The role of muscles in joint degeneration and osteoarthritis.

The purpose of this work was to establish a controlled and reversible muscle weakness model for studying the effects of weakness on joint degeneration leading to osteoarthritis (OA). The knee extensor muscles of rabbits were injected with single or repeat doses of Botulinum type-A toxin (BTX-A) to partially inhibit acetylcholine (ACh) release at the neuromuscular junction. BTX-A-injected muscles atrophied, they became weaker and push-off forces during hopping were reduced compared to control. BTX-A injections had the greatest effect at short-muscle length and low-stimulation frequencies. Superimposing BTX-A injections on anterior cruciate ligament transection did not cause greater muscle atrophy or weakness than BTX-A injections alone. Monthly repeat injections could be used to keep muscles weak for half a year without any obvious adverse effects to the animals. Gross morphology of the knees and histology of articular cartilage suggested that, in some animals, 4 weeks of muscle weakness resulted in initial signs of joint degeneration, indicating that weakness may be an independent risk factor for joint degeneration leading to OA.