OBJECTIVE: Despite improve-ments in research on osteoporosis in the elder-ly, the specific mechanism remains unknown. In order to develop better treatment regimens with better efficacy and fewer adverse reactions (ARs), it is vital to unravel the pathogenesis of osteoporosis in the elderly. The GEO chip was used to screen differential genes in senile os-teoporosis and analyze their interaction mech-anisms in order to obtain potential therapeutic pathways and targets.MATERIALS AND METHODS: GSE35956 was downloaded from GEO database and used as the research object for KEGG pathway enrich-ment analysis, GO enrichment analysis and pro-tein-protein interaction (PPI) network analysis, respectively, to explore the related mechanisms of the occurrence and development of osteopo-rosis in the elderly.RESULTS: There were 156 differentially ex-pressed genes in the elderly (72 years old) and middle-aged (42 years old) diagnosed with oste-oporosis, of which 6 were up-regulated and 150 were down-regulated. An analysis of gene en-richment using GO (gene body) revealed that dif-ferentially expressed genes (DEG) were main-ly distributed in extracellular matrix (ECM) and other cell structures. Its functions include ossi-fication, parathyroid hormone metabolism, mul-ticellular biological signaling pathway, vitamin catabolism, interleukin-5 metabolism, trans -membrane transporter activity, receptor sig-naling pathway, calcium metabolism and other molecular functions. According to the Kyoto En-cyclopedia of Genes and Genomes (KEGG), an online resource, signaling pathways associat-ed with age-related osteoporosis (OP) are sig-nificantly enriched. The DEG enrichment path-ways include Wnt, ECM-receptor interaction, cGMP-PKG, GAG degradation, and calcium sig-naling. A protein and protein interaction (PPI) network was constructed for 14 key genes, in-cluding CD44, GRIA1, KNG1 and IL7R.CONCLUSIONS: The findings of this study in-dicate that CD44, GRIA1, KNG1, IL7R, and other differential genes affect the Wnt signaling path-way in the elderly, which can provide new targets for the follow-up basic research and treatment of osteoporosis in the elderly.