Effects of Growth Hormone-Releasing Hormone on Bone Turnover in Human Immunodeficiency Virus-Infected Men with Fat Accumulation

Abstract

GHRH is a potentially appealing strategy to simultaneously improve fat distribution and increase bone turnover in HIV-infected patients. We investigated the effects of GHRH (1 mg sc twice a day over 12 wk) in 31 HIV-infected men with abdominal fat accumulation (age 46 +/- 1 yr, body mass index 26.2 +/- 0.6 kg/m2) in a randomized, double-blind, placebo-controlled study. We previously reported significant effects of GHRH on IGF-I and truncal fat. In this study, we assessed whether GHRH increased markers of bone turnover. At baseline, 32% of our subjects (n = 10) demonstrated a bone density Z score less than -1.0 sd and greater than or equal to -2.5 sd, and 3% (n = 1) demonstrated a Z score of less than -2.5 sd. IGF-I correlated with N-terminal telopeptide (NTx) (r = 0.49, P = 0.005) and tended to correlate with C-terminal telopeptide (CTx) (r = 0.35, P = 0.06) at baseline. Of the bone resorption markers, CTx increased significantly (0.16 +/- 0.07 vs. -0.03 +/- 0.03 ng/ml, GHRH vs. placebo, P = 0.02), and NTx tended to increase in response to GHRH (2.8 +/- 1.4 vs. -0.5 +/- 1.0 nm bone collagen equivalent, GHRH vs. placebo, P = 0.07). Of the bone formation markers, N-terminal propeptide of type 1 procollagen increased (14.6 +/- 9 vs. -6.8 +/- 3.1 microg/liter, GHRH vs. placebo, P = 0.03) and osteocalcin tended to increase (8.4 +/- 3.0 vs. 2.0 +/- 1.6 ng/ml, GHRH vs. placebo, P = 0.06) in response to GHRH. The calciotropic hormones, calcium and phosphorus, did not change significantly. The change in IGF-I correlated with the change in NTx (r = 0.45, P = 0.02), CTx (r = 0.38, P = 0.05), and osteocalcin (r = 0.55, P = 0.002). GHRH improves fat distribution and bone metabolism in men with HIV-related fat accumulation. Long-term studies are needed to determine whether the stimulatory effects of GHRH on bone turnover will translate into increased bone density in this population.