Knee muscle atrophy is a risk factor for development of knee osteoarthritis in a rat model

OBJECTIVES: The objective of this study was to investigate the effect of botulinum toxin type A (BTX-A)–induced quadriceps muscle atrophy on the cartilage and subchondral bone in an otherwise intact rat joint model. METHODS: The rat right quadriceps muscle atrophy was established by intramuscular injection of BTX-A. Twenty-four rats were divided randomly into 3 groups: The BTX-A–treated 4-week group; the BTX-A–treated 8-week group; and the control group injected with phosphate buffer saline were observed for 8 weeks. Muscle atrophy level was measured by weighing and histology examinations. Serum interleukin-1β level was tested by ELISA (enzyme linked immunosorbent assay); the subchondral bone was analysed by micro–computed tomography and the cartilage was measured by histology examinations (gross view, haematoxylin and eosin staining and Safranin-O/fast green staining) and immunohistochemistry test {collagen X [ColX]}. RESULTS: BTX-A intramuscular injection led to muscle atrophy. Characteristics of muscle atrophy appeared in two BTX-A–injected groups but not in the control group. Quadriceps atrophy did not affect interleukin-1β level in serum, but resulted in subchondral bone abnormal changes with reduced bone volume/total tissue volume ​and increased Structure Model Index. Furthermore, the more the severe cartilage damage, the higher the histologic damage scores, followed by the higher the percentage of collagen X–positive chondrocytes caused by muscle atrophy. CONCLUSIONS: Quadriceps muscle atrophy triggered the subchondral bone abnormal change and cartilage degeneration, which would be a risk factor for development of osteoarthritis. THE TRANSLATIONAL POTENTIAL OF THIS ARTICLE: Our results indicate that anti-quadriceps muscle atrophy can be a candidate therapeutic target in the prevention of knee osteoarthritis.