Department of Orthopedic Surgery, Hirosaki University Graduate School of Medicine, 5 Zaifu-cho, Hirosaki, Aomori, 036-8562, Japan.
Department of Obstetrics and Gynecology, Hirosaki University Graduate School of Medicine, Hirosaki, Japan.
Sci Rep. 2021 Mar 2;11(1):4931. doi: 10.1038/s41598-021-84584-0.
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.
一项最近的流行病学研究表明，50 岁及以上女性中早期膝关节骨关节炎（OA）的患病率最高。早期膝 OA 的主要致病因素是性别。尽管雌激素在评估 OA 中的软骨和骨代谢中具有相关性，但由于绝经过渡期女性激素模式不稳定，难以进行临床监测。抗苗勒管激素（AMH）已被发现是预测绝经的一种新的稳定生物标志物。本研究旨在通过使用血清生物标志物，特别是 AMH，探讨绝经过渡与早期膝 OA 之间的关系。共纳入 518 名参加磐城队列研究的女性志愿者，分为绝经前组和绝经后组。采用 Kellgren-Lawrence（KL）分级对负重前后膝关节 X 线片进行分类，KL 分级≥2 定义为放射学膝关节 OA。在 KL 分级为 0 和 1 的患者中，Luyten 标准定义为早期膝关节 OA。测定女性激素的 AMH、促黄体生成素、卵泡刺激素、雌二醇（pg/ml）、催乳素和睾酮。测定桡骨远端的骨密度。通过 ROC 分析（比较曲线下面积，AUC）和回归分析来评估女性激素对早期膝 OA 的预测能力。52 名患者（10.0%）被诊断为早期膝 OA，204 名患者（39.4%）为放射学膝关节 OA。在 393 名女性（75.9%）中，绝经开始。在绝经前女性的 ROC 分析中，AMH 检测早期膝 OA 的截断值为 0.08ng/ml（AUC，0.712；95%CI，0.527-0.897；p 值，0.025；比值比，8.28）。其他女性激素的 AUC 未达到 AMH 水平（范围为催乳素的 0.513 至雌二醇的 0.636）。重点关注绝经过渡时 AMH 降低的 logistic 回归分析显示，相关的 AMH 低于 0.08ng/ml 与早期膝 OA 的存在显著相关（p=0.035；比值比，5.55）。中年女性血清 AMH 水平降低与早期膝 OA 的存在相关，这可能是一种有用的血清生物标志物。
