Effect of growth hormone (GH) treatment on bone in postpubertal GH-deficient patients: a 2-year randomized, controlled, dose-ranging study.
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 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 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.
Shalet
Stephen M
SM
Department of Endocrinology, Christie Hospital NHS Trust, Manchester M20 4BX, United Kingdom. stephen.m.shalet@man.ac.uk
Shavrikova
Elena
E
Cromer
Morris
M
Child
Christopher J
CJ
Keller
Eberhard
E
Zapletalová
Jirina
J
Moshang
Thomas
T
Blum
Werner F
WF
Chipman
John J
JJ
Quigley
Charmian A
CA
Attanasio
Andrea F
AF
D015502:Absorptiometry, Photon; D000328:Adult; D000469:Alkaline Phosphatase / Q000378:metabolism; D001827:Body Height / Q000187:drug effects; D015519:Bone Density / Q000187:drug effects; D001846:Bone Development / Q000187:drug effects*; D001842:Bone and Bones / Q000201:enzymology; D002113:Calcification, Physiologic / Q000187:drug effects; D015331:Cohort Studies; D024042:Collagen Type I / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D013006:Growth Hormone / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D019382:Human Growth Hormone / Q000172:deficiency*; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D008297:Male; D011446:Prospective Studies; D011627:Puberty / Q000502:physiology; D012727:Sex Characteristics
D024042:Collagen Type I; D019382:Human Growth Hormone; D007334:Insulin-Like Growth Factor I; D013006:Growth Hormone; D000469:Alkaline Phosphatase