Bird Steven T, Gelperin Kate, Smith Elizabeth R, Jung Tae Hyun, Lyu Hai, Thompson Aliza, Easley Olivia, Naik Kushal B, Zhao Yueqin, Kambhampati Rekha, Wernecke Michael, Niak Ali, Zemskova Marina, Chillarige Yoganand, Kelman Jeffrey A, Graham David J
Office of Pharmacovigilance and Epidemiology, Center for Drug Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, Maryland (S.T.B., K.G., A.N., D.J.G.).
Acumen, Burlingame, California (E.R.S., H.L., K.B.N., M.W., Y.C.).
Ann Intern Med. 2025 Jan;178(1):29-38. doi: 10.7326/M24-0013. Epub 2024 Nov 19.
There is a paucity of data on treatment of osteoporosis in patients with advanced chronic kidney disease (CKD).
To assess the risk for emergently treated hypocalcemia with denosumab by stage of CKD and presence of CKD-mineral and bone disorder (CKD-MBD).
Target trial emulation.
Medicare fee-for-service data with prescription drug coverage, 2012 to 2020.
Female patients aged 65 years or older initiating denosumab, oral bisphosphonates, or intravenous (IV) bisphosphonates for osteoporosis.
Hospital and emergency department admissions (that is, emergent care) for hypocalcemia were assessed in the first 12 treatment weeks. Inverse probability of treatment weighted cumulative incidence and weighted risk differences (RDs) were calculated.
A total of 361 453 patients treated with denosumab, 829 044 treated with oral bisphosphonates, and 160 413 treated with IV bisphosphonates were identified. Risk for emergently treated hypocalcemia with denosumab versus oral bisphosphonates increased with worsening CKD stage ( < 0.001), with greatest risk among dialysis-dependent (DD) patients (3.01% vs. 0.00%; RD, 3.01% [95% CI, 2.27% to 3.77%]) and non-dialysis-dependent (NDD) patients with CKD stages 4 and 5 (0.57% vs. 0.03%; RD, 0.54% [CI, 0.41% to 0.68%]). Among patients with stages 4 and 5 CKD (NDD + DD), denosumab had a greater risk for emergently treated hypocalcemia versus oral bisphosphonates in those with CKD-MBD (1.53% vs. 0.02%; RD, 1.51% [CI, 1.21% to 1.78%]) than in those without CKD-MBD (0.22% vs. 0.03%; RD, 0.19% [CI, 0.08% to 0.31%]). Denosumab also showed increased risk compared with IV bisphosphonates.
Generalizability to men and non-Medicare populations.
Risk for emergently treated hypocalcemia with denosumab increased with worsening CKD stage and was highest in DD patients and those with CKD-MBD.
U.S. Food and Drug Administration.
关于晚期慢性肾脏病（CKD）患者骨质疏松症治疗的数据匮乏。
评估按CKD分期及是否存在CKD-矿物质和骨异常（CKD-MBD），使用地诺单抗治疗后发生紧急治疗的低钙血症的风险。
目标试验模拟。
2012年至2020年有处方药覆盖的医疗保险按服务收费数据。
65岁及以上开始使用地诺单抗、口服双膦酸盐或静脉注射（IV）双膦酸盐治疗骨质疏松症的女性患者。
在治疗的前12周评估因低钙血症住院和急诊科就诊情况（即紧急治疗）。计算治疗加权累积发病率的逆概率和加权风险差异（RDs）。
共识别出361453例接受地诺单抗治疗的患者、829044例接受口服双膦酸盐治疗的患者和160413例接受静脉注射双膦酸盐治疗的患者。与口服双膦酸盐相比，地诺单抗治疗后发生紧急治疗的低钙血症的风险随CKD分期加重而增加（P<0.001），在依赖透析（DD）的患者中风险最高（3.01%对0.00%；RD，3.01%[95%CI，2.27%至3.77%]），在CKD 4期和5期的非透析依赖（NDD）患者中也是如此（0.57%对0.03%；RD，0.54%[CI，0.41%至0.68%]）。在CKD 4期和5期患者（NDD+DD）中，与口服双膦酸盐相比，地诺单抗在患有CKD-MBD的患者中发生紧急治疗的低钙血症的风险更高（1.53%对0.02%；RD，1.51%[CI，1.21%至1.78%]），高于未患有CKD-MBD的患者（0.22%对0.03%；RD，0.19%[CI，0.08%至0.31%]）。与静脉注射双膦酸盐相比，地诺单抗的风险也有所增加。
对男性和非医疗保险人群的可推广性。
地诺单抗治疗后发生紧急治疗的低钙血症的风险随CKD分期加重而增加，在DD患者和患有CKD-MBD的患者中风险最高。
美国食品药品监督管理局。
