Treatment With Once-Weekly Alendronate 70 mg Compared With Once-Weekly Risedronate 35 mg in Women With Postmenopausal Osteoporosis: A Randomized Double-Blind Study

Abstract

Once-weekly alendronate 70 mg and once-weekly risedronate 35 mg are indicated for the treatment of postmenopausal osteoporosis. These two agents were compared in a 12-month head-to-head trial. Greater gains in BMD and greater reductions in markers of bone turnover were seen with alendronate compared with risedronate with similar tolerability. Introduction:The nitrogen-containing bisphosphonates, alendronate and risedronate, are available in onceweekly (OW) formulations for the treatment of postmenopausal osteoporosis. A 12-month, head-to-head study was performed to compare these agents in the treatment of postmenopausal women with low BMD. Materials and Methods: A total of 1053 patients from 78 U.S. sites were randomized to OW alendronate 70 mg (N ‫ס‬ 520) or risedronate 35 mg (N ‫ס‬ 533), taken in the morning after fasting. Endpoints included BMD changes over 6 and 12 months at the hip trochanter, total hip, femoral neck, and lumbar spine (LS); percent of patients with predefined levels of change in trochanter and LS BMD at 12 months; and change in biochemical markers of bone turnover at 3, 6, and 12 months. Tolerability was evaluated by adverse experience (AE) reporting. Results: Significantly greater increases in hip trochanter BMD were seen with alendronate (3.4%) than risedronate (2.1%) at 12 months (treatment difference, 1.4%; p < 0.001) as well as 6 months (treatment difference, 1.3%; p < 0.001). Significantly greater gains in BMD were seen with alendronate at all BMD sites measured (12-month difference: total hip, 1.0%; femoral neck, 0.7%; LS, 1.2%). Significant differences were seen as early as 6 months at all sites. A greater percentage of patients had Ն0% (p < 0.001) and Ն3% (p < 0.01) gain in trochanter and spine BMD at 12 months with alendronate than risedronate. Significantly greater (p < 0.001) reductions in all biochemical markers of bone turnover occurred with alendronate compared with risedronate by 3 months. No significant differences were seen between treatment groups in the incidence of upper gastrointestinal AEs or AEs causing discontinuation. Conclusions: In this 12-month, head-to-head trial of alendronate and risedronate, given in accordance with the approved OW regimens for treatment of osteoporosis in postmenopausal women, alendronate produced greater gains in BMD and greater reductions in markers of bone turnover than risedronate. The greater antiresorptive effect of alendronate was seen as early as 3 months, and the tolerability profiles were similar.

Comment on Putting evidence-based medicine into clinical practice: comparing anti-resorptive agents for the treatment of osteoporosis

“…It may be pertinent to note that head-to-head trials with BMD (Bone Mineral Density) endpoints have yielded results consistent with our analysis [15][16][17][18][19][20][21][22] . We therefore continue to believe that, in the absence of evidence from head-to-head trials with fracture endpoints, the adjusted indirect comparisons provide valuable information for clinical decision-making and remains the best means today by which clinicians can compare the efficacy of anti-resorptive treatments in reducing the risk of fracture.…”

Corrigendum: A systematic review and economic evaluation of bisphosphonates for the prevention of fragility fractures

“…87 Both RCTs recruited postmenopausal women with osteoporosis according to the current WHO definition. 1 Mean age, years since menopause and BMI was 64.5 years, 18.5 years and 25.3 kg/m 2 , respectively, in the US study 90 and 64.1 years, 16.9 years and 25.3 kg/m 2 , respectively, in the international study. 87 The last RCT reported that participants with conditions or medications affecting bone metabolism were excluded.…”

“…92 Two further RCTs undertaken by the same study group compared 70 mg per week of alendronic acid with 35 mg per week of risedronic acid in postmenopausal women. 87,90 One was undertaken as a 12-month multicentre RCT in the USA, 90 with a 12-month extension to 24 months, 104 and the other was a 12-month multicentre RCT across 75 centres in 27 countries in Europe, the Americas and the Asia-Pacific region, 87 with a 12-month extension to 24 months. 105 Sponsor details were the same across these RCTs.…”

“…105 Sponsor details were the same across these RCTs. The number randomised was 1053 in the US study 90 and 936 in the multinational study. 87 Both RCTs recruited postmenopausal women with osteoporosis according to the current WHO definition.…”

“…90 The multinational study reported that 33.7% of participants had a history of fractures (not described), and that 41% had a family history of osteoporosis. 87 Across both RCTs, clinical fractures that occurred during the trial, regardless of association with trauma or skeletal site, were reported by investigators as clinical AEs.…”