Endocrine Abstracts

JOINT1259

Background: Achondroplasia is a genetic disorder caused by a gain-of-function mutation in FGFR3, leading to impaired bone growth and disproportionate short stature. Children with achondroplasia often present with muscular hypotonia at birth, though its underlying pathophysiology remains incompletely understood. In 2021, Vosoritide was approved as the first targeted medication for achondroplasia. This C-type natriuretic peptide (CNP) analog counteracts the overactive FGFR3 signaling, promoting endochondral ossification and consequently increasing longitudinal bone growth. As muscle and bone development are closely connected, we investigated whether the increased growth during Vosoritide treatment is associated with changes in muscle function.

Methods and Patients: This retrospective observational study included 15 patients with achondroplasia treated with Vosoritide at our center, between October 2021 and October 2024. As part of routine clinical assessments, muscle function parameters were measured using a two-legged jump on the "Leonardo Ground Reaction Force Platform", while auxological parameters were recorded using a stadiometer and a sitting scale. Measurements were converted into z-scores using LMS data from a healthy cohort and analyzed at three time points: baseline, 12 months, and 24 months after initiating Vosoritide therapy. Statistical analysis was performed using GraphPad Prism software.

Results: 15 patients (3 female) aged 6. 7 to 15. 3 years at therapy initiation were included in the analysis. The median CDC height z-score for the entire cohort (n = 15) at baseline was -5. 93 (IQR -6. 87;-4. 83), improving to -5. 64 (IQR -8. 02;-3. 84) after 12 months of therapy (n = 15). In nine children with available 24-month data, a median z-score change of +0. 89 (n = 9) was observed after 24 months, representing a significant increase (P = 0. 0059). Median z-scores for weight and BMI showed no significant changes after 24 months. Z-scores for muscle function parameters, including maximal relative power, maximal velocity, and jump height, did not show significant changes over time. However, the median z-score for maximal relative force decreased after 24 months of therapy (P = 0. 0039).

Conclusion: Compared to references from a healthy cohort, no significant changes were observed in z-scores for maximal relative power, maximal velocity, or jump height. Thus, over 12 (n = 15) and 24 months (n = 9), patients developed similarly to children without achondroplasia regarding these parameters. The observed decrease in maximal relative force, despite unchanged maximal relative power, may indicate an improved movement efficiency.