Evaluation of the Synergistic Effects Of ???Hyaluronic Acid And Dhea??? Intra Articular Injection In Rabbit Models With Osteoarthritis
Osteoarthritis (OA) is one of the most common joint disease affecting the eldery population. It is characterized by progressive destruction of the articular cartilage and con-comitant changes in the subchondral bone. Current treatments for OA including steroids and NSAIDs, with little satisfaction. A relatively new treatment, Hyaluronic acid (HA) intra articular (IA) injection, is reported to improve joint lubrication and can alleviate pain. The major disadvantage of all current treatments is that they are limited to improve the symptoms but their intervention is not disease modifying. On the other hand, Dehyroepiandrosteron (DHEA) IA injection, has been reported to have protecting and regenerating effects on cartilage in new animal studies. The aim of this study was to evaluate the probable synergistic effect of HA IA injections with DHEA in rabbit models with collagenase induced OA. The study was performed on 10 mature, male, white New Zealand rabbits (24weeks, 2-2.5 kg). The animals were divided into two major groups; collagenase control group with 1 rabbit and treatment group with 9 rabbits. Collagenase type Ι(clostridium histolyticum) was intra-articularly injected into both right and left knee of the rabbits in the treatment group, and right knee of collagenase control group. The injections were given twice (on day 1 and 4) in concentration of 1mg as IA in to the joints. After Six weeks of last dose of collagenase injection, the cartilage samples of the rabbit in the control group were obtained for further evaluations. Once the diagnosis of OA was confirmed in the controlled rabbit, the drug injections in the treatment group was initiated. The animals in the treatment group were then randomly divided into 3 groups and received weekly IA injections with 0.3 ml DHEA (100μmole/L), HA (10mg/ml) and combination of DHEA and HA(0.15 ml of each) into their right knees respectively for the next 5 consecutive weeks. At the same time all rabbits were receiving 0.3ml of the normal saline into their left knees. All rabbits were euthanized one week after the last dose of injection and cartilage samples were obtained and evaluated by gross morphologic, histomorphometric and histologic methods. The results showed that, the “HA” group had the best overall improvement and the “DHEA” group had the best histomorphometric results in comparison. The combination of “DHEA&HA“group had the worsening affect when compared against the other groups. In another words, this study do suggest that, IA injections of combination of “DHEA& HA” may have a negative effects on cartilage in rabbit models with OA. This negative pathological effect may be due to physical incompatibility or insufficient doses of each drug when used in combination. This is only a hypothesis where the authors do believe more research with larger samples may be required.
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