Search Results (318)

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

Background: Bone Marrow Edema Syndrome (BMEs) encompasses primary clinical conditions characterized by pain and high-intensity signals on fluid-sensitive magnetic resonance imaging at the subchondral bone level. This study aimed to evaluate bone mineral density (BMD) and turnover markers in BMEs patients compared to a healthy control group. Methods: We selected from the records 165 patients—comprising Complex Regional Pain Syndrome type 1 (CRPS-1, n = 61), hip BMEs (n = 42), and knee BMEs (n = 62)—alongside 150 age- and sex-matched healthy controls. Assessments included bone turnover markers, vitamin D levels, and BMD at the lumbar spine and femur by Dual-Energy X-ray Absorptiometry. Trabecular Bone Score (TBS) was calculated to estimate bone microarchitecture. Results: BMEs patients demonstrated significantly lower BMD across all skeletal sites and reduced TBS values compared to controls. Osteoporosis prevalence was significantly higher in all BMEs subgroups, with CRPS-1 and hip BMES patients showing higher rates than those with knee BMEs. No significant differences were observed in vitamin D or bone turnover markers between groups. Conclusions: Patients with CRPS-1 and BMEs of the hip or knee exhibit a higher prevalence of osteoporosis and compromised bone microarchitecture. These findings highlight a significant association between BME-related conditions and altered BMD/TBS parameters, suggesting a potential shared pathophysiological link. Full article

Background/Objectives: Chronic Kidney Disease–Mineral and Bone Disorder (CKD-MBD) is a frequent complication of chronic kidney disease, characterized by altered bone mineral density and mineral–hormonal metabolism. Therapeutic exercise may help attenuate these alterations, but evidence remains limited. This systematic review and meta-analysis evaluated the effects of therapeutic exercise on bone mineral density and mineral–bone and hormonal biomarkers in adults with CKD, focusing on CKD-MBD-related outcomes. Methods: Following a PROSPERO-registered protocol (CRD420251245021), Scopus, PubMed, Cochrane Central Register of Controlled Trials CENTRAL, and Web of Science were searched from inception to January 2026. Randomized controlled trials, including pilot randomized controlled trials, comparing therapeutic exercise with usual care or non-exercise control conditions in adults with CKD were included. Methodological quality and risk of bias were assessed with the PEDro scale and RoB 2, respectively. Results: Six studies involving 398 participants were included. Most interventions lasted 22 to 24 weeks and used resistance or combined aerobic and resistance exercise across inpatient and outpatient settings. Qualitative synthesis suggested improvements in femoral neck and lumbar spine bone mineral density and favorable biomarker changes. The assessed outcomes included femoral neck and lumbar spine BMD, calcium, phosphorus, sclerostin, PTH, FGF23, and klotho. Meta-analysis showed significant effects favoring therapeutic exercise for bone mineral density (MD = 0.05; 95% CI: 0.03 to 0.06; p < 0.00001; I² = 39%), mineral and bone-related biomarkers (SMD = 0.71; 95% CI: 0.42 to 0.99; p < 0.00001; I² = 75%), and hormonal biomarkers (SMD = 1.32; 95% CI: 0.88 to 1.77; p < 0.00001; I² = 85%). Conclusions: Therapeutic exercise may have beneficial effects on bone mineral density and selected mineral and hormonal biomarkers in adults with CKD. However, confidence in these findings is limited by the small number of studies, differences in CKD stage and exercise protocols, methodological limitations, risk of bias, and substantial heterogeneity in several pooled analyses. No definitive conclusions can currently be drawn regarding the optimal exercise modality, dose, or effects across CKD stages. Full article

Background/Objectives: Children with autoimmune gastrointestinal diseases are at increased risk of impaired bone health due to chronic inflammation, nutritional deficiencies, growth disturbances, and treatment-related factors. While dual-energy X-ray absorptiometry (DXA) is the standard method for assessing bone mineral density (BMD), it provides limited information on bone microarchitecture. The trabecular bone score (TBS), derived from lumbar spine DXA images, has emerged as a complementary marker of bone quality. This study aimed to evaluate bone mass and TBS in children with autoimmune gastrointestinal diseases and to assess the clinical utility of TBS in comparison with children with a history of fractures and healthy controls. Methods: This study included 152 children aged 5–18 years: 45 with autoimmune gastrointestinal diseases (Crohn’s disease, ulcerative colitis, or celiac disease), 37 with a history of fractures, and 70 healthy controls. Anthropometric measurements, serum 25-hydroxyvitamin D [25(OH)D] concentrations, DXA-derived parameters, and TBS values were analyzed. Bone mineral density was assessed at the lumbar spine and total body less head (TBLH), with additional adjustment for height-for-age Z-score (HAZ). TBS values were expressed as sex- and pubertal stage-adjusted Z-scores. Results: Low bone mass (aBMD_{for age} Z-score ≤ −2) was observed in 30.3% of participants at TBLH and 11.1% at the lumbar spine, whereas a TBS Z-score ≤ −2 was identified in 5.2% of children. No significant differences in TBS or TBS Z-scores were found among the study groups. In multivariable analysis, fracture history was independently associated with lower absolute TBS, whereas no independent predictors of TBS Z-score were identified. Children with fractures had significantly lower HAZ-adjusted lumbar spine aBMD Z-scores than children with autoimmune gastrointestinal diseases and controls. TBS Z-scores correlated positively with age-adjusted and HAZ-adjusted aBMD values but showed no association with BMI or serum 25(OH)D concentrations. Conclusions: In this cross-sectional study, TBS did not distinguish children with autoimmune gastrointestinal diseases from those with fractures or healthy controls in the unadjusted analyses. Although TBS was associated with selected DXA-derived measures of bone mineral density and fracture history was independently associated with lower absolute TBS after multivariable adjustment, no independent predictors of TBS Z-score were identified. These findings suggest that the clinical role of TBS in the assessment of pediatric bone health remains to be established. Larger prospective studies are crucial to determine whether TBS provides clinically meaningful information complementary to conventional DXA for the assessment of skeletal health and fracture risk in children. Larger prospective studies are needed to clarify the clinical value of TBS for fracture risk assessment in pediatric autoimmune gastrointestinal diseases. Full article

Osteoporosis is a major public health problem characterized by reduced bone mineral density (BMD) and increased fracture risk. Early identification of individuals with low bone density remains essential for prevention. This study aimed to evaluate a multivariable logistic regression-based model integrating clinical and Radiofrequency Echographic Multi Spectrometry (REMS)-derived parameters for the detection of low bone density in women. A total of 324 women undergoing REMS assessment of the lumbar spine and hip were included. Clinical variables (age, body mass index [BMI], menopausal status, and lifestyle factors) and REMS-derived measurements were analyzed. Binary logistic regression was used to identify independent factors associated with low BMD (T-score < −1 SD). Model performance was assessed using odds ratios (ORs), omnibus chi-square testing, pseudo-R² statistics, and classification accuracy. The Youden index was applied to determine optimal cut-off values. Age, menopausal status, BMI, and basal metabolic rate (BMR) were identified as independent factors associated with low lumbar spine and femoral neck BMD. Increasing age and menopause were associated with higher odds of low bone density, whereas higher BMI and BMR were inversely associated with low bone density. In conclusion, a logistic regression model combining clinical and REMS-derived parameters demonstrated the ability to identify women with low bone density, supporting improved individualized risk stratification in clinical practice. Full article

Background/Objectives: Osteoporosis is a major contributor to vertebral compression fractures (VCFs) and other skeletal complications, yet quantitative bone mineral density (BMD) assessment using dual-energy X-ray absorptiometry (DEXA) is not routinely available in many spine surgery workflows. This study proposes an anatomically guided and optimization-refined radiomics framework for opportunistic osteoporosis assessment from routine lumbar spine magnetic resonance imaging (MRI). Methods: The proposed pipeline employs a hierarchical template-matching strategy to automatically localize the L1–L4 vertebral region, followed by an optimization-based refinement procedure that adapts vertebral regions of interest (ROIs) using intensity, texture, boundary, and geometric constraints. Anatomically consistent ROIs are subsequently used for extraction of handcrafted radiomic descriptors, including statistical, textural, gradient-based, frequency-domain, and shape-related features. The extracted features were evaluated using conventional support vector classification (SVC) and a NeurodynamicSVMRBFTanh classification framework for osteoporosis-related classification. Results: Experimental results demonstrated robust and anatomically consistent vertebral localization across heterogeneous lumbar MRI acquisitions. The NeurodynamicSVMRBFTanh framework achieved the best screening-oriented performance, yielding 85.2% classification accuracy and 100.0% sensitivity on an independent test set. In addition, exploratory BMD regression analysis demonstrated the feasibility of estimating DEXA-derived BMD directly from MRI-derived radiomic features, achieving mean absolute percentage errors of approximately 15–20% across lumbar vertebral levels. Conclusions: These findings suggest that anatomically guided vertebral radiomics extracted from routine lumbar spine MRI contain clinically meaningful information associated with osteoporosis-related bone quality changes and may provide a practical tool for automated opportunistic osteoporosis assessment in settings where DEXA measurements are unavailable. Full article

Background/Objectives: Oxidative stress is closely tied to diabetic bone disorders. Superoxide dismutase (SOD) is a key antioxidant enzyme, yet its sex-specific link with osteoporosis in type 2 diabetes mellitus (T2DM) remains unclear. This study aimed to investigate this association and explore its potential biological mechanism. Methods: A retrospective cross-sectional study was performed on 2023 T2DM patients (1137 males, 886 females) grouped by bone mineral density (BMD). Multivariate logistic regression was used, and in vitro experiments validated SOD3’s effect on osteoclast differentiation. Results: After adjustment for potential confounders, higher serum SOD activity (>135 U/mL) was independently associated with approximately 50% lower odds of prevalent osteoporosis at the lumbar spine and femoral neck in women, whereas no significant association was observed in men. Recombinant SOD3 inhibited osteoclast differentiation in a concentration-dependent way. Conclusions: Higher serum SOD activity was independently associated with a lower prevalence of osteoporosis in women with T2DM. Serum SOD activity may serve as a potential biomarker associated with osteoporosis in this population. These findings provide new insights into the relationship between oxidative stress and diabetic bone disease and warrant validation in prospective studies. Full article

Background: Eldecalcitol (ELD) and denosumab are some of the most common therapeutic options for osteoporosis management. ELD effectively increases bone mineral density (BMD) in osteoporotic patients, independent of baseline vitamin D status or calcium intake. However, the efficacy of denosumab combined with either ELD or native vitamin D plus calcium in postmenopausal Chinese women with osteoporosis has not been established. Methods: In this single-center, randomized, open-label, active-controlled clinical trial, postmenopausal women with osteoporosis (defined as a BMD T-score ≤ −2.5 at the lumbar spine [LS], total hip [TH], or femoral neck [FN], or low bone mass with fragility fracture history) were enrolled from Xi’an Honghui Hospital in China and randomized 1:1 to two 12-month treatment regimens: the ELD group received ELD (0.75 μg orally daily) combined with denosumab (60 mg subcutaneously every 6 months), while the control group received the same denosumab regimen plus native vitamin D (800 IU orally daily) and calcium (600 mg orally daily). The primary endpoint was the 12-month percent change in LS BMD from baseline. Secondary endpoints included changes in FN- and TH-BMD from baseline, bone turnover markers, serum parathyroid hormone, quality of life, and the incidence of new fractures. Results: Of the 100 randomized participants, 45 in the ELD group and 46 in the control group were included in the efficacy analysis. After 12 months of treatment, LS-BMD increased significantly in both groups (both p < 0.05), with a greater increase in the ELD group than in the control group (6.75% vs. 4.99%), yielding a statistically significant between-group least-squares mean difference of 1.75% (95% CI, 0.10 to 3.41; p = 0.038). The reduction in serum β-CTX was significantly smaller in the ELD group than in the control group at 3 months (91.00% vs. 93.62%, p = 0.002), with no significant between-group differences thereafter. Seven fractures were reported (one non-vertebral in the ELD group; one vertebral and five non-vertebral in the control group). No significant between-group differences in FN- or TH-BMD, quality of life, or overall adverse event rates were observed. Both regimens were generally well-tolerated, without clinically meaningful calcium-related safety signals. Conclusions: Combination therapy with denosumab and eldecalcitol improved LS-BMD more effectively than denosumab with native vitamin D and calcium in postmenopausal Chinese women with osteoporosis. Clinical trial number: ClinicalTrials.gov identifier NCT05884372, registered on 1 June 2023. Full article

Background: Chronic kidney disease (CKD) is associated with early disturbances in mineral metabolism that contribute to bone fragility. Secondary hyperparathyroidism is a key component of chronic kidney disease–mineral and bone disorder (CKD-MBD) and may affect bone even during the early stages of CKD. This study evaluated the association between serum parathyroid hormone (PTH) concentrations and bone mineral density (BMD) in patients with stage 3 CKD. Methods: A multicenter cross-sectional observational study was conducted in 203 patients with stage 3 CKD. Blood and 24 h urine samples were collected to measure creatinine, calcium, phosphate, magnesium, 25-hydroxyvitamin D, fibroblast growth factor 23 (FGF23), and PTH. Bone mineral density was assessed by dual-energy X-ray absorptiometry (DXA). Associations between serum PTH concentrations and BMD were analyzed. Results: Elevated serum PTH concentrations were associated with lower femoral BMD and less favorable femoral T-scores, whereas no significant associations were observed at the lumbar spine. Serum PTH concentrations were inversely correlated with femoral BMD and femoral T-scores. Patients with reduced femoral BMD also showed higher FGF23 concentrations and lower renal function, while serum calcium, phosphate, magnesium, and 25-hydroxyvitamin D concentrations did not differ significantly among the groups. Conclusions: Elevated serum PTH concentrations were associated with reduced femoral BMD in patients with stage 3 CKD, supporting preferential early involvement of cortical bone. Serum PTH may represent an accessible biomarker for the early identification of patients at increased risk of cortical bone loss before conventional biochemical abnormalities become clinically apparent. Full article

Background/Objectives: Discontinuation of long-term denosumab (Dmab) remains a major clinical challenge because of rebound activation of bone remodeling and increased vertebral fracture risk. Intravenous zoledronate (ZOL) is widely recommended as sequential therapy, although evidence after very prolonged Dmab exposure is limited. We report a patient who developed two rare adverse events—acute hepatocellular injury and delayed inflammatory polyarthritis—following a single ZOL infusion administered after 12 years of continuous Dmab treatment. The subsequent management of persistent rebound bone turnover with oral alendronate (ALN) highlights the therapeutic challenges encountered when repeat ZOL administration is not feasible. Methods: A 65-year-old woman with postmenopausal osteoporosis received a single 5 mg ZOL infusion 6 months after her final Dmab injection following 12 years of continuous therapy. Within 24 h, she developed a typical acute phase response. Three days later, marked hepatocellular injury was detected, characterized by substantial elevations in transaminases and gamma-glutamyl transferase, while viral and autoimmune hepatitis were excluded. Liver enzymes normalized within five days with supportive management. Thirty-two days after ZOL administration, she developed inflammatory polyarthritis in the absence of previous rheumatologic disease and with negative immunologic testing. Treatment with low-dose prednisone (5 mg/day) resulted in rapid clinical and biochemical remission. At 6 months, bone turnover markers remained markedly elevated (CTX 0.82 ng/mL, P1NP 95 ng/mL), indicating insufficient suppression of rebound bone turnover after Dmab discontinuation. Because of the adverse events, the patient declined repeat ZOL administration. Results: Weekly oral alendronate (ALN) (70 mg) was initiated and was associated with partial suppression of bone turnover markers. Despite a decline in bone mineral density (BMD) of approximately 5% at both the lumbar spine and total hip over 12 months, BMD remained within the osteopenic range, and no new fragility fractures occurred during follow-up. Conclusions: This case illustrates two rare sequential immune-mediated adverse events following ZOL infusion and underscores the therapeutic challenges of managing Dmab discontinuation after long-term treatment when repeat ZOL administration is contraindicated. Sequential intravenous ZOL and oral ALN therapy was associated with partial suppression of bone turnover markers and protection from incident fractures during follow-up, despite a modest decline in BMD of approximately 5%. Full article

Axial spondyloarthritis (axSpA) is a chronic inflammatory disease affecting the sacroiliac joints and spine and is associated with an increased risk of fractures due to persistent inflammation, reduced mobility and treatment-related factors. In radiographic axSpA (r-axSpA), assessment of bone mineral density (BMD) using dual-energy X-ray absorptiometry (DXA) may be limited by structural spinal changes. This cross-sectional study, conducted between March 2024 and June 2025, evaluated skeletal fragility in patients with r-axSpA using Radiofrequency Echographic Multi-Spectrometry (REMS)-derived Fragility Score (FS). Ninety patients with r-axSpA and sex-matched healthy controls underwent clinical assessment and REMS evaluation of lumbar spine and hip BMD, T-scores and spinal FS. Patients with r-axSpA had lower body mass index and higher rates of smoking, prior fractures and inflammatory markers compared with controls, while disease activity reflected a moderate burden. No significant differences in BMD or T-scores were observed between groups. However, FS was significantly higher in patients with r-axSpA (46.6 ± 15.4 vs. 31.2 ± 13.3, p = 0.004), corresponding to a higher fracture risk category, whereas correlations between FS and clinical parameters were not statistically significant. These findings suggest that REMS-derived FS may identify increased skeletal fragility in r-axSpA beyond conventional BMD measurements. Full article

Background: With the global population aging, osteoporosis and associated vertebral compression fractures are increasingly prevalent. While bone mineral density (BMD) remains the standard clinical parameter for diagnosing osteoporosis, it provides an incomplete assessment of holistic spinal bone health. Paraspinal muscles are essential for spinal stability and movement. This narrative review aims to evaluate the interplay between paraspinal muscle status and lumbar spine BMD, thereby providing a scientific foundation for comprehensive bone health management. Methods: A comprehensive literature search was conducted in PubMed using relevant keywords to identify studies evaluating the functional and morphological interactions between paraspinal muscles and bone mineral density. Discussion: Current evidence demonstrates a significant negative correlation between paraspinal muscle FI and lumbar spine BMD. High FI is identified as an independent risk factor for osteoporotic vertebral fractures and a robust predictor of postoperative complications. The relationship between paraspinal muscle CSA and BMD remains debated. Nevertheless, targeted high-impact and resistance training generate substantial mechanical loading through muscle contraction, providing biological stimuli for trabecular BMD preservation. Conclusions: Evidence highlights a critical synergy between paraspinal muscle status and bone mineral density, with muscle fat infiltration acting as a key marker for bone loss and fracture susceptibility. Integrating these muscle parameters with traditional BMD measurements improves fracture risk stratification and osteoporosis management. Full article

Background: Selective estrogen receptor modulators (SERMs) are widely used for postmenopausal osteoporosis, yet whether treatment response attenuates with aging in routine practice remains unclear. We examined age- and site-specific responses to SERM therapy. Methods: We retrospectively analyzed postmenopausal women with primary osteoporosis treated with a SERM for 1 year (2017–2021). Participants were stratified by age (50–64, 65–74, and ≥75 years). We evaluated changes in bone mineral density (BMD) at the lumbar spine (L2–4) and femoral neck and changes in urinary NTX and serum BAP. Multivariable linear regression modeled BMD change ratios (1-year/baseline) adjusting for baseline site-specific BMD, estimated glomerular filtration rate (eGFR), and active vitamin D co-therapy (none, alfacalcidol, or eldecalcitol). The primary endpoint was the 1-year change in lumbar spine BMD; secondary endpoints included femoral neck BMD and bone turnover markers. Results: Lumbar spine BMD increased significantly across all age groups, whereas femoral neck BMD increased significantly only in women aged 50–64 years. However, BMD change ratios did not differ among age groups at either site. In adjusted models, age was not independently associated with BMD change at the lumbar spine or femoral neck. Lower baseline BMD predicted larger relative gains at both sites, and eldecalcitol co-therapy was independently associated with femoral neck BMD response. Conclusions: In real-world practice, BMD changes observed during SERM treatment were site-specific rather than clearly age-dependent. Lumbar spine BMD improved across age groups, whereas femoral neck changes were smaller and less consistent. Full article

Background: This study aimed to determine the prevalence of DXA-detected lumbar scoliosis in postmenopausal women based on dual-energy X-ray absorptiometry (DXA) scans and identify associated risk factors. Methods: A total of 261 postmenopausal women aged ≥50 years who underwent lumbar spine DXA before June 2021 were included. Lumbar scoliosis was defined as a Cobb angle ≥ 10° measured from DXA images. Logistic regression analysis was performed to evaluate associated risk factors. Diagnostic performance of DXA-based Cobb angle measurements was assessed in the radiographic validation subgroup using radiography as the reference standard. Results: The prevalence of DXA-detected lumbar scoliosis was 14.9% (39/261; 95% CI, 10.8–19.9%). Increasing age was significantly associated with scoliosis, while body mass index, bone mineral density, and T-scores at the lumbar spine, hip, and femoral neck were not. DXA and radiographic Cobb angle measurements demonstrated strong agreement (ICC = 0.91, 95% CI 0.73–0.96), with a mean difference of −2.63°. Diagnostic accuracy was 82.1%, with sensitivity 62.1%, specificity 97.4%, PPV 94.7%, and NPV 77.0%. ROC analysis demonstrated good discriminative performance (AUC = 0.88, 95% CI, 0.79–0.98); an exploratory cutoff of 6.5° yielded the highest Youden index. Conclusions: DXA-detected lumbar scoliosis was identified in 14.9% of postmenopausal women undergoing DXA. DXA-based Cobb angle measurements demonstrated strong agreement with radiographic assessment and may facilitate opportunistic case detection of likely lumbar scoliosis during routine BMD assessment. Full article

Background/Objectives: Approximately 53.4 million U.S. adults aged 50 or older have low bone mass, yet male bone health remains under-researched. This study evaluated the effects of one year of prune supplementation on bone health in older men susceptible to, or with, osteopenia. Methods: A total of 59 men (aged 55–80 years) were randomly assigned to one of three groups: 100 g prunes, 50 g prunes, or 0 g prunes (control; multivitamin only) daily, with each group also receiving 450 mg elemental calcium and 800 IU vitamin D₃ via a multivitamin. Dual-energy X-ray absorptiometry (Lunar model DXA; GE Healthcare, CA, USA) scans and blood samples were collected at baseline, 3 months, 6 months, and 12 months. Results: No significant changes were observed in total bone mineral density (BMD) or lumbar spine BMD over one year. There were no significant changes in C-reactive protein (CRP). Osteoprotegerin (OPG) decreased significantly in all groups; however, the decrease was significantly greater in the control group compared to the levels in both prune groups. Sclerostin (SOST) significantly increased over time within all groups. Tartrate-resistant acid phosphatase-5b (TRAP5b) increased in all groups, albeit in the control group, it increased significantly more over time compared to the increase in the 100 g group. Conclusions: Overall, prune supplementation, regardless of dosing, did not increase total or lumbar BMD or aid in maintaining bone density beyond the levels achieved by Ca++ and vitamin D₃ supplementation in older men susceptible to, or with, osteopenia (with a negative T-score down to –2.5 standard deviations (SD) below the mean). Although between-group differences were observed in select secondary biomarkers (OPG, TRAP5b), these did not correspond to detectable changes in BMD and should therefore be considered exploratory rather than directly indicative of clinical bone benefit. Additional research is needed to fully understand the effects of prunes on bone metabolism in men. Full article