Beyond growth hormone: association of short stature types and growth hormone with scoliosis

Abstract

Study Design: Cross-sectional and retrospective cohort study. Objective: We investigated the effect of three types of short stature (partial growth hormone deficiency [GHD], GHD, and idiopathic short stature [ISS]) and recombinant human growth hormone (rhGH) therapy on scoliosis. Summary of Background Data: In short stature, rhGH is widely used and the concentration of growth hormone varies among types. The epidemiologic characteristics of scoliosis and the role of rhGH on scoliosis remain unclear. Methods: A cross-sectional study was conducted among 3896 patients with short stature (partial GHD, GHD, and ISS), and a 1:1 age- and sex-matched control group with preexisting whole-spine radiographs. The cohort study included 2605 subjects who underwent radiography more than twice to assess scoliosis development, progression, and the need for bracing and surgery. Adjusted logistic regression were used to assess differences in the prevalence of scoliosis among patients with partial GHD, GHD, ISS, and controls. The Kaplan-Meier method was used to analyze the time course of scoliosis development and progression. Cox regression was applied to assess the independent factors related to scoliosis development and progression. Mendelian randomization analyses were also performed. Results: Compared with controls, patients with short stature had a higher incidence of scoliosis (34.47% in partial GHD, 31.85% in GHD, 32.94% in ISS vs 8.83% in control, P <0.001), a higher risk of scoliosis development (HR=1.964 in partial GHD, P <0.001; HR=1.881 in GHD, P =0.001; HR=1.706 in ISS, P =0.001), but not a higher risk of progression, brace, or surgery. Among three types of short stature, there was no differences in the incidence, development and progression of scoliosis or the need for bracing or surgery. RhGH treatment increased the risk of scoliosis development in each short stature group (HR=2.673 in partial GHD, P<0.001; HR=1.924 in GHD, P=0.049; HR=1.564 in ISS, P=0.004). Vitamin D supplementation was protective against scoliosis development (HR=0.456 in partial GHD, P =0.003; HR=0.42 in GHD, P =0.013; HR=0.838 in ISS, P =0.257). Conclusions: More attention should be paid to the spinal curve in patients with partial GHD, GHD or ISS. For short stature treated with rhGH, the risk of scoliosis development was increased. Vitamin D supplementation may be beneficial for prevention. Level of evidence: 3.