The paradox of bone mineral density and fracture risk in type 2 diabetes.

Fracture risk in type 2 diabetes (T2D) patients is paradoxically increased despite no decrease in areal bone mineral density (BMD). This phenomenon, known as the "diabetic bone paradox", has been attributed to various factors including alterations in bone microarchitecture and composition, hyperinsulinemia and hyperglycemia, advanced glycation end products (AGEs), and comorbidities associated with T2D. Zhao et al. recently investigated the relationship between T2D and fracture risk using both genetic and phenotypic datasets. Their findings suggest that genetically predicted T2D is associated with higher BMD and lower fracture risk, indicating that the bone paradox is not observed when confounding factors are controlled using Mendelian randomization (MR) analysis. However, in prospective phenotypic analysis, T2D remained associated with higher BMD and higher fracture risk, even after adjusting for confounding factors. Stratified analysis revealed that the bone paradox may disappear when T2D-related risk factors are eliminated. The study also highlighted the role of obesity in the relationship between T2D and fracture risk, with BMI mediating a significant portion of the protective effect. Overall, managing T2D-related risk factors may be crucial in preventing fracture risk in T2D patients.

Deciphering the complex relationship between type 2 diabetes and fracture risk with both genetic and observational evidence.

The 'diabetic bone paradox' suggested that type 2 diabetes (T2D) patients would have higher areal bone mineral density (BMD) but higher fracture risk than individuals without T2D. In this study, we found that the genetically predicted T2D was associated with higher BMD and lower risk of fracture in both weighted genetic risk score (wGRS) and two-sample Mendelian randomization (MR) analyses. We also identified ten genomic loci shared between T2D and fracture, with the top signal at SNP rs4580892 in the intron of gene RSPO3. And the higher expression in adipose subcutaneous and higher protein level in plasma of RSPO3 were associated with increased risk of T2D, but decreased risk of fracture. In the prospective study, T2D was observed to be associated with higher risk of fracture, but BMI mediated 30.2% of the protective effect. However, when stratified by the T2D-related risk factors for fracture, we observed that the effect of T2D on the risk of fracture decreased when the number of T2D-related risk factors decreased, and the association became non-significant if the T2D patients carried none of the risk factors. In conclusion, the genetically determined T2D might not be associated with higher risk of fracture. And the shared genetic architecture between T2D and fracture suggested a top signal around RSPO3 gene. The observed effect size of T2D on fracture risk decreased if the T2D-related risk factors could be eliminated. Therefore, it is important to manage the complications of T2D to prevent the risk of fracture.

Correlation Between TRAb and Early Onset Hypothyroidism After 131I Treatment for Graves' Disease.

The aim of the study was to explore the clinical features related to early hypothyroidism and the relationship between the changes of thyrotropin receptor antibodies (TRAb) and early hypothyroidism in the course of 131I treatment for Graves' disease. This study was a retrospective observation, including 226 patients who received the first 131I treatment. The general information and laboratory tests were collected before and after 131I treatment, and the laboratory data affecting the difference in disease outcome were analyzed. According to the changes of antibodies in the third month, whether the changes of antibodies were involved in the occurrence of early-onset hypothyroidism was analyzed. Early onset hypothyroidism occurred in 165 of 226 patients, and the results showed that the incidence of early hypothyroidism was higher in patients with low baseline TRAb level (p=0.03) and increased TRAb after treatment (p=0.007). Both baseline TRAb levels (p<0.001) and the 24-hour iodine uptake rate (p=0.004) are significant factors influencing the changes in TRAb. The likelihood of a rise in TRAb was higher when the baseline TRAb was less than 18.55 U/l and the 24-hour iodine uptake level exceeded 63.61%. Low baseline and elevated post-treatment levels of TRAb were significantly associated with early-onset hypothyroidism after 131I treatment. Monitoring this index during RAI treatment is helpful in identifying early-onset hypothyroidism and mastering the clinical outcome and prognosis of Graves' disease.

Circadian rhythm and circulating cell-free DNA release on healthy subjects.

In the last decade, clinical studies have investigated the clinical relevance of circulating cell-free-DNA (ccfDNA) as a diagnostic and prognosis tool in various diseases including cancers. However, limited knowledge on ccfDNA biology restrains its full development in the clinical practice. To improve our understanding, we evaluated the impact of the circadian rhythm on ccfDNA release in healthy subjects over a 24-h period. 10 healthy female subjects underwent blood sampling at 8am and 20 healthy male subjects underwent serial blood sampling (8:00 AM, 9:00 AM, 12:00 PM, 4:00 PM, 8:00 PM, 12:00 AM, 4 AM (+ 1 Day) and 8 AM (+ 1 Day)). We performed digital droplet-based PCR (ddPCR) assays to target 2 DNA fragments (69 & 243 bp) located in the KRAS gene to determine the ccfDNA concentration and fragmentation profile. As control, half of the samples were re-analyzed by capillary miniaturized electrophoresis (BIAbooster system). Overall, we did not detect any influence of the circadian rhythm on ccfDNA release. Instead, we observed a decrease in the ccfDNA concentration after meal ingestion, suggesting either a post-prandial effect or a technical detection bias due to a higher plasma load in lipids and triglycerides. We also noticed a potential effect of gender, weight and creatinine levels on ccfDNA concentration.

Inflammation and cardiometabolic diseases induced by persistent organic pollutants and nutritional interventions: Effects of multi-organ interactions.

The development and outcome of inflammatory diseases are associated with genetic and lifestyle factors, which include chemical and nonchemical stressors. Persistent organic pollutants (POPs) are major groups of chemical stressors. For example, dioxin-like polychlorinated biphenyls (PCBs), per- and polyfluoroalkyl substances (PFASs), and polybrominated diphenyl ethers (PBDEs) are closely associated with the incidence of inflammatory diseases. The pathology of environmental chemical-mediated inflammatory diseases is complex and may involve disturbances in multiple organs, including the gut, liver, brain, vascular tissues, and immune systems. Recent studies suggested that diet-derived nutrients (e.g., phytochemicals, vitamins, unsaturated fatty acids, dietary fibers) could modulate environmental insults and affect disease development, progression, and outcome. In this article, mechanisms of environmental pollutant-induced inflammation and cardiometabolic diseases are reviewed, focusing on multi-organ interplays and highlighting recent advances in nutritional strategies to improve the outcome of cardiometabolic diseases associated with environmental exposures. In addition, advanced system biology approaches are discussed, which present unique opportunities to unveil the complex interactions among multiple organs and to fuel the development of precision intervention strategies in exposed individuals.

Deciphering Protein O-GalNAcylation: Method Development and Disease Implication.

Mucin-type O-glycosylation is an important protein post-translational modification that is abundantly expressed on cell surface proteins. Protein O-glycosylation plays a variety of roles in cellular biological functions including protein structure and signal transduction to the immune response. Cell surface mucins are highly O-glycosylated and are the main substance of the mucosal barrier that protects the gastrointestinal or respiratory tract from infection by pathogens or microorganisms. Dysregulation of mucin O-glycosylation may impair mucosal protection against pathogens that can invade cells to trigger infection or immune evasion. Truncated O-glycosylation, also known as Tn antigen or O-GalNAcylation, is highly upregulated in diseases such cancer, autoimmune disorders, neurodegenerative diseases, and IgA nephropathy. Characterization of O-GalNAcylation helps decipher the role of Tn antigen in physiopathology and therapy. However, the analysis of O-glycosylation, specifically the Tn antigen, remains challenging due to the lack of reliable enrichment and identification assays compared to N-glycosylation. Here, we summarize recent advances in analytical methods for O-GalNAcylation enrichment and identification and highlight the biological role of the Tn antigen in various diseases and the clinical implications of identifying aberrant O-GalNAcylation.

Intratumor heterogeneity and cell secretome promote chemotherapy resistance and progression of colorectal cancer.

The major underlying cause for the high mortality rate in colorectal cancer (CRC) relies on its drug resistance, to which intratumor heterogeneity (ITH) contributes substantially. CRC tumors have been reported to comprise heterogeneous populations of cancer cells that can be grouped into 4 consensus molecular subtypes (CMS). However, the impact of inter-cellular interaction between these cellular states on the emergence of drug resistance and CRC progression remains elusive. Here, we explored the interaction between cell lines belonging to the CMS1 (HCT116 and LoVo) and the CMS4 (SW620 and MDST8) in a 3D coculture model, mimicking the ITH of CRC. The spatial distribution of each cell population showed that CMS1 cells had a preference to grow in the center of cocultured spheroids, while CMS4 cells localized at the periphery, in line with observations in tumors from CRC patients. Cocultures of CMS1 and CMS4 cells did not alter cell growth, but significantly sustained the survival of both CMS1 and CMS4 cells in response to the front-line chemotherapeutic agent 5-fluorouracil (5-FU). Mechanistically, the secretome of CMS1 cells exhibited a remarkable protective effect for CMS4 cells against 5-FU treatment, while promoting cellular invasion. Secreted metabolites may be responsible for these effects, as demonstrated by the existence of 5-FU induced metabolomic shifts, as well as by the experimental transfer of the metabolome between CMS1 and CMS4 cells. Overall, our results suggest that the interplay between CMS1 and CMS4 cells stimulates CRC progression and reduces the efficacy of chemotherapy.

Scalable Formation of Highly Viable and Functional Hepatocellular Carcinoma Spheroids in an Oxygen-Permeable Microwell Device for Anti-Tumor Drug Evaluation.

For high-throughput anti-cancer drug screening, microwell arrays may serve as an effective tool to generate uniform and scalable tumor spheroids. However, microwell arrays are commonly anchored in non-oxygen-permeable culture plates, leading to limited oxygen supply for avascular spheroids. Herein, a polydimethylsiloxane (PDMS)-based oxygen-permeable microwell device is introduced for generating highly viable and functional hepatocellular carcinoma (HCC) spheroids. The PDMS sheets at the bottom of the microwell device provide a high flux of oxygen like in vivo neighboring hepatic sinusoids. Owing to the better oxygen supply, the generated HepG2 spheroids are larger in size and exhibit higher viability and proliferation with less cell apoptosis and necrosis. These spheroids also exhibit lower levels of anaerobic cellular respiration and express higher levels of liver-related functions. In anti-cancer drug testing, spheroids cultured in PDMS plates show a significantly stronger resistance against doxorubicin because of the stronger stem-cell and multidrug resistance phenotype. Moreover, higher expression of vascular endothelial growth factor-A produces a stronger angiogenesis capability of the spheroids. Overall, compared to the spheroids cultured in conventional non-oxygen-permeable plates, these spheroids can be used as a more favorable model for early-stage HCCs and be applied in high-throughput anti-cancer drug screening.

Frontiers in single cell analysis: multimodal technologies and their clinical perspectives.

Single cell multimodal analysis is at the frontier of single cell research: it defines the roles and functions of distinct cell types through simultaneous analysis to provide unprecedented insight into cellular processes. Current single cell approaches are rapidly moving toward multimodal characterizations. It replaces one-dimensional single cell analysis, for example by allowing for simultaneous measurement of transcription and post-transcriptional regulation, epigenetic modifications and/or surface protein expression. By providing deeper insights into single cell processes, multimodal single cell analyses paves the way to new understandings in various cellular processes such as cell fate decisions, physiological heterogeneity or genotype-phenotype linkages. At the forefront of this, microfluidics is key for high-throughput single cell analysis. Here, we present an overview of the recent multimodal microfluidic platforms having a potential in biomedical research, with a specific focus on their potential clinical applications.

Recent development of analytical methods for disease-specific protein O-GlcNAcylation.

The enzymatic modification of protein serine or threonine residues by N-acetylglucosamine, namely O-GlcNAcylation, is a ubiquitous post-translational modification that frequently occurs in the nucleus and cytoplasm. O-GlcNAcylation is dynamically regulated by two enzymes, O-GlcNAc transferase and O-GlcNAcase, and regulates nearly all cellular processes in epigenetics, transcription, translation, cell division, metabolism, signal transduction and stress. Aberrant O-GlcNAcylation has been shown in a variety of diseases, including diabetes, neurodegenerative diseases and cancers. Deciphering O-GlcNAcylation remains a challenge due to its low abundance, low stoichiometry and extreme lability in most tandem mass spectrometry. Separation or enrichment of O-GlcNAc proteins or peptides from complex mixtures has been of great interest because quantitative analysis of protein O-GlcNAcylation can elucidate their functions and regulatory mechanisms in disease. However, valid and specific analytical methods are still lacking, and efforts are needed to further advance this direction. Here, we provide an overview of recent advances in various analytical methods, focusing on chemical oxidation, affinity of antibodies and lectins, hydrophilic interaction, and enzymatic addition of monosaccharides in conjugation with these methods. O-GlcNAcylation quantification has been described in detail using mass-spectrometric or non-mass-spectrometric techniques. We briefly summarized dysregulated changes in O-GlcNAcylation in disease.

Circulating Ubiquitous RNA, A Highly Predictive and Prognostic Biomarker in Hospitalized Coronavirus Disease 2019 (COVID-19) Patients.

BACKGROUND: Approximately 15-30% of hospitalized coronavirus disease 2019 (COVID-19) patients develop acute respiratory distress syndrome, systemic tissue injury, and/or multi-organ failure leading to death in around 45% of cases. There is a clear need for biomarkers that quantify tissue injury, predict clinical outcomes, and guide the clinical management of hospitalized COVID-19 patients. METHODS: We herein report the quantification by droplet-based digital polymerase chain reaction (ddPCR) of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNAemia and the plasmatic release of a ubiquitous human intracellular marker, the ribonuclease P (RNase P) in order to evaluate tissue injury and cell lysis in the plasma of 139 COVID-19 hospitalized patients at admission. RESULTS: We confirmed that SARS-CoV-2 RNAemia was associated with clinical severity of COVID-19 patients. In addition, we showed that plasmatic RNase P RNAemia at admission was also highly correlated with disease severity (P < .001) and invasive mechanical ventilation status (P < .001) but not with pulmonary severity. Altogether, these results indicate a consequent cell lysis process in severe and critical patients but not systematically due to lung cell death. Finally, the plasmatic RNase P RNA value was also significantly associated with overall survival. CONCLUSIONS: Viral and ubiquitous blood biomarkers monitored by ddPCR could be useful for the clinical monitoring and the management of hospitalized COVID-19 patients. Moreover, these results could pave the way for new and more personalized circulating biomarkers in COVID-19, and more generally in infectious diseases, specific from each patient organ injury profile.

A Rationally Designed Supercharged Protein-Enzyme Chimera Self-Assembles In Situ to Yield Bifunctional Composite Textiles.

Catalytically active materials for the enhancement of personalized protective equipment (PPE) could be advantageous to help alleviate threats posed by neurotoxic organophosphorus compounds (OPs). Accordingly, a chimeric protein comprised of a supercharged green fluorescent protein (scGFP) and phosphotriesterase from Agrobacterium radiobacter (arPTE) was designed to drive the polymer surfactant (S-)-mediated self-assembly of microclusters to produce robust, enzymatically active materials. The chimera scGFP-arPTE was structurally characterized via circular dichroism spectroscopy and synchrotron radiation small-angle X-ray scattering, and its biophysical properties were determined. Significantly, the chimera exhibited greater thermal stability than the native constituent proteins, as well as a higher catalytic turnover number (kcat). Furthermore, scGFP-arPTE was electrostatically complexed with monomeric S-, driving self-assembly into [scGFP-arPTE][S-] nanoclusters, which could be dehydrated and cross-linked to yield enzymatically active [scGFP-arPTE][S-] porous films with a high-order structure. Moreover, these clusters could self-assemble within cotton fibers to generate active composite textiles without the need for the pretreatment of the fabrics. Significantly, the resulting materials maintained the biophysical activities of both constituent proteins and displayed recyclable and persistent activity against the nerve agent simulant paraoxon.

Induction of osteoclast formation by LOX mutant (LOXG473A) through regulation of autophagy.

BACKGROUND: Lysyl oxidase (LOX) has been identified to modulate osteoclast activity, so we explored the role of LOXG473A, the highest frequency single nucleotide polymorphism in LOX, in osteoclast formation and its potential relationship to autophagy. METHODS: The ability of the LOX mutant, LOXG473A, to promote autophagy and osteoclast formation was evaluated in the pre-osteoclast cell line RAW264.7. Furthermore, autophagy-related protein expression and autophagosomes were detected by western blot and electron microscopy, respectively. Simultaneously, osteoclast formation and resorption ability were also detected using TRAP staining assay and bone resorption assay. In addition, the osteoclast-related proteins and mRNAs, as well as p-AMPKα and p-mTOR proteins, were further evaluated by western blot and qPCR assays. RESULTS: Autophagy inhibitor 3-MA suppressed the Beclin-1 and ATG5 protein levels and the ratio of LC3-II to LC3-I, as well as autophagosome formation in RAW264.7 transfected with the MUT plasmid and enhanced p62 protein expression. Simultaneously, 3-MA also reduced osteoclast formation and resorption, as well as the F-actin ring level of osteoclasts. In addition, 3-MA inhibited osteoclast-related protein and mRNA expression, including NFATC1, ACP5, CTSK. And the autophagy-related pathway protein p-AMPKα was increased and p-mTOR was reduced by 3-MA treatment. However, autophagy agonist RAPA reversed the effect of 3-MA on RAW264.7 with LOXG473A mutation, indicating that promoting autophagy could enhance the ability of LOXG473A to induce osteoclast formation. CONCLUSIONS: LOX mutant (LOXG473A) might promote osteoclast formation for RAW264.7 by enhancing autophagy via the AMPK/mTOR pathway, which is a new direction for bone disease research.

LOXG473A induces the formation of osteoclasts in RAW264.7 cells via IL-6/JAK2/STAT3 signaling.

Formation of osteoclasts is known to be closely associated with osteoporosis progression. LOX is a key enzyme that catalyzes the synthesis of collagen, which is the new mediator in osteoclast formation. However, the effect of LOXG473A on of osteoclast formation needs to be explored. Thereby, we sought to explore the effect of LOXG473A on formation of osteoclasts and its underlying mechanism. To investigate the function of LOXG473A in osteoclast formation, Raw264.7 cells were stably transfected with LOX-WT or LOX-MUT (LOXG473A). Real-time PCR and western blotting were used to detect the relative levels of osteoclast formation related genes and proteins. TRAP staining and immunofluorescence staining were used to test the ability of Raw264.7 cells to form osteoclasts and the ability of cells to form rings, respectively. Bone erosion assay was used to test bone resorptive activity. The data indicated that LOXG473A significantly enhanced the ability of osteoclasts forming, ring-forming and bone resorpting in Raw264.7 cells. Mechanically, LOXG473A upregulated the expressions of NFATC1, ACP5, CTSK, IL-6, and the proportion of p-JAK2/JAK2 and p-STAT3/STAT3, thereby promoting the formation of osteoclasts. In conclusion, we have verified that LOXG473A induces the proliferation of osteoclasts in Raw264.7 cells via IL-6/JAK2/STAT3 signaling, suggesting a novel strategy for studying osteoporosis.

Technological Advances in Tumor-On-Chip Technology: From Bench to Bedside.

Tumor-on-chip technology has cemented its importance as an in vitro tumor model for cancer research. Its ability to recapitulate different elements of the in vivo tumor microenvironment makes it promising for translational medicine, with potential application in enabling personalized anti-cancer therapies. Here, we provide an overview of the current technological advances for tumor-on-chip generation. To further elevate the functionalities of the technology, these approaches need to be coupled with effective analysis tools. This aspect of tumor-on-chip technology is often neglected in the current literature. We address this shortcoming by reviewing state-of-the-art on-chip analysis tools for microfluidic tumor models. Lastly, we focus on the current progress in tumor-on-chip devices using patient-derived samples and evaluate their potential for clinical research and personalized medicine applications.

An artificial membrane binding protein-polymer surfactant nanocomplex facilitates stem cell adhesion to the cartilage extracellular matrix.

One of the major challenges within the emerging field of injectable stem cell therapies for articular cartilage (AC) repair is the retention of sufficient viable cell numbers at the site of injury. Even when delivered via intra-articular injection, the number of stem cells retained at the target is often low and declines rapidly over time. To address this challenge, an artificial plasma membrane binding nanocomplex was rationally designed to provide human mesenchymal stem cells (hMSCs) with increased adhesion to articular cartilage tissue. The nanocomplex comprises the extracellular matrix (ECM) binding peptide of a placenta growth factor-2 (PlGF-2) fused to a supercharged green fluorescent protein (scGFP), which was electrostatically conjugated to anionic polymer surfactant chains to yield [S-]scGFP_PlGF2. The [S-]scGFP_PlGF2 nanocomplex spontaneously inserts into the plasma membrane of hMSCs, is not cytotoxic, and does not inhibit differentiation. The nanocomplex-modified hMSCs showed a significant increase in affinity for immobilised collagen II, a key ECM protein of cartilage, in both static and dynamic cell adhesion assays. Moreover, the cells adhered strongly to bovine ex vivo articular cartilage explants resulting in high cell numbers. These findings suggest that the re-engineering of hMSC membranes with [S-]scGFP_PlGF2 could improve the efficacy of injectable stem cell-based therapies for the treatment of damaged articular cartilage.

Biopolymeric Coacervate Microvectors for the Delivery of Functional Proteins to Cells.

The extent to which biologic payloads can be effectively delivered to cells is a limiting factor in the development of new therapies. Limitations arise from the lack of pharmacokinetic stability of biologics in vivo. Encapsulating biologics in a protective delivery vector has the potential to improve delivery profile and enhance performance. Coacervate microdroplets are developed as cell-mimetic materials with established potential for the stabilization of biological molecules, such as proteins and nucleic acids. Here, the development of biodegradable coacervate microvectors (comprising synthetically modified amylose polymers) is presented, for the delivery of biologic payloads to cells. Amylose-based coacervate microdroplets are stable under physiological conditions (e.g., temperature and ionic strength), are noncytotoxic owing to their biopolymeric structure, spontaneously interacted with the cell membrane, and are able to deliver and release proteinaceous payloads beyond the plasma membrane. In particular, myoglobin, an oxygen storage and antioxidant protein, is successfully delivered into human mesenchymal stem cells (hMSCs) within 24 h. Furthermore, coacervate microvectors are implemented for the delivery of human bone morphogenetic protein 2 growth factor, inducing differentiation of hMSCs into osteoprogenitor cells. This study demonstrates the potential of coacervate microdroplets as delivery microvectors for biomedical research and the development of new therapies.

[A Wearable System for Cervical Spondylosis Prevention Based on Artificial Intelligence].

Accompanied by changes in modern work and lifestyle, the incidence of cervical spondylosis has increased year by year. In view of the fact long-term fixed posture of the head and neck is one of the main causes of cervical spondylosis, a set of wearable cervical spondylosis prevention system is developed. The system comprises a head and neck movement collection module based on the acceleration sensor and a head and neck motion recognition module based on artificial intelligence. Experimental results showed that the system can accurately identify long-term posture of the head and neck, and guide users to complete effective exercise therapy under the supervision of motion recognition module. Using this system can be beneficial for the prevention of cervical spondylosis.

LOX gene polymorphisms are associated with osteoporotic vertebral compression fracture in postmenopausal Chinese women.

INTRODUCTION: Collagen cross-linking, which is regulated by lysyl oxidase (LOX), plays critical roles in bone mechanical strength. LOX can influence bone remodeling by modulating osteoblast and osteoclast activity. This study aimed to explore the effect of LOX gene polymorphisms on osteoporotic fractures susceptibility in postmenopausal Chinese women. METHODS: This was a prospective study of postmenopausal women who visited the outpatient and community clinics of the local Hospital. Five tagging single nucleotide polymorphisms (SNPs) in the LOX gene were determined. Bone mineral density (BMD) was measured at the lumbar spine, femoral neck, and hip using dual-energy X-ray absorptiometry. Fractures were confirmed by X-ray and divided into: vertebral compression fracture (OVCF) and non-OVCF (all other fractures). RESULTS: This study included 602 patients with non-traumatic fractures and 1343 healthy volunteers. The rs1800449 was significantly associated with vertebral compression fracture (OVCF) after adjusting for age and BMI (P = 0.012). Compared with subjects with the GG genotype, the risk of having OVCF was 1.28 and 1.74, respectively for subjects with the GA and AA genotypes (P = 0.043 and P = 0.018). A recessive genetic model showed that carriers of the AA genotype had higher fracture risk compared to G carriers (GA and GG genotypes) (P = 0.015). The rs2288393 SNP exhibited marginally significant association with OVCF (P = 0.051). Haplotype analyses corroborated our single SNP results: both haplotype CGA and CCG contained rs10519694, rs2288393, and rs1800449, and were significant associated with OVCF (P = 0.048 and P = 0.032, respectively). On the other hand, we found no evidence of an association of LOX gene allelic variants with either BMD or non-OVCF (all P > 0.05). CONCLUSION: The results suggest that genetic polymorphisms in LOX may contribute to susceptibility to OVCF in Chinese postmenopausal women.