Objective: The pathogenesis of the temporomandibular joint osteoarthritis (TMJ OA) has not been clearly revealed. This study aimed to investigate the pathogenesis of TMJ OA based on bone metabolism. Methods: Fifty-nine young (mean age 23.4 ± 3.4 years) and 41 post-menopausal females (mean age 57.2 ± 4.6 years) were enrolled. Areal bone mineral density (aBMD) was measured via dual-energy X-ray absorptiometry of the lumbar spine, femoral neck, total hip, and ultradistal radius. Levels of four bone resorption markers, serum ionized calcium and C-telopeptide of type I collagen (CTx) and urinary N-telopeptide of type I collagen and deoxypyridinoline, two bone formation markers, serum bone alkaline phosphatase and osteocalcin, and serum 25-dihydroxyvitamin D were analyzed at baseline and after 12 months. Condylar bone quality was assessed by 3D reconstructed CT images. Results: Significant differences in condylar bone quality and aBMDs of the lumbar spine in accordance with TMJ OA stages were observed in young and post-menopausal females. The level of CTx was significantly associated with the development and progression of TMJ OA only in young females, whereas 25-dihydroxyvitamine D demonstrated significant associations in young and post-menopausal females. Progression of TMJ OA was accompanied by reduced condylar bone quality and concomitant with lower lumbar spine aBMDs in young and post-menopausal females. Conclusion: Bone metabolism and condylar quality might be involved in the development and progression of TMJ OA. Clinical relevance: CTx could be considered as a potential diagnostic and monitoring marker in young females, and vitamin D showed a therapeutic potential for TMJ OA.