Departmental Papers (Dental)

Document Type

Journal Article

Date of this Version


Publication Source

Calcified Tissue International








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 bisphosphonate-associated osteonecrosis of the jaw (BRONJ), we examine whether 99Tc-MDP represents a new class of bisphosphonate for anti-resorptive 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 (BMD) and trabecular bone volume in comparison to the untreated OVX group by inhibiting osteoclasts and enhancing osteogenic differentiation of bone marrow mesenchymal stem cells (BMMSCs). To determine the potential of inducing BRONJ, 99Tc-MDP/dexamethasone (Dex) or zoledronate/Dex were 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 (Tregs) nor activated the inflammatory T-helper-producing interleukin 17 cells (Th17). 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.

Copyright/Permission Statement

This is a post-peer-review, pre-copyedited version of an article published in [Calcified Tissue International]. The final authenticated version is available online at:


At the time of publication, author Chider Chen was affiliated with the University of Southern California. Currently, he is a faculty member at the School of Dental Medicine at the University of Pennsylvania.


Tc-MDP, bisphosphonate-related osteonecrosis of the jaw, ovariectomized mice, bone mineral density, bone marrow mesenchymal stem cells

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Dentistry Commons



Date Posted: 25 February 2022

This document has been peer reviewed.