Objective：To investigate the role of differential genes and lncRNA RAD51⁃AS1 in primary osteoporosis(OP)，which provides new insights for the diagnosis and treatment of primary osteoporosis. Methods：The GSE35956 microarray data from the GEO database was used for analysis. Differentially expressed genes(DEG)were obtained by using the DEseq2，and the ClusterProfiler was used to find the enrichment of DEGs. The microarrays were then reannotated to discover the differential long ⁃ non coding RNA (lncRNA)in OP. The expression of RAD51⁃AS1 in hBMSC was verified by qRT⁃PCR. Finally，the effects of RAD51⁃AS1 on hBMSC proliferation and osteogenic differentiation were examined by MTT，colony formation，and ALP staining. Results：A total of 1 440 DEG was obtained about mRNAs in this study，whose functions were mainly enriched in processes such as receptor ⁃ ligand activity and monocyte differentiation. A total of 105 DEG regarding lncRNAs were also acquired. We found that RAD51 ⁃ AS1 expression was significantly downregulated in osteoporosis. The proliferation and ALP activity of hBMSC was reduced after silencing RAD51⁃AS1. Conclusions：The PI3K ⁃Akt signaling pathway and monocyte differentiation plays important roles in osteoporosis by bioinformatics. LncRNA RAD51 ⁃ AS1 regulates the proliferation and differentiation of bone marrow mesenchymal stem cells to ameliorate the progression of osteoporosisby cytological verification.