Osteoporosis is a skeletal disease mainly affecting women over 50 years old and it represents a serious public health problem because of the high socioeconomic burden. This disease is characterized by deterioration of bone microarchitecture, low bone mineral density (BMD), and increased risk of fragility fractures. This study aimed to identify serum useful proteins as biomarkers for the diagnosis and/or prognosis of osteoporosis and fracture risk. We collected 446 serum samples from postmenopausal women aged ≥45 years old. Based on the BMD measurement, we classified the participants into three groups: osteoporotic, osteopenic, and normal. In an initial discovery stage, we conducted a proteomic approach using two-dimensional differential gel electrophoresis (2D-DIGE). The peptides into the spots of interest were identified through matrix-assisted laser desorption/ionization-time of flight (MALDI-TOF/TOF). Enzyme-linked immunosorbent assay (ELISA) was performed to validate the proteins of interest. We identified 27 spots of interest when comparing low BMD versus normal BMD postmenopausal women. Based on their relevance in bone metabolism, we analyzed three proteins: ceruloplasmin (CP), gelsolin (GSN), and vitamin D-binding protein (VDBP). Our results demonstrated that low serum VDBP levels correlate with low BMD (osteopenic and osteoporotic). Therefore, VDBP could be considered as a novel, potential, and non-invasive biomarker for the early detection of osteoporosis.

Genome-wide association studies in people with European ancestry suggest that polymorphisms in genes involved in vitamin D (VD) metabolism have an effect on serum concentrations of 25-hydroxyvitamin D. However, nothing is known about these polymorphisms in populations with Amerindian ancestry. Our aim was to evaluate the association between genetic variants on the vitamin D receptor (VDR) and the vitamin D binding protein (GC) genes, involved in the VD pathway, and VD deficiency in 689 unrelated Mexican postmenopausal women. We also described the frequencies of these variants in 355 postmenopausal women from different ethnic groups. Based on our preliminary results of 400 unrelated Mexican postmenopausal women, three single nucleotide polymorphisms (SNPs) were selected for genotyping. The SNPs rs4516035 in VDR and rs2282679 in GC were associated with VD deficiency. Additionally, women who carried three risk alleles had a 3.67 times higher risk of suffering VD deficiency, compared to women with no risk alleles (p = 0.002). The rs4516035-C allele frequency in the Amerindian population was enriched in the South East region of Mexico. In contrast, the highest frequency of the rs2298850-C allele, a proxy for the tag SNP rs2282679, was observed in the South region. Our results indicate that genetic variants in VDR and GC genes are associated with VD deficiency in Mexican postmenopausal women. Moreover, an association was observed for the variants rs3794060 and rs4944957 of the DHCR7/NADSYN1 gene with osteopenia/osteoporosis.

Bone remodeling, crucial for maintaining the balance between bone resorption and formation, relies on the coordinated activity of osteoclasts and osteoblasts. During osteoclastogenesis, hematopoietic stem cells (HSCs) differentiate into the osteoclast lineage through the signaling pathways OPG/RANK/RANKL. On the other hand, during osteoblastogenesis, mesenchymal stem cells (MSCs) differentiate into the osteoblast lineage through activation of the signaling pathways TGF-β/BMP/Wnt. Recent studies have shown that bone remodeling is regulated by post-transcriptional mechanisms including microRNAs (miRNAs). miRNAs are small, single-stranded, noncoding RNAs approximately 22 nucleotides in length. miRNAs can regulate virtually all cellular processes through binding to miRNA-response elements (MRE) at the 3’ untranslated region (3′UTR) of the target mRNA. miRNAs are involved in controlling gene expression during osteogenic differentiation through the regulation of key signaling cascades during bone formation and resorption. Alterations of miRNA expression could favor the development of bone disorders, including osteoporosis. This review provides a general description of the miRNAs involved in bone remodeling and their significance in osteoporosis development.