Partial chondroprotective effect of zoledronate in a rabbit model of inflammatory arthritis

J Rheumatol. 1999 Sep;26(9):1972-82.


Objective: To test the hypothesis that bisphosphonate treatment has a chondroprotective effect in the carrageenan model of inflammatory arthritis (IA).

Methods: Experimental IA was induced in rabbits by intraarticular injections of carrageenan. One group also received subcutaneous injections of zoledronate, a new bisphosphonate. After 4 weeks, the joints were harvested. Articular cartilage degradation and the degree of synovitis were assessed by light microscope using qualitative grading scores. Articular cartilage and subchondral and cancellous bone were evaluated histomorphometrically. Bone microhardness was measured.

Results: Carrageenan injected knees showed changes of inflammatory arthritis with cartilage erosion. Zoledronate treatment partially protected the articular cartilage from degradation. This effect was unlikely due to an antiinflammatory effect of the drug as the carrageenan induced synovitis was unaffected by zoledronate treatment. The treatment preserved subchondral bone thickness and cancellous bone volume and prevented focal breaks in the osteochondral barrier. The subchondral bone hardness was also maintained.

Conclusion: Zoledronate had a partial effect in a rabbit model of inflammatory arthritis. The chondroprotection may be due to the prevention of bone resorption. By maintaining an intact subchondral bone, normal joint loading may have been maintained and contact between the bone marrow and the articular cartilage averted.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Arthritis, Rheumatoid / drug therapy*
  • Arthritis, Rheumatoid / pathology
  • Carrageenan
  • Cartilage, Articular / drug effects*
  • Cartilage, Articular / pathology*
  • Diphosphonates / administration & dosage*
  • Disease Models, Animal
  • Female
  • Imidazoles / administration & dosage*
  • Injections, Subcutaneous
  • Knee Joint / drug effects
  • Knee Joint / pathology
  • Osteochondritis / prevention & control
  • Rabbits
  • Reference Values
  • Synovial Membrane / drug effects*
  • Synovial Membrane / pathology*
  • Zoledronic Acid


  • Diphosphonates
  • Imidazoles
  • Zoledronic Acid
  • Carrageenan