A study identified two plasma microRNA (miRNA) signatures associated with skeletal muscle wasting in post-menopausal osteoporotic women. The research analyzed 28 post-menopausal osteoporotic women, divided into three tertiles based on appendicular skeletal muscle mass index (ASMMI). Five miRNAs were down-regulated and two were up-regulated in the first tertile (low ASMMI) compared to the third tertile (high ASMMI). These miRNAs showed high diagnostic potential, with area under the curve (AUC) values exceeding 0.8. Two miRNA signatures, hsa-miR-126-5p, hsa-miR-146a-5p, and hsa-miR-425-5p, and hsa-miR-126-5p, hsa-miR-146a-5p, hsa-miR-145-5p, and hsa-miR-25-3p, demonstrated the highest AUC values of 0.914 and 0.901, respectively. These signatures could serve as potential biomarkers for skeletal muscle mass wasting in post-menopausal osteoporotic women. The study also evaluated adipo-myokines, but no significant differences were found between the tertiles. The findings suggest that miRNA profiling could be a valuable tool for early diagnosis of skeletal muscle loss in post-menopausal osteoporotic women. The study highlights the importance of understanding the endocrine crosstalk between bone and muscle in aging and the potential of miRNAs as biomarkers for osteosarcopenia. The results indicate that miRNA signatures could improve the diagnosis and monitoring of skeletal muscle wasting in post-menopausal osteoporotic women.A study identified two plasma microRNA (miRNA) signatures associated with skeletal muscle wasting in post-menopausal osteoporotic women. The research analyzed 28 post-menopausal osteoporotic women, divided into three tertiles based on appendicular skeletal muscle mass index (ASMMI). Five miRNAs were down-regulated and two were up-regulated in the first tertile (low ASMMI) compared to the third tertile (high ASMMI). These miRNAs showed high diagnostic potential, with area under the curve (AUC) values exceeding 0.8. Two miRNA signatures, hsa-miR-126-5p, hsa-miR-146a-5p, and hsa-miR-425-5p, and hsa-miR-126-5p, hsa-miR-146a-5p, hsa-miR-145-5p, and hsa-miR-25-3p, demonstrated the highest AUC values of 0.914 and 0.901, respectively. These signatures could serve as potential biomarkers for skeletal muscle mass wasting in post-menopausal osteoporotic women. The study also evaluated adipo-myokines, but no significant differences were found between the tertiles. The findings suggest that miRNA profiling could be a valuable tool for early diagnosis of skeletal muscle loss in post-menopausal osteoporotic women. The study highlights the importance of understanding the endocrine crosstalk between bone and muscle in aging and the potential of miRNAs as biomarkers for osteosarcopenia. The results indicate that miRNA signatures could improve the diagnosis and monitoring of skeletal muscle wasting in post-menopausal osteoporotic women.