Fracture rate increases after immune checkpoint inhibitor treatment: a potential new immune related adverse event.

Introduction: T cell activation can lead to osteoporosis and while there are several case reports of fractures occurring after immune checkpoint inhibitor (ICI) use, to date, there are no population level studies looking at fracture risk related to ICI use.

Methods: Using Alberta Cancer Registry data, we identified all individuals treated with ICI for cancer between September 29, 2010, and March 31, 2019. Linked records from Alberta's healthcare administrative databases were assessed for the presence of fracture diagnostic codes in the year prior to and up to two years after ICI initiation. Fracture rate was stratified based on the time-period before and after ICI initiation. Fracture rates after ICI were compared to baseline.

Results: The study cohort consisted of 1600 ICI users (mean age 65.7 years, 60% male). Most patients were treated with an anti-PD-1 agent (73.9%). ICIs were initiated on average 707.8 days after cancer diagnosis. 76 (4.8%) individuals had a remote history of a major fracture, and 141 (8.8%) had been treated with an osteoporosis medication prior to ICI treatment. The fracture rate in the year prior to ICI initiation was 11.3 per 1000 patient-years. The fracture rate in the year after ICI initiation was significantly higher at 27.3 per 1000 patient-years. The fracture rate dropped to 17.6 per 1000 patient-years in the second year after ICI initiation. The incidence rate ratio of sustaining a major fracture in the year after compared to the year prior to ICI initiation was 2.43 (95% CI 1.34-4.27).

Conclusions: Fracture risk may be increased in cancer patients early after initiation of ICI, and this may represent a novel immune-related adverse event.