The relationship between the environment and diseases is a crucial and complex topic that has garnered significant attention in recent years. In our study, we also follow the thread and explore the correlation between microplastics (MPs) and osteoporosis (OP).

We found that MPs were detected in the blood samples of nearly all participants. Moreover, It was compelling that PVC and PET emerged as the most common MP polymers in our study. A verification process was conducted comparing the clinical data with the results of MPs detection. This analysis revealed a significant exposure risk to MPs from sources such as bottled water, take-out containers. Through molecular biology techniques, we confirmed that MPs have a significant toxic effect on osteoblasts and associated with abnormal gene expression.

MPs may be considered to have a potential correlation with the progression of OP.

Postmenopausal women undergo significant changes in endogenous hormones, which lead to reduced bone mineral density (BMD) and alterations in body composition. However, the relationship between body composition and cognitive function in this demographic has not yet been explored. This study aims to examine this relationship in postmenopausal women with osteoporosis.This survey will involve 120 postmenopausal women with osteoporosis. Dual-energy X-ray absorptiometry (DXA) will be used to assess L1-L4 BMD, fat mass (FM), trunk fat mass (TFM), fat-free mass (FFM), and appendicular skeletal muscle mass (ASMM). The relationship between body composition and cognitive function will be analyzed using t-tests and multiple linear regression.Our findings suggest that in postmenopausal women with osteoporosis, cognitive function (MMSE score) is positively correlated with body composition indicators such as FM and BMD, and positively correlated with educational level, but negatively correlated with age. FM plays a significant role in influencing cognitive function and is a crucial indicator of body composition in postmenopausal women with osteoporosis.

Bone mineral density is affected by many gene regions. Osteoporosis is a disease that occurs due to decreased bone mineral density and has a polygenetic multifactorial pathogenesis. The aim of this study was to examine the effect of gene variants in eight gene regions related to bone mineral density in patients diagnosed with osteopenia or osteoporosis.

A total of 60 patients diagnosed with osteoporosis, 50 patients diagnosed with osteopenia, and 40 healthy volunteers (control group) were included in the study. Collagen type I alpha 1 1997G/T, estrogen receptor α PvuII, estrogen receptor α XbaI, vitamin D receptor BsmI, lactase gene, osteoprotegerin G209A, osteoprotegerin T245G, and interleukin-6 G174C gene variants were analyzed.

No important difference was found in the distribution of collagen type I alpha 1 1997G/T, estrogen receptor α PvuII, estrogen receptor α XbaI, vitamin D receptor BsmI, lactase gene T13910C, osteoprotegerin T245G, and interleukin-6 G174C gene variants between groups. A significant difference was detected between the distribution of osteoprotegerin G209A gene variants in the patient groups and the distribution of osteoprotegerin G209A gene variants in the control group. On the other hand, no important difference was detected in the distribution of osteoprotegerin G209A gene variants between patient groups.

The osteoprotegerin G209A gene variant may be associated with the risk of osteopenia and osteoporosis in the Turkish population. Other gene variants analyzed that affect bone mineral density were not associated with the risk of osteopenia and osteoporosis.

The impact of fatty liver disease on lumbar bone mineral density (BMD) represents an intriguing area of study, particularly in light of established research linking obesity to bone metabolism. However, there remains limited investigation into the correlation between quantifying liver fat content (LFC) and lumbar BMD among overweight and obese populations, particularly within the Chinese demographic. This study aims to accurately quantify LFC and investigate its association with lumbar BMD in overweight or obese individuals.

This cross-sectional study was conducted at the Health Management Center of Henan Provincial People's Hospital from January 2019 to February 2023, involving 6996 participants with a body mass index (BMI) of 24 kg/m² or higher. LFC and lumbar BMD were assessed using computed tomography. The study utilized one-way ANOVA, subgroup analysis, multifactor regression analysis, smooth curve fitting, and threshold and saturation effect analysis to explore the relationship between LFC and lumbar BMD. Furthermore, inflammatory cell analysis was included to investigate the potential mediating role of inflammatory cells in the association between LFC and lumbar BMD.

After adjusting for confounding variables, multivariate regression analysis revealed a significant negative association between LFC and lumbar BMD (β = -0.323, 95% CI: -0.464 to -0.183, P < 0.001). Particularly, participants in the highest baseline LFC quartile (Q4 group) exhibited a more pronounced negative impact on lumbar BMD compared to those in the lowest quartile (Q1 group) (β = -5.026, 95% CI: -7.040 to -3.012, P < 0.001). Threshold saturation effect analysis identified a turning point in the LFC-BMD relationship (K = 5.4). Below this point, LFC showed a positive correlation with lumbar BMD (β = 0.962, 95% CI: 0.016-1.907, P < 0.05), whereas above it, LFC was significantly negatively correlated with lumbar BMD (β = -0.405, 95% CI: -0.558 to -0.253, P < 0.001). Additionally, mediation analysis indicated that leukocytes and monocytes potentially mediated the association between LFC and lumbar BMD, with mediation ratios of -5.78 and -6.68%, respectively.

Among individuals categorized as overweight or obese, elevated levels of LFC were associated with reduced lumbar BMD, particularly noticeable above a threshold of 5.4%. Additionally, various types of inflammatory cells are presumed to exert a substantial mediating influence on the correlation between LFC and lumbar BMD.

Osteoporosis (OP) represents a widespread bone remodeling disorder within the domain of orthopedics, markedly compromising the quality of life in the elderly population. The need to develop more efficient therapeutic approaches to attenuate bone resorption by suppressing the excessive activation of osteoclasts (OCs) remains urgent. The plant flavonoid Isorhamnetin (Iso), recognized for its potent antioxidant properties, has been the subject of extensive research regarding its potential in treating bone-related conditions.

This study adopts a comprehensive methodology to evaluate Iso's impact on bone metabolism and its therapeutic possibilities for treating OP. By integrating network pharmacology, molecular dynamics simulations, and surface plasmon resonance (SPR), we performed in vitro phenotypic analyses to systematically evaluate the inhibitory effect of Iso on OC differentiation. The mechanisms behind Iso's inhibition of OC differentiation were further elucidated. In vivo testing was also performed to substantiate the therapeutic effects of Iso in an OP animal model.

At low concentrations, Iso showed no cytotoxicity and did not interfere with cell proliferation in RAW 264.7 cells. Iso effectively inhibited RANKL-induced osteoclast differentiation in these cells, while downregulating related genes levels (Nfatc1, Ctsk, Trap, c-Fos). Molecular dynamics simulations and surface plasmon resonance confirmed Iso's dual binding to both RANKL and RANK. KEGG pathway enrichment analysis results indicated that Iso modulates the MAPK, NF-κB/PI3K-AKT, and calcium signaling pathways. Western blot analysis revealed that Iso treatment targeting the RANKL/RANK binding pathway significantly downregulated phosphorylation levels of JNK, P38, AKT, and p65. Concurrently, Iso stimulation markedly increased IκBα expression, thereby rescuing its degradation. Furthermore, Iso demonstrated a robust inhibitory effect on reactive oxygen species levels in vitro. Furthermore, in OVX mice, Iso treatment increased bone density, modulated serum bone metabolism markers, and downregulated transcriptional levels of OC marker genes.

Iso exhibits therapeutic potential for OP by selectively targeting and disrupting the RANKL-RANK interaction. This intervention modulates the expression of intracellular transcription factors and multiple signaling pathways, thereby inhibiting the maturation of OCs. Through mitigating OC-mediated bone loss, Iso holds significant promise as a potent therapeutic agent for OP.

Increasing evidence has demonstrated that non-coding RNAs, including the lncRNA MIR155HG, are involved in the pathogenesis of postmenopausal osteoporosis (PMOP). In the current study, we studied MIR155HG function in regulation of osteogenic differentiation and tried to reveal the underlying mechanisms.

Forty blood samples taken from 20 PMOP patients (PMOP group) and 20 postmenopausal individuals without osteoporosis (control group) were used to compare the contents of MIR155HG and miR-155-5p via RT-PCR. Alizarin red S staining and ALP staining were used to evaluate the osteogenic differentiation potential of bone marrow mesenchymal stem cells (BMSCs).

Elevated levels of MIR155HG and miR-155-5p were observed in the blood samples of the PMOP group. Upregulation of MIR155HG resulted in decreased expression of OPN, OSX, ALP, RUNX2 and β-catenin but increased DKK1 expression, together with decreased Alizarin red S + and ALP + staining areas. However, downregulation of DKK1 did not obviously change the above indices induced by MIR155HG upregulation. Further experiments revealed that MIR155HG caused an increase in the expression of miR-155-5p, which also serves as an inhibitor of the osteogenic differentiation of BMSCs through binding to β-catenin. Consistent with DKK1 knockdown, downregulation of miR-155-5p only also did not obviously reverse the repressive effect of MIR155HG on osteoblastic differentiation, but downregulation of DKK1 and miR-155-5p synchronously restored the osteogenic differentiation ability of BMSCs suppressed by MIR155HG overexpression.

MIR155HG suppressed the osteoblastic differentiation of BMSCs by regulating miR-155-5p and DKK1 expression. Either inhibition of miR-155-5p and DKK1 or direct suppression of MIR155HG may be effective approaches for treating PMOP.

In the context of osteoporosis closely linked to bone metabolism imbalance caused by estrogen deficiency, total flavonoids of Rhizoma Drynariae (TFRD) exhibit potential anti-osteoporotic activity, yet their multicomponent synergistic mechanism and association with the PI3K/AKT signaling pathway remain unclear. This study aimed to systematically elucidate the molecular mechanisms by which TFRD regulate bone metabolism and improve osteoporosis in ovariectomized (OVX) rats through the PI3K/AKT pathway, integrating network pharmacological predictions with animal experimental validation. Methods involved identifying TFRD's active components using UPLC/MS-MS, predicting targets with SwissTargetPrediction, constructing a "component-target-disease" network, and performing GO/KEGG enrichment analysis with MetaScape (v3.5). In vivo experiments established an OVX rat model, randomized into sham, OVX, low-/high-dose TFRD, and sim groups, assessing bone mineral density (BMD) and mandibular Micro-CT parameters after 12 weeks. Western blot analyzed PI3K, p-AKT1, and related protein expressions. Results showed the high-dose TFRD group significantly increased BMD, improved trabecular bone quantity and structure, and upregulated PI3K, p-PI3K, and p-AKT1 protein expressions compared to the OVX group. Molecular docking confirmed stable binding energy between core components and PI3K/AKT targets. TFRD may ameliorate estrogen deficiency-induced osteoporosis by activating the PI3K/AKT signaling pathway, inhibiting bone resorption, and promoting osteogenic differentiation, providing pharmacological evidence for multitarget treatment of osteoporosis with traditional Chinese medicine.

To investigate the effectiveness and safety of combining zoledronic acid with calcium supplements and calcitriol in treating primary osteoporosis in elderly patients.

Seventy-eight elderly patients with primary osteoporosis were recruited. They were randomly assigned in a 1:1 ratio to either the CC group (calcium carbonate D3 tablets + calcitriol soft capsules) or the CCZ group (calcium carbonate D3 tablets + calcitriol soft capsules + zoledronic acid injection). The treatment duration was 1 year. Bone mineral density (BMD), bone metabolism markers, quality of life (QoL), clinical efficacy, and incidence of adverse reactions (ARs) were assessed.

CCZ group showed increased BMD in the lumbar spine (L1~L4 segments), femoral neck, and hip after treatment relative to CC group. Serum levels of bone-specific alkaline phosphatase, cross-linked type 1 collagen C-terminal peptide, and N-terminal propeptide of type 1 procollagen decreased, while osteocalcin levels increased. The QoL Questionnaire of the European Foundation for Osteoporosis scores decreased (P < 0.05 for all comparisons). The clinical effective rates were 76.93% in the CC group and 92.31% in the CCZ group, with AR rates of 23.08% and 12.82%, respectively (P < 0.05 for both).

Zoledronic acid treatment in elderly patients with primary osteoporosis demonstrates significant efficacy by increasing bone density, improving bone metabolism, enhancing QoL, and exhibiting high safety.

Many observational studies have found an association between osteoporosis and postural instability. However, it is unclear whether there is a genetic causal relationship between osteoporosis and postural instability. In this study, we conducted a two-sample Mendelian randomization (MR) analysis to investigate the causal relationship between osteoporosis and postural instability, with osteoporosis represented by bone mineral density (BMD). We used random effects Inverse Variance Weighted (IVW), weighted median, and MR-Egger methods after Steiger filtering, followed by FDR correction, to assess the causal relationship. We also used the Cochran Q statistic and MR-PRESSO to detect and exclude heterogeneity, the MR-Egger intercept to detect horizontal pleiotropy, and the leave-one-out method for sensitivity analyses. After excluding the heterogeneity in causal estimates across different SNPs and after Steiger filtering, the inverse variance weighted analysis showed a significant negative correlation between femoral neck BMD (FN-BMD) and the occurrence of postural instability, with an OR of 0.9171 (95% CI: 0.8745-0.9617; FDR P.value = 0.0009). Similar results were obtained in the weighted median analysis, with an OR of 0.923 (95% CI: 0.8717-0.9733; FDR P = 0.0180), and in the analysis of lumbar spine BMD (LS-BMD) in IVW, with an OR of 0.9491 (95% CI: 0.9156-0.9838; FDR P.value = 0.0129). However, there was no significant correlation between forearm BMD (FA-BMD) and postural instability. Further analysis showed no horizontal pleiotropy or heterogeneity in FN-BMD and LS-BMD after excluding heterogeneous SNPs. This study demonstrates a causal association between BMD and postural instability, suggesting that individuals with osteoporosis may be at higher risk of experiencing postural instability.

Osteoporosis is a progressive, systemic, skeletal disorder characterized by increased bone fragility and susceptibility to fracture. Prior fractures are a strong predictor of subsequent fractures, but it is essential to identify further clinical and demographic characteristics of patients with osteoporosis that are associated with subsequent fracture risk.

In this retrospective observational cohort study, male and female patients over the age of 55 years with osteoporosis who experienced vertebral fractures between 2019 and 2021 were included. All patients' basic clinical data, serum biochemical and bone turnover markers, bone mineral density, and other indicators were recorded uniformly. The incidence of subsequent fractures during the two-year follow-up period was analyzed. Independent risk factors for subsequent fractures were identified by binary logistic regression analysis.

A total of 1,096 patients were included. Of these, 311 (28.4%) patients suffered a subsequent fracture during the two-year follow-up period. The incidences of subsequent fracture sites were 18.4% vertebral, 14.2% forearm/wrist/hand, and 9.9% hip/femur. Compared with the non-subsequent fracture group (non-SFG), binary logistic regression analysis showed that body mass index (BMI) (OR [95% CI] 0.825 [0.720-0.945]; P = 0.006), femoral neck bone mineral density (BMD) T-score (OR [95% CI] 0.067 [0.012-0.385]; P = 0.002), and C-terminal telopeptide of type 1 collagen (CTX) levels (OR [95% CI] 6.089 [1.735-21.375]; P = 0.005) were independent risk factors associated with subsequent fractures.

Patients with osteoporosis and previous vertebral fractures are at a higher risk of further fractures at a two-year follow-up period. BMI, femoral neck BMD T-score, and CTX levels were independent risk factors for refracture. Integrating BMI, femoral neck BMD, and CTX levels into an individualized care plan for patients with osteoporotic vertebral fractures may help prevent subsequent fractures in high-risk populations.

To analyze the expression and determine the significance of cytokines in peripheral blood and vertebral blood in the bone microenvironment of patients with osteoporotic vertebral compression fractures (OVCFs) and Kummell's disease (KD).

From October 2022 to April 2023, 16 patients with osteoporotic vertebral compression fracture (OVCF), 14 patients with Kummell (KD) disease, and 19 patients with lumbar degenerative disease were included in the study. The patients were divided into the OVCF group, KD group and control group. The levels of interleukin-1 (IL-1), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α) and transforming growth factor-β (TGF-β) in peripheral blood and vertebral blood in the bone microenvironment were detected by enzyme-linked immunosorbent assay. Receiver operating characteristic (ROC) curve analysis was used to determine the correlation between cytokines and the occurrence of OVCF and KD.

The levels of IL-1, IL-6, TGF-β and TNF-α in vertebral blood in the bone microenvironment of the KD group were significantly higher than those in peripheral blood (p = 0.001, p < 0.001, p = 0.017, p < 0.001). Compared with the control group, the OVCF displayed a marked increase in the expression of IL-1, IL-6, and TNF-α and a significant reduction in the expression of TGF-β (p < 0.001). In addition, compared with the vertebral blood in the bone microenvironment of the control group, the levels of IL-1, IL-6 and TNF-α in the vertebral blood in the bone microenvironment of the KD group were significantly increased (p < 0.001). and compared with the vertebral blood in the bone microenvironment of OVCF group, the levels of IL-1, IL-6 and TNF-α in the vertebral blood in the bone microenvironment of the KD group were significantly increased (p = 0.014, p = 0.020, p = 0.006). Moreover, Compared to peripheral blood, the vertebral blood within the bone microenvironment demonstrated increased area under the curve (AUC) values for the associations of IL-1, IL-6, and TNF-α with OVCF and Kummell's disease KD.

The expression levels of IL-1, IL-6 and TNF-α in OVCFs and KD were increased, but that of TGF-β was decreased. The levels of IL-1, IL-6 and TNF-α in the vertebral blood of KD patients were significantly increased, which can promote vertebral osteonecrosis and bone nonunion in KD patients. Alterations in the expression levels of these proinflammatory cytokines maybe demonstrate a significant correlation with the pathogenesis of OVCF and KD.

To explore the associations between hormones, metabolic markers, and low bone mass in perimenopausal and postmenopausal women.

A total of 198 women were enrolled in this study. The correlations between hormones, metabolic markers, and BMD were analyzed. Risk factors for bone loss were identified. Receiver operating characteristic (ROC) curves were used to display the predictive power of these risk factors.

The years since menopause and the levels of glucose (GLU), follicle-stimulating hormone (FSH), and luteinizing hormone (LH) were inversely correlated with BMD, while estrogen and testosterone were positively correlated with BMD. Age (odds ratio [OR] 1.232; 95% confidence interval [CI] 1.106-1.372; p < 0.001), GLU (OR 1.848; 95% CI 1.116-3.059; p = 0.017), and FSH (OR 1.089; 95% CI 1.003-1.182; p = 0.042) were identified as risk factors for bone loss. Age (AUC = 0.884, 95% CI 0.833-0.935), FSH (AUC = 0.824, 95% CI 0.760-0.888), and GLU (AUC = 0.683, 95% CI 0.599-0.768) demonstrated significant discrimination capability for bone loss. The combined application of these factors resulted in a better prediction effect (AUC = 0.930, 95% CI 0.893-0.967).

Age, FSH, and GLU were found to be specific risk factors for bone loss. The utilization of these factors offers compelling predictive power for bone loss in perimenopausal and postmenopausal women.

Osteoporosis is divided into primary and secondary types. Primary osteoporosis may result from estrogen deficiency in postmenopausal women, imbalanced bone remodeling in the elderly, or imbalanced adolescent-type bone development. Secondary osteoporosis can be caused by factors like long-term glucocorticoid treatment, chronic kidney disease (CKD), estrogen deprivation, oxidative stress, diabetes, and obesity. This review focuses on the therapeutic potential of soy isoflavones for osteoporosis. At the cellular level, soy isoflavones, as natural plant extracts and phytoestrogens, are crucial for osteoblastogenesis and differentiation, osteoclastogenesis, osteoclast mineralization, and bone marrow mesenchymal stromal cell differentiation. They also maintain calcium homeostasis by regulating extracellular calcium and vitamin D levels. In terms of oxidative stress, soy isoflavones mitigate it in the endoplasmic reticulum and mitochondria, thus regulating cellular senescence, autophagy, and bone remodeling processes. Moreover, soy isoflavones can relieve symptoms related to CKD and inhibit glucocorticoid secretion, which directly or indirectly benefits the treatment of osteoporosis. Overall, soy isoflavones have the potential to treat osteoporosis by enhancing bone health, regulating metabolism, and alleviating oxidative stress. Future research should explore the potential of soy isoflavones as phytoestrogens for treating osteoporosis. This exploration should focus on clarifying the safety, identifying potential side effects, determining the optimal dosage regimen, and developing strategies to mitigate any adverse reactions. In addition, further large-scale, multicenter human clinical trials are necessary to accurately evaluate the actual therapeutic effect of soy isoflavones on osteoporosis.

The liver exerts profound influence on skeletal health, while osseous tissues reciprocally modulate hepatic function. This bidirectional metabolic axis between these two organ systems plays a pivotal role in both physiological homeostasis and pathological states.

To investigate and analyze the literatures on liver-bone axis using bibliometrics.

A comprehensive literature search pertaining to the liver-bone axis was conducted using the Science Citation Index Expanded within the Web of Science Core Collection. Subsequently, visualization and bibliometric analyses were performed utilizing VOSviewer (version 1.6.20), Citespace (version 6.2.R4), and the R programming language.

This comprehensive analysis encompasses 855 publications, comprising 694 articles and 161 reviews, authored by 4988 researchers from 425 institutions across 61 countries. The United States and China emerge as the leading nations in terms of publication volume. The University of California system stands out as the most influential institution in liver-bone axis research. Guanabens N is identified as the most prolific author in this field. The annual increase in publications related to the liver-bone axis underscores its growing prominence as a research focus. The study highlights key areas of investigation, including osteoporosis, bone metabolism, non-alcoholic fatty liver disease, and insulin-like growth factor-1, which represent both current and prospective hot topics within this domain.

This investigation employs bibliometric methodologies to conduct a systematic analysis of liver-bone axis literature spanning from 2001 to 2024. The exponential growth in publications over the past two decades underscores the significance of synthesizing research outcomes in this domain. Through rigorous statistical analyses, we delineate fundamental contributions to the field while providing strategic direction for emerging scholars. Furthermore, we illuminate current research trajectories and identify promising future investigative directions. Investigation of the liver-bone axis enhances our comprehension of inter-organ communication networks. Conceptualizing these organs as an integrated system provides profound insights into pathophysiological mechanisms and disease management strategies. This paradigm not only facilitates the development of sophisticated diagnostic modalities but also catalyzes the discovery of novel therapeutic agents targeting these mechanistic pathways, thereby advancing our capacity to diagnose and treat hepatic and skeletal disorders.

Osteoporosis is a systemic disease with high morbidity and significant adverse effects. Increasing evidence supports the close relationship between oxidative stress and osteoporosis, suggesting that treatment with antioxidants may be a viable approach. This study evaluated the antioxidant properties of dichotomitin (DH) and its potential protective effects against osteoporosis.

SD rats were divided into three groups: Sham, OVX, and OVX + DH (5 mg/kg, intraperitoneal injection twice weekly). After three months, blood samples, femurs, and tibiae were collected for analysis. Micro-CT evaluated the femoral, while histological examination assessed tibial tissues. Serum osteogenic biochemical markers were measured. In vitro, osteogenic differentiation was induced with varying concentrations of DH, followed by ALP and ARS staining. RT-qPCR and western blot were used to assess the expression of osteogenesis-related genes and proteins. Additionally, an oxidative stress cell model was established, dividing cells into control, H2O2-treated, and H2O2 + DH-treated groups. Expression of oxidative stress-related genes and proteins was assessed using real-time quantitative PCR and western blotting.

Micro-CT and histological staining revealed decreased and disrupted bone trabeculae in the OVX group, whereas the DH-treated group exhibited enhanced bone trabecular area and structure compared to the OVX group. In vitro studies showed that DH enhanced ALP activity and elevated expression of RUNX2, OPN, OCN, SOD1, and SOD2.

DH has the potential to enhance osteoblast differentiation and alleviate osteoporosis through the attenuation of oxidative stress.

To test the efficacy and feasibility of pelvic bone marrow sparing intensity modulated radiation therapy (PBMS-IMRT) in reducing bone density loss for patients with cervical cancer undergoing pelvic radiation therapy (RT).

Patients with nonsurgical cervical cancer with stage Ib2-IIIc cancer were randomly allocated into the PBMS group or the control group. The PBMS group additionally received pelvic bone marrow dose constraint. Computed tomography (CT) imaging sets were acquired at baseline and at 1, 3, 6, 9, and 12 months after treatment. Radiation dose and Hounsfield unit were registered. Bone density loss rates and fracture events at different follow-up time points were recorded.

Data from 90 patients in the PBMS group and 86 patients in the control group were used for statistical analysis, which included 30 and 26 patients with extended-field radiation therapy (EFR), respectively. The median follow-up for all patients was 12 months. Compared with baseline, the bone density of all bones at the last follow-up decreased by 43% and 53% in the PBMS and control groups, respectively, with the most significant decline at 1 month after treatment. Although patients without EFR received minimal irradiation in the upper lumbar spine, a 22.33% decrease in bone density was detected. In the group of patients with EFR, the decrease was 51.18% (P < .01). Lumbar or pelvic fracture incidence rates of patients in the PBMS and control groups were 7.8% and 12.79%, respectively. Among the dosimetric parameters, mean dose had the strongest correlation with bone density loss.

In patients undergoing pelvic RT, the loss of bone density can begin to appear early after RT, and it can occur either inside or outside of the irradiation field. Results of this study showed that PBMS-IMRT reduced bone mineral density loss compared with IMRT alone.

Osteoporosis is characterized by excessive osteoclast activity leading to bone loss, decreased bone mineral density, and increased susceptibility to fractures. Through in vivo/vitro experiments, along with network pharmacology analysis, we aimed to explore the underlying mechanisms of Isoginkgetin (IGG) in inhibiting osteoclastogenesis, providing valuable insights for further research in the future. Firstly, we ascertained the safe concentration of IGG stimulation on BMMs, followed by a systematic exploration of the concentration gradient at which IGG inhibited osteoclastogenesis using TRAP analysis. An osteoporosis model was established to further validate the in vitro experimental findings by combining Micro-CT and immunohistochemical analysis. The results show that IGG did not exhibit cytotoxicity or proliferative effects on BMMs at concentrations equal to or less than 10 μM. Additionally, IGG inhibited the activity of osteoclastogenesis and bone resorption function at lower concentrations. RT-PCR and Western Blot results demonstrated that IGG could downregulate genes and proteins associated with osteoclastogenesis. The Western Blot results also showed that IGG inhibited the phosphorylation expression of P38, ERK, and P65 in the MAPK and NF-κB pathways. At the same time, it rescued the degradation of IκB-α at 15 and 60 min. IGG can also impact the relative expression levels of oxidative proteins such as SOD-1, HO-1, and catalase, thereby influencing cellular equilibrium and stress levels, ultimately inhibiting the formation of mature OC. In vivo experiments demonstrated that IGG alleviated bone loss caused by osteoclasts and improved relevant parameters of trabecular bone. So, IGG effectively attenuated osteoclastogenesis, and improved bone density, thereby portraying its role in osteoporosis management.

Evidence has revealed that oestrogen deprivation-induced osteolysis is microbiota-dependent and can be treated by probiotics. However, the underlying mechanism require further investigation. This study aims to provide additional evidence supporting the use of probiotics as an adjuvant treatment and to explore the pathophysiology of oestrogen-deprived osteolysis.

Forty-five SD rats were randomly divided into five groups (n = 9). Rats from four groups were ovariectomised and treated with NS, calcium, probiotics, or calcium + probiotics, while one group underwent a sham operation and was treated with NS. The osteometabolic effects were evaluated, and the mechanistic role of the probiotic supplement was explored.

Intragastric administration of Bifidobacterium animalis subsp. lactis LPL-RH (LPL-RH) markedly suppressed osteoclastic activation and bone calcium loss by downregulating TRAP enzymatic activity, the OPG/RANKL ratio, and the downstream signalling pathway RANKL/TRAF6/NF-κB/NFATc1/TRAP in ovariectomised SD rats. LPL-RH also reduced CD4+IL-17 A+ TH17 cells in the bone marrow, the pro-osteoclastogenic cytokine IL-17 A, pro-inflammatory molecules (LPS), and its binding protein (LBP) in the blood. LPL-RH restored intestinal ZO-1, occludin, claudin 2, claudin 12, and claudin 15, which improved ileal histopathology, reduced ileal oxidative stress, and attenuated the LPS-responsive TLR4/MyD88/NF-κB pathway. Furthermore, 16 S rRNA sequencing revealed that LPL-RH altered the faecal microbiome by reducing the relative abundance of S24-7 at the family level and promoting Prevotella and Bacteroides at the genus level.

Collectively, LPL-RH suppressed osteoclastogenesis and osteolysis by modulating type 17 immunity and gut microbiome.

Osteoporosis has increasingly become a major public health concern because of its associated heightened risk of bone fragility and fractures. In order to avoid the adverse risk of hormone therapy, scientists have considered isoquercitrin (IQ) as a natural phytoestrogen to potentially prevent osteoporosis. However, IQ has poor solubility and bioavailability which culminates in rapid elimination of phytoestrogen. Herein, this study sought to solve limited applications of IQ by preparing IQ-loaded PEGylated long circulating liposomes (IQ-Lips) via thin-film hydration method. After appropriate characterization using zeta-potential, polydispersed index (PDI), particle size and entrapment efficiency (EE), IQ-Lips were applied to ovariectomized rat models to evaluate their effect on osteoporosis. The results showed that the prepared IQ-Lips exhibited smaller sized nanoparticles (125.35 ± 4.50 nm), excellent PDI (0.244 ± 0.001) and zeta-potential (-28.64 ± 0.71 mV) with stable property and higher EE (92.10 ± 0.32%). Importantly, administration of IQ-Lips through oral route increased aqueous solvability, bioavailability and circulation time of IQ. Moreover, the IQ-Lips could increase bone microstructural densities and bone mass, as well as reduce oxidative stress in ovariectomized rat models. Altogether, the IQ-Lips may serve as a novel avenue to potentially prolong the circulation of IQ in the body and improve the bioavailability of IQ for treatment of osteoporosis.

Achyranthes bidentata Blume (ABB), a plant of Amaranthaceae family, has been one of the more commonly used phytomedicine remedies for thousands of years, and recent studies have highlighted the efficacy of its extracts in the treatment of osteoporosis. Nonetheless, a thorough analysis of its benefits is currently absent.

This meta-analysis assessed the effects of ABB root extract (ABBRE) on osteoporotic rats and provides a rationale for future clinical studies.

Searches were conducted in seven different Chinese and English databases, and the search period was from their establishment to January 2024. This study was registered in PROSPERO (CRD42023418917). Selected research regarding the ABBRE treatment of osteoporotic rats, and the corresponding research has distinctly reported outcomes, and the data on the bone mineral density (BMD), bone histomorphometrics, biomechanical parameters, and bone biochemical markers of osteoporotic rats can be extracted.

Through screening, 11 studies met the eligibility requirements for inclusion, in which 222 animals were studied. The treatment group with ABBRE exhibited increased bone mineral density (standardized mean difference [SMD] = 1.64, 95% CI = 0.52 to 2.77). Based on subgroup analysis, the greatest increase in bone mineral density was observed when the dose of ABBRE was ≤ 400 mg/kg/day and the duration of treatment was ≤ 12 weeks.

ABBRE is a phytomedicine that can effectively promote the enhancement of bone mineral density and ease osteoporosis. It can be developed into a new alternative therapy by conducting experiments and clinical studies on larger samples.

Bone is a complex tissue that fulfills the role of a resistance structure. This quality is most commonly assessed by bone densitometry, but bone strength may not only be related to bone mineral density but also to the preservation of bone cytoarchitectonics. The study included two groups of rats, ovariectomized and non-ovariectomized. Each group was divided into three batches: control, simvastatin-treated, and fenofibrate-treated. In the ovariectomized group, hypolipidemic treatment was instituted at 12 weeks post ovariectomy. One rat from each of the 6 batches was sacrificed 8 weeks after the start of treatment in the group. The experimental study was performed using a Bruker Minispec mq 20 spectrometer operating at a frequency of 20 MHz, subsequently also performed by 1H T2-T2 molecular exchange maps. The results were represented by T2-T2 molecular exchange maps that showed, comparatively, both pore size and their interconnectivity at the level of the femoral epiphysis, being able to evaluate both the effect of estrogen on bone tissue biology and the effect of the lipid-lowering medication, simvastatin, and fenofibrate, in both the presence and absence of estrogen. T2-T2 molecular exchange maps showed that the absence of estrogen results in an increase in bone tissue pore size and interconnectivity. In the presence of estrogen, lipid-lowering medication, both simvastatin and fenofibrate alter bone tissue cytoarchitectonics by reducing pore interconnectivity. In the absence of estrogen, fenofibrate improves bone tissue cytoarchitectonics, the T2-T2 molecular exchange map being similar to that of non-osteoporotic bone tissue.

The study aimed to investigate the correlation between fat fraction (FF), R2* value of vertebrae based on IDEAL-IQ sequence and bone mineral density (BMD) based on QCT, and their diagnostic value for low BMD and osteoporosis.

Subgroups were divided according to different gender, age, BMI, and bone mass to compare the differences in parametric variables. One-way ANOVA, independent samples t-test, correlation coefficient analysis, linear regression analysis, and ROC curve analysis were performed.

Significant differences were found in FF among different bone mass groups, and between different gender and age groups. While R2* only had a significant difference between different gender groups and males with different ages. BMD was significantly negatively correlated with FF, especially in women, and FF significantly negatively affected BMD after controlling for gender, age, and BMI. There was mildly positive correlation between BMD and R2* in men, and R2* significantly positively influenced BMD controlling for the confounders. In addition, FF was positively correlated with age, whereas R2* was negatively correlated with age in men. FF had high diagnostic efficacy for low bone mass and osteoporosis, while R2* alone was weakly diagnostic.

Vertebral FF can be served as a potentially important imaging biomarker for assessing low BMD and osteoporosis, and R2* of males can be utilized as a complementary parameter for evaluating osteoporosis.

The IDEAL-IQ sequence has the potential to be used as an accessory examination in the diagnosis of osteoporosis, assessment of treatment efficacy, and prediction of fracture risk.

Aging is a universal biological process characterized by a progressive, cumulative decline in homeostatic capabilities and physiological functions, which inevitably increases vulnerability to diseases. A number of molecular pathomechanisms and hallmarks of aging have been recognized, yet we miss a thorough understanding of their complex interconnectedness. This review explores the molecular and cellular mechanisms underlying human aging, with a focus on the multiple roles of high mobility group Box 1 protein (HMGB1), the archetypal damage-associated molecular pattern (DAMP) molecule. In the nucleus, this non-histone chromatin-associated protein functions as a DNA chaperone and regulator of gene transcription, influencing DNA structure and gene expression. Moreover, this versatile protein can translocate to the cytoplasm to orchestrate other processes, such as autophagy, or be unconventionally secreted into the extracellular environment, where it acts as a DAMP, combining inflammatory and regenerative properties. Notably, lower expression of HMGB1 within the cell and its heightened extracellular release have been associated with diverse age-associated traits, making it a suitable candidate as a universal biomarker of aging. In this review, we outline the evidence implicating HMGB1 in aging, also in light of an evolutionary perspective on its functional pleiotropy, and propose critical issues that need to be addressed to gauge the value of HMGB1 as a potential biomarker across age-related diseases and therapeutic target to promote healthy longevity.

Osteoporosis is characterized by increased bone turnover and reduced bone mass, leading to skeletal fragility and heightened fracture risk. It is a growing public health concern with expectations for a continued significant rise of fractures by 50% in 2030. Diagnosis is typically based on body mineral density with a T-score of -2.5 or lower indicating osteoporosis. Treatment duration varies, and is determined by careful monitoring of fracture risk and timing for potential drug holidays. Emerging therapies and ongoing research continue to evolve the landscape of osteoporosis management, aiming to reduce fracture risk and improve patient outcomes.

The problem of population aging is intensifying worldwide. Osteoporosis has become an important cause affecting the health status of older populations. However, the diagnosis of osteoporosis and people's understanding of it are seriously insufficient. We aim to develop a deep learning model to automatically measure bone mineral density (BMD) and improve the diagnostic rate of osteoporosis.

The images of 801 subjects with 2,080 vertebral bodies who underwent chest or abdominal paired computer tomography (CT) and quantitative computer tomography (QCT) scanning was retrieved from June 2020 to January 2022. The BMD of T11-L4 vertebral bodies was measured by QCT. Developing a multistage deep learning-based model to simulate the segmentation of the vertebral body and predict BMD. The subjects were randomly divided into training dataset, validation dataset and test dataset. Analyze the fitting effect between the BMD measured by the model and the standard BMD by QCT. Accuracy, precision, recall and f1-score were used to analyze the diagnostic performance according to categorization criterion measured by QCT.

410 males (51.2%) and 391 females (48.8%) were included in this study. Among them, there were 154 (19.2%) males and 118 (14.7%) females aged 23-44; 182 (22.7%) males and 205 (25.6%) females aged 45-64; 74 (9.2%) males and 68 (8.5%) females aged 65-84. The number of vertebral bodies in the training dataset, the validation dataset, and the test dataset was 1433, 243, 404, respectively. In each dataset, the BMD of males and females decreases with age. There was a significant correlation between the BMD measured by the model and QCT, with the coefficient of determination (R2) 0.95-0.97. The diagnostic accuracy based on the model in the three datasets was 0.88, 0.91, and 0.91, respectively.

The proposed multistage deep learning-based model can achieve automatic measurement of vertebral BMD and performed well in the prediction of osteoporosis.

The study aimed to explore the potential of QiangJin mixture (QJM), a Chinese herbal compound prescription, in regulating MC3T3-E1 cell differentiation and to analyze the ingredients and therapeutic targets of QJM against osteoporosis based on network pharmacology. MC3T3-E1 cells were incubated with different concentrations of QJM-contained rat serum (5, 10, or 20%). After 14 days of cell culture, Alizarin Red staining was performed to assess the mineralization ability of osteoblasts. RT-qPCR was used to measure mRNA levels of osteogenesis-related genes. Western blot was conducted to measure protein levels of factors related to the BMP2/Smads pathway. Functional and pathway enrichment of overlapping targets for QJM and osteoporosis were analyzed using gene ontology and KEGG analyses. As shown by experimental results, QJM-contained serum led to calcium deposition, increased expression levels of osteogenesis-related genes, and activated BMP2/Smad/Runx2 signaling in MC3T3-E1 cells. A total of 125 active compounds and 162 disease-related targets were identified. The core targets were MAPK8, TP53, ESR1, STAT3, MAPK3, IL6, NFKB1, JUN, MAPK1 and AKT1. In conclusion, QJM promotes the osteogenic differentiation of MC3T3-E1 cells by activating the BMP2/Smads signaling. Additionally, QJM is an anti-osteoporotic mixture by regulating diverse therapeutic targets and signaling pathways.

Dysregulated bone homeostasis contributes to multiple diseases including osteoporosis (OP). In this study, osteoporotic mice were successfully generated using ovariectomy to investigate the role of nuclear receptor subfamily 3 group C member 1 (NR3C1) in OP. NR3C1, identified as a significantly upregulated gene in OP using bioinformatic tools, was artificially downregulated in osteoporotic mice. NR3C1 expression was significantly elevated in the femoral tissues of osteoporotic patients, and downregulation of NR3C1 alleviated bone loss and restored bone homeostasis in osteoporotic mice, as manifested by increased ALP- and OCN-positive cells and reduced RANKL/OPG ratio. Downregulation of NR3C1 inhibited osteoclastic differentiation of RAW264.7 cells and mouse bone marrow-derived macrophages (BMDM) and promoted osteogenic differentiation of MC3T3-E1 cells. The transcription factor NR3C1 bound to the cystatin-3 (CST3) promoter to repress its transcription in both RAW264.7 and MC3T3-E1 cells. The downregulation of CST3 reversed the protective effect of NR3C1 downregulation against OP. Ubiquitin-specific-processing protease 10 (USP10)-mediated deubiquitination of NR3C1 improved NR3C1 stability. Downregulation of USP10 inhibited osteoclastic differentiation of RAW264.7 cells and BMDM while promoting osteogenic differentiation of MC3T3-E1 cells. Taken together, USP10-mediated deubiquitination of NR3C1 regulates bone homeostasis by controlling CST3 transcription, providing an attractive therapeutic strategy to alleviate OP.

The aim was to investigate the relationship between metabolic indices and abnormal bone mass (ABM), analyse the association between osteoprotegerin (OPG) gene mutations and ABM, and explore the interaction effect of type 2 diabetes mellitus (T2DM) and OPG gene mutations on bone mineral density (BMD) in postmenopausal women to provide a new supplementary index and a reliable basis for the early identification of osteoporosis (OP) in postmenopausal women in the clinical setting.

Postmenopausal women hospitalized within the Department of Endocrinology of the First Affiliated Sanatorium of Shihezi University from June 2021 to March 2023 were retrospectively analysed, and the bone mineral density of lumbar vertebrae 1-4 (BMD (L1-4)) of the studied subjects was measured once via twin-energy X-ray absorptiometry. The studied subjects were divided into a normal bone mass (NBM) group and an ABM group according to their bone mineral density, and the general data of the studied subjects were recorded once. Blood biochemical indices were determined, and genotyping of the rs4355801 locus of the OPG gene was performed. Differences in the overall data and biochemical indices of the two groups were evaluated via the rank-sum test, and the relationship between blood glucose levels and mutations of the rs4355801 locus of the OPG gene and ABM or BMD (L1-4) was evaluated via binary logistic regression analysis or linear regression analysis. A bootstrap test was performed to test whether uric acid (UA) levels mediate the association between blood glucose levels and BMD (L1-4). Simple effect analysis was performed to analyse the interaction between T2DM and mutations at the rs4355801 locus of the OPG gene on BMD (L1-4).

① After adjusting for confounding factors, the risk of ABM increased by 50% (95% CI 21-85%) for each unit increase in fasting plasma glucose (FPG) levels and 31% (95% CI 2-69%) for each unit increase in glycosylated haemoglobin (HbA1c) levels (both P < 0.05). FPG levels were negatively correlated with BMD (L1-4) (both P < 0.05), and uric acid in blood sugar and BMD (L1-4) played a significant mediating role in the model; this mediation accounted for 21% of the variance. ② After adjusting for confounding factors, women with the mutant genotypes GA and GG + GA of the OPG gene rs4355801 locus had a lower risk of ABM than did those with the wild-type genotype AA (OR = 0.71, 95% CI = 0.52-1.00; OR = 0.51, 95% CI = 0.28-0.92, P < 0.05). The mutant genotypes GG, GA and GG + GA were positively correlated with BMD (L1-4) (all P < 0.05). The interaction between T2DM and mutations in the OPG gene rs4355801 locus had an effect on BMD (L1-4), and this site mutation weakened the increase in blood glucose levels and led to an increase in the risk of ABM (P < 0.05).

Elevated blood glucose levels in postmenopausal women were associated with an increased risk of ABM, and UA played a mediating role in the relationship FPG levels and BMD (L1-4), accounting for 21% of the variance. Mutations at the rs4355801 locus of the OPG gene were associated with a reduced risk of ABM in postmenopausal women. The interaction between T2DM and mutations at the rs4355801 locus of the OPG gene in postmenopausal women affects BMD (L1-4), and mutations at this locus attenuate the increased risk of ABM due to elevated blood glucose levels.

Background/Objectives: Lumbar degenerative disease is a common age-related condition, with epidural steroid injection (ESI) being a widely employed conservative treatment approach. However, the potential effect of ESI on osteoporosis and fracture risk remains unclear. This study investigated the risk of osteoporotic vertebral compression fractures (OVCFs) in patients with lumbar degenerative disease who underwent ESI treatment. Methods: A cohort of 64 patients who received ESI treatment and a control group of 256 patients were included in this study. Demographic data, clinical characteristics, and follow-up information were collected. Cox proportional hazards models were used to analyze risk factors for OVCF, and subgroup analyses were conducted. Results: OVCF was more common in the ESI group than in the control group (hazard ratio [HR]: 3.49, 95% confidence interval [CI]: 1.06-11.43, p = 0.039). After confounding factors were adjusted for, ESI remained an independent risk factor for OVCF (HR: 4.60, 95% CI: 1.01-20.89, p = 0.048). In a subgroup analysis, lower socioeconomic status was associated with higher OVCF risk (HR: 11.82, 95% CI: 1.06-131.26, p = 0.044). The ESI group had improved short-term pain relief, with nonsignificant long-term effects. Conclusions: Patients with lumbar degenerative disease receiving ESI treatment are at an increased risk of OVCF, particularly those with lower socioeconomic status. These findings underscore the importance of regular bone density monitoring and fracture prevention following ESI treatment. Clinicians should carefully weigh the short-term benefits of ESI against the long-term risks and develop individualized follow-up plans for high-risk patients.

We aimed to investigate the knowledge and awareness level of osteoporosis, its risk factors, the possible causes of underdiagnosis, as well as the preventive measures and lifestyle behavior of the Romanian population.

A non-interventional, cross-sectional study was performed, consisting of an in-person survey, in 10 pharmacies located in both urban and rural settings in Romania. The survey was distributed to patients ≥40 years old.

Of 189 respondents, 78.8% were women, the majority age group being 60-69 (31.7%) and 50-59 (30.7%) years old and coming from urban areas (69.3%). Although 75.1% of participants declared knowing about osteoporosis, having a moderate level of knowledge, and women being more aware of the pathology, 77.3% have never performed a DXA test. Moreover, participants already diagnosed with osteoporosis did not show a better disease knowledge than those without a diagnosis. Nearly half of the respondents did not know that a family history of the disease increases the risk of developing it and 60% of them thought that symptoms may develop before a fracture occurs. The preventive strategies tend to be disregarded and thus, underused. Moreover, 42.9% of participants reported being diagnosed with osteoporosis, do not undergo treatment, although they are aware of the existence of effective strategies. The dataset was used to build a participant compatibility network. The network's clustering revealed six relevant communities, which are not correlated with questionnaire results but reflect the patterns of feature associations.

Preventive and therapeutic osteoporosis education programs are urgently needed in the Romanian population to decrease disability and high mortality risks and thus, to improve the quality of life.

Background/Objectives: Numerous European countries, including Romania, are facing the concern of rapid ageing of their populations. Moreover, Romania's life expectancy ranks among the lowest in the European Union. In light of this, it is imperative that the assessment of medication-related harm be given national priority in order to secure and enhance pharmacotherapy and the medical act. In this study, we sought to describe and evaluate the under-prescribing practices among the Romanian elderly population. Methods: We conducted a cross-sectional study in urban areas of two counties in Western Romania (Timis and Arad) from November 2017 to February 2019. We collected chronic electronic prescriptions issued for elderly patients (>65 years old) with chronic conditions. The medication was prescribed by generalist or specialist physicians for periods ranging between 30 and 90 days. To assess inappropriate prescribing behaviours, a multidisciplinary team of specialists applied the Screening Tool of Older Persons' Prescriptions/Screening Tool to Alert to Right Treatment (STOPP/START) v.2 criteria to the collected prescriptions. Results: Within the 1498 prescriptions included in the study, 57% were issued to females, the mean age was 74.1 ± 6.95, and the average number of medicines per prescription was 4.7 ± 1.51. The STOPP criteria most commonly identified were the (1) long treatment duration (23.6%) and (2) prescription of neuroleptics (14.6%) or zopiclone (14.0%) as medications that increase the risk of falls. According to START criteria, the following medicines were under-prescribed: (1) statins (47.4%), (2) beta-blockers (24.5%), (3) antiresorptive therapy (10.0%), and (4) β2-agonists and muscarinic antagonists for chronic obstructive pulmonary disease (COPD) (4.5%). Within our study group, the prevalence of potentially inappropriate medications was 18.58%, whereas the prevalence of potential prescribing omissions was 49.2%. Conclusions: To decrease medication-related harm and morbid-mortality, and to increase the quality of life for elderly people in Romania, immediate actions are needed from national authorities. These actions include reinforcing primary care services, providing periodic training for physicians, implementing medication review services by pharmacists, and utilising electronic health records at their full capacity.

Osteoporosis, a common bone disease in older individuals, involves the progression influenced by N6-methyladenosine (m6A) modification. This study aimed to elucidate the effects of VDAC3 m6A modification on human bone mesenchymal stromal cell (BMSC) senescence and osteogenic differentiation. BMSCs were treated with etoposide to induce senescence. Senescence was assessed by β-galactosidase staining and quantitative real-time PCR (qPCR), and osteogenic differentiation was evaluated using Western blot, alkaline phosphatase, and alizarin red S staining. VDAC3 and ALKBH5 expression were quantified by qPCR, and their interaction was assessed by RNA immunoprecipitation (RIP) and luciferase reporter assay. m6A methylation was analyzed using the Me-RIP assay. VDAC3 expression was significantly decreased in etoposide-treated BMSCs (1.00 ± 0.13 vs. 0.26 ± 0.06). VDAC3 overexpression reduced etoposide-induced senescence and promoted osteogenic differentiation. ALKBH5 overexpression inhibited VDAC3 m6A modification (1.00 ± 0.095 vs. 0.233 ± 0.177) and its stability. ALKBH5 knockdown decreased etoposide-induced senescence and promoted osteogenic differentiation, effects that were reversed by VDAC3 knockdown. YTHDF1 was identified as the m6A methylation reader, and its overexpression inhibited VDAC3 stability. We demonstrated that ALKBH5 inhibited osteogenic differentiation of etoposide-induced senescent cells through the inhibition of VDAC3 m6A modification, and YTHDF1 acted as the m6A methylation reader. These findings provide a novel theoretical basis for the treatment of osteoporosis.

Weightlessness osteoporosis, which progresses continuously and has limited protective effects, has become one of the major problems that need to be solved in manned spaceflight. Our study aims to investigate the regulatory role of PHF8 in disuse osteoporosis by observing the expression of PHF8 in bone marrow mesenchymal stem cells (BMSCs) under simulated weightlessness conditions. Therefore, we used the model of ground-based microgravity simulated by disuse osteoporosis patients and tail suspension in mice to simulate microgravity in vivo, and measured the expression of PHF8 in bone tissue. Subsequently, we used the 2D gyroscope to simulate the weightless effect on bone marrow mesenchymal stem cells. In the weightless condition, we detected the proliferation, apoptosis, osteogenesis, and osteogenic differentiation functions of BMSCs. We also detected the expression of osteogenic-related transcription factors after knocking down and overexpressing PHF8. Our results show that the weightless effect can inhibit the proliferation, osteogenesis, and osteogenic differentiation functions of BMSCs, while enhancing their apoptosis; and overexpression of PHF8 can partially alleviate the osteoporosis caused by simulated weightlessness, providing new ideas and clues for potential drug targets to prevent weightlessness and disuse osteoporosis.

The pathological mechanism of osteoporosis (OP) involves increased bone resorption mediated by osteoclasts and decreased bone formation mediated by osteoblasts, leading to an imbalance in bone homeostasis. Identifying key molecules in osteoclast-mediated OP progression is crucial for the prevention and treatment of OP.

Differential expression analysis and weighted gene co-expression network analysis (WGCNA) were performed on the OP patient datasets from the GEO database. The results were intersected with the differential expression results from the osteoclast differentiation dataset to identify key genes. These key genes were then subjected to disease relevance analysis, and consensus clustering was performed on OP patient samples based on their expression profiles. The subgroups were analyzed for differences, followed by GO, KEGG, GSEA, and GSVA analyses, and immune infiltration. Finally, osteoclast differentiation model was constructed. After validating the success of the model using TRAP and F-actin staining, the differential expression of key genes was validated in vitro via Western blot.

CTRL, ARHGEF5, PPAP2C, VSIG2, and PBLD were identified as key genes. These genes exhibited strong disease relevance (AUC > 0.9). Functional enrichment results also indicated their close association with OP and osteoclast differentiation. In vitro differential expression validation showed that during osteoclast differentiation, CTRL was downregulated, while ARHGEF5, PPAP2C, VSIG2, and PBLD were upregulated, with all differences being statistically significant (P < 0.05).

Currently, there are no studies on the effects of these five genes on osteoclast differentiation. Therefore, it is meaningful to design in vivo and in vitro perturbation experiments to observe the impact of each gene on osteoclast differentiation and OP progression.

CTRL, ARHGEF5, PPAP2C, VSIG2, and PBLD show high potential as molecular targets for basic and clinical research in osteoclast-mediated OP.

The musculoskeletal system, which is vital for movement, support, and protection, can be impaired by disorders such as osteoporosis, osteoarthritis, and muscular dystrophy. This review focuses on the advances in tissue engineering and regenerative medicine, specifically aimed at alleviating these disorders. It explores the roles of cell therapy, particularly Mesenchymal Stem Cells (MSCs) and Adipose-Derived Stem Cells (ADSCs), biomaterials, and biomolecules/external stimulations in fostering bone and muscle regeneration. The current research underscores the potential of MSCs and ADSCs despite the persistent challenges of cell scarcity, inconsistent outcomes, and safety concerns. Moreover, integrating exogenous materials such as scaffolds and external stimuli like electrical stimulation and growth factors shows promise in enhancing musculoskeletal regeneration. This review emphasizes the need for comprehensive studies and adopting innovative techniques together to refine and advance these multi-therapeutic strategies, ultimately benefiting patients with musculoskeletal disorders.

Postmenopausal osteoporosis (PMO) is characterized by bone loss and microstructural damage, and it is most common in older adult women. Currently, there is no cure for PMO. The flavonoid chemical 7,8-dihydroxyflavone (7,8-DHF) specifically activates tropomyosin receptor kinase B (TRKB). Furthermore, 7,8-DHF has various biological characteristics, including anti-inflammatory and antioxidant effects. However, the specific implications and fundamental mechanisms of 7,8-DHF in PMO remain unclear. We used protein imprinting, flow cytometry, tissue staining, and other methods to estimate the preventive mechanisms of 7,8-DHF against hydrogen peroxide (H2O2)-induced apoptosis in primary mouse bone marrow mesenchymal stem cells (BMSCs), osteogenic differentiation ability, and bone mass in ovariectomized (OVX) mice. We found that 7,8-DHF effectively prevented H2O2-induced reductions in the viability and osteogenic differentiation capacity of primary BMSCs. Mechanistically, 7,8-DHF induced the TRKB to activate the PI3K/AKT/NRF2 pathway. In vivo experiments with the OVX mouse model confirmed that 7,8-DHF can inhibit oxidative stress and promote bone formation, indicating that 7,8-DHF improves the viability and osteogenic differentiation ability of BMSCs stimulated via H2O2 by activating the TRKB/PI3K/AKT and NRF2 pathways, thereby improving PMO.

Osteoporosis is a major health concern for postmenopausal women, and the effect of simvastatin (Sim) on bone metabolism is controversial. This study aimed to investigate the effect of simvastatin on the bone microstructure and bone mechanical properties in ovariectomized (OVX) mice.

24 female C57BL/6J mice (8-week-old) were randomly allocated into three groups including the OVX + Sim group, the OVX group and the control group. At 8 weeks after operation, the L4 vertebral bones were dissected completely for micro-Computed Tomography (micro-CT) scanning and micro-finite element analysis (µFEA). The differences between three groups were compared using ANOVA with a LSD correction, and the relationship between bone microstructure and mechanical properties was analyzed using linear regression.

Bone volume fraction, trabecular number, connectivity density and trabecular tissue mineral density in the OVX + Sim group were significantly higher than those in the OVX group (P < 0.05). For the mechanical properties detected via µFEA, the OVX + Sim group had lower total deformation, equivalent elastic strain and equivalent stress compared to the OVX group (P < 0.05). In the three groups, the mechanical parameters were significantly correlated with bone volume fraction and trabecular bone mineral density.

The findings suggested that simvastatin had a potential role in the treatment of osteoporosis. The results of this study could guide future research on simvastatin and support the development of simvastatin-based treatments to improve bone health.