Long-term effects of growth hormone (GH) on bone mineral status and bone turnover markers in patients with isolated GH deficiency and multiple pituitary hormone deficiency

Objective: This study was designed to assess the long-term effects of growth hormone (GH) replacement therapy on bone mass and bone turnover markers in children with isolated GH deficiency (IGHD) and multiple pituitary hormone deficiency (MPHD). Materials and methods: Fifty children (35 IGHD, 15 MPHD) receiving GH replacement therapy were enrolled in the study. The patients were followed for 38.6 ± 15.7 months (1-5 years). Bone mineral density (BMD) of the lumbar region and bone turnover markers [PTH, osteocalcin, bone-specific alkaline phosphatase (boneALP), and the carboxyterminal propeptide of type-1 collagen (CPP-I)] were assessed annually. Results: The height standard deviation score (SDS) of patients with IGHD and MPHD at diagnosis was statistically significant (P = 0.012), and the change in height SDS during 3 years (Δheight SDS_{3 years}) was statistically similar between these two groups (P = 0.651). The BMD z-scores of the two groups were comparable at the start of GH therapy (P = 0.083), and then increased in both groups similarly during 5 years of GH replacement therapy (F = 0.349, P = 0.567). When the BMD z-scores during 5 years of GH therapy were analysed in the IGHD and MPHD groups separately, it was found that the BMD z-score increased significantly in IGHD (P < 0.001) but the increase was not significant in MPHD (P = 0.140). Multiple regression analysis showed that the change in BMD z-score during 3 years of GH therapy (ΔBMD z-score_{3 years}) was predicted by the BMD z-score and height SDS at the start of GH therapy and by Δheight SDS _{3 years} in the IGHD group (t = -2.582, P = 0.02; t = 2.322, P = 0.034 and t = 2.908, P = 0.01, respectively). Age and BMD z-score and height SDS at diagnosis were found to have predictive values for the ΔBMD z-score _{3 years} (t = -3.652, P = 0.022; t = -4.073, P = 0.015 and t = 3.389, P = 0.028, respectively) in the MPHD group. The changes in boneALP, osteocalcin, CPP-1 and PTH levels during the therapy were statistically similar between the IGHD and MPHD groups. Conclusion: BMD increased during GH therapy in the IGHD and MPHD groups. GH had a positive effect on bone mass in the short as well as the long term. Early diagnosis and treatment could improve peak bone mass in patients with MPHD. The time and dose of sex steroids for pubertal induction and progression, which mimics physiological secretion, might also contribute to bone accretion in patients with MPHD.