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Technetium-99 Conjugated with Methylene Diphosphonate Ameliorates Ovariectomy-Induced Osteoporotic Phenotype without Causing Osteonecrosis in the Jaw

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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 bisphosphonate-related 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.

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Acknowledgments

This work was supported by grants from the U.S. National Institute of Dental and Craniofacial Research, National Institutes of Health, Department of Health and Human Services (R01DE017449, R01DE019932, and R01DE019413 to S.S.) and from the National Basic Research Program (973 Program) of China (2011CB964700).

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Authors and Affiliations

  1. Center for Craniofacial Molecular Biology, Herman School of Dentistry, University of Southern California, 2250 Alcazar Street, CSA 103, Los Angeles, CA, 90033, USA

    Yinghua Zhao, Lei Wang, Yi Liu, Kentaro Akiyama, Chider Chen, Ikiru Atsuta & Songtao Shi

  2. Stomatology Hospital of Xi’an Jiaotong University, Xi’an, 710004, Shaanxi, People’s Republic of China

    Yinghua Zhao

  3. Department of Oral Histology and Pathology, School of Stomatology, Fourth Military Medical University, 145 West Changle Road, Xi’an, 710032, Shaanxi, People’s Republic of China

    Lei Wang, Tao Zhou, Xiaohong Duan & Yan Jin

  4. Engineering Technology Center for Tissue Engineering of Xi’an, 145 West Changle Road, Xi’an, 710032, Shaanxi, People’s Republic of China

    Yan Jin

  5. Center for Craniofacial Molecular Biology, Ostrow School of Dentistry, University of Southern California, 2250 Alcazar Street, CSA 103, Los Angeles, CA, 90033, USA

    Songtao Shi

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  1. Yinghua Zhao
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Correspondence to Yan Jin or Songtao Shi.

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Yinghua Zhao and Lei Wang contributed equally to this study.

The authors have stated that they have no conflict of interest.

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Zhao, Y., Wang, L., Liu, Y. et al. Technetium-99 Conjugated with Methylene Diphosphonate Ameliorates Ovariectomy-Induced Osteoporotic Phenotype without Causing Osteonecrosis in the Jaw. Calcif Tissue Int 91, 400–408 (2012). https://doi.org/10.1007/s00223-012-9649-7

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