Long-term use of high-dose corticosteroids often results in bone loss, which may lead to osteoporosis-related fractures. This was a multicenter, double-blind study in which 290 ambulatory men and women receiving high-dose oral corticosteroid therapy (prednisone > 7.5 mg/day or equivalent) for 6 or more months were randomized to receive placebo, risedronate 2.5 mg/day, or risedronate 5 mg/day for 12 months. All patients received calcium 1 g and vitamin D 400 IU daily. The primary endpoint was lumbar spine bone mineral density (BMD) at month 12. Additional measurements included BMD at the femoral neck and trochanter and the incidence of vertebral fractures. Overall, there were statistically significant treatment effects on BMD at 12 months at the lumbar spine (p < 0.001), femoral neck (p ‫؍‬ 0.004), and trochanter (p ‫؍‬ 0.010). Risedronate 5 mg increased BMD at 12 months by a mean (SEM) of 2.9% (0.49%) at the lumbar spine, 1.8% (0.46%) at the femoral neck, and 2.4% (0.54%) at the trochanter, whereas BMD was maintained only in the control group. Although not powered to show fracture efficacy, we observed a reduction in the incidence of vertebral fractures of 70% in the combined risedronate treatment groups, relative to placebo (p ‫؍‬ 0.042). Risedronate was well tolerated, had a good safety profile, and was not associated with gastrointestinal adverse events. We conclude that risedronate increases BMD and potentially reduces the incidence of vertebral fractures in patients with corticosteroid-induced osteoporosis. (J Bone Miner Res 2000;15:1006 -1013)

Male osteoporosis is increasingly recognized as a major public health issue. This multinational, 2-yr, randomized, double-blind, placebo-controlled study was conducted to determine the efficacy and safety of 35 mg once-a-week risedronate in men with osteoporosis. Patients had to be men 30 yr old, with lumbar spine T-score 22.5 and femoral neck T-score 21 SD or lumbar spine T-score 21 and femoral neck T-score 22 SD (based on young normal men). Patients were randomized 2:1 to risedronate 35 mg once a week or placebo for 2 yr; all patients took 1000 mg elemental calcium and 400-500 IU vitamin D daily. Lumbar spine BMD at month 24 using last observation carried forward was the primary endpoint. Other endpoints included lumbar spine BMD at time points other than month 24, proximal femur BMD, bone turnover markers (BTMs), new vertebral fractures, clinical fractures, and adverse event (AE) assessment. There were 284 men enrolled in the study. Treatment with risedronate resulted in a significant increase from baseline to endpoint in lumbar spine BMD compared with placebo (4.5%; 95% CI: 3.5%, 5.6%; p < 0.001). Few new vertebral and nonvertebral fractures were reported, with no differences in fracture rates between the two groups. There was a significant (p < 0.01) reduction from baseline in BTMs for the risedronate group compared with placebo at all time points. No apparent differences in the pattern or distribution of AEs including serious and upper gastrointestinal AEs were observed. Risedronate therapy was well tolerated during this 2-yr study and was rapidly effective as indicated by significant BTM decreases at month 3 and BMD increases at month 6 (the earliest time points tested). The effects of risedronate treatment on BMD and BTMs in this study were similar to those previously shown to be associated with fracture risk reductions in women with postmenopausal osteoporosis.

Risedronate 5 mg prevents bone loss in early postmenopausal women, is well tolerated, and represents an effective choice to maintain bone mass and prevent osteoporosis.

One year of discontinuation of risedronate treatment in patients who had received 2 or 7 yr of risedronate therapy led to increases in NTX/Cr levels toward baseline and decreases in femoral trochanter and total hip BMD.

SummaryBone mineral density response to once weekly delayed-release formulation of risedronate, given before or following breakfast, was non-inferior to that seen with traditional immediate-release risedronate given daily before breakfast. Delayed-release risedronate is a convenient dosing regimen for oral bisphosphonate therapy that might avoid poor compliance.IntroductionThis 2-year, randomized, controlled, non-inferiority study assessed the efficacy and safety of a delayed-release (DR) 35-mg weekly oral formulation of risedronate that allows subjects to take their weekly risedronate dose before or immediately after breakfast. Results from the first year of the study were published previously (McClung et al. Osteoporos Int 23(1):267-276, 2012); we now report the final results after 2 years.MethodsWomen with postmenopausal osteoporosis were randomly assigned to receive risedronate 5 mg immediate-release (IR) daily (n = 307) at least 30 min before breakfast, or risedronate 35 mg DR weekly, either immediately following breakfast (FB, n = 307) or at least 30 min before breakfast (BB, n = 308). Bone mineral density (BMD), bone turnover markers (BTMs), fractures, adverse events, and bone histomorphometry were evaluated.ResultsA total of 248 subjects (80.8 %) in the IR daily group, 234 subjects (76.2 %) in the DR FB weekly group, and 240 subjects (77.9 %) in the DR BB weekly group completed the 2-year study. After 2 years of treatment, BMD increases at the lumbar spine and total hip with the weekly DR doses similar to or greater than that with the IR daily dose. Decreases in BTMs were similar or significantly lower in the DR groups. Bone histomorphometry results did not differ among the DR weekly and the IR daily formulations. The three regimens were similarly well tolerated.ConclusionsRisedronate 35 mg DR weekly is as effective and as well tolerated as risedronate 5 mg IR daily, and will allow subjects to take their weekly risedronate dose immediately after breakfast.