Increased risk for atypical fractures associated with bisphosphonate use.

Background: Studies suggest an increasing occurrence of atypical femoral fractures with the use of bisphosphonates.

Objective: To examine whether the use of bisphosphonates increases the risk for atypical fractures.

Design: Systematic review and meta-analysis.

Data Sources: Literature search of MEDLINE, Embase and Cochrane CENTRAL (1948-June 2013).

Selection Criteria: (i) randomized controlled trial or an observational study, (ii) evaluated bisphosphonate therapy versus no treatment and (iii) reported an incidence of subtrochanteric or diaphyseal fracture individually, or a composite of both. Two independent investigators completed study selection, data extraction and validity assessment. The Cochrane Risk of Bias Tool was used to assess the quality of included studies.

Results: Ten (n = 658497) studies were included in the meta-analysis which demonstrated a statistically significant increased risk of subtrochanteric or diaphyseal fracture with bisphosphonate use [adjusted odds ratios (AOR) = 1.99, 95% confidence intervals (CI)= 1.28-3.10] with I (2) = 84.3% (95% CI = 73.5%-89.5%) and Egger P = 0.01. Subtrochanteric fractures showed an AOR = 2.71 (95% CI = 1.86-3.95) with I (2) = 83.6% (95% CI = 64.3%-90.3%) and Egger's P = 2.29. Diaphyseal fractures had an AOR = 2.06 (95% CI = 1.70-2.50), I (2) = 29.7% (95% CI = 0%-73.7%) and Egger's P = 1.22.

Conclusion: Results suggest there is an increased risk for atypical fractures associated with bisphosphonates and raises awareness to the potential complications related with bisphosphonates. These findings warrant the comprehensive evaluation of patients before initiating bisphosphonate therapy and highlights the need for additional medical decision analyses in future studies to compare the benefit over potential harms of bisphosphonate therapy.