Vosoritide Treatment Does Not Change the Robust Bone Phenotype of Children with Achondroplasia

Vosoritide treatment did not alter the robust bone phenotype in children with achondroplasia over 5 years, maintaining bone strength.

Summary and findings

This study measured bone morphological parameters in 30 children with achondroplasia treated with vosoritide over 5 years. Key measurements included second metacarpal length and cortical area. The findings indicated no alteration in the robust bone phenotype due to treatment.

Abstract

<title>Abstract</title> <p>Background Vosoritide is an FDA-approved bone-lengthening treatment for children with achondroplasia, the most common form of disproportionate short stature. Whether this bone-lengthening treatment provides commensurate changes in cross-sectional morphology, to ensure bone strength is not deleteriously affected, is unknown. Thus, we sought to characterize the bone morphological parameters of children with achondroplasia on vosoritide using measurements of the second metacarpal. Methods This study included deidentified anteroposterior hand/wrist radiographs from 30 children with achondroplasia (13 males, 17 females; age 5.8 − 11.1 years). Proprietary hand films were collected at screening (pre-treatment) and at 5 years on treatment. Measurements included second metacarpal length and midshaft width, cortical thickness, robustness (total area/length) and cortical area, which correlates with strength. Measurements were compared between the two time-points via non-parametric Wilcoxon tests, and with 378 radiographs from 114 average-statured controls who did not receive vosoritide treatment (61 males, 53 females; age 6 − 16 years) via Kruskal-Wallis tests (p < 0.05). Results Compared to average-stature controls, children with achondroplasia exhibited a more robust bone phenotype (p < 0.001). After 5 years of vosoritide treatment, children with achondroplasia demonstrated increased metacarpal length and cortical area compared to their own baseline values (all p < 0.05). No sex differences were observed. Conclusions Altogether, increases in metacarpal total area and cortical area kept up with increases in metacarpal length over the course of 5 years of vosoritide treatment. As the bones lengthened, subperiosteal expansion continued at a pace which maintained robustness, allowing the bone to remain strong. This preliminary data suggests that vosoritide did not alter the naturally robust bone phenotype of children with achondroplasia. Clinical trial registration Clinical trial registry: ClinicalTrials.gov. Clinical trial numbers: NCT02055157 (registered January 13, 2014) and NCT02724228 (registered January 26, 2016).</p>

Limitations

Not reported in abstract.

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