Department of Medicine, University of Toronto, Ontario, Canada.
J Bone Miner Res. 2011 Aug;26(8):1829-35. doi: 10.1002/jbmr.403.
The incidences of osteoporosis and chronic kidney disease (CKD) both increase with increasing age, yet there is a paucity of data on treatments for osteoporosis in the setting of impaired kidney function. We examined the efficacy and safety of denosumab (DMAb) among subjects participating in the Fracture Reduction Evaluation of Denosumab in Osteoporosis Every 6 Months (FREEDOM) Study. We estimated creatinine clearance (eGFR) using Cockcroft-Gault and classified levels of kidney function using the modified National Kidney Foundation classification of CKD. We examined incident fracture rates; changes in bone mineral density (BMD), serum calcium, and creatinine; and the incidence of adverse events after 36 months of follow-up in subjects receiving DMAb or placebo, stratified by level of kidney function. We used a subgroup interaction term to determine if there were differences in treatment effect by eGFR. Most (93%) women were white, and the mean age was 72.3 ± 5.2 years; 73 women had an eGFR of 15 to 29 mL/min; 2817, between 30 to 59 mL/min; 4069, between 60 to 89 mL/min, and 842 had an eGFR of 90 mL/min or greater. None had stage 5 CKD. Fracture risk reduction and changes in BMD at all sites were in favor of DMAb. The test for treatment by subgroup interaction was not statistically significant, indicating that treatment efficacy did not differ by kidney function. Changes in creatinine and calcium and the incidence of adverse events were similar between groups and did not differ by level of kidney function. It is concluded that DMAb is effective at reducing fracture risk and is not associated with an increase in adverse events among patients with impaired kidney function.
骨质疏松症和慢性肾脏病 (CKD) 的发病率均随年龄增长而增加，但在肾功能受损的情况下，关于骨质疏松症治疗的数据却很少。我们研究了 denosumab（DMAb）在参与每 6 个月评估 denosumab 在骨质疏松症骨折减少（FREEDOM）研究的受试者中的疗效和安全性。我们使用 Cockcroft-Gault 方程估算肌酐清除率（eGFR），并使用改良的美国国家肾脏病基金会 CKD 分级系统对肾功能进行分级。我们在接受 DMAb 或安慰剂的受试者中，根据肾功能水平，研究了 36 个月随访期间骨折发生率、骨密度（BMD）、血清钙和肌酐的变化以及不良事件的发生率。我们使用亚组交互项来确定 eGFR 对治疗效果的差异。大多数（93%）女性为白人，平均年龄为 72.3±5.2 岁；73 名女性的 eGFR 为 15 至 29mL/min；2817 名女性的 eGFR 为 30 至 59mL/min；4069 名女性的 eGFR 为 60 至 89mL/min，842 名女性的 eGFR 为 90mL/min 或更高。没有女性处于 CKD 5 期。所有部位的骨折风险降低和 BMD 变化均有利于 DMAb。治疗亚组交互作用的检验无统计学意义，表明肾功能对治疗效果没有影响。两组间肌酐和钙的变化以及不良事件的发生率相似，且与肾功能水平无关。结论是，DMAb 可有效降低骨折风险，且在肾功能受损的患者中不会增加不良事件。
