title: Antiinflammatory and chondroprotective effects of the aminobisphosphonate incadronate (YM175) in adjuvant induced arthritis.
abstract: OBJECTIVE
  Incadronate is a third-generation bisphosphonate that suppresses bone resorption and is used to treat skeletal disorders and prevent bone loss in pathological conditions. We evaluated its therapeutic potential and antiinflammatory effects in established adjuvant induced arthritis (AIA), a rat model of rheumatoid arthritis (RA).
  
  
  METHODS
  Rats were administered incadronate subcutaneously at a dose of either 0.1 or 1.0 mg/kg/day, or 0.1 or 1.0 mg/kg/week, while a positive control group received phosphate buffered saline alone from Day 14 (after the onset of arthritis) to Day 42. The destruction of bone and cartilage and the antiinflammatory effects of incadronate in rats with established AIA were assessed during treatment, with reference to the arthritis index, hind paw volume, and radiological and histological examinations. To establish whether incadronate affects the migration of inflammatory cells, a chemotaxis assay was carried out using macrophage-like RAW 264.7 cells. Results. In vivo, incadronate suppressed the clinical manifestations of AIA in a dose-dependent manner. In vitro, the various concentrations of incadronate suppressed the migration of macrophages, but the viability and adhesion of these cells were not suppressed.
  
  
  CONCLUSIONS
  Incadronate not only inhibits bone destruction but also reduces cartilage degeneration and joint inflammation in rats with established AIA. The mechanism underlying these antiinflammatory actions of incadronate may be attributable to the inhibition of macrophage migration to the site of inflammation. Bisphosphonates might be effective in preventing the progressive joint destruction and inflammation seen in patients with RA.
authors.affiliation: Department of Orthopaedic Surgery, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Matsuo
authors.forename: Toshihide
authors.initials: T
authors.lastname: Shuto
authors.forename: Go
authors.initials: G
authors.lastname: Hirata
authors.forename: Hideshi
authors.initials: H
authors.lastname: Satoh
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Matsumoto
authors.forename: Hongpu
authors.initials: H
authors.lastname: Zhao
authors.forename: Yukihide
authors.initials: Y
authors.lastname: Iwamoto
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D001169:Arthritis, Experimental / Q000188:drug therapy* / Q000276:immunology* / Q000473:pathology; D002111:Calcaneus / Q000473:pathology; D002356:Cartilage / Q000473:pathology; D004164:Diphosphonates / Q000494:pharmacology*; D005260:Female; D006614:Hindlimb; D008297:Male; D051381:Rats; D011917:Rats, Inbred Lew; D013639:Tarsal Bones / Q000473:pathology; D013977:Tibia / Q000473:pathology
chemical_list: D000893:Anti-Inflammatory Agents; D004164:Diphosphonates; C071542:cimadronate