Changes in Noradrenergic Synthesis and Dopamine Beta-Hydroxylase Activity in Response to Oxidative Stress after Iron-induced Brain Injury.

Noradrenaline (NA) levels are altered during the first hours and several days after cortical injury. NA modulates motor functional recovery. The present study investigated whether iron-induced cortical injury modulated noradrenergic synthesis and dopamine beta-hydroxylase (DBH) activity in response to oxidative stress in the brain cortex, pons and cerebellum of the rat. Seventy-eight rats were divided into two groups: (a) the sham group, which received an intracortical injection of a vehicle solution; and (b) the injured group, which received an intracortical injection of ferrous chloride. Motor deficits were evaluated for 20 days post-injury. On the 3rd and 20th days, the rats were euthanized to measure oxidative stress indicators (reactive oxygen species (ROS), reduced glutathione (GSH) and oxidized glutathione (GSSG)) and catecholamines (NA, dopamine (DA)), plus DBH mRNA and protein levels. Our results showed that iron-induced brain cortex injury increased noradrenergic synthesis and DBH activity in the brain cortex, pons and cerebellum at 3 days post-injury, predominantly on the ipsilateral side to the injury, in response to oxidative stress. A compensatory increase in contralateral noradrenergic activity was observed, but without changes in the DBH mRNA and protein levels in the cerebellum and pons. In conclusion, iron-induced cortical injury increased the noradrenergic response in the brain cortex, pons and cerebellum, particularly on the ipsilateral side, accompanied by a compensatory response on the contralateral side. The oxidative stress was countered by antioxidant activity, which favored functional recovery following motor deficits.

Proteomic Biomarkers Associated with Low Bone Mineral Density: A Systematic Review.

Osteoporosis is a globally relevant public health issue. Our study aimed to summarize the knowledge on the proteomic biomarkers for low bone mineral density over the last years. We conducted a systematic review following the PRISMA guidelines; the scoured databases were PubMed, Web of Sciences, Scopus, and EBSCO, from inception to 2 June 2023. A total of 610 relevant studies were identified and 33 were assessed for eligibility. Finally, 29 studies met the criteria for this systematic review. The risk of bias was evaluated using the Joanna Briggs Institute Critical Appraisal Checklist tool. From the studies selected, 154 proteins were associated with changes of bone mineral density, from which only 10 were reported in at least two articles. The protein-protein network analysis indicated potential biomarkers involved in the skeletal system, immune system process, regulation of protein metabolic process, regulation of signaling, transport, cellular component assembly, cell differentiation, hemostasis, and extracellular matrix organization. Mass spectrometry-based proteomic profiling has allowed the discovery of new biomarkers with diagnostic potential. However, it is necessary to compare and validate the potential biomarkers in different populations to determine their association with bone metabolism and evaluate their translation to the clinical management of osteoporosis.

Administration of Tamoxifen Can Regulate Changes in Gene Expression during the Acute Phase of Traumatic Spinal Cord Injury.

Traumatic spinal cord injury (SCI) causes irreversible damage leading to incapacity. Molecular mechanisms underlying SCI damage are not fully understood, preventing the development of novel therapies. Tamoxifen (TMX) has emerged as a promising therapy. Our aim was to identify transcriptome changes in the acute phase of SCI and the effect of Tamoxifen on those changes in a rat model of SCI. Four groups were considered: (1) Non-injured without TMX (Sham/TMX-), (2) Non-injured with TMX (Sham/TMX+), (3) injured without TMX (SCI/TMX-), and (4) injured with TMX (SCI/TMX+). Tamoxifen was administered intraperitoneally 30 min after injury, and spinal cord tissues were collected 24 h after injury. Clariom S Assays Array was used for transcriptome analysis. After comparing Sham/TMX- versus SCI/TMX-, 708 genes showed differential expression. The enriched pathways were the SCI pathway and pathways related to the inflammatory response. When comparing SCI/TMX- versus SCI/TMX+, only 30 genes showed differential expression, with no pathways enriched. Our results showed differential expression of genes related to the inflammatory response after SCI, and Tamoxifen seems to regulate gene expression changes in Ccr2 and Mmp12. Our study contributes data regarding the potential value of tamoxifen as a therapeutic resource for traumatic SCI during the acute phase.

Genetic polymorphisms rs1800871 and rs1800872 of IL-10 gene are associated with dengue infection, especially with serotype 1 and DwoWS in Mexican population.

INTRODUCTION: Dengue infection is generated by a complex interaction between DENV (Dengue Virus) and the host's immune response. Interleukin-10 is an immunoregulatory cytokine during DENV infection. The objective of this study was to investigate whether genetic variants in IL-10 could be useful as a predictive and susceptibility marker in the prognosis of DENV infection, particularly with serotype 1, and in participants with dengue without warning signs. MATERIAL AND METHODS: A study of cases (n = 365) and controls (n = 364) was carried out. Genotyping was performed by real-time PCR using TaqMan probes. Sample size power was calculated using Quanto software RESULTS: This is the first report showing the independent association of the T allele of rs1800871 (P = 0.023) and the A allele of rs1800872 (P = 0.010) with the risk of dengue infection. Statistical analysis established the genotypic association of IL-10 SNPs with DENV infection under different inheritance models. Our results also showed the association of the CC, TC, and CA haplotypes (P = 0.0064, P = 0.0032, and P = 0.0010 respectively) with infection. Furthermore, both polymorphic sites were associated with the risk of DwoWS and serotype 1 (Den-1) under different inheritance models. Finally, under the dominant model, we identified a positive correlation between IL-10 levels vs. IFN-γ and IL-8. CONCLUSION: Our results show the first independent association of the T and A alleles of the polymorphic sites rs1800871 and rs1800872, with dengue infection, particularly with Den-1, and in participants with DwoWs.

Unraveling the role of relative telomere length and CAG expansion on initial symptoms of juvenile Huntington disease.

BACKGROUND AND PURPOSE: Juvenile-onset Huntington disease (JHD) is defined when symptoms initiate before 20 years of age. Mechanisms explaining differences between juvenile and adult onset are not fully understood. Our aim was to analyze the distribution of initial symptoms in a cohort of JHD patients and to explore its relationship with CAG expansion and relative telomere length (RTL). METHODS: A total of 84 JHD patients and 54 neurologically healthy age and sex matched individuals were recruited. CAG length was measured by southern blot or triplet repeat primed polymerase chain reaction. RTL was measured using the Cawthon method. RESULTS: Psychiatric symptoms were most frequent when considering the entire cohort. When divided into onset before or after 10 years, cognitive symptoms were more frequent in the youngest, whilst in the older group psychiatric symptoms prevailed. Motor symptoms were rare in the youngest and epilepsy was observed only in this group as well as a larger CAG expansion. RTL analysis revealed shorter telomeres in JHD patients compared to controls. This difference is not influenced by age, initial symptoms, time of disease or CAG expansion. CONCLUSIONS: To the best of our knowledge this is the largest cohort of JHD patients reported. Psychiatric manifestations deserve special attention when JHD is suspected and epilepsy is especially important in the youngest patients. Initial symptoms seem to be influenced by CAG expansion and therefore age of onset. RTL is significantly reduced in JHD patients which can influence the characteristic neurodegeneration of JHD and contribute to the clinical discrepancy between adult and juvenile forms of Huntington disease.

Dietary inflammatory index and bone mineral density in Mexican population.

Dietary inflammatory index has been associated with bone loss. In this longitudinal study, we reported that changes in dietary inflammatory index were associated with a reduction in bone mineral density of the total hip and femoral neck in males and females ≥ 45 years, but not in individuals < 45 years. PURPOSE: Previous studies have suggested that an inflammatory environment can affect bone mineral density (BMD). However, most of the studies have been done in postmenopausal women. Thus, longitudinal studies in different age groups and sex are necessary to evaluate the longitudinal association between dietary inflammatory index (DII) and BMD in Mexican adults. METHODS: A total of 1,486 participants of the Health Workers Cohort Study were included in this study. The DII was estimated with data retrieved through a semi-quantitative food frequency questionnaire. Total hip, femoral neck, and lumbar spine BMD were measured by dual-energy X-ray absorptiometry. Linear regression models for cross-sectional associations and fixed effects linear regression models for longitudinal association were estimated, and both models were stratified by sex and age groups (< 45 and ≥ 45 years). RESULTS: We did not observe cross-sectional associations between DII and the different BMD sites at baseline. In contrast, women and men ≥ 45 years in the 25th quartile of changes in DII were associated with a gain of 0.067 g/cm2 and 0.062 g/cm2 of total hip BMD, while those in the 75th quartile of DII was associated with a reduction of - 0.108 g/cm2 and - 0.100 g/cm2, respectively. These results were similar for femoral neck BMD in women. In contrast, we did not observe association with femoral neck BMD in men. We did not observe statistically significant changes for lumbar spine BMD. CONCLUSION: Our data suggest that changes in the DII score are associated with changes in total hip and femoral neck BMD among Mexican population.

Association of high-risk human papillomavirus with ocular surface squamous neoplasia: a case-control study in Mexico.

OBJECTIVE: To investigate the association of high-risk hu-man papilloma virus (HR-HPV) and other risk factors with ocular surface squamous cell neoplasia (OSSN). MATERIALS AND METHODS: We obtained DNA from 22 fresh frozen OSSN tissues and 22 pterygia as controls, we used a broad-spectrum HPV DNA amplification short PCR fragment to identify HPV infection in all specimens and then genotyped HPV by a reverse hybridization line probe assay. We also obtained demographic, sun exposure, and tobacco consump-tion information. RESULTS: HR-HPV frequency was 40.9% in the OSSN group and 4.5% in the pterygia group (p=0.009). After covariate adjustment, OSSN was associated with HR-HPV (OR=16.3, 95%CI=1.2,218.1, p=0.03) and sunburn (OR=10.8, 95%CI=1.8,86.0, p=0.02). CONCLUSIONS: Ocular surface squamous cell neoplasia is a multifactorial disease. The strong association between HR-HPV and OSSN, suggests that HR-HPV could play an etiological role in OSSN development.

Unravelling the Contribution of the rs7041 and rs4588 Polymorphisms of the GC Gene and Serum VDBP Levels for Developing Metabolic Syndrome in the Mexican Population.

Metabolic syndrome (MetS) is a multifactorial disorder integrated by a constellation of cardiovascular risk factors. The genetic and environmental determinants of MetS are not fully elucidated. This study investigated the association of two common single nucleotide polymorphisms (SNPs) on GC, rs7041 and rs4588, derived haplotypes, and serum vitamin D binding protein (VDBP) levels with the susceptibility to suffer MetS in Mexican adults. We included 1924 individuals; clinical and biochemical data were obtained through standard methods. Genotyping was performed through predesigned TaqMan assays. Logistic regression models were used to assess the associations of interest. Prevalence of MetS was 52.9% in the whole population, being more frequent in women. We observed that some association results differed between sexes. The GG genotype of the rs7041 was associated with increased odds of MetS in women. For the rs4588, the CA genotype had a protective effect against MetS in women. The haplotype GC2 was associated with reduced odds for MetS and some of its components in women. Our data suggest that VDBP serum levels were influenced by genotypes/haplotypes and this interplay seems to influence the risk of MetS. Our data provide reliable evidence regarding the association of GC polymorphisms with MetS risk in Mexican women.

A proposed HLA-B*27 screening method for ankylosing spondylitis detection based on tag-single nucleotide polymorphisms: a preliminary study.

BACKGROUND: Ankylosing spondylitis (AS) is a type of inflammatory arthritis that affects primarily the spine. There is a strong association of the HLA-B*27 allele with AS pathogenesis, but recent studies have demonstrated the participation of ERAP1 gene in the genetic susceptibility. The aim of this study was to determine whether HLA-B tag-single nucleotide polymorphisms (SNPs) and ERAP1-related genetic variations associated with AS have equal or similarly performance in patients´ screening compared to HLA-B*27 standard genotyping in Mexican population. METHODS AND RESULTS: Genomic DNA from patients with AS and population-based controls from Mexico City was analyzed for five single nucleotide polymorphisms (SNPs): rs4349859, rs13202464, rs116488202, tagging HLA-B*27; and rs30187 and rs27044 in ERAP1 gene. TaqMan genotype assay method was used for SNPs genotyping. We found a significant association between AS and the heterozygote genotypes and minor alleles of the HLA-B*27 tag-SNPs, as well as for their haplotypes. With respect to ERAP1 polymorphisms, no significant associations were observed (p > 0.05). The sensitivity and specificity analysis showed values of 0.96 and 1.00 for the rs4349859 SNP, and 0.96 and 0.94 for the rs116488202 SNP, respectively, in detecting HLA-B*27 compared to the B27 test as the gold standard. CONCLUSIONS: HLA-B*27 tag-SNPs are associated with AS susceptibility; furthermore, the rs4349859 SNP by its own have an outstanding performance in detecting HLA-B*27 and therefore can be proposed as screening marker in the identification of HLA-B*27 in our population.

Ultrastructural changes in giant cell tumor of bone cultured cells exposed to quercetin.

Giant cell tumor of bone (GCTB) is a primary bone tumor that affects skeletally mature people and whose main treatment is surgical. Because there are few pharmacological alternatives for the treatment of this tumor to find other molecules or compounds that could be potential therapeutic agents is desirable. Quercetin is a flavonoid with described antitumoral effect in different types of cancer cell lines that could be a possible option in GCTB treatment. However, there is no literature about the effect of quercetin on GCTB. In the present paper, we reported the ultrastructural changes in GCTB cells exposed to quercetin and also determined the expression of RIP1K, Caspase 3 and Caspase 8 on the exposed cells. For this purpose, GCTB sample was obtained from one patient and cultured. Quercetin affected all the histological components of the GCTB. The ultrastructural changes consisted mainly in necroptosis, autophagocytosis and secondary necrosis. This is the first report about quercetin effects on giant cell tumor of bone cultured cells. Further studies in other models could be done to support the use of quercetin as a complementary treatment in giant cell tumor of bone.Abbreviations: Giant cell tumor of bone (GCTB); transmission electron microscopy (TEM); reverse transcription - polymerase chain reaction (RT-PCR); receptor interacting protein kinase 1 (RIP1K); Dulbecco's Modified Eagle's Medium (DMEM).

Single-nucleotide polymorphism rs10036727 in the SLIT3 gene is associated with osteoporosis at the femoral neck in older Mexican postmenopausal women.

AIMS: Osteoporosis (OP) remains a major public health problem worldwide. The most serious complications of this disease are fragility fractures, which increase morbidity and mortality. Management of OP represents an economic burden for health systems. Therefore, it is necessary to develop new screening strategies to identify the population at risk and implement preventive measures. We previously identified the SNPs rs3801387 in WNT16, rs7108738 in SOX6, rs10036727 in SLIT3 and rs7584262 in PKDCC as associated with bone mineral density in postmenopausal women through a genome-wide association study. The aim of this study was to validate those SNPs in two independent cohorts of non-related postmenopausal women. MATERIALS AND METHODS: We included 1160 women classifying them as normal, osteopenic or osteoporotic and a group with hip fragility fracture. Genotyping was performed using predesigned TaqMan assays. RESULTS: The variants rs10036727 and rs7108738 showed a significant association with BMD at the femoral neck. SLIT3 has been previously proposed as a potential biomarker and therapeutic resource. CONCLUSIONS: Our results provide new evidence regarding a possible involvement of SLIT3 in bone metabolisms and encourage the development of more studies in different populations to support these observations.

Association of the IL6 rs1800796, but not of the IL6 rs1800795, IL6R rs4845617 and rs2228145 polymorphisms with hip fracture in elderly Mexican women.

BACKGROUND AND AIMS: Polymorphisms in Interleukin-6 (IL6) and its receptor (IL6R) have been associated with bone mineral density. In this work, the G-174C and G-572C polymorphisms in IL6, G-208A, and Asp358Ala in IL6R were analyzed in Mexican women with hip fracture. METHODS: Postmenopausal Mexican women (60 years or over) with hip fragility fracture (77.97 ± 8 years) and without hip fracture (70.5 ± 7.02 years) were genotyped by real-time PCR. RESULTS: The rs1800796 GG genotype was associated with low risk of fracture (p = 0.05), while GC genotype was associated with high risk of fracture [p = 0.047, OR 2.3 (95% CI 1.013-5.2)]. The AA genotype of the rs2228145 SNP (IL6R) was significantly different [p = 0.033, OR 1.94 (95% CI 1.01-3.75)], but when data were adjusted by age and body mass index, there were no differences (p = 0.9). CONCLUSION: Our results suggest that the IL6 rs1800796 SNP is a good marker for hip fracture risk in Mexican women.

Dermochondrocorneal dystrophy (Francois syndrome) in a Mexican patient and literature review.

Dermochondrocorneal Dystrophy (OMIM 221800) is a very rare disease first described by Francois in 1949. It is characterized by the appearance of skin nodules, osteochondral deformities, and corneal opacities during childhood. Only a few cases have been reported. There is uncertainty about the inheritance pattern and no gene or genes have been associated to this disease. We report a patient from Mexican mestizo origin with the classic manifestations of Dermochondrocorneal Dystrophy. We perform a multidisciplinary assessment in order to contribute to the knowledge of the clinical presentation of this uncommon condition. Among the few documented patients, this is the third patient of Mexican ancestry reported with this syndrome.

Human telomeres that carry an integrated copy of human herpesvirus 6 are often short and unstable, facilitating release of the viral genome from the chromosome.

Linear chromosomes are stabilized by telomeres, but the presence of short dysfunctional telomeres triggers cellular senescence in human somatic tissues, thus contributing to ageing. Approximately 1% of the population inherits a chromosomally integrated copy of human herpesvirus 6 (CI-HHV-6), but the consequences of integration for the virus and for the telomere with the insertion are unknown. Here we show that the telomere on the distal end of the integrated virus is frequently the shortest measured in somatic cells but not the germline. The telomere carrying the CI-HHV-6 is also prone to truncations that result in the formation of a short telomere at a novel location within the viral genome. We detected extra-chromosomal circular HHV-6 molecules, some surprisingly comprising the entire viral genome with a single fully reconstituted direct repeat region (DR) with both terminal cleavage and packaging elements (PAC1 and PAC2). Truncated CI-HHV-6 and extra-chromosomal circular molecules are likely reciprocal products that arise through excision of a telomere-loop (t-loop) formed within the CI-HHV-6 genome. In summary, we show that the CI-HHV-6 genome disrupts stability of the associated telomere and this facilitates the release of viral sequences as circular molecules, some of which have the potential to become fully functioning viruses.

Association of the COL1A1 gene polymorphisms in Mexican postmenopausal women with fracture or with low bone mineral density at the hip.

BACKGROUND AND AIMS: Osteoporosis leads to high fracture risk and evidence suggests that genetic factors play an important role in this disease. The aim was to evaluate the association of two polymorphisms (-1997G/T, +1245G/T) in the collagen type1 alpha 1 gene (COL1A1) with fracture or with low bone mineral density (BMD) at the hip in postmenopausal Mexican women. METHODS: BMD was determined by bone densitometry and the risk factors were collected with a questionnaire. Genotyping was performed by real-time PCR. RESULTS: The polymorphisms were in Hardy-Weinberg equilibrium. The -1997G/+1245T haplotype showed, after adjustment for confounders, a fourfold increased risk of hip fracture [OR 4.32; p = 0.041 (95 % CI 1.07-17.43)]; while in the women with low BMD at the hip, the risk was increased threefold [OR 3.36; p = 0.022 (95 % CI 1.20-9.40)]. CONCLUSIONS: The results support the association of COL1A1 gene polymorphisms with fracture and with low BMD at the hip in Mexican population.

Association of a (TTTA)n microsatellite and a TCT del/ins polymorphisms in the aromatase gene (CYP19) with hip fracture risk in Mexican postmenopausal women.

A (TTTA)n polymorphism in the aromatase gene has been studied in relation to bone mineral density (BMD). The low number of TTTA repeats has been associated with low BMD and fracture risk. The aim of this study was to search for associations of TTTA copy number with hip fracture and lumbar spine osteoporosis in Mexican peri and postmenopausal women. The allele with seven repeats was present in the two reported versions, with or without a TCT deletion upstream of the microsatellite (A1 and A2, respectively). After adjustment by confounders, the A1 allele and the A1A1 genotype were significantly associated with an elevated risk of fracture (p = 0.034, OR = 3.2 [95% CI, 1.09-9.41] and p = 0.019, OR = 2.26 [95% CI, 1.14-4.49], respectively) and the A2 allele was associated with protection of hip fracture (p = 0.04, OR = 0.48, [95% CI, 0.22-1.05]) as the A2A2 genotype (p = 0.048, OR = 0.29 [95% CI, 0.06-1.16]). The analysis allowed us to defining the usefulness of the (TTTA)n polymorphism in the aromatase gene as an indicator of hip fracture risk in Mexican population.

The roles of WRN and BLM RecQ helicases in the Alternative Lengthening of Telomeres.

Approximately 10% of all cancers, but a higher proportion of sarcomas, use the recombination-based alternative lengthening of telomeres (ALT) to maintain telomeres. Two RecQ helicase genes, BLM and WRN, play important roles in homologous recombination repair and they have been implicated in telomeric recombination activity, but their precise roles in ALT are unclear. Using analysis of sequence variation present in human telomeres, we found that a WRN- ALT+ cell line lacks the class of complex telomere mutations attributed to inter-telomeric recombination in other ALT+ cell lines. This suggests that WRN facilitates inter-telomeric recombination when there are sequence differences between the donor and recipient molecules or that sister-telomere interactions are suppressed in the presence of WRN and this promotes inter-telomeric recombination. Depleting BLM in the WRN- ALT+ cell line increased the mutation frequency at telomeres and at the MS32 minisatellite, which is a marker of ALT. The absence of complex telomere mutations persisted in BLM-depleted clones, and there was a clear increase in sequence homogenization across the telomere and MS32 repeat arrays. These data indicate that BLM suppresses unequal sister chromatid interactions that result in excessive homogenization at MS32 and at telomeres in ALT+ cells.

Skin pigmentation related variants in Mexican population and interaction effects on serum 25(OH)D concentration and vitamin D deficiency.

Skin pigmentation is negatively associated with circulating vitamin D (VD) concentration. Therefore, genetic factors involved in skin pigmentation could influence the risk of vitamin D deficiency (VDD). We evaluated the impact genetic variants related to skin pigmentation on VD in Mexican population. This cross-sectional analysis included 848 individuals from the Health Worker Cohort Study (ratio males to females ~ 1:3). Eight genetic variants: rs16891982 (SLC45A2), rs12203592 (IRF4), rs1042602 and rs1126809 (TYR), rs1800404 (OCA2), rs12913832 (HERC2), rs1426654 (SLC24A5), and rs2240751 (MFSD12); involved in skin pigmentation were genotyped. Skin pigmentation was assessed by self-report. Linear and logistic regression were used to assess the association between the variants of interest and VD and VDD, as appropriate. In our study, eight genetic variants were associated with skin pigmentation. A genetic risk score built with the variants rs1426654 and rs224075 was associated with lower VD levels (ß = - 1.38, 95% CI - 2.59, - 0.17, p = 0.025). Nevertheless, when examining gene-gene interactions, we observed that rs2240751 × rs12203592 were associated with VD levels (P interaction = 0.021). Whereas rs2240751 × rs12913832 (P interaction = 0.0001) were associated with VDD. Our results suggest that skin pigmentation-related gene variants are associated with lower VD levels in Mexican population. These results underscore the importance of considering genetic interactions when assessing the impact of genetic polymorphisms on VD levels.

The Involvement of microRNAs in Bone Remodeling Signaling Pathways and Their Role in the Development of 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-ß/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.

Label-free quantitative proteomics in serum reveals candidate biomarkers associated with low bone mineral density in Mexican postmenopausal women.

Postmenopausal osteoporosis is a public health problem leading to an increased risk of fractures, negatively impacting women's health. The absence of sensitive and specific biomarkers for early detection of osteoporosis represents a substantial challenge for improving patient management. Herein, we aimed to identify potential candidate proteins associated with low bone mineral density (BMD) in postmenopausal women from the Mexican population. Serum samples from postmenopausal women (40 with normal BMD, 40 with osteopenia (OS), and 20 with osteoporosis (OP)) were analyzed by label-free LC-MS/MS quantitative proteomics. Proteome profiling revealed significant differences between the OS and OP groups compared to individuals with normal BMD. A quantitative comparison of proteins between groups indicated 454 differentially expressed proteins (DEPs). Compared to normal BMD, 14 and 214 DEPs were found in OS and OP groups, respectively, while 226 DEPs were identified between OS and OP groups. The protein-protein interaction and enrichment analysis of DEPs were closely linked to the bone mineral content, skeletal morphology, and immune response activation. Based on their role in bone metabolism, a panel of 12 candidate biomarkers was selected, of which 1 DEP (RYR1) was found upregulated in the OS and OP groups, 8 DEPs (APOA1, SHBG, FETB, MASP1, PTK2B, KNG1, GSN, and B2M) were upregulated in OP and 3 DEPs (APOA2, RYR3, and HBD) were downregulated in OS or OP. The proteomic analysis described here may help discover new and potentially non-invasive biomarkers for the early diagnosis of osteoporosis in postmenopausal women.