Bone anabolic effects of separate and combined therapy with growth hormone and parathyroid hormone on femoral neck in aged ovariectomized osteopenic rats

Abstract

Previous studies have demonstrated that growth hormone (GH) has a marked anabolic effect on cortical bone and parathyroid hormone (PTH) has been shown to increase cancellous bone and cortical bone markedly in ovariectomized (OVX) rats. Most previous combination therapies used the bone anabolic agent (PTH) and the anti-resorptive agents. In this study, two bone anabolic hormones, GH and PTH, were used in rebuilding bone following loss due to ovariectomy in the femoral neck, which contains both cortical and cancellous bones. Twelve-month-old female F344 rats were divided into five groups: Sham+solvent vehicle, OVX+solvent vehicle, OVX+GH (2.5 mg/kg/day), OVX+PTH (80 microg/kg/day), and OVX+GH (2.5 mg/kg/day)+PTH (80 microg/kg/day). Following surgery, the animals were left for 4 months to become osteopenic before the beginning of hormone therapies. Hormone administrations were given 5 days per week for 2 months and the animals sacrificed. The right femurs were removed and the femoral necks were examined by pQCT densitometry and by histomorphometry. There was a 12.3% decrease in total bone mineral content (BMC) (P<0.01), a 6.2% decrease in total bone mineral density (BMD) (P<0.01), a 12.8% decrease in cortical BMC (P<0.05), a 25.9% decrease in cancellous BMC (P<0.0001), a 20.4% decrease in cancellous BMD (P<0.01), and a 34.2% decrease in cancellous bone volume (BV/TV) (P<0.0001) in vehicle-treated OVX rats. Growth hormone, PTH and GH+PTH treatment increased total BMC of the OVX rats by 14.4% (P<0.01), 23.5% (P<0.0001) and 30.6% (P<0.0001), respectively; increased total BMD by 7.0% (P<0.01), 9% (P<0.001) and 14.8% (P<0.0001), respectively; increased cortical BMC by 15.9% (P<0.05), 25.5% (P<0.001) and 29% (P<0.001), respectively; increased cancellous BMC by 40.9% (P<0.0001), 61.9% (P<0.0001) and 86.8% (P<0.0001), respectively; increased cancellous BMD by 31% (P<0.001), 41.8% (P<0.0001) and 61.8% (P<0.0001), respectively; increased cancellous BV/TV by 30.6% (P<0.05), 76.3% (P<0.0001) and 94.9% (P<0.0001), respectively; and increased trabecular thickness by 26.4% (P<0.05), 41.5% (P<0.001) and 43.2% (P<0.001), respectively, compared to the age-matched vehicle-treated OVX controls. In conclusion, both GH and PTH increased cortical and cancellous bone mass at the osteopenic femoral neck. Using two techniques, it was observed that the effects of PTH were mostly more marked than those of GH. Combined therapy with GH+PTH was more effective in rebuilding cortical bone and cancellous bone than either therapy alone in the aged ovariectomized osteopenic rats, which is in line with our hypothesis.