Growth hormone releasing hormone (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 BID over 12 weeks in 31 HIV-infected men with abdominal fat accumulation (age 46 ± 1 yr, BMI 26.2 ± 0.6 kg/m²) in a randomized, double-blind, placebo controlled study. We have 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, thirty-two percent (n = 10) of our subjects demonstrated a bone density Z score < -1.0 SD and -2.5 SD and 3% (n = 1) demonstrated a Z score of < -2.5 SD. IGF-I correlated with NTx (r=0.49, P=0.005) and tended to correlate with 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 BCE, GHRH vs. placebo, P=0.07). Of the bone formation markers, PINP increased (14.6 ± 9 vs. -6.8 ± 3.1 µg/L, 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.