Atypical fractures at non-classical sites associated with anti-resorptive therapy: A Systematic Review.

Abstract

Background: Osteoporosis is common, affecting more than 20% of women and 6% of men globally over the age of 50 (1). Anti-resorptive drugs, bisphosphonates and denosumab, have been effective treatments for osteoporosis for more than 30 years. Rare complications of anti-resorptive therapy include medication-related osteonecrosis of the jaw and atypical femur fractures (AFF). The American Society for Bone and Mineral Research (ASBMR) proposed a case definition for these atypical femoral fractures in 2010, which was updated in 2013. However, atypical fractures at non-classical sites have been increasingly described.

Aims: We aimed to systematically identify atypical fracture cases, excluded from the ASBMR AFF case definition in patients receiving anti-resorptive medication for longer than three years.

Methods: A structured search of electronic databases, including PubMed, Medline (Ovid), Embase (Ovid), Cochrane and Web of Sciences, and hand-searching of conference abstracts was undertaken. All full-text articles written in English describing an atypical fracture in patients (aged >18 years) and receiving anti-resorptive medication for >3 years were included, with data extracted and analysed by two independent reviewers.

Results: Sixty-six articles were identified, describing 151 cases of atypical fractures in 114 individuals. The most frequent fracture site was the ulna, followed by the tibia. All patients were taking anti-resorptive treatment prior to or at the time of fracture, most frequently alendronate monotherapy (44%). Most commonly, fractures were transverse in nature (95%), following minimal or no trauma (96%), non-comminuted (98%) with cortical thickening of the surrounding bone (69%). Anti-resorptive treatment was ceased following atypical fracture in the majority (89%).

Conclusions: Atypical fractures are rare and should not deter physicians from appropriate anti-resorptive therapy for osteoporosis. However, clinicians should be alert to their presence, at additional sites to the femur. An update of the current ASBMR AFF case definition to include other skeletal sites could be timely.