Authors' objectives:

The aim of this systematic review was to assess the clinical effectiveness of etidronate, alendronate, and risedronate in the primary and secondary prevention of osteoporotic fractures in postmenopausal women receiving these agents, compared with untreated women, over a follow-up period of at least one year.

Authors' results and conclusions: After reviewing the evidence for the oral bisphosphonates as therapeutic options for the primary and secondary prevention of osteoporotic fractures, it was found that etidronate has a beneficial effect on the reduction of vertebral fractures only when used for secondary prevention. The data do not support an effect of etidronate on the reduction of vertebral fractures when used for primary prevention or for reductions in non-vertebral, hip, or wrist fractures if used for primary or secondary prevention. Alendronate reduced the risk of vertebral, non-vertebral, hip, and wrist fractures when used for secondary prevention. There were no statistically significant reductions for the primary prevention of osteoporotic fractures by alendronate, with the exception of vertebral fractures. The data for risedronate support a beneficial effect in the reduction of risk of vertebral, non-vertebral, and hip fractures (but not for wrist), when it is used for secondary prevention. No estimates were possible for use of risedronate for primary prevention. There were limitations to the data, in that the systematic review was not based on individual patient data, issues related to study quality were identified (i.e., lack of clarity of allocation concealment, large losses to follow-up), and the length of follow-up in the included trials was short. Comparisons of the adverse event potential of the drugs were complicated by the fact that the randomized controlled trials that formed the basis of the meta-analyses tended to enrol healthier participants, and did not consistently report or measure rare events. Additionally, these trials were underpowered to detect differences in rare event rates, so it is difficult to make any conclusive statements about adverse drug events and the longterm tolerability of these drugs.

Authors' recommendations: Overall evidence varies, depending on the bisphosphonate. For etidronate, most trials enrolled a small number of participants and were not necessarily designed to measure fractures, which limits our findings. Available evidence for alendronate and risedronate is more robust. Acknowledging the available evidence, we conclude that the main benefit of the three bisphosphonates available on the Canadian market for the management of osteoporotic fractures, is the secondary prevention of such fractures. Etidronate, used at 400 mg per day, demonstrated a main benefit in the secondary prevention of vertebral fractures. No statistically significant reductions in vertebral fractures were observed when it was used in primary prevention. No statistically significant reductions in non-vertebral, hip, or wrist fractures were found, whether etidronate was used for primary or secondary prevention. Alendronate demonstrated a main benefit in the secondary prevention of all osteoporotic fractures. At a dose of 10 mg per day, statistically significant reductions in vertebral, nonvertebral, hip, and wrist fractures were observed. There were no statistically significant reductions found for the primary prevention of osteoporotic fractures, with the exception of vertebral fractures. Risedronate demonstrated a main benefit in the secondary prevention of most osteoporotic fractures. At a dose of 5 mg per day, statistically significant reductions in vertebral, nonvertebral, and hip fractures were observed (but not for wrist). Estimates of risk reductions for primary prevention were not possible, because only one trial was included in the review, and no fractures were observed.

Authors' methods: Systematic review

Project Status: Completed

URL for project: http://www.cadth.ca/media/pdf/371_Bisphosphonates_tr_e_NoAppendix.pdf

Year Published: 2006

English language abstract: An English language summary is available

Publication Type: Not Assigned

Country: Canada

Organisation Name: Canadian Agency for Drugs and Technologies in Health

Contact Address: 600-865 Carling Avenue, Ottawa, ON K1S 5S8 Canada. Tel: +1 613 226 2553; Fax: +1 613 226 5392;

Contact Name: requests@cadth.ca

Contact Email: requests@cadth.ca

Copyright: Canadian Agency for Drugs and Technologies in Health (CADTH)