Cardiovascular and bone health outcomes in older people with subclinical hypothyroidism treated with levothyroxine: a systematic review and meta-analysis.

BACKGROUND: Thyroid dysfunction is common in older people, with females at higher risk. Evidence suggests that thyroid-stimulating hormone (TSH) levels naturally increase with age. However, as uniform serum TSH reference ranges are applied across the adult lifespan, subclinical hypothyroidism (SCH) diagnosis is more likely in older people, with some individuals also being commenced treatment with levothyroxine (LT4). It is unclear whether LT4 treatment in older people with SCH is associated with adverse cardiovascular or bone health outcomes. METHODS: A systematic review and meta-analysis were performed to synthesise previous studies evaluating cardiovascular and bone health outcomes in older people with SCH, comparing LT4 treatment with no treatment. PubMed, Embase, Cochrane Library, MEDLINE, and Web of Science databases were searched from inception until March 13, 2023, and studies that evaluated cardiovascular and bone health events in people with SCH over 50 years old were selected. RESULTS: Six articles that recruited 3853 participants were found, ranging from 185 to 1642 participants, with the proportion of females ranging from 45 to 80%. The paucity of data resulted in analysis for those aged over 65 years only. Additionally, a study with 12,212 participants aged 18 years and older was identified; however, only data relevant to patients aged 65 years and older were considered for inclusion in the systematic review. Of these 7 studies, 4 assessed cardiovascular outcomes, 1 assessed bone health outcomes, and 2 assessed both. A meta-analysis of cardiovascular outcomes revealed a pooled hazard ratio of 0.89 (95% CI 0.71-1.12), indicating no significant difference in cardiovascular risk between older individuals with SCH treated with LT4 compared to those without treatment. Due to overlapping sub-studies, meta-analysis for bone health outcomes was not possible. CONCLUSIONS: This systematic review and meta-analysis found no significant association between LT4 use and cardiovascular and bone health outcomes in SCH participants over 65 years. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42022308006.

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.

Analysis and validation of biomarkers of immune cell-related genes in postmenopausal osteoporosis: An observational study.

Postmenopausal osteoporosis (PMOP) is a common metabolic inflammatory disease. In conditions of estrogen deficiency, chronic activation of the immune system leads to a hypo-inflammatory phenotype and alterations in its cytokine and immune cell profile, although immune cells play an important role in the pathology of osteoporosis, studies on this have been rare. Therefore, it is important to investigate the role of immune cell-related genes in PMOP. PMOP-related datasets were downloaded from the Gene Expression Omnibus database. Immune cells scores between high bone mineral density (BMD) and low BMD samples were assessed based on the single sample gene set enrichment analysis method. Subsequently, weighted gene co-expression network analysis was performed to identify modules highly associated with immune cells and obtain module genes. Differential analysis between high BMD and low BMD was also performed to obtain differentially expressed genes. Module genes are intersected with differentially expressed genes to obtain candidate genes, and functional enrichment analysis was performed. Machine learning methods were used to filter out the signature genes. The receiver operating characteristic (ROC) curves of the signature genes and the nomogram were plotted to determine whether the signature genes can be used as a molecular marker. Gene set enrichment analysis was also performed to explore the potential mechanism of the signature genes. Finally, RNA expression of signature genes was validated in blood samples from PMOP patients and normal control by real-time quantitative polymerase chain reaction. Our study of PMOP patients identified differences in immune cells (activated dendritic cell, CD56 bright natural killer cell, Central memory CD4 T cell, Effector memory CD4 T cell, Mast cell, Natural killer T cell, T follicular helper cell, Type 1 T-helper cell, and Type 17 T-helper cell) between high and low BMD patients. We obtained a total of 73 candidate genes based on modular genes and differential genes, and obtained 5 signature genes by least absolute shrinkage and selection operator and random forest model screening. ROC, principal component analysis, and t-distributed stochastic neighbor embedding down scaling analysis revealed that the 5 signature genes had good discriminatory ability between high and low BMD samples. A logistic regression model was constructed based on 5 signature genes, and both ROC and column line plots indicated that the model accuracy and applicability were good. Five signature genes were found to be associated with proteasome, mitochondria, and lysosome by gene set enrichment analysis. The real-time quantitative polymerase chain reaction results showed that the expression of the signature genes was significantly different between the 2 groups. HIST1H2AG, PYGM, NCKAP1, POMP, and LYPLA1 might play key roles in PMOP and be served as the biomarkers of PMOP.

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.

Vitamin A - discovery, metabolism, receptor signaling and effects on bone mass and fracture susceptibility.

The first evidence of the existence of vitamin A was the observation 1881 that a substance present in small amounts in milk was necessary for normal development and life. It was not until more than 100 years later that it was understood that vitamin A acts as a hormone through nuclear receptors. Unlike classical hormones, vitamin A cannot be synthesized by the body but needs to be supplied by the food as retinyl esters in animal products and ß-carotene in vegetables and fruits. Globally, vitamin A deficiency is a huge health problem, but in the industrialized world excess of vitamin A has been suggested to be a risk factor for secondary osteoporosis and enhanced susceptibility to fractures. Preclinical studies unequivocally have shown that increased amounts of vitamin A cause decreased cortical bone mass and weaker bones due to enhanced periosteal bone resorption. Initial clinical studies demonstrated a negative association between intake of vitamin A, as well as serum levels of vitamin A, and bone mass and fracture susceptibility. In some studies, these observations have been confirmed, but in other studies no such associations have been observed. One meta-analysis found that both low and high serum levels of vitamin A were associated with increased relative risk of hip fractures. Another meta-analysis also found that low levels of serum vitamin A increased the risk for hip fracture but could not find any association with high serum levels of vitamin A and hip fracture. It is apparent that more clinical studies, including large numbers of incident fractures, are needed to determine which levels of vitamin A that are harmful or beneficial for bone mass and fracture. It is the aim of the present review to describe how vitamin A was discovered and how vitamin A is absorbed, metabolized and is acting as a ligand for nuclear receptors. The effects by vitamin A in preclinical studies are summarized and the clinical investigations studying the effect by vitamin A on bone mass and fracture susceptibility are discussed in detail.

Links among Obesity, Type 2 Diabetes Mellitus, and Osteoporosis: Bone as a Target.

Obesity, type 2 diabetes mellitus (T2DM) and osteoporosis are serious diseases with an ever-increasing incidence that quite often coexist, especially in the elderly. Individuals with obesity and T2DM have impaired bone quality and an elevated risk of fragility fractures, despite higher and/or unchanged bone mineral density (BMD). The effect of obesity on fracture risk is site-specific, with reduced risk for several fractures (e.g., hip, pelvis, and wrist) and increased risk for others (e.g., humerus, ankle, upper leg, elbow, vertebrae, and rib). Patients with T2DM have a greater risk of hip, upper leg, foot, humerus, and total fractures. A chronic pro-inflammatory state, increased risk of falls, secondary complications, and pharmacotherapy can contribute to the pathophysiology of aforementioned fractures. Bisphosphonates and denosumab significantly reduced the risk of vertebral fractures in patients with both obesity and T2DM. Teriparatide significantly lowered non-vertebral fracture risk in T2DM subjects. It is important to recognize elevated fracture risk and osteoporosis in obese and T2DM patients, as they are currently considered low risk and tend to be underdiagnosed and undertreated. The implementation of better diagnostic tools, including trabecular bone score, lumbar spine BMD/body mass index (BMI) ratio, and microRNAs to predict bone fragility, could improve fracture prevention in this patient group.

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.

Changes in thoracic radio density after living donor liver transplantation.

BACKGROUND: The outcomes after liver transplantation have greatly improved, which has resulted in greater focus on improving non-hepatic outcomes of liver transplantation. The present study aimed to evaluate thoracic spine radio density in children and adolescents after liver transplantation. METHODS: A total of 116 patients who underwent living donor liver transplantation were retrospectively analyzed. The radio density at the eleventh thoracic vertebra was measured using computed tomography scan performed preoperatively then annually for 5 years postoperatively and subsequently every 2 or 3 years. RESULTS: The mean thoracic radio density of male recipients of male grafts had the lowest values during the study. The radio density of patients receiving a graft from a female donor was higher than in recipients with grafts from males. Total mean radio density decreased for first 5 years postoperatively and then increased. Changes in radio density were equally distributed in both steroid withdrawal and no steroid withdrawal groups for 5 years, after which patients with steroid withdrawal had a greater increase. Changes in radio density were equally distributed in both the steroid withdrawal and no steroid withdrawal groups up to age 20, after which patients in the steroid withdrawal group had a greater increase. CONCLUSIONS: Gender differences may affect the outcome of radio density changes after transplantation. Given the moderate association between thoracic radio density and bone mineral density in skeletally mature adults and further studies are needed to validate this relationship between thoracic radio density and bone mineral density changes in pediatric liver transplantation.

High insertion torque versus regular insertion torque: early crestal bone changes on dental implants in relation to primary stability-a retrospective clinical study.

The aim of the presented retrospective study was to evaluate the early crestal bone changes around an implant type designed for high primary stability. A total number of 111 implants placed clinically were evaluated regarding insertion torque, bone density, implant stability quotient (ISQ) and early crestal bone loss from standardized digital radiographs. The implants were allocated in two groups: the "regular torque " group contained all implants that achieved less than 50 Ncm as final insertion torque (n = 63) and the "high torque" group contained the implants that achieved 50-80 Ncm (n = 48). To avoid possible damage either to the implant´s inner connection or to the bone by application of excessive force, a limit of 80 Ncm was set for all surgeries. All implants underwent submerged healing for three months. ISQ measurements and standardized digital radiographs were taken at day of insertion and at day of second stage surgery. The bone loss was measured on the mesial and distal aspect of the implant. The data evaluation showed the following results: Mean bone loss was 0.27 ± 0.30 mm for the high torque group and 0.24 ± 0.27 mm for the regular torque group. The difference was not statistically significant (p = 0.552). In the two groups, no complications nor implant loss occurred. For the evaluated implant type, there was no significant difference in crestal bone changes and complication rate between high and regular insertion torque in the early healing period.

Age and sex are excellent predictors of bone complications in patients with type 2 diabetes with no history of osteoporotic fracture or treatment for osteoporosis.

OBJECTIVE: To identify patients with type 2 diabetes mellitus (T2DM) with no history of fracture or osteoporosis treatment who are at risk of bone complications through the assessment of bone quality and quantity. METHODS: Of the outpatients attending our clinic during 2021 to 2022, we retrospectively enrolled 137 (men/women: 85/52, median age: 65 years) consecutive patients aged ≥40 years who had T2DM but no history of fracture or osteoporosis treatment. The lumbar spine and femoral neck bone mineral density and the trabecular bone score were determined using dual-energy X-ray absorptiometry. Independent factors associated with bone disease were identified using logistic regression analysis, and odds ratios (ORs) were calculated. RESULTS: Age and female sex were significantly associated with high ORs for development of bone disease. The integrated risk of bone complications was nearly 40-fold higher in older (≥65 years) women than in younger (<65 years) men. This difference remained after adjustment for the duration of T2DM, body mass index, and HbA1c level. CONCLUSIONS: Older women have the highest risk of osteopenia and osteoporosis among patients with T2DM who have no history of fracture or osteoporosis treatment. These patients should undergo intensive monitoring for bone fragility from an early stage of their disease.

The influence of immediate occlusal loading on micro/nano-structure of peri-implant jaw bone in rats.

PURPOSE: The objective of the present study was to ascertain the effect of immediate occlusal loading after implant placement on osseointegration and the micro/nanostructure of the surrounding bone. METHODS: After extraction of a rat maxillary right second molar, an implant was placed immediately with initial fixation (2 N< ). The implants were placed to avoid occlusal loading due to mastication, and in the loaded group, a superstructure was fabricated and subjected to occlusal loading. Bone morphometry, collagen fiber anisotropy, and biological apatite (BAp) crystallite alignment were quantitatively evaluated in both groups after extraction and fixation of the jaw bone at Days 7 and 21 after surgery. RESULTS: Osseointegration was observed in both groups. Bone morphometry showed significant differences in bone volume, trabecular number, trabecular thickness and bone mineral density (BMD) at Days 21 postoperatively (P < 0.05). A significant difference was also found in the trabecular separation at Days 7 postoperatively (P < 0.05). In the evaluation of collagen fiber anisotropy, collagen fiber bundles running differently from the existing bone were observed in both groups. In terms of BAp crystallite alignment, a specific structure was observed in the reconstructed new bone after implantation, and preferential orientation of BAp crystallite alignment was observed in the longitudinal direction of the implants in the Day 21 postoperative loaded group. CONCLUSION: When sufficient initial fixation is achieved at the time of dental implant placement, then the applied masticatory load may contribute to rapidly achieving not only bone volume, but also adequate bone quality after implant placement.

Exploring the nexus between fatigue, body composition, and muscle strength in hemodialysis patients.

BACKGROUND: Fatigue is a relatively prevalent condition among hemodialysis patients, resulting in diminished health-related quality of life and decreased survival rates. The purpose of this study was to investigate the relationship between fatigue and body composition in hemodialysis patients. METHODS: This cross-sectional study included 92 patients in total. Fatigue was measured by Functional Assessment of Chronic Illness Therapy - Fatigue (FACIT-F) (cut-off ≤ 34). Body composition was measured based on quantitative computed tomography (QCT), parameters including skeletal muscle index (SMI), intermuscular adipose tissue (IMAT), and bone mineral density (BMD). Handgrip strength was also collected. To explore the relationship between fatigue and body composition parameters, we conducted correlation analyses and binary logistic regression. RESULTS: The prevalence of fatigue was 37% (n = 34), abnormal bone density was 43.4% (n = 40). There was a positive correlation between handgrip strength and FACIT-F score (r = 0.448, p < 0.001). Age (r = - 0.411, p < 0.001), IMAT % (r = - 0.424, p < 0.001), negatively associated with FACIT-F score. Multivariate logistic regression analysis shows that older age, lower serum phosphorus, higher IMAT% are associated with a high risk of fatigue. CONCLUSION: The significantly increased incidence and degree of fatigue in hemodialysis patients is associated with more intermuscular adipose tissue in paraspinal muscle.

Causal relationship between intervertebral disc degeneration and osteoporosis: a bidirectional two-sample Mendelian randomization study.

Introduction: The relationship between intervertebral disc degeneration (IVDD) and osteoporosis (OP), diagnosed primarily using bone mineral density (BMD), remains unclear so far. The present study, therefore, aimed to investigate the potential relationship between osteoporosis and intervertebral disc degeneration using Mendelian randomization and genome-wide association analyses. Specifically, the impact of bone mineral density on the development of intervertebral disc degeneration was evaluated. Materials and methods: The genome-wide association studies (GWAS) summary data of OP/BMDs and IVDD were collected from the FinnGen consortium, the GEFOS consortium, and MRC-IEU. The relationship between IVDD and OP was then explored using TSMR. The inverse-variance weighted (IVW) method was adopted as the primary effect estimate, and the reliability and stability of the results were validated using various methods, including MR-Egger, weighted median, simple mode, weighted mode, and MR-PRESSO. Results: No significant causal relationship was observed between OP and IVDD (IVW, P > 0.05) or between femoral neck BMD (FA-BMD) and IVDD when OP and FA-BMD were used as exposures. However, increased levels of total body BMD (TB-BMD) and lumbar spine BMD (LS-BMD) were revealed as significant risk factors for IVDD (TB-BMD: IVW, OR = 1.201, 95% CI: 1.123-1.284, P = 8.72 × 10-8; LS-BMD: IVW, OR = 1.179, 95% CI: 1.083-1.284, P = 1.43 × 10-4). Interestingly, both heel BMD (eBMD) and femur neck BMD (FN-BMD) exhibited potential causal relationships (eBMD: IVW, OR = 1.068, 95% CI: 1.008-1.131, P = 0.0248; FN-BMD, IVW, OR = 1.161, 95% CI: 1.041-1.295, P = 0.0074) with the risk of IVDD. The reverse MR analysis revealed no statistically causal impact of IVDD on OP and the level of BMD (P > 0.05). Conclusion: OP and the level of FA-BMD were revealed to have no causal relationship with IVDD. The increased levels of TB-BMD and LS-BMD could promote the occurrence of IVDD. Both eBMD and FN-BMD have potential causal relationships with the risk of IVDD. No significant relationship exists between IVDD and the risk of OP. Further research is warranted to comprehensively comprehend the molecular mechanisms underlying the impact of OP and BMD on IVDD and vice versa.

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.

ED-71 Improves Bone Mass in Ovariectomized Rats by Inhibiting Osteoclastogenesis Through EphrinB2-EphB4-RANKL/OPG Axis.

Purpose: Estrogen deficiency is the main reason of postmenopausal osteoporosis. Eldecalcitol (ED-71) is a new active vitamin D analogue clinically used in the treatment of postmenopausal osteoporosis. We aimed to investigate whether EphrinB2-EphB4 and RANKL/RANK/OPG signaling cooperate in mediating the process of osteoporosis by ED-71. Methods: In vivo, the ovariectomized (OVX) rats were administered orally with 30 ng/kg ED-71 once a day for 8 weeks. HE staining, Masson staining and Immunofluorescence staining were used to evaluate bone mass, bone formation, osteoclastogenesis associated factors and the expression of EphrinB2, EphB4, RANKL and OPG. In vitro, H2O2 stimulation was used to simulate the cell environment in osteoporosis. Immunofluorescence, quantitative real time PCR (qRT-PCR), enzyme-linked immunosorbent assay (ELISA) and Western Blot were applied to detect the expression of EphrinB2, EphB4, RANKL and OPG. In osteoblasts, EphB4 was knocked down by EphB4 small-interfering RNA (siRNA) transfection. LY294002 (PI3K inhibitor) or ARQ092 (AKT inhibitor) was used to block PI3K/AKT pathway. An indirect co-culture system of osteoblasts and osteoclasts was established. The mRNA and protein expression of osteoclastogenes is associated factors were tested by qRT-PCR and Western Blot. Results: ED-71 increased bone mass and decreased the number of osteoclasts in OVX rats. Moreover, ED-71 promoted the expression of EphrinB2, EphB4, and decreased the RANKL/OPG ratio in osteoblasts. Osteoclastogenesis was restrained when osteoclasts were indirectly co-cultured with ED-71-treated osteoblasts. After silencing of EphB4 expression in osteoblasts, ED-71 inhibited the expression of P-PI3K and P-AKT and increased the ratio of RANKL/OPG. This reversed the inhibitory effect of ED-71 on osteoclastogenes. Therefore, in ED-71-inhibited osteoclastogenes, EphB4 is a key factor affecting the secretion of RANKL and OPG by osteoblasts. EphB4 suppressed the RANKL/OPG ratio through activating PI3K/AKT signaling in osteoblasts. Conclusion: ED-71 inhibits osteoclastogenesis through EphrinB2-EphB4-RANKL/OPG axis, improving bone mass in ovariectomized rats. PI3K/AKT pathway is involved this process.

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.

Relationship between paraspinal muscle properties and bone mineral density based on QCT in patients with lumbar disc herniation.

OBJECTIVE: Increasing research suggests that paraspinal muscle fat infiltration may be a potential biological marker for the assessment of osteoporosis. Our aim was to investigate the relationship between lumbar paraspinal muscle properties on MRI and volumetric bone mineral density (vBMD) based on QCT in patients with lumbar disc herniation (LDH). METHODS: A total of 383 patients (aged 24-76 years, 193 females) with clinically and radiologically diagnosed LDH were enrolled in this retrospective study. The muscle cross-sectional area (CSA) and the proton density fat fraction (PDFF) were measured for the multifidus (MF), erector spinae (ES) and psoas major (PS) at the central level of L3/4, L4/5 and L5/S1 on lumbar MRI. QCT was used to measure the vBMD of two vertebral bodies at L1 and L2 levels. Patients were divided into three groups based on their vBMD values: normal bone density group (> 120 mg/cm3), osteopenia group (80 to 120 mg/cm3) and osteoporosis group (< 80 mg/cm3). The differences in paraspinal muscle properties among three vBMD groups were tested by one-way ANOVA with post hoc analysis. The relationships between paraspinal muscle properties and vBMD were analyzed using Pearson correlation coefficients. Furthermore, the association between vBMD and paraspinal muscle properties was further evaluated using multiple linear regression analysis, with age and sex also included as predictors. RESULTS: Among the 383 LDH patients, 191 had normal bone density, 129 had osteopenia and 63 had osteoporosis. In LDH patients, compared to normal and osteopenia group, paraspinal muscle PDFF was significantly greater in osteoporosis group, while paraspinal muscle CSA was lower (p < 0.001). After adjusting for age and sex, it was found that MF PDFF and PS CSA were found to be independent factors influencing vBMD (p < 0.05). CONCLUSION: In patients with LDH, paraspinal muscle properties measured by IDEAL-IQ sequence and lumbar MR scan were found to be related to vBMD. There was a correlation between the degree of paraspinal muscle PDFF and decreasing vBMD, as well as a decrease paraspinal muscle CSA with decreasing vBMD. These findings suggest that clinical management should consider offering tailored treatment options for patients with LDH based on these associations.

The magnetic resonance imaging-based vertebral bone quality scoring system: A novel method to evaluate endplate changes in patients with primary single-level disk herniation and Modic changes.

OBJECTIVES: This study aimed to investigate differences in vertebral fat distribution and bone density between patients with and without Modic changes (MCs) using a magnetic resonance imaging (MRI)-based vertebral bone quality (VBQ) scoring system. PATIENTS AND METHODS: In this retrospective study, 189 patients (95 males, 94 females; mean age: 54±2.2 years; range, 18 to 82 years) with primary single-level disk herniation were reviewed between June 2021 and June 2022. The patients were divided into the MC group (n=99) and the non-MC (NMC) group (n=90). The subcutaneous fat tissue thickness and bone mineral density were determined. The system consisted of two scores: the VBQ score, which reflected the fatty infiltration within the vertebral body, and the endplate bone quality (EBQ) score, which reflected the signal intensity (SI) of the upper and lower endplates. The EBQ score is a novel measurement that we introduced in this study. The VBQ and EBQ were measured and scored using MRI scans. The mean SI of the upper and lower endplates (endplate SI)/the bone marrow SI (marrow SI) was measured. RESULTS: There was a considerable difference in subcutaneous fat tissue thickness between the MC and NMC groups (1.40 vs. 1.16 cm, p=0.01). The EBQ scores of the L4 and L5 vertebrae and endplate SI/marrow SI of all vertebral body levels were significantly higher in the MC group. CONCLUSION: The occurrence of MCs in the lumbar spine may be associated with abnormal fat distribution. The distribution of vertebral fat in patients with MCs is distributed earlier in the upper and lower endplates of the vertebral body, and this trend is not observed in patients without MC. The thickness of subcutaneous fat tissue is a key factor in the occurrence of MCs.

Hydrolyzed egg yolk peptide prevented osteoporosis by regulating Wnt/ß-catenin signaling pathway in ovariectomized rats.

Hydrolyzed egg yolk peptide (YPEP) was shown to increase bone mineral density in ovariectomized rats. However, the underlying mechanism of YPEP on osteoporosis has not been explored. Recent studies have shown that Wnt/ß-catenin signaling pathway and gut microbiota may be involved in the regulation of bone metabolism and the progression of osteoporosis. The present study aimed to explore the preventive effect of the YPEP supplementation on osteoporosis in ovariectomized (OVX) rats and to verify whether YPEP can improve osteoporosis by regulating Wnt/ß-catenin signaling pathway and gut microbiota. The experiment included five groups: sham surgery group (SHAM), ovariectomy group (OVX), 17-ß estradiol group (E2: 25 µg /kg/d 17ß-estradiol), OVX with low-dose YPEP group (LYPEP: 10 mg /kg/d YPEP) and OVX with high-dose YPEP group (HYPEP: 40 mg /kg/d YPEP). In this study, all the bone samples used were femurs. Micro-CT analysis revealed improvements in both bone mineral density (BMD) and microstructure by YPEP treatment. The three-point mechanical bending test indicated an enhancement in the biomechanical properties of the YPEP groups. The serum levels of bone alkaline phosphatase (BALP), bone gla protein (BGP), calcium (Ca), and phosphorus (P) were markedly higher in the YPEP groups than in the OVX group. The LYPEP group had markedly lower levels of alkaline phosphatase (ALP), tartrate-resistant acid phosphatase (TRAP) and C-terminal telopeptide of type I collagen (CTX-I) than the OVX group. The YPEP groups had significantly higher protein levels of the Wnt3a, ß-catenin, LRP5, RUNX2 and OPG of the Wnt/ß-catenin signaling pathway compared with the OVX group. Compared to the OVX group, the ratio of OPG/RANKL was markedly higher in the LYPEP group. At the genus level, there was a significantly increase in relative abundance of Lachnospiraceae_NK4A136_group and a decrease in Escherichia_Shigella in YPEP groups, compared with the OVX group. However, in the correlation analysis, there was no correlation between these two bacteria and bone metabolism and microstructure indexes. These findings demonstrate that YPEP has the potential to improve osteoporosis, and the mechanism may be associated with its modulating effect on Wnt/ß-catenin signaling pathway.

Genetic influence on within-person longitudinal change in anthropometric traits in the UK Biobank.

The causes of temporal fluctuations in adult traits are poorly understood. Here, we investigate the genetic determinants of within-person trait variability of 8 repeatedly measured anthropometric traits in 50,117 individuals from the UK Biobank. We found that within-person (non-directional) variability had a SNP-based heritability of 2-5% for height, sitting height, body mass index (BMI) and weight (P ≤ 2.4 × 10-3). We also analysed longitudinal trait change and show a loss of both average height and weight beyond about 70 years of age. A variant tracking the Alzheimer's risk APOE- E 4 allele (rs429358) was significantly associated with weight loss ( ß = -0.047 kg per yr, s.e. 0.007, P = 2.2 × 10-11), and using 2-sample Mendelian Randomisation we detected a relationship consistent with causality between decreased lumbar spine bone mineral density and height loss (bxy = 0.011, s.e. 0.003, P = 3.5 × 10-4). Finally, population-level variance quantitative trait loci (vQTL) were consistent with within-person variability for several traits, indicating an overlap between trait variability assessed at the population or individual level. Our findings help elucidate the genetic influence on trait-change within an individual and highlight disease risks associated with these changes.