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Effect of Growth Hormone (GH) Treatment on Bone in Postpubertal GH-Deficient Patients: A 2-Year Randomized, Controlled, Dose-Ranging Study

Christie Hospital (S.M.S.), Manchester M20 4BX, United Kingdom; PSI (E.S.), 191119 St. Petersburg, Russia; Eli Lilly & Company (M.C., J.J.C., C.A.Q.), Indianapolis, Indiana 46285; Universität Klinik (E.K.), Leipzig D-04317, Germany; Palacky University Hospital (J.Z.), Olomouc 772 00, Czech Republic; Children’s Hospital (T.M.), Philadelphia, Pennsylvania 19104-4399; Eli Lilly and Company Windlesham (C.J.C.), Surrey GU20 6PH, United Kingdom; Bad Homburg (W.F.B.) D-61350, Germany; and Sesto Fiorentino (A.F.A.) 50019, Italy

Address all correspondence and requests for reprints to: Dr. Stephen M. Shalet, Department of Endocrinology, Christie Hospital NHS Trust, Wilmslow Road, Manchester M20 4BX, United Kingdom. E-mail: stephen.m.shalet{at}man.ac.uk.

GH treatment in children with GH 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 GH in attainment of peak bone mass, we performed a multinational, controlled, 2-yr study in patients who had terminated pediatric GH at final height. Patients were randomized to: GH at 25.0 µg/kg·day (pediatric dose, n = 58) or 12.5 µg/kg·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 µg/liter; pediatric dose: 178.5 ± 143.7 µg/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 GH replacement after final height in severely GH-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 GH dose regimen.

Abbreviations: ANCOVA, Analysis of covariance; AO, adult onset; BAP, bone-specific alkaline phosphatase; BMC, bone mineral content; BMD, bone mineral density; CO, childhood onset; DXA, dual-energy x-ray absorptiometry; GHD, GH deficiency; ICTP, type I collagen -cross-linked C-terminal telopeptide; IGFBP, IGF-binding protein.

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