Markers of joint tissue turnover in joint fluids from hips with osteonecrosis of the femoral head

Osteonecrosis of the femoral head often results in secondary osteoarthritis of the hip joint; however, the pathologic processes underlying the destruc tion of articular cartilage are not fully understood. Molecular markers in the hip joint fluids were measured to examine the changes in turnover of ca rtilage and other joint tissues. Marker data were related to clinical, radi ological, and histopathological changes in the articular cartilage of the h ip. Forty-five patients (median age: 43 years) were studied. The median tim e between the onset of symptoms and sampling of hip synovial fluid was 6 mo nths. Aggrecan fragments, C-propeptide of type-II collagen, matrix metallop roteinase-3, and tissue inhibitor of metalloproteinases-1 levels in joint f luid were determined by immunoassay. Osteonecrosis of the femoral head was graded by radiology as minimal collapse of the femoral head (stage 2: 26 pa tients), severe collapse (stage 3: 15 patients), or severs collapse with os teoarthritis (stage 4: four patients). Histological changes of the articula r cartilage, consistent with early-stage osteoarthritis, were evident at st age 3 and were more advanced at stage 3. The average concentrations of prot eoglycan fragments and C-propeptide of type-II collagen were 207 (SD 182) m ug/ml and 19.6 (SD 19.3) ng/ml, respectively. The average concentrations of matrix metalloproteinase-3 and tissue inhibitor of metalloproteinases-1 we re 177 (SD 291) nM and 23.0 (SD 9.9) nM, respectively. Measurable levels fo r all markers assayed were noted in the earliest stage of the disease, only a few months after the onset of symptoms and well before the appearance of radiological changes. Levels of matrix metalloproteinase-3 and molar ratio s of matrix metalloproteinase-3/tissue inhibitor of metalloproteinases-1 we re higher in early stage disease than in later stage disease.