Factors affecting bone age maturation during 3 years of growth hormone treatment in patients with idiopathic growth hormone deficiency and idiopathic short stature: Analysis of data from the LG growth study

Abstract

To investigate the progression rate of bone age (BA) and associated factors during the first 3 years of growth hormone (GH) treatment in children with idiopathic GH deficiency (iGHD) and idiopathic short stature (ISS).Data for prepubertal children with iGHD and ISS who were treated with recombinant human GH were obtained from the LG Growth Study Database and analyzed. Height, weight, BA, insulin-like growth factor-1 (IGF-1) level, and GH dose were recorded every 6 months. Differences between BA and chronological age (CA), BA-CA, were calculated at each measurement. This study included 92 (78 iGHD and 14 ISS) subjects.After 3 years of GH treatment, the height z-score was -1.09 ± 0.71 (P < .001 compared to baseline), BA-CA was -1.21 ± 1.18 years (P < .001), and IGF-1 standard deviation score (SDS) was 0.43 ± 1.21 (P < .001) in the iGHD subjects; the change in BA over the 3 years was 3.68 ± 1.27 years. In the ISS subjects, the height z-score was -1.06 ± 0.59 (P < .001), BA-CA was -0.98 ± 1.23 years (P = .009), and IGF-1 SDS was 0.16 ± 0.76 (P = .648); the change in BA over the 3 years was 3.88 ± 1.36 years. The only significant factor associated with the BA progression was the BA-CA at 1 year of GH treatment (OR = 2.732, P = .001). The baseline BA-CA, IGF-1 SDS, and GH dose did not influence BA progression.Prepubertal subjects with iGHD and ISS showed height improvement and mild BA acceleration over the first 3 years of GH treatment. However, because the BA progression rate was considered to be clinically acceptable, GH treatment may increase the predicted adult height during this period.

Figure 1

BA-CA changes during GH treatment in subjects with iGHD (A) and ISS (B) are shown. ^∗P < .05 compared to baseline BA-CA by the MMRM approach. BA = bone age, CA = chronological age, GH = growth hormone, iGHD = idiopathic GHD, ISS = idiopathic short stature, MMRM = mixed-effect model repeated measure.

Figure 2

IGF-1 SDS changes during GH treatment in subjects with iGHD (A) and ISS (B) are shown. ^∗P < .05 compared to baseline IGF-1 SDS by the MMRM approach. GH = growth hormone, IGF-1 = insulin-like growth factor-1, iGHD = idiopathic GHD, ISS = idiopathic short stature, MMRM = mixed-effect model repeated measure, SDS = standard deviation score.

Figure 3

Progression of bone age during GH treatment according to baseline characteristics in subjects with iGHD. GH = growth hormone, iGHD = idiopathic GHD.

Figure 4

BA1-CA1 was significantly positively associated with BA3-CA3 (OR = 2.732; 95% CI: 1.495–4.993; P = .001). BA1-CA1 = difference between BA and CA at the end of the first year of GH treatment, BA3-CA3 = difference between BA and CA at the end of the third year of GH treatment. BA = bone age, CA = chronological age, CI = confidence interval, GH = growth hormone, OR = odds ratio.