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Background  The etiology of bone marrow lesions (BMLs) without knee osteoarthritis (KOA) and their association with bone fragility are unclear. We aimed to investigate the association between BMLs, bone mineral density (BMD), and bone markers in women without radiographic evidence of KOA.    Methods  This single-center cross-sectional study in a Japanese population included 266 women without radiographic evidence of KOA, which was defined as a Kellgren-Lawrence grade < 2. All participants underwent coronal and sagittal T2-weighted fat-suppressed magnetic resonance imaging of their right knee. BML severity was scored according to the Whole-Organ MRI Scoring method. BMD was measured by dual-energy X-ray absorptiometry of the forearm. Levels of bone markers (bone-alkaline phosphatase [BAP], type I procollagen N-terminal propeptide [PINP], cross-linked N-telopeptide of type I collagen [NTx], and tartrate-resistant acid phosphatase-5b [TRACP-5b]), pentosidine, and homocysteine were assessed in the serum. Knee symptoms were evaluated on the basis of the Knee injury and Osteoarthritis and Outcome Score (KOOS). Participants were divided into symptomatic knee and asymptomatic knee groups on the basis of their KOOS according to the classification criteria for early KOA. Multiple linear regression analysis was performed to evaluate the relationship between BMLs, BMD, and bone markers.    Results  The prevalence of BML was 35.3%. Age and some bone marker levels (BAP, PINP, NTx, and TRACP-5b) were higher, and all KOOS subscale scores and BMD were lower in participants with BMLs than in those without BMLs. On multiple linear regression analysis, BMD was negatively associated with BMLs ( p  = 0.014) in participants with symptomatic knees. There was no such association in participants with asymptomatic knees ( p  = 0.918). Among the bone markers, BAP ( p  = 0.006) and PINP ( p  = 0.043) were positively associated with BMLs in participants with symptomatic knees, while BAP ( p  = 0.038) and TRACP-5b ( p  = 0.011) were positively associated with BMLs in participants with asymptomatic knees.    Conclusions  In symptomatic Japanese women without radiographic evidence of KOA, BMD is negatively associated and some bone markers are positively associated with BMLs after adjustment for age and BMI. Thus, maintaining systemic bone metabolism could contribute to BML prevention in patients with pre-radiographic KOA.

Symptomatic bone marrow lesions induced by reduced bone mineral density in middle-aged women: a cross-sectional Japanese population study