Fracture risk associated with continuation versus discontinuation of bisphosphonates after 5 years of therapy in patients with primary osteoporosis: a systematic review and meta-analysis

PURPOSE The risks and benefits of continuing bisphosphonate therapy beyond 5 years in patients with primary osteoporosis have not been well established. METHODS We searched MedLine, EMBase, CENTRAL, CINAHL, and AgeLine prior to February 2010. Bibliographies were also searched and experts in the field contacted. The ProQuest Dissertations and Theses database and relevant conference proceedings were searched to identify unpublished or ongoing studies. Two authors independently reviewed search results. Randomized controlled trials and comparative nonrandomized controlled trials examining post-menopausal women or men ≥50 years of age with primary osteoporosis assigned to continue versus discontinue bisphosphonate therapy after ≥5 years of therapy were included. Of 1188 identified articles, three studies (n = 1443) met criteria for inclusion in data synthesis. Data were extracted and risk of bias assessed by two independent reviewers using predefined criteria. RESULTS No statistically significant association was found between fracture incidence and the discontinuation of therapy beyond 5 years for any type of fracture: clinical nonvertebral fracture (relative risk [RR] = 0.97; 95% confidence interval [CI] 0.77-1.23), clinical vertebral fracture (RR = 0.61; 95% CI 0.32-1.19), or morphometric vertebral fracture (RR = 0.90; 95% CI 0.5-1.64). No differences in adverse events were identified between the two groups. CONCLUSION We found no significant difference in fracture risk or adverse events between postmenopausal women with primary osteoporosis who continued bisphosphonate therapy versus those who discontinued bisphosphonate therapy after 5 years of treatment. However, given the small number and limited quality of available studies, no firm conclusions or recommendations can be made.