Inflammatory Effects of Nitrogen-Containing Bisphosphonates (N-BPs): Modulation by Non-N-BPs

• Shima Kazuhiro

  Division of Orthodontics and Dentofacial Orthopedics, Graduate School of Dentistry, Tohoku University Division of Molecular Regulation, Tohoku University Graduate School of Dentistry

• Tsuchiya Masahiro

  Tohoku Fukushi University

• Oizumi Takefumi

  Division of Oral and Maxillofacial Surgery, Tohoku University Graduate School of Dentistry, Tohoku University

• Takano-Yamamoto Teruko

  Division of Orthodontics and Dentofacial Orthopedics, Graduate School of Dentistry, Tohoku University

• Sugawara Shunji

  Division of Molecular Regulation, Tohoku University Graduate School of Dentistry

• Endo Yasuo

  Division of Oral and Maxillofacial Surgery, Tohoku University Graduate School of Dentistry, Tohoku University

抄録

Bisphosphonates (BPs) are used against diseases with enhanced bone resorption. Those classed as nitrogen-containing BPs (N-BPs) exhibit much stronger anti-bone-resorptive effects than non-nitrogen-containing BPs (non-N-BPs). However, N-BPs carry the risk of inflammatory/necrotic side effects. Depending on their side-chains, BPs are divided structurally into cyclic and non-cyclic types. We previously found in mice that etidronate and clodronate (both non-cyclic non-N-BPs) could reduce the inflammatory effects of all three N-BPs tested (cyclic and non-cyclic types), possibly by inhibiting their entry into soft-tissue cells via SLC20 and/or SLC34 phosphate transporters. Tiludronate is the only available cyclic non-N-BP, but its effects on N-BPs’ side effects have not been examined. Here, we compared the effects of etidronate, clodronate, and tiludronate on the inflammatory effects of six N-BPs used in Japan [three cyclic (risedronate, zoledronate, minodronate) and three non-cyclic (pamidronate, alendronate, ibandronate)]. Inflammatory effects were evaluated in mice by measuring the hind-paw-pad swelling induced by subcutaneous injection of an N-BP (either alone or mixed with a non-N-BP) into the hind-paw-pad. All of six N-BPs tested induced inflammation. Etidronate, clodronate, and the SLC20/34 inhibitor phosphonoformate inhibited this inflammation. Tiludronate inhibited the inflammatory effects of all N-BPs except ibandronate and minodronate, which have higher molecular weights than the other N-BPs. The mRNAs of SLC20a1, SLC20a2, and SLC34a2 (but not of SLC34a1 and SLC34a3) were detected in the soft-tissues of hind-paw-pads. These results suggest that etidronate, clodronate, and phosphonoformate may act non-selectively on phosphate transporter members, while tiludronate may not act on those transporting N-BPs of higher molecular weights.

収録刊行物

• Ｂｉｏｌｏｇｉｃａｌ　＆　Ｐｈａｒｍａｃｅｕｔｉｃａｌ　Ｂｕｌｌｅｔｉｎ

  Ｂｉｏｌｏｇｉｃａｌ　＆　Ｐｈａｒｍａｃｅｕｔｉｃａｌ　Ｂｕｌｌｅｔｉｎ 40 (1), 25-33, 2017

  公益社団法人 日本薬学会

キーワード

• bisphosphonate
• side effect
• inflammation
• phosphate transporter
• phosphonoformate
• tiludronate

詳細情報

• CRID: 1390001204632817664
• NII論文ID: 130005188786
• NII書誌ID: AA10885497
• DOI: 10.1248/bpb.b16-00521
• ISSN: 13475215
• ISSN: 09186158
• NDL書誌ID: 027818740
• PubMed: 28049945
• Web Site: https://ndlsearch.ndl.go.jp/books/R000000004-I027818740
• Web Site: https://www.jstage.jst.go.jp/article/bpb/40/1/40_b16-00521/_pdf
• Web Site: https://search.jamas.or.jp/link/ui/2017254535
• 本文言語コード: en
• データソース種別:
  • JaLC
  • NDL
  • Crossref
  • PubMed
  • CiNii Articles
  • KAKEN
• 抄録ライセンスフラグ: 使用不可