Effects of exercise training on bone health in elderly people with type 2 diabetes without osteoporosis: A randomised clinical trial.

The impact of alcohol consumption on bone mineral density: Insights from cross-sectional and Mendelian randomization studies.

Dual-energy X-ray absorptiometry (DXA) remains the clinical gold standard for assessing bone mineral density (BMD), guiding diagnosis and therapeutic decisions. However, conventional DXA analysis suffers from several limitations, including insensitivity to early microarchitectural changes, operator dependence, limited availability in primary care settings, and an insufficient ability to predict fracture risk when used alone. Artificial intelligence (AI), incorporating machine learning (ML) and deep learning (DL), offers transformative potential in enhancing DXA-based bone health assessment. The purpose of this review is to describe the integration of AI algorithms into DXA image interpretation, highlighting improvements in diagnostic accuracy, and fracture risk stratification beyond traditional methods. Using AI-driven models, complex features of DXA images can be extracted, increasing sensitivity to microstructural deterioration that is typically not detected by standard BMD measurements. A combination of quantitative image features and comprehensive demographic and clinical data enhance the early detection of osteoporosis and fracture susceptibility, enabling personalised treatment strategies. In comparison to classical DXA or fracture risk assessment tool (FRAX) algorithms, convolutional neural networks (CNNs) and ensemble methods demonstrate superior predictive performance, with average area under the curve (AUC) values often about 0.90. In addition to minimising inter-operator variability and improving reproducibility, AI improves DXA technical challenges such as region-of-interest selection and image segmentation. In addition to providing indirect measurements of bone microarchitecture, AI-enabled indices, such as the trabecular bone score (TBS), contribute to the improvement of fracture risk prediction. It has been demonstrated in large-scale clinical validations that AI-assisted DXA can enhance bone health diagnostic capability.

IntroductionPsoriatic arthritis (PsA) is a chronic inflammatory disease with a complex clinical spectrum. Sphingosine-1-phosphate (S1P) and its receptor (S1PR) are key lipid mediators involved in immunity and bone remodelling. This study evaluates the inter-relationship between serum levels of S1P and S1PR and clinical activity, radiological findings and different stages of PsA.MethodsA cross-sectional observational study was conducted including 64 subjects: 21 healthy controls and 43 patients with PsA: 16 with recent-onset PsA and 27 with established PsA (EPsA). Clinical variables such as disease activity in PsA (DAPSA), bone mineral density (BMD), Trabecular Bone Score, 3D-Shaper and inflammatory activity by Doppler ultrasound and MRI were assessed. S1P and S1PR levels were measured by ELISA.ResultsS1P levels were significantly higher in the PsA group compared with controls (p=0.013), with the highest values observed in the EPsA subgroup (p=0.009). Although no significant correlation was observed with the DAPSA Score, S1PR levels were significantly higher in patients with Achilles enthesitis detected by ultrasound (p=0.046) and in those with bone proliferation/structural damage (p=0.03). Patients with EPsA showed significantly higher cortical volumetric BMD compared with controls (p=0.027).ConclusionsThe S1P/S1PR axis is dysregulated in PsA and is associated with disease progression. Its correlation with ultrasound findings of enthesitis and new bone formation suggests that S1P acts as a critical mediator in the osteoimmunology of the enthesis, positioning it as a potential biomarker of structural damage and a novel therapeutic target.

Effect of combination versus sequential teriparatide initiation on vertebral bone marrow microenvironment in postmenopausal women with prior denosumab treatment: A propensity score-matched study.

Background: Juvenile Systemic Lupus Erythematosus (jSLE) is a multisystem inflammatory disease associated with bone loss. However, some patients experience fractures prior to the impairment of bone mineral density (BMD), suggesting that other bone microarchitectural properties, including the Trabecular Bone Score (TBS), may contribute to an increased risk of fragility fractures. Purpose: To assess TBS values in patients diagnosed with jSLE; to compare them with data from an age- and sex-matched sample of healthy individuals; to associate TBS with BMD values; and to evaluate the correlation between TBS and clinical risk factors, fractures, and BMD. Research Design: An observational, analytical, retrospective study. Study Sample: Patients with jSLE aged between 5 and 19 years. Data Collection: Clinical data and BMD values obtained by DXA between 2017 and 2022 at a quaternary care center were analysed. The BMD and TBS data were compared with existing published data from healthy Brazilian children and adolescents after age and sex matching. Results: Ninety-four examinations from 50 jSLE patients were analysed. Twenty-one (22.3%) examinations showed significantly lower TBS values than controls. TBS was lower in female patients aged 14-16 and 17-19 years compared with their peers (1.381 vs 1.466 and 1.397 vs 1.479, respectively). BMD and TBS were concordant in 80/94 (85.1%) examinations, demonstrating a moderate and positive correlation (p < 0.0001). There was no correlation between TBS and previous fractures, disease duration, high disease activity, cumulative glucocorticoid dose, or the presence of fragility fractures. Conclusion: Patients with jSLE exhibited bone microarchitectural impairment, regardless of previous fragility fractures, disease duration, disease activity, or cumulative glucocorticoid exposure.

Background/AimMigraine and osteoporosis are highly prevalent in women and represent a substantial socio-health burden. We aimed to comprehensively assess bone status in women with frequent migraine.Patients and MethodsAdult women with high-frequency episodic migraine (HFEM) or chronic migraine (CM) were recruited and compared with age- and body mass index-matched female controls. Serum parameters of bone metabolism, including 25-hydroxyvitamin D (25[OH]D), calcium and parathyroid hormone (PTH), as well as bone turnover markers (procollagen type 1 N-terminal propeptide [P1NP] and C-terminal telopeptide of type I collagen [CTX]), were measured. Bone mineral density (BMD), T-scores and trabecular bone score (TBS) were assessed by dual-energy X-ray absorptiometry.ResultsA total of 108 women with CM/HFEM and 129 matched controls were included. Compared with controls, women with migraine had lower serum 25(OH)D and calcium levels (p ≤ 0.001) and higher adjusted CTX levels (p = 0.039). Densitometric assessment revealed significantly reduction in BMD at femoral neck (g/cm2 and T-score) and total hip (T-score) in the migraine group (p < 0.001). Lumbar TBS was also lower in CM/HFEM patients (p < 0.001). After multivariable adjustment, TBS remained independently associated with migraine status. These alterations remained in women with HFEM and in those younger than 50 years, and were associated with reduced physical activity and sun exposure.ConclusionsWomen with frequent migraine exhibit impaired bone health, characterized by alterations in bone mass and trabecular microarchitecture. TBS appears to be a sensitive marker of early skeletal involvement in this population. The presence of bone impairment in HFEM and in premenopausal women supports early assessment of bone status and reinforcement of lifestyle interventions, including adequate physical activity and sun exposure.

The association of obesity- related markers such as Visceral Adiposity Index (VAI) and Lipid Accumulation Product (LAP) and bone health is controversial. This study aimed to evaluate this association among men using data from of the second recruitment of the Bushehr Elderly Health (BEH) program. A cross-sectional analysis was conducted on 851 men aged 50 years and older using data from the BEH program. Demographic information, laboratory data, bone mineral density (BMD) and trabecular bone score (TBS) were collected. Participants with a T-score ≤ - 2.5 at the lumbar spine, total hip, or femoral neck were classified as having osteoporosis, while others were not. Low BMD (osteopenia/osteoporosis), was defined as a T-score ≤ - 1 at any of these sites. Associations of adiposity measures and bone health were investigated using linear and logistic regression analyses. The mean age of the participants was 62.9 ± 0.2 years and 151 (17.7%) were diagnosed with osteoporosis. Compared to individuals without osteoporosis, those with osteoporosis had lower mean of VAI (2.3 vs. 2.7, p = 0.001) and LAP (44.5 vs. 61.6, p < 0.001). After adjusting for known and measured confounders, VAI exhibited a positive association with BMD at total hip and LAP exhibited a negative association with TBS. Each one unit increases in VAI was associated with 0.0192 gr/cm2 increase in lumbar spine BMD, while one-unit increase in LAP was associated with 0.0011 gr/cm2 decrease in TBS. Moreover, in logistic regression analysis, VAI was related with lower odds of having low BMD (odds ratio = 0.725, p = 0.041). These findings highlighted that some adiposity parameters may serve as valuable markers in evaluating bone health in older adult men. A deeper understanding of these associations may improve clinical approaches for the prevention and management of osteoporosis in this population.

Bone strength is influenced by the stiffness and spatial distribution of mineralized tissue. Bone mineral density (BMD) is used to assess osteoporosis but is limited in evaluating microarchitectural and geometric changes. We investigated Trabecular Bone Score (TBS), BMD, and hip structural analysis (HSA) in celiac disease (CD) patients. A cross-sectional study compared bone density factors in CD patients with a healthy control group matched for gender, BMI, and age. Dual-energy X-ray absorptiometry (DXA) assessed BMD at the femoral neck, hip, and lumbar spine (L1-L4). TBS was measured at the lumbar spine, and HSA evaluated geometry at the narrow neck (NN), femoral shaft (FS), and intertrochanteric (IT) regions. The study included 73 CD patients and 93 healthy controls. The prevalence of low BMD for age at the lumbar spine, total hip, femoral neck, and at any skeletal site was significantly higher in the CD group compared with controls (P < 0.05). No significant differences were found in TBS between groups (P > 0.05). IT buckling ratio (BR), FS BR, and FS endocortical diameter were significantly higher in the CD group, while IT cortical thickness, FS cross-sectional area, and FS cortical thickness were significantly higher in controls (P < 0.05). Patients with celiac disease demonstrated adverse DXA-derived structural and densitometric skeletal parameters, which may potentially contribute to increased skeletal fragility, highlighting the importance of assessing both BMD and structural factors.

Telomere biology disorders (TBD) are a group of diseases that interfere with normal maintenance of telomeres, the ends of chromosomes that protect them from DNA damage. The most common manifestations are bone marrow failure, pulmonary and liver fibrosis. Systematic data on bone health in patients with TBD are scarce. Our aim was to elucidate the bone phenotype of these patients. The cohort comprises 36 adult patients (20 women and 16 men), with genetically confirmed TBD. Demographic, clinical and genetic characteristics, dual-energy X-ray absorptiometry (DXA) scans, spine X-rays and treatment details were reviewed. Median age of patients was 53.5 (43.0, 64.2) years. (Likely) pathogenic variants of the TERT gene were present in most patients. Osteopenia was diagnosed in 38.9% and osteoporosis in 25.0% of patients, 25.0% had a clinical fracture within the past 5years, and 40.0% had at least one prevalent vertebral fracture (grade 1-3). T-score at the lumbar spine (-0.98±1.48SD) was lower than at the femoral neck (-0.60±1.09SD). Mean trabecular bone score (TBS) T-score was -1.32±1.29SD. Bone-active therapy was used by 44.4% of the population, mostly oral bisphosphonates (85.7%). To conclude, we reported a high prevalence of osteopenia, osteoporosis, recent fractures and prevalent vertebral fractures, in patients with TBD. These results highlight the necessity of addressing the risk of osteoporosis and fractures in these patients during medical assessments. Most importantly, additionally to a DXA scan, a vertebral fracture assessment (VFA) or spine X-ray, is recommended to evaluate vertebral fractures.

Pituitary adenomas are common intracranial neoplasms and represent a clinically relevant but frequently underrecognized cause of secondary osteoporosis and fragility fractures. Hormonal excess, coexisting pituitary deficiencies, and the iatrogenic burden of multimodal treatments act synergistically to impair bone remodeling, microarchitecture, and mechanical strength. Consequently, skeletal fragility may manifest at a relatively young age and is often inadequately predicted by dual-energy X-ray absorptiometry (DXA)-derived areal bone mineral density (aBMD) alone.This narrative review summarizes current evidence on skeletal involvement in functioning pituitary adenomas, including acromegaly, Cushing's disease (CD), prolactinomas, and thyrotropin [TSH]-secreting adenomas (TSHomas), with a specific focus on sex-related differences relevant to clinical practice. Although several pituitary adenomas are more prevalent in women, male patients frequently present with delayed diagnoses, harboring larger and more aggressive tumors. Consequently, men may be affected by a longer cumulative exposure to hormone excess and a higher prevalence and severity of panhypopituitarism, often exacerbated by the mass effect and multiline therapies. Across clinical cohorts, these interacting factors are consistently associated with an increased burden of fragility fractures, particularly in male patients.In pituitary disorders, fracture risk is commonly underestimated because DXA-derived aBMD does not adequately capture alterations in bone quality and structural integrity. Comprehensive skeletal evaluation, including systematic vertebral morphometry, trabecular bone score (TBS), and selected advanced imaging techniques, improves detection of occult fractures and refines fracture risk stratification. Moreover, the persistently low awareness, diagnosis, and treatment rates of osteoporosis in men represent a substantial and potentially modifiable gap in care, particularly in secondary forms related to endocrine diseases.This review highlights the need for a proactive, sex-aware clinical approach that integrates endocrine management with appropriate skeletal assessment and bone-directed therapy, with the aim of reducing fracture burden and improving long-term outcomes in patients with pituitary diseases.

Objectives: Bone mineral density (BMD) assessment, the gold standard for diagnosing osteoporosis, does not account for bone quality and fracture susceptibility. Trabecular bone score (TBS) adds value to traditional densitometry. No studies have been conducted in the Polish population to date to confirm the association between TBS and fracture occurrence. This study aimed to evaluate the TBS derived from lumbar spine (L1–L4) dual-energy X-ray absorptiometry (DXA) scans in Polish women aged 40–76 years, both with and without osteoporotic fractures. The relationship between TBS, fracture risk (assessed by FRAX and TBS-adjusted FRAX), and BMD at the lumbar spine, femoral neck, and total hip was investigated. Methods: A total of 933 Caucasian women (760 without fracture and 173 with fracture) who underwent DXA examinations (Hologic Discovery A) between 2022 and 2024 were included. Lumbar TBS, BMD, and clinical fracture risk factors were analyzed, excluding subjects with scan artefacts or extreme BMI. Group differences were assessed using t-tests and chi-square tests. Pearson correlation was used to evaluate associations between TBS, age, and BMI. Logistic regression models assessed TBS and BMD as fracture discrimination, and model performance was compared using the Akaike Information Criterion (AIC) and the area under the receiver operating characteristic (ROC) curve (AUC). Results: TBS values were significantly lower in the fracture group (p < 0.001). TBS demonstrated negative correlations with age (r ≈ −0.36) and BMI (r ≈ −0.14). Low TBS values (≤1.23) were associated with the highest fracture prevalence (28.8%) and a threefold increased risk compared to high TBS (odds ratio = 3.0). Each one standard-deviation decrease in BMD or TBS T-score increased fracture risk by 56–67% (both p < 0.001). Models combining TBS and BMD improved discrimination, as indicated by higher AUC and lower AIC, with TBS remaining an independent predictor. In subgroups with osteopenia or osteoporosis, TBS retained statistical significance. Conclusions: TBS combined with BMD effectively discriminates fracture risk in Polish women and offers superior diagnostic accuracy compared to BMD alone. Integrating TBS with BMD enhances fracture accuracy. Routine assessment of TBS may improve clinical management of osteoporosis. Prospective studies are needed to confirm its long-term predictive value.

Anemia, inflammation and iron deficiency are linked to Fibroblast growth factor 23 (FGF23). Aim of this study was to explore the dynamics of FGF23 in Hereditary Hemochromatosis type-I (HH1). Twenty-six consecutive patients with genetically confirmed and uncomplicated HH1 and nineteen healthy age-matched voluntary blood donors (CTR) were enrolled for the study. Intact (iFGF23) and C-terminal (cFGF23) FGF23 and iron status markers were evaluated at baseline (T0) and seven days (T7) after phlebotomy/voluntary blood donation (VBD). Bone mineral density (BMD) and vertebral fracture assessment (VFA) were also evaluated at T0. Cross-sectional and longitudinal analyses failed to reveal significant differences in iFGF23 in both HH1 (T0: 54.27 ± 14.42 pg/mL; T7: 54.70 ± 15.48 pg/mL) and CTR (T0: 52.77 ± 17.63 pg/mL; T7: 53.27 ± 15.88 pg/mL) groups. Absence of significant difference was also observed for cFGF23 at baseline between the two groups (HH1, T0: 0.98 ± 0.39 pmol/L; CTR, T0: 1.18 ± 0.91 pmol/L) but not at T7 when the values (HH1, T7: 01.20 ± 0.89; CTR, T7: 1.84 ± 1.11 pmol/L) were significantly increased in CTR compared to T0 (p = 0.0003) and to HH1 (p = 0.0240). After phlebotomy/VBD, in both HH1 and CTR groups, serum levels of phosphate were unchanged from baseline while serum iron, ferritin and transferrin saturation and erythrocyte-related parameters (red blood cells, hemoglobin and hematocrit) were significantly reduced (all p < 0.0001). Serum iron, ferritin, and transferrin saturation were significantly higher in HH1 than in CTR (p = 0.0002 for serum iron and p < 0.0001 for both ferritin and transferrin saturation) at T7. In the CTR group, these parameters showed a trend toward iron deficiency whereas in HH1 they remained near the upper limit of the normal range, suggesting a persistent mild iron overload. Correlation and regression analyses did not show significant associations between circulating FGF23 (both iFGF23 and cFGF23) and iron status markers. BMD and VFA were not significantly different between HH1 and CTR. Furthermore, BMD and Trabecular Bone Score values were not associated with circulating FGF23 levels. This pilot study indicates that the serum levels of iFGF23 and cFGF23 and skeletal health evaluated through BMD and VFA do not differ between patients with uncomplicated HH1 and healthy subjects at baseline. The absence of changes in the serum levels of iFGF23 and cFGF23 in HH1 patients with uncomplicated HH1 after phlebotomy may reflect the persistence of iron overload which could counteract the physiological hypoxia-driven stimulation of FGF23 production and cleavage observed in healthy subjects after VBD.

Trabecular bone score in glucocorticoid-induced osteoporosis: A systematic review and meta-analysis.

Background:The Fracture Risk Assessment Tool (FRAX) is widely used as an intervention threshold for postmenopausal osteoporosis but has not been validated specifically for axial spondyloarthritis (axSpA).Objectives:To validate FRAX thresholds and predictive ability for fragility fractures in axSpA patients.Design:A cross-sectional study.Methods:Patients diagnosed with axSpA according to the 2009 ASAS criteria, aged 40–90 years, and treated at Phramongkutklao Hospital between December 2019 and October 2024 were consecutively included. Bone mineral density (BMD), trabecular bone score (TBS), and vertebral fracture assessment were measured using Dual-energy X-ray absorptiometry. The Thai reference database calculated FRAX probabilities for major osteoporotic fracture (MOF) and hip fracture (HF). The predictive performance of FRAX (with and without BMD) was evaluated against actual fracture occurrence, using FRAX thresholds for MOF and HF at 10% and 3%, respectively. Optimal cutoffs for FRAX against fractures were determined using receiver operating characteristic (ROC) curves and the Youden index.Results:Among 125 axSpA patients (73.6% male; mean age 50.9 ± 10.8 years; disease duration 9.7 ± 9.9 years), osteoporotic fractures were found in 24.0%, with vertebral fractures being most common. Patients with fractures had significantly higher disease activity (Bath Ankylosing Spondylitis Disease Activity Index 4.2 vs 2.2, p = 0.004; Ankylosing Spondylitis Disease Activity Score (ASDAS) 3.1 vs 1.7, p < 0.001) and higher median FRAX scores for MOF (4.9% vs 1.9% without BMD; 4.7% vs 2.4% with BMD) and HF (0.8% vs 0.2% without BMD; 0.9% vs 0.5% with BMD; all p < 0.05). Higher ASDAS scores were independently associated with increased fracture risk (odds ratio 2.35, 95% confidence interval 1.39–3.98). FRAX thresholds (MOF ⩾10%, HF ⩾3%) showed low sensitivity (MOF: 0% without BMD, 18.5% with BMD; HF: 23.3% without BMD, 22.2% with BMD) but high specificity (>84%). Optimal ROC-derived FRAX cutoffs without BMD (MOF ⩾4%, HF ⩾1.5%) improved predictive accuracy (MOF: sensitivity 40%, specificity 85.3%, area under the ROC curve (AUC) = 0.770; HF: sensitivity 46.7%, specificity 75.8%, AUC = 0.674).Conclusion:FRAX (without BMD) is a viable predictor of fractures in axSpA, yet its optimal intervention thresholds (⩾4% MOF and ⩾1.5% HF) fall substantially below standard thresholds for postmenopausal women. Adjusting clinical thresholds downward is warranted to ensure timely prevention and better reflect the specific axSpA risk profile.

Chronic exposure to glucocorticoids (GC) is a leading cause of secondary osteoporosis and fractures. While the skeletal effects of long-term oral GC are wellestablished, the bone effects of intermittent high-dose intravenous pulse methylprednisolone therapy remain less clearly defined. This study aimed to evaluate its impact on skeletal health in adults not receiving antiosteoporosis treatment. This meta-analysis was conducted according to PRISMA guidelines and prospectively registered. PubMed, Scopus, Embase, and Google Scholar were searched up to September 2025. Studies included longitudinal cohort and case-control studies with appropriate comparators and randomised controlled trials reporting pre- and post-intravenous methylprednisolone bone outcomes. Eight studies (n=192, 72% females) were included. Pulse intravenous methylprednisolone did not significantly reduce bone mineral density (BMD) at the lumbar spine (mean difference [MD] 0.01 g/cm2; 95% confidence interval [CI] -0.02 to 0.03), femoral neck (MD -0.01 g/cm2; 95% CI -0.03 to 0.01), or total hip (MD -0.03 g/cm2; 95% CI -0.06 to 0.01) over a mean followup period of 5.5 months. Trabecular bone score showed no significant pooled change (MD -0.01 g/cm2). In contrast, procollagen type-1 N-terminal propeptide (MD -36.95 ng/mL; 95% CI -56.86 to -17.03) and C-terminal telopeptide (MD -0.19 ng/dL; 95% CI -0.32 to -0.07) significantly decreased. Serum 25-hydroxyvitamin D increased modestly, while serum calcium and parathyroid hormone remained unchanged. Pulse intravenous methylprednisolone does not cause short-term BMD loss, though it is associated with measurable suppression of bone turnover markers. Larger controlled studies with standardised sampling, peripheral site assessment, and fracture outcomes are needed to determine long-term skeletal risk from pulse regimens.

Assessment of bone microarchitecture in postmenopausal women with primary hyperparathyroidism using trabecular bone score.

Validation of a deep learning model for bone fragility detection from conventional radiographs: an international cohort study

Osteoporosis in men is a common but often neglected health problem. We aim to compare the efficacy and safety of denosumab, zoledronic acid and alendronate in men with osteoporosis. In this randomized, comparative, open-label study, 390 men with osteoporosis or osteopenia were included. They were randomized to receive the treatment of denosumab, alendronate, or zoledronic acid for 12months. The percentage changes in bone mineral density (BMD), trabecular bone score (TBS) and bone turnover biomarkers (BTMs) during the treatment were evaluated. Safety parameters were observed. The baseline characteristics were well balanced among the three groups. After 12months of treatment, denosumab, alendronate and zoledronic acid significantly increased BMD by 4.83 ± 0.89%, 4.32 ± 0.77%, 5.18 ± 0.73% at lumbar spine, by 2.75 ± 0.51%, 2.50 ± 0.61% and 2.83 ± 0.59% at total hip, TBS was significantly increased by 2.44 ± 0.52%, 2.00 ± 0.64%, 2.29 ± 0.55%, respectively, without significant differences among the three groups. Serum levels of BTMs decreased significantly and similarly in all three groups (all P < .05 vs. baseline). Denosumab and alendronate group had fewer adverse events than zoledronic acid group. Denosumab had similar efficacy in patients with different gonadal functions. In patients previously receiving bone resorption inhibitors, denosumab continued to increase BMD and TBS, but the increments were reduced by approximately 30% in BMD at lumbar spine compared with treatment-naive patients. Denosumab, alendronate and zoledronic acid significantly and similarly reduced BTMs, increased BMD and TBS in men with osteoporosis, whether the gonadal function of patients was normal or decreased. Previous anti-bone resorption therapy may partially diminish the efficacy of denosumab.

Prediabetes comprises heterogeneous metabolic phenotypes that may differentially affect bone quality. While type 2 diabetes increases fracture risk despite preserved bone mineral density, phenotype-specific effects on bone quality during prediabetes remain unclear. We compared trabecular bone score (TBS) across prediabetes phenotypes and examined visceral adiposity's mediating role. We analyzed 876 individuals with prediabetes (451 men, 425 postmenopausal women) from the Cardiovascular and Metabolic Diseases Etiology Research Center cohort. Participants underwent oral glucose tolerance testing for phenotype classification (impaired fasting glucose [IFG], impaired glucose tolerance [IGT], combined IFG+IGT) and dual-energy X-ray absorptiometry for TBS and body composition. Bootstrap mediation analysis (5,000 iterations) tested whether visceral adipose tissue (VAT) accounted for phenotype-TBS associations. Prediabetes phenotypes showed distinct, sex-specific patterns of bone quality impairment linked to visceral fat. In men, IGT had the lowest TBS (1.46 ± 0.09) compared with IFG (1.49 ± 0.08) and IFG+IGT (1.48 ± 0.07, both p < 0.05). In women, IFG+IGT had the lowest TBS (1.42 ± 0.08) versus IFG (1.44 ± 0.07, p < 0.05). VAT paralleled these TBS patterns and mediated 51% (95% CI 28-74%) of the IGT effect in men and 26% (95% CI 8-45%) of the IFG+IGT effect in women. Prediabetes phenotypes are associated with distinct TBS patterns-IGT in men and IFG+IGT in women showing the lowest values. Visceral adiposity mediated approximately half of the association in men with IGT, suggesting sex- and phenotype-specific pathways linking prediabetes to bone microarchitecture.