more, RANKL expression (r1⁄4-0.89, p<0.001) and RANKL/OPG ratio (r1⁄40.74, p1⁄40.01) in cartilage from AIA rabbits were inversely related to subchondral bone mineral density. Significant differences in the expression of RANKL resulted from the comparison of OA and healthy rabbits (204.92 52.47 vs 64.15 22.26, p1⁄40.014). Peri-cellular RANKL expression was observed throughout all cartilage zones, especially increased and mainly detected in the extracellular matrix, near the vessels, of calcified cartilage in AIA rabbits. The cartilage from OA rabbits showed the same peri-cellular expression pattern but no extra-cellular expression was detected. Co-cultures demonstrated that PGE2-induced RANKL synthesis from human chondrocytes induced osteoclasts differentiation from PBMC. Conclusions: Our data suggest that the increased RANKL expression observed in the cartilage from OA and AIA could be responsible, at least partially, of the development of juxta-articular osteoporosis associated with chronic arthritis. However, this mechanism of bone loss is less manifest in early OA than in chronic arthritis.