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

Abstract

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.

Adult GH deficiency throughout lifetime

“…These recommendations are based on studies by Drake et al that showed that cessation of GH replacement in adolescents at the completion of linear growth is associated with negligible further gain in median total body bone mineral content (BMC) over 1 year (C2.4%, PZ0.5), whereas adolescents who continue to receive GH replacement continue to increase their median BMC (C6.0%, P!0.001) (56). Shalet et al confirmed these findings with a 2-year, multi-centre, randomised, non-blinded study comparing an adult GH replacement dose (12.5 mg/kg per day) to a paediatric GH replacement dose (25 mg/kg per day) and to no GH replacement in adolescents who had achieved final height; in addition to confirming the adverse effect of non-treatment with GH, this study demonstrated no additional benefit in BMC from the higher GH dose (57). Interestingly, lumbar spine was the area that accrued the most additional BMC with GH therapy, an area particularly at risk from osteoporotic fractures.…”

“…However, mild childhood-onset GHD (peak GH 3-11.8 mg/l on provocation testing) appears to be associated with normal BMD (12) and improvements in BMC have been seen with what could be considered sub-therapeutic IGF1 levels (57). These observations suggest that modest improvements in GH status may be adequate to improve bone outcomes in younger patients.…”

EXTENSIVE EXPERTISE IN ENDOCRINOLOGY: UK stance on adult GH replacement: the economist vs the endocrinologist

“…The bone abnormalities described in the adults with CO GHD are consistent with the studies of GH deficient post-pubertal patients (mean age 19 years) in whom the acquisition of peak bone mass is sub-optimal if they remain off GH replacement following treatment in childhood (33). It should be emphasised however that the most persuasive evidence that GH replacement significantly increases total BMC in this situation was obtained in severely GH deficient subjects defined by an IGF1 level below the first centile (33).…”

“…It should be emphasised however that the most persuasive evidence that GH replacement significantly increases total BMC in this situation was obtained in severely GH deficient subjects defined by an IGF1 level below the first centile (33).…”

Erişkinlerde büyüme hormonu tedavisi

“…Bilinmesi gereken önemli bir ayrıntı da tedavinin 12. ayından önce yapılan kemik mineral dansitesinde (KMD) azalma görülebileceğidir [20]. Bu nedenle BH tedavisinin 18-24. ayında KMD ölçülmelidir [21]. BH eksikliği olan çocuklarda erişkin boya ulaşılsa bile iskelet ve kas maturasyonunun maksimum olması için geçiş dönemi boyunca BH tedavisine devam edilmesi önerilmektedir [6].…”