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Abstract Objectives Osteoarthritis (OA) is increasingly considered a disease of the whole joint, yet the interplay between the articular cartilage and the subchondral bone remains obscure. We here set out to investigate the impact of bone mass on the progression of surgically induced knee OA in the mouse. Methods OA was induced in the right knees of female C57BL/6 (low bone mass) and STR/ort (high bone mass) mice via anterior cruciate ligament transection and destabilization of the medial meniscus. At 36 weeks of age, left and right knee joints were histologically compared for cartilage degeneration and via microCT analysis for subchondral bone plate thickness. In addition, femora were analyzed for bone mass at diaphysis and distal meta- and epiphysis. Results The severity of cartilage deterioration did not differ under high and low bone mass conditions. However, the extent of bone sclerosis differed and was proportional to the baseline subchondral bone plate thickness. Moreover, the cancellous bone loss following OA progression was inversely related to the bone mass: high bone mass restricted the loss to the epiphysis, whereas low bone mass allowed for a more widespread loss extending into the metaphysis. Conclusions Our results suggest that cartilage degeneration is independent of the underlying bone mass. In contrast, subchondral bone remodeling associated with OA progression seem to correlate with the initial bone mass and suggest an enhanced crosstalk between the deteriorating cartilage and the subchondral bone under low bone mass conditions.