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

Abstract
Technetium-99 conjugated with methylene diphosphonate ((99)Tc-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-related osteonecrosis of the jaw (BRONJ), we examined whether (99)Tc-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 (99)Tc-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, (99)Tc-MDP/dexamethasone (Dex) or zoledronate/Dex was administered into C57BL/6J mice via the tail vein, followed by extraction of maxillary first molars. Interestingly, (99)Tc-MDP treatment showed less risk to induce osteonecrosis in the maxillary bones compared to zoledronate treatment group, partially because (99)Tc-MDP neither suppressed adaptive regulatory T cells nor activated the inflammatory T-helper-producing interleukin-17 cells. Taken together, our findings demonstrate that (99)Tc-MDP therapy may be a promising approach in the treatment of osteoporosis with less risk of causing BRONJ.
AuthorsYinghua Zhao, Lei Wang, Yi Liu, Kentaro Akiyama, Chider Chen, Ikiru Atsuta, Tao Zhou, Xiaohong Duan, Yan Jin, Songtao Shi
JournalCalcified tissue international (Calcif Tissue Int) Vol. 91 Issue 6 Pg. 400-8 (Dec 2012) ISSN: 1432-0827 [Electronic] United States
PMID23064899 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
Chemical References
  • Bone Density Conservation Agents
  • Radiopharmaceuticals
  • Technetium Tc 99m Medronate
Topics
  • Animals
  • Bisphosphonate-Associated Osteonecrosis of the Jaw (etiology, metabolism, pathology)
  • Bone Density
  • Bone Density Conservation Agents (adverse effects)
  • Female
  • Mice
  • Mice, Inbred C3H
  • Mice, Inbred C57BL
  • Osteoporosis (drug therapy, physiopathology)
  • Ovariectomy
  • Phenotype
  • Radiopharmaceuticals (adverse effects)
  • Technetium Tc 99m Medronate (adverse effects)

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