Department of Pediatrics, Vanderbilt University Medical Center, Vanderbilt University, Village at Vanderbilt, 1500 21st Ave South, Suite 1514, Nashville, TN 37212, USA.
Department of Pediatrics, Children's Mercy Kansas City, Adele Hall Campus, 2401 Gillham Rd, Kansas City, MO 64108, USA; University of Missouri - Kansas City School of Medicine, 2411 Holmes St, Kansas City, MO 64108, USA; University of Kansas School of Medicine, 3901 Rainbow Blvd, Kansas City, KS 66160, USA.
Bone. 2020 Aug;137:115413. doi: 10.1016/j.bone.2020.115413. Epub 2020 May 14.
Asfotase alfa is an enzyme replacement therapy approved for treatment of patients with pediatric-onset hypophosphatasia (HPP), a rare, inherited, systemic disease causing impaired skeletal mineralization, short stature, and reduced physical function in children. The role of dual X-ray absorptiometry (DXA) in the assessment of children with HPP has been insufficiently explored. This post hoc analysis included pooled DXA data from 2 open-label, multicenter studies in 19 children with HPP. The study population was aged ≥5 to <18 years and had received asfotase alfa for ≤6.6 years at enrollment (male: 79%; median age at enrollment: 10.4 y [range: 5.9-16.7]; treatment duration: 6.3 y [range: 0.1-6.6]. Baseline height Z-scores indicated short stature (median [min, max]: -1.26 [-6.6, 0]); mean [SD]: -2.30 [1.97]), thus requiring height adjustment of DXA Z-scores. At Baseline, few patients had height-adjusted bone mineral density (BMD) Z-scores of -2 or less for whole body (n = 3) or lumbar spine (n = 5). In treated patients, mean whole body and lumbar spine BMDZ-scores did not change over time, but whole body and lumbar spine height- adjusted bone mineral content (BMC) Z-scores increased significantly from Baseline to Last Assessment (P ≤ 0.0056). Improvements in Radiographic Global Impression of Change (RGI-C) scale scores correlated significantly with increases in whole body and lumbar spine BMCZ-scores (P < 0.05) but not BMDZ-Scores. Improvements in Rickets Severity Score (RSS) correlated significantly with increases in lumbar spine BMDZ-scores and whole body BMC Z-scores (P < 0.05). No significant correlations were observed between any DXA and bone histomorphometry measure. These findings suggest that DXA BMD Z-scores, which are commonly used in clinical practice, have limited utility in assessing deficient bone mineralization in patients with HPP. Although BMCZ-scores increased significantly over time with asfotase alfa therapy, the lack of significant changes in more than one DXA parameter suggests that this tool may not be useful in everyday clinical practice. Furthermore, the use of BMC as an independent metric is not typical or recommended by guidelines. Complementary measures, such as skeletal radiographs supplemented with age-appropriate functional assessments, should be considered.
阿法特磷酸酶用于治疗儿科发病的低磷酸酶血症（HPP）患者，HPP 是一种罕见的遗传性系统性疾病，会导致骨骼矿化受损、身材矮小和身体功能下降。双能 X 线吸收法（DXA）在 HPP 患儿评估中的作用尚未得到充分探索。本事后分析纳入了两项 HPP 患儿开放性、多中心研究的汇总 DXA 数据。研究人群年龄≥5 岁且<18 岁，入组时接受阿法特磷酸酶治疗≤6.6 年（男：79%；中位入组年龄：10.4 岁[范围：5.9-16.7]；治疗持续时间：6.3 年[范围：0.1-6.6]）。基线时身高 Z 评分表明身材矮小（中位数[最小，最大]：-1.26[-6.6,0]），需要对 DXA Z 评分进行身高校正。基线时，少数患者全身体（n=3）或腰椎（n=5）的校正后骨密度（BMD）Z 评分低于-2。在接受治疗的患者中，全身体和腰椎 BMDZ 评分随时间无变化，但全身体和腰椎校正后骨矿物质含量（BMC）Z 评分从基线到最后评估显著增加（P≤0.0056）。放射学总体印象变化（RGI-C）量表评分的改善与全身体和腰椎 BMCZ 评分的增加显著相关（P<0.05），但与 BMDZ 评分无关。佝偻病严重程度评分（RSS）的改善与腰椎 BMDZ 评分和全身体 BMCZ 评分的增加显著相关（P<0.05）。DXA 和骨组织形态计量学指标之间未观察到显著相关性。这些发现表明，DXA 中的 BMDZ 评分在临床上常用，但在评估 HPP 患者的骨矿物质缺乏方面作用有限。尽管阿法特磷酸酶治疗后 BMCZ 评分随时间显著增加，但多于一个 DXA 参数无显著变化，提示该工具在日常临床实践中可能无用。此外，使用 BMC 作为独立指标不符合指南建议。应考虑使用骨骼 X 线片补充年龄适当的功能评估等补充措施。
