The Development of Botulinum Type-A Toxin-Induced Muscle Weakness Model of Osteoarthritis

Osteoarthritis (OA) is a prevalent degenerative joint disease. The aetiology of OA is multi-factorial and the exact cause is unclear. Identifying the potential role of risk factors, such as muscle weakness, in the development and progression of OA could help understand the disease aetiology and possible prevention. As the association between OA and muscle weakness is based on clinical observations only, the general goal of this PhD project was to investigate the effect of muscle weakness on the microstructure of the knee cartilage. Muscle weakness was induced by intramuscular injection of botulinum type-A toxin (BTX-A) in New Zealand White (NZW) rabbits. After animals were sacrificed, the cartilage microstructures were assessed by the Mankin scoring system. To eliminate the limitations of the Mankin system, we modified it in such a way to account for the extent and number of lesions in any given joint. The two systems were similar in reliability and result interpretation. Therefore, the standard Mankin system was adequate for our study goals.

First, we induced isolated quadriceps muscle weakness. This was associated with increased degeneration in the retro-patellar cartilage. We speculate that this degeneration might be attributed to an imbalance in the quadriceps muscles, which could have led to altered joint loading. Adding daily exercise to the isolated quadriceps weakness model was associated with early degeneration in the otherwise healthy lateral tibiofemoral joint. The lateral tibiofemoral compartment degeneration was attributed to changes in mechanical loading as a consequence of muscle imbalance or altered gait.

Finally, we induced weakness of all leg extensor muscles for 1- and 3-months. The degenerative changes of the experimental and control animal groups were similar. However, the BTX-A groups showed greater degeneration after 3-months versus 1-month of degeneration. We speculate that BTX-A animals reduced loading on the weak limbs, which had an initial protective effect, but over time this interfered with cartilage nutrition and health.

In conclusion, the series of studies performed have provided evidence that short term muscle weakness is not associated with progression of cartilage degeneration in the NZW rabbit knee. However, if muscle weakness causes altered joint loading or is combined with exercise, increased cartilage degeneration occurs.