title: Treatment with the oral growth hormone secretagogue MK-677 increases markers of bone formation and bone resorption in obese young males.
abstract: 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-1 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.
authors.affiliation: Research Centre for Endocrinology and Metabolism, Sahlgrenska University Hospital, Göteborg, Sweden.
authors.forename: J
authors.initials: J
authors.lastname: Svensson
authors.forename: C
authors.initials: C
authors.lastname: Ohlsson
authors.forename: J O
authors.initials: JO
authors.lastname: Jansson
authors.forename: G
authors.initials: G
authors.lastname: Murphy
authors.forename: D
authors.initials: D
authors.lastname: Wyss
authors.forename: D
authors.initials: D
authors.lastname: Krupa
authors.forename: K
authors.initials: K
authors.lastname: Cerchio
authors.forename: W
authors.initials: W
authors.lastname: Polvino
authors.forename: B
authors.initials: B
authors.lastname: Gertz
authors.forename: D
authors.initials: D
authors.lastname: Baylink
authors.forename: S
authors.initials: S
authors.lastname: Mohan
authors.forename: B A
authors.initials: BA
authors.lastname: Bengtsson
mesh_terms: D000284:Administration, Oral; D000328:Adult; D015415:Biomarkers / Q000097:blood; D015519:Bone Density / Q000187:drug effects; D016723:Bone Remodeling / Q000187:drug effects*; D003094:Collagen / Q000097:blood; D024042:Collagen Type I; D004311:Double-Blind Method; D006801:Humans; D007211:Indoles / Q000008:administration & dosage / Q000627:therapeutic use*; D018974:Insulin-Like Growth Factor Binding Protein 4 / Q000097:blood*; D018975:Insulin-Like Growth Factor Binding Protein 5 / Q000097:blood*; D007378:Interleukins / Q000097:blood; D008297:Male; D008875:Middle Aged; D009765:Obesity / Q000097:blood / Q000188:drug therapy*; D015675:Osteocalcin / Q000097:blood; D010446:Peptide Fragments / Q000097:blood; D010455:Peptides / Q000097:blood; D011347:Procollagen / Q000097:blood; D013141:Spiro Compounds / Q000008:administration & dosage / Q000627:therapeutic use*
chemical_list: D015415:Biomarkers; D024042:Collagen Type I; D007211:Indoles; D018974:Insulin-Like Growth Factor Binding Protein 4; D018975:Insulin-Like Growth Factor Binding Protein 5; D007378:Interleukins; D010446:Peptide Fragments; D010455:Peptides; D011347:Procollagen; D013141:Spiro Compounds; C052929:collagen type I trimeric cross-linked peptide; C041876:procollagen Type III-N-terminal peptide; C042813:procollagen type I carboxy terminal peptide; D015675:Osteocalcin; D003094:Collagen; C094817:ibutamoren mesylate