Technetium-99 conjugated with methylene diphosphonate ameliorates ovariectomy-induced osteoporotic phenotype without causing osteonecrosis in the jaw

Technetium-99 conjugated with methylene diphosphonate (⁹⁹Tc-MDP) is a novel bisphosphonate derivative without radioactivity and has been successfully used to treat arthritis in China for years. Since bisphosphonate therapy has the potential to induce bisphosphonaterelated osteonecrosis of the jaw (BRONJ), we examined whether ⁹⁹Tc-MDP represents a new class of bisphosphonate for antiresorptive therapy to ameliorate estrogen deficiency-induced bone resorption with less risk of causing BRONJ. We showed that ⁹⁹Tc-MDP-treated, ovariectomized (OVX) mice had significantly improved bone mineral density and trabecular bone volume in comparison to the untreated OVX group by inhibiting osteoclasts and enhancing osteogenic differentiation of bone marrow mesenchymal stem cells. To determine the potential of inducing BRONJ, ⁹⁹Tc-MDP/dexamethasone (Dex) or zoledronate/Dex was administered into C57BL/6J mice via the tail vein, followed by extraction of maxillary first molars. Interestingly, ⁹⁹Tc-MDP treatment showed less risk to induce osteonecrosis in the maxillary bones compared to zoledronate treatment group, partially because ⁹⁹Tc-MDP neither suppressed adaptive regulatory T cells nor activated the inflammatory T-helper-producing interleukin- 17 cells. Taken together, our findings demonstrate that ⁹⁹Tc-MDP therapy may be a promising approach in the treatment of osteoporosis with less risk of causing BRONJ.