Abstract
Objective: 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. Methods: 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. Results: 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. Conclusion: 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.