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Osteoporosis has many causes (see Table 26 10) Additionally, osteopenia and fractures can be caused by osteomalacia (see below) and bone marrow neoplasia such as myeloma or metastatic bone disease These conditions coexist in many patients
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Several treatment options are available, so a regimen is tailored to each patient Generally, treatment is indicated for all women with osteoporosis (T scores below 25) and for all patients who have had fragility fractures Prophylactic treatment should also be considered for patients with advanced osteopenia (T scores between 20 and 25) 1 Vitamin D and calcium Osteoporosis and osteomalacia often coexist (see Osteomalacia section) Sun exposure and
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30 60 mg by slow intravenous infusion in normal saline solution every 3 6 months Transient postinfusion fever occurs fairly commonly (26%) Osteonecrosis of the jaw has been reported in patients receiving intravenous zoledronic acid and pamidronate for treatment of hypercalcemia and bone metastases, for which the drugs had been administered more frequently than for osteoporosis Both oral and parenteral bisphosphonates can cause bone, joint, or muscle pains as well as fatigue The onset of pain may occur from 1 day to 1 year after therapy is initiated, with a mean of 14 days The pain can be transient, lasting several days and usually resolving spontaneously but typically recurring with subsequent doses When the bisphosphonate is discontinued, most patients experience gradual relief of pain Some patients taking alendronate or risedronate for osteoporosis have experienced bone osteonecrosis: painful, necrotic, nonhealing lesions of the jaw, particularly after tooth extraction For such patients with painful exposed bone, treatment is 90% effective (without resolution of the exposed bone) using antibiotics along with 012% chlorohexidine antiseptic mouth wash Patients receiving bisphosphonates must receive regular dental care and try to avoid dental extraction Another reported adverse effect reported with bisphosphonates is ocular inflammation, manifested by blurred vision, eye pain, uveitis, conjunctivitis, and scleritis, which remits after discontinuation of the drug Other side effects can include nausea, anemia, dyspnea, and leg edema In patients taking bisphosphonates, hypercalcemia is seen in 20% and serum PTH levels increase above normal in 10%, mimicking primary hyperparathyroidism All bisphosphonates inhibit osteoclastic bone resorption by binding to active bone remodeling sites and inhibiting osteoclasts; the half-life of alendronate in bone is 10 years The effects of long-term bisphosphonate therapy on bone strength are unknown Therefore, patients with mild osteoporosis may discontinue bisphosphonates after a 5-year course of therapy Regular bone densitometry follow-up is recommended 3 Sex hormones Hypogonadal women who take estrogen replacement therapy have a lower risk of developing osteoporosis Postmenopausal estrogen replacement is valuable as an osteoporosis prevention measure and this should be one factor in the complex decision about whether to take HRT Low doses of estrogen appear to be adequate to prevent postmenopausal osteoporosis (see Estrogen Replacement Therapy) Once osteoporosis has developed, estrogen replacement is not an effective treatment Although HRT does increase bone mineral density in postmenopausal women with osteoporosis, it has not been demonstrated to significantly reduce fracture rates Treatment with a selective estrogen receptor modulator (SERM) should also be considered Men with hypogonadism may be treated with testosterone (see Male Hypogonadism) 4 Selective estrogen receptor modulators Raloxifene, 60 mg/d orally, can be used by postmenopausal women in place of estrogen for prevention of osteoporosis Bone density increases about 1% over 2 years in postmenopausal women versus 2% increases with estrogen replacement It reduces the risk of vertebral fractures by about 40% but does not appear to reduce the risk of nonvertebral fractures Raloxifene pro-
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vitamin D supplementation are useful in preventing osteomalacia Vitamin D supplementation reduces the incidence of vertebral fractures by 37% and may slightly reduce the incidence of nonvertebral fractures Oral vitamin D is given in doses of 400 1000 IU daily Higher doses of vitamin D may be required during winter months and for patients having prolonged hospitalization or nursing home care, for patients with serum levels of 25-hydroxyvitamin D below 30 ng/mL, and those with intestinal malabsorption Calcium supplementation alone has only a minor effect on the prevention of osteoporosis and such supplementation has not been established to reduce fracture risk significantly Therefore, calcium supplementation is an optional preventive measure, indicated principally for those with diets low in calcium More important is the assurance of adequate vitamin D through sun exposure or oral vitamin D supplementation, and calcium supplementation should include vitamin D Calcium supplementation may be given as calcium citrate (04 07 g elemental calcium per day) or calcium carbonate (1 15 g elemental calcium per day) 2 Bisphosphonates Bisphosphonates work similarly, inhibiting osteoclast-induced bone resorption They increase bone density significantly and reduce the incidence of both vertebral and nonvertebral fractures Bisphosphonates have also been effective in preventing corticosteroid-induced osteoporosis To ensure intestinal absorption, oral bisphosphonates must be taken in the morning with at least 8 oz of plain water at least 30 minutes before consumption of anything else The patient must remain upright after taking bisphosphonates to reduce the risk of esophagitis These medications are excreted in the urine However, no dosage adjustments are required for patients with creatinine clearances above 35 mL/min There has been little experience giving bisphosphonates to patients with severe renal insufficiency; if given, the dose would need to be greatly reduced and serum phosphate levels monitored Bisphosphonates may be given orally once monthly or weekly; which is more convenient than daily therapy and equally effective Available oral preparations include alendronate, 70 mg orally once weekly (tablet or solution), and risedronate, 35 mg orally once weekly Both these medications reduce the risk of both vertebral and nonvertebral fractures Studies sponsored by the manufacturer of alendronate found that alendronate was significantly more potent than risedronate and equally well tolerated Another bisphosphonate, ibandronate sodium, is taken once monthly in a dose of 150 mg orally Once-monthly ibandronate is convenient and reduces the risk of vertebral fractures but not nonvertebral fractures; its effectiveness has not been directly compared with other bisphosphonates Oral bisphosphonates can cause esophagitis, especially in patients with hiatal hernia and gastroesophageal reflux For patients who cannot tolerate oral bisphosphonates or for whom oral bisphosphonates are contraindicated, intravenous bisphosphonates are available Zoledronic acid is a third-generation bisphosphonate and a potent osteoclast inhibitor It can be given every 6 12 months in doses of 2 4 mg intravenously over 15 30 minutes Pamidronate is an older parenteral bisphosphonate that can be given in doses of
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