Biochemical markers of bone turnover in tibia fracture patients randomly assigned to growth hormone (GH) or placebo injections: Implications for detection of GH abuse

Growth Horm IGF Res. 2011 Dec;21(6):331-5. doi: 10.1016/j.ghir.2011.08.003. Epub 2011 Oct 1.

Abstract

Context: It has been argued that increased levels of bone remodelling markers are not suitable indicators of GH abuse, as bone injuries per se increase the expression levels of these markers.

Objective: To investigate the impact of a recovering tibia fracture on circulating bone markers in subjects receiving placebo or GH treatment.

Design and setting: A randomised, double-blind, placebo-controlled trial of up to 16weeks GH treatment, followed by a 16-week washout.

Participants and intervention: Subjects (406 adult males and females) with a tibia fracture were randomly allocated within three days after surgery, to either placebo or GH treatment (15, 30 or 60μg/kg daily) until fracture healing or 16weeks after treatment initiation.

Main outcome measures: IGF-I, serum C-terminal telopeptide of type I collagen (CTX), osteocalcin (OST) and bone-specific alkaline phosphatase (BAP) were measured during and after treatment.

Results: Dose-dependent increases were observed in groups receiving GH, and mean levels in the highest GH dose group peaked at eight (IGF-I, CTX) or 12weeks (OST) after treatment initiation. Statistically significant differences between GH treatment and placebo were seen for IGF-I, CTX and OST in all GH dose groups throughout the treatment period, and persisted until eight (CTX) or 12 (OST) weeks after cessation of treatment.

Conclusion: IGF-I, CTX and OST are suitable candidate markers of prolonged, illicit administration of GH. Furthermore, CTX and OST have potentials to serve as markers also after cessation of GH administration.

Trial registration: ClinicalTrials.gov NCT00254514.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Alkaline Phosphatase / blood
  • Biomarkers / blood*
  • Bone Remodeling / drug effects*
  • Collagen Type I / blood
  • Doping in Sports*
  • Double-Blind Method
  • Female
  • Human Growth Hormone / administration & dosage*
  • Humans
  • Insulin-Like Growth Factor I / metabolism
  • Male
  • Middle Aged
  • Osteocalcin / blood
  • Peptides / blood
  • Tibial Fractures / blood
  • Tibial Fractures / diagnosis*
  • Young Adult

Substances

  • Biomarkers
  • Collagen Type I
  • Peptides
  • collagen type I trimeric cross-linked peptide
  • Osteocalcin
  • Human Growth Hormone
  • Insulin-Like Growth Factor I
  • Alkaline Phosphatase

Associated data

  • ClinicalTrials.gov/NCT00254514