Department of Inter-Organ Communication Research, Niigata University Graduate School of Medical and Dental Sciences, Asahimachi 1-757, Chuo-ku, Niigata, 951-8510, Japan.
Sado General Hospital, Niigata, Japan.
J Bone Miner Metab. 2022 Jan;40(1):157-166. doi: 10.1007/s00774-021-01272-9. Epub 2021 Nov 3.
Polypharmacy is associated with an increased risk of fracture in aging populations, but no study has accounted for the impact of kidney function on this association. This study aimed to examine the association between polypharmacy and incident fragility fracture based on chronic kidney disease (CKD) status.
Participants were 2023 patients (55% men; mean age, 69 years) of Sado General Hospital enrolled in the Project in Sado for Total Health (PROST) between June 2008 and December 2016. Among these, 65%, 28%, and 7% had non-CKD, non-dialysis-dependent CKD, and dialysis-dependent CKD, respectively. Multivariable Cox proportional hazards analysis was conducted with adjustments for potential confounders.
Prevalences of polypharmacy (≥ 5 medications) and hyperpolypharmacy (≥ 10 medications) among participants were 43% and 9% for non-CKD, 62% and 23% for non-dialysis-dependent CKD, and 85% and 34% for dialysis-dependent CKD, respectively. During a median follow-up of 5.6 years, 256 fractures occurred. More medications were associated with a higher risk of fractures. Specifically, compared to participants without polypharmacy, adjusted hazard ratios were 1.32 (95% CI 0.96-1.79) and 1.99 (1.35-2.92) for those with polypharmacy and hyperpolypharmacy, respectively, after adjusting for osteoporosis risk factors, CKD status, and comorbidities. No effect modification by CKD status was observed (interaction P = 0.51). Population-attributable fractions of hyperpolypharmacy for fracture were 9.9% in the total cohort and 42.1% in dialysis-dependent CKD patients.
Hyperpolypharmacy is associated with an increased risk of fragility fracture regardless of CKD status, and has a strong impact on incident fragility fractures in dialysis-dependent CKD patients.
在老龄化人群中，多种药物治疗与骨折风险增加相关，但尚无研究考虑肾功能对这种关联的影响。本研究旨在根据慢性肾脏病（CKD）的状况，检查多种药物治疗与脆性骨折事件之间的关联。
参与者为 2023 名患者（55%为男性；平均年龄 69 岁），他们于 2008 年 6 月至 2016 年 12 月期间参加了 Sado 综合医院的 Sado 全民健康计划（PROST）。其中，分别有 65%、28%和 7%的患者患有非 CKD、非透析依赖性 CKD 和透析依赖性 CKD。采用多变量 Cox 比例风险分析进行调整潜在混杂因素。
参与者中非 CKD、非透析依赖性 CKD 和透析依赖性 CKD 患者的多种药物治疗（≥5 种药物）和高多种药物治疗（≥10 种药物）的患病率分别为 43%和 9%、62%和 23%、85%和 34%。在中位数为 5.6 年的随访期间，发生了 256 例骨折。服用的药物越多，骨折的风险越高。具体而言，与没有多种药物治疗的患者相比，在调整骨质疏松症风险因素、CKD 状况和合并症后，服用多种药物治疗和高多种药物治疗的患者骨折的调整后危险比分别为 1.32（95%CI，0.96-1.79）和 1.99（1.35-2.92）。未观察到 CKD 状况的效应修饰作用（交互 P=0.51）。高多种药物治疗在总队列中的骨折人群归因分数为 9.9%，在透析依赖性 CKD 患者中为 42.1%。
高多种药物治疗与脆性骨折风险增加相关，无论 CKD 状况如何，并且对透析依赖性 CKD 患者的脆性骨折事件有很大影响。
