Reduced Bone Mass Research Articles

Sex-specific association between platelet content and bone mineral density in adults: a cross-sectional study

BackgroundOsteoporosis (OP) is a complex skeletal disorder characterized by reduced bone mass, microarchitectural deterioration of bone tissue, and increased susceptibility to fractures. Bone mineral density (BMD), as the best indicator of bone mineral content per unit area of bone, is one of the key diagnostic factors for OP. Platelets (PLT), serving as important immune cells and components of the coagulation system, have been demonstrated to be associated with bone formation, resorption, and remodeling processes. However, no research has established the relationship between BMD and platelet count (PC) in the American population thus far. This study aims to investigate the correlation between BMD and PC among the American population, and to appraise the effects of additional risk factors on this association.MethodsThis investigation examined the relationship between BMD and PC by analyzing data from the National Health and Nutrition Examination Survey (NHANES) between 2011 and 2018. A weighted multivariate logistic regression analysis was employed to assess this correlation. Additionally, subgroup and smooth curve analyses were conducted to delve deeper into the BMD-PC relationship and to identify other potential determinants of PC.ResultsThis study reveals a significant negative correlation between BMD and PC in the American adult population (β=-15.05, 95% CI: -22.07 to -8.03, p < 0.0001). Subgroup analysis highlights notable differences in this correlation between genders and various racial groups. Smooth curve fitting and generalized additive models were applied to further explore the relationship between BMD and PC, considering the influence of multiple factors.ConclusionThe present study investigated the correlation between BMD and PC in adults, with a particular focus on the potential risk factors for thrombocytopenia. This negative correlation was found to be markedly pronounced in males, an association not observed in females. Additionally, a potential inverse relationship between BMD and hemoglobin (HGB) levels was identified. Consequently, for individuals with elevated bone mass or osteoporosis (OP), we advocate for routine complete blood count monitoring to identify hematological irregularities. Considering the significant variations by sex, age, and race, special vigilance is advised for changes in PC among non-Hispanic white males under the age of 55.

Efficacy of Magnetic Field on Risk of Falling and Bone Mineral Density in Elderly Osteoporotic Women

Background: Osteoporosis, a prevalent condition affecting equally women and men, has been marked by reduced bone mass and structural degeneration. PEMFs promote bone formation, reduce inflammation, and improve bone remodeling by boosting osteoblast development and differentiation. Objective: The aim of this study was to examine the efficacy of pulsed electromagnetic field on bone mineral density and risk of falling in old women with osteoporosis. Methods: The study included sixty older women with osteoporosis. The subjects were separated into two groups: 30 in each one. Group A received pulsed electromagnetic field and closed chain exercise; and group B received the closed chain exercises. Results: A statistically significant improvement in the study group compared to the control group with percentage of improvement in femur BMD, lumbar BMD, risk of falling, BBS, ALP, VAS for L.L, VAS for back and OQLQ by 27.71 %, 27.84 %, 21.86 %, 21.64 %, 31.29 %, 54.06 %, 53.01 % and 33.45 % respectively. Conclusion: Pulsed Electro Magnetic Field (PEMF) is a significant intervention, and it is recommended to be a part of physical therapy &amp; rehabilitation protocols of elderly osteoporotic women.

Effects of coagulation factors on bone cells and consequences of their absence in haemophilia a patients

Haemophilia is associated with reduced bone mass and mineral density. Due to the rarity of the disease and the heterogeneity among the studies, the pathogenesis of bone loss is still under investigation. We studied the effects of coagulation factors on bone cells and characterized in a pilot study the osteoclastogenic potential of patients’ osteoclast precursors. To evaluate the effect of coagulation factors on osteoclasts, we treated Healthy Donor-Peripheral Blood Mononuclear Cells (HD-PBMC) with Factor VIII (FVIII), von Willebrand Factor (VWF), FVIII/VWF complex, activated Factor IX (FIXa), activated Factor X (FXa) and Thrombin (THB). FVIII, VWF, FVIII/VWF, FXa and THB treatments reduced osteoclast differentiation of HD-PBMC and VWF affected also bone resorption. Interestingly, PBMC isolated from patients with moderate/severe haemophilia showed an increased osteoclastogenic potential due to the alteration of osteoclast precursors. Moreover, increased expression of genes involved in osteoclast differentiation/activity was revealed in osteoclasts of an adult patient with moderate haemophilia. Control osteoblasts treated with the coagulation factors showed that FVIII and VWF reduced ALP positivity; the opposite effect was observed following THB treatment. Moreover, FVIII, VWF and FVIII/VWF reduced mineralization ability. These results could be important to understand how coagulation factors deficiency influences bone remodeling activity in haemophilia.

The interplay between osteoarthritis and osteoporosis: Mechanisms, implications, and treatment considerations – A narrative review

This comprehensive review examines the relationship between osteoarthritis (OA) and osteoporosis (OP), two common disorders in the elderly. OA involves joint cartilage degeneration and pain, while OP leads to fractures due to reduced bone mass. Despite different pathologies, both conditions share risk factors such as age and genetics. Studies reveal mixed results: some show higher bone mineral density (BMD) in OA patients, suggesting an inverse relationship, while others find no significant link. Proposed mechanisms include mechanical loading, bone remodeling, and inflammation. Clinical strategies focus on maintaining bone health in OA and monitoring joint health in OP, with treatments like bisphosphonates and exercise. Understanding these interactions is crucial for developing integrated treatments to improve patient outcomes and quality of life. Further research is needed to clarify these complex mechanisms.

Identification of osteoporosis genes using family studies.

Osteoporosis is a multifactorial bone disease characterised by reduced bone mass and increased fracture risk. Family studies have made significant contribution in unravelling the genetics of osteoporosis. Yet, most of the underlying molecular and biological mechanisms remain unknown prompting the need for further studies. This review outlines the proper phenotyping and advanced genetic techniques in the form of high-throughput DNA sequencing used to identify genetic factors underlying monogenic osteoporosis in a family-based setting. The steps related to variant filtering prioritisation and curation are also described. From an evolutionary perspective, deleterious risk variants with higher penetrance tend to be rare as a result of negative selection. High-throughput sequencing (HTS) can identify rare variants with large effect sizes which are likely to be missed by candidate gene analysis or genome-wide association studies (GWAS) wherein common variants with small to moderate effect sizes are identified. We also describe the importance of replicating implicated genes, and possibly variants, identified following HTS to confirm their causality. Replication of the gene in other families, singletons or independent cohorts confirms that the shortlisted genes and/or variants are indeed causal. Furthermore, novel genes and/or variants implicated in monogenic osteoporosis require a thorough validation by means of in vitro and in vivo assessment. Therefore, analyses of families can continue to elucidate the genetic architecture of osteoporosis, paving the way for improved diagnostic and therapeutic strategies.

The effect of body mass index on bone density by age distribution in women.

Osteoporosis significantly affects public health, especially among postmenopausal women, by reducing bone mass and increasing the risk of fractures. While the influence of body mass index (BMI) on Bone Mineral Density (BMD) is acknowledged, the specific age range in which BMI most significantly affects bone density remains unclear. This study aims to explore the relationship between BMI and BMD in different age groups to identify potential age-specific risk factors for osteoporosis. In a retrospective cohort study at the University of Health Sciences Turkey, X Hospital, DXA scans of 240 postmenopausal women aged 40 to 80 were analyzed between February 2018 and February 2020. The study used statistical analyses, including ANCOVA and Pearson correlation, to investigate the effects of BMI on BMD, adjusting for age and other variables. Analysis revealed a complex interaction between BMI and BMD. Controlling for BMI showed a statistically significant difference in measurements of lumbar T, neck T, and trochanter T between age groups (P < .05). Specifically, bone density in the 40 to 49 age range was found to be lower when adjusted for BMI, suggesting that the protective effect of higher BMI is less pronounced in younger postmenopausal ages but decreases less negatively in older groups. The impact of BMI on trochanter T measurements was markedly different, increasing in the 40 to 49 age group, while decreasing in others. BMI, along with body weight and age, are important determinants of BMD, but not the sole factors influencing bone loss. The study highlights the need for a personalized approach to osteoporosis risk, considering a broader spectrum of genetic, hormonal and lifestyle factors. It recommends further evaluation of other risk factors in larger cohorts and emphasizes the importance of future longitudinal research to elucidate the dynamic relationship between BMI and BMD over time.

Osteoporosis in postmenopausal women is associated with disturbances in gut microbiota and migration of peripheral immune cells

BackgroundPostmenopausal osteoporosis (PMO) results from a reduction in bone mass and microarchitectural deterioration in bone tissue due to estrogen deficiency, which may increase the incidence of fragility fractures. In recent years, the “gut-immune response-bone” axis has been proposed as a novel potential approach in the prevention and treatment of PMO. Studies on ovariectomized murine model indicated the reciprocal role of Th17 cells and Treg cells in the aetiology of osteoporosis. However, the relationship among gut microbiota, immune cells and bone metabolic indexes remains unknown in PMO.MethodsA total of 77 postmenopausal women were recruited for the study and divided into control (n = 30), osteopenia (n = 19), and osteoporosis (n = 28) groups based on their T score. The frequency of Treg and Th17 cells in lymphocytes were analyzed by flow cytometry. The serum levels of interleukin (IL)-10, 17 A, 1β, 6, tumor necrosis factor (TNF)-α, and lipopolysaccharide (LPS) were determined via enzyme-linked immunosorbent assay. Additionally, 16S rRNA gene V3-V4 region sequencing analysis was performed to investigate the gut microbiota of the participants.ResultsThe results demonstrated decreased bacterial richness and diversed intestinal composition in PMO. In addition, significant differences of relative abundance of the gut microbial community in phylum and genus levels were found, mainly including increased Bacteroidota, Proteobacteria, and Campylobacterota, as well as reduced Firmicutes, Butyricicoccus, and Faecalibacterium. Intriugingly, in the osteoporosis group, the concentration of Treg cells and associated IL-10 in peripheral circulation was negatively regulated, while other chronic systemic proinflammatory cytokines and Th17 cells showed opposite trends. Moreover, significantly elevated plasma lipopolysaccharide (LPS) in patients with osteoporosis indicated that disrupted intestinal integrity and permeability. A correlation analysis showed close relationships between gut bacteria and inflammation.ConclusionsCollectively, these observations will lead to a better understanding of the relationship among bone homeostasis, the microbiota, and circulating immune cells in PMO. The elevated LPS levels of osteoporosis patients which not only indicate a breach in intestinal integrity but also suggest a novel biomarker for assessing osteoporosis risk linked to gut health.

6536 National Trends in Prevalence of Prediabetes and Diabetes Among Women With Low Bone Mineral Density: 2009-2018

Abstract Disclosure: A. Atri: None. C. Anastasopoulou: None. Introduction: In recent years, bone fragility has emerged as a complication of prediabetes (preDM) and diabetes mellitus (DM), resulting in reduced bone mass and increased fracture risk, and is an important, though under-studied risk factor for osteoporosis. However, the converse relationship, trends in prevalence of preDM and DM in women with low bone mineral density (BMD) in the United States, are not well established. Methods: We used data from the National Health and Nutrition Examination Survey (NHANES) for the years 2009-10, 2013–14 and 2017–18 to include U.S. women aged ≥ 50 years with T-score ≤ -1. Osteoporosis assessment in NHANES was not completed in 2011–12 and 2015–16, and therefore not included in the analysis. Osteopenia and osteoporosis were defined by a femoral neck BMD ≤1 to 2.5, and ≤2.5 standard deviations (SDs) below the BMD of a young female adult mean (T-score). Femur neck BMD was measured by dual energy x-ray absorptiometry (DEXA). PreDM and DM were defined using HbA1c values of 5.7 - 6.4% and ≥ 6.5% respectively. Participants with missing HbA1c and BMD data were excluded. Descriptive statistics were used for comparing means and medians. The Cochran-Armitage test was utilized for trend analysis. Results: In this nationally representative sample of US women with low BMD, the median (IQR) T-score at femoral neck worsened from -1.74 (-1.4 to -2.17) in 2009-10 to -1.87 (-1.43 to -2.32) in 2017-18 (trend p = 0.001). Similarly, the prevalence of osteoporosis increased from 13.7% to 16.9% (trend p = 0.001). Overall, in this cohort, the national prevalence of both preDM and DM decreased from 40% to 32.9% and 9.6% to 9%, respectively (trend p = 0.001). Along with a reduction in the overall prevalence of osteopenia (86.3% to 83.1%, p=0.001), the prevalence of both preDM and DM decreased from 39.2% to 32.6% and 10% to 9% (p = 0.001). In those with osteoporosis, the prevalence of preDM decreased from 45.2% to 34.4% (p trend=0.001), however, the prevalence of DM increased from 7.5% to 8.7% (p trend =0.001). Overall rates of uncontrolled DM (HbA1c &amp;gt; 7%) in women with osteoporosis showed significant improvement (5.8% to 3.5%, p = 0.001). Discussion Despite worsening trend in femoral neck BMD among US women age ≥ 50 years from 2009-10 to 2017-18, the overall prevalence of preDM and DM improved by 7.1% and 0.6% respectively. However, this favorable trend was not observed among women with osteoporosis, where the overall prevalence of DM increased by 1.2%, though the rate of uncontrolled DM significantly decreased by 2.3%. Targeted interventions to improve blood glucose control among women with low BMD, especially those with osteoporosis are warranted, to improve bone health, as well as reduce fall and fracture risk. Presentation: 6/2/2024

Mechanical analysis of modified femoral neck system in the treatment of osteoporotic femoral neck fractures

BackgroundDespite the explicit biomechanical advantages associated with FNS, it is currently inconclusive, based on the existing literature, whether Femoral Neck System (FNS) outperforms Cannulated cancellous screws (CSS) in all aspects. Due to variances in bone morphology and bone density between the elderly and young cohorts, additional research is warranted to ascertain whether the benefits of FNS remain applicable to elderly osteoporosis patients. This study aimed to investigate the biomechanical properties of FNS in osteoporotic femoral neck fractures and propose optimization strategies including additional anti-rotation screw.MethodsThe Pauwels type III femoral neck fracture models were reconstructed using finite element numerical techniques. The CSS, FNS, and modified FNS (M-FNS) models were created based on features and parameterization. The various internal fixations were individually assembled with the assigned normal and osteoporotic models. In the static analysis mode, uniform stress loads were imposed on all models. The deformation and stress variations of the femur and internal fixation models were recorded. Simultaneously, descriptions of shear stress and strain energy were also incorporated into the figures.ResultsFollowing bone mass reduction, deformations in CSS, FNS, and M-FNS increased by 47%, 52%, and 40%, respectively. The equivalent stress increments for CSS, FNS, and M-FNS were 3%, 43%, 17%, respectively. Meanwhile, variations in strain energy and shear stress were observed. The strain energy increments for CSS, FNS, and M-FNS were 4%, 76%, and 5%, respectively. The shear stress increments for CSS, FNS, and M-FNS were 4%, 65% and 44%, respectively. Within the osteoporotic model, M-FNS demonstrated the lowest total displacement, shear stress, and strain energy.ConclusionModified FNS showed better stability in the osteoporotic model (OM). Using FNS alone may not exhibit immediate shear resistance advantages in OM. Concurrently, the addition of one anti-rotation screw can be regarded as a potential optimization choice, ensuring a harmonious alignment with the structural characteristics of FNS.

Vertebral body density role in determining vertebral osteoporotic fracture type and its progression.

Vertebral osteoporotic fractures (VOF) are among the most frequent fractures in the elderly, often leading to an impaired lifestyle and a high economic burden. Although a reduced bone mass density is considered one of the main risk factors for VOF, its role in determining the fracture type, using the AO spine-DGOU classification for osteoporotic thoracolumbar fractures, as well as its progression, is unknown. The current study aimed to: (1) reveal whether the bone density of the vertebral bodies of fractured and non-fractured vertebrae predicts the type of fracture, (2) examine whether bone density is associated with the initial and progressive collapse of the vertebral body, and (3) provide predictive measures for fracture progression. The study sample included 124 patients (40 males and 84 females) with an acute osteoporotic vertebral fracture who underwent a computerized tomography scan at the time of diagnosis and an x-ray at least 3 months later. The bone density of the fractured and adjacent (non-fractured) vertebrae was measured at diagnosis. The magnitude of the collapse and the progression of the fracture over time were calculated from height measurements of the vertebral bodies at diagnosis and follow-up. Age was a significant factor in predicting the fracture type and magnitude of collapse, whereas sex and bone density were not. The severity of the fracture was involved in predicting its progression, demonstrating that severe-type fractures tended to continue to collapse after diagnosis. However, when each type was examined independently, the density of the fractured vertebra had a protective effect on fracture progression. To conclude, identifying the type of fracture is beneficial in determining patient prognosis. Furthermore, the density of the fractured vertebra, the magnitude of collapse, and patient age are valuable predictors of fracture progression.

Osteoporosis in older men

Osteoporosis, characterized by reduced bone mass and compromised skeletal microarchitecture, significantly increases the risk of fractures and is the most prevalent metabolic bone disease. While it is commonly associated with post-menopausal women, osteoporosis and subsequent fractures are also substantial concerns in men. Men experience sustained bone loss after the sixth decade, with estimates indicating that 20% of Americans with osteopenia or osteoporosis are men. Approximately one in eight men over 50 will suffer an osteoporotic fracture, with hip fractures in men leading to a two- to threefold increase in mortality compared to women. The prevalence of osteoporosis in men has risen, doubling in prevalence since the early 1990s. Men generally have higher peak bone mass and greater bone size, offering some protection against osteoporosis; however, aging leads to increased bone resorption and decreased bone formation, exacerbated by lower androgen and estrogen levels. Secondary causes, such as hypogonadism and chronic glucocorticoid use, are prevalent in men. Diagnosis primarily involves bone mineral density (BMD) measurements using dual-energy X-ray absorptiometry (DXA), with fracture risk assessment tools like FRAX and MORES aiding in clinical decisions. Treatment includes calcium and vitamin D supplementation, bisphosphonates, denosumab, and anabolic agents like teriparatide and abaloparatide. Special considerations are necessary for men undergoing androgen deprivation therapy for prostate cancer due to accelerated bone loss. Effective management requires early diagnosis, lifestyle modifications, and appropriate pharmacological interventions to reduce fracture risk and improve patient outcomes.

Piezo1 expression in mature osteocytes is dispensable for the skeletal response to mechanical loading

Mechanical loading is essential for bone growth and homeostasis, with osteocytes considered the primary mechanosensors. Deleting the mechanosensitive ion channel Piezo1 from Dmp1-Cre-targeted cells, which include both osteoblasts and osteocytes, resulted in reduced bone mass and impaired skeletal responses to mechanical stimuli. To specifically isolate Piezo1's role in osteocytes, we used Sost-Cre mice to generate mice with Piezo1 deletion exclusively in mature osteocytes. These mice exhibited lower bone mineral density, decreased cancellous bone mass, and reduced cortical thickness with decrease periosteal expansion. However, unlike mice lacking Piezo1 in both osteoblasts and osteocytes, those with Piezo1 deletion in mature osteocytes responded normally to mechanical loading. These findings suggest that Piezo1 expression in mature osteocytes contributes to bone maintenance under normal physiological condition, but is dispensable for the skeletal response to mechanical loading.

Analysis of the Effectiveness of a Fall Prevention Program Incorporating an Interprofessional Team Collaboration Model on Reducing Fall Risk in Elderly Living in Long-term Care Facilities

Concurrent with population ageing, falls have become a significantly more challenging public health issue among older adults. Three years of data collected recently from a nursing home in northern Taiwan reveals an increasing trend in fall density that is primarily associated with aging, physiological decline, chronic diseases, polypharmacy, osteoporosis, and lack of exercise. The percentage of nursing home residents at high risk of falls is currently at 12.6%, and the fall rate has been reported as reaching as high as 30% annually. A fall prevention program was implemented to reduce the fall incidence rate to 18%, with secondary goals of improving fall prevention awareness, behavior, self-efficacy, lower limb muscle strength, balance, and gait by 10% on average, respectively, between pre-test and post-test. From September 30, 2023 to February 29, 2024, a health promotion activity and fall prevention exercise course were implemented using an interdisciplinary team collaboration model over a six-week period, providing individualized exercise for the participants. The study included 20 older adults with an average age of 88 years. Most (90%; n = 18) had chronic diseases, 25% (n = 5) were on more than nine medications, 70% (n = 14) had reduced bone mass, and 40% (n = 8) were at high risk of falls, with a fall incidence rate of 30% during the immediately preceding year. Post-intervention, the fall incidence rate dropped to 5%, fall prevention awareness, behavior, and self-efficacy increased by 18.3%, and lower limb muscle strength, balance, and gait improved by 11.7%. The post-test results in fall prevention awareness, behavioral changes, self-efficacy, and lower limb strength, balance, and gait were all significantly better than pre-test results, with all results achieving statistical significance. The project results support the positive effects of the developed intervention effectively on elderly physical fitness and fall risk, providing valuable insights for the implementation of fall prevention strategies in nursing homes.

Europium-Containing Nanospheres for Treating Ovariectomy-Induced Osteoporosis: Targeted Bone Remodeling and Macrophage Polarization Modulation.

Osteoporosis, characterized by reduced bone mass and structural deterioration, poses a significant healthcare challenge. Traditional treatments, while effective in reducing fracture risks, are often limited by side effects. This study introduces a novel nanocomplex, europium (Eu) ions-doped superparamagnetic iron oxide (SPIO) nanocrystals encapsulated in poly(lactic-co-glycolic acid) (PLGA) nanospheres, abbreviated as SPIO:Eu@PLGA nanospheres, as a potential therapeutic agent for osteoporosis by modulating macrophage polarization, enhancing osteoblast differentiation and inhibiting osteoclastogenesis. SPIO and SPIO:Eu nanocrystals were synthesized through pyrolysis and encapsulated in PLGA using an emulsification method. To evaluate the impact of SPIO:Eu@PLGA nanospheres on macrophage reprogramming and reactive oxygen species (ROS) production, flow cytometry analysis was conducted. Furthermore, an ovariectomized (OVX) rat model was employed to assess the therapeutic efficacy of SPIO:Eu@PLGA nanospheres in preventing the deterioration of osteoporosis. In vitro, SPIO:Eu@PLGA nanospheres significantly attenuated M1 macrophage activation induced by lipopolysaccharides, promoting a shift towards the M2 phenotype. This action is linked to the modulation of ROS and the NF-κB pathway. Unlike free Eu ions, which do not achieve similar results when not incorporated into the SPIO nanocrystals. SPIO:Eu@PLGA nanospheres enhanced osteoblast differentiation and matrix mineralization while inhibiting RANKL-induced osteoclastogenesis. In vivo studies demonstrated that SPIO:Eu@PLGA nanospheres effectively targeted trabecular bone surfaces in OVX rats under magnetic guidance, preserving their structure and repairing trabecular bone loss by modulating macrophage polarization, thus restoring bone remodeling homeostasis. The study underscores the critical role of Eu doping in boosting the anti-osteoporotic effects of SPIO:Eu@PLGA nanospheres, evident at both cellular and tissue levels in vitro and in vivo. The inclusion of Eu into SPIO matrix suggests a novel approach for developing more effective osteoporosis treatments, particularly for conditions induced by OVX. This research provides essential insights into SPIO:Eu@PLGA nanospheres as an innovative osteoporosis treatment, addressing the limitations of conventional therapies through targeted delivery and macrophage polarization modulation.

Evaluation of Potential Roles of Zinc Finger Homeobox 3 (Zfhx3) Expressed in Chondrocytes and Osteoblasts on Skeletal Growth in Mice.

Bone formation is tightly modulated by genetically encoded molecular proteins that interact to regulate cellular differentiation and secretion of bony matrix. Many transcription factors are known to coordinate these events by controlling gene transcription within networks. However, not all factors involved are known. Here, we identified a novel function forZinc Finger Homeobox 3(Zfhx3), a gene encoding a transcription factor, as a regulator of bone metabolism. We knocked outZfhx3conditionally in mice in either chondrocytes or osteoblasts and characterized their bones by micro-CT in 12-week-old mice. We observed a negative effect in linear bone growth in both knockout mice but reduced bone mass only in mice withZfhx3deleted in osteoblasts. Loss of Zfhx3 expression in osteoblasts affected trabecular bone mass in femurs and vertebrae in both sexes but influenced cortical bone volume fraction only in females. Moreover, transcriptional analysis of femoral bones in osteoblastZfhx3conditional knockout mice revealed a reduced expression of osteoblast genes, and histological evaluation of trabecular bones suggests that Zfhx3 causes changes in bone formation and not resorption. The loss of Zfhx3 causes reductions in trabecular bone area and osteoid volume, but no changes in the expression of osteoclast differentiation markers or number of TRAP stained osteoclasts. These studies introduce Zfhx3 as a relevant factor toward understanding gene regulatory networks that control bone formation and development of peak bone mass.

Secreted protein TNA: a promising biomarker for understanding the adipose-bone axis and its impact on bone metabolism

BackgroundOsteoporosis (OP) is a systemic bone disease characterized by reduced bone mass and deterioration of bone microstructure, leading to increased bone fragility. Platelets can take up and release cytokines, and a high platelet count has been associated with low bone density. Obesity is strongly associated with OP, and adipose tissue can influence platelet function by secreting adipokines. However, the biological relationship between these factors remains unclear.MethodsWe conducted differential analysis to identify OP platelet-related plasma proteins. And, making comprehensive analysis, including functional enrichment, protein-protein interaction network analysis, and Friends analysis. The key protein, Tetranectin (TNA/CLEC3B), was identified through screening. Then, we analyzed TNA’s potential roles in osteogenic and adipogenic differentiation using multiple RNA-seq data sets and validated its effect on osteoclast differentiation and bone resorption function through in vitro experiments.ResultsSix OP-platelet-related proteins were identified via differential analysis. Then, we screened the key protein TNA, which was found to be highly expressed in adipose tissue. RNA-seq data suggested that TNA may promote early osteoblast differentiation. In vitro experiments showed that knockdown of TNA expression significantly increased the expression of osteoclast markers, thereby promoting osteoclast differentiation and bone resorption.ConclusionsWe identified TNA as a secreted protein that inhibits osteoclast differentiation and bone resorption. While, it potentially promoted early osteoblast differentiation from bioinformatic results. TNA may play a role in bone metabolism through the adipose-bone axis.

Lif-deficiency promote systemic Iron metabolism disorders and increases the susceptibility of osteoblasts to ferroptosis

Leukemia inhibitory factor (LIF) is a multifunctional cytokine that plays a crucial role in various biological processes. However, LIF involvement in iron metabolism remains almost unexplored. This study aimed to explore the impact of LIF on systemic iron transportation and its potential role in ferroptosis in osteoblasts. We observed that the Lif-deficient (Lif−/−) mice is characterized by a reduction in bone mass and a decrease in bone mineral density compared with wild-type (WT) mice. Energy-dispersive X-ray spectroscopy revealed a marked increase in iron content on the surface of femurs from Lif−/− mice. Meanwhile, iron stores test lower iron levels in the spleens and higher levels in the femurs of Lif−/− mice. Besides, Lif−/− mice display increased levels of serum iron, total iron-binding capacity, unsaturated iron-binding capacity, and transferrin saturation and serum ferritin relative to WT mice. Hepcidin mRNA expression reduction in the liver of Lif−/− mice. It also holds true in the AML-12 hepatocyte cell line after Lif-knockdown. Immunohistochemistry and RT-PCR revealed elevated ferroportin (FPN) in duodenal cells of Lif−/− mice. Lif-deficiency decreases SLC7A11 levels in osteoblasts. In addition, overexpression of LIF downregulates CD71, DCYTB, and DMT1, thereby reducing iron uptake in iron-overloaded cells. Femur immunohistochemistry (IHC) revealed increased ACSL4 and decreased GPX4 and SLC7A11, indicating an increase in ferroptosis of osteoblasts in Lif−/− mice. Whole-transcriptome sequencing showed gene expression changes after Lif-knockdown, exhibiting a negative correlation with genes involved in long-chain fatty acid transport, mitochondrial organization, and the p38 MAPK signaling pathway. These results demonstrate that Lif-deficiency alter systemic iron metabolism and increases the susceptibility of osteoblasts to ferroptosis.

Measurement of Grip Strength in Postmenopausal Women of Different Socioeconomic Conditions

Background: Grip strength is a crucial indicator of physical ability, particularly in postmenopausal women who experience muscle and bone mass reduction due to declining estrogen levels. This study aims to evaluate grip strength among postmenopausal women from different socioeconomic backgrounds.Objective: To assess the grip strength in postmenopausal women of varying socioeconomic conditions.Methods: A cross-sectional study was conducted with 106 postmenopausal women aged 50-70 years. Participants were selected through convenience sampling and assessed using a handheld dynamometer. Two grip strength readings for both dominant and non-dominant hands were recorded, with a one-minute interval between trials. Mean grip strength values were calculated. Data were analyzed using ANOVA in SPSS version 26. Ethical approval was obtained.Results: A significant difference in grip strength was observed with increasing age. For the non-dominant hand, mean grip strength decreased from 15.58 kg (SD = 3.95) in the 50-54 age group to 11.03 kg (SD = 3.25) in the 65-70 age group (p = 0.003). However, no significant differences were found in grip strength across socioeconomic conditions (p &gt; 0.314).Conclusion: Age significantly affects grip strength in postmenopausal women, but socioeconomic status does not show a significant impact.

Mechanical impact of regional structural deterioration and tissue-level compensation on proximal femur trabecular bone.

Osteoporosis-induced changes in bone structure and composition significantly reduce bone strength, particularly in the human proximal femur. This study examines how these changes affect the mechanical performance of trabecular bone to enhance diagnosis, prevention, and treatment strategies. A proximal femur sample was scanned using micro-CT at 40μm resolution. Five regions of interest were selected within the femoral head, femoral neck, and greater trochanter. Structural models simulating various stages of osteoporosis were created using image processing software. Micro-finite element analysis evaluated the mechanical properties of trabecular bone under different conditions of structural deterioration and tissue-level elastic modulus variations. The combined effects of structural deterioration and tissue-level mechanical properties on trabecular bone mechanical performance were further analyzed. The mechanical performance of trabecular bone generally follows a power-law relationship with its microstructural characteristics. However, in any specific region, the apparent mechanical properties linearly decrease with structural deterioration. The femoral neck and greater trochanter are more sensitive to structural deterioration than the femoral head. A 5% bone mass loss in the femoral head led to a 7% reduction in mechanical performance, while the femoral neck experienced a 12% loss. Increasing tissue-level elastic modulus improved mechanical performance, partially offsetting bone mass reduction effects. Trabecular bone in low bone mass regions is more affected by bone mass loss. Structural deterioration primarily reduces bone strength, but improvements in tissue-level properties can mitigate this effect, especially in early osteoporosis. Targeted assessments and interventions are crucial for effective management. Future research should explore heterogeneous deterioration models to better understand osteoporosis progression.

Bmi-1 Epigenetically Orchestrates Osteogenic and Adipogenic Differentiation of Bone Marrow Mesenchymal Stem Cells to Delay Bone Aging.

With the increase in the aging population, senile osteoporosis (SOP) has become a major global public health concern. Here, it is found that Prx1 and Bmi-1 co-localized in trabecular bone, bone marrow cavity, endosteum, and periosteum. Prx1-driven Bmi-1 knockout in bone-marrow mesenchymal stem cells (BMSCs) reduced bone mass and increased bone marrow adiposity by inhibiting osteoblastic bone formation, promoting osteoclastic bone resorption, downregulating the proliferation and osteogenic differentiation of BMSCs, and upregulating the adipogenic differentiation of BMSCs. However, Prx1-driven Bmi-1 overexpression showed a contrasting phenotype to Prx1-driven Bmi-1 knockout in BMSCs. Regarding mechanism, Bmi-1-RING1B bound to DNMT3A and promoted its ubiquitination and inhibited DNA methylation of Runx2 at the region from 45047012 to 45047313bp, thus promoting the osteogenic differentiation of BMSCs. Moreover, Bmi-1-EZH2 repressed the transcription of Cebpa by promoting H3K27 trimethylation at the promoter region -1605 to -1596 bp, thus inhibiting the adipogenic differentiation of BMSCs. It is also found that Prx1-driven Bmi-1 overexpression rescued the SOP induced by Prx1-driven Bmi-1 knockout in BMSCs. Thus, Bmi-1 functioned as a hub protein in the epigenetic regulation of BMSCs differentiation to delay bone aging. The Prx1-driven Bmi-1 overexpression in BMSCs can be used as an approach for the translational therapy of SOP.