論文

査読有り
2005年10月

Comparative appraisal of clodronate, aspirin and dexamethasone as agents reducing alendronate-induced inflammation in a murine model

BASIC & CLINICAL PHARMACOLOGY & TOXICOLOGY
  • ZQ Yu
  • ,
  • H Funayama
  • ,
  • Deng, X
  • ,
  • T Kuroishi
  • ,
  • T Sasano
  • ,
  • S Sugawara
  • ,
  • Y Endo

97
4
開始ページ
222
終了ページ
229
記述言語
英語
掲載種別
研究論文(学術雑誌)
DOI
10.1111/j.1742-7843.2005.pto_138.x
出版者・発行元
BLACKWELL PUBLISHING

Among the bisphosphonates, the nitrogen-containing bisphosphonates have much stronger anti-bone-resorptive activities than bisphosphonates containing no nitrogen, but nitrogen-containing bisphosphonates mostly have inflammatory side effects. Our previous murine-model experiments with a single intraperitoneal bisphosphonate injection demonstrated that (i) nitrogen-containing bisphosphonates induce various inflammatory reactions via an IL-1-dependent mechanism, (ii) alendronate (an nitrogen-containing bisphosphonate) produces a clear sclerotic line in the tibia that is easily detectable by radiography a few weeks later (tentatively called the bisphosphonate line, a useful marker for the anti-bone-resorptive activities of bisphosphonates), and (iii) clodronate (a non-nitrogen-containg bisphosphonate) reduces the inflammatory reactions induced by alendronate but does not reduce the bisphosphonate line formation induced by alendronate. We compared the effects of clodronate, aspirin and dexamethasone on the inflammatory reactions induced by alendronate (40 mu mol/kg) (induction of the histamine-forming enzyme, accumulation of pleural exudate and splenomegaly) and on the bisphosphonate line formation induced by alendronate (0.1 mu mol/kg). The effects of aspirin (833 mu mol/kg) were weak. However, like clodronate, dexamethasone (10 mu mol/kg, injected 5 min. after alendronate), strongly inhibited the alendronate-induced inflammatory reactions but did not reduce the alendronate-induced bisphosphonate line formation. Alendronate produced normal bisphosphonate lines in IL-1-deficient mice, too. These results suggest that clodronate and/or dexamethasone may be suitable for preventing or reducing the inflammatory side effects of nitrogen-containing bisphosphonates while preserving their powerful anti-bone-resorptive activities (although in practice the known side effects of dexamethasone may limit its use), and that the anti-bone resorptive activities of nitrogen-containing bisphosphonates are not influenced by IL-1.

Web of Science ® 被引用回数 : 17

リンク情報
DOI
https://doi.org/10.1111/j.1742-7843.2005.pto_138.x
Web of Science
https://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=JSTA_CEL&SrcApp=J_Gate_JST&DestLinkType=FullRecord&KeyUT=WOS:000231981400007&DestApp=WOS_CPL

エクスポート
BibTeX RIS