Alterations in mineral composition observed in osteoarthritic joints of cynomolgus monkeys

Osteoarthritis (OA) is a prevalent joint disease that affects more than 40 million Americans and is characterized by degeneration of the articular cartilage and thickening of the underlying subchondral bone. Although subchondral bone thickening has been implicated in articular cartilage degeneration, very little is known about the composition of subchondral bone in OA. In the present study, infrared microspectroscopy (IRMS) was used to determine the chemical composition of the calcified cartilage-subchondral bone plate in a monkey model of OA. Specifically, the levels of mineralization (mineral/protein ratio), carbonate accumulation (carbonate/protein ratio), crystallinity, and collagen structure were determined as a function of animal age and OA severity. OA severity was assessed using a grading scheme that included scores or measurements for several histomorphometric parameters including articular cartilage fibrillation or clefting, subchondral bone thickness, and numbers of tidemarks and chondrocyte clones. Individual scores and measurements were summarized using principal components (factor) analysis. Results demonstrated that the level of mineralization and carbonate content increased as a function of animal age. In addition, bone mineralization level increased as subchondral bone thickness increased. Dramatic increases in the mineralization level and carbonate accumulation were also observed as a function of the number of tidemarks. The presence of multiple tidemarks indicates the occurrence of one or more additional phases of cartilage calcification, suggesting that the observed compositional changes are due to cartilage mineralization. Our results support a reactivation of endochondral ossification that occurs with age, which is more pronounced in OA. No relationships were observed between mineral crystallinity and collagen cross-linking as a function of age or OA severity. In summary, compositional analysis of the mineralized plate beneath the articular cartilage in OA is characterized by thickened, overmineralized calcified cartilage or subchondral bone, which likely puts added mechanical stress on the joint, contributing to the progression of OA.