Search Results (321)

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

Background: Rotator cuff disease and osteoporosis are frequently overlapping pathologies in the older patient population. Increasing evidence suggests that impaired bone health negatively impacts rotator cuff tear development and healing after repair. Methods: An online search of PubMed and MEDLINE was performed from inception to April 2026, using the keywords “osteoporosis” and “rotator cuff”. Thirty-two studies met all criteria. These studies summarize the current literature on the relationship between osteoporosis and rotator cuff disease, with an emphasis on epidemiology, evaluation, treatment implications, and future directions. Results: Osteoporosis is associated with rotator cuff tear development, poorer local bone quality, and impaired tendon-to-bone healing following repair. Chronic rotator cuff pathology may also contribute to localized osteopenia of the greater tuberosity, suggesting a bidirectional relationship between bone loss and rotator cuff degeneration. Despite this overlap, osteoporosis remains under-recognized and under-treated in patients with rotator cuff disease. Vitamin D status, bone health assessment, and emerging bone-active therapies have demonstrated improved outcomes. Conclusions: Osteoporosis is an important comorbidity to consider in patients with rotator cuff disease. Improved recognition and optimization of bone health may enhance both skeletal and shoulder-specific outcomes. Further prospective studies are needed to better define optimal management strategies. Full article

Cancer cachexia (CC) is a devastating, multi-organ syndrome historically defined by the progressive wasting of skeletal muscle and adipose tissue. However, emerging evidence suggests that the skeletal system is also a major, yet underappreciated target of this catabolic state. While bone loss in oncology is primarily attributed to skeletal metastasis or cancer treatment-induced bone loss (CTIBL), clinical and preclinical data has increasingly demonstrated that tumor and host-derived systemic signals can drive severe bone deterioration even in non-metastatic disease. This review synthesizes current information available on bone loss, osteopenia, and skeletal decline in the context of CC, with a specific focus on non-metastatic disease. By examining the available literature, we argue that bone loss is a “hidden” yet fundamental systemic manifestation of the cachectic state. Furthermore, we aim to highlight how concurrent muscle and bone deterioration (osteosarcopenia) dramatically worsens prognosis in several different cancers in both the adult and pediatric populations. Ultimately, this review highlights the potential contribution of cancer cachexia to osteoporosis and skeletal fragility, supporting the need for greater clinical awareness, improved musculoskeletal screening, and the development of targeted therapeutic strategies. Full article

Background: Bone disease remains a major long-term complication after kidney transplantation. However, the relationship between circulating bone turnover markers (BTMs) and densitometric skeletal parameters in kidney transplant recipients (KTRs) remains incompletely understood. Methods: This single-center, cross-sectional comparative study included 50 stable adult KTRs and 56 non-transplanted individuals with dual-energy X-ray absorptiometry (DXA)-confirmed osteopenia or osteoporosis. Serum bone formation markers, bone-specific alkaline phosphatase (BALP) and procollagen type I N-terminal propeptide (P1NP), and bone resorption markers, β-C-terminal telopeptide of type I collagen (β-CTX) and tartrate-resistant acid phosphatase 5b (TRAP5b), were quantified by enzyme-linked immunosorbent assay (ELISA). Bone mineral density (BMD), Z-scores, and Fracture Risk Assessment Tool (FRAX) estimates were obtained by DXA. Between-group comparisons were adjusted for age, sex, body mass index (BMI) and postmenopausal status, with sensitivity analyses restricted to participants with low bone mass. An exploratory receiver operating characteristic (ROC) analysis was performed to assess the association of BTMs with KTR status. Results: KTRs showed lower DXA-derived Z-scores at the total hip, femoral neck and lumbar spine despite being younger. After adjustment for age, sex, BMI and postmenopausal status, KTRs had significantly higher BALP (adjusted Δ = 129.96 ng/mL, p < 0.001) and PTH, and lower eGFR and magnesium than the reference group, whereas unadjusted differences in P1NP and lumbar spine BMD did not persist; β-CTX and TRAP5b did not differ between groups. BALP remained significantly higher in KTRs across the low-bone-mass restricted and propensity-score overlap analyses. BTMs showed no significant correlations with DXA parameters in KTRs. In the exploratory ROC analysis of study-group status, BALP showed the strongest separation between KTRs and the reference group (AUC = 0.808, p < 0.001). Conclusions: Long-term KTRs exhibit a distinct bone remodeling profile characterized most consistently by elevated BALP, which remained significant after adjustment and showed the strongest separation regarding KTR status. The limited BTM–DXA associations require confirmation in longitudinal studies. Full article

Skeletal safety of glucagon-like peptide-1 receptor agonists (GLP-1RAs) remains uncharted, with emerging evidence suggesting a divergence between mono- and dual-agonist therapies. GLP-1RA monotherapy appears bone-neutral, with modest or no adverse effects on bone mineral density (BMD), whilst dual agonists may confer a relatively higher risk of osteoporosis and fractures, plausibly mediated by greater weight loss magnitude and concomitant reductions in lean body mass (LBM) rather than direct osteotoxicity. Intensified surveillance is warranted in susceptible phenotypes, including older adults and postmenopausal women with low baseline BMD under conditions of rapid weight loss. Osteoporosis risk is further amplified by pre-existing osteopenia, nutritional deficiencies, and concomitant exposure to bone-active agents. Given the limitations of serial dual-energy X-ray absorptiometry (DXA), including cumulative radiation exposure and limited sensitivity to early remodeling changes, biochemical markers potentially depict bone turnover more dynamically. Measurement of dynamic bone resorption markers enables early identification of skeletal disturbances, supporting proactive adjustment of therapeutic strategy, dosing, and duration. Specifically, deoxypyridinoline (DPD), a bone-specific collagen crosslink, is a highly sensitive and rapidly responsive urine biomarker of osteoclastic activity. Incorporating DPD urine testing into monitoring frameworks potentially facilitates individualized therapeutic modulation, optimizing the metabolic efficacy of GLP-1RAs while safeguarding skeletal integrity. Full article

Background/Objectives: Osteoporosis is a major public health concern associated with increased fracture risk and reduced quality of life if not detected at an early stage. Automated analysis of knee X-ray images using artificial intelligence has shown promising potential for opportunistic osteoporosis screening. This study aims to develop and evaluate a multi-stage deep learning and machine learning framework for osteoporosis classification, with particular emphasis on external validation, calibration drift, and cross-domain generalization performance. Methods: Knee X-ray images were categorized into three classes: Normal, Osteopenia, and Osteoporosis. Deep features were extracted using pretrained convolutional neural networks, including ResNet18, EfficientNetB0, and DenseNet121. The extracted features were subsequently classified using multiple machine learning models, including Neural Network, Efficient Linear, Support Vector Machine, and Naive Bayes classifiers. Two data augmentation strategies were investigated: targeted minority-class augmentation and full 3× dataset expansion with class balancing. Model performance was evaluated using accuracy, precision, recall, F1-score, and AUC on internal validation, independent test sets, and external validation datasets. Additional analyses included reliability calibration assessment, isotonic recalibration, and class-prior boosting with cross-validated threshold optimization to address external domain shift. Results: EfficientNetB0 and DenseNet121 consistently outperformed ResNet18 across most evaluation metrics. Under the balanced augmentation strategy, EfficientNetB0 combined with Efficient Linear demonstrated strong and stable performance, while DenseNet121 paired with a Neural Network achieved the highest overall classification performance. External validation revealed a substantial discrepancy between AUC and threshold-based metrics, indicating the presence of calibration drift and class-prior mismatch across imaging domains. Reliability analysis showed severe probability collapse in the Osteopenia class during external testing. Post-hoc recalibration improved probability reliability, while class-prior boosting substantially increased Osteopenia sensitivity and improved balanced accuracy and macro F1-score under external validation conditions. Conclusions: The proposed framework demonstrates the feasibility of combining pretrained CNN-based deep feature extraction with machine learning classifiers for osteoporosis classification from knee X-ray images. The findings further highlight that maintaining model performance under external testing conditions may require not only strong feature extraction capability but also adaptive recalibration and deployment-aware threshold optimization to address calibration drift and cross-domain variability. While the results are encouraging, the present study should be considered a proof-of-concept investigation. Although the framework was evaluated using an independent public external dataset, further validation using larger and more diverse multi-center clinical cohorts is necessary to establish generalizability and clinical utility before routine clinical implementation can be considered. 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

Aim: To evaluate cytokine, RANKL/OPG, and oxidative stress biomarker profiles in postmenopausal women with differing bone mineral density (BMD) and to apply machine learning (ML) models for early identification of low BMD. Materials & Methods: Seventy-one postmenopausal women were classified as normal BMD (N), osteopenia (OSN), or osteoporosis (OSR) using ISCD/WHO criteria. Ten cytokines, RANKL, OPG, and five oxidative stress markers were quantified. Group differences were assessed using nonparametric statistics and rank-biserial correlation. ML classifiers were developed within the PyCaret automated machine learning framework and evaluated using repeated stratified cross-validation to distinguish N vs. low BMD (L = OSN + OSR) and OSN vs. OSR using cytokine-only, bone/oxidative, and integrated biomarker panels, while SHapley Additive exPlanations (SHAP) were employed to interpret feature contributions. Results: Low BMD was associated with elevated pro-resorptive cytokines (TNF-α, IL-6, IL-12) and reduced anti-resorptive cytokines (IL-4, IL-10, IL-23). OPG and antioxidant enzymes (catalase, SOD2, PRX2) were significantly lower in L. Effect-size findings confirmed strong associations of IL-4, IL-10, IL-23, and OPG with normal BMD, and IL-6, IL-12p70, and TNF-α with low BMD. Logistic regression integrating cytokines with OPG and SOD2 achieved the best N vs. L performance (mean F1 ≈ 0.90, SD = 0.09). Biomarkers showed limited ability to discriminate OSN from OSR (maximum F1 ≈ 0.70, SD = 0.18). Conclusions: Integrating cytokine, bone-regulatory, and oxidative stress markers enhances ML-based prediction of low BMD and supports improved early osteoporosis risk stratification. Full article

Background: Hyperprolactinemia is a common endocrine disorder with significant reproductive and systemic implications. This study aimed to investigate the nationwide epidemiological trends, longitudinal shifts in pharmacological treatment, and the temporal associations of concurrent conditions and long-term sequelae in Korean women with claims-based hyperprolactinemia. Methods: A nationwide, population-based retrospective cohort study was conducted using data from the Health Insurance Review & Assessment Service (HIRA) of South Korea from 2009 to 2021. Female patients aged 10–59 years with hyperprolactinemia diagnostic claims were evaluated. We analyzed annual prevalence, incidence, diagnostic procedures, and dopamine agonist prescription patterns. Associated clinical conditions were classified into two categories based on the timing of their diagnosis relative to hyperprolactinemia: concurrent or underlying conditions present at baseline, and long-term complications that developed during the follow-up period. Results: A total of 95,616 female patients were identified after applying the selection criteria. The prevalence and incidence of hyperprolactinemia peaked among women in their early thirties, with an absolute peak at age 32. A significant pharmacological paradigm shift was observed: bromocriptine was the predominant therapy during the early study period, but cabergoline prescriptions surpassed bromocriptine in 2017. Regarding clinical work-ups, only 5.3% of the entire cohort underwent a sella magnetic resonance imaging (MRI). Regarding associated clinical conditions, reproductive disorders such as infertility (28.0%) and polycystic ovary syndrome (24.8%) showed high overall prevalence but low incidence of new diagnoses during the follow-up period. Conversely, among the patients affected by bone disorders, more than 60% of the total osteoporosis and osteopenia cases were diagnosed subsequent to the initial hyperprolactinemia diagnosis. Significant post-diagnosis incidence was also observed for metabolic disorders, including dyslipidemia and diabetes mellitus. Conclusions: Hyperprolactinemia in Korean women is highly concentrated in the peak reproductive years. The shift toward cabergoline reflects evolving clinical guidelines and improved drug accessibility. Our findings highlight that while reproductive issues often present concurrently, bone loss and metabolic complications frequently emerge as post-diagnosis sequelae. Therefore, clinical management should extend beyond prolactin normalization to include proactive, multidisciplinary screening for skeletal and metabolic health. Full article

Background: Regional periarticular bone mineral density may influence fixation and survivorship in total knee arthroplasty, but its relationship to coronal alignment remains unclear. This study assessed the association between coronal knee alignment and osteoporosis using CT Hounsfield Unit (HU)-based thresholds. Methods: Patients aged ≥ 50 years with standing long-leg radiographs and phantomless knee-CT (2008–2025) were retrospectively identified. Exclusion criteria included >12 months between studies, incomplete CT, non-120 kV acquisition, prior fracture or surgery, or metabolic bone disease other than osteopenia or osteoporosis. Mean trabecular attenuation was measured over 15 mm of epiphyseal bone in the distal femur and proximal tibia. Osteoporosis was defined using CT-HU thresholds. Coronal alignment was measured using hip–knee–ankle angle (HKAA) and categorized as varus (<178°), neutral (178–182°), or valgus (>182°). Measurements were performed by a reviewer blinded to osteoporosis classification. Multivariable logistic regression adjusted for age, sex, body mass index, and Kellgren–Lawrence grade. Results: Among 306 patients (mean age 66.9 ± 9.0 years; 51.3% female), 99.3% underwent CT for arthroplasty planning. Osteoporosis prevalence was 34.3% of varus, 58.2% of neutral, and 68.6% of valgus knees. Increasing valgus alignment was associated with higher osteoporosis odds, whereas varus alignment showed lower odds. Female sex (OR 3.06; p < 0.001), age (OR 1.06/year; p < 0.001), and HKAA (OR 1.05/degree; p = 0.042) remained independently associated with osteoporosis, whereas Kellgren–Lawrence grade was nonsignificant. Conclusions: Coronal alignment was associated with CT-defined regional knee osteoporosis. Valgus alignment showed increased odds of osteoporosis, whereas varus alignment showed lower prevalence. Full article

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. Full article

Background: Osteoporosis, a chronic disease with a major epidemiologic impact amid menopause might be aggravated by co-ailments such as adrenal tumours, with an increasing incidence due to a larger access to imaging evaluation. The objective was to evaluate bone profile in relationship with adrenal profile in non-functioning adrenal tumours (NFATs), based on menopausal DXA categories (osteoporosis, osteopenia and normal). Methods: A retrospective real-life study was conducted amid a cross-sectional analysis in anti-osteoporotic drugs naïve subjects. Adrenal profile included baseline morning plasma cortisol (base-cortisol), second-day cortisol (DST-cortisol) after 1 mg dexamethasone testing, ACTH, and largest tumour diameter at CT (D-CT). Results: Ninety-five patients (mean age 61.59 ± 7.83 years) had 24.21% osteoporosis, 47.37% osteopenia, and 28.42%—normal DXA. Base-cortisol, DST-cortisol, ACTH and D-CT were similar between the groups. Total serum calcium was lower in osteoporosis versus osteopenia, versus normal DXA (9.26 ± 0.52 versus 9.61 ± 0.41 mg/dL, p = 0.005, respectively, 9.79 ± 0.47 mg/dL, p < 0.001). Osteocalcin, respectively, CrossLaps were elevated in osteoporosis versus osteopenia. MACS prevalence was 27.37% (no between-group difference). Osteoporosis group: CrossLaps correlated with DST-cortisol (r = −0.550, p = 0.019). Multiple linear regression model to predict lumbar BMD explained 47.1% of the variance in lumbar BMD (R² = 0.471). ACTH was an independent variable for lumbar BMD (p = 0.007). BMI represented the main influential contributor to this model having the highest β of 0.490, and it also explained 49.1% (R² = 0.491) of total hip BMD variation. Conclusions: This study emphasises a heterogeneous connection between adrenal profile in NFATs and clinical evaluation of the bone status. More comprehensive prospective studies are mandatory to assess this multifactorial bone–adrenal interplay in order to improve the overall management. Full article

Background/Objectives: Glycogen storage disease type IX (GSD IX) is an inherited metabolic disorder characterized by marked clinical heterogeneity and variable severity. Dietary therapy is considered the cornerstone of management, but evidence on treatment strategies, efficacy, and safety remains limited. This study aimed to systematically synthesize available data on therapeutic approaches and clinical outcomes in GSD IX. Methods: A focused analysis of treatment-related data was conducted from a previously performed PRISMA-based systematic review. Clinical studies reporting treatment and follow-up data in genetically confirmed GSD IX patients were included. Results: Among 400 patients identified in the original review, 129 from 26 studies had treatment and follow-up data available. Dietary management combined with uncooked cornstarch (UCCS) was the most common approach (96.1%), with highly heterogeneous protocols. Hepatic manifestations improved in 59/129 (45.7%) of patients, and hypoglycemia in 45/129 (34.9%). Growth outcomes were variable, with catch-up growth in 14.0% and persistent impairment in 19.4%, although data were often missing. Muscle involvement was rarely assessed. No treatment-related adverse events were reported. However, disease-related complications were described, including liver cirrhosis, neurological involvement, osteopenia/osteoporosis, and two deaths in GSD IXa patients. Conclusions: Dietary therapy combined with UCCS remains the mainstay of treatment in GSD IX and is associated with improvement in key clinical domains. However, evidence is limited, heterogeneous, and largely based on small studies. Data on modified cornstarch formulations, such as Glycosade^®, are scarce. Prospective studies and standardized treatment protocols are needed to support evidence-based management. Full article

As life expectancy for people living with human immunodeficiency virus (HIV) (PLWH) increases, long-term comorbidities, such as bone mineral density (BMD) loss, have emerged as significant clinical challenges. This study evaluated the prevalence and determinants of skeletal demineralization in a contemporary Romanian HIV cohort. A cross-sectional study was conducted among 180 PLWH (mean age 41.86 ± 12.69 years) undergoing stable antiretroviral therapy. Bone health was assessed via dual-energy X-ray absorptiometry (DXA), while body composition and metabolic status were evaluated using bioelectrical impedance analysis (BIA) and serum lipid profiling. A high prevalence of reduced skeletal mass (58.3%) was observed, with 10% of the cohort diagnosed with osteoporosis at a mean age of only 45.7 years. Significant correlations were identified between osteoporosis and a history of AIDS, active smoking, and hypertriglyceridemia. Notably, women with osteoporosis exhibited significantly lower current CD4+ T-cell counts (268.4 ± 180.5 cells/μL) compared to those with normal BMD. While the body mass index was an inconsistent predictor of bone health, BIA-derived bone mass effectively identified subclinical depletion. Our findings underscore a phenotype of premature skeletal aging in PLWH, driven by an interplay of immunological history, metabolic disturbances, and lifestyle factors. Early screening via DXA and BIA, alongside aggressive management of modifiable risks, is essential for mitigating fragility fractures in this aging population. Full article