Research on zoledronic acid's synergistic improvement of intervertebral disc degeneration and osteoporosis by regulating inflammation matrix microenvironment.

Intervertebral disc degeneration (IVDD) and osteoporosis (OP) are two highly prevalent degenerative diseases of the skeleton, and recent epidemiologic data have shown that the co-morbidity rate of IVDD and OP is as high as 32-45% in the elderly population, suggesting that there may be a potential molecular association. Currently, there is a lack of in-depth exploration of the co-morbidity mechanism and synergistic therapeutic targets. The aim of this study was to analyze the common pathogenic pathways of IVDD and OP and to verify the potential regulatory effects of zoledronic acid (ZOLA), a first-line anti-osteoporosis drug, on IVDD, which would provide a theoretical basis for the development of synergistic therapeutic strategies. A total of 665 co-morbid core genes were obtained from the intersection of IVDD and OP, and GO analysis showed that these genes were significantly enriched in the biological processes of inflammatory response regulation, extracellular matrix catabolism, and osteoblast differentiation, and the KEGG pathway was mainly involved in peroxisome and osteoclasts. Twelve potential targets were mapped by ZOLA, and seven core targets were obtained by intersecting with IVDD-OP co-morbid genes. Molecular docking confirmed the stable binding ability of ZOLA with FDPS, GGPS1, FDFT1, and MVD targets. This study reveals that IVDD and OP share a core molecular network of inflammation-matrix metabolic imbalance and confirms that the anti-osteoporosis drug ZOLA can intervene in the process of intervertebral disc degeneration through multi-target synergy. This finding not only provides a new perspective for the "co-treatment" of degenerative bone diseases but also lays a theoretical foundation for the clinical application of ZOLA.