Search Results (518)

Postmenopausal osteoporosis (PMOP) is characterized by excessive bone resorption caused by increased osteoclast activity. Estrogen remains an effective therapeutic option for preventing bone loss; however, its regulatory effects on osteoclast cytoskeletal remodeling have not been fully clarified. In this study, an ovariectomized (OVX) rat model and RANKL-induced RAW264.7 osteoclasts were used to investigate the role of the RhoA-Pkn3-c-Src signaling pathway in the anti-resorptive effects of estrogen. Bone microarchitecture was evaluated by micro-computed tomography, while osteoclast activity and pathway-related proteins were assessed using histological staining and immunofluorescence. In vitro, osteoclast differentiation, bone resorption, actin ring formation, and protein interactions were analyzed, with additional validation using a RhoA agonist. Estrogen treatment markedly alleviated OVX-induced bone loss, reduced osteoclast number and activity, and improved trabecular bone microarchitecture. These changes were accompanied by decreased expression of RhoA, Pkn3, c-Src, and Pyk2 in osteoclasts. Consistently, estrogen suppressed RANKL-induced osteoclast differentiation, bone resorption, and cytoskeletal remodeling in vitro, whereas activation of RhoA partially attenuated these effects. Collectively, these findings suggest that the protective effects of estrogen against osteoclast-mediated bone resorption are associated with modulation of the RhoA-Pkn3-c-Src signaling pathway, providing additional insight into the mechanisms underlying PMOP. Full article

Background: Each year, hundreds of thousands of geriatric patients suffer proximal femur fractures, which often result in irreversible functional decline. Although anti-osteoporotic medications have been shown to reduce the incidence of fragility fractures, the effects of pharmacotherapy on fracture injury patterns, postoperative ambulatory capacity, and survival outcomes are not yet fully understood. Methods: We conducted a retrospective cohort study using the AltersTraumaRegister DGU ^® (ATR-DGU), a multicenter prospective registry spanning 196 certified geriatric trauma centers in Germany, Austria, and Switzerland (2016 through 2024). We included patients aged 70 years or older with isolated, surgically treated proximal femur fractures and stratified them by documented use of osteoporosis medication before the index fracture (OM group) versus no pre-fracture therapy (no-OM group). Primary endpoints were mortality during the acute hospital stay and at 120-day follow-up, as well as walking ability—defined as any functional ambulation versus none—at 7 and 120 days postoperatively. The main secondary endpoint was fracture morphology. We fitted multivariable logistic and linear regression models adjusted for age, sex, ASA classification, and anticoagulation; walking-ability models were additionally adjusted for pre-fracture ambulatory status. Results: Of 70,386 patients (mean age, 84.4 years; 70.4% female), 15,771 (22.4%) were receiving osteoporosis medication prior to the index fracture. Patients in the OM group were frailer with worse ASA Scores (80.3% vs. 72.5% with an ASA ≥3) and lower ambulation (62.5% vs. 50.4% requiring at least two crutches or not able to ambulate out of the home environment). Patients in the OM group had a 19% higher chance of sustaining a trochanteric versus a femoral neck fracture than patients in the no-OM group (51.9% vs. 46.8%; adjusted odds ratio 1.19; 95% CI, 1.15 to 1.24; p < 0.001). Pre-existing therapy showed no association with mortality during the acute hospital stay (adjusted OR, 0.93; 95% CI, 0.86 to 1.01; p = 0.098) or with walking ability at 7 days (adjusted OR, 1.03; 95% CI, 0.98 to 1.09; p = 0.198). At the 120-day follow-up (n = 19,544 in the adjusted model follow-up cohort), slightly higher odds of death were observed in the frailer OM group (adjusted OR, 1.12; 95% CI, 1.01 to 1.25; p = 0.04), though the lower confidence bound approached unity. A trend toward improved ambulation was seen in the OM group at 120-day follow-up (adjusted OR, 1.11; 95% CI, 0.99 to 1.25; p = 0.074). Conclusions: Pre-existing osteoporosis therapy was associated with lower odds of femoral neck versus trochanteric fracture patterns. A trend toward improved ambulation accompanied a slightly increased risk of mortality in patients with pre-existing osteoporosis therapy at 120-day follow-up, although this must be weighed against substantial loss to follow-up and residual confounding. More research is needed to understand the effects of anti-osteoporosis medications on patients who do suffer hip fractures despite osteoporotic therapy. Full article

Background: Osteoporosis is a multifactorial skeletal disorder characterized by reduced bone mass, impaired bone remodeling, and an increased risk of fractures, particularly under estrogen-deficient conditions. Artocarpus integer (Thunb.) Merr. contains prenylated flavonoids and chalcone derivatives with diverse biological activities; however, its anti-osteoporotic potential remains largely unexplored. This study investigated the phytochemical composition, molecular mechanisms, and anti-osteoporotic effects of A. integer leaf extract in an ovariectomized (OVX) rat model. Methods: Phytochemical profiling was performed using liquid chromatography–high-resolution mass spectrometry (LC–HRMS). Network pharmacology was employed to identify potential osteoporosis-related targets and signaling pathways. The anti-osteoporotic activity of the extract was evaluated in OVX rats through physiological and biochemical assessments, including body weight gain, uterine weight, serum biomarkers, femoral calcium content, and RT-PCR analysis of genes associated with osteogenesis, osteoclastogenesis, and estrogen signaling. Results: LC–HRMS analysis identified several bioactive compounds, including isobavachalcone, artocarpesin, morachalcone A, genistein, apigenin, luteolin, naringenin, catechin derivatives, and mangiferin. Network pharmacology revealed 96 overlapping targets between A. integer phytochemicals and osteoporosis-related genes, highlighting pathways involved in estrogen signaling, PI3K–Akt signaling, osteoclast differentiation, inflammation, and metabolic regulation. In vivo, OVX rats exhibited increased body weight gain, uterine atrophy, elevated leptin levels, reduced adiponectin concentrations, and decreased femoral calcium content. Treatment with A. integer attenuated OVX-induced metabolic alterations, improved adipokine profiles, and increased femoral calcium content, particularly in the medium-dose group. RT-PCR analysis demonstrated the upregulation of the osteogenic markers Runx2 and Osx, together with the downregulation of the osteoclastogenic markers TRAP. Conclusions: Artocarpus integer leaf extract exhibited promising anti-osteoporotic activity through the coordinated regulation of osteogenesis, osteoclastogenesis, estrogen-related signaling, and bone mineral preservation. These findings support the potential development of A. integer as a nutraceutical candidate for the prevention or management of postmenopausal osteoporosis. Full article

Background: Whether routinely available laboratory measures are associated with longitudinal bone mineral density (BMD) change in clinical practice remains uncertain, particularly when treatment exposure and other major skeletal determinants are incompletely recorded. This study examined BMD trajectories and incident osteoporosis in a Saudi dual-energy X-ray absorptiometry (DXA) cohort. Anti-osteoporosis therapy, glucocorticoid exposure and menopausal status were unavailable, limiting causal interpretation. Methods: This retrospective longitudinal cohort included DXA examinations performed at King Saud University Medical City (KSUMC), Riyadh, from 2016 to 2021. The trajectory analysis comprised 2147 patients with at least two scans and a minimum one-year interval. Diagnostic category was based on the lowest T-score across the lumbar spine, bilateral femoral necks and distal radius. Twenty linear mixed-effects (LME) models evaluated time-by-biomarker interactions with Benjamini–Hochberg correction. Cox proportional hazards (PH) regression was the primary analysis of incident osteoporosis among 789 patients without osteoporosis at baseline. Results: During 2045 person-years of observation, 107 patients developed osteoporosis (5.2 events per 100 person-years). No event occurred among 124 patients with normal baseline BMD, compared with 107 events among 665 patients with baseline osteopenia (log-rank p < 0.001). In the complete-case Cox model (n = 384; 53 events; C-index = 0.679), baseline osteopenia had a hazard ratio (HR) of 3.12 (95% Confidence interval (CI) 0.89–10.97; p = 0.076); no modelled covariate reached statistical significance. None of the 20 time-by-biomarker interactions remained significant after multiplicity correction (smallest q = 0.214). Four nominal terms with raw p < 0.10 were below the measurement-based clinical threshold and were compatible with chance variation. Conclusions: No routinely measured biomarker demonstrated clinical utility for identifying BMD trajectory in this cohort. Baseline DXA category separated the observed progression pattern, although this partly reflects the distance from the diagnostic threshold and should not be interpreted as a validated prediction model. The principal contribution is a carefully characterised null result. Prospective studies with explicit treatment tracking and repeated bone-turnover measurements are required for confirmation. Full article

Bone remodeling is a dynamic and tightly regulated process that maintains skeletal homeostasis through a balance between bone formation by osteoblasts and bone resorption by osteoclasts. Disruption of this balance contributes to the development of bone-related disorders, particularly osteopenia, osteoporosis and osteogenesis imperfecta, which weaken, deform, or cause fractures. Increasing evidence indicates that oxidative stress and chronic inflammation impair osteoblast functions while promoting osteoclast differentiation and activity. Heme oxygenase-1 (HO-1) is a stress-inducible enzyme with cytoprotective, antioxidant, and anti-inflammatory properties. Besides its primary role in cellular defense against oxidative stress and inflammatory damage, HO-1 has been shown to be involved in both osteoblast differentiation and osteoclastogenesis. Through its interaction with key regulatory systems, including the receptor activator of nuclear factor κB (RANK)–receptor activator of nuclear factor κB ligand (RANKL)–osteoprotegerin axis and redox-sensitive signaling pathways, HO-1 contributes to maintenance of optimal bone remodeling. The enzyme also plays a role in modulating metabolic processes in the bone. This review highlights the role of HO-1 in bone formation, bone resorption, and related pathophysiologic conditions. Furthermore, the therapeutic potential of HO-1 as a target for bone disorders is discussed. Full article

Excessive osteoclast formation is a key contributor to pathological bone loss in disorders such as osteoporosis and rheumatoid arthritis. Asarinin, a natural lignan, has not previously been examined in the context of osteoclast differentiation. Here, we investigated the anti-osteoclastogenic effects of asarinin using RANKL-stimulated RAW264.7 cells. Asarinin significantly suppressed TRAP-positive multinucleated osteoclast formation. Mechanistically, asarinin selectively inhibited RANKL-induced phosphorylation of p38 and ERK MAPKs, leading to reduced c-Fos expression and inhibition of NFATc1 activation. In addition, asarinin disrupted actin ring formation in mature osteoclasts. Collectively, these findings identify asarinin as a pathway-selective inhibitor of osteoclast differentiation, acting through a mechanism consistent with modulation of the p38/ERK–c-Fos–NFATc1 signaling cascade while sparing parallel signaling pathways. Full article

Background: Aging of the population increases the incidence of osteoporosis with atlantoaxial instability. Poor bone microarchitecture causes high rates of screw loosening, implant failure, and revision surgery, which remains a critical challenge for upper cervical surgery. Traditional atlantoaxial fixation is less effective in those with low bone mineral density, while thoracolumbar screw augmentation techniques are limited by the complex craniocervical anatomy. Methods: This review systematically summarizes the mainstream screw optimization strategies from a bioengineering perspective, including low-modulus alloy substrate modification, bionic threaded structural design, bioactive surface coatings, expandable screws, and cement-augmented cannulated screws. We compare the biomechanical anchorage performance, osteogenic capacity, and clinical complications of each technique. Results: Low-elastic-modulus titanium alloys reduce stress shielding; gradient multi-thread, bicortical, and CBT trajectory designs significantly improve anti-pullout stability; HA, tantalum, and composite extracellular matrix coatings promote osseointegration; and expandable screws and fenestrated cement screws can achieve reliable reinforcement. However, a narrow atlantoaxial space restricts the application of cement augmentation and expandable implants, and long-term, large-sample clinical evidence for the efficacy of novel screws is insufficient. Conclusion: Patient-specific porous degradable screws, which combine 3D-printed biomaterials, gradient alloys, and sustained-release bioactive coatings, represent a promising future research direction. This review provides theoretical support for the development of atlantoaxial internal fixation devices targeting elderly osteoporotic patients. Full article

Osteosarcopenia—defined as the coexistence of sarcopenia and osteoporosis—is increasingly recognized as a clinically important geriatric syndrome associated with falls, fractures, frailty, disability, and mortality. Beyond the simple coexistence of bone and muscle loss, emerging data suggest that osteosarcopenia may reflect systemic dysregulation of the bone–muscle–immune–metabolic network. In this narrative review, we synthesize evidence linking inflammaging, immune-cell polarization, mitochondrial dysfunction, nutrient metabolic dyshomeostasis, and gut-derived metabolites to the pathogenesis of osteosarcopenia. Multiple pathological processes—including chronic low-grade inflammation, Th17/Treg imbalance, macrophage polarization, oxidative stress, impaired mitophagy, insulin resistance, ectopic fat accumulation, and altered microbial metabolites—may converge to disrupt bone–muscle crosstalk. Notably, direct evidence from osteosarcopenic populations remains limited, and many mechanistic insights are extrapolated from osteoporosis, sarcopenia, and aging models. We further discuss current and emerging therapeutic strategies, including exercise, nutritional interventions, anti-osteoporotic agents, metabolic modulators, mitochondrial-targeted therapies, and gut-directed approaches. Longitudinal cohorts, multi-omics studies, and randomized controlled trials are urgently required to validate immunometabolic biomarkers and develop integrated interventions for osteosarcopenia. Full article

Objective: This study aimed to systematically evaluate risk prediction models for new vertebral fracture after vertebral augmentation in elderly patients with osteoporotic vertebral compression fractures (OVCFs) and to summarize their modeling methods, predictors, predictive performance, and methodological quality. Methods: This systematic review was prospectively registered in the Open Science Framework (OSF; DOI:10.17605/OSF.IO/S259R). PubMed, Embase, Web of Science, Cochrane Library, CNKI, Wanfang, and VIP were searched from inception to January 2026. Studies reporting model development, internal validation, external validation, or model updating for prediction models of new vertebral fracture after vertebral augmentation in elderly patients with OVCFs were included. Two reviewers independently screened the literature and extracted data. Methodological quality and risk of bias were assessed using the Prediction Model Risk of Bias Assessment Tool (PROBAST). Results: A total of 24 studies containing 29 prediction models were included, all of which were conducted in China. The incidence of new vertebral fracture after vertebral augmentation ranged from 10.60% to 38.08%. Logistic regression and nomograms were the most common modeling method and presentation format, respectively. The AUC values of the models ranged from 0.648 to 0.990. Only three studies conducted external validation. Bone mineral density, bone cement leakage, and anti-osteoporosis treatment were the leading predictive factors. PROBAST assessment confirmed that all included studies had a high overall risk of bias, with the statistical analysis domain being the most problematic area. Fourteen studies reported decision curve analysis (DCA), suggesting potential clinical utility within the development datasets. However, no study evaluated real-world clinical impact, and the overall high risk of bias and limited external validation substantially restrict confidence in clinical applicability. Conclusions: Although several models demonstrated moderate-to-good discrimination performance, methodological limitations, high overall risk of bias, and insufficient external validation substantially limit confidence in their clinical applicability. These models are not reliable for routine clinical use and should currently be regarded as research tools. Standardized study design, bias control, adequate external validation, and optimized statistical strategies are urgently required to establish credible prediction models for clinical practice. Full article

Osteoporosis is a progressive skeletal disorder characterized by decreased bone strength and an increased risk of fractures. It presents a high global prevalence, thus imposing a significant clinical and economic burden. This narrative review includes current evidence on the role of combined calcium and vitamin D supplementation in the management and prevention of osteoporosis, as well as its effect on reducing fracture risk and maintaining bone mineral density. It aims to provide an overview of osteoporosis pathophysiology, the importance of adequate calcium levels and 25-hydroxyvitamin D concentrations and the prevalence of their deficiencies. The review examines the evidence supporting combined supplementation and its importance in patients receiving anti-osteoporotic pharmacological therapies. Current clinical guidelines and consensus statements, along with their recommendations for dosing, formulation, and monitoring of calcium and vitamin D supplements, are included. Barriers to the effective implementation, gaps in clinical practice, patient adherence, and primary care challenges are discussed. Ultimately, this review examines the cost-effectiveness of supplementation and the areas for improvement in real-world evidence and research in the field of osteoporosis. This work aims to provide clinicians and healthcare professionals with an updated, evidence-based framework for optimizing calcium and vitamin D supplementation in the care of patients with osteoporosis. Full article

This 24-month retrospective, exploratory observational study evaluated longitudinal spinal morphometric changes in 128 postmenopausal women with osteoporosis receiving anabolic therapy (n = 30) or non-anabolic anti-osteoporotic therapy (n = 98). Lumbar BMD, lower lumbar vertebral heights, disc height indices, and sagittal spinopelvic parameters were assessed at baseline and 24 months. Unweighted and baseline-severity adjusted linear regression models were used; IPTW and overlap-weighted analyses were performed as sensitivity analyses. Both groups showed significant lumbar BMD improvement. Patients receiving anabolic therapy were older and had lower baseline lumbar BMD and greater thoracolumbar kyphosis, indicating confounding by indication. In unweighted models, anabolic therapy was associated with greater L5 anterior height loss and L5/S1 disc height index preservation; however, these associations were attenuated after adjustment for baseline lumbar BMD and thoracolumbar kyphosis and were not consistently supported by propensity-score-weighted sensitivity analyses. Pelvic incidence showed more consistent level-specific associations, being negatively associated with L5 anterior height change and positively associated with L5/S1 disc height index preservation. Given substantial confounding by indication and limited treatment-group overlap, treatment-related associations should not be interpreted causally. These findings suggest that spinopelvic morphology may influence lower lumbar structural adaptation, whereas treatment-related morphometric findings remain exploratory and require confirmation. Full article

The genus Epimedium L. comprises a group of perennial herbs widely distributed across East Asia, with five representative species that include Epimedium grandiflorum C. Morren, Epimedium brevicornu Maxim., Epimedium sagittatum (Sieb. et Zucc.) Maxim., Epimedium koreanum Nakai. and Epimedium pubescens Maxim. For centuries, these species have been used in traditional Chinese medicine for their aphrodisiac, anti-osteoporotic and estrogen-like properties in the treatment of erectile dysfunction, osteoporosis, rheumatoid arthritis and menopausal symptoms. The aim of this review is to present an extensive and updated synthesis of the phytochemistry, biological activities and therapeutic properties of these five species by examining the relationship between the phytochemical composition and their pharmacological properties. Phytochemical analyses indicate that Epimedium spp. are defined by their significant content of prenylated flavonol glycosides, including icariin, icaritin, icariside, baohuoside and epimedin A-C. Recent studies have confirmed that these compounds are responsible for the genus’ therapeutic potential. They possess a variety of effects, ranging from aphrodisiac and antioxidant properties to anti-inflammatory and immunomodulatory activities, as well as neuroprotective, cardioprotective and anticancer benefits. Although preclinical findings are increasingly compelling, robust clinical evidence is still lacking for all five species. Taken together, the data summarized here position Epimedium spp. as a valuable source of bioactive prenylated flavonoids, while underscoring that standardized methodologies and rigorous clinical trials are essential to translate this potential into validated therapeutic applications. Full article

Background: The objective of this study was to compare the effects of bisphosphonates and denosumab on sarcopenia-related parameters, contributing to a better understanding of osteosarcopenia management. Methods: This cross-sectional, comparative study assessed physical performance, muscle strength, muscle mass, and sarcopenia category in postmenopausal women aged 65 to 80 years with osteoporosis who were receiving either bisphosphonates or denosumab. Additional groups consisted of untreated osteoporotic patients and controls without osteoporosis (n = 50 per group). Muscle mass was assessed using bioelectrical impedance analysis, and the classification of sarcopenia was assessed according to the EWGSOP2 criteria. Results: Among the osteoporotic groups, the 4 m walking speed, 5-chair stand test, and timed up-and-go performance did not differ significantly, although denosumab-treated patients had numerically shorter completion times. Nondominant handgrip strength was the only grip parameter showing a significant between-group difference (p = 0.026), mainly due to higher values in denosumab-treated patients than in untreated osteoporotic patients; dominant and maximum handgrip strength were comparable. Skeletal muscle mass was higher in the denosumab group than in both the bisphosphonate-treated and untreated osteoporosis groups (p = 0.045), whereas ALM, ASM, and the ASMI did not differ significantly. No statistically significant between-group differences were observed in SARC-F scores or sarcopenia classifications. Controls had significantly higher odds of sarcopenia absence compared with untreated osteoporotic patients, and treatment duration was not correlated with sarcopenia-related parameters. Conclusions: These findings suggest a favorable but limited association between denosumab treatment and selected muscle-related parameters. Prospective longitudinal studies are needed to determine whether anti-osteoporotic therapies influence osteosarcopenia. Full article

Background: COVID-19-related mobility restrictions may have affected physical activity and post-fracture care in older adults. This study compared outcomes before and after age-based mobility restrictions, focusing on reported activity, documented combined postoperative physiotherapy and anti-osteoporotic pharmacologic treatment, and secondary fragility fractures. Methods: This retrospective single-center pre–post study included patients aged 65 years or older who underwent bipolar hemiarthroplasty for low-energy osteoporotic femoral neck fracture. Patients treated during the year before restrictions were compared with those treated during the post-restriction year. Outcomes included reported pre-fracture activity category, all-cause mortality, mobility among survivors, documented combined postoperative physiotherapy and anti-osteoporotic pharmacologic treatment, and secondary fragility fractures. Results: The pre-pandemic and post-restriction groups included 65 and 122 patients, respectively. Regular outdoor walking/activity before fracture was less frequent in the post-restriction group than in the pre-pandemic group (45.1% vs. 72.3%; p < 0.001), whereas home-limited activity was more frequent (54.9% vs. 27.7%). All-cause mortality during follow-up was 24.6% and 29.5%, respectively (p = 0.499). Mobility among survivors did not differ significantly (p = 0.832). Among survivors, documented combined postoperative physiotherapy and anti-osteoporotic pharmacologic treatment was uncommon: 14.3% and 17.4%, respectively (p = 0.809). Secondary fragility fractures were recorded only in the post-restriction group (8/86 survivors, 9.3%; p = 0.051). Conclusions: In this retrospective pre–post comparison, the post-restriction group showed a lower proportion of reported outdoor activity, while documented combined postoperative physiotherapy and anti-osteoporotic pharmacologic treatment remained uncommon among survivors. Secondary fragility fractures were observed only in the post-restriction group and should be interpreted with caution, given the exploratory design and limited number of events. Structured rehabilitation referral, osteoporosis treatment, fall-prevention strategies, and follow-up pathways remain important components of post-fracture care following femoral neck fracture. Full article

Background and Aims: The “quantity” of bone can be evaluated by dual-energy X-ray absorptiometry (DXA) scans, but not its “quality. We aim to study the clinical relevance of urinary-N-terminal telopeptide (NTx) in a retrospective exploratory study. Patients and Methods: The medical records of patients with osteoporosis, osteopenia with or without fractures, and with available urinary NTx were retrospectively reviewed; those on anti-osteoporotic medication before the start of the study were excluded. In all NTx levels, bone-specific alkaline phosphatase (BSAP), parathormone, serum calcium, and vitamin D were measured. In all cases, a recent DXA scan and fracture risk assessment (FRAX) had been performed. Appropriate statistics were applied using SPSS. 15. Results: Included were 93 patients (17.2% males); thirty-one (33.33%) had osteoporosis, 56 (60.21%) osteopenia, whereas 36 (38.7%) had prior or existing fractures. Older participants had lower NTx levels, and females had higher NTx levels, albeit NS. A negative correlation was found between the T-score of the left hip and NTx levels (p = 0.015) but not of the right hip or lumbar spine. In multivariate analysis, NTx levels (p = 0.013) and FRAX (p = 0.001) were significantly associated with fractures. Patients with osteoporosis had higher NTx levels when compared to patients with osteopenia (p = 0.015). NTx at a cut-off value of 207.4 showed a sensitivity of 80.6% and a specificity of 56.1% for the diagnosis of previous fracture with an area under the curve (AUC) of 0.72 (95% CI: 0.61, 0.83). Conclusions: Elevated NTx levels were significantly associated with existing or prior fractures. Combining DXA scan and FRAX, with NTx testing, may provide a comprehensive approach to osteoporosis assessment and treatment. Further prospective studies are warranted to validate its clinical utility. Full article