Poster Presentation ANZBMS-MEPSA-ANZORS 2022

Atypical fractures are a rare adverse skeletal outcome of antiresorptive treatment and predominantly associated with long-term bisphosphonate use(1-3). Highest incidence occurs with long-term (>8yrs) alendronate use at ~13 per 10,000 patient-years, but drops by >50% one year and >80% three years after ceasing bisphosphonate(2). Published cases have been associated with denosumab, most with extensive prior bisphosphonate exposure(2-8), with fewer atypical fractures associated with denosumab involving very short-term bisphosphonate use(9,10). Five cases are reported in bisphosphonate-naïve patients taking denosumab(11-14).

The best characterised fracture type is atypical femur fracture (AFF) with specific radiological and clinical definition criteria(15). Atypical stress reactions of the femoral diaphysis and atypical or stress fractures at other sites, including periprosthetic, have also been associated with antiresorptives(4,16-18). Fractures meeting AFF criteria have additionally been reported in the absence of antiresorptive exposure(19-21), with additional risk factors including metabolic bone disorders, femur geometry (lateral bowing, varus hip alignment), inflammatory arthritis, glucocorticoid and proton-pump inhibitor (PPI) use(19).  

We describe a series of three patients with minimal-trauma atypical or stress fractures in the setting of denosumab use for osteoporosis, two of which occurred in the absence of prior bisphosphonate exposure and one with previous bisphosphonate use (Table 1). Common across the cases is relatively young age at treatment onset and no prior fracture. Two patients were mobile and active throughout their treatment. Two had body mass index >32kg/m2, and one had asymmetrical antalgic gait, which possibly contributed to fracture site mechanical loading. All had significant improvement in bone mineral density (BMD) measured around the time of fracture, which may suggest an exaggerated response to denosumab. However, as post-fracture bone density was performed on the contralateral femur in two cases, another postulation is of pre-existing significant between-hip variation in BMD, with mechanical asymmetry predisposing to atypical fracture.