Dose–response relationship between growth hormone treatment and the development of scoliosis in children with short stature

BACKGROUND: We sought to investigate whether growth hormone (GH) treatment increases the risk of scoliosis in children with short stature and analyse a dose-response relationship. METHODS: A retrospective cross-sectional and cohort study design was used. The cross-sectional study included 1160 children with short stature (355 and 805 in the GH-exposed and non-exposed groups, respectively). The scoliosis prevalence was compared. A total of 313 short stature children without scoliosis at baseline were enrolled in the cohort study (158 and 155, respectively, in the GH and non-GH groups). The median follow-up time was approximately 4.5 years. The relationship between risk factors and GH dose and the occurrence of scoliosis was evaluated with the outcome of new-onset scoliosis. RESULTS: The incidence of scoliosis in the GH exposure group was significantly higher than that in the non-exposure group (5.40% vs. 2.40%, p=0.008). The risk of scoliosis in the GH group was 2.726 times higher than that in the non-GH group (HR=2.726, 95%CI: 1.326-5.605, p=0.006). The total GH dose was positively correlated with scoliosis risk, and there was a dose-response relationship between the total GH dose and the risk (HR=1.002, 95%CI: 1.001-1.003, p<0.001). A dose-response relationship was confirmed, with the predicted probability of scoliosis increasing continuously with cumulative GH dose. CONCLUSIONS: GH therapy is an independent risk factor for scoliosis in children with short stature, with a significant dose-response relationship. The cumulative GH dose can be used as a preliminary reference indicator for risk stratification and personalized monitoring.