title: Chondroprotective effect of high-dose zoledronic acid: An experimental study in a rabbit model of osteoarthritis.
abstract: To address the need to impact the subchondral bone-articular cartilage interaction for the treatment of degenerative osteoarthritis (OA), bisphosphonates may be used as a means to inhibit the subchondral bone resorption. The purpose of the present study is to evaluate the chondroprotective effect of zoledronic acid (ZOL) in a model of OA. Eighteen adult male rabbits underwent an anterior cruciate ligament transection and were separated into two groups: ZOL group (n=10) received 0.6 mg/kg intravenous injection of ZOL on day 1, 15, and 29 and placebo group (n=8) received saline. The animals were euthanized at 8 weeks. Macroscopically, the ZOL group had significantly milder ulcerations, cartilage softening and fibrillation compared to the placebo group. Microscopically, morphology of the articular cartilage was better in the ZOL treated group compared with the placebo group, without complete disorganization in any section of the ZOL group. Furthermore, the chondrocytes in the ZOL treated group were mainly cloning, indicating cartilage repairing and regeneration process, while in the placebo group hypocellularity predominated. Additionally, subchondral necrosis was evident in some specimens of the placebo group. Zoledronic acid, in a high-dose regimen, proved to be chondroprotective in a well-established animal model of OA.
authors.affiliation: Laboratory for Research of the Musculoskeletal System "Theodoros Garofalidis", University of Athens, KAT General Hospital, Athens, Greece; Third Orthopaedic Department, University of Athens, KAT General Hospital, Athens, Greece.
authors.forename: Kalliopi
authors.initials: K
authors.lastname: Lampropoulou-Adamidou
authors.forename: Ismene
authors.initials: I
authors.lastname: Dontas
authors.forename: Ioannis P
authors.initials: IP
authors.lastname: Stathopoulos
authors.forename: Lubna
authors.initials: L
authors.lastname: Khaldi
authors.forename: Pavlos
authors.initials: P
authors.lastname: Lelovas
authors.forename: John
authors.initials: J
authors.lastname: Vlamis
authors.forename: Ioannis K
authors.initials: IK
authors.lastname: Triantafillopoulos
authors.forename: Nikolaos A
authors.initials: NA
authors.lastname: Papaioannou
mesh_terms: D000818:Animals; D050071:Bone Density Conservation Agents / Q000494:pharmacology*; D019902:Chondrocytes / Q000187:drug effects*; D004164:Diphosphonates / Q000494:pharmacology*; D004195:Disease Models, Animal; D007093:Imidazoles / Q000494:pharmacology*; D008297:Male; D010003:Osteoarthritis / Q000188:drug therapy*; D011817:Rabbits; D000077211:Zoledronic Acid
chemical_list: D050071:Bone Density Conservation Agents; D004164:Diphosphonates; D007093:Imidazoles; D000077211:Zoledronic Acid
keywords: animal model; cartilage; osteoarthritis; subchondral bone; zoledronic acid