Search Results (744)

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

Background: Osteodysplastic syndromes comprise a very diverse group of clinically and genetically heterogeneous disorders characterized by defects in bone and connective tissue development, as well as in bone density. Here, we report the case of a 48-year-old female with a complex medical history characterized by bone dysplasia, hyperostosis, and partial tooth agenesis. Methods: Genetic testing was performed using WES analysis and Sanger sequencing. Molecular modeling analysis and dynamics simulation explored the impact of detected pathogenic variants. Results: The genetic analysis detected multiple pathogenic variants in genes CREB3L1, SLCO2A1, SFRP4, LRP5, and LRP6, each of which has been associated with rare osteodysplastic syndromes. The patient was homozygous for the same rare alleles associated with three of the identified autosomal recessive disorders osteogenesis imperfecta type XVI, primary hypertrophic osteoarthropathy, and metaphyseal dysplasia Pyle type. She also had a variant linked to autosomal dominant endosteal hyperostosis and a variant previously associated with increased risk of osteoporosis and bone fractures. Two of the detected variants are predicted to cause abnormal splicing, while molecular modeling and dynamics simulations analysis suggest that the other three variants probably confer altered local secondary structure and flexibility that may have functionally devastating consequences. Conclusions: Our case highlights the rare coexistence of multiple osteodysplastic syndromes in a single patient that may complicate differential diagnosis. Furthermore, this case emphasizes the necessity for early genetic investigation of such complex cases with overlying phenotypic traits, followed by genetic counseling, facilitating orchestration of clinical interventions and allowing prevention and/or prompt management of manifestations. 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

Tea is one of the most consumed beverages in the world, belonging to the category of compounds known as tannins and flavonoids. One of the polyphenols found in large amounts in green tea leaves (Camellia sinensis) is epigallocatechin-3-O-gallate (EGCG). Though EGCG has shown some pharmacological effects, to date, it has not been utilised as a therapeutic agent. This is attributed to the fact that EGCG lacks adequate stability, and it is known to degrade through epimerization or auto-oxidation processes, especially when it is exposed to light, temperature fluctuations, some pH values, or the presence of oxygen. Consuming green tea with EGCG can alleviate the effects of bone diseases, such as osteoporosis, and support faster bone regeneration in the case of fractures. Therefore, this review focuses on the current state of research, highlighting the effects of EGCG on bone biology, such as enhancing osteoblast differentiation, promoting bone mineralisation, improving bone microarchitecture, and inhibiting osteoclastogenesis through the modulation of the RANK/RANKL/OPG pathway. Additionally, EGCG exerts antioxidant, anti-inflammatory, and dose-dependent effects on bone cells. It also downregulates inflammatory markers (TNF-α, IL-1β, and COX-2) and reduces oxidative stress via the inhibition of reactive oxygen species generation and the activation of protective signalling pathways (e.g., MAPK and NF-κB). Studies in animal models confirm that EGCG supplementation leads to increased bone mass and strength. These findings collectively support the further exploration of EGCG as an adjunct in the treatment and prevention of metabolic bone diseases. The authors aim to present the relationship between EGCG and bone health, highlighting issues for future research and clinical applications. Full article

Background/Objectives: Vertebral fractures (VFs) are a global health issue caused by traumatic or pathological factors that compromise spinal integrity. The burden of VFs is increasing, particularly in older adults. Methods: Data from the Global Burden of Disease 2021 were analyzed to estimate the prevalence, mortality, and years lived with disability due to VFs from 1990 to 2021. Estimates were stratified according to age, sex, and region. Bayesian meta-regression models were used to generate age-standardized rates, and projections for 2050 were calculated using demographic trends and the sociodemographic index. Das Gupta’s decomposition assessed the relative contributions of population growth, aging, and prevalence changes to future case numbers. Results: In 2021, approximately 5.37 million people (95% Uncertainty Interval [UI]: 4.70–6.20 million) experienced VFs globally, with an age-standardized prevalence of 65 per 100,000. Although the rates have declined slightly since 1990, the absolute burden has increased owing to population aging. VF prevalence was the highest in Eastern and Western Europe and in high-income regions. Males had higher VF rates until 70 years of age, after which females surpassed them, reflecting postmenopausal osteoporosis. Falls and road injuries were the leading causes of VF. By 2050, the number of VF cases is expected to increase to 8.01 million (95% UI: 6.57–8.64 million). Conclusions: While the age-standardized VF rates have decreased slightly, the global burden continues to increase. Targeted strategies for the early diagnosis, osteoporosis management, and fall prevention are necessary to reduce the impact of VFs. Full article

Osteoporosis and sarcopenia are two aspects of the geriatric syndrome that frequently occur together and affect one another in a condition referred to as osteosarcopenia. Preventive and treatment options for osteosarcopenia exist but are mainly focused on the treatment of osteoporosis, as there is still no FDA-approved treatment for sarcopenia. Drugs for osteoporosis include antiresorptive and anabolic drugs and hormonal replacement therapies and are prescribed based on age, BMD and other patient characteristics, which, however, do not include the possible co-existence of sarcopenia. As several studies and clinical trials have shown that the pharmacological treatment of osteoporosis can also affect muscle tissue, in either a positive or negative manner, sarcopenia should be another factor affecting the choice of treatment, especially when facing equal treatment options for osteoporosis. The aim of this review was to summarize our current knowledge on the effects of FDA-approved drugs for the treatment of osteoporosis on muscle quality, mass and function. A better understanding of the effects that certain drugs have on muscle tissue might in the future help us to simultaneously at least partially also address the wasting of muscle tissue and avoid further pharmacologically induced decline. 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

Osteoporosis is a prevalent disease among the elderly, with fractures being one of the most serious consequences. Early diagnosis and accurate assessment of fracture risk could help prevent fractures. Radiomics employs advanced image analysis techniques for the development of diagnostic tools, thereby improving the accuracy of disease diagnosis and treatment strategies. Specifically, in the application of bone diseases, radiomics has proven effective in the diagnosis and prognostic evaluation of osteoporosis, osteoarthritis, and bone tumors. Radiomics allowed for quantitative characterization of bone geometry, material distribution, and microstructure, making it applicable to osteoporosis as well. In this review, an overview was provided regarding the current progress of radiomics based on clinical bone imaging in osteoporosis, including bone strength assessment, osteoporosis diagnosis, and fracture risk prediction. Additionally, the potential and challenges for their clinical application were summarized. Full article

Fracture risk is a serious yet underrecognized complication among patients with chronic kidney disease (CKD), especially in those with stages G3-G5D. The overlap between CKD-Mineral and Bone Disorder (CKD-MBD) and osteoporosis leads to complex bone changes that increase the likelihood of fragility fractures. Studies show that 18% to 32% of CKD patients also have osteoporosis, and these individuals are more than 2.5 times as likely to suffer from fractures compared to those without CKD. In the advanced stages of the disease, fracture risk is up to four times higher than in the general population, with the femur, forearm, and humerus being the most commonly affected sites. Hip fractures are of particular concern as they are linked to longer hospital stays and higher rates of morbidity and mortality. Furthermore, dialysis patients who experience hip fractures have a mortality rate 2.4 times higher than those in the general population with similar fractures. This increased risk underscores the need for proactive bone health maintenance in CKD patients to prevent fractures and related complications. This review explores the underlying pathophysiological mechanisms, diagnostic challenges, and treatment options related to bone fragility in CKD. Diagnostic tools, such as bone mineral density (BMD) assessments, the trabecular bone score (TBS), and biochemical markers, remain underused, especially in advanced CKD stages. Recent treatment strategies emphasize a multidisciplinary, stage-specific approach, incorporating calcium and vitamin D supplements, anti-resorptive agents like denosumab, and anabolic therapies such as teriparatide and romosozumab. Effective management needs to be tailored to the patient’s bone turnover status and stage of CKD. Despite progress in understanding bone fragility in CKD, significant gaps remain in both diagnosis and treatment. Personalized care, guided by updated KDIGO recommendations and based on an interdisciplinary approach, is essential to reduce fracture risk and improve outcomes in this vulnerable population. Further research is needed to validate risk assessment tools and refine therapeutic protocols. Full article

Osteoporosis (OP) is a chronic disease characterized by reduced bone mass and altered microarchitecture, leading to bone fragility and fractures. Due to its high morbidity, disability, and healthcare costs, identifying new biomarkers and therapeutic strategies is crucial for improving OP diagnosis and prevention. In this context, this narrative review aims to depict the role of carbohydrate-binding proteins Galectins (Gals) in the combined processes of inflammation and aging contributing to bone fragility by exploring their potential as novel therapeutic targets for OP. Full article

Background and Objectives: Bisphosphonates (BP) like zoledronic acid (ZA) and alendronic acid (AA) are used for osteoporosis (OP) or other bone-related conditions as well as to prevent the spread of metastases and in rheumatoid arthritis treatment. However, they have been associated with an increased risk of osteonecrosis of the jaw (ONJ). This systematic review aimed to assess the incidence and risk of ONJ in osteoporotic patients treated with ZA or AA and evaluate the impact of treatment duration. Material and Methods: The systematic literature review was conducted following PRISMA guidelines. The keywords “Zoledronic acid,” “Alendronic acid,” “Osteoporosis,” and “Osteonecrosis” were searched in PubMed and ScienceDirect databases. Selection criteria included studies on humans written in English, published from 2014. The systematic review protocol was registered in the PROSPERO register under the following number: CRD42024587046. Results: A total of 7 studies with 98,717 osteoporotic patients met the criteria, showing a higher ONJ incidence with ZA than AA. Six studies linked longer BP use to increased ONJ risk, which quadrupled after 5 years of AA use. A positive correlation was found between BP use (≥3 years) and ONJ in OP patients, primarily affecting females over 60. ONJ appeared after 1 year with AA, increasing over time, while ZA-related ONJ emerged as early as 5 months with a higher overall incidence. Conclusions: ZA poses a higher ONJ risk and incidence and earlier onset than AA, occurring within 5 months versus 1 year for AA. These findings emphasize the need for careful monitoring, especially in long-term BP therapy with additional risk factors. Full article

Background: Sarcopenia and osteoporosis are common age-related conditions that markedly increase fracture risk and morbidity in the elderly. Leptin, an adipokine secreted by adipose tissue, has been implicated in musculoskeletal health, but its clinical relevance in aging populations remains uncertain. This study aimed to evaluate the associations between serum leptin levels, skeletal muscle mass, muscle strength, bone mineral density (BMD), and fracture risk in elderly women. Methods: This observational analysis included 79 community-dwelling women aged 65 years and older. Participants underwent assessments of body composition, serum leptin concentration, grip strength, and femoral neck BMD. Sarcopenia and obesity were classified based on established criteria. Correlation analyses and binomial logistic regression were performed to examine the relationships among leptin levels, musculoskeletal parameters, and fracture occurrence. Results: Leptin concentrations were significantly associated with fat-related parameters, including BMI, fat index, and total body fat percentage, but showed no significant correlation with skeletal muscle mass (ASM), grip strength, or BMD. Obese participants demonstrated higher leptin levels and fat parameters compared with non-obese participants, but no significant differences were observed in grip strength or BMD. Binomial logistic regression analysis identified femoral neck BMD and grip strength as significant independent predictors of fracture risk, whereas leptin and ASM were not identified as such. Conclusions: In elderly women, serum leptin levels primarily reflect adiposity rather than musculoskeletal health. Leptin is not an independent predictor of spinal fracture risk. These findings highlight the critical importance of maintaining bone density and muscle strength for fracture prevention in aging populations. Full article

Background/Objectives: This study aimed to establish the potential osteotropic effect of pine pollen on bone metabolism in male rats during the development of osteopenia induced by orchidectomy (ORX). We also established the effect of gonadectomy and pine pollen on the characteristics of calf muscles. Methods: This study was conducted using 40 male Wistar rats divided into one sham-operated (SHO) and four ORX groups. The SHO rats and one ORX group (negative control) were treated with physiological saline (PhS). The remaining ORX groups received exclusively testosterone (positive control) and two doses of pine pollen (50 and 150 mg/kg b.w.), respectively. The rats were killed 60 days later and their right tibia and left pelvic limbs were isolated. The tibia was analyzed using densitometry, computed tomography, and a bending machine to determine densitometry, structure, and mechanical properties, respectively. The left pelvic limb allowed for measurements of area, density, and fat tissue in the calf muscle. Results: The dose of 150 mg/kg b.w. inhibited the development of atrophic changes, both in the cortical and trabecular bone tissue. The dose of 50 mg/kg b.w. also has a protective effect on bones but is less pronounced and concerns only the trabecular bone tissue. The higher dose of pine pollen inhibited the catabolism of the calf muscles by maintaining the density and surface area as in the SHO group. It also limited the accumulation of intramuscular and subcutaneous adipose tissue. Conclusions: It is worth emphasizing the osteoprotective effectiveness of pine pollen, especially when administered in larger doses, which demonstrates the possibility of its use in the prevention of the development of osteoporosis in males. Full article

Background: Bisphosphonate-related osteonecrosis of the jaw (BRONJ) represents a severe complication associated with bisphosphonate therapy commonly used in patients with osteoporosis and malignancies. Methods: This retrospective study evaluates the risk factors and clinical outcomes of BRONJ patients treated at the Oral and Maxillofacial Surgery Clinic in Iaşi, Romania, with the goal of optimizing preventive and therapeutic strategies. Data from 72 BRONJ patients treated between January 2013 and December 2023 were analyzed. Results: The majority (83.3%) of patients had underlying malignancies, predominantly breast and prostate cancers. The mandible was most affected, with tooth extraction identified as the primary triggering event. Systemic comorbidities, notably arterial hypertension, diabetes mellitus, and concurrent chemotherapy, were significantly associated with increased BRONJ severity. Surgical intervention was frequently required, with sequestrectomy being the predominant procedure, reflecting advanced disease at the time of diagnosis. Conclusions: The findings underline the critical importance of early identification, preventive dental management, and a collaborative multidisciplinary approach to improve patient prognosis. Full article