Technetium-99 conjugated with methylene diphosphonate ameliorates ovariectomy-induced osteoporotic phenotype without causing osteonecrosis in the jaw.
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.
Center for Craniofacial Molecular Biology, Herman School of Dentistry, University of Southern California, 2250 Alcazar Street, CSA 103, Los Angeles, CA 90033, USA.
Yinghua
Y
Zhao
Lei
L
Wang
Yi
Y
Liu
Kentaro
K
Akiyama
Chider
C
Chen
Ikiru
I
Atsuta
Tao
T
Zhou
Xiaohong
X
Duan
Yan
Y
Jin
Songtao
S
Shi
D000818:Animals; D059266:Bisphosphonate-Associated Osteonecrosis of the Jaw / Q000209:etiology / Q000378:metabolism / Q000473:pathology*; D015519:Bone Density; D050071:Bone Density Conservation Agents / Q000009:adverse effects*; D005260:Female; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D010024:Osteoporosis / Q000188:drug therapy* / Q000503:physiopathology; D010052:Ovariectomy; D010641:Phenotype; D019275:Radiopharmaceuticals / Q000009:adverse effects*; D013669:Technetium Tc 99m Medronate / Q000009:adverse effects*
D050071:Bone Density Conservation Agents; D019275:Radiopharmaceuticals; D013669:Technetium Tc 99m Medronate