PTH (1-34) and growth hormone in prevention of disuse osteopenia and sarcopenia in rats

Abstract

Osteopenia and sarcopenia develops rapidly during disuse. The study investigated whether intermittent parathyroid hormone (1-34) (PTH) and growth hormone (GH) administered alone or in combination could prevent or mitigate disuse osteopenia and sarcopenia in rats. Disuse was achieved by injecting 4IU botulinum toxin A (BTX) into the right hindlimb musculature of 12-14-week-old female Wistar rats. Seventy-two rats were divided into six groups: 1. Baseline; 2. Ctrl; 3. BTX; 4. BTX+GH; 5. BTX+PTH; 6. BTX+PTH+GH. PTH (1-34) (60μg/kg/day) and GH (5mg/kg/day). The animals were sacrificed after 6weeks of treatment. Sarcopenia was established by histomorphometry, while the skeletal properties were determined using DXA, μCT, mechanical testing, and dynamic bone histomorphometry. Disuse resulted in lower muscle mass (-63%, p<0.05), trabecular BV/TV (-28%, p<0.05), Tb.Th (-11%, p<0.05), lower diaphyseal cortical thickness (-10%, p<0.001), and lower bone strength at the distal femoral metaphysis (-27%, p<0.001) compared to Ctrl animals. PTH fully counteracted the immobilization-induced lower BV/TV, Tb.Th, and distal femoral metaphyseal strength. GH increased muscle mass (+17%, p<0.05) compared to BTX, but did not prevent the immobilization-induced loss of bone strength, BV/TV, and cortical trabecular thickness. Combination of PTH and GH increased distal femoral metaphyseal bone strength (+45%, p<0.001), BV/TV (+50%, p<0.05), Tb.Th (+40%, p<0.05), and whole femoral aBMD (+15%, p<0.001) compared to BTX and muscle mass (+21%, p<0.05) compared to BTX+PTH. In conclusion, PTH and GH in combination is more efficient at preventing the disuse-related deterioration of bone strength, density, and micro-architecture than either PTH or GH given as monotherapy. Furthermore, GH, either alone or in combination with PTH, attenuated disuse-induced loss of muscle mass. The combination of PTH and GH resulted in a more effective treatment than PTH and GH as monotherapy.

Keywords: Biomechanics; GH; Histomorphometry; Immobilization; MicroCT; PTH.