Treatment with the Oral Growth Hormone Secretagogue MK‐677 Increases Markers of Bone Formation and Bone Resorption in Obese Young Males

The effect of 2 months of treatment with the oral growth hormone (GH) secretagogue MK‐677 on markers of bone metabolism was determined in healthy obese male subjects. This was a randomized, double‐blind, parallel, placebo‐controlled study. Twenty‐four healthy obese males, 19–49 years of age, with body mass index > 30 kg/m2 were treated with MK‐677 (25 mg/day; n = 12) or placebo (n = 12) for 8 weeks. MK‐677 increased markers of bone formation; a 23% increase in the carboxy‐terminal propeptide of type I procollagen levels and a 28% increase in procollagen III peptide levels were seen with as little as 2 weeks of MK‐677 treatment (p < 0.01 and p = 0.001 vs. placebo, respectively) while a 15% increase in serum levels of osteocalcin was not detected until 8 weeks of treatment (p < 0.01 vs. placebo). Markers of bone resorption were induced within 2 weeks of treatment with MK‐677; serum levels of the carboxy‐terminal cross‐linked telopeptide of type I collagen were increased 26% at 8 weeks (p = 0.001 vs. placebo), and urine hydroxyproline/creatinine and calcium/creatinine ratios at 8 weeks were increased by 23% (p < 0.05 vs. placebo) and 46% (p < 0.05 vs placebo), respectively. MK‐677 increased serum insulin‐like growth factor binding protein‐5 (IGFBP‐5) by 43–44% after 2–8 weeks of treatment (p < 0.01 vs. placebo). Serum IGFBP‐4 was increased by 25% after 2 weeks of treatment (p < 0.001 vs. placebo) but no significant change from baseline was observed after 8 weeks of treatment. Plasma interleukin‐6 was not significantly changed by active treatment. In conclusion, short‐term treatment of healthy obese male volunteers with the GH secretagogue MK‐677 increases markers of both bone resorption and formation. Large increases in serum levels of IGF‐I and IGFBP‐5 and a transient increase in serum IGFBP‐4 were found. Future long‐term studies are needed to investigate if prolonged treatment with MK‐677 increases bone mass.