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

Yinghua Zhao, Lei Wang, Yi Liu, Kentaro Akiyama, Chider Chen, Ikiru Atsuta, Tao Zhou, Xiaohong Duan, Yan Jin, Songtao Shi

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9 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)400-408
Number of pages9
JournalCalcified Tissue International
Volume91
Issue number6
DOIs
Publication statusPublished - Dec 2012
Externally publishedYes

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Keywords

  • Tc-MDP
  • Bisphosphonate-related osteonecrosis of the jaw
  • Bone marrow mesenchymal stem cell
  • Bone mineral density
  • Ovariectomized mouse

ASJC Scopus subject areas

  • Orthopedics and Sports Medicine
  • Endocrinology, Diabetes and Metabolism
  • Endocrinology

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