Osteoarthritis (OA) is a slowly progressive degenerative joint disease that is associated with joint space narrowing, osteophyte formation and subchondral sclerosis. Despite extensive effort actual breakthroughs in the field of genetic or biochemical biomarkers of OA are limited. As secretory apolipoprotein J/clusterin (sCLU) has been implicated in both inflammatory and apoptotic molecular processes which contribute to the OA phenotype, the sCLU concentration in human serum and synovial fluid during advanced primary knee and hip OA was analysed. Elevated sCLU protein levels were shown in these two biological fluids. sCLU mRNA expression was also studied in normal cartilage and in advanced primary knee and hip OA samples. A significant up-regulation of sCLU mRNA expression (~25-fold) was found in samples collected from the tibial bone that was osteotomized during total knee arthroplasty in patients with primary knee OA, as compared to healthy tissue samples collected from the femoral head of macroscopically normal cartilage during the surgical treatment of subcapital fractures. By studying sCLU mRNA expression levels in samples collected during total hip arthroplasty in patients with advanced primary hip OA, an additional up-regulation of the sCLU mRNA expression (~4-fold), as compared to advanced primary knee OA, was found. Taken together, these observations indicate that the sCLU protein or mRNA expression level may be of a significant diagnostic and/or prognostic value during OA progression.