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


METHODS
Community-dwelling older men received GnRH agonist plus 5 or 10 g testosterone gel plus 0, 3, or 5 microg 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.


CONCLUSIONS
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.
Bhasin
Shalender
S
Section of Endocrinology, Diabetes, and Nutrition, Boston University School of Medicine, Boston Medical Center, Boston, Massachusetts 02118, USA. bhasin@bu.edu
He
E Jiaxiu
EJ
Kawakubo
Miwa
M
Schroeder
E Todd
ET
Yarasheski
Kevin
K
Opiteck
Gregory J
GJ
Reicin
Alise
A
Chen
Fabian
F
Lam
Raymond
R
Tsou
Jeffrey A
JA
Castaneda-Sceppa
Carmen
C
Binder
Ellen F
EF
Azen
Stanley P
SP
Sattler
Fred R
FR
D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers / Q000097:blood*; D001835:Body Weight; D013006:Growth Hormone / Q000627:therapeutic use*; D006400:Hematocrit; D019382:Human Growth Hormone / Q000097:blood; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D016729:Leuprolide / Q000627:therapeutic use; D008297:Male; D053580:Muscle Strength / Q000502:physiology*; D010446:Peptide Fragments / Q000097:blood*; D011347:Procollagen / Q000097:blood*; D011994:Recombinant Proteins / Q000627:therapeutic use*; D012044:Regression Analysis; D013739:Testosterone / Q000627:therapeutic use*; D013997:Time Factors
D015415:Biomarkers; D010446:Peptide Fragments; D011347:Procollagen; D011994:Recombinant Proteins; C041876:procollagen Type III-N-terminal peptide; D019382:Human Growth Hormone; D013739:Testosterone; D007334:Insulin-Like Growth Factor I; D013006:Growth Hormone; D016729:Leuprolide