Hypophosphatasia (HPP) is a rare, inherited, systemic disease characterized by deficient tissue-nonspecific alkaline phosphatase activity. Common manifestations in children include impaired skeletal mineralization, short stature, and reduced physical function. Asfotase alfa is an enzyme replacement therapy approved for treatment of patients of any age with pediatric-onset HPP. The utility of dual X-ray absorptiometry (DXA) as a diagnostic tool or measure of treatment effectiveness in children with HPP is unclear. This post hoc analysis pooled DXA data from 19 children with pediatric-onset HPP aged ≥5 to <18 years at enrollment who were treated with asfotase alfa for up to 7 years (median [min, max] age at enrollment: 10.4 [5.9, 16.7] y; treatment duration: 6.3 (0.1, 6.6) y; male: 79%) in 2 open-label, multicenter studies (study 006/008 [NCT00952484/NCT01203826]; study 009 [NCT01163149]). DXA was performed at Baseline and approximately every 6 months thereafter. Baseline height Z-scores generally reflected short stature in these patients (median [min, max]: -1.26 [-6.6, 0]), necessitating height adjustment of DXA Z-scores. At Baseline, bone mineral density (BMD) Z-scores for whole body (including the head) and lumbar spine were <-2 in 17% and 28% of patients, respectively. Absolute values for whole body and lumbar spine bone mineral content (BMC) and BMD increased over time vs. Baseline, with significant increases at Last Assessment (P<0.0001). Whole body and lumbar spine BMC Z-scores also increased significantly from Baseline to Last Assessment (P≤0.0056); BMD Z-scores did not. Increases in whole body and lumbar spine BMC Z-scores correlated positively with Radiographic Global Impression of Change (RGI-C) scale scores (Pearson's correlation coefficients [r]=0.40.6 [P≤0.01]). No significant correlations were observed between BMD Z-scores and RGI-C. Significant correlations with Rickets Severity Scale scores were observed for whole body BMC Z-score and lumbar spine BMD Z-score (both r=-0.4 [P≤0.02]). Data from this post hoc analysis demonstrate that whole body and lumbar spine BMD Z-scores are not uniformly low (<-2) in children with HPP; therefore, these scores have limited utility in diagnosis of HPP or assessment of disease severity. Although absolute BMC and BMD values and BMC Z-scores increased over time, the relative contributions of asfotase alfa and natural accumulation of BMD due to growth were unclear, as BMD Z-scores did not change. Based on these data, DXA may not be a useful tool in assessing bone deficits in patients with HPP. Other complementary measures may need to be considered.
19 - 21 Sep 2019
European Society for Paediatric Endocrinology