N-Terminal Propeptide of Type III Procollagen as a Biomarker of Anabolic Response to Recombinant Human GH and Testosterone

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.LBMandappendicularskeletalmusclemass(ASM)weremeasuredbydual-energyx-rayabsorptiometry. Results:One hundred twelve men completed treatment; 106 underwent serum P3NP measurements. P3NP levels were higher at wk 4 than baseline (6.61 Ϯ 2.14 vs. 4.51 Ϯ 1.05, P Ͻ 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 ϭ 0.26, P ϭ 0.007; r ϭ 0.53, P Ͻ 0.001) and ASM (r ϭ 0.17, P ϭ 0.07; r ϭ 0.40, P Ͻ 0.0001). Importantly, for participants receiving only testosterone, P3NP increases at wk 4 and 16 were related to muscle strength gains (r ϭ 0.20, P ϭ 0.056 and r ϭ 0.36, P ϭ 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. The past decade has witnessed substantial pharmaceutical and academic investment in the development of function promoting anabolic therapies that improve physical function and health-related outcomes (1). The leading function promoting anabolic molecules that are under development, androgens, myostatin inhibitors, and GH, are potential promyogenic agents that are expected to improve physical function primarily by increasing skeletal muscle mass. Considering the enormous resources required for conducting large efficacy trials, serum biomar-