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

To optimize osteoporosis therapy with the parathyroid hormone fragment teriparatide (PTH1-34), we sought to determine whether strontium (Sr) could potentiate bone anabolic action of intermittent PTH1-34 in ovariectomized rats. Female rats were either Sham-operated or ovariectomized (Ovx) at 6 months of age. 8 weeks after operations, Ovx rats received either vehicle solutions, 625 mg/kg/day Sr (5 days per week), 8 µg/kg/day PTH1-34 (5 days per week), or both combined treatments for 8 weeks. PTH1-34 treatment totally reversed the deleterious effects of Ovx on trabecular bone microarchitecture, material properties and strength, while Sr had no significant beneficial effects. Co-treatment with Sr and PTH1-34 further increased trabecular thickness, bone material properties (higher force and working energy) and trabecular bone strength in comparison to PTH1-34 treatment alone. Whereas PTH1-34 treatment enhanced cortical bone volume and thickness, co-treatment with Sr and PTH1-34 further elevated cortical thickness and demonstrated a significant beneficial effect on cortical bone strength. Stimulations of osteoblast cultures with Sr, PTH1-34 or both agents increased Rankl expression and decreased that of Opg , which was consistent with elevated urinary deoxypyridinoline levels reflecting higher bone resorption in Ovx rats receiving the same treatments. Finally, Sr and PTH1-34 alone augmented Igf1 and Alpl expressions in osteoblast cultures, whereas co-stimulation with both agents further enhanced those gene expressions. To conclude, Sr treatment potentiates beneficial effects of intermittent PTH1-34 treatment on bone volume and strength by improving bone material properties and by synergistically stimulating bone formation.