title: Positive effect of alendronate on subchondral bone healing and subsequent cartilage repair in a rabbit osteochondral defect model.
abstract: BACKGROUND
  Cartilage and subchondral bone have recently been considered an osteochondral unit. The treatment of osteochondral lesions is still challenging, but better subchondral bone repair may result in higher quality repaired cartilage.
  
  
  OBJECTIVE
  Alendronate accelerates bone formation in osteochondral defects and affects the quality of the repaired cartilage.
  
  
  METHODS
  Controlled laboratory study.
  
  
  METHODS
  Osteochondral defects were made on the left trochleas of 50 rabbits, which were assigned to 1 of 3 groups: control, ALN (weekly subcutaneous injection of 0.14 mg/mL alendronate), and ALN-S (alendronate injection in the first 8 weeks only). They were evaluated at 4, 8, 24, and 52 weeks. Bone repair was evaluated with microcomputed tomography and histologic evaluation. Cartilage repair was evaluated with ultrasound and histologic analyses.
  
  
  RESULTS
  At 4 weeks, the defects were filled, and cartilage-like repair tissue was observed in the ALN group, whereas the defects were incompletely filled in the control group. Alendronate treatment enhanced early bone formation and mineralization in the osteochondral defect for the first 8 weeks. The continuous injection of alendronate for 24 weeks resulted in delayed bone remodeling, but the rabbits in the ALN-S group showed good integrity of the subchondral bone plate, without delayed remodeling. At 52 weeks, the ALN-S group had a columnar arrangement of chondrocytes that had less fibrillation and looked superior to those in the ALN and control groups. Ultrasound analysis showed better quality of repaired cartilage of the ALN and ALN-S group than the control group.
  
  
  CONCLUSIONS
  Alendronate accelerated bone formation without inhibiting its mineralization but thereafter inhibited bone remodeling in an osteochondral defect. The withdrawal of alendronate at 8 weeks avoided the delayed remodeling and showed better subchondral bone repair. At 52 weeks, better subchondral bone repair resulted in better cartilage quality.
  
  
  CONCLUSIONS
  Alendronate administered in the early period accelerates bone formation and improves the quality of the repaired cartilage.
authors.affiliation: Department of Orthopaedic Surgery, Graduate School of Medicine, Kyoto University, 54 Kawahara-cho, Shogoin, Sakyo-ku, Kyoto, Japan.
authors.forename: Kohei
authors.initials: K
authors.lastname: Nishitani
authors.forename: Takaaki
authors.initials: T
authors.lastname: Shirai
authors.forename: Masahiko
authors.initials: M
authors.lastname: Kobayashi
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kuroki
authors.forename: Yoshiaki
authors.initials: Y
authors.lastname: Azuma
authors.forename: Yasuaki
authors.initials: Y
authors.lastname: Nakagawa
authors.forename: Takashi
authors.initials: T
authors.lastname: Nakamura
mesh_terms: D019386:Alendronate / Q000494:pharmacology*; D000818:Animals; D050071:Bone Density Conservation Agents / Q000494:pharmacology*; D016723:Bone Remodeling / Q000187:drug effects; D002356:Cartilage / Q000000981:diagnostic imaging / Q000187:drug effects* / Q000293:injuries; D004164:Diphosphonates; D017102:Fracture Healing / Q000187:drug effects*; D010007:Osteochondritis / Q000601:surgery; D011817:Rabbits; D014463:Ultrasonography
chemical_list: D050071:Bone Density Conservation Agents; D004164:Diphosphonates; D019386:Alendronate