Gene expression profiles of circulating monocytes were analyzed to identify key genes associated with osteoporosis. Raw microarray data were downloaded from gene expression omnibus under accession number GSE7158, including 8 microarray dataset for patients with high peak bone mass (PBM) and 8 for low PBM. Package linear models for microarray data of R was adopted to screen out differentially expressed genes (DEGs). Gene ontology enrichment analysis and Kyoto encyclopedia of genes and genomes pathway analysis were performed with plug-ins of cytoscape. Protein-protein interaction network was constructed using FunCoup. A total of 283 DEGs were identified in low-PBM group, including 135 up- and 148 down-regulated genes. A considerable part of DEGs were localized in plasma membrane. Several ion transport-related pathways were revealed, such as mineral absorption and carbohydrate digestion and absorption. A range of DEGs were identified and some of them were related to calcium transport as well as osteoporosis. These findings are helpful in disclosing the pathogenetic mechanisms of osteoporosis.