Ziyin Bushen Fang improves Diabetic Osteoporosis by Inhibiting Autophagy and Oxidative Stress In vitro and In vivo.

OBJECTIVE: Diabetic osteoporosis (DOP) belongs to the group of diabetes-induced secondary osteoporosis and is the main cause of bone fragility and fractures in many patients with diabetes. The aim of this study was to determine whether Ziyin Bushen Fang (ZYBSF) can improve DOP by inhibiting autophagy and oxidative stress. METHODS: Type 1 diabetes mellitus (T1DM) was induced in rats using a high-fat high-sugar diet combined with streptozotocin. Micro-CT scanning was used to quantitatively observe changes in the bone microstructure in each group. Changes in the serum metabolites of DOP rats were analyzed using UHPLC-QTOF-MS. The DOP mouse embryonic osteoblast precursor cell model (MC3T3-E1) was induced using high glucose levels. RESULTS: After ZYBSF treatment, bone microstructure significantly improved. The bone mineral density, trabecular number, and trabecular thickness in the ZYBSF-M and ZYBSF-H groups significantly increased. After ZYBSF treatment, the femur structure of the rats was relatively intact, collagen fibers were significantly increased, and osteoporosis was significantly improved. A total of 1239 metabolites were upregulated and 1527 were downregulated in the serum of T1DM and ZYBSF-treated rats. A total of 20 metabolic pathways were identified. In cellular experiments, ZYBSF reduced ROS levels and inhibited the protein expression of LC3II / I, Beclin-1, and p-ERK. CONCLUSION: ZYBSF may improve DOP by inhibiting the ROS/ERK-induced autophagy signaling pathway.

CircCOX6A1 suppresses osteogenic differentiation and aggravates osteoporosis via miR-512-3p/DYRK2 axis.

BACKGROUND: Osteoporosis (OP), characterized by compromised bone integrity and increased fracture risk, poses a significant health challenge. Circular RNAs (circRNAs) have emerged as crucial regulators in various pathophysiological processes, prompting investigation into their role in osteoporosis. This study aimed to elucidate the involvement of circCOX6A1 in OP progression and understand its underlying molecular mechanisms. The primary objective was to explore the impact of circCOX6A1 on bone marrow-derived mesenchymal stem cells (BMSCs) and its potential interactions with miR-512-3p and DYRK2. METHODS: GSE161361 microarray analysis was employed to assess circCOX6A1 expression in OP patients. We utilized in vitro and in vivo models, including BMSC cultures, osteogenic differentiation assays, and an OVX-induced mouse model of OP. Molecular techniques such as quantitative RT-PCR, western blotting, and functional assays like alizarin red staining (ARS) were employed to evaluate circCOX6A1 effects on BMSC proliferation, apoptosis, and osteogenic differentiation. The interaction between circCOX6A1, miR-512-3p, and DYRK2 was investigated through dual luciferase reporter assays, RNA immunoprecipitation, and RNA pull-down assays. RESULTS: CircCOX6A1 was found to be upregulated in osteoporosis patients, and its expression inversely correlated with osteogenic differentiation of BMSCs. CircCOX6A1 knockdown enhanced osteogenic differentiation, as evidenced by increased mineralized nodule formation and upregulation of osteogenic markers. In vivo, circCOX6A1 knockdown ameliorated osteoporosis progression in OVX mice. Mechanistically, circCOX6A1 acted as a sponge for miR-512-3p, subsequently regulating DYRK2 expression. CONCLUSION: This study provides compelling evidence for the role of circCOX6A1 in osteoporosis pathogenesis. CircCOX6A1 negatively regulates BMSC osteogenic differentiation through the miR-512-3p/DYRK2 axis, suggesting its potential as a therapeutic target for mitigating OP progression.

A Causal Relationship Between Type 1 Diabetes and Risk of Osteoporosis: A Univariable and Multivariable Mendelian Randomization Study.

Objective: This Mendelian randomization (MR) analysis aims to investigate the causal relationship between type 1 diabetes (T1D) and osteoporosis (OP). Methods: Single nucleotide polymorphisms (SNPs) associated with T1D were selected from the summary statistics of the genome-wide association study (GWAS) in European ancestry as instrumental variables (IVs) for univariable MR (UVMR) to explore the causal relationship between T1D and OP. Inverse variance weighting (IVW) was the primary method used to assess possible causality between T1D and OP. MR-PRESSO and MR-Egger intercepts were used to assess the horizontal pleiotropy of the IVs, and Q tests and the "leave-one-out" method were used to test for heterogeneity of MR results. Multivariable MR (MVMR) analysis was used to account for potential confounders such as smoking, obesity, drinking, and serum 25-hydroxyvitamin D (25OHD) concentrations. Result: Inverse variance weighted estimates suggest T1D may increase risk of OP (UVMR: OR = 1.06, 95% CI: 1.02-1.10, p = 0.002) (MVMR: OR = 1.50, 95% CI: 1.07-1.90, p < 0.001). Conclusion: Our findings suggest that T1D can increase the risk of OP.

The Suitable Population for Opportunistic Low Bone Mineral Density Screening Using Computed Tomography.

Objective: To explore the suitable population of CT value for predicting low bone mineral density (low-BMD). Methods: A total of 1268 patients who underwent chest CT examination and DXA within one-month period retrospectively analyzed. The CT attenuation values of trabecular bone were measured in mid-sagittal plane from thoracic vertebra 7 (T7). Receiver operating characteristic (ROC) curves were used to evaluate the ability to diagnose low-BMD. Results: The AUC for diagnosing low BMD was larger in women than in men (0.894 vs 0.744, p < 0.05). The AUC increased gradually with the increase of age but decreased gradually with the increase in height and weight (p < 0.05). In females, when specificity was adjusted to approximately 90%, a threshold of 140.25 HU has a sensitivity of 69.3%, which is higher than the sensitivity of 36.5% in males for distinguishing low-BMD from normal. At the age of 70 or more, when specificity was adjusted to approximately 90%, a threshold of 126.31 HU has a sensitivity of 76.1%, which was higher than that of other age groups. Conclusion: For patients who had completed chest CTs, the CT values were more effective in predicting low-BMD in female, elderly, lower height, and lower weight patients.

Carboxypeptidase M modulates BMSCs osteogenesis-adipogenesis via the MAPK/ERK pathway: An integrated single-cell and bulk transcriptomic study.

The pathogenesis of osteoporosis (OP) is closely associated with the disrupted balance between osteogenesis and adipogenesis in bone marrow-derived mesenchymal stem cells (BMSCs). We analyzed published single-cell RNA sequencing (scRNA-seq) data to dissect the transcriptomic profiles of bone marrow-derived cells in OP, reviewing 56 377 cells across eight scRNA-seq datasets from femoral heads (osteoporosis or osteopenia n = 5, osteoarthritis n = 3). Seventeen genes, including carboxypeptidase M (CPM), were identified as key osteogenesis-adipogenesis regulators through comprehensive gene set enrichment, differential expression, regulon activity, and pseudotime analyses. In vitro, CPM knockdown reduced osteogenesis and promoted adipogenesis in BMSCs, while adenovirus-mediated CPM overexpression had the reverse effects. In vivo, intraosseous injection of CPM-overexpressing BMSCs mitigated bone loss in ovariectomized mice. Integrated scRNA-seq and bulk RNA sequencing analyses provided insight into the MAPK/ERK pathway's role in the CPM-mediated regulation of BMSC osteogenesis and adipogenesis; specifically, CPM overexpression enhanced MAPK/ERK signaling and osteogenesis. In contrast, the ERK1/2 inhibitor binimetinib negated the effects of CPM overexpression. Overall, our findings identify CPM as a pivotal regulator of BMSC differentiation, which provides new clues for the mechanistic study of OP.

DDX58 variant triggers IFN-ß-induced autophagy in trabecular meshwork and influences intraocular pressure.

Singleton-Merten syndrome (SMS) is a rare immunogenetic disorder affecting multiple systems, characterized by dental dysplasia, aortic calcification, glaucoma, skeletal abnormalities, and psoriasis. Glaucoma, a key feature of both classical and atypical SMS, remains poorly understood in terms of its molecular mechanism caused by DDX58 mutation. This study presented a novel DDX58 variant (c.1649A>C [p.Asp550Ala]) in a family with childhood glaucoma. Functional analysis showed that DDX58 variant caused an increase in IFN-stimulated gene expression and high IFN-ß-based type-I IFN. As the trabecular meshwork (TM) is responsible for controlling intraocular pressure (IOP), we examine the effect of IFN-ß on TM cells. Our study is the first to demonstrate that IFN-ß significantly reduced TM cell viability and function by activating autophagy. In addition, anterior chamber injection of IFN-ß remarkably increased IOP level in mice, which can be attenuated by treatments with autophagy inhibitor chloroquine. To uncover the specific mechanism underlying IFN-ß-induced autophagy in TM cells, we performed microarray analysis in IFN-ß-treated and DDX58 p.Asp550Ala TM cells. It showed that RSAD2 is necessary for IFN-ß-induced autophagy. Knockdown of RSAD2 by siRNA significantly decreased autophagy flux induced by IFN-ß. Our findings suggest that DDX58 mutation leads to the overproduction of IFN-ß, which elevates IOP by modulating autophagy through RSAD2 in TM cells.

Societal costs before and up to 1 year after the first fracture liaison service visit in patients requiring anti-osteoporosis treatments.

This study aimed to estimate societal and healthcare costs incurred before and 1 year after the first fracture liaison services (FLS) visit and to explore differences in fracture type. All costs after 1 year significantly decreased compared to costs preceding the first visit. Fracture type did not significantly affect costs. INTRODUCTION: Limited literature is available on resource utilization and costs of patients visiting fracture liaison services (FLS). This study aimed to estimate the societal and healthcare costs incurred by patients with a recent fracture requiring anti-osteoporosis medication before and 1 year after the first FLS visit and to explore differences according to fracture type. METHODS: Resource utilization was collected through a self-reported questionnaire with a 4-month recall on health resource utilization and productivity losses immediately following the first FLS visit, and 4 and 12 months later. Unit costs derived from the national Dutch guideline for economic evaluations were used to compute societal and healthcare costs. Linear mixed-effect models, adjusted for confounders, were used to analyze societal and healthcare costs over time as well as the effect of fracture type on societal and healthcare costs. RESULTS: A total of 126 patients from two Dutch FLS centers were included, of whom 72 sustained a major fracture (hip, vertebral, humerus, or radius). Societal costs in the 4 months prior to the first visit (€2911) were significantly higher compared to societal costs 4 months (€711, p-value = 0.009) and 12 months later (€581, p-value = 0.001). Fracture type did not have a significant effect on total societal or healthcare costs. All costs 12 months after the initial visit were numerically lower for major fractures compared to others. CONCLUSION: Societal and healthcare costs in the year following the first FLS visit significantly decreased compared to those costs preceding the first visit.

Interaction between MARK3 (rs11623869), PLCB4 (rs6086746) and GEMIN2 (rs2277458) variants with bone mineral density and serum 25-hidroxivitamin D levels in Mexican Mestizo women.

Introduction: Understanding the genetic factors contributing to variations in bone mineral density (BMD) and vitamin D could provide valuable insights into the pathogenesis of osteoporosis. This study aimed to evaluate the association of single nucleotide variants in MARK3 (rs11623869), PLCB4 (rs6086746), and GEMIN2 (rs2277458) with BMD in Mexican women. Methods: The gene-gene interaction was evaluated in these variants in serum 25(OH)D levels and BMD. A genetic risk score (GRS) was created on the basis of the three genetic variants. Genotyping was performed using predesigned TaqMan assays. Results: A significant association was found between the rs6086746-A variant and BMD at the total hip, femoral neck, and lumbar spine, in women aged 45 years or older. However, no association was observed between the variants rs11623869 and rs2277458. The rs11623869 × rs2277458 interaction was associated with total hip (p=0.002) and femoral neck BMD (p=0.013). Similarly, for vitamin D levels, we observed an interaction between the variants rs6086746 × rs2277458 (p=0.021). GRS revealed a significant association with total hip BMD (p trend=0.003) and femoral neck BMD (p trend=0.006), as well as increased vitamin D levels (p trend=0.0003). These findings provide evidence of the individual and joint effect of the MARK3, PLCB4, and GEMIN2 variants on BMD and serum vitamin D levels in Mexican women. Discussion: This knowledge could help to elucidate the interaction mechanism between BMD-related genetic variants and 25OHD, contributing to the determination of the pathogenesis of osteoporosis and its potential implications during early interventions.

Relationship Between Prepatellar Fat Thickness and Bone Mineral Density.

OBJECTIVE: To evaluate the relationship between bone mineral density (BMD) by measuring the prepatellar fat thickness with knee radiography and to gain a measurement method that has not been done before in the literature. STUDY DESIGN: Cross-sectional descriptive study. Place and Duration of the Study: Department of Physical Medicine and Rehabilitation, Training and Research Hospital, Sanliurfa, Turkiye, between January and June 2020. METHODOLOGY: Patients' age, body mass index (BMI) data, prepatellar fat thickness (mm), L1-L4 total, bone mineral density femoral neck, femur trochanter major, and femur total T scores were recorded. The relationships between these three groups (normal, osteopenia, osteoporosis) and between prepatellar fat tissue measurement were evaluated. One-way analysis of variance (ANOVA) and Post Hoc Tukey tests were used in the analysis. RESULTS:  A statistically significant difference was found in terms of trochanter major T score measurements (X2 = 20.435; p <0.001) and BMI (X2 = 66.535; p <0.001) measurements of prepatellar fat thickness measurement. A statistically significant difference was found between the three groups in terms of prepatellar fat thickness measurement, L1-4 T-score, femoral neck, and femur total values (p <0.001). CONCLUSION:  Prepatellar fat thickness in postmenopausal Turkish women was positively correlated with BMD; BMD increases as the prepatellar fat thickness increases. This explains that perapatellar fat thickness creates a mechanical load on the bones and causes an increase in BMD. KEY WORDS: Osteoporosis, Fat thickness, Bone mineral density.

Secondary osteoporosis prevention: three-year outcomes from a Fracture Liaison Service in elderly hip fracture patients.

BACKGROUND: Hip fractures are the most serious fragility fractures due to their associated disability, higher hospitalization costs and high mortality rates. Fracture Liaison Service (FLS) programs have enhanced the management of osteoporosis-related fractures and have shown their clinical effectiveness. AIMS: To analyze the effect of the implementation of a FLS model of care over the survival and mortality rates following a hip fracture. METHODS: We conducted a prospective cohort study on patients over 60 years of age who suffered a hip fracture before and after the implementation of the FLS in our center (between January 2016 and December 2019). Patients were followed for three years after the index date. Mortality, complications and refracture rates were compared between the two groups using a Multivariate Cox proportional hazard model. RESULTS: A total of 1366 patients were included in this study (353 before FLS implementation and 1013 after FLS implementation). Anti-osteoporotic drugs were more frequently prescribed after FLS implementation (79.3% vs 12.5%; p < 0.01) and there was an increase in adherence to treatment (51.7% vs 30.2%; p < 0.01). A total of 413 (40.8%) patients after FLS implementation and 141 (39.9%) individuals before (p = 0.47) died during the three-years follow-up period. A second fracture occurred in 101 (10.0%) patients after FLS implementation and 37 (10.5%) individuals before (p = 0.78). Patients after the implementation of the FLS protocol had a lower all cause one-year mortality [adjusted Hazard Ratio (HR) 0.74 (0.57-0.94)] and a decreased risk of suffering a second osteoporotic fracture [adjusted HR 0.54 (0.39-0.75) in males and adjusted HR 0.46 (0.30-0.71) in females]. CONCLUSIONS: The implementation of a FLS protocol was associated with a lower all-cause one-year mortality rate and a higher survivorship in elderly hip fracture patients. However, no three-year mortality rate differences were observed between the two groups. We also found a reduction in the complication and second-fracture rates.

Osteoporosis in Parkinson's disease and the role of lean body mass: a cross-sectional study in a Brazilian tertiary center.

Background: Parkinson's disease (PD) is the second most common neurodegenerative illness and has the highest increase rate in recent years. There is growing evidence to suggest that PD is linked to higher osteoporosis rates and risk of fractures. Objective: This study aims to estimate the prevalence and factors associated with osteoporosis as defined by the National Osteoporosis Foundation (NOF) and World Health Organization in patients with mild to moderate PD. Methods: We performed a cross-sectional study at a tertiary public hospital in Fortaleza, Brazil, dating from May 2021 until April 2022. The study sample was comprised of patients with mild to moderate PD who were at least 40 years old and who had the ability to walk and stand unassisted. Bone Mineral Density (BMD) of both the hip (neck of the femur) and the lumbar spine were obtained via properly calibrated Dual Energy X-ray Absorptiometry (DXA) scanning. The FRAX (Fracture Risk Assessment Tool) score was used to determine a person's 10-year risk of major osteoporotic fracture. The Revised European Working Group on Sarcopenia in Older People (EWGSOP 2) was used as a basis to confirm a sarcopenia diagnosis with the following parameters: low muscle strength gauged by handgrip strength and low muscle quantity by DXA. Physical performance was carefully evaluated by using the Short Physical Performance Battery test. Osteoporosis and osteopenia were diagnosed following the NOF guidelines and WHO recommendations. Results: We evaluated 107 patients in total, of whom 45 (42%) were women. The group's mean age was 68 ± 9 years, and the mean disease time span was 9.9 ± 6.0 years and mean motor UPDRS was 43 ± 15. We found that 42.1% and 34.6% of the sample had osteopenia and osteoporosis following NOF criteria, respectively, and 43% and 33.6% following the WHO recommendations. Lower lean appendicular mass was associated to osteopenia and osteoporosis in multinomial logistic regression analysis in both diagnostic criteria. Conclusion: Our findings provide additional evidence for the protective role of lean mass against osteoporosis in patients with PD.

Bone health and awareness of osteoporosis in women aged 40 to 60 years in Jiaxing City, China.

The objective of this study is to evaluate the pattern of bone mineral density (BMD) in native Jiaxing women, and to investigate their awareness of osteoporosis. A total of 538 native Jiaxing women aged 40 to 60 years were recruited from January 2022 to December 2023 when they had routine examinations in the physical examination center of Jiaxing Maternal and Child Health Hospital. The Chinese version of Osteoporosis Prevention and Cognition Tool was used to evaluate participants' cognitive level of osteoporosis. BMD of participants' lumbar spine (L1-L4) and left hip (Neck/Troch/Ward) was measured by dual-energy X-ray absorptiometry. The mean total score of the awareness about osteoporosis (general knowledge, complications, and prevention) was 22.08 ±â€…2.74, which was suboptimal. The higher the education level, the higher the score of awareness (P < .01). Medical staff had the highest awareness rate of osteoporosis and the farmer had the lowest. Lumber spine and hip BMD of all sites was significantly decreased with increasing age (P < .001). Premenopausal women had higher BMD than postmenopausal women at all lumbar spine and hip sites (P < .01). The overall frequency of osteoporosis was 10.8% in the lumbar spine, 8.6% in the total hip, and 17.7% in either site. Osteoporosis and osteopenia are highly prevalent among native Jiaxing women but their awareness of osteoporosis is inadequate. To reduce the prevalence of osteoporosis, especially among the unemployed, we should carry out effective health education through multimedia to raise their awareness of osteoporosis. In addition, menopausal hormone therapy should also be considered in menopausal women.

Application of machine learning algorithms to identify people with low bone density.

Background: Osteoporosis is becoming more common worldwide, imposing a substantial burden on individuals and society. The onset of osteoporosis is subtle, early detection is challenging, and population-wide screening is infeasible. Thus, there is a need to develop a method to identify those at high risk for osteoporosis. Objective: This study aimed to develop a machine learning algorithm to effectively identify people with low bone density, using readily available demographic and blood biochemical data. Methods: Using NHANES 2017-2020 data, participants over 50 years old with complete femoral neck BMD data were selected. This cohort was randomly divided into training (70%) and test (30%) sets. Lasso regression selected variables for inclusion in six machine learning models built on the training data: logistic regression (LR), support vector machine (SVM), gradient boosting machine (GBM), naive Bayes (NB), artificial neural network (ANN) and random forest (RF). NHANES data from the 2013-2014 cycle was used as an external validation set input into the models to verify their generalizability. Model discrimination was assessed via AUC, accuracy, sensitivity, specificity, precision and F1 score. Calibration curves evaluated goodness-of-fit. Decision curves determined clinical utility. The SHAP framework analyzed variable importance. Results: A total of 3,545 participants were included in the internal validation set of this study, of whom 1870 had normal bone density and 1,675 had low bone density Lasso regression selected 19 variables. In the test set, AUC was 0.785 (LR), 0.780 (SVM), 0.775 (GBM), 0.729 (NB), 0.771 (ANN), and 0.768 (RF). The LR model has the best discrimination and a better calibration curve fit, the best clinical net benefit for the decision curve, and it also reflects good predictive power in the external validation dataset The top variables in the LR model were: age, BMI, gender, creatine phosphokinase, total cholesterol and alkaline phosphatase. Conclusion: The machine learning model demonstrated effective classification of low BMD using blood biomarkers. This could aid clinical decision making for osteoporosis prevention and management.

Self Emulsifying Delivery System of Cissus quadrangularis: Evidence of Enhanced Efficacy and Promising Pharmacokinetic Profile in the Management of Osteoporosis.

Treatment therapies used to manage osteoporosis are associated with severe side effects. So worldwide herbs are widely studied to develop alternative safe & effective treatments. Cissus quadrangularis (CQ) has a significant role in bone health and fracture healing. It is documented that its extracts increase osteoblastic differentiation & mineralization. Currently, Cissus quadrangularis is available in the form of tablets in the market for oral delivery. But these conventional forms are associated with poor bioavailability. There is a need for a novel drug delivery system with improving oral bioavailability. Therefore, a Cissus quadrangularis-loaded self-emulsifying drug delivery system (CQ-SEDDS) was developed which disperses rapidly in the gastrointestinal fluids, yielding nano-emulsions containing a solubilized drug. This solubilized form of the drug can be easily absorbed through lymphatic pathways and bypass the hepatic first-pass effect. The emulsification efficiency, zeta potential, globule size, in-vitro dissolution, ex-vivo, in-vivo and bone marker studies were performed to assess the absorption and permeation potential of CQ incorporated in SEDDS. CQ-SEDDS with excipients Tween 80, Cremophor RH40, Transcutol HP & α-Tocopherol acetate had shown about 76% enhancement in the bioavailability of active constituents of CQ. This study provided the pre-clinical data of CQ-SEDDS using osteoporotic rat model studies.

Guidelines for fracture risk assessment and management of osteoporosis in postmenopausal women and men above the age of 50 in Qatar.

We present comprehensive guidelines for osteoporosis management in Qatar. Formulated by the Qatar Osteoporosis Association, the guidelines recommend the age-dependent Qatar fracture risk assessment tool for screening, emphasizing risk-based treatment strategies and discouraging routine dual-energy X-ray scans. They offer a vital resource for physicians managing osteoporosis and fragility fractures nationwide. PURPOSE: Osteoporosis and related fragility fractures are a growing public health issue with an impact on individuals and the healthcare system. We aimed to present guidelines providing unified guidance to all healthcare professionals in Qatar regarding the management of osteoporosis. METHODS: The Qatar Osteoporosis Association formulated guidelines for the diagnosis and management of osteoporosis in postmenopausal women and men above the age of 50. A panel of six local rheumatologists who are experts in the field of osteoporosis met together and conducted an extensive review of published articles and local and international guidelines to formulate guidance for the screening and management of postmenopausal women and men older than 50 years in Qatar. RESULTS: The guidelines emphasize the use of the age-dependent hybrid model of the Qatar fracture risk assessment tool for screening osteoporosis and risk categorization. The guidelines include screening, risk stratification, investigations, treatment, and monitoring of patients with osteoporosis. The use of a dual-energy X-ray absorptiometry scan without any risk factors is discouraged. Treatment options are recommended based on risk stratification. CONCLUSION: Guidance is provided to all physicians across the country who are involved in the care of patients with osteoporosis and fragility fractures.

Causal roles of educational duration in bone mineral density and risk factors for osteoporosis: a Mendelian randomization study.

BACKGROUND: Educational duration might play a vital role in preventing the occurrence and development of osteoporosis(OP). PURPOSE: To assess the causal effect of educational duration on bone mineral density(BMD) and risk factors for OP by Mendelian randomization(MR) study. METHODS: The causal relationship was analyzed using data from genome-wide association study(GWAS). Inverse variance weighting (IVW) was used as the main analysis method. Horizontal pleiotropy was identified by MR-Egger intercept test, MR pleiotropy residual sum and outlier (MR-PRESSO) test. The leave-one-out method was used as a sensitivity analysis. RESULTS: The IVW results indicated that there was a positive causal relationship between educational duration and BMD (OR = 1.012, 95%CI:1.003-1.022), physical activity(PA) (OR = 1.156, 95%CI:1.032-1.295), calcium consumption (OR = 1.004, 95%CI:1.002-1.005), and coffee intake (OR = 1.019, 95%CI:1.014-1.024). There was a negative association between whole body fat mass (OR = 0.950, 95%CI:0.939-0.961), time for vigorous PA (OR = 0.955, 95%CI:0.939-0.972), sunbath (OR = 0.987, 95%CI:0.986-0.989), salt consumption (OR = 0.965, 95%CI:0.959-0.971), fizzy drink intake (OR = 0.985, 95%CI:0.978-0.992), smoking (OR = 0.969, 95%CI:0.964-0.975), and falling risk (OR = 0.976, 95%CI:0.965-0.987). There was no significant association between educational duration and lean mass, time for light-to-moderate PA, milk intake, and alcohol intake. Horizontal pleiotropy was absent in this study. The results were robust under sensitivity analyses. CONCLUSION: A longer educational duration was causally linked with increased BMD. No causal relationship had been found between educational duration and lean mass, time for light-to-moderate PA, milk intake, and alcohol consumption as risk factors for osteoporosis.

Type 2 diabetic mellitus related osteoporosis: focusing on ferroptosis.

With the aging global population, type 2 diabetes mellitus (T2DM) and osteoporosis(OP) are becoming increasingly prevalent. Diabetic osteoporosis (DOP) is a metabolic bone disorder characterized by abnormal bone tissue structure and reduced bone strength in patients with diabetes. Studies have revealed a close association among diabetes, increased fracture risk, and disturbances in iron metabolism. This review explores the concept of ferroptosis, a non-apoptotic cell death process dependent on intracellular iron, focusing on its role in DOP. Iron-dependent lipid peroxidation, particularly impacting pancreatic ß-cells, osteoblasts (OBs) and osteoclasts (OCs), contributes to DOP. The intricate interplay between iron dysregulation, which comprises deficiency and overload, and DOP has been discussed, emphasizing how excessive iron accumulation triggers ferroptosis in DOP. This concise overview highlights the need to understand the complex relationship between T2DM and OP, particularly ferroptosis. This review aimed to elucidate the pathogenesis of ferroptosis in DOP and provide a prospective for future research targeting interventions in the field of ferroptosis.

The role of traditional Chinese medicine on fracture surgery, hospitalization, and total mortality risks in diabetic patients with osteoporosis.

BACKGROUND: Studies have confirmed that osteoporosis has been considered as one of the complications of diabetes, and the health hazards to patients are more obvious. This study is mainly based on the Taiwan National Health Insurance Database (TNHID). Through the analysis of TNHID, it is shown that the combined treatment of traditional Chinese medicine (TCM) medicine in patients of diabetes with osteoporosis (T2DOP) with lower related risks. METHODS: According to the study design, 3131 patients selected from TNHID who received TCM treatment were matched by 1-fold propensity score according to gender, age, and inclusion date as the control group. Cox proportional hazards analyzes were performed to compare fracture surgery, hospitalization, and all-cause mortality during a mean follow-up from 2000 to 2015. RESULTS: A total of 1055/1469/715 subjects (16.85%/23.46%/11.42%) had fracture surgery/inpatient/all-cause mortality of which 433/624/318 (13.83%/19.93%/10.16%) were in the TCM group) and 622/845/397 (19.87%/26.99%/12.68%) in the control group. Cox proportional hazards regression analysis showed that subjects in the TCM group had lower rates of fracture surgery, inpatient and all-cause mortality (adjusted HR = 0.467; 95% CI = 0.225-0.680, P<0.001; adjusted HR = 0.556; 95% CI = 0.330-0.751, P<0.001; adjusted HR = 0.704; 95% CI = 0.476-0.923, P = 0.012). Kaplan-Meier analysis showed that the cumulative risk of fracture surgery, inpatient and all-cause mortality was significantly different between the case and control groups (all log-rank p<0.001). CONCLUSION: This study provides longitudinal evidence through a cohort study of the value of integrated TCM for T2DOP. More research is needed to fully understand the clinical significance of these results.

Hyperthyroidism-driven bone loss depends on BMP receptor Bmpr1a expression in osteoblasts.

Hyperthyroidism is a well-known trigger of high bone turnover that can lead to the development of secondary osteoporosis. Previously, we have shown that blocking bone morphogenetic protein (BMP) signaling systemically with BMPR1A-Fc can prevent bone loss in hyperthyroid mice. To distinguish between bone cell type-specific effects, conditional knockout mice lacking Bmpr1a in either osteoclast precursors (LysM-Cre) or osteoprogenitors (Osx-Cre) were rendered hyperthyroid and their bone microarchitecture, strength and turnover were analyzed. While hyperthyroidism in osteoclast precursor-specific Bmpr1a knockout mice accelerated bone resorption leading to bone loss just as in wildtype mice, osteoprogenitor-specific Bmpr1a deletion prevented an increase of bone resorption and thus osteoporosis with hyperthyroidism. In vitro, wildtype but not Bmpr1a-deficient osteoblasts responded to thyroid hormone (TH) treatment with increased differentiation and activity. Furthermore, we found an elevated Rankl/Opg ratio with TH excess in osteoblasts and bone tissue from wildtype mice, but not in Bmpr1a knockouts. In line, expression of osteoclast marker genes increased when osteoclasts were treated with supernatants from TH-stimulated wildtype osteoblasts, in contrast to Bmpr1a-deficient cells. In conclusion, we identified the osteoblastic BMP receptor BMPR1A as a main driver of osteoporosis in hyperthyroid mice promoting TH-induced osteoblast activity and potentially its coupling to high osteoclastic resorption.