Elevation of pro-inflammatory cytokine levels following anti-resorptive drug treatment is required for osteonecrosis development in infectious osteomyelitis

Mayu Morita, Ryotaro Iwasaki, Yuiko Sato, Tami Kobayashi, Ryuichi Watanabe, Takatsugu Oike, Satoshi Nakamura, Yosuke Keneko, Kana Miyamoto, Kazuyuki Ishihara, Yoichiro Iwakura, Ken Ishii, Morio Matsumoto, Masaya Nakamura, Hiromasa Kawana, Taneaki Nakagawa, Takeshi Miyamoto

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Abstract

Various conditions, including bacterial infection, can promote osteonecrosis. For example, following invasive dental therapy with anti-bone resorptive agents, some patients develop osteonecrosis in the jaw; however, pathological mechanisms underlying these outcomes remain unknown. Here, we show that administration of anti-resorptive agents such as the bisphosphonate alendronate accelerates osteonecrosis promoted by infectious osteomyelitis. Potent suppression of bone turnover by these types of agents is considered critical for osteonecrosis development; however, using mouse models we found that acceleration of bone turnover by teriparatide injection did not prevent osteonecrosis but rather converted osteoclast progenitors to macrophages expressing inflammatory cytokines, which were required for osteonecrosis development. In fact, we demonstrate that TNFα-, IL-1α/β- or IL-6-deficient mice as well as wild-type mice administered a TNFα-inhibitor were significantly resistant to development of osteonecrosis accompanying infectious myelitis, even under bisphosphonate treatment. Our data provide new insight into mechanisms underlying osteonecrosis and suggest new ways to prevent it.

Original languageEnglish
Article number46322
JournalScientific reports
Volume7
DOIs
Publication statusPublished - 2017 Apr 7

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    Morita, M., Iwasaki, R., Sato, Y., Kobayashi, T., Watanabe, R., Oike, T., Nakamura, S., Keneko, Y., Miyamoto, K., Ishihara, K., Iwakura, Y., Ishii, K., Matsumoto, M., Nakamura, M., Kawana, H., Nakagawa, T., & Miyamoto, T. (2017). Elevation of pro-inflammatory cytokine levels following anti-resorptive drug treatment is required for osteonecrosis development in infectious osteomyelitis. Scientific reports, 7, [46322]. https://doi.org/10.1038/srep46322