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

Section of Endocrinology, Diabetes, and Nutrition (S.B.), Boston University School of Medicine, Boston Medical Center, Boston, Massachusetts 02118; Department of Medicine (F.R.S.), School of Dentistry (E.J.H.), Division of Biokinesiology (E.T.S.), and Department of Preventive Medicine (M.K., S.P.A.), University of Southern California, Los Angeles, California 90089; Merck Research Laboratories (G.J.O., A.R., F.C., R.L., J.A.T.), Rahway, New Jersey 07065; Washington University School of Medicine (K.Y., E.F.B.), St. Louis, Missouri 63110; Jean Mayer U.S. Department of Agriculture Human Nutrition Research Center on Aging (C.C.-S.), Tufts University, Boston, Massachusetts 02111

Address all correspondence and requests for reprints to: Shalender Bhasin, M.D., Professor of Medicine and Director, Boston Claude D. Pepper Older Americans Independence Center for Function Promoting Therapies, 670 Albany Street, Second Floor, Boston Medical Center, Boston, Massachusetts 02118. E-mail: bhasin{at}bu.edu.

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.