Effect of Intra-articular Injection of AOD9604 with or without Hyaluronic Acid in Rabbit Osteoarthritis Model

Kwon DR, Park GY · Annals of Clinical and Laboratory Science

At nine weeks the saline group had the highest gross morphological (Yoshimi) and histological (modified Mankin) scores on the lateral femoral condyle, and every treated group scored lower (p under 0.05). The combination scored lower than either hyaluronic acid or AOD9604 alone, and AOD9604 alone did not differ from hyaluronic acid alone. Lameness resolved in 25 plus or minus 2 days on saline, 15 plus or minus 3 on hyaluronic acid, 16 plus or minus 2 on AOD9604 and 11 plus or minus 4 on the combination. The scores themselves are shown only in figures, without numbers or confidence intervals.

Population

Male New Zealand white rabbits, 12 weeks old, given two intra-articular injections of collagenase type II into the right knee three days apart to induce osteoarthritis

Intervention

Weekly ultrasound-guided intra-articular injections into the right knee from week 4 to week 7 after the first collagenase dose: 0.25 mg AOD9604 in 0.6 mL, or 0.25 mg AOD9604 with 6 mg high-molecular-weight hyaluronic acid (eight rabbits per group)

Comparator

0.6 mL saline, or 6 mg hyaluronic acid alone, on the same schedule (eight rabbits per group)

Limitations

Eight animals per group, a four-week treatment window and no follow-up beyond nine weeks; scores are reported as figures without means or intervals, and the lameness observers were blinded while the injectors were not stated to be. The drug was supplied by Metabolic Pharmaceuticals, the paper's dose rationale rests on that company's unpublished chondrocyte work, and the text names no funding source; the methods and the figure legend disagree on the collagenase dose (2 mg against 0.25 mg) and on the timing of the treatment injections. The authors themselves say the sample size is too small to generalise from.