Objective. To evaluate the relationships among cartilage and subchondral bone before and after the onset of cartilage degeneration in the Hartley guinea pig model of spontaneous osteoarthritis (OA) as compared with those in Weiser-Maple guinea pigs, which do not develop OA.Methods. Mice from each strain were used at ages 2, 3, 5, and 8 months (n ؍ 7 at each time point). The region observed was the medial tibial plateau. Cartilage degeneration was evaluated histologically. Subchondral bone structure was evaluated based on subchondral bone plate thickness and subchondral cancellous bone trabecular parameters calculated from the microfocal computed tomography 3-dimensional reconstruction image. The bone mineral density (BMD) of the subchondral cancellous bone as well as levels of urinary N-telopeptide of type I collagen (NTX) and serum osteocalcin (OC) were measured.Results. In Hartley guinea pigs, the number of chondrocytes in the surface layer started to decrease at 3 months. At 8 months, fibrillation expanded to the radial zone. In Weiser-Maple guinea pigs, no cartilage degeneration was noted even at 8 months. Subchondral bone plate thickness was significantly lower in Hartley guinea pigs than in Weiser-Maple guinea pigs at 2 months. The subchondral bone had a rod-like and convex structure at 2 months in Hartley guinea pigs. BMD was significantly lower in Hartley guinea pigs than in Weiser-Maple guinea pigs at 2 months. The serum OC level was significantly higher in Hartley guinea pigs than in Weiser-Maple guinea pigs at 2 months and 3 months, whereas the urinary NTX level was significantly lower in Hartley guinea pigs at 3 months.Conclusion. Subchondral bone is fragile, and bone formation may be promoted in subchondral bone before the onset of cartilage degeneration in Hartley guinea pigs. Subchondral bone may be involved in the development of OA.Osteoarthritis (OA) is the most prevalent of joint diseases, and its pathology is characterized by the degeneration of articular cartilage, sclerosis of subchondral bone, and osteophyte formation. Localization of the early lesions of OA has not been clarified, but many researchers have focused on articular cartilage (1,2) and have considered that changes in subchondral bone occur subsequent to the degeneration of articular cartilage. However, a low bone mineral density (BMD), particularly in the knee joint with OA (3,4), high bone turnover (5-7), and efficacy of bone resorption inhibitors for OA (8)(9)(10)(11)(12)(13)(14) have recently been reported, suggesting that subchondral bone plays an important role in the pathogenesis of knee OA. Burr (15) reported that microdamage to subchondral bone by mechanical overload was repaired and led to bone sclerosis, by which bone turnover was enhanced and resulted in the deterioration of subchondral bone, suggesting the importance of subchondral bone and bone turnover in the progression of OA. Most of these clinical and experimental studies of subchondral bone were related to OA progression, but there have been fewer studies con...