Svensson J, Lall S, Dickson S L, Bengtsson B A, Rømer J, Ahnfelt-Rønne I, Ohlsson C, Jansson J O
Research Centre for Endocrinology and Metabolism, Sahlgrenska University Hospital, Göteborg, Sweden.
J Endocrinol. 2000 Jun;165(3):569-77. doi: 10.1677/joe.0.1650569.
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 secretagogues (GHSs), increases serum concentrations of biochemical markers of bone formation and bone resorption. The aim of the present study was to investigate 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 vehicle administered continuously s.c. via osmotic minipumps for 12 weeks. The animals were followed in vivo by dual X-ray absorptiometry (DXA) measurements 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 use of Archimedes' principle and by determinations of ash weights. All treatments increased body weight and total tibial and vertebral BMC measured by DXA in vivo compared with vehicle-treated controls. However, total BMC corrected for the increase in body weight (total BMC:body weight ratio) was unaffected. Tibial area bone mineral density (BMD, BMC/area) was increased, but total and vertebral area BMDs were unchanged. The pQCT measurements in vitro revealed that the increase in the cortical BMC was due to an increased cross-sectional bone area, whereas the cortical volumetric BMD was unchanged. Femur and vertebra L6 volumes were increased but no effect was seen on the volumetric BMDs as measured by Archimedes' principle. Ash weight was increased by all treatments, but the mineral concentration was unchanged. We conclude that treatment of adult female rats with the GHSs ipamorelin and GHRP-6 increases BMC as measured by DXA in vivo. The results of in vitro measurements using pQCT and Archimedes' principle, in addition to ash weight determinations, show that the increases in cortical and total BMC were due to an increased growth of the bones with increased bone dimensions, whereas the volumetric BMD was unchanged.
生长激素（GH）对正常的骨重塑至关重要。最近一项临床研究表明，一类生长激素促分泌素（GHSs）的成员MK-677可提高骨形成和骨吸收生化标志物的血清浓度。本研究的目的是调查GHSs——伊帕莫林（IPA）和生长激素释放肽-6（GHRP-6）——是否能增加成年雌性幼鼠的骨矿物质含量（BMC）。13周龄的雌性斯普拉格-道利大鼠连续12周通过皮下渗透微型泵给予IPA（0.5毫克/千克/天；n = 7）、GHRP-6（0.5毫克/千克/天；n = 8）、GH（3.5毫克/千克/天；n = 7）或赋形剂。每4周通过双能X线吸收测定法（DXA）对动物进行体内跟踪测量。动物处死后，通过骨干中段外周定量计算机断层扫描（pQCT）对股骨进行体外分析。此后，使用阿基米德原理并通过测定骨灰重量对切除的股骨和L6椎体进行分析。与赋形剂处理的对照组相比，所有处理均增加了通过DXA在体内测量的体重以及胫骨和椎体的总BMC。然而，校正体重增加后的总BMC（总BMC：体重比）未受影响。胫骨区域骨矿物质密度（BMD，BMC/面积）增加，但总BMD和椎体区域BMD未改变。体外pQCT测量显示，皮质BMC的增加是由于骨横截面积增加，而皮质体积BMD未改变。股骨和L6椎体体积增加，但通过阿基米德原理测量的体积BMD未见影响。所有处理均增加了骨灰重量，但矿物质浓度未改变。我们得出结论，用GHSs伊帕莫林和GHRP-6治疗成年雌性大鼠可增加通过DXA在体内测量的BMC。使用pQCT、阿基米德原理以及骨灰重量测定进行的体外测量结果表明，皮质和总BMC的增加是由于骨骼生长增加以及骨尺寸增大，而体积BMD未改变。
