The accumulation of reactive oxygen species (ROS) within cells regulates the formation and function of osteoclasts, which is crucial therapeutic target for the treatment of osteoporosis. Ergothioneine (EGT) is a rare amino acid with strong antioxidant and anti-inflammatory properties. However, its application on osteoporosis has not been reported. In this study, we investigated the effects of EGT on osteoclastogenesis in vitro and in ovariectomized (OVX) mice. The results revealed that EGT could suppress RANKL-induced podosome belt formation and osteoclast development in vitro, while reducing intracellular ROS levels by upregulating key antioxidant enzymes, including HO-1 and Catalase. EGT was also found to downregulate the expression of critical osteoclast-specific proteins such as Trap, c-Fos, and Ctsk through attenuation of MAPK signaling. The potential of EGT to protect against trabecular bone loss in OVX mice was further demonstrated by micro-CT imaging, possibly by reducing osteoclast numbers shown by histological outcomes. These findings together highlighted the potential value of EGT as a novel tool for treating osteoporosis through its ability to suppress osteoclastogenesis and mitigate the accumulation of intracellular ROS.

The decreased osteogenesis of bone marrow mesenchymal stem cells (BMSCs) is an important factor causing bone loss. Nevertheless, its deep molecular mechanism has still not been fully clarified. To elucidate the regulatory mechanisms underlying BMSC osteogenesis, we conducted a bioinformatics screen using public datasets from the Gene Expression Omnibus (GEO) database to identify genes displaying significant expression dynamics during the osteogenic differentiation of BMSCs. We observed a significant upregulation of FK506 Binding Protein 5 (FKBP5) expression during the osteogenic differentiation of BMSCs. Besides, knockdown and overexpression of FKBP5 could reduce and increase osteogenic markers and Alizarin Red S (ARS) staining, respectively. Enrichment analysis of RNA sequencing (RNA-seq) demonstrated that downregulation of FKBP5 activated IFNα/β signaling pathway. FKBP5 overexpression relieved the inhibitory effect of IFNβ on osteogenesis. In addition, one of the upregulated interferon-stimulated genes (ISG), interferon-induced protein with tetratricopeptide repeats 2 (IFIT2), negatively regulated osteogenesis of BMSCs. IFIT2 knockdown rescued negative effect on osteogenesis caused by downregulation of FKBP5. Hydroxyapatite scaffold implanted in nude mice and drilled tibiae model in C57BL/6 mice confirmed positive role of FKBP5 in osteogenesis in vivo. Therefore, we determined the beneficial effect of FKBP5 on osteogenesis of BMSCs and validated the critical role of FKBP5/IFIT2 axis in this process. These findings might contribute to comprehension and treatment of bone diseases, like osteoporosis and bone fracture.

To develop a multidisciplinary consensus outlining key recommendations to prevent fragility fractures and improve care through coordinated efforts across healthcare sectors.

An international group of experts, coordinated by the Spanish National Hip Fracture Registry (RNFC), engaged over 300 professionals and 31 scientific societies. Using a nominal group technique, the committee reviewed scientific evidence and collaboratively developed ten core recommendations. The consensus was refined through multiple telematic reviews and finalized at the 7th RNFC Annual Meeting in March 2024.

The consensus presents ten actionable recommendations: (1) inclusion of osteoporosis and fragility fractures in health policies, (2) early detection and management of frailty and falls, (3) implementation of clinical practice guidelines, (4) promotion of fracture registries and audits, (5) support for Orthogeriatric Units and Fracture Liaison Services (FLS), (6) adoption of a "Fragility Fracture Code," (7) empowerment of Primary Care in fracture prevention, (8) increased patient association involvement, (9) public awareness campaigns, and (10) promotion of research including patient-reported outcomes.

Fragility fractures are a major public health issue with rising incidence, disability, and healthcare costs. This consensus offers unified, evidence-based guidance for policy makers, healthcare professionals, and patient organizations. Broad dissemination and implementation of these recommendations aim to reduce fracture rates and enhance patient outcomes through coordinated, multidisciplinary care.

Bone remodeling process is the basis for maintaining normal bone microstructure and promoting fracture repair. Recent studies have proven that integrins can promote bone formation and fracture repair. Integrin-linked kinase (ILK), as the proximal effector of the integrin receptor, is a key protein factor linking integrin and cytoskeleton. It is involved in crucial cellular processes including proliferation, survival, differentiation, migration, invasion, and angiogenesis reflects on systemic changes in the kidney, heart, muscle, skin, and vascular system. At present, the regulation effect of ILK in bone formation attracts the attention of researchers. This review emphasizes that ILK as a key molecule affects the functions of bone marrow stromal cells (BMSCs) and osteoblasts, and regulates bone formation. Additionally, ILK plays a key role in the process of"angiogenic-osteogenic coupling ". The present role of ILK in the pathogenesis of osteoporosis is also described. Strategies that target ILK may as a new prospective treatment for osteoporosis (OP).

The feasibility of dental implants in patients with osteoporosis remains controversial, with limited prospective studies on quantitative changes in bone mineral density (BMD) and bone turnover markers (BTMs). This study assessed implant survival and clinical outcomes while evaluating systemic changes during 1 year of implant treatment.

Postmenopausal women requiring dental implants were enrolled at the Yonsei University Dental Hospital. BMD and BTMs were evaluated in collaboration with the endocrinology department. Participants were divided into two groups: Group A (T-score ≥ -2) and Group B (T-score < -2). All implants used in the study were surface-treated with hydroxyethyl piperazine ethane sulfonic acid (HEPES), and clinical, radiographic, and systemic parameters were monitored for over 1 year.

Between April 2022 and May 2024, 45 implants were placed in 36 patients (mean age: 68 years). Group A included 17 patients with 21 implants (mean age: 66 years), and Group B included 19 patients with 24 implants (mean age: 70 years). The cumulative survival rate was 100%. Resonance frequency analysis at 12 months revealed a mean implant stability tester value of 71.4 ± 5.52, indicating excellent osseointegration. Peri-implant bone loss averaged 0.54 ± 0.35 mm. No implant failures occurred, with stable plaque scores, probing depths, and bleeding upon probing. BMD and BTMs changes were minimal.

Both groups achieved high implant survival and stable clinical outcomes. Systemic evaluations confirmed only minor changes in BMD and BTMs over 1 year. Larger multicenter studies are required to confirm the systemic safety of dental implants in patients with osteoporosis.

Dental implants show excellent survival and stability in postmenopausal women with osteoporosis, with minimal impact on bone density and turnover-supporting their safe use in this population.

This study was prospectively registered at the Clinical Research Information Service of the National Research Institute of Health, Republic of Korea (KCT0007100). The registration details can be accessed at https://cris.nih.go.kr .

Herein, a novel anti-osteoporosis agent is presented, namely, RGDS (Arg-Gly-Asp-Ser)-conjugated UA (ursolic acid) (abbreviated as UA-RGDS). In ultrapure water, UA-RGDS existed as a tetramer. In the serum of ovariectomized (OVX) mice and at 10-4 M concentration, the self-assembled UA-RGDS formed nano-particles of 16-156 nm in height, suitable for transportation in blood circulation. In vivo bio-distribution data showed that UA-RGDS was only distributed in the femur of OVX mice, while null distribution was found in the blood and other organs. These observations suggested that UA-RGDS can target the femur, thereby preventing bone loss. ELISA results showed that as an anti-osteoporosis agent, UA-RGDS downregulated the expressions of IL-1β in the serum of OVX mice. Thus, serum IL-1β levels could be a biomarker to clinically detect menopause, and UA-RGDS could help prevent bone loss.

Our study investigated the associations between bone turnover markers (BTMs) and bone mineral density (BMD) and fracture risk over the next 10 years. The objective of the study was to evaluate the potential effects of BTMs in fracture risk.

Our cross-sectional study enrolled 580 participants (380 postmenopausal women and 200 men over the age of 50). All participants completed a questionnaire and dual-energy X-ray absorptiometry examination. We obtained BMD values for the lumbar spine, femoral neck, and total hip joint and biochemical indicators such as creatinine, type 1 procollagen N-terminal propeptide (P1NP), and beta cross-linked C-telopeptide of type 1 collagen (β-CTX). Furthermore, we used an online fracture risk assessment tool (FRAX) to calculate the probability of major osteoporotic fractures (PMOF) and hip fractures (PHF) over the next 10 years. We divided the participants into three groups based on the BMD T-score criteria: normal bone mass group (T-score ≥ - 1.0 SD), osteopenic group (- 2.5 SD < T-score < - 1.0 SD), and osteoporotic group (T-score ≤ - 2.5 SD). We compared differences in BTMs, BMD, and fracture risks among the three groups. Additionally, we evaluated differences in indicators between males and females and explored risk factors associated with BMD and fracture risk.

Postmenopausal women showed higher bone turnover markers, osteoporosis prevalence, and fracture risks compared to men. In a multivariate stepwise regression analysis, we identified P1NP was positively correlated with fracture risk for both PMOF (β = 0.087, p = 0.005) and PHF (β = 0.135, p < 0.001) over the next 10 years. In the logistic regression analysis, after adjusting for sex, we found that for every standard deviation increase in P1NP, the future 10-year risk of fractures increased by approximately 5.2-fold in the high PMOF group and 5.6-fold in the high PHF group.

Our study demonstrated that elevated serum P1NP levels were associated with increased fracture risk over a 10-year period. These findings suggested that serum P1NP measurement could be a valuable complementary tool alongside BMD measurements and FRAX assessments for identifying individuals at high risk of fracture.

Objectives: This study aimed to investigate the relationship between osteoporosis and cerebral small vessel disease (CSVD) burden in stroke-free individuals, as well as its specific imaging markers, including lacunes, enlarged perivascular spaces (EPVSs), white matter hyperintensities (WMHs), and brain atrophy (BA). Methods: A total of 684 stroke-free patients who underwent both bone mineral density (BMD) assessments and brain MRI were included. Clinical data, CSVD burden scores, imaging markers of CSVD, and bone density parameters were collected. Logistic regression models were used to evaluate the relationship between BMD and CSVD burden and imaging markers. Results: Osteoporosis, including hip and vertebral osteoporosis, was independently associated with CSVD burden (OR = 2.332, 95%CI: [1.345, 4.039], p = 0.003; OR = 2.598, 95%CI: [1.540, 4.384], p < 0.001; OR = 1.515, 95%CI: [1.010, 2.272], p = 0.044). Increased BMD in the hip and spine correlated with reduced CSVD burden (OR = 0.929, 95%CI: [0.887, 0.972], p = 0.001; OR = 0.952, 95%CI: [0.917, 0.989], p = 0.012). Hip osteoporosis was a risk factor for lacunes (OR = 2.215, 95%CI: [1.197, 4.1], p = 0.011), multiple lacunes (OR = 2.274, 95%CI: [1.039, 4.980], p = 0.04), severe WMH (OR = 2.611, 95%CI: [1.171, 5.823], p = 0.019), and EPVS ≥ 2 (OR = 1.99, 95%CI: [1.133, 3.495], p = 0.017). No significant association was found between osteoporosis and BA (p = 0.928). In sex-stratified analyses, both hip and vertebral osteoporosis were independently associated with a higher CSVD burden in female patients (hip: OR = 2.529, 95%CI: [1.122, 5.703], p = 0.025; vertebral: OR = 3.129, 95%CI: [1.517, 6.455], p = 0.002; general osteoporosis: OR = 1.755, 95%CI: [1.057, 2.912], p = 0.03), whereas no significant association was observed in male patients (all p > 0.05). Conclusions: Osteoporosis was independently associated with an increased burden of CSVD, particularly evident in female patients. These findings suggest that bone health may be important in CSVD management, particularly for women.

Early identification of osteoporosis promotes timely treatment. This retrospective study demonstrated that bone cortical percentage (2MCP) measured on hand X-ray in patients with inflammatory arthritis correlates significantly with bone density, fracture risk and fracture incidence. Routine hand X-ray 2MCP reporting could support identification of patients at risk of osteoporotic fractures.

Effective osteoporotic screening facilitates earlier identification and treatment of patients at risk. Bone mineral density (BMD) alone has limited sensitivity and may not always be available. This study aimed to show whether radiographic second metacarpal cortical thickness percentage (2MCP) correlates with BMD and fracture incidence.

This retrospective cohort study measured 2MCP in 230 patients with inflammatory arthropathies who underwent both DXA and hand radiograph within 6 months. BMD, FRAX and fracture history was gathered.

2MCP correlated with femoral neck BMD (p < 0.001), T-scores (p < 0.001), FRAX (p < 0.001) and major and all osteoporotic fracture incidence (p < 0.001) across all patient groups. 2MCP ≤ 55% was 88% sensitive and 51% specific in identifying patients with osteoporotic BMD (AUC 0.7893). 2MCP ≤ 65% and ≤ 73% were 100% sensitive for osteoporotic and osteopenic BMD respectively, whilst ≤ 30% and ≤ 39% were 100% specific. 2MCP ≤ 59% demonstrated 92% sensitivity for all low-impact fractures and 2MCP ≤ 56% was 87% sensitive for major osteoporotic fracture (MOF). 2MCP showed superior sensitivity and specificity to osteopenic femoral neck T-score for predicting MOF incidence (AUC 0.7009 and 0.6590). Combining 2MCP with T-score parameters enhanced sensitivity to 94.6% for MOF up to 2 years beyond the hand radiograph.

2MCP presents a fast, inexpensive adjunct to evaluate fracture risk. This technology may enhance BMD sensitivity in predicting MOF and improve global bone health assessment accessibility. 2MCP automation and routine inclusion in hand radiographs could optimise early awareness and diagnosis of patients at risk of osteoporosis and fractures.

The aim of this study is to estimate the diagnostic efficiency of VBQ score for assessing osteopenia and osteoporosis in different Roussouly types in lumbar degenerative disease.

We reviewed the preoperative data of 501 patients with lumbar degenerative diseases who underwent lumbar spine surgery between July 2019 and December 2022 with available T1-weighted magnetic resonance imaging and dual-energy X-ray absorptiometry. Receiver operating characteristic (ROC) curves were plotted to analyze the diagnostic performance of VBQ score in different Roussouly classifications. For each Roussouly type, one-way ANOVA was applied to compare VBQ score across different lumbar segments. Statistical significance was set at P < 0.05.

No statistical difference was found between the VBQ score of L1, L2, L3 and L4. Lumbar lordosis and sacral slope were not independently associated with VBQ score. According to the ROC curve, Roussouly type 1 to 4 showed AUC of 0.738, 0.799, 0.764 and 0.817, respectively, in diagnosing osteopenia. Roussouly type 1 to 4 showed AUC of 0.690, 0.703, 0.851 and 0.643, respectively, in diagnosing osteoporosis.

Different Roussouly types would not affect the diagnosis efficiency of VBQ score in diagnosing osteopenia. However, VBQ score showed better performance in diagnosing osteoporosis for Roussouly type 3. When VBQ score was applied as opportunistic screening method for osteoporosis, choosing appropriate patients was important to improve the diagnostic accuracy.

Background/Objectives: Osteoporosis is a major public health concern, due to its high risk of fractures and disability and associated medical costs. Romosozumab, an anabolic agent, has been approved for the treatment of osteoporosis in postmenopausal women at high risk of fractures. However, limited data exist on its long-term effects in the Korean population, particularly regarding its impact on bone mineral density (BMD), bone turnover markers, and body composition. This study aimed to evaluate the 12-month effects of romosozumab treatment on BMD, bone turnover markers, and body composition in postmenopausal Korean women with high-fracture-risk osteoporosis (T-scores ≤ -3.0). Additionally, the impact of concomitant postmenopausal hormone therapy (MHT) on BMD changes was assessed. Methods: This multicenter, retrospective observational study included 50 postmenopausal women diagnosed with osteoporosis (T-scores ≤ -3.0) who received 12 monthly doses of romosozumab (210 mg) at two hospitals in Korea. Changes in BMD in the lumbar spine, femoral neck, and total hip were assessed using dual-energy X-ray absorptiometry (DXA). Bone turnover markers, including procollagen type 1 N-terminal propeptide (P1NP) and C-terminal telopeptide of type 1 collagen (CTX), were measured at baseline and at 3, 6, and 12 months. Changes in body composition, including the skeletal muscle index (SMI), body mass index (BMI), and visceral adipose tissue (VAT), were also analyzed. Results: After 12 months of romosozumab treatment, BMD significantly increased at the lumbar spine (14.65%), femoral neck (6.58%), and total hip (4.19%) (p < 0.05). P1NP levels increased significantly at 3 months (+37.9%), but returned to baseline at 6 months, while CTX levels continuously decreased (-27.8%) over 12 months. No significant changes were observed in SMI or BMI, but the VAT showed a slight decreasing trend (p < 0.05). Additionally, patients receiving concomitant MHT demonstrated a significantly greater increase in lumbar spine BMD compared to those receiving romosozumab alone (p < 0.05), while no significant differences were observed in femoral neck and total hip BMD. Conclusions: This study demonstrated that 12 months of romosozumab treatment significantly improved BMD and bone turnover markers in postmenopausal Korean women with severe osteoporosis. The combination of romosozumab and MHT further enhanced lumbar spine BMD gains. These findings support the use of romosozumab as an effective treatment for high-risk osteoporotic fractures in postmenopausal Korean women, and suggest potential benefits of a combined therapeutic approach.

Osteoporosis and osteopenia are common among patients undergoing posterior spine fusion surgery, presenting challenges such as pseudarthrosis, screw loosening, and poor patient outcomes. While pharmacological interventions are available, no consensus exists regarding the optimal perioperative treatment for these patients. Furthermore, the effectiveness of various treatment options in improving fusion rates and minimizing complications remains uncertain.

To compare the effects of teriparatide, bisphosphonates, denosumab, and romosozumab in patients with posterior spine fusion with low bone mineral density (BMD).

Systematic review and meta-analysis PATIENT SAMPLE: Adult patients with low BMD receiving osteoporosis medications and undergoing posterior spine fusion surgery OUTCOME MEASURES: Fusion rate, subsequent vertebral fracture (VF), screw loosening, cage subsidence, proximal junctional kyphosis(PJK), and patient-reported outcomes (PROs), particularly the Visual Analogue Scale (VAS) and Oswestry Disability Index (ODI).

A systematic search was conducted using PubMed, EMBASE, and Cochrane Library. Two reviewers independently selected and assessed relevant studies. Four groups were analyzed to evaluate the comparative effectiveness of antiosteoporosis medication on the outcome measures: Bisphosphonate versus Control; Teriparatide versus Control; Teriparatide versus Bisphosphonate; and Denosumab versus Control.

Bisphosphonate showed reduced subsequent VFs (odds ratio [OR]=0.27, 95% confidence interval [CI]=0.09-0.81) and cage subsidence (OR=0.29, 95% CI=0.11-0.75) and improved ODI scores at 12 months (standardized mean difference [SMD] [95% CI]=-0.75 [-1.42, -0.08]) compared to the control. Teriparatide showed a higher fusion rate (OR=3.52, 95% CI=1.84-6.75), lower screw loosening (OR=0.23, 95% CI=0.09-0.60), and improved ODI scores at 24 months (SMD [95% CI]=-0.57 [-0.99, -0.15]) compared to the control. Moreover, teriparatide showed a higher fusion rate (OR=2.28, 95% CI=1.67-3.11), lower subsequent VF (OR=0.22, 95% CI=0.09-0.51), and improved VAS score for back pain (VASB) (mean difference [MD] [95% CI]=-0.30 [-0.54, -0.07]) and ODI (SMD [95% CI]=-0.38[-0.64, -0.12]) scores at 12 months compared to bisphosphonate. Denosumab showed no significant difference in fusion rate or other complications compared to control.

Our results indicated that teriparatide should be used as the first-line perioperative treatment for patients with poor bone quality scheduled for posterior spine fusion. Teriparatide exhibited better fusion rates and reduced complications than controls and bisphosphonates, resulting in improved PROs. Moreover, bisphosphonates can be utilized in patients with contraindications to teriparatide since the former prevents osteoporosis-related complications compared to controls, resulting in improved PROs. Further studies are warranted to evaluate the potential effects of denosumab and romosozumab.

The aim of the current study was to examine the effects of light- to moderate intensity aerobic exercise on bone mineral density (BMD) in postmenopausal osteopenic women by using bone formation and resorption markers. In the current study, P1NP and CTX levels increased in both the exercise and the control group. The aim of the current study was to examine the effects of light- to moderate-intensity aerobic exercise on bone mineral density (BMD) in postmenopausal osteopenic women by using rapidly responsive bone formation and resorption markers.

In this prospective, randomized, controlled, single-blind clinical study, women aged 45-65 years with BMD T scores between - 1 and - 2.5 measured by double X-ray absorptiometry (DXA) were included after evaluation of exclusion criteria and the women were divided into 2 groups: aerobic exercise group and control group (exercise, n = 25; control, n = 25). At baseline and at the 12-week follow-up, the serum levels of bone formation and resorption biomarkers, including procollagen type 1 N-terminal propeptide (P1NP), cross-linked C-telopeptide of type I collagen (CTX), osteocalcin, oxidative markers such as malondialdehyde, nonbone-specific total alkaline phosphatase, 25(OH)D3, and parathyroid hormone (PTH), were examined in all patients.

A statistically significant increase in P1NP and CTX levels was noted in both the exercise and control groups at the 12-week evaluation compared to baseline (p > 0.05). Although there was no significant change in osteocalcin levels in the control group (p > 0.05), a statistically significant increase was observed in the exercise group (p < 0.05). In the exercise group, no significant changes were observed in bone formation or resorption markers, including P1NP, CTX, osteocalcin, and total ALP, or in oxidative stress markers, such as malondialdehyde, compared to those in the control group (p > 0.05).

In conclusion, the current study revealed that regular walking exercise of light to moderate intensity significantly contributes to improvements in pain, walking speed, balance, lower extremity dynamic balance, and activities of daily living in postmenopausal women with osteopenia compared to inactive individuals.

Clinical Trial Number NCT06866561.

Background/Objectives: Osteoporosis is prevalent in the elderly and increases fracture risk. Bone density is commonly assessed using dual-energy X-ray absorptiometry (DEXA). The femoral cortical thickness index (CTI) also provides indirect information for osteoporosis. It remains unclear whether there are intra-individual differences and if a correlation to fracture risk of the CTI in fractured femora results due to fracture related malrotation during X-rays. The aim of this study was to investigate the individual bilateral CTI in patients with proximal femoral fractures. Methods: A retrospective analysis of 200 surgically treated patients (100 trochanteric, 100 femoral neck fractures) was performed. Measurements included the bilateral CTI at 10 and 15 cm below the lesser trochanter. Analysis of the correlation of those examinations, in comparison to the contralateral CTI at 15 cm, and correlation of the CTI with the body mass index (BMI) and age was performed. Results: Results showed significant differences (p < 0.001) in bilateral CTIs for both fracture types at 15 cm with a strong inter-rater reliability (ICC > 0.9). There was no significant correlation between age and CTI, as well as BMI and CTI in both cohorts (p > 0.1). Sex-specific subgroup analyses revealed that females exhibited significant differences in CTI between fractured and non-fractured sides (p < 0.001). Conclusions: In conclusion, CTI, and the modified CTI at 15 cm below the lesser trochanter in fractured proximal femora, is lower compared to the non-fractured side. The femoral CTI could help in daily clinical routines and circumstances, where more detailed risk prediction tools are lacking.

Metabolic bone disease (MBD), as one of the most severe metabolic disorders, remains a focal point and challenge in medical research. Numerous studies have demonstrated the efficacy of Traditional Chinese Medicine (TCM) in preventing and treating MBD. However, the inherent complexity of TCM metabolites poses significant limitations in elucidating their mechanisms of action. The advancement of omics technologies, including metabolomics, proteomics, and transcriptomics, has greatly facilitated research on MBD. These approaches enable the identification of potential biomarkers and the exploration of metabolic pathways and mechanisms underlying TCM interventions for MBD. Evidence indicates that TCM monomers, single botanical drugs, and herbal formulations are effective, safe, and well-tolerated in MBD prevention and treatment. This review summarizes recent applications and key findings of transcriptomics, proteomics, and metabolomics in studying the mechanisms of TCM interventions for MBD. It highlights the role of omics technologies in uncovering relevant metabolites and pathways under TCM treatment, providing valuable insights and clinical references for TCM-based strategies in managing MBD.

This study investigates the association between blood Mn and bone mineral density (BMD), focusing on the mediating role of sex steroids, using data from 8617 participants in the National Health and Nutrition Examination Survey (NHANES) 2013-2018. Weighted multiple linear regression models were used to examine the association of blood Mn and total BMD, and mediation analyses were used to explored the roles of total testosterone (TT), estradiol (E2), and sex hormone-binding globulin (SHBG) in the Mn-BMD relationship, stratified by sex and menopausal status. Blood Mn was negatively associated with BMD in both sexes, with a pronounced effect in postmenopausal women. SHBG mediated 37.16% of the Mn-BMD association in men, whereas no mediating effects were found in women. E2 exhibited a significant indirect effect, suggesting that reduced E2 levels may amplify Mn's effect on BMD. These findings indicate that Mn exposure is associated with decreased BMD, potentially through alterations in sex steroids, highlighting the importance of considering hormone status when evaluating the impact of Mn exposure on BMD.

Phytohormones have garnered considerable interest as potential modulators of the gut-bone axis. Denosumab (Deno), a widely utilized therapeutic agent for postmenopausal osteoporosis, has not been previously investigated for its effects on gut health. The objective of this study was to assess the efficacy of isoflavones (SI), naringin (Nar), and Deno in the management of postmenopausal osteoporosis by targeting the gut-bone axis.

The postmenopausal osteoporosis model in mice was established via bilateral oophorectomy. Subsequently, mice in the Deno group received subcutaneous injections of Deno at a dosage of 10 mg/kg, administered twice weekly. In contrast, mice in the SI and Nar groups were subjected to oral gavage with 200 mg/kg/day of SI and Nar, respectively. The treatment period for all groups lasted for 8 weeks. Upon the conclusion of the experiment, a thorough evaluation of the effects of SI, Nar, and Deno on bone and gut health in mice was conducted through immunological, pathological, imaging, and multi-omics methodologies.

Deno, SI, and Nar significantly alleviated the physical symptoms in postmenopausal mice. However, only SI and Nar significantly modulated the gut microbiota. Akkermansia was significantly enriched after the gavage of SI and Nar. Akkermansia has the capacity to not only augment bone mass and alleviate strength deterioration via extracellular vesicles, but it also influences bone metabolism by diminishing inflammation and modulating lipid metabolism. Notably, no significant changes in the gut microbiota were observed in the Deno group, which may be attributed to the differences in the method of administration, as Deno was administered via subcutaneous injection rather than gavage.

SI and Nar may influence the gut-bone axis through Akkermansia and have the potential of alternative treatment options for postmenopausal osteoporosis. Although the gut microbiota is not significantly affected by the subcutaneous administration of Deno, the long-term management of postmenopausal osteoporosis and the exploration of various management models warrant additional scrutiny. Furthermore, this study has yet to establish a dose-response relationship, indicating that further research is essential to clarify the regulatory effects of varying doses of SI and Nar on postmenopausal osteoporosis especially the modulation of gut microbiota.

Thalassemia patients often exhibit low bone mineral density (BMD). The iron overload associated with thalassemia elevates oxidative stress levels, leading to reduced BMD. Melatonin improves BMD in postmenopausal osteopenia, however, its effect on BMD in thalassemia patients with iron overload has not been investigated. A randomized controlled study was conducted at Hematology Clinic, Faculty of Medicine, Chiang Mai University. Thalassemia patients with osteopenia and iron overloaded condition, as indicated by BMD Z-score <-2 at l-spine, femoral neck, or total hip, and serum ferritin level > 500 μg/L were recruited in this study. Patients were randomized to receive either melatonin 20 mg/day or placebo at bedtime for 12 months. BMD was re-evaluated 12 months after interventions. Bone turnover markers (BTM), malondialdehyde (MDA as an oxidative stress marker), and pain scores were assessed at baseline, 6, and 12 months. The outcomes, including BMD, BTM, MDA, and pain scores, were evaluated in all patients. Forty-one thalassemia patients (18 males) were enrolled in the study and randomly assigned to either the melatonin group (n = 21) or the placebo group (n = 20). Characteristics of patients were not differences between groups. Mean age was 30.8 ± 6.2 years old. Thirty-three patients (80.4%) were transfusion-dependent patients. At 12 months, mean BMD at l-spine in melatonin group was not significantly different from placebo group (p = 0.069). However, l-spine BMD at 12 months in the melatonin group was significantly greater than baseline (p = 0.029). Serum levels of P1NP and MDA were significantly reduced at 6 months compared to baseline following melatonin treatment. The melatonin group experienced a notable decrease in back pain scores after 12 months compared to the initial measurements. 20 mg daily melatonin supplementation for 12 months alleviated l-spine BMD loss in iron-overloaded thalassemia with low BMD. Melatonin also significantly reduced circulating oxidative stress and mitigated back pain in these patients.

The aim of this study was to establish the optimal prediction model by comparing the prediction effect of 6 kinds of prediction models containing biochemical indexes on the risk of osteoporosis in middle-aged and elderly women in Tibet. This study adopted a multi-stage cluster random sampling cross-sectional survey method. From January 2022 to January 2024, we obtained biochemical and bone mineral density (BMD) data from high altitudes in Tibet. We built a predictive model of osteoporosis in three steps. First, we performed feature selection to identify factors associated with osteoporosis. Next, the eligible participants were randomly divided into a training set and a test set in a ratio of 8:2. Then, the prediction model of osteoporosis was established based on Random Forest, ANN, XGB, and SVM. Finally, we compared the performance of the prediction models using sensitivity, specificity, and the area under the receiver operating characteristic curve (AUC) to select the best prediction model. Correlation analysis was used to screen indicators with statistical differences from T-score. Finally, Age (P < 0.01), LDL-C (P < 0.05), UA (P < 0.01), AST (P < 0.05), CREA (P < 0.01), BMI (P < 0.01), ALT (P < 0.01) were associated with osteoporosis. In train set, the order of AUC from highest to lowest is Random Forest (1.000), XGB (0.887), SVM (0.868), regression (0.801), ANN (0.793) and OSTA (0.739). In test set, the order of AUC from highest to lowest is XGB (0.848), regression (0.801), Random Forest (0.772), SVM (0.755), OSTA (0.739), ANN (0.732). SVM and XGB algorithm models had better screening effect on osteoporosis than OSTA in middle-aged and elderly Tibetan residents in Tibet. Compared with Random Forest, ANN and SVM, the established XGB model had the best prediction ability and can be used to predict the risk of osteoporosis on biochemical indexes. The model needs to be further improved through large sample research.

Aged osteoporosis poses a significant threat to the well-being and longevity of older individuals, yet evidence regarding the relationship between osteoporosis risk and mortality among the elderly population in Asia remains unknown.

Our study aimed to investigate associations between osteoporosis risk and all-cause mortality, as well as cause-specific mortality, among the Chinese elderly population.

Pooled data from the Chinese Longitudinal Healthy Longevity Survey (CLHLS) conducted between 2002 and 2018 were utilized to analyze the associations between osteoporosis risk and all-cause, heart disease, cardiovascular disease (CVD), respiratory disease, and cancer mortality. Cox proportional hazards models were employed for this analysis. Osteoporosis risk was assessed using the Osteoporosis Self-Assessment Tool for Asians (OSTA). Restricted cubic spline (RCS) functions were applied to explore the nonlinear relationship between OSTA and mortality. The robustness of the Cox models was evaluated through internal verification, subgroup analyses, and sensitivity analyses.

A total of 12,711 elderly individuals aged ≥ 65 years were included for analysis at baseline. During a 16-year follow-up, 7,963 individuals in the cohort were identified as deceased. Compared to those with low osteoporosis risk, elderly individuals with high osteoporosis risk demonstrated a significantly elevated risk of all-cause, heart disease, CVD, respiratory disease and cancer mortality. The relationship between OSTA level and all-cause and cause-specific mortality exhibited a significant L-shaped pattern.

The risk of osteoporosis is independently associated with the prediction of mortality. The OSTA may serve as a suitable predictor for mortality related to osteoporosis among the Asian population.

Gastric polyps indicate the disturbance of gastric microecology and inflammatory status, which may affect bone metabolism. We aimed to investigate the association between gastric polyps and bone mineral density (BMD) in patients with chronic gastritis (CG). In this cross-sectional study, we collected the clinical data of 627 inpatients with CG between July 2017 and August 2022. Gastric polyps were diagnosed through gastroscopy. BMD was measured using dual energy X-ray absorptiometry. Osteopenia or osteoporosis was defined as decreased BMD. Linear regression analysis was employed to assess the relationship between BMD with gastric polyps. Logistic regression analysis was conducted to evaluate the correlation between decreased BMD and gastric polyps. In results, the prevalence of gastric polyps in males and females with CG was 17.3% and 18.3%, respectively. The occurrence of decreased BMD was observed in 51.4% and 65.1% of males and females, respectively. Gastric polyps were negatively correlated with lumbar spine, femoral neck, and total femur BMD (β=-0.025, -0.043, -0.029, p ≤ 0.005) in females with CG. Furthermore, gastric polyps significantly elevated the risk of osteoporosis or osteopenia (OR = 2.672, p = 0.010) among females with CG. However, no significant correlation between gastric polyps and BMD was detected in males with CG. In addition, gastric polyps in females were positively correlated with hypertension and high low-density lipoprotein cholesterol levels, while negatively correlated with high phosphorus levels. In conclusion, gastric polyps are negatively correlated with BMD and significantly increase the risk of osteoporosis or osteopenia in females with CG.

Osteoporosis is a systemic microstructural degradation of bone tissue, often accompanied by fractures, pain, and other complications, resulting in a decline in patients' life quality. In response to the increased incidence of osteoporosis, related drug discovery has attracted more and more attention, but it is often faced with challenges due to long development cycle and high cost. Deep learning with powerful data processing capabilities has shown significant advantages in the field of drug discovery. With the development of technology, it is more and more applied to all stages of drug discovery. In particular, large models, which have been developed rapidly recently, provide new methods for understanding disease mechanisms and promoting drug discovery because of their large parameters and ability to deal with complex tasks. This review introduces the traditional models and large models in the deep learning domain, systematically summarizes their applications in each stage of drug discovery, and analyzes their application prospect in osteoporosis drug discovery. Finally, the advantages and limitations of large models are discussed in depth, in order to help future drug discovery.

This meta-analysis aims to quantify the relationship between coffee and tea consumption and the risk of osteoporosis and explore whether such consumption positively or negatively impacts this risk, thereby providing a scientific basis for understanding the effects of coffee and tea on bone health.

We systematically searched PubMed, the Cochrane Library, and Embase for observational studies published up to November 5, 2024, using medical subject headings (MeSH) and keywords related to "osteoporosis, tea, and coffee." Statistical analyses were conducted using Stata software version 14.0. A fixed-effects model was used when heterogeneity was low (I 2 ≤ 50% and p > 0.1). A random-effects model was used for greater heterogeneity (I 2 > 50%). Publication bias was assessed using funnel plots and Egger's regression tests.

This meta-analysis included 14 observational studies comprising 562,838 participants published between 2008 and 2024. The pooled analysis showed that coffee consumption is significantly associated with a reduced risk of osteoporosis (odds ratio [OR] = 0.79, 95% confidence interval [CI]: 0.73-0.84, I 2 = 28.9%, p < 0.05). Tea consumption also demonstrated a protective effect, with a lower risk of osteoporosis (OR = 0.75, 95% CI: 0.62-0.91, I 2 = 80.4%, p < 0.05). Subgroup analysis revealed that high-frequency coffee consumption (more than one cup per day) was associated with a greater reduction in osteoporosis risk (OR = 0.83, 95% CI: 0.74-0.93, p = 0.001) compared to low-frequency consumption (less than one cup per day), which showed no statistically significant reduction (OR = 0.86, 95% CI: 0.68-1.07, p = 0.171). Similarly, high-frequency tea consumption (more than four times per week) exhibited a slightly stronger protective effect against osteoporosis compared to low-frequency consumption (OR = 0.82, 95% CI: 0.70-0.97, p = 0.02).

This meta-analysis suggests that long-term coffee and tea consumption is associated with a reduced risk of osteoporosis. Moreover, a higher frequency of consumption within a moderate range appeared to enhance the protective effect against osteoporosis.

https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42024612101, PROSPERO CRD42024612101.

Polymorphisms within the collagen 1 alpha 1 gene (COLIA1) have been shown to be associated with bone mineral density (BMD). This study aimed to test the hypothesis that COLIA1 polymorphisms are associated with bone loss and fragility fractures.

The study involved 809 postmenopausal women aged 60 years and above in the Dubbo Osteoporosis Epidemiology Study who had COLIA1 genotypes and at least two BMD measurements over a 30-year period. BMD at the lumbar spine (LSBMD) and femoral neck (FNBMD) was measured biennially by dual-energy X-ray absorptiometry (GE-Lunar Prodigy). Fragility fracture has been ascertained by X-ray reports between 1990 and 2020. The G-> T polymorphism at the Sp1-binding site in the COLIA1 gene (rs1800012) was determined by the PCR-based method, and coded as GG, GT, and TT.

Women homozygous for the minor allele (TT) tended to have greater bone loss (-0.72%/year) than those with GT (-0.58%/year) or GG (-0.56%/year) though the difference did not achieve statistical significance (P = 0.84). Women of the TT genotype were associated with a two-fold greater risk of any fracture (adjusted hazard ratio: 2.21; 95%CI 1.42-3.46) and almost fourfold greater risk of hip fracture (3.78; 1.83-7.82) than those with either GG or GT genotype.

Polymorphisms at the Sp1 site in the COLIA1 gene are associated with fracture risk, independent of bone loss.

Spinal cord injury (SCI) is associated with increased cardiovascular risks, and cardiovascular disease (CVD) remains a leading cause of death for individuals with SCI. Osteoporosis, a condition associated with SCI, has been linked to CVD. However, the cardiovascular risk profile of individuals with SCI with osteoporosis remains unclear.

We conducted a retrospective cohort study by using data from the TriNetX Research Network. We included adults with osteoporosis with or without a diagnosis of SCI between 2015 and 2020: case (SCI group, N = 7,308) and control (non-SCI group, N = 843,235) cohorts. Propensity score matching was performed to balance baseline characteristics between the cohorts (N = 7,296 in each group). A Cox regression model was employed to estimate the hazard ratio (HR) for the primary outcomes: the development of acute myocardial infarction (AMI), atrial fibrillation (AF), or heart failure (HF).

Individuals with SCI with osteoporosis have a significantly higher risk of cardiovascular events (HR: 1.15, 95 % confidence interval [CI]: 1.08-1.22)-including AMI (HR: 1.17 95 % CI: 1.02-1.33), AF (HR: 1.14, 95 % CI: 1.04-1.24), and HF (HR: 1.14, 95 % CI: 1.05-1.24)-than do those without SCI. Furthermore, mortality risk is higher in individuals with SCI, particularly those with pathological fracture. Subgroup analyses based on sex and age supported these findings.

The complex interplay between SCI, osteoporosis, and cardiovascular health underscores the requirement for comprehensive management strategies for individuals with SCI who also have osteoporosis.

Osteoporosis is a growing public health concern in aging populations such as Taiwan, where limited utilization of dual-energy X-ray absorptiometry (DXA) often leads to underdiagnosis and even delayed treatment. Therefore, we leveraged machine learning (ML) and aimed to develop a simple and easily accessible model that effectively identifies individuals at high risk of osteoporosis.

This retrospective analysis enrolled 5510 men aged ≥50 years and 4720 postmenopausal women who underwent DXA at the Kaohsiung Veterans General Hospital, with another cohort of 610 men and 523 women for validation. We developed separate models for men and women using decision trees, random forests, support vector machines, k-nearest neighbors, extreme gradient boosting, and artificial neural networks (ANNs) to predict osteoporosis. Furthermore, we compared each model with the traditional Osteoporosis Self-Assessment Tool for Asians (OSTA) model.

We identified age, height, weight, and BMI as variables for our prediction model and evaluated the model's performance using the area under the receiver operating characteristic curve (AUC). The ANN model significantly outperformed the OSTA model and all the other ML models for both men and women (AUC: 0.67 for men; 0.77 for women). The validation data for the ANN model showed similar AUCs for both men and women.

This study developed ML models to help identify individuals at high risk of osteoporosis in postmenopausal women and men aged ≥50 years in southern Taiwan. Our ML models, especially the ANN model, surpassed the OSTA model and consistently performed well across different populations.

Background/Objectives: Given the significant economic and social burden of osteoporosis, there is growing interest in developing an efficient alternative to the traditional dual-energy X-ray absorptiometry (DXA). Radiofrequency Echographic Multi Spectrometry (REMS) is an innovative, non-ionizing imaging technique that recently emerged as a viable tool to diagnose osteoporosis and estimate the fragility fracture risk. Nevertheless, its clinical use is still limited due to its novelty and continuing uncertainty of long-term performance. Methods: In order to evaluate the accuracy of the REMS, a systematic review of the English-language literature was conducted. Three databases were searched for relevant publications from 1 January 2015 until 1 December 2024 using the keyword combinations "(radiofrequency echographic multi spectrometry OR REMS) AND (dual-energy X-ray absorptiometry OR DXA)". The initial search yielded 602 candidate articles. After screening the titles and abstracts following the eligibility criteria, 17 publications remained for full-text evaluation. Results: The reviewed studies demonstrated strong diagnostic agreement between REMS and DXA. Additionally, REMS showed enhanced diagnostic capabilities in cases where lumbar bone mineral density measurements by DXA were impaired by artifacts such as vertebral fractures, deformities, osteoarthritis, or vascular calcifications. REMS exhibited excellent intra-operator repeatability and precision, comparable to or exceeding the reported performance of DXA. The fragility score (FS), a parameter reflecting bone quality and structural integrity, effectively discriminated between fractured and non-fractured patients. Moreover, REMS proved to be a radiation-free option for bone health monitoring in radiation-sensitive populations or patients requiring frequent imaging to assess fracture risk. Conclusions: This current study underscores the robustness of REMS as a reliable method for diagnosing and monitoring osteoporosis and evaluating bone fragility via the FS. It also identifies critical knowledge gaps and emphasizes the need for further prospective studies to validate and expand the clinical applications of REMS across diverse patient populations.

Introduction: Comparative studies on Hounsfield units (HU) and bone volume fraction (BVF%) for the demonstration of cancellous bone density in the entire spine and in the various intravertebral regions are rare. The aim of the present study was to determine HU in various segments and sectional planes (sagittal, axial, coronary) of the spine and their description in the context of bone density measurement on micro-CT, as well as the significance of the values for bone loss and fracture risk. Materials/Methods: The spines of 11 body donors were analyzed by means of high-resolution spiral CT and micro-CT. Vertebral deformities were identified on sagittal reformations and classified. Cancellous bone density in the individual vertebrae from C3 to L5, expressed in HU, was measured on CT images (in all 242 vertebral bodies). For this purpose, a manually positioned ROI was established in mid-vertebral cancellous bone in the axial, sagittal, and coronary planes. Using a Jamshidi® needle, we obtained 726 specimens from prepared vertebrae extracted from three quadrants (QI: right-sided edge, QII: central, QIII: left-sided edge) and analyzed these on a micro-CT device (SKYSCAN 1172, RJL Micro & Analytic GmbH, Germany). The study design with multiple measurements was reflected by a General Linear Model Repeated Measures. The model was adjusted to the bone density values of both procedures (HU, BVF%) in the viewed sectional planes and quadrants for 22 vertebrae, with the predictors gender and fracture status, controlled for age and body mass index (BMI). Analysis of variance provided estimations of density values and comparisons of several subgroups. Results: All spines were osteoporotic. Both procedures revealed a significant reduction in cancellous bone density from C3 to L5 (p ≤ 0.018). Gender (p = 0.002) and fracture status (p = 0.001) have an impact on bone density: men have higher bone density values than women; cases with fewer fractures also have higher bone density values. CT revealed both effects (p = 0.002 for each) with greater clarity. HU on CT measurements in the axial plane showed higher density values than in the sagittal or coronary planes. CT measurement profiles along the spine as well as along the individual profiles of the 11 body donors were independent of the measured quadrants, but the micro-CT measurements were not. Discussion: The craniocaudal reduction in bone density was demonstrated in different degrees of clarity by the two procedures. Likewise, the procedure-related visualization of differences in cancellous bone density between genders, fracture groups, sectional planes, and quadrants indicates the need for a better understanding of the advantages of each procedure for patient-oriented approaches to the diagnosis of osteoporosis. Future research should be focused on the determination of standard values and their clinical application for the prevention and treatment of osteoporosis.

The aim of this study was to determine in a prospective patient study the accuracy of areal bone mineral density (aBMD) measurements with spectral localizer radiographs obtained with a clinical photon-counting detector computed tomography (PCD-CT) scanner in comparison with dual-energy x-ray absorptiometry (DXA).

In this institutional review board-approved, prospective study, 41 patients (15 females, 26 males; mean age 61.3 years, age range 35-78 years) underwent PCD-CT of the abdomen with a spectral localizer radiograph (tube voltage 140 kVp, tube current 30 mA) and DXA within a median of 45 days. aBMD values were derived for lumbar vertebrae L1-L4 from both methods and were compared with linear regression, Pearson correlation, intraclass correlation coefficients (ICCs), and Bland-Altman plots. T-scores were calculated on a patient level and were compared between methods.

DXA and spectral localizer radiographs showed strong correlation in aBMD measurements (R = 0.97, P < 0.001) and patient level T-scores (R = 0.99, P < 0.001). There was a strong agreement between aBMD from both methods (ICC, 0.96; 95% CI, 0.94-0.97). Bland-Altman analysis revealed a very small mean difference in aBMD between methods (mean absolute error 0.019 g/cm2) with narrow limits of agreement (-0.083 g/cm2 to 0.121 g/cm2). Similarly, there were small differences in regard to the T-score (mean absolute error 0.156) with narrow limits of agreement (-0.422 to 0.734) between methods. ICCs indicated an excellent agreement between T-scores from DXA and spectral localizer radiographs (ICC, 0.98; 95% confidence interval, 0.95-0.99).

Our prospective patient study indicates that spectral localizer radiographs obtained with a clinical PCD-CT system enable accurate quantification of the lumbar bone areal mineral density. This opens up the opportunity for opportunistic screening of osteoporosis in patients who undergo CT for other indications.

This study evaluated the efficacy of teriparatide (TPTD) and alendronate (ALN) in mitigating bone loss, enhancing bone structure, and facilitating motor function recovery following spinal cord injury (SCI).

All the rats were allocated into four groups: a sham surgery group (SHAM group), a normal saline group (SCI + NS group), a TPTD treatment group after SCI (SCI + TPTD group), and an ALN treatment group after SCI (SCI + ALN group). The Basso, Beattie, and Bresnahan (BBB) scores and gait analyses were used to assess the motor abilities of rats following SCI and the effects of treatment. HE staining, Masson's trichrome staining, and LFB staining were performed to evaluate the extent of spinal cord tissue damage. Micro-CT was used to measure 12 bone-related parameters of the proximal tibia and create 3D images, and structural changes in the proximal tibial bone tissue were observed under a light microscope after HE staining.

After 12 weeks of treatment, the micro-CT data indicated that TPTD significantly increased key bone indicators, such as bone mineral density, after SCI (p < 0.01), whereas ALN did not significantly improve these indicators (p > 0.05). Compared with the SCI + NS group, the SCI + TPTD group presented significantly greater BBB scores and near-normal gait parameters (p < 0.05). Analyses of pathological sections revealed that TPTD significantly reduced the cavity area in the spinal cord after SCI, decreased the proportion of scar tissue, and increased the retention of neural myelin (p < 0.05). However, ALN had no significant effect on these indicators (p > 0.05).

TPTD was more effective than ALN at mitigating bone loss and promoting motor function recovery after SCI, and it demonstrated significant advantages in reducing spinal cord damage and improving tissue structure.

Population ageing in Africa is increasing healthcare demands. Hip fractures require multidisciplinary care and are considered an indicator condition for age-related health services. We aimed to estimate current hip fracture incidence in Zimbabwe, compare rates against other regional estimates and estimate future fracture numbers.

All hip fracture cases in adults aged ≥40 years, presenting to any hospital in Harare over 2 years, were identified. From this, age- and sex-specific hip fracture incidence rates per 100 000 person-years were estimated using 2022 Zimbabwean Census data and compared with South African and Botswanan estimates. Furthermore, using the United Nations population projections, future hip fracture numbers were estimated to 2052 for Zimbabwe.

In 2022, 1 83 312 women and 1 79 212 men aged ≥40 years were living in Harare (14.9% of the city's population). Over 2 years 243 hip fracture cases, 133 (54.7%) female, mean (SD) age 71.2 (15.9) years, were identified. Most presented to public hospitals (202 [83.1%]) and were fragility hip fractures (211 [86.8%]); high-impact trauma (eg, traffic accidents) was more common in younger men. Presentation delays of >2 weeks were common (37.4%). Incidence rates for adults aged ≥40 years in Harare (observed) and Zimbabwe (estimated) were 33.5 and 53.8/100 000 person-years, respectively. Over age 50, rates increased with age, with the highest rates seen in women aged ≥85 years (704/100 000 person-years). Age-standardised hip fracture incidence rates are broadly comparable between Zimbabwe, Botswana and Black South Africans in those aged 40-69 years; thereafter, rates in Zimbabwean women and men exceed those in Botswana and South Africa. Across Zimbabwe, the number of hip fractures occurring annually is expected to increase more than 2.5-fold from 1709 in 2022 to 4414 by 2052.

In Zimbabwe, most hip fractures in adults ≥50 years are fragility fractures, consistent with age-associated osteoporosis; incidence rates exceed those previously reported regionally. Demands on already challenged healthcare systems will increase.

Mendelian randomization is believed to attenuate the biases inherent in observational studies, yet a meta-analysis of Mendelian randomization studies in osteoporosis has not been conducted thus far. This study aims to evaluate the connection between potential causal factors and the risk of osteoporosis by synthesizing evidence from Mendelian randomization studies.

The databases PubMed, Web of Science, and Embase were systematically searched for Mendelian randomization studies investigating factors influencing osteoporosis up to May 2024. Meta-analyses were conducted to assess the associations between various potential pathogenic factors and osteoporosis using Mendelian Randomization studies. The quality of the study was evaluated according to the Strengthening the Reporting of Observational Studies in Epidemiology via Mendelian Randomization (STROBE-MR) guidelines.

A total of 706 potentially relevant articles were screened, resulting in the inclusion of 53 studies in the systematic review, of which 30 were eligible for the meta-analysis. The combined findings from these 30 studies revealed that rheumatoid arthritis, inflammatory bowel disease, sex hormone binding globulin, depression, non-alcoholic fatty liver disease, primary biliary cholangitis and asthma are associated with increased risk of osteoporosis, while basal metabolic rate and gut microbiota (NB1n) serves as a protective factor. However, the association between obesity, type 2 diabetes mellitus, metformin, ulcerative colitis, leisure sedentary behaviors, systemic lupus erythematosus, serum iron and osteoporosis was found to be nonsignificant.

In summary, our meta-analysis indicates that significant causal relationships with osteoporosis's onset and progression have been established for rheumatoid arthritis, inflammatory bowel disease, primary biliary cholangitis, non-alcoholic fatty liver disease, depression, sex hormone binding globulin, basal metabolic rate, gut microbiota (NB1n), and asthma.

https://www.crd.york.ac.uk/prospero/, identifier PROSPERO CRD42024540504.

The Beclin-1/Bcl-2 complex plays a pivotal role in regulating both autophagy and apoptosis in osteoblasts affected by osteoporosis. This study first investigates whether the Bushen Jianpi Huoxue Formula can enhance the cellular function of osteoblasts. Additionally, it initially explores the functional mechanism of Beclin-1/Bcl-2-related apoptosis.

Osteoblasts were isolated from the calvaria of three-day-old Sprague-Dawley female rats. The lyophilized power of the Bushen Jianpi Huoxue Formula was prepared from the following ingredients: Fructus Psoraleae, Epimedii Folium, Desertliving Cistanche, Prepared Rehmannia Radix, Radix paeoniae alba, Astragali Radix, Semen Cuscuta, Radix Salviae miltiorrhizae, Angelica sinensis, and Jujube. The primary components were detected by HPLC-MS. Beclin-1 overexpressed osteoblasts were constructed by transfection. Gene expression and protein level were examined by qRT-PCR and immunoblotting assay. Cell viability, apoptosis, and autophagy were assayed with CCK-8, flow cytometer, MDC staining, and Lyso-Tracker staining, respectively. Osteogenic differentiation was assayed by ALP staining, and mineralization by ARS staining. The complex of Beclin-1/Bcl-2 was detected by immunoprecipitation.

The results of this study indicated that the Bushen Jianpi Huoxue Formula could enhance both the proliferative activity, differentiation and mineralization of osteoblasts induced by Beclin-1 overexpression. This may be related to its role in activation of the WNT/β-CATENIN by increasing protein expression of WNT1 and β-CATENIN more than 1-fold. The formula effectively inhibited autophagy rate and apoptosis rate of osteoblasts by 50%. Furthermore, the formula was effective in attenuating endoplasmic reticulum stress by decreasing protein expression of AFT4, CHOP, eIF2α, and GRP78 more than 50%, which may play functions by suppressing the PERK signaling pathway. However, Mif treatment significantly weakened the effects of the formula.

Bushen Jianpi Huoxue Formula effectively enhanced the osteogenic activity by inhibiting Beclin-1-induced autophagy instead of the binding of Beclin-1 and Bcl-2. This underscores the formula's multifaceted role in promoting bone health and managing cellular stress, and offers novel insights into its therapeutic potential against osteoporosis.

As the global population ages, the incidence of age-related musculoskeletal diseases continues to increase, driven by numerous complex and poorly understood factors. WNT-1 inducible secreted protein 1 (WISP-1), a secreted matrix protein, plays a critical role in the growth and development of the musculoskeletal system, including chondrogenesis, osteogenesis, and myogenesis. Numerous in vivo and in vitro studies have demonstrated that WISP-1 is significantly upregulated in age-related musculoskeletal conditions, such as osteoarthritis, osteoporosis, and sarcopenia, suggesting its involvement in the pathogenesis of these diseases. Regulating WISP-1 expression holds promise as a therapeutic strategy for improving musculoskeletal function, potentially offering new avenues for treating age-related musculoskeletal diseases in clinical practice. This review highlights the signaling pathways associated with WISP-1, its physiological roles within the musculoskeletal system, and its therapeutic potential in treating age-related musculoskeletal disorders.

Serum uric acid (SUA) may play positive roles in diseases associated with oxidative stress, such as osteoporosis (OP). Nevertheless, the specific impact of SUA levels on both bone mineral density (BMD) and the risk of OP remains uncertain. Considering such information crucial for clinicians when making decisions about urate-lowering therapy (ULT), we sought to fill this gap by conducting dose-response meta-analyses.

PubMed, EMBASE, and Cochrane Library were searched for studies that met the inclusion criteria. Pooled standardized mean difference (SMD) for BMDs and the odds ratio (OR) for OP between the highest and lowest SUA categories as well as the nonlinear dose-response relationships were estimated.

Pooled SMDs indicate that participants in the highest category of SUA have greater BMDs at the lumbar spine (SMD = 0.37; 95% CI: 0.27, 0.46), femoral neck (SMD = 0.25; 95% CI: 0.21, 0.29), total hip (SMD = 0.34; 95% CI: 0.26, 0.42), and lower risk of OP (OR = 0.59, 95% CI: 0.52, 0.67) compared with the lowest. The nonlinear dose-response relationships were also observed. However, when the SUA level exceeded 6 mg/dL, the dose-response curve between SUA levels and the risk of OP tended to be flattened.

Nonlinear dose-response relationships were found that higher SUA levels are associated with greater BMDs and lower risk of OP. For patients receiving ULT, maintaining SUA level at around 6 mg/dL may be appropriate from the perspective of bone metabolism.