Increase in major osteoporotic fractures after therapy with immune checkpoint inhibitors

Background Immune checkpoint inhibitors (ICIs) can cause severe and sometimes long-standing immune-related adverse events (irAEs). Enhanced immune activation from ICI can theoretically result in osteoclast activation, bone loss and fracture. The objective of this study was to evaluate the incidence rates of major osteoporotic fractures (MOFs) in patients with melanoma treated with ICI. Methods We conducted a before–after cohort study using a commercial healthcare claims dataset of adult patients with melanoma from the USA who received ICI therapy between 2011 and 2022. Incidence rates of MOF before and after ICI initiation were ascertained using International Classification of Diseases 9/10 diagnostic codes. Results The study cohort included 3137 patients, mean age was 68 years, of which 2010 (64%) were men. 40 (1.3%) patients had an MOF in the year before ICI initiation and 57 (1.8%) and 34 (1.8%) had an MOF in the first and second years after ICI initiation, respectively. The HR for MOF over the first year after versus the year before the first ICI dose was 1.82 (95% CI 1.24 to 2.66), and it was 1.85 (95% CI 1.12 to 2.90) over the second year. Prior fracture, older age, female sex and combination ICI therapy were associated with greater risk of MOF after ICI initiation. Conclusion Patients who receive ICI are at increased risk of MOF after receiving therapy. Given the plausible biological pathway, osteoporosis and osteoporotic fractures may represent a novel irAE of ICI therapy.