Department of Medicine, Section of Endocrinology, Yale School of Medicine, New Haven, CT 06520-8020, USA.
Yale Center for Analytical Sciences, Yale School of Public Health, New Haven, CT 06510, USA.
J Clin Endocrinol Metab. 2024 Feb 20;109(3):e1061-e1071. doi: 10.1210/clinem/dgad642.
In clinical trials, burosumab ameliorates symptoms of pain, fatigue, and stiffness and improves performance on certain muscle function studies in patients with X-linked hypophosphatemia (XLH).
This work aimed to determine if burosumab increases adenosine triphosphate (ATP) synthesis in skeletal muscle of treatment-naive adults with XLH, and if so, whether that correlates with improved muscle function.
Ten untreated, symptomatic adults with XLH had ATP synthesis rates measured in the right calf using the 31P magnetic resonance spectroscopy saturation transfer technique. Baseline muscle function tests and symptoms of pain, fatigue, stiffness, and lower-extremity joint pain were quantified. All participants were treated with burosumab, 1 mg/kg every 4 weeks for 12 weeks. ATP synthesis rates and muscle function tests were repeated 2 weeks ("peak") and 4 weeks ("trough") after the third dose of burosumab.
All symptoms improved with treatment. Performance on the 6-Minute Walk Test (6MWT) and Sit to Stand (STS) tests also improved. Muscle strength and ATP synthesis rates did not change over the 3 months of the study. When individuals whose performances on the 6MWT and STS test were at or better than the median outcome for those tests were compared to those whose outcomes were below the median, no difference was observed in the rate of change in ATP synthesis. Intracellular muscle concentrations of phosphate were normal.
The improvement in the 6MWT and STS test without changes in muscle strength or ATP synthesis rates suggests that reductions in pain, fatigue, and stiffness may partly explain the improved performance. Intracellular phosphate in skeletal muscle is insulated from hypophosphatemia in XLH.
在临床试验中，布罗索尤单抗可改善 X 连锁低磷血症（XLH）患者的疼痛、疲劳和僵硬症状，并改善某些肌肉功能研究的表现。
本研究旨在确定布罗索尤单抗是否能增加初治 XLH 成年患者骨骼肌中的三磷酸腺苷（ATP）合成，如果能，是否与肌肉功能的改善相关。
使用 31P 磁共振波谱饱和转移技术测量 10 名未经治疗、有症状的 XLH 成年患者右小腿的 ATP 合成率。定量评估基线肌肉功能测试和疼痛、疲劳、僵硬以及下肢关节疼痛的症状。所有患者均接受布罗索尤单抗治疗，1mg/kg，每 4 周 1 次，共 12 周。在第三次布罗索尤单抗给药后 2 周（“峰值”）和 4 周（“谷值”）重复测量 ATP 合成率和肌肉功能测试。
所有症状均随治疗而改善。6 分钟步行测试（6MWT）和坐站测试（STS）的表现也有所改善。肌肉力量和 ATP 合成率在研究的 3 个月内没有变化。将 6MWT 和 STS 测试结果处于或优于这些测试中位数的个体与测试结果低于中位数的个体进行比较时，未观察到 ATP 合成率的变化差异。细胞内肌肉磷酸盐浓度正常。
6MWT 和 STS 测试的改善而肌肉力量或 ATP 合成率没有变化表明，疼痛、疲劳和僵硬的减轻可能部分解释了表现的改善。XLH 患者骨骼肌内的磷酸盐与低磷血症隔离。
