Effect of human growth hormone HGH treatment on bone in postpubertal HGH-deficient patients: a 2-year randomized, controlled, dose-ranging study.
Shalet SM - J Clin Endocrinol Metab - 01-SEP-2003; 88(9): 4124-9
From NIH/NLM MEDLINE
NLM Citation ID:
12970274 (PubMed)
Full Source Title:
Journal of Clinical Endocrinology and Metabolism
Publication Type:
Clinical Trial; Journal Article; Multicenter Study; Randomized Controlled Trial
Language:
English
Author Affiliation:
Department of Endocrinology, Christie Hospital NHS Trust, Manchester M20 4BX, United Kingdom. stephen.m.shalet@man.ac.uk
Authors:
Shalet SM; Shavrikova E; Cromer M; Child CJ; Keller E; Zapletalová J; Moshang T; Blum WF; Chipman JJ; Quigley CA; Attanasio AF
Abstract:
HGH treatment in children with HGH deficiency is frequently terminated at final height. However, in healthy individuals bone mass continues to accrue until peak bone mass is achieved. Because no prospective data specifically prove the role of HGH in attainment of peak bone mass, we performed a multinational, controlled, 2-yr study in patients who had terminated pediatric HGH at final height. Patients were randomized to: GH at 25.0 microg/kg x day (pediatric dose, n = 58) or 12.5 microg/kg x day (adult dose, n = 59), or no GH treatment (control, n = 32). Bone mineral content (BMC) and density were measured by dual-energy x-ray absorptiometry and evaluated centrally. Laboratory measurements were also performed centrally. After 2 yr, significant increases were seen with both GH treatments, compared with control in bone-specific alkaline phosphatase (P = 0.004) and type I collagen C-terminal telopeptide:creatinine ratio (P < 0.001), but there were no significant dose effects. Total BMC increased by 9.5 +/- 8.4% in the adult dose group, 8.1 +/- 7.6% in the pediatric dose group, and 5.6 +/- 8.4% in controls (analysis of covariance, P = 0.008), with no significant GH dose effect. BMC increased predominantly at the lumbar spine (11.0 +/- 10.6%, P = 0.015) rather than at the femoral neck or hip. In contrast, a significant dose-dependent increase was seen in IGF-I concentrations (adult dose: 114.5 +/- 119.4 microg/liter; pediatric dose: 178.5 +/- 143.7 microg/liter; P = 0.023). There were no gender-related differences in BMC changes with either dose, whereas the IGF-I increase was significantly higher with the pediatric than with the adult dose in females (P < 0.001) but not males (P = 0.606). In summary, reinstitution of HGH replacement after final height in severely HGH-deficient patients induced significant progression toward peak bone mass. Although there was a by-gender dose effect on IGF-I concentration, the treatment effect on bone was obtained in both males and females with the adult HGH dose regimen.
Major Subjects:
- Bone Development / * drug effects
- Growth Hormone / administration & dosage / adverse effects / * therapeutic use
- Human Growth Hormone / * deficiency
Additional Subjects:
- Adult
- Alkaline Phosphatase / metabolism
- Body Height / drug effects
- Bone Density / drug effects
- Bone and Bones / enzymology
- Calcification, Physiologic / drug effects
- Cohort Studies
- Collagen Type I / metabolism
- Densitometry, X-Ray
- Dose-Response Relationship, Drug
- Double-Blind Method
- Female
- Humans
- Insulin-Like Growth Factor I / metabolism
- Male
- Prospective Studies
- Puberty / physiology
- Sex Characteristics
Chemical Compound Name:
(Collagen Type I); 12629-01-5(Human Growth Hormone); 67763-96-6(Insulin-Like Growth Factor I); 9002-72-6(Human Growth Hormone); EC 3.1.3.1(Alkaline Phosphatase)