Abstract

Abstract Objectives To investigate the impact of rhGH on measures of skeletal muscle strength, power, endurance, agility, and lean body mass accrual in prepubertal boys with significant short stature compared to age-matched healthy controls growing normally. Methods 40 prepubertal boys were recruited, 25 with significant short stature -either isolated GH deficiency or idiopathic (mean (SE) age: 8.9±0.3yrs; HT SDS: -2.3±0.1) and 15 normally growing healthy controls (age: 8.8±0.4yrs; HT SDS: -0.3±0.2). All had testing at baseline including anthropometry, blood, DEXA scan (body composition), and indirect calorimetry (resting energy expenditure (REE)). Protocolized muscle function tests were performed by expert personnel including measures of skeletal muscle strength (isokinetic dynamometry (flexion/extension) upper and lower extremities), power (vertical jump), endurance (modified push-ups), and agility (timed shuttle-runs). Boys with short stature were started on daily rhGH (Norditropin®, 0.3mg/kg/w) and baseline studies repeated identically in all at 6 and 12 months. Mixed effects model ANOVA (and 2 sample t-test) was used to compare main outcomes over time between groups (significance p ≤0.05). Results Baseline N=40, 6 months N=34, 12 months N=27 participants thus far. All grew well and remained prepubertal throughout the study. At baseline, there were measurable differences in fat free mass (FFM) between groups: short stature: 15.9±0.5kg, controls: 20.4±1.1 (p=0.001); both groups gained FFM at 12 months, short stature group gained 27.3% (p<0.001) vs. controls 10.7% (p<0.001) (p<0.001 between groups). Measures of agility and power were comparable at baseline between groups, agility improved by 12 months 5.5% in the rhGH-treated group (p=0.007) vs. 2.7% in controls (p=0.178) (p=0.157 between groups); measures of power improved 9.1% in the rhGH-treated group (p=0.001) vs. 3.8% in controls (p=0.386) at 12 months (p<0.258 between groups). There were significant differences between groups in muscle strength at baseline, lower particularly in elbow flexion (biceps) in the short stature group: 79.7±3.7 Newtons vs. controls: 97.6±5.5 (p=0.008), and knee flexion (hamstrings): 82.6±3.4 Newtons vs. 95.7±3.2 (p=0.013). At 12 months the rhGH-treated group improved biceps strength (25.7%, p<0.001), vs. controls (12.5%, p=0.008) (p=0.019 between groups); whereas hamstrings strength improved comparably at 12 months in the rhGH-treated group (24.1%, p=0.008) vs. controls (28.0%, p=0.01) (p=0.79 between groups). Measures of endurance (modified push-ups) at baseline were 17.5±1.5 reps in the short stature group vs. 24.9±3.3 in controls (p=0.057), improving in the rhGH-treated (63%, p<0.001) vs. controls (43%, p=0.07) at 12 months (p=0.959 between groups). There were no significant differences in REE (kcal/kg/d) between groups during 12 months. Conclusion There are significant differences in FFM and skeletal muscle strength and endurance in prepubertal boys with severe short stature compared to healthy age-matched controls. FFM accrual and isokinetic measures of muscle strength, endurance, agility and power improve after 12 months of rhGH, changes approaching measures of those of healthy controls. Presentation: Saturday, June 11, 2022 1:00 p.m. - 3:00 p.m.

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