Effect of parathyroid hormone on healing in osteoporotic fractures via a phospholipase C-independent pathway

Objective This study was performed to investigate the effect of parathyroid hormone (PTH) on healing in osteoporotic fractures via a phospholipase C (PLC)-independent pathway and explore the mechanism of PTH-mediated bone formation. Methods Ninety-six 12-week-old C57BL/6J female mice underwent bilateral ovariectomy. One month later, the lower third of the femur was fractured and the mice were treated using saline, PTH(1-28), PTH(1-34), zoledronic acid (ZA), PTH(1-28)+ZA, and PTH(1-34)+ZA. The mice were killed at weeks 2 and 4 in each group. Biomechanical testing and micro-computed tomography were performed. Results The formation and strength of the callus increased in all but the saline group. The mice treated with PTH(1-34) showed a significantly higher ultimate bending force, bending rigidity, bone mineral density, percent bone volume, and trabecular thickness than those treated with PTH(1-28). The PTH(1-34)+ZA group demonstrated the greatest improvements in the ultimate bending force, bending rigidity, bone mineral density, and relative bone volume. Conclusions PTH can promote fracture healing and callus hardness in ovariectomized mice by increasing callus formation and reconstructing trabecular bone via a PLC-independent pathway. PTH combined with ZA has a cumulative effect on the healing of fractures in ovariectomized mice.