Relationship between growth hormone in vivo bioactivity, the insulin-like growth factor-I system and bone mineral density in young, physically fit men and women

Context: Bone mineral density (BMD) is influenced by growth factors, such as growth hormone (GH) and insulin-like growth factor-I (IGF-I). The in vivo bioassay for GH (bioGH) provides a more physiologically relevant measurement than an in vitro immunoassay, since bioGH is quantified on a biological outcome. Objective: To determine if bioGH and components of the IGF-I system were associated with BMD in age-matched men (M; n = 41, 19.1 ± 0.2 year, 70 ± 3 kg, 163 ± 25 cm) and women (W; n = 39, 18.6 ± 0.3 year, 66 ± 3 kg, 141 ± 15 cm). Design: Blood was analyzed for growth-related hormones [bioGH, immunoreactive growth hormone (iGH), IGF-I and associated binding proteins], and BMD was measured by pDXA, pQCT, and central DXA (spine, hip). For the bioGH assay, hypophysectomizied female Sprague-Dawley rats were injected with a s.c. bolus of either a GH standard or unknown (each subject's plasma) in four daily injections. The tibia was then examined for epiphyseal growth plate width from which bioGH concentrations were extrapolated. Results: M had greater (P < 0.05) calcaneal BMD when measured by pDXA (M: 1.27 ± 0.02; W: 1.14 ± 0.02 g/cm²), while pQCT-assessed BMD at the tibia was not different (M: 777 ± 16; W: 799 ± 16 g/cm²). bioGH was similar between M (5388 ± 800 μg/L) and W (4282 ± 643 μg/L) and was not correlated with BMD. The only BMD-related biomarkers in women were acid-labile subunit (ALS; r = 0.40) and IGFBP-3 (r = 0.42) with DXA-measured spine and femoral neck BMD, and ALS (r = 0.47) with pQCT-assessed tibial BMD and cortical thickness, respectively. Conclusion: Although bioGH was not associated with BMD, IGF-I and associated binding proteins (IGFBP-3 and ALS) emerged as correlates in W only.