The GH secretagogues ipamorelin and GH-releasing peptide-6 increase bone mineral content in adult female rats

Growth hormone (GH) is of importance for normal bone remodelling. A recent clinical study demonstrated that MK-677, a member of a class of GH secretag ogues (GHSs), increases serum concentrations of biochemical markers of bone formation and bone resorption. The aim of the present study was to investi gate whether the GHSs, ipamorelin (IPA) and GH-releasing peptide-6 (GHRP-6) , increase bone mineral content (BMC) in young adult female rats. Thirteen- week-old female Sprague-Dawley rats were given IPA (0.5 mg/kg per day; n = 7), GHRP-6 (0.5 mg/kg per day; n = 8), GH (3.5 mg/kg per day; n = 7), or ve hicle administered continuously s.c. via osmotic minipumps for 12 weeks. Th e animals were followed in vivo by dual X-ray absorptiometry (DXA) measurem ents every 4th week. After the animals were killed, femurs were analysed in vitro by mid-diaphyseal peripheral quantitative computed tomography (pQCT) scans. After this, excised femurs and vertebrae L6 were analysed by the us e of Archimedes' principle and by determinations of ash weights. All treatm ents increased body weight and total tibial and vertebral BMC measured by D XA in vivo compared with vehicle-treated controls. However, total BMC corre cted for the increase in body weight (total BMC:body weight ratio) was unaf fected. Tibial area bone mineral density (BMD, BMC/area) was increased, but total and vertebral area BMDs were unchanged. The pQCT measurements in vit ro revealed that the increase in the cortical BMC was due to an increased c ross-sectional bone area, whereas the cortical volumetric BMD was unchanged . Femur and vertebra L6 volumes were increased but no effect was seen on th e volumetric BMDs as measured by Archimedes' principle. Ash weight was incr eased by all treatments, but the mineral concentration was unchanged. We co nclude that treatment of adult female rats with the GHSs ipamorelin and GHR P-6 increases BMC as measured by DXA in viva. The results of in vitro measu rements using pQCT and Archimedes' principle, in addition to ash weight det erminations, show that the increases in cortical and total BMC were due to an increased growth of the bones with increased bone dimensions, whereas th e volumetric BMD was unchanged.