpitations, elevated serum thyroxine, low level of thyroid-stimulating hormone, and elevated urinary calcium and hydroxyproline.
  5. Hyperparathyroidism. Elevated calcium, low or normal phosphorus, and elevated serum parathormone level. Radiographic evidence of endosteal and periosteal resorption. Biopsy shows osteitis fibrosa cystica and tunneling resorption.
  6. Renal osteodystrophy. Uremia, elevated phosphorus, low calcium, and ectopic calcification are diagnostic clues.
  7. Gastrointestinal disease. Symptoms of malabsorption or a history of previous gastrointestinal surgery suggests a cause for OP or OM.

IV. Treatment

  1. Orthopedic
    1. Limb fractures. Routine fracture care, followed by bone mass assessment and appropriate treatment.
    2. Spine fractures. Back pain from vertebral fractures often lasts between 4 and 6 weeks. It can be associated with ileus, pneumonia, skin decubitus ulcers, and thromboembolic complications. Bed rest and analgesics are recommended until the patient is comfortable (e.g., 1 week). Mobilize and ambulate as tolerated (pool therapy may help). Avoid long-term use of back braces, which ultimately weaken spinal muscles . Calcitonin for treatment of OP and pain. The development of such fractures should prompt an assessment of bone mass and treatment of OP.
    3. Physical therapy. Daily walking; lumbar flexion and thoracic extension exercises. Sit-ups should be avoided.
  2. Medical (in the presence of defined osteopenia or osteoporosis)
    1. Calcium carbonate (1,500 mg elemental daily) or calcium citrate (1,200 mg daily).
    2. Vitamin D 3 (400 to 800 IU/d PO).
    3. Estrogen (hormone replacement therapy). Consider strongly at menopause but beneficial at all postmenopausal ages. Increases bone mass and decreases fracture risk by 50%. Progesterone cyclically or in low doses continuously is required to prevent endometrial cancer. Improvement in bone mass and cardiovascular protection outweighs possible increased risk for breast cancer in many clinical situations.
    4. Calcitonin in nasal form (i.e., 200 U of Miacalcin daily) increases spinal bone mass and decreases vertebral fracture risk by 37% but does not protect the hip. It may provide analgesia in the settings of vertebral fractures. Its complication rate is low (nasal irritation in 2% of cases).
    5. Bisphosphonates (alendronate). Alendronate (10 mg daily) increases spine and bone mass and decreases the risk for fracture by 50%, a rate equal to that of hormone replacement therapy. Esophagitis is the main potential complication but can be eliminated by slow buildup of dosage and appropriate administration. Etidronate, at a dose of 400 mg orally/d for two weeks every three months is an alternative.
    6. Selective estrogen receptor modifiers. Raloxifene (60 mg daily) is an anti-estrogen that inhibits bone resorption. It increases bone mass and affords fracture prevention for the spine. It increases postmenopausal symptoms and leg cramps (8%) but does not appear to be associated with uterine cancer at this time. One study suggests a 60% diminution in the risk for breast cancer. Tamoxifen, a breast cancer therapeutic agent, also limits bone resorption but is not approved for OP.
    7. Combination therapy. If bone mass does not increase or fragility fractures continue to occur, combinations such as estrogen replacement therapy and bisphosphonate appear to be synergistic (15% enhancement over single agents ).
    8. Exercise (see below).
  3. Prevention
    1. Calcium supplementation with vitamin D 3 . Doses of calcium should be increased with increasing age, to a maximum of 1,500 mg in postmenopausal women. The total daily calcium regimen can be taken as a combination of food and calcium pills (i.e., calcium carbonate or citrate). In a postmenopausal woman , three units of calcium are required daily. One unit is equivalent to a 500-mg calcium tablet, two pieces of cheese, one jar of yogurt, or one 8-oz glass of milk. The dosage of vitamin D 3 is 400 to 800 IU daily.
    2. Exercise. Impact, stretching, strengthening, balance training. Tai-chi decreases the number of falls by 47%. Walking 20 minutes per day 3 times per week is helpful and is practical for most patients.
    3. Estrogen. Consider low doses in patients with natural or premature menopause or other risk factors.
    4. Selective estrogen receptor modifiers. Because it increases postmenopausal symptoms, raloxifene should be given at least 5 years after menopause (see above).
    5. Bisphosphonates. Alendronate (5 mg daily or 10 mg thrice weekly) is effective in preventing bone loss.
  4. Steroid-induced osteoporosis. Corticosteroids, especially when taken on a long-term basis, have a significant negative impact on bone mass. They increase bone resorption, decrease bone formation, and lead to secondary hyperparathyroidism. To counter these adverse actions, the following regimen is recommended for all patients treated with steroids for more than 1 month:
    1. Bone mass measurement at baseline and yearly thereafter. These results will guide future therapeutic decisions.
    2. Daily intake of 1,500 mg of calcium and 800 U of vitamin D 3 .
    3. Estrogen replacement therapy in postmenopausal women.
    4. Assessment of testosterone levels in men with decreased bone mass and replacement treatment if appropriate.
    5. Use of bisphosphonates or calcitonin in patients with persistently low bone mass or the development of new fragility fractures despite nutritional supplements and estrogen replacement therapy.

V. Prognosis

  1. By maximizing peak bone mass and reducing the rate of bone loss, bone mass can be maintained above the fracture threshold.
  2. Reduced bone mass is permissive of fractures. Fractures heal, but morbidity and mortality are high. Twenty percent of women die within 1 year of fracturing their hip.
  3. Presently, bone mass can be augmented only by exercise and the use of antiresorptive agents in patients with high-turnover OP.
  4. Experimental treatments may be beneficial for low-turnover OP.
    1. Continuous 1,25- (OH) 2 -vitamin D.
    2. Third-generation bisphosphonates.
    3. Sodium fluoride.
    4. Intermittent parathyroid hormone.

Bibliography

Black DM, et al. Randomized trial of effect of alendronate on risk of fracture in women with existing vertebral fractures. Lancet 1996;348:1535.

Dawson-Hughes B. Osteoporosis treatment and the calcium requirement. Am J Clin Nutr 1998;67:5.

Delmas PD, et al. Effects of raloxifene on bone mineral density, serum cholesterol concentrations, and uterine endometrium in postmenopausal women. N Engl J Med 1997;337:1641.

Eastell R. Treatment of postmenopausal osteoporosis. N Engl J Med 1998;338:736.

Ettinger B. Overview of estrogen replacement therapy: historical prospective . Proc Soc Exp Biol Med 1998;217:2.

Lane JM: Osteoporosis. Spine 1997;22[24S]:32.

Marshall D, Johnell D, Wedel H. Meta-analyses of how well measures of bone mineral density predict occurrence of osteoporotic fractures. Br Med J 1996;312:1254.

Uusi-Rasi K, et al. Associations of physical activity and calcium intake with bone mass and size in healthy women at different ages. J Bone Miner Res 1998;13:133.

Books@Ovid
Copyright 2000 by Lippincott Williams & Wilkins
Stephen A. Paget, M.D., Allan Gibofsky, M.D., J.D. and John F. Beary, III, M.D.
Manual of Rheumatology and Outpatient Orthopedic Disorders

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Manual of Rheumatology and Outpatient Orthopedic Disorders (LB Spiral Manuals)
Manual of Rheumatology and Outpatient Orthopedic Disorders (LB Spiral Manuals)
ISBN: N/A
EAN: N/A
Year: 2000
Pages: 315

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