The aim of this work was to develop an equine metacarpophalangeal joint model that induces osteoarthritis that is not primarily mediated by instability or inflammation. The study involved six Standardbred horses. Standardized cartilage surface damage or “grooves” were created arthroscopically on the distal dorsal aspect of the lateral and medial metacarpal condyles of a randomly chosen limb. The contralateral limb was sham operated. After 2 weeks of stall rest, horses were trotted 30 minutes every other day for 8 weeks, then evaluated for lameness and radiographed. Synovial fluid was analyzed for cytology and biomarkers. At 10 weeks post-surgery, horses were euthanized for macroscopic and histologic joint evaluation. Arthroscopic grooving allowed precise and identical damage to the cartilage of all animals. Under the controlled exercise regime, this osteoarthritis groove model displayed significant radiographic, macroscopic, and microscopic degenerative and reactive changes. Histology demonstrated consistent surgically induced grooves limited to non-calcified cartilage and accompanied by secondary adjacent cartilage lesions, chondrocyte necrosis, chondrocyte clusters, cartilage matrix softening, fissuring, mild subchondral bone inflammation, edema, and osteoblastic margination. Synovial fluid biochemistry and cytology demonstrated significantly elevated total protein without an increase in prostaglandin E2, neutrophils, or chondrocytes. This equine metacarpophalangeal groove model demonstrated that standardized non-calcified cartilage damage accompanied by exercise triggered altered osteochondral morphology and cartilage degeneration with minimal or inefficient repair and little inflammatory response. This model, if validated, would allow for assessment of disease processes and the effects of therapy.

SUMMARY We studied the course of adjuvant arthritis in rats by measuring clinical, biochemical, and histological parameters on day 36 after induction (representing the secondary reaction) and on day 171, which is at the stage of permanent deformity. The effect of SR 41319, a new diphosphonate, was evaluated on days 36 and 171, after three weeks of treatment (days 14-35 inclusive). In the absence of treatment all the measured parameters were markedly abnormal on day 36, indicating the presence of lesions that were still evolving. On day 171 clinical parameters and the lesion histological index remained the same, whereas the biochemical parameters and disease activity histological index had returned to normal, indicating that the lesions at this stage although severe were not inflammatory and consequently not progressing. SR 41319 treatment reduced the severity and progression of the disease both on day 36 and on day 171. We conclude that SR 41319 may be a potentially useful drug for the treatment of rheumatoid arthritis.

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