Search Results (198)

Background/Objectives: Osteoporosis remains a leading cause of morbidity in postmenopausal women, yet many high-risk individuals remain undiagnosed or untreated. This study aimed to assess the prevalence of osteoporosis and osteopenia, treatment patterns, and skeletal fragility indicators in a large cohort of postmenopausal women undergoing DXA screening. Methods: We analyzed data from 1669 postmenopausal women aged 40–89 years who underwent DXA evaluation. BMD status was categorized as normal, osteopenia, or osteoporosis. Treatment status was classified based on active antiosteoporotic therapy, calcium/vitamin D supplementation, hormonal therapy (historical use), or no treatment. Logistic regression models were used to explore independent predictors of osteoporosis and treatment uptake. Results: A total of 45.0% of women had osteoporosis and 43.5% had osteopenia. Despite this, 58.5% of the population, over half of women with osteoporosis, were not receiving any active pharmacologic treatment. Bisphosphonates were the most prescribed therapy (17.9%), followed by calcium/vitamin D supplements (20.6%). A prior history of fragility fractures and radiological bone lesions were significantly associated with lower BMD (p < 0.05). Historical hormone replacement therapy (HRT) use was not associated with current BMD (p = 0.699), but women with HRT use reported significantly fewer fractures (p < 0.001). In multivariate analysis, later menopause age and low BMD status predicted higher odds of receiving active treatment. Conclusions: Our findings highlight a substantial care gap in osteoporosis management, with treatment primarily initiated reactively in more severe cases. Improved screening and earlier intervention strategies are urgently needed to prevent fractures and reduce the long-term burden of osteoporosis. Full article

Background and Objectives: Emerging evidence indicates that individuals exposed to adverse childhood experiences (ACEs) face elevated risks for various chronic illnesses. However, the association between ACEs and osteoporosis risk remains underexplored, particularly regarding potential modifications by genetic susceptibility. This prospective cohort study aims to examine the relationship of ACEs with incident osteoporosis and investigate interactions with polygenic risk score (PRS). Materials and Methods: This study analyzed 124,789 UK Biobank participants initially free of osteoporosis. Cumulative ACE burden (emotional neglect, emotional abuse, physical neglect, physical abuse, sexual abuse) was ascertained through validated questionnaires. Multivariable-adjusted Cox proportional hazards models assessed osteoporosis risk during a median follow-up of 12.8 years. Moderation analysis examined genetic susceptibility interactions using a standardized PRS incorporating osteoporosis-related SNPs. Results: Among 2474 incident osteoporosis cases, cumulative ACEs showed dose–response associations with osteoporosis risk (adjusted hazard ratio [HR]_{per one-unit increase} = 1.07, 95% confidence interval [CI] 1.04–1.11; high ACEs [≥3 types] vs. none: HR = 1.26, 1.10–1.43). Specifically, emotional neglect (HR = 1.14, 1.04–1.25), emotional abuse (HR = 1.14, 1.03–1.27), physical abuse (HR = 1.17, 1.05–1.30), and sexual abuse (HR = 1.15, 1.01–1.31) demonstrated comparable effect sizes. Sex-stratified analysis revealed stronger associations in women. Joint exposure to high ACEs/high PRS tripled osteoporosis risk (HR = 3.04, 2.46–3.76 vs. low ACEs/low PRS) although G × E interaction was nonsignificant (P-interaction = 0.10). Conclusions: These results suggest that ACEs conferred incremental osteoporosis risk independent of genetic predisposition. These findings support the inclusion of ACE screening in osteoporosis prevention strategies and highlight the need for targeted bone health interventions for youth exposed to ACEs. Full article

Senescent cells secrete pro-inflammatory cytokines, collectively referred to as the senescence-associated secretory phenotype (SASP). Certain pro-inflammatory SASP factors are known to inhibit the differentiation of bone-forming osteoblast while promoting the differentiation of bone-resorbing osteoclasts, thereby causing osteoporosis. In this study, we screened cabozantinib, a tyrosine kinase inhibitor used to treat medullary thyroid cancer, for its ability to reduce doxorubicin-induced cellular senescence in both osteoblast and osteoclast progenitors. This non-cytotoxic agent suppressed the secretion of SASP factors (e.g., TNFα, IL1α, IL1β, IL6, and CCL2) from senescent osteoblast and osteoclast progenitors, resulting in enhanced osteoblast differentiation and reduced osteoclast differentiation. Furthermore, intraperitoneal administration of cabozantinib to age-related estrogen-deficient mice subjected to ovariectomy prevented bone loss without apparent side effects, increasing osteoblast numbers and reducing osteoclast numbers along the surface of the trabecular bone. In summary, our findings suggest that anti-aging cabozantinib has potential as a preventive anti-osteoporotic agent by promoting osteogenesis and inhibiting osteoclastogenesis through the repression of SASP. Full article

Objectives: The early detection of low bone mineral density (BMD) is essential for preventing osteoporosis and related complications. While dual-energy X-ray absorptiometry (DXA) remains the gold standard for diagnosis, its cost and limited availability restrict its use in large-scale screening. This study investigated whether raw bioelectrical impedance analysis (BIA) data combined with explainable machine learning (ML) models could accurately classify osteopenia in women aged 40 to 55. Methods: In a cross-sectional design, 138 women underwent same-day BIA and DXA assessments. Participants were categorized as osteopenic (T-score between −1.0 and −2.5; n = 33) or normal (T-score ≥ −1.0) based on DXA results. Overall, 24.1% of the sample were classified as osteopenic, and 32.85% were postmenopausal. Raw BIA outputs were used as input features, including impedance values, phase angles, and segmental tissue parameters. A sequential forward feature selection (SFFS) algorithm was employed to optimize input dimensionality. Four ML classifiers were trained using stratified five-fold cross-validation, and SHapley Additive exPlanations (SHAP) were applied to interpret feature contributions. Results: The neural network (NN) model achieved the highest classification accuracy (92.12%) using 34 selected features, including raw impedance measurements, derived body composition indices such as regional lean mass estimates and the edema index, as well as a limited number of categorical variables, including self-reported physical activity status. SHAP analysis identified muscle mass indices and fluid distribution metrics, features previously associated with bone health, as the most influential predictors in the current model. Other classifiers performed comparably but with lower precision or interpretability. Conclusions: ML models based on raw BIA data can classify osteopenia with high accuracy and clinical transparency. This approach provides a cost-effective and interpretable alternative for the early identification of individuals at risk for low BMD in resource-limited or primary care settings. Full article

Background: Duchenne muscular dystrophy (DMD) is a severe X-linked neuromuscular disorder caused by mutations in the DMD gene, leading to progressive muscle degeneration, loss of ambulation, and multi-systemic complications. Beyond its impact on mobility, DMD is associated with significant endocrine and metabolic dysfunctions that develop over time. Objective: To provide a comprehensive analysis of growth disturbances, endocrine dysfunctions, and metabolic complications in DMD including bone metabolism, considering the underlying mechanisms, clinical implications, and management strategies for daily clinical guidance. Methods: In this narrative review, an evaluation of the literature was conducted by searching the Medline database via the PubMed, Scopus, and Web of Science interfaces. Results: Growth retardation is a hallmark feature of DMD, with patients exhibiting significantly shorter stature compared to their healthy peers. This is exacerbated by long-term glucocorticoid therapy, which disrupts the growth hormone/insulin-like growth factor-1 (GH/IGF-1) axis and delays puberty. Obesity prevalence follows a biphasic trend, with increased risk in early disease stages due to reduced mobility and corticosteroid use, followed by a decline in body mass index (BMI) in later stages due to muscle wasting. Metabolic complications, including insulin resistance, altered lipid metabolism, and hepatic steatosis, further characterize disease burden. Osteoporosis and increased fracture risk, primarily due to reduced mechanical loading and glucocorticoid-induced bone resorption, are major concerns, needing early screening and intervention. The RANK/RANKL/OPG signaling pathway has emerged as a critical factor in bone deterioration, providing potential therapeutic targets for improving skeletal health. Conclusions: Growth and endocrine disorders in DMD are complex and multifactorial, requiring proactive monitoring and early intervention. Addressing these issues requires a multidisciplinary approach integrating endocrine, nutritional, and bone health management. Further research is essential to refine treatment strategies that mitigate growth and metabolic disturbances while preserving overall patient well-being. Full article

Background/Objectives: Osteoporosis is a widespread and chronic systemic bone disease that affects the jaws and teeth and, therefore, also dentistry. Osteoporosis can be diagnosed by different radiological methods. Dental cone beam computed tomography (CBCT) plays an important role in dentistry imaging. The aim of our retrospective pilot study was to find criteria in CBCT that point to the possible existence of osteoporosis. Methods: Pilot study. The hard palate thickness (HPT) of the patients was measured at a defined location in the CBCT. Additionally, the CBCT images were presented to a radiologist for visual assessment. Both results were compared with the DXA measurements—as the “gold standard”—and patient history. Results: We found a consistent correlation between the visual assessments using established radiological criteria, including the new criterion of hard palate thickness (HPT), and the diagnosis of normal or pathological bone density. Secondly, for the HPT measurement all “pathologic” CBCT had an HPT of ≤0.9 mm, and all normal patients had an HPT of ≥0.9 mm. Conclusions: Despite the small sample size, this CBCT pilot study showed a correlation between HPT and systemic bone disease. Therefore, as our main result, we found a new CBCT diagnostic criterion, which quickly and uncomplicatedly points to the possible existence of bone disease, especially osteoporosis. We propose HPT as a new criterion in the evaluation of CBCT images. A threshold of <0.9 mm may be indicative for osteoporosis or osteopenia, indicating a need for further evaluation. Full article

Objectives: The aim of this study was to develop AI-based predictive models to assess the risk of osteoporosis in postmenopausal women using panoramic radiographs (OPTs). Methods: A total of 301 panoramic radiographs (OPTs) from postmenopausal women were collected and labeled based on DXA-assessed bone mineral density. Of these, 245 OPTs from the Hospital of San Giovanni Rotondo were used for model training and internal testing, while 56 OPTs from the University of Parma served as an external validation set. A mandibular region of interest (ROI) was defined on each image. Predictive models were developed using classical radiomics, deep radiomics, and convolutional neural networks (CNNs), evaluated based on AUC, accuracy, sensitivity, and specificity. Results: Among the tested approaches, classical radiomics showed limited predictive ability (AUC = 0.514), whereas deep radiomics using DenseNet-121 features combined with logistic regression achieved the best performance in this group (AUC = 0.722). For end-to-end CNNs, ResNet-50 using a hybrid feature extraction strategy achieved the highest AUC in external validation (AUC = 0.786), with a sensitivity of 90.5%. While internal testing yielded high performance metrics, external validation revealed reduced generalizability, highlighting the challenges of translating AI models into clinical practice. Conclusions: AI-based models show potential for opportunistic osteoporosis screening from OPT images. Although the results are promising, particularly those obtained with deep radiomics and transfer learning strategies, further refinement and validation in larger and more diverse populations are essential before clinical application. These models could support the early, non-invasive identification of at-risk patients, complementing current diagnostic pathways. Full article

Background/Objectives: Semiquantitative grading of the vertebral body (SQ) is an easy screening method for vertebral body deformation. The validity of SQ as a risk factor and screening tool for incident osteoporotic fractures in the vertebral body (OF) was investigated using retrospective case-control data. Methods: Outpatients with osteoporosis who were followed up for ≥2 years as patients with osteoporosis were recruited. All of them were tested using X-ray images of the lateral thoracolumbar view and other tests at baseline. Patients were classified according to the SQ grade, and potential risk factors were compared for each SQ group. Cox regression analyses were conducted on the incident OFs. Statistical differences in the possible risk factors among the groups and the likelihood of incident OFs in the variables were examined. After propensity score matching (PSM) and inverse probability of treatment weighting (IPTW) for confounding factors, the possibility of incident OFs was compared between the SQ grade groups. Results: In the crude dataset, the probability of incident OF in SQ Grade 3 was significantly higher than in other grade groups. Using a Cox regression analysis in multivariate mode, SQ grade was the only statistically significant factor for incident OF. However, no significant differences were observed between PSM and IPTW. Conclusions: These results suggest that the SQ classification was inappropriate for predicting incident OFs. However, the grading showed a significantly higher risk than that available for screening. Full article

Celiac disease (CeD) is an autoimmune disorder that is triggered by gluten ingestion in genetically predisposed individuals. Untreated or poorly controlled CeD leads to various disease complications, such as malnutrition, osteoporosis, autoimmune diseases, or refractory celiac disease (RCD). Accumulating recent research has highlighted the association between CeD and the development of malignancies, particularly enteropathy-associated T-cell lymphoma (EATL) and small bowel carcinoma (SBC), which are neoplasms with extremely poor prognoses. Genetic alterations in the JAK1–STAT3 pathway and the high prevalence of microsatellite instability may be the main drivers of CeD-associated lymphomagenesis and small bowel oncogenesis and therefore could be an attractive therapeutic target to block cancer transformation. However, to date, the risk factors and exact mechanisms underlying malignancy development in patients with CeD remain unclear, and prospective cohort studies that include molecular profiling are needed. Moreover, current guidelines on the management of CeD do not provide standardized protocols for cancer surveillance—particularly regarding screening intervals, risk stratification, and monitoring strategies for high-risk patients such as those with RCD. This paper reviews the existing knowledge on malignancies in CeD, highlights diagnostic challenges, and discusses future perspectives on the early detection, monitoring, and treatment of CeD-associated neoplasms. Full article

Background: Considering the increasing interest in strategies to prevent osteoporosis and other bone-related conditions, it is relevant to critically assess the existing evidence on the potential benefits of phenolic compounds in wine on bone metabolism. Objectives: This integrative review aims to evaluate clinical and animal studies investigating the influence of wine consumption on bone mineral density (BMD). Methods: The search was conducted in PubMed, Scopus, and Embase databases until April 2025. The key question was: “Does wine consumption influence BMD?”. Results: After searching the identified databases, 108 studies were screened, and 7 were included in the final analysis. Conclusions: This review suggests a possible association between light to moderate wine consumption and favorable effects on BMD, particularly in the spine and femoral neck. However, these findings should be interpreted cautiously due to the predominance of observational studies. Future RCTs and systematic reviews must clarify wine’s potential role in bone health and explore non-alcoholic or low-alcohol wine alternatives with similar polyphenol content. Full article

Background: Oral bisphosphonates (BPs) are the standard therapy for osteoporosis and skeletal metastases, and exhibit anti-tumor properties in preclinical models. Observational studies assessing their impact on colorectal cancer (CRC) risk have yielded inconsistent results. We aimed to systematically review and meta-analyze the association between oral bisphosphonate use and CRC risk, applying a unified exposure definition. Methods: A systematic search was conducted in PubMed, Embase, and Scopus (January 1966–April 2025) to identify cohort, nested case–control, or population-based case–control studies reporting adjusted estimates of relative risk, odds ratios (ORs), or hazard ratios (HRs) for CRC among oral bisphosphonate users. Two reviewers independently screened studies, extracted data, and assessed quality using the Newcastle–Ottawa Scale. Random-effects meta-analyses pooled risk estimates for “any use” of bisphosphonates, with subgroup analyses by duration of use (<1, 1–3, >3 years). We assessed publication bias through Egger’s test and the trim-and-fill method. Results: A total of eight studies published between 2010 and 2020, including 29,169 CRC cases, fulfilled the inclusion criteria. Any bisphosphonate use was not significantly associated with CRC risk (pooled OR 0.97; 95% C.I., 0.90–1.03). However, 1–3 years of use conferred a protective effect (OR 0.86; 95% C.I., 0.73–0.99), as did >3 years (OR 0.91; 95% C.I., 0.85–0.97). Heterogeneity was moderate, and no significant publication bias was detected. Conclusions: While overall oral bisphosphonate exposure is not significantly linked to CRC risk, prolonged use (≥1 year) appears to reduce risk. Prospective studies and randomized trials are needed to confirm these chemo-preventive effects and guide clinical recommendations. Full article

Background: This institutional, register-based analysis aimed to evaluate the feasibility of using CT-based sacral Hounsfield units (HUs) for assessing bone density in pelvic fragility fractures and to explore their potential correlation with DEXA measurements and osteological laboratory diagnostics. Methods: Patients aged > 80 years, admitted between 2003 and 2019 with pelvic ring fractures, were analyzed in this retrospective single-center study. CT scans were evaluated according to the classification of fragility fractures of the pelvis (FFPs), which guided treatment decisions (conservative or surgical). The diagnosis of a fragility fracture was based on both fracture morphology and patient history, including the presence of low-energy trauma. Bone health was assessed using standardized laboratory diagnostics including serum calcium, phosphate, alkaline phosphatase, and 25(OH)-vitamin D, in addition to DEXA scans and CT-derived Hounsfield units. Vitamin D levels and bone density evaluations were analyzed to identify possible correlations among these factors and with fracture patterns. Results: A total of 456 patients (mean age 87.3 years, 79.6% female) were included. The CT-based FFP classification identified Type II as the most common fracture type (66.7%). Conservative treatment was the predominant approach (84.9%). Serum 25(OH)-vitamin D deficiency was observed in 62.7% of the patients, while osteopenia and osteoporosis were found in 34.3% and 46.5% of cases, respectively. HU values at S1 showed significant correlation with femoral neck T-scores, highlighting the utility of CT scans for bone density assessment. Conclusions: This study emphasizes the complementary roles of CT-derived HU values and DEXA T-scores in evaluating bone quality and fracture severity in geriatric patients with FFP. While DEXA remains the gold standard, CT imaging offers valuable early insights, supporting the timely initiation of osteoporosis therapy. Given the high prevalence of fragility fractures in this age group, early CT-based screening may facilitate earlier initiation of osteoporosis-specific therapy, including anabolic agents where indicated. Further research is needed to explore the relationships between vitamin D levels, bone density assessments, and fracture types. Full article

Osteoporosis (OP) is a prevalent metabolic bone disease, with several million cases of fractures resulting from osteoporosis worldwide each year. This phenomenon contributes to a substantial increase in direct medical expenditures and poses a considerable socioeconomic burden. Despite its prevalence, our understanding of the underlying mechanisms remains limited. Recent studies have demonstrated the involvement of serum glucocorticoid-regulated protein kinase 1 (SGK1) in multiple signaling pathways that regulate bone metabolism and its significant role in the development of osteoporosis. Therefore, it is of great significance to deeply explore the mechanism of SGK1 in osteoporosis and its therapeutic potential. In this paper, we present a comprehensive review of the structure and activation mechanism of SGK1, its biological function, the role of SGK1 in different types of osteoporosis, and the inhibitors of SGK1. The aim is to comprehensively assess the latest research progress with regards to SGK1’s role in osteoporosis, clarify its role in the regulation of bone metabolism and its potential as a therapeutic target, and lay the foundation for the development of novel therapeutic strategies and personalized treatment in the future. Furthermore, by thoroughly examining the interactions between SGK1 and other molecules or signaling pathways, potential biomarkers may be identified, thereby enhancing the efficacy of early screening and intervention for osteoporosis. Full article

Background/Objectives: Osteoporosis is an important health issue worldwide, and bisphosphonates are commonly prescribed for its treatment. However, certain complications can occur with long-term bisphosphonate therapy. The complication highlighted in this study was atypical femoral fractures, which are rare but significant. The orthopedic consensus identifies surgical intervention as the gold-standard treatment for atypical femoral fractures, typically involving intramedullary or cephalomedullary nailing (CMN). The aim was to monitor patients for a follow-up period exceeding six months after surgical fixation with a CMN, with the majority of patients being followed up for more than 18 months after their initial surgery. Methods: This single-center analysis was conducted on a mixed cohort comprising a total of 10 patients. The study was conducted between September and November 2024. The inclusion criterion was surgical treatment for bisphosphonate-related atypical femoral fractures (AFFs) between June 2022 and November 2024 at a Level 1 Trauma Center, Cork University Hospital in the Republic of Ireland. The patients were monitored through a structured follow-up protocol that extended beyond six months, with the majority of patients being followed up for over 18 months. Follow-up assessments were conducted at defined intervals, including key evaluations at 3 and 6 months and at their final review. Clinical parameters such as pain, functional recovery, and radiological healing were considered. Results: No significant functional difference was observed at follow-up between the patients who sustained displaced fractures and those who presented with undisplaced fractures. Sixty percent of the patients remained pain-free from the 3-month postoperative follow-up, and the same percentage continued to be pain-free at the final follow-up. Conclusions: Cephalomedullary nailing is a safe option for the treatment of atypical femoral fractures. Patients with a bisphosphonate atypical femoral fracture should undergo bilateral screening and should be followed up for a longer period than the standard post-traumatic care intervals that are in place for typical femoral fractures. Full article

Osteoporosis is a prevalent metabolic bone disorder characterized by decreased bone mineral density and increased fracture risk, particularly among aging populations. While conventional pharmacological treatments exist, they often have adverse effects, necessitating the search for alternative therapies. Resveratrol, a naturally occurring polyphenol, has gained significant attention for its potential osteoprotective properties through various molecular mechanisms. This systematic review aims to comprehensively analyze the molecular pathways through which resveratrol protects against osteoporosis. Using an advanced search strategy in the Scopus, PubMed, and Web of Science databases, we identified 513 potentially relevant articles. After title and abstract screening, followed by full-text review, 28 studies met the inclusion criteria. The selected studies comprised 14 in vitro studies, 8 mixed in vitro and in vivo studies, 6 in vivo studies, and 1 cross-sectional study in postmenopausal women. Our findings indicate that resveratrol exerts its osteoprotective effects by enhancing osteoblast differentiation through the activation of the Phosphoinositide 3-Kinase/Protein Kinase B (PI3K/Akt), Sirtuin 1 (SIRT1), AMP-Activated Protein Kinase (AMPK), and GATA Binding Protein 1 (GATA-1) pathways while simultaneously inhibiting osteoclastogenesis by suppressing Mitogen-Activated Protein Kinase (MAPK) and TNF Receptor-Associated Factor 6/Transforming Growth Factor-β-Activated Kinase 1 (TRAF6/TAK1). Additionally, resveratrol mitigates oxidative stress and inflammation-induced bone loss by activating the Hippo Signaling Pathway/Yes-Associated Protein (Hippo/YAP) and Nuclear Factor Erythroid 2-Related Factor 2 (NRF2) pathways and suppressing Reactive Oxygen Species/Hypoxia-Inducible Factor-1 Alpha (ROS/HIF-1α) and NADPH Oxidase 4/Nuclear Factor Kappa-Light-Chain-Enhancer of Activated B Cells (Nox4/NF-κB). Despite promising preclinical findings, the low bioavailability of resveratrol remains a significant challenge, highlighting the need for novel delivery strategies to improve its therapeutic potential. This review provides critical insights into the molecular mechanisms of resveratrol in bone health, supporting its potential as a natural alternative for osteoporosis prevention and treatment. Further clinical studies are required to validate its efficacy and establish optimal dosing strategies. Full article