Effects of separate and combined therapy with growth hormone and parathyroid hormone on lumbar vertebral bone 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 markedly and cortical bone to some extent in ovariectomized (ovx) rats. Combined therapies mostly focused on combining a bone anabolic agent with an antiresorptive agent. The following study was carried out to examine the efficacy of combined therapy with GH and PTH, two bone anabolic agents in rebuilding bone after loss due to ovariectomy in lumbar vertebrae, which contain 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 μg/kg/day), and ovx + GH (2.5 mg/kg/day) + PTH (80 μg/kg/day). After surgery, animals were left for 4 months to become osteopenic before the beginning of therapy. Hormone administrations were given 5 days per week for 2 months and the animals were killed. The L3 vertebra was removed and examined by pQCT densitometry and by histomorphometry. Compared with age-matched, sham-operated controls, there was a 21% decrease in total bone mineral content (BMC) ( p < 0.0001), 17.0% decrease in total bone mineral density (BMD) ( p < 0.0001), 25.4% decrease in cortical BMC ( p < 0.001), 3.1% decrease in cortical BMD ( p < 0.05), 50.5% decrease in cancellous BMC ( p < 0.01), 47.3% decrease in cancellous BMD ( p < 0.01), and 14.5% decrease in cancellous bone volume (BV/TV) ( p < 0.05) in the vehicle-treated ovx rats. Compared with age-matched, vehicle-treated ovx controls, GH, PTH, and GH + PTH increased total BMC by 22.8% ( p < 0.001), 32.4% ( p < 0.0001), and 72.7% ( p < 0.0001), respectively; total BMD by 9.7% ( p > 0.05), 22.6% ( p < 0.001), and 38.8% ( p < 0.0001), respectively; cortical BMC by 28.8% ( p < 0.01), 50.8% ( p < 0.0001), and 98.4% ( p < 0.0001), respectively; and cortical BMD by 4.5% ( p < 0.01), 2.9% ( p < 0.05), and 6.3% ( p < 0.0001), respectively. PTH and GH + PTH significantly increased cancellous BMC by 95.3% ( p < 0.01) and 255.8% ( p < 0.0001), respectively; cancellous BMD by 77.6% ( p < 0.05) and 181% ( p < 0.0001), respectively; cancellous BV/TV by 38.6% ( p < 0.0001) and 55.9% ( p < 0.0001), respectively; and trabecular thickness by 48% ( p < 0.0001) and 68.3% ( p < 0.0001), respectively. Note that GH by itself had no significant effect on vertebral cancellous BMC, cancellous BMD, and cancellous BV/TV. In conclusion, the effect of PTH was mostly more marked than that of GH. GH acted mainly by increasing cortical bone with less effect on cancellous bone, while PTH acted by increasing both cortical and cancellous bones. Combined therapy with GH and PTH was more effective in rebuilding bone after ovariectomy than either therapy alone. The effects of combined therapy with GH and PTH were additive in vertebral bone in the aged osteopenic rats.