Batteux Benjamin, Nowak Alban, Séjourné Alice, Penet Clémence, Masmoudi Kamel, Brazier François, Laville Solène M, Bennis Youssef, Gras-Champel Valérie, Choukroun Gabriel, Liabeuf Sophie
Department of Clinical Pharmacology, Amiens University Medical Center, Amiens, France.
MP3CV Laboratory, EA7517, Jules Verne University of Picardie, Amiens, France.
Clin Kidney J. 2022 Dec 9;16(3):571-584. doi: 10.1093/ckj/sfac265. eCollection 2023 Mar.
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.
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.
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 ( = .022) and for the wrist ( = .028).
This study suggests that the exposure to loop diuretics and opioids increases the risk of fracture in kidney transplant recipients.
肾移植受者发生脆性骨折的风险很高，据报道类固醇是主要原因。已知会诱发脆性骨折的其他药物已在普通人群中进行了研究，但未在肾移植受者中进行研究。在此，我们调查了该人群中长期暴露于可损伤骨骼的药物（即维生素K拮抗剂、胰岛素、袢利尿剂、质子泵抑制剂、阿片类药物、选择性5-羟色胺再摄取抑制剂、抗癫痫药和苯二氮䓬类药物）与骨折发生率以及T值随时间变化之间的关联。
2006年至2019年期间共纳入了613例连续的肾移植受者。全面记录了研究期间的药物暴露情况和骨折发生情况，并定期进行双能X线吸收测定。使用带有时间依存性协变量的Cox比例风险模型和线性混合模型对数据进行分析。
63例患者发生了骨折，骨折发生率为每1000人年16.9例。暴露于袢利尿剂[风险比（95%置信区间）2.11（1.17 - 3.79）]和阿片类药物[5.94（2.14 - 16.52）]与骨折发生有关。暴露于袢利尿剂与腰椎（P = 0.022）和腕部（P = 0.028）的T值随时间下降有关。
本研究表明，暴露于袢利尿剂和阿片类药物会增加肾移植受者的骨折风险。
