Hsu Simon, Bansal Nisha, Denburg Michelle, Ginsberg Charles, Hoofnagle Andrew N, Isakova Tamara, Ix Joachim H, Robinson-Cohen Cassianne, Wolf Myles, Kestenbaum Bryan R, de Boer Ian H, Zelnick Leila R
Division of Nephrology and Kidney Research Institute, Department of Medicine, University of Washington, Seattle, WA 98195, United States.
Division of Nephrology, Children's Hospital of Philadelphia, Philadelphia, PA 19104, United States.
J Bone Miner Res. 2024 May 2;39(4):433-442. doi: 10.1093/jbmr/zjae021.
Fracture risk is high in chronic kidney disease (CKD) and underlying pathophysiology and risk factors may differ from the general population. In a cohort study of 3939 participants in the chronic renal insufficiency cohort (CRIC), we used Cox regression to test associations of putative risk factors with the composite of first hip or vertebral fracture assessed using hospital discharge codes. Mean age was 58 years, 45% were female, 42% were Black, and 13% were Hispanic. There were 82 hip and 24 vertebral fractures over a mean (SD) 11.1 (4.8) years (2.4 events per 1000 person-years [95% CI: 2.0, 2.9]). Measured at baseline, diabetes, lower body mass index (BMI), steroid use, proteinuria, and elevated parathyroid hormone (PTH) were each associated with fracture risk after adjusting for covariates. Lower time-updated estimated glomerular filtration rate (eGFR) was associated with fractures (HR 1.20 per 10 mL/min/1.73m2 lower eGFR; 95% CI: 1.04, 1.38) as were lower time-updated serum calcium and bicarbonate concentrations. Among time-updated categories of kidney function, hazard ratios (95% CI) for incident fracture were 4.53 (1.77, 11.60) for kidney failure treated with dialysis and 2.48 (0.86, 7.14) for post-kidney transplantation, compared with eGFR ≥60. Proton pump inhibitor use, dietary calcium intake, measures of vitamin D status, serum phosphate, urine calcium and phosphate, and plasma fibroblast growth factor-23 were not associated with fracture risk. In conclusion, lower eGFR in CKD is associated with higher fracture risk, which was highest in kidney failure. Diabetes, lower BMI, steroid use, proteinuria, higher serum concentrations of PTH, and lower calcium and bicarbonate concentrations were associated with fractures and may be modifiable risk factors.
慢性肾脏病（CKD）患者骨折风险较高，其潜在病理生理学和风险因素可能与普通人群不同。在一项针对慢性肾功能不全队列（CRIC）中3939名参与者的队列研究中，我们使用Cox回归来检验假定风险因素与根据医院出院编码评估的首次髋部或椎体骨折复合事件之间的关联。平均年龄为58岁，45%为女性，42%为黑人，13%为西班牙裔。在平均（标准差）11.1（4.8）年的时间里，共发生了82例髋部骨折和24例椎体骨折（每1000人年2.4例事件[95%置信区间：2.0，2.9]）。在基线时测量，糖尿病、较低的体重指数（BMI）、使用类固醇、蛋白尿和甲状旁腺激素（PTH）升高在调整协变量后均与骨折风险相关。较低的时间更新估计肾小球滤过率（eGFR）与骨折相关（eGFR每降低10 mL/min/1.73m2，风险比为1.20；95%置信区间：1.04，1.38），较低的时间更新血清钙和碳酸氢盐浓度也与骨折相关。在时间更新的肾功能类别中，与eGFR≥60相比，接受透析治疗的肾衰竭患者发生骨折的风险比（95%置信区间）为4.53（1.77，11.60），肾移植后患者为2.48（0.86，7.14）。使用质子泵抑制剂、饮食钙摄入量、维生素D状态指标、血清磷酸盐、尿钙和磷酸盐以及血浆成纤维细胞生长因子-23与骨折风险无关。总之，CKD患者较低的eGFR与较高的骨折风险相关，在肾衰竭患者中风险最高。糖尿病、较低的BMI、使用类固醇、蛋白尿、较高的血清PTH浓度以及较低的钙和碳酸氢盐浓度与骨折相关，可能是可改变的风险因素。
