CONTEXT In clinical trials, burosumab ameliorates symptoms of pain, fatigue and stiffness and improves performance on certain muscle function studies in patients with XLH. OBJECTIVE Determine if burosumab increases ATP synthesis in skeletal muscle of treatment-naïve adults with XLH. If so, whether that correlates with improved muscle function. METHODS 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 q 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. RESULTS All symptoms improved with treatment. Performance on the 6-Minute Walk (6MW) and Sit to Stand (STS) tests also improved. Muscle strength and ATP synthesis rates didn't change over the three months of study. When individuals whose performances on the 6MW and STS tests 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 phosphorus were normal. CONCLUSION The improvement in the 6MW and STS tests 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.

中文翻译：

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burosumab 对 XLH 成人骨骼肌功能和力量以及 ATP 合成率的影响。

背景 在临床试验中，burosumab 可改善 XLH 患者的疼痛、疲劳和僵硬症状，并提高某些肌肉功能研究的表现。目的 确定 burosumab 是否会增加未经治疗的 XLH 成人骨骼肌中的 ATP 合成。如果是这样，这是否与肌肉功能的改善相关。方法 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 成人的右小腿 ATP 合成率。对基线肌肉功能测试和疼痛、疲劳、僵硬和下肢关节疼痛的症状进行量化。所有参与者均接受 burosumab 治疗，剂量为 1 mg/kg，每 4 周一次，持续 12 周。第三次注射 burosumab 后 2 周（“峰值”）和 4 周（“谷值”）重复 ATP 合成率和肌肉功能测试。结果 所有症状均通过治疗得到改善。6 分钟步行 (6MW) 和坐站 (STS) 测试的表现也有所提高。在三个月的研究中，肌肉力量和 ATP 合成率没有变化。当将 6MW 和 STS 测试表现等于或优于这些测试中值结果的个体与结果低于中值的个体进行比较时，没有观察到 ATP 合成变化率的差异。细胞内肌肉磷浓度正常。结论 6MW 和 STS 测试的改善没有改变肌肉力量或 ATP 合成率，这表明疼痛、疲劳和僵硬的减少可能部分解释了性能的改善。XLH 中骨骼肌中的细胞内磷酸盐与低磷血症无关。