Inhibition of inflammatory and bone-resorption-inhibitory effects of alendronate by etidronate

H. Funayama, M. Ohsako, Y. Monma, H. Mayanagi, S. Sugawara, Y. Endo

研究成果: Article査読

21 被引用数 (Scopus)

抄録

Among the bisphosphonates (BPs), the aminobisphosphonates (aminoBPs) have much stronger bone-resorption-inhibitory activities (BRIAs) than nonaminobisphosphonates (nonaminoBPs). However, aminoBPs have inflammatory effects. We previously reported that in mice: (i) all aminoBPs tested (10-40 μmol/kg) induced various inflammatory reactions (including induction of histidine decarboxylase), whereas clodronate (a non-aminoBP) (10-160 μmol/kg) inhibited these reactions; and (ii) a clear sclerotic line (tentatively called the BP line) was detectable in the tibia by radiography a few weeks after a single injection of either alendronate (a typical aminoBP) (1.6 μmol/kg) or clodronate (160 μmol/kg), and this BP-line formation (a marker for the BRIAs of BPs) was not reduced in mice given both alendronate and clodronate. In this study, using this murine model, we compared clodronate, etidronate (another typical non-aminoBP), alendronate, etidronate + alendronate, and clodronate + alendronate in terms of their inflammatory effects and/or BP-line formation. For BP-line formation, 480 μmol/kg etidronate was needed (single injection). At 160 μmol/kg, etidronate inhibited the histidine decarboxylase induction, but not the other inflammatory reactions induced by alendronate. However, etidronate (unlike clodronate) also inhibited alendronate-induced BP-line formation (even at 40 μmol/kg). Etidronate (160 μmol/kg) also inhibited the physicochemical changes in the tibia induced by six, weekly injections of alendronate. Therefore, depending on the dose, etidronate can inhibit alendronate's inflammatory actions and its BRIA. These results, together with those reported previously, suggest that a strategy utilizing clodronate (but not etidronate) plus an aminoBP might prevent or reduce the inflammatory side effects induced by aminoBPs while preserving their powerful BRIAs. We discuss the mechanisms underlying the antagonism between aminoBPs and non-aminoBPs.

本文言語English
ページ(範囲)448-457
ページ数10
ジャーナルCalcified Tissue International
76
6
DOI
出版ステータスPublished - 2005 6月

ASJC Scopus subject areas

  • 内分泌学、糖尿病および代謝内科学
  • 整形外科およびスポーツ医学
  • 内分泌学

フィンガープリント

「Inhibition of inflammatory and bone-resorption-inhibitory effects of alendronate by etidronate」の研究トピックを掘り下げます。これらがまとまってユニークなフィンガープリントを構成します。

引用スタイル