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

Authors: BHASIN, SHALENDER - Boston University Medical Center; HE, JIAXIU - University Of Southern California; KAWAKUBO, MIWA - University Of Southern California; SCHROEDER, TODD - University Of Southern California; YARASHESKI, KEVIN - Washington University School Of Medicine; OPITECK, GREGORY - Merck Research Laboratories; REICIN, ALISE - Merck Research Laboratories; CHEN, FABIAN - Merck Research Laboratories; LAM, RAYMOND - Merck Research Laboratories; TSOU, JEFFREY - Merck Research Laboratories; CASTANEDA-SCEPPA, CARMEN - Jean Mayer Human Nutrition Research Center On Aging At Tufts University; BINDER, ELLEN - Washington University School Of Medicine; AZEN, STANLEY - University Of Southern California; SATTLER, FRED - University Of Southern California

Submitted to: Journal of Clinical Endocrinology and Metabolism
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 8/21/2009
Publication Date: 1/1/2009
Citation: Bhasin, S., He, J.E., Kawakubo, M., Schroeder, T.E., Yarasheski, K., Opiteck, G.J., Reicin, A., Chen, F., Lam, R., Tsou, J.A., Castaneda-Sceppa, C., Binder, E.F., Azen, S.P., Sattler, F.R. 2009. N-terminal propeptide of type III procollagen as a biomarker of anabolic response to recombinant human GH and testosterone. Journal of Clinical Endocrinology and Metabolism. 94(11):4224-4233.

Interpretive Summary: The purpose of this study was to examine biomarkers (compounds in the blood) that predict the muscle’s response to anabolic therapies (treatments that increase muscle mass) like testosterone and growth hormone. We investigated N-terminal propeptide of type III procollagen (P3NP) as a biomarker of lean body mass and muscle strength gains in response to testosterone and growth hormone. Community-dwelling older men received a neurohormone plus testosterone gel and some testosterone gel plus recombinant human growth hormone daily. P3NP levels, muscle mass and strength were measured throughout the study. P3NP levels were higher at wk 4 than baseline 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 growth hormone. Increases in P3NP from baseline to wk 4 and 16 were significantly associated with gains in lean body mass. Early changes in serum P3NP levels were associated with subsequent changes in lean body mass during testosterone and growth hormone administration. In conclusion, serum P3NP may be a useful biomarker of muscle growth.

Technical Abstract: 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 _g 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 and30%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 P3NPmaybe a useful early predictive biomarker rof anabolic response to GH and testosterone.