Background: Patients with mutations of the short-stature-homeobox-containing (SHOX) gene likely have impaired growth, with or without a spectrum of skeletal anomalies consistent with mesomelic skeletal dysplasia. In a multinational clinical trial, GH has been shown to increase growth rate and final height (FH).
Objective and hypotheses: The aim of this analysis was to describe FH outcome after GH treatment in an observational setting (Genetics and Neuroendocrinology of Short Stature International Study (GeNeSIS)) and in a monitored randomized clinical trial (B9R-MC-GDFN).
Method: Twenty-eight prepubertal children (54% girls) with SHOX deficiency from the clinical trial and 85 children (72% girls) from GeNeSIS who had attained FH during observation were included in both analyses. Last observed height was considered FH (SDS/chronological ages) if any of the following criteria applied: closed epiphyses, height velocity <2 cm/year, last bone age >14 years in girls/>16 years in boys.
Results: Due to inclusion criteria, patients were younger at start of GH treatment (mean±SD; 9.2±2.4 and 11.1±2.3 years) and treatment duration was longer (6.0±2.0 and 4.2±2.3 years) in the clinical trial than in GeNeSIS respectively. Other relevant variables were similar between the two cohorts: baseline height SDS (−3.2±0.8 and −3.0±0.9), GH dose (0.36±0.02 and 0.32±0.11 mg/kg per week) at GH start, age at FH (15.5±1.3 and 15.5±1.5 years) and FH SDS (−2.0±1.3 and −2.2±1.2) each respectively. FH Height SDS gain from baseline (1.3±0.9 and 0.9±1.2) was notable for both cohorts. FH in the normal range (>−2 SDS) was achieved by 57 and 49% of the patients respectively.
Conclusion: In conclusion, GH treatment results in gain in height SDS at FH in SHOX deficient patients, both in a regulated clinical trial and in a real life observational study setting. In real life, GH treatment was initiated at an older age, probably a more advanced tanner stage and administered for a shorter duration.
20 - 22 Sep 2014
European Society for Paediatric Endocrinology