Effect of Intra-articular Injection of AOD9604 with or without Hyaluronic Acid in Rabbit Osteoarthritis Model.
This study investigated the effects of intra-articular injections of AOD9604 (a synthetic peptide fragment of human growth hormone) alone and in combination with hyaluronic acid (HA) in a collagenase-induced knee osteoarthritis (OA) rabbit model. Thirty-two mature New Zealand white rabbits had OA induced in both knees via collagenase injection, then were divided into four groups receiving weekly intra-articular injections of saline, HA alone, AOD9604 alone, or AOD9604 combined with HA. At eight weeks, outcomes were assessed via gross morphology, histopathology of cartilage, and lameness scoring. The study found that all treatment groups showed significantly less cartilage degeneration than the saline control group. The combination of AOD9604 and HA produced significantly lower cartilage damage scores and shorter lameness periods compared to either treatment alone. While these findings suggest a potential chondroprotective and synergistic effect, the study is limited by its animal-only design, relatively small group sizes, and the use of a chemically induced OA model that may not fully replicate human OA pathology. No human data were collected, so translation of findings to clinical practice remains uncertain.
Why this grade: The study was conducted exclusively in a rabbit model (n=32) with no human subjects, providing no direct evidence of efficacy or safety in humans.
Background To investigate the effects of AOD9604 intra-articular injections with or without hyaluronic acid (HA) in a collagenase-induced knee osteoarthritis (OA) rabbit model. Design Mature New Zealand white rabbits (n=32) were randomly administered 2 mg collagenase type II twice in each knee joint. Weekly injections of 0.6 mL saline (Group 1), 6 mg HA (Group 2), 0.25 mg AOD9604 (Group 3), and 0.25 mg AOD9604 with 6 mg HA (Group 4) were administered for 4-7 weeks after the first intra-articular collagenase injection. The degree of cartilage degeneration was assessed using morphological and histopathological findings, and the degree of lameness was observed at 8 weeks after the first collagenase injection. Results Mean gross morphological and histopathological scores were significantly higher in Group 1 than in Groups 2, 3, and 4, and the scores were significantly lower in Group 4 than in Groups 2 and 3. The lameness period in Group 4 was significantly shorter than those in Groups 1, 2, and 3. The lameness period in Group 1 was significantly longer than those in Groups 2 and 3. Conclusion Intra-articular AOD9604 injections using ultrasound guidance enhanced cartilage regeneration, and combined AOD9604 and HA injections were more effective than HA or AOD9604 injections alone in the collagenase-induced knee OA rabbit model.
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