Growth Hormone (GH) Effects on Bone and Collagen Turnover in Healthy Adults and Its Potential as a Marker of GH Abuse in Sports: A Double Blind, Placebo-Controlled Study¹

Abstract

The effects of GH on bone remodeling in healthy adults have not been systematically investigated. An analysis of these effects might provide insights into GH physiology and might yield data useful for the detection of GH doping in sports. The aim of this study was to evaluate the effects of GH administration on biochemical markers of bone and collagen turnover in healthy volunteers. Ninety-nine healthy volunteers of both sexes were enrolled in a multicenter, randomized, double blind, placebo-controlled study and assigned to receive either placebo (40 subjects) or recombinant human GH (0.1 IU/kg day in 29 subjects and 0.2 IU/kg x day in 30 subjects). The treatment duration was 28 days, followed by a 56-day wash-out period. The biochemical markers evaluated were the bone formation markers osteocalcin and C-terminal propeptide of type I procollagen, the resorption marker type I collagen telopeptide, and the soft tissue marker procollagen type III. All variables increased on days 21 and 28 in the two active treatment groups vs. levels in both the baseline (P < 0.01) and placebo (P < 0.01) groups. The increment was more pronounced in the 0.2 IU/kg-day group and remained significant on day 84 for procollagen type III (from 0.53 +/- 0.13 to 0.61 +/- 0.14 kU/L; P < 0.02) and osteocalcin (from 12.2 + 2.9 to 14.6 +/- 3.6 UG/L; P < 0.02), whereas levels of C-terminal propeptide of type I procollagen and type I collagen telopeptide declined after day 42 and were no longer significantly above baseline on day 84 (from 3.9 +/- 1.2 to 5.1 +/-1.5 microg/L and from 174 +/- 60 to 173 +/- 53 microg/L, respectively). Gender-related differences were observed in the study; females were less responsive than males to GH administration with respect to procollagen type III and type I collagen telopeptide (P < 0.001). In conclusion, exogenous GH administration affects the biochemical parameters of bone and collagen turnover in a dose- and gender-dependent manner. As GH-induced modifications of most markers, in particular procollagen type III and osteocalcin, persist after GH withdrawal, they may be suitable markers for detecting GH abuse.

Potential parameters for the detection of hGH doping

“…The hGH dosage applied in our study (0.06 IU hGH/kg BW per day) was relatively small compared to the dosage used in the "GH 2000" study and in other publications (0.1 to 0.2 IU hGH/kg BW per day) [6,7]. It was presumed that athletes usually apply doses between 0.04 and 0.2 IU/kg BW per day; this is probably true except for non-Olympic disciplines like bodybuilding etc.…”

“…The IGF-I concentrations were much more elevated in studies with higher hGH doses. This was not the case in IGFBP-3 levels which seemed mostly independent from the applied dose of hGH [5,6,7].…”

“…Previous studies showed, that females are less responsive than males to the same dose of hGH [6,7]. In order to exclude gender-related differences we confined this study to males only.…”

“…A long-term hGH treatment study with healthy subjects aiming to develop a detection method of the hGH abuse has shown that bone markers scatter across a wide range inter-individually [7]. The authors published a discriminant function including serum levels of different bone markers as well as of the soft tissue marker N-terminal propeptide of type III procollagen (PIIINP).…”

“…The authors published a discriminant function including serum levels of different bone markers as well as of the soft tissue marker N-terminal propeptide of type III procollagen (PIIINP). By using this discriminant function the authors distinguished between treated and untreated subjects with approximately 2% false positive results [7].…”