Department of Neurosurgery, Medical University of Vienna, Vienna, Austria.
Institute of Pathophysiology and Allergy Research, Center for Pathophysiology, Infectiology, and Immunology, Medical University of Vienna, Vienna, Austria.
J Bone Miner Res. 2022 Nov;37(11):2156-2164. doi: 10.1002/jbmr.4694. Epub 2022 Sep 23.
Metabolic bone disease is a devastating condition in critically ill patients admitted to an intensive care unit (ICU). We investigated the effects of early administration of the antiresorptive drug denosumab on bone metabolism in previously healthy patients. Fourteen patients with severe intracerebral or subarachnoid hemorrhage were included in a phase 2 trial. Within 72 hours after ICU admission, they were randomized in a 1:1 ratio to receive denosumab 60 mg or placebo subcutaneously. The primary endpoint was group differences in the percentage change of C-terminal telopeptide of type 1 collagen (CTX-1) levels in serum from denosumab/placebo application to 4 weeks thereafter. Changes in serum levels of bone formation markers and urinary calcium excretion were secondary outcome parameters. Regarding serum levels of CTX-1, changes over time averaged -0.45 ng/mL (95% confidence interval [CI] -0.72, -0.18) for the denosumab group and 0.29 ng/mL (95% CI -0.01, 0.58) for the placebo group. The primary endpoint, the group difference in changes between baseline and secondary measurement, adjusted for baseline serum levels and baseline neurological status, averaged -0.74 ng/mL (95% CI -1.14, -0.34; p = 0.002). The group difference in changes between baseline and secondary osteocalcin measurement averaged -5.60 ng/mL (95% CI -11.2, -0.04; p = 0.049). The group difference in averaged change between baseline and secondary measurement of 24-hour urine calcium excretion was significant (-1.77 mmol/L [95% CI -3.48, -0.06; p = 0.044]). No adverse events could be attributed to the study medication. The investigation proved that a single application of denosumab early after admission to an ICU prevents acute immobilization-associated increase in bone resorption among previously healthy individuals. © 2022 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).
代谢性骨病是重症监护病房（ICU）收治的危重症患者的一种破坏性疾病。我们研究了早期给予抗吸收药物地舒单抗对既往健康患者骨代谢的影响。14 名患有严重颅内或蛛网膜下腔出血的患者参与了一项 2 期试验。在 ICU 入院后 72 小时内，他们以 1:1 的比例随机接受地舒单抗 60mg 或皮下安慰剂治疗。主要终点是地舒单抗/安慰剂应用后 4 周内血清 1 型胶原 C 端肽（CTX-1）水平变化的组间差异。骨形成标志物和尿钙排泄变化是次要观察指标。关于血清 CTX-1 水平，地舒单抗组的变化时间平均为-0.45ng/mL（95%置信区间-0.72，-0.18），安慰剂组为 0.29ng/mL（95%置信区间-0.01，0.58）。主要终点是调整基线血清水平和基线神经状态后，从基线到二次测量的组间变化差异，平均为-0.74ng/mL（95%置信区间-1.14，-0.34；p=0.002）。从基线到二次骨钙素测量的组间变化差异平均为-5.60ng/mL（95%置信区间-11.2，-0.04；p=0.049）。从基线到二次 24 小时尿钙排泄的平均变化差异具有统计学意义（-1.77mmol/L[95%置信区间-3.48，-0.06；p=0.044]）。没有与研究药物相关的不良事件。该研究证明，在 ICU 入院后早期单次应用地舒单抗可预防既往健康个体急性制动相关的骨吸收增加。
