Brener Avivit, Lebenthal Yael, Cleper Roxana, Kapusta Livia, Zeitlin Leonid
Pediatric Endocrinology and Diabetes Unit, Dana-Dwek Children's Hospital, Tel Aviv Sourasky Medical Center, 6 Weizmann Street, Tel Aviv, 6423906, Israel.
Pediatric Endocrinology and Diabetes Unit, Dana-Dwek Children's Hospital, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel; Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
Ther Adv Endocrinol Metab. 2021 Mar 16;12:20420188211001150. doi: 10.1177/20420188211001150. eCollection 2021.
Burosumab, a recombinant anti-FGF23 monoclonal antibody, was recently introduced as a treatment for X-linked hypophosphatemia (XLH). Burosumab normalizes blood phosphate levels, thereby healing rickets, decreasing leg bowing, and reducing pain. We aimed to explore the body composition and cardiometabolic health of pediatric patients with XLH treated with burosumab.
This observational real-life study was conducted on growing children and adolescents. The outcome measures included changes in sex- and age-adjusted anthropometric and body composition parameters [fat mass (FM), fat-free mass (FFM), appendicular skeletal muscle mass (ASMM), muscle-to-fat ratio (MFR)], blood pressure, laboratory evaluation, and radiographic rickets severity [Thacher Rickets Severity Score (TRSS)]. Body composition was assessed by bioelectrical impedance analysis (BIA). Percentiles for FFM% and ASMM% were calculated according to BIA pediatric reference curves. The delta variable was calculated as the variable at 12 months minus the variable at baseline.
A total of 15 pediatric patients with XLH are treated in our clinic; included in the analyses were 7 children and adolescents (3 males, mean age 8.7 ± 3.2 years) with XLH without comorbidities. Baseline BIA revealed an unfavorable physique, with increased body fat percentage in five patients and decreased muscle mass in six. Indices of lean body mass significantly increased after 6 and 12 months of treatment: FFM(kg) ( = 0.001, = 0.046, respectively) and ASMM(kg) ( = 0.012, = 0.034, respectively), without any significant change in FM(kg). The percentile of ASMM% increased significantly after 6 months of treatment ( = 0.006) and stabilized thereafter. TRSS improved significantly after 12 months of therapy ( = 0.005). Age was positively correlated with delta TRSS ( = 0.814, = 0.026), and delta TRSS was negatively correlated with delta MFR ( = -0.826, = 0.022).
There was a heretofore unrecognized improvement in body composition of growing children and adolescents with XLH who were treated with burosumab. These findings highlight the need to initiate burosumab treatment at a younger age when rickets is less severe.
布罗索尤单抗是一种重组抗成纤维细胞生长因子23（FGF23）单克隆抗体，最近被用于治疗X连锁低磷血症（XLH）。布罗索尤单抗可使血磷水平正常化，从而治愈佝偻病，减少腿部弯曲并减轻疼痛。我们旨在探讨接受布罗索尤单抗治疗的XLH儿科患者的身体成分和心脏代谢健康状况。
本观察性实际研究针对正在成长的儿童和青少年进行。观察指标包括经性别和年龄调整的人体测量和身体成分参数[脂肪量（FM）、去脂体重（FFM）、四肢骨骼肌量（ASMM）、肌肉与脂肪比率（MFR）]的变化、血压、实验室评估以及放射影像学佝偻病严重程度[撒切尔佝偻病严重程度评分（TRSS）]。通过生物电阻抗分析（BIA）评估身体成分。根据BIA儿科参考曲线计算FFM%和ASMM%的百分位数。增量变量计算为12个月时的变量减去基线时的变量。
我们诊所共治疗了15例XLH儿科患者；纳入分析的有7例无合并症的XLH儿童和青少年（3例男性，平均年龄8.7±3.2岁）。基线BIA显示身体状况不佳，5例患者体脂百分比增加，6例患者肌肉量减少。治疗6个月和12个月后，瘦体重指数显著增加：FFM（kg）（分别为P = 0.001，P = 0.046）和ASMM（kg）（分别为P = 0.012，P = 0.034），而FM（kg）无显著变化。治疗6个月后，ASMM%的百分位数显著增加（P = 0.006），此后保持稳定。治疗12个月后，TRSS显著改善（P = 0.005）。年龄与TRSS增量呈正相关（r = 0.814，P = 0.026），TRSS增量与MFR增量呈负相关（r = -0.826，P = 0.022）。
接受布罗索尤单抗治疗的XLH成长中儿童和青少年的身体成分有此前未被认识到的改善。这些发现凸显了在佝偻病不太严重的较年轻年龄开始布罗索尤单抗治疗的必要性。
