Bone density and local growth factors in generalized osteoarthritis

Osteoarthritis is usually considered to be a primary disorder of chondrocyte function with secondary changes in bones. However, a defect in the subchondral bone resulting in loss of its shock absorbing capacity could transfer the stress of loading directly to the articular cartilage with secondary changes in the cartilage. Review of histomorphometric and bone densitometric studies at sites of osteoarthritis at the hip or knee revealed that cartilage fibrillation could not be dissociated from bony changes even in the earliest stages of osteoarthritis and that subchondral trabeculae are thickened and more spaced in osteoarthritis. Microfractures of subchondral trabecular bone were less frequently seen in osteoarthritis compared to controls. Changes of the tidemark were found to be multiform and metabolically active in the osteoarthritic process. Endochondral ossification depletes the calcified cartilage at the cartilage/bone interface and the tidemark has been thought of as a calcification front advancing in the direction of non-calcified cartilage. Duplication of the tidemark is cited as evidence of this advancement. In the few experimental animal studies of subchondral bone in osteoarthritis, thicker trabeculae which were closer together were found in guinea pigs already when only mild cartilage changes were present. In the dog, with cruciate ligament transection, changes in bone were later than in the cartilage, but the changes in bone could still contribute to the progression of osteoarthritis. To study if bone changes may precede injury to the cartilage and if metabolic and systemic influences can also alter the subchondral bone, rendering it less able to withstand normal mechanical stresses, bone at different sites in the body has been studied extensively by the authors. Epidemiological and case control studies have revealed that osteoarthritis cases have more bone at all sites than expected and that bone in cases with generalized osteoarthritis shows both quantitative and qualitative differences, including increased contents of growth factors and hypermineralization. These findings suggest that a more generalized bone alteration may be the basis of the pathogenesis of osteoarthritis.