N-terminal propeptide of Type III procollagen as a biomarker of anabolic response to recombinant human GH and testosterone

N-terminal propeptide of Type III procollagen as a biomarker of anabolic response to recombinant human GH and testosterone
Bhasin, Shalender, 1953- (Author)
He, E. Jiaxiu (Author)
Kawabuko, Miwa (Author)
Schroeder, E. Todd (Author)
Yarasheski, Kevin (Author)
Opitek, Gregory J. (Author)
Reicin, Alise (Author)
Chen, Fabian (Author)
Lam, Raymond (Author)
Tsou, Jeffrey A. (Author)
Castaneda-Sceppa, Carmen (Author)
Binder, Ellen F. (Author)
Azen, Stanley P. (Author)
Sattler, Fred R. (Author)
The Endocrine Society
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Context: Biomarkers that predict musculoskeletal response to anabolic therapies should expedite drug development. During collagen synthesis in soft lean tissue, N-terminal propeptide of type III procollagen (P3NP) is released into circulation. We investigated P3NP as a biomarker of lean body mass (LBM) and muscle strength gains in response to testosterone and GH.

Design: Community-dwelling older men received GnRH agonist plus 5 or 10 g testosterone gel plus 0, 3, or 5 μg recombinant human GH daily. P3NP levels were measured at baseline and wk 4, 8, 12, and 16. LBM and appendicular skeletal muscle mass (ASM) were measured by dual-energy x-ray absorptiometry.

Results: One hundred twelve men completed treatment; 106 underwent serum P3NP measurements. P3NP levels were higher at wk 4 than baseline (6.61 ± 2.14 vs. 4.51 ± 1.05, P < 0.0001) and reached plateau by wk 4 in men receiving testosterone alone. However, wk 8 P3NP levels were higher than wk 4 levels in men receiving testosterone plus recombinant human GH. Increases in P3NP from baseline to wk 4 and 16 were significantly associated with gains in LBM (r = 0.26, P = 0.007; r = 0.53, P < 0.001) and ASM (r = 0.17, P = 0.07; r = 0.40, P < 0.0001). Importantly, for participants receiving only testosterone, P3NP increases at wk 4 and 16 were related to muscle strength gains (r = 0.20, P = 0.056 and r = 0.36, P = 0.04). In stepwise regression, change in P3NP explained 28 and 30% of the change in ASM and LBM, respectively, whereas change in testosterone but not IGF-I and age provided only small improvements in the models.

Conclusion: Early changes in serum P3NP levels are associated with subsequent changes in LBM and ASM during testosterone and GH administration. Serum P3NP may be a useful early predictive biomarker of anabolic response to GH and testosterone.

Originally published in the Journal of Clinical Endocrinology & Metabolism v.94 no.11 (November 1, 2009), pp.4224-4233. DOI: 10.1210/jc.2009-1434

Subjects and keywords:
Biochemical markers
Musculoskeletal system - Metabolism
Recombinant human somatotropin
anabolic therapy
type III procollagen (P3NP)
lean body mass (LBM)
quantitative study
Endocrinology, Diabetes, and Metabolism