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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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