Reduced serum levels of anti-Mullerian hormone is a putative biomarker of early knee osteoarthritis in middle-aged females at menopausal transition

A recent epidemiological study revealed that the highest prevalence of early knee osteoarthritis (OA) was observed in females aged ≥ 50 years. The major causal factor of early knee OA was sex. Despite the relevance of estrogen in evaluating chondral and bone metabolism in OA, it is not easily clinically monitored because irregular menstrual cycles induce unstable female hormone patterns during menopausal transitions. Anti-Mullerian hormone (AMH) has been found to be a new stable biomarker to predict menopause. This study aimed to investigate the association between menopausal transition and early knee OA by using serum biomarkers, with special focus on AMH. A total of 518 female volunteers who participated in the Iwaki cohort study were enrolled and divided into pre-menopause and post-menopause groups. Weight-bearing anterior–posterior knee radiographs were classified by Kellgren–Lawrence (KL) grade, and grade ≥ 2 was defined as radiographic knee OA. In participants with KL grades 0 and 1, early knee OA was defined by Luyten’s criteria. AMH, luteinizing hormone, follicle-stimulating hormone, estradiol (pg/ml), prolactin, and testosterone were measured on the female hormones. Bone mineral density at a distal radius was measured. The predictive power of female hormones for early knee OA was estimated by ROC analysis (comparison of area under curve, AUC) and regression analysis. Fifty-two participants (10.0%) were diagnosed with early knee OA and 204 (39.4%) with radiographic knee OA. In 393 (75.9%) females, menopause began. From the ROC analysis in pre-menopausal females, cutoff value of AMH for detecting early knee OA was 0.08 ng/ml (area under curve (AUC), 0.712; 95% CI, 0.527–0.897; p value, 0.025; odds ratio, 8.28). AUCs of other female hormones did not reach the level of AMH (range, 0.513 of prolactine to 0.636 of estradiol). Logistic regression analysis focusing on AMH reduction at menopausal transition showed that the related AMH below 0.08 ng/ml was significantly related to the presence of early knee OA (p = 0.035; odds ratio, 5.55). Reduced serum levels of AMH in middle-aged females were correlated with the presence of early knee OA, which might be a useful serum biomarker.