Drugs associated with incident fragility fractures in kidney transplant recipients

Abstract

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 (VKAs), 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 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 both 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 = 0.022) and for the wrist (P = 0.028). Conclusions This study suggests that the exposure to loop diuretics and opioids increases the risk of fracture in kidney transplant recipients.

Post-Transplant Bone Disease in Kidney Transplant Recipients: Diagnosis and Management

“…Exposure to vitamin K antagonists, loop diuretics and opioids was significantly associated with incident fractures. Interestingly, in this study, the use of bisphosphonates and steroids was not associated with incident fractures [56]. Furthermore, exposure to loop diuretics demonstrated a significantly negative correlation with changes in T-score for the lumbar spine and wrist over time [56].…”

“…Interestingly, in this study, the use of bisphosphonates and steroids was not associated with incident fractures [56]. Furthermore, exposure to loop diuretics demonstrated a significantly negative correlation with changes in T-score for the lumbar spine and wrist over time [56]. In the general population, in women over the age of 65 years with a prior fragility fracture, without knowledge of their BMD, it is cost-effective to prescribe pharmacological treatment [45].…”

“…Moreover, certain drug classes contribute to the risk of fragility fractures post-transplantation. The use of loop diuretics and the use of bisphosphonates were significantly associated with prevalent fractures [56]. Exposure to vitamin K antagonists, loop diuretics and opioids was significantly associated with incident fractures.…”

“…The risk factors for incident fragility fractures in patients living with a kidney transplant are older age, female sex, concurrent diabetes, prior fracture, receipt of pre-transplantation dialysis, dialysis vintage, glomerulonephritis and hypertension as the aetiology of kidney failure, receipt of a kidney from a deceased donor, HLA-DR mismatch and elevated urine protein-to-creatinine ratio [55]. Batteux et al showed that in kidney transplant recipients, older age, female sex, concurrent thyroid disorders, prior fractures, especially vertebral fractures, lower serum bone-specific alkaline phosphatase, lower serum osteocalcin, lower serum PTH and lower serum creatinine were characteristics significantly associated with incident fractures [56]. Two-thirds of patients with incident fractures were shown to have osteopenia in the lumbar spine (46.3%), total hip (72.2%), or any site (47.6%), while 35.9% had osteoporosis at the wrist [56].…”

“…Batteux et al showed that in kidney transplant recipients, older age, female sex, concurrent thyroid disorders, prior fractures, especially vertebral fractures, lower serum bone-specific alkaline phosphatase, lower serum osteocalcin, lower serum PTH and lower serum creatinine were characteristics significantly associated with incident fractures [56]. Two-thirds of patients with incident fractures were shown to have osteopenia in the lumbar spine (46.3%), total hip (72.2%), or any site (47.6%), while 35.9% had osteoporosis at the wrist [56]. There is evidence showing that osteopenia and osteoporosis in the total hip BMD were associated with a significantly increased risk of fracture compared to normal BMD, independent of age, sex and diabetes status [8].…”