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Context: Risedronate, a potent bisphosphonate, has been shown to be effective in the treatment of Paget disease of bone and other metabolic bone diseases but, to our knowledge, it has not been evaluated in the treatment of established postmenopausal osteoporosis., Objective: To test the efficacy and safety of daily treatment with risedronate to reduce the risk of vertebral and other fractures in postmenopausal women with established osteoporosis., Design, Setting, and Participants: Randomized, double-blind, placebo-controlled trial of 2458 ambulatory postmenopausal women younger than 85 years with at least 1 vertebral fracture at baseline who were enrolled at 1 of 110 centers in North America conducted between December 1993 and January 1998., Interventions: Subjects were randomly assigned to receive oral treatment for 3 years with risedronate (2.5 or 5 mg/d) or placebo. All subjects received calcium, 1000 mg/d. Vitamin D (cholecalciferol, up to 500 IU/d) was provided if baseline levels of 25-hydroxyvitamin D were low., Main Outcome Measures: Incidence of new vertebral fractures as detected by quantitative and semiquantitative assessments of radiographs; incidence of radiographically confirmed nonvertebral fractures and change from baseline in bone mineral density as determined by dual x-ray absorptiometry., Results: The 2.5 mg/d of risedronate arm was discontinued after 1 year; in the placebo and 5 mg/d of risedronate arms, 450 and 489 subjects, respectively, completed all 3 years of the trial. Treatment with 5 mg/d of risedronate, compared with placebo, decreased the cumulative incidence of new vertebral fractures by 41 % (95% confidence interval [CI], 18%-58%) over 3 years (11.3 % vs 16.3%; P= .003). A fracture reduction of 65% (95% CI, 38%-81 %) was observed after the first year (2.4% vs 6.4%; P<.001). The cumulative incidence of nonvertebral fractures over 3 years was reduced by 39% (95% CI, 6%-61 %) (5.2 % vs 8.4%; P = .02). Bone mineral density increased significantly compared with placebo at the lumbar spine (5.4% vs 1.1 %), femoral neck (1.6% vs -1.2%), femoral trochanter (3.3% vs -0.7%), and midshaft of the radius (0.2% vs -1.4%). Bone formed during risedronate treatment was histologically normal. The overall safety profile of risedronate, including gastrointestinal safety, was similar to that of placebo., Conclusions: These data suggest that risedronate therapy is effective and well tolerated in the treatment of women with established postmenopausal osteoporosis.

We now have conclusive proof that intensive treatment reduces the microvascular complications of IDDM. ACE inhibitors appear to slow the progression of established nephropathy. Drug-induced malabsorption has the potential to increase levothyroxine dose requirement.

Corticotropin deficiency may occur after pituitary surgery, and, if unrecognized and untreated, it can be fatal. In this study the insulin tolerance test was used to assess hypothalamic-pituitary-adrenal reserve five to seven days after pituitary surgery, and postoperative morning serum cortisol concentration was compared with the insulin tolerance test for predicting corticotropin deficiency. In 35 patients with pituitary tumors studied prospectively, 27 had normal insulin tolerance test results five to seven days after pituitary surgery; in these patients, the morning serum cortisol concentration two to three days after surgery was 250 nmol/L (9 micrograms/dL) or greater. Eight patients had subnormal insulin tolerance test results or clinical evidence of adrenal insufficiency; the morning serum cortisol concentration in these patients was 80 nmol/L (3 micrograms/dL) or less. Postoperative adrenal insufficiency was transient (one to three months) in five of these eight patients. We retrospectively identified 45 patients whose postoperative morning serum cortisol values were 200 nmol/L (7 micrograms/dL) or greater; none of these patients had clinical evidence of adrenal insufficiency. We conclude that a morning serum cortisol level obtained two to three days after surgery and 24 hours after the discontinuation of hydrocortisone accurately predicts postoperative corticotropin reserve.