Yin Qing, Yang Rui, Yu Haibo
Department of Orthopedics, Dianjiang Traditional Chinese Medicine Hospital Chongqing 408300, China.
Department of Orthopedics, Affiliated Traditional Chinese Medicine Hospital of Chongqing Three Gorges Medical College Chongqing 404100, China.
Am J Transl Res. 2025 Jul 15;17(7):5320-5331. doi: 10.62347/JRIQ2431. eCollection 2025.
To evaluate the diagnostic and predictive value of miR-146a for osteoporosis and bisphosphonate treatment outcomes, and to investigate the underlying mechanism by which bisphosphonates exert therapeutic effects via miR-146a regulation.
A retrospective cohort of 96 patients with osteoporosis and 90 healthy individuals undergoing routine health examinations was analyzed. Serum miR-146a levels were measured to assess their diagnostic utility for osteoporosis. Changes in miR-146a levels before and after one year of bisphosphonate treatment and their correlation with treatment efficacy were also analyzed. In addition, in vitro experiments were conducted to examine the effects of miR-146a and bisphosphonates on osteoclast differentiation and function.
Serum miR-146a levels were significantly lower in osteoporosis patients and negatively correlated with disease severity, demonstrating strong diagnostic performance (AUC=0.910, sensitivity =97.78%; specificity =77.08%). Following bisphosphonate treatment, miR-146a levels increased significantly and were positively associated with treatment response, showing moderate predictive value (AUC=0.761; sensitivity =82.29%, specificity =60.42%). Bisphosphonates inhibited osteoclast differentiation, an effect reversed by miR-146a inhibition and enhanced by miR-146a overexpression.
Serum miR-146a shows promise as a diagnostic and predictive biomarker for osteoporosis and the efficacy of bisphosphonate therapy. It plays a role in suppressing osteoclast differentiation, and bisphosphonates may exert their therapeutic effects in part by upregulating miR-146a. These findings suggest that targeting miR-146a could be a novel strategy for osteoporosis management.
评估miR-146a对骨质疏松症的诊断和预测价值以及双膦酸盐治疗效果，并探究双膦酸盐通过调控miR-146a发挥治疗作用的潜在机制。
分析了96例骨质疏松症患者和90例接受常规健康检查的健康个体的回顾性队列。测量血清miR-146a水平以评估其对骨质疏松症的诊断效用。还分析了双膦酸盐治疗一年前后miR-146a水平的变化及其与治疗效果的相关性。此外，进行体外实验以研究miR-146a和双膦酸盐对破骨细胞分化和功能的影响。
骨质疏松症患者血清miR-146a水平显著降低，且与疾病严重程度呈负相关，显示出较强的诊断性能（曲线下面积=0.910，敏感性=97.78%；特异性=77.08%）。双膦酸盐治疗后，miR-146a水平显著升高，并与治疗反应呈正相关，显示出中等的预测价值（曲线下面积=0.761；敏感性=82.29%，特异性=60.42%）。双膦酸盐抑制破骨细胞分化，miR-146a抑制可逆转该作用，而miR-146a过表达则增强该作用。
血清miR-146a有望成为骨质疏松症及双膦酸盐治疗疗效的诊断和预测生物标志物。它在抑制破骨细胞分化中起作用，双膦酸盐可能部分通过上调miR-146a发挥其治疗作用。这些发现表明，靶向miR-146a可能是骨质疏松症管理的一种新策略。
