Strontium treatment potentiates bone anabolic action of intermittent PTH in ovariectomized rats

Abstract

To optimize osteoporosis therapy with the parathyroid hormone fragment teriparatide (PTH1-34), we sought to determine whether strontium (Sr) could potentiate the bone anabolic action of intermittent PTH1-34 in ovariectomized rats. Female rats were either Sham-operated or ovariectomized (Ovx) at 6 months of age. Eight weeks after surgery, Ovx rats received either vehicle solutions, 625 mg/kg/day Sr (5 days per week), 8 {micro}g/kg/day PTH1-34 (5 days per week), or the combined treatments for 8 weeks. PTH1-34 reversed Ovx-induced deterioration of trabecular microarchitecture, apparent volumetric bone mineral density (vBMD), and strength, whereas Sr alone increased tissue-level vBMD without significantly affecting trabecular bone mass. Co-treatment with Sr and PTH1-34 further increased trabecular thickness, apparent and tissue-level vBMD, bone material properties (force and working energy), and trabecular bone strength compared with PTH1-34 alone. In cortical bone, PTH1-34 increased bone volume, cortical thickness, and apparent vBMD, while co-treatment further enhanced cortical thickness and apparent vBMD, maintained the Sr-induced increase in tissue-level vBMD, and significantly improved bone strength. In primary osteoblast cultures, Sr and PTH1-34, administered either alone or in combination, increased Rankl and decreased Opg expression, consistent with the elevated urinary levels of the bone resorption marker deoxypyridinoline in vivo. Sr or PTH1-34 alone stimulated Igf1 and Alpl expression, whereas co-stimulation further enhanced these osteogenic markers. In conclusion, combining Sr with PTH1-34 integrates the osteoanabolic effects of PTH1-34 on bone mass with the mineral-level effects of Sr on bone material properties, leading to synergistic stimulation of bone formation and superior improvements in bone quality and strength.