Early knee osteoarthrosis after meniscectomy : studies in rabbits

Sammanfattning: Post-traumatic osteoarthrosis develops after intraarticular injuries. It is a disease, which affects both articular cartilage and subchondral bone, and progresses over 10-20 years. Irreversible damage has often occurred by the time clinical diagnosis is possible. More knowledge about the early phase of the disease might yield measures to detect and delay or even prevent progression. This thesis evaluates changes in articular cartilage and subchondral bone at an early stage of post-traumatic osteoarthrosis.Simultaneous changes in articular cartilage and subchondral bone were evaluated 3 to 40 weeks post-operatively in a rabbit meniscectomy model for post-traumatic osteoarthrosis. Rabbits were meniscectomized in the right knee and sham-operated in the left knee. Osteoarthrotic cartilage changes were evaluated by histology. Changes in the subchondral bone were evaluated by histology, scintimetry and dual-energy X-ray absorptiometry (DEXA). Joint space narrowing, and its utility as diagnostic tool at early stages of osteoarthrosis, was assessed with weight-bearing radiographs. The prognostic value of transforming growth factor-ßI (TGF-ß1) and proteoglycan fragment concentrations in the joint fluid at an early stage was also assessed.We found slight cartilage changes and an increased metabolic activity in the subchondral bone as early as 3 weeks after meniscectomy. However, sham-operated knees displayed similar changes, although to a lesser degree. Cartilage fibrillation progressed at areas of high load within the meniscectomized knee joint. The subchondral bone showed a general response such as high scintimetric activity 3 weeks after surgery, and a decreased bone mineral density at later time points. Local adaptation in areas of high load within the subchondral bone was also seen. There was an increased osteoid content at the border between the cancellous bone and the marrow cavity already 3 weeks after meniscectomy, and at 13 weeks the subchondral bone plate was thickened. This thickening of the bone plate persisted up to 40 weeks. Joint space narrowing occurred after removal of the meniscus, but weight-bearing radiographs were not sensitive enough to measure early cartilage changes. Increased concentration of TGF-ß1 in the joint fluid at 3 weeks after surgery was associated with a higher degree of histological osteoarthrotic changes at a later time point.Simultaneous changes in both cartilage and bone were apparent already 3 weeks after surgery, indicating that both tissues are involved from a very early stage. The localisation of cartilage changes illustrates that mechanical consequences of meniscectomy play a crucial role in progression of the disease. Surgical trauma resulted in increased release of TGF-ß1 at 3 weeks after surgery. This was found to be indicative for the severity of later osteoarthrosis. Thus, factors solely associated with the surgical trauma may also be important for the progression of osteoarthrosis.