Drugs associated with incident fragility fractures in kidney transplant recipients

Background: The risk of fragility fractures is high in kidney transplant recipients, and steroids are reportedly a major cause. Other drugs known to induce fragility fractures have been studied in the general population but not in kidney transplant recipients. Here, we investigated the association between exposure over time to drugs that can injure bone (namely vitamin K antagonists, insulin, loop diuretics, proton pump inhibitors, opioids, selective serotonin reuptake inhibitors, antiepileptics and benzodiazepines) and incident fractures and changes over time in T-scores in this population.

Methods: A total of 613 consecutive kidney transplant recipients were included between 2006 and 2019. Drug exposures and incident fractures during the study period were comprehensively documented, and dual-energy X-ray absorptiometry was performed regularly. The data were analyzed using Cox proportional hazards models with time-dependent covariates and linear mixed models.

Results: Incident fractures occurred in 63 patients, giving a fracture incidence of 16.9 per 1000 person-years. Exposures to loop diuretics [hazard ratio (95% confidence interval) 2.11 (1.17-3.79)] and opioids [5.94 (2.14-16.52)] were associated with incident fractures. Exposure to loop diuretics was associated with a decrease over time in the T-score for the lumbar spine (P = .022) and for the wrist (P = .028).

Conclusions: This study suggests that the exposure to loop diuretics and opioids increases the risk of fracture in kidney transplant recipients.