Bone [JOURNAL]
Sun
200 papers
Akt2 regulates autophagy and osteogenesis in diabetic osteoporosis via PI3K/AKT/mTOR signaling axis.
Ye Q, Fu T, Li P … +7 more , Long X, Zhang Z, Ye L, Zhou Y, Peng S, Tao Q, Xiao J
Bone · 2026 Mar · PMID 41453425 · Publisher ↗
Adipose-derived stem cells (ASCs) are crucial seed cells for bone defect repair. In diabetic osteoporosis (DOP), however, their osteogenic potential is impaired. This study found that ASCs from a pre-clinical DOP model,...
Adipose-derived stem cells (ASCs) are crucial seed cells for bone defect repair. In diabetic osteoporosis (DOP), however, their osteogenic potential is impaired. This study found that ASCs from a pre-clinical DOP model, established in C57BL/6 J mice using a high-fat/high-sucrose diet combined with streptozotocin-induced insulin deficiency, exhibited suppressed osteogenic differentiation and impaired autophagy flux. This was accompanied by hyperactivation of the PI3K/AKT/mTOR signaling, particularly elevated AKT2 phosphorylation. Transcriptomic analysis confirmed enrichment of related pathways. Mechanistically, Akt2 overexpression suppressed osteogenesis and autophagy, while its knockdown restored both. Crucially, implanting shAkt2-treated DOP-ASCs into calvarial defects of DOP mice enhanced bone regeneration, improving bone volume, trabecular number, and collagen deposition. These findings identify Akt2 as a key regulator of ASC dysfunction in DOP and demonstrate that its targeted inhibition rescues osteogenic potential, offering a promising therapeutic strategy for diabetic osteoporotic bone repair.
Repurposing osteoporosis medications for other diseases: a narrative review by the European Calcified Tissue Society (ECTS).
Makras P, Yavropoulou MP, Anastasilakis AD … +8 more , Appelman-Dijkstra NM, Carey JJ, Naciu AM, Paccou J, Rolvien T, Winter EM, Papapoulos SE, Lems WF
Bone · 2026 Mar · PMID 41448559 · Publisher ↗
PURPOSE: This narrative review explores the therapeutic potential of repurposing medications originally developed or approved for osteoporosis to treat non-osteoporotic conditions. Given their pharmacologic profiles and...
PURPOSE: This narrative review explores the therapeutic potential of repurposing medications originally developed or approved for osteoporosis to treat non-osteoporotic conditions. Given their pharmacologic profiles and safety data, these agents offer promising therapeutic alternatives in both rare and common diseases with unmet clinical needs. PRINCIPAL RESULTS: Evidence from preclinical models, observational data, and randomised trials supports the repositioning of several osteoporosis drugs. Cyclic etidronate has shown efficacy in halting arterial calcification progression in pseudoxanthoma elasticum. Pamidronate has demonstrated symptom improvement in adult chronic nonbacterial osteitis. Neridronate is approved only in Italy for complex regional pain syndrome type I. Denosumab has shown therapeutic effects in Langerhans cell histiocytosis and has structural benefits in erosive hand osteoarthritis and rheumatoid arthritis. Parathyroid hormone analogues (rhPTH [1-84] and teriparatide) improve calcium-phosphate homeostasis in chronic and genetic hypoparathyroidism. Calcilytics, though originally discontinued for osteoporosis, show emerging promise in autosomal dominant hypoparathyroidism. In contrast, zoledronic acid has not demonstrated consistent clinical benefit in knee osteoarthritis. Strontium ranelate, despite showing structure-modifying effects in osteoarthritis, is no longer marketed due to safety concerns. Alendronate and denosumab in fibrous dysplasia yielded mixed results, with concerns about rebound effects after denosumab withdrawal. CONCLUSIONS: Repurposing osteoporosis medications represents a cost-effective, timely strategy to expand treatment options across diverse clinical indications. While promising outcomes have been demonstrated-particularly in rare diseases-rigorous, indication-specific clinical trials are essential to confirm efficacy, safety, and long-term outcomes. The accumulated pharmacologic and clinical experience with these agents offers a strong foundation for their continued exploration beyond osteoporosis.
Corrigendum to "LIPUS promotes osteogenesis via the mcirc_9393-miR-217/326-SIRT1 axis in porous Ti6Al4V scaffolds" [Bone 201 (2025) 117647].
Cao H, Yu Y, Wu L … +1 more , Hao F
Bone · 2026 Mar · PMID 41436307 · Publisher ↗
Abstract loading — click title to view on PubMed.
Primary trabecular bone formation in vitro by the OmGFP66 osteogenic cell line: Multiscale symmetry breaking and characterization in 3D.
Khurshid B, Mousa A, Dallas SL … +3 more , Deering J, Reznikov N, McKee MD
Bone · 2026 Mar · PMID 41436000 · Full text
Osteocytes are abundant bone cells that serve as central regulators of skeletal homeostasis. Within mineralized bone tissue, osteocytes and their cell processes/dendrites maintain cell connectivity through a lacunocanali...
Osteocytes are abundant bone cells that serve as central regulators of skeletal homeostasis. Within mineralized bone tissue, osteocytes and their cell processes/dendrites maintain cell connectivity through a lacunocanalicular network morphologically positioned for executing myriad cell signaling pathways, including those related to mechanosensation, mineral ion homeostasis, and extracellular matrix mineralization. Given the complexity of osteocyte morphological transitions within mineralized bone, there are few robust in vitro models that reproduce the mineralized bone microenvironment. A recently developed mouse calvarial osteocyte cell line, OmGFP66, overcomes many of these limitations. Here we provide a comprehensive 3D multiscale characterization of mineralized, primary bone-like trabeculae formed by OmGFP66 cells in vitro, with a comparison to mouse calvariae. Submicron X-ray microcomputed tomography (μCT) was used to image and reveal quantitative features of thousands of discrete, variably shaped trabeculae formed by OmGFP66 cells with osteocyte lacunae having features quantitatively similar to those of neonatal mouse calvarial primary bone. Moreover, FIB-SEM and TEM analyses revealed the 3D ultrastructure of an extended lacunocanalicular network formed by the OmGFP66 cells within mineralized extracellular matrix and extending through an osteoid layer to osteoblasts at the surface, comparable to bone in vivo. At the nanoscale-to-microscale, again like bone, OmGFP66 trabeculae exhibit a 3D crossfibrillar mineral tessellation pattern. We also fit OmGFP66 trabecular morphology patterning and mineralization to the Gray-Scott model of oscillating reaction-diffusion patterns to describe symmetry breaking that initiates and facilitates mineralization through the combined dynamics of diffusing mineral ions and inhibitors. Together, these findings establish OmGFP66 cell cultures as a powerful in vitro bone model for studying osteocyte differentiation, matrix mineralization, and pattern formation.
Deep learning-based micro-CT grayscale analysis for early detection and staging of osteoporosis in rats.
Zhang Y, Cheng H, Deng J … +4 more , Chen B, Ran Y, Kou Y, Jiang B
Bone · 2026 Mar · PMID 41435999 · Publisher ↗
BACKGROUND: Rat models are widely used in preclinical osteoporosis research to study disease mechanisms and evaluate therapies. Current Micro-CT studies mostly rely on cross-sectional comparisons at a single time point,...
BACKGROUND: Rat models are widely used in preclinical osteoporosis research to study disease mechanisms and evaluate therapies. Current Micro-CT studies mostly rely on cross-sectional comparisons at a single time point, and there is a lack of standardized reference data across multiple time points. To address this gap, the present study provides standardized reference data from multiple time points using a deep learning-based Micro-CT grayscale analysis, enabling early detection and precise staging of osteoporosis. METHODS: A standardized osteoporosis model was established in ovariectomized Sprague-Dawley rats (n = 32) with a sham-operated group (n = 32). Femurs were harvested at 4, 8, 16, and 24 weeks post-surgery. The proximal 0-250 slice region adjacent to the growth plate was defined as the region of interest (ROI), and six representative slices per femur were analyzed. Voxels within each ROI were classified into four grayscale regions: 0-50 (non-bone), 51-100 (bone-nonbone transition), 101-150 (defined bone), and 151-255 (highly mineralized bone). The percentage areas of the four regions across the six slices (4 × 6 input) were used to train a custom deep learning model. Diagnostic performance for early osteoporosis detection and staging was compared with conventional trabecular parameters. RESULTS: Both the grayscale-based algorithm and conventional Micro-CT parameters distinguished Sham and OVX rats at 4 weeks, enabling early detection, whereas DXA only detected differences at 16 weeks. In osteoporosis staging within the OVX group, the grayscale-based model achieved higher accuracy (88.4 % ± 6.4 %) than conventional parameters (55.9 % ± 8.4 %, p < 0.05). For single-time-point osteoporosis diagnosis, the grayscale-based algorithm (98.3 % ± 3.4 %) also outperformed conventional parameters (85.3 % ± 3.4 %, p < 0.05). CONCLUSION: The grayscale-based deep learning method allows sensitive early detection and more accurate staging of osteoporosis, providing a robust quantitative tool for assessment of osteoporotic progression in OVX rats.
Multiaxial physiological loading generates complex fluid flow and strain patterns in the osteocyte lacunar-canalicular system.
Muñoz A, De Paolis A, Cardoso L … +1 more , Carriero A
Bone · 2026 Mar · PMID 41421425 · Publisher ↗
Osteocytes, embedded within the lacunar-canalicular system in bone, play a central role in sensing mechanical stimuli and directing bone adaptation. Fluid-structure interaction (FSI) models have emerged as valuable tools...
Osteocytes, embedded within the lacunar-canalicular system in bone, play a central role in sensing mechanical stimuli and directing bone adaptation. Fluid-structure interaction (FSI) models have emerged as valuable tools to simulate the mechanical environment surrounding osteocytes, but in silico studies have relied on idealized loading conditions to simplify the complex, multiaxial loading that osteocytes are likely exposed to in vivo. In this study, we model the mechanical environment within the lacunar-canalicular system using multiaxial physiologically relevant loading conditions, by incorporating human tibia strains experimentally measured during walking and running by Lanyon et al. (1975) [1], into 3D osteocyte-scale FSI simulations. We here evaluate how interstitial fluid flow and osteocyte strain patterns generated by physiological loading differ from those obtained using a simplified uniaxial sinusoidal loading. Our findings show that despite similar interstitial fluid velocity magnitude, the spatial flow under multiaxial physiological loading is definitely more complex. Multiaxial physiological loading generates fluid velocities and strains that are highly heterogeneous and shift in direction over time, with dendritic strain exceeding by over an order of magnitude the ones of the cell body. Instead, uniaxial sinusoidal loading produces uniform, periodic flows aligned with the primary loading axis, with minimal strain in dendrites perpendicular to this axis. Notably, multiaxial physiological loading induces localized recirculation zones and broader velocity distributions within canaliculi - with extremely low Reynolds number confirming the laminar flow and excluding true turbulence - that can amplify osteocyte mechanosensitive signals. These are not observed in uniaxial sinusoidal loading. These findings highlight the limitations of uniaxial sinusoidal loading as a model of physiological osteocyte mechanics.
Effect of bisphosphonate treatment on the oim mouse middle ear ossicles' structure, composition and hearing.
Ugarteburu M, Doube M, Rau C … +7 more , Antipova O, Li LX, Stock SR, Tan X, Cardoso L, Richter CP, Carriero A
Bone · 2026 Mar · PMID 41418894 · Publisher ↗
Hearing loss is common in people with osteogenesis imperfecta (OI or brittle bone disease). Bisphosphonates are widely used to treat long bone fragility in children with OI. However, its impact on the bone quality of the...
Hearing loss is common in people with osteogenesis imperfecta (OI or brittle bone disease). Bisphosphonates are widely used to treat long bone fragility in children with OI. However, its impact on the bone quality of the middle ear ossicles and hearing remains unknown. This study determines whether bisphosphonates treatment itself may contribute to hearing loss in OI by evaluating its effects in the oim/oim mouse model of severe OI having normal auditory function. Specifically, this study reports the effects of alendronate (ALN), a nitrogen-containing bisphosphonate, on ossicle morphology, porosity, and elemental composition in 14-week-old oim/oim mice treated weekly, starting at 2 weeks of age. The ossicles were examined using synchrotron microtomography and X-ray fluorescence microscopy (XFM). Hearing was assessed longitudinally until 26 weeks of age by determining auditory brainstem response (ABR) thresholds in another group of mice also treated weekly starting at 2 weeks of age. ALN treatment further reduces in size the already small oim/oim ossicles, specifically in female mice. Porosity, bone composition, and hearing function, however, were generally not affected by the ALN treatment. Furthermore, ALN does not prevent joint fusions, excessive bone formations, or enlarged joint spaces in WT or oim/oim experimental groups. One ALN-treated oim/oim mouse with a bone formation in the interior of the footplate, and one ALN-treated WT mouse with a fixed footplate had frequency-specific hearing loss. Since footplate abnormalities are not observed in PBS-treated mice in this study, it remains unclear whether ALN fails to prevent these changes or contributes to their development. Future studies should investigate the mechanisms of ossicular abnormalities and bisphosphonates modulatory role in the ossicles.
Association between advanced glycation end products and bone mineral density in Mexican population.
Aparicio-Bautista DI, Salmerón J, Jiménez-Ortega RF … +4 more , López-Pérez TV, Becerra-Cervera A, Velázquez-Cruz R, Rivera-Paredez B
Bone · 2026 Mar · PMID 41412236 · Publisher ↗
BACKGROUND: Evidence shows that advanced glycation end products (AGEs) play a key role in skeletal deterioration by impacting bone quality and strength. However, there is limited long-term research on their association w...
BACKGROUND: Evidence shows that advanced glycation end products (AGEs) play a key role in skeletal deterioration by impacting bone quality and strength. However, there is limited long-term research on their association with bone mineral density (BMD), especially among different sexes and age groups. OBJECTIVE: To evaluate the longitudinal association between serum AGEs and BMD in adults, stratified by sex and age groups (<45 years and ≥45 years). METHODS: We conducted a longitudinal analysis using data from 1138 adults enrolled in the Health Workers Cohort Study, followed over a six-year period (2004-2010). BMD (g/cm) was measured at various skeletal sites using dual-energy X-ray absorptiometry. Generalized estimating equations (GEE) and fixed-effects models were employed, stratified by sex and age group, and adjusted for potential confounders. RESULTS: In GEE models, a 100 μU/mL increase in AGEs was significantly associated with lower BMD at the hip, femoral neck, and lumbar spine in women aged ≥45 years (β = -0.003, β = -0.004, β = -0.011, respectively). Among men ≥45 years, higher AGEs were also associated with lower BMD at the hip and femoral neck (β = -0.004 and β = -0.006, respectively). In women <45 years, AGEs were inversely associated with hip and femoral neck BMD (β = -0.003 for both). Fixed-effects models yielded consistent results, particularly among women ≥45 years. No significant associations were observed in men <45 years. CONCLUSIONS: Elevated serum AGEs levels are associated with lower BMD over time, particularly among women. These findings suggest a potential role of AGEs in bone deterioration and their relevance in clinical risk assessment.
FSH and longitudinal changes in bone marrow adipose tissue composition in older adults.
Kim TY, Hue TF, Ewing SK … +12 more , Li X, Sigurdsson S, Gudnason V, Vlug AG, Kado DM, Vittinghoff E, Wu KC, Koh EH, Rosen CJ, Zaidi M, Schwartz AV, Schafer AL
Bone · 2026 Mar · PMID 41407177 · Publisher ↗
Bone marrow adipose tissue (BMAT) expansion and distinct BMAT composition profiles, including lower unsaturated levels, are cross-sectionally associated with older age. Prospective changes in BMAT composition with aging...
Bone marrow adipose tissue (BMAT) expansion and distinct BMAT composition profiles, including lower unsaturated levels, are cross-sectionally associated with older age. Prospective changes in BMAT composition with aging and the effect of serum follicle stimulating hormone (FSH), which influences both bone and fat metabolism, are unknown. We examined these associations in the AGES-Reykjavik Bone Marrow Adipose cohort, using sex-stratified linear regression models adjusted for covariates including estradiol and testosterone. At baseline, 236 women and 245 men had mean age 81 (SD 4) and 83 (4) years, respectively. Over a mean 3.3 years for 154 women and 2.6 years for 151 men, there was no significant change in total or saturated BMAT. However, mean unsaturated BMAT increased in women (+0.26 %/year, 95 % CI +0.21 %/year to +0.32 %/year) and men (+0.24 %/year, 95 % CI +0.18 %/year to +0.30 %/year). Among women, greater increases in unsaturated BMAT were associated with significantly greater reductions in vertebral trabecular volumetric BMD. At baseline, women in the highest FSH quartile had highest total (66.6 %, 95 % CI 64.3 %-69.0 %) and saturated BMAT (95 % CI 49.3 %, 47.5 %-51.0 %). No relationship existed between FSH and unsaturated BMAT in women or any BMAT outcome in men. Longitudinally, in women, higher FSH was associated with greater increase in unsaturated BMAT. There was no relationship between FSH and change in total or saturated BMAT in women or any change outcome in men. In older adults, total BMAT was stable, but BMAT composition changed with increases in unsaturated BMAT. In women, higher FSH correlated cross-sectionally with higher saturated BMAT but longitudinally with greater gain in unsaturated BMAT. These novel findings warrant further longitudinal studies to better characterize BMAT changes and the role of FSH.
Craniofacial and whole-skeleton fracture patterns in osteogenesis imperfecta: Findings from a nationwide U.S. insurance claims database.
Sung HH, Whitney DG, Kozloff KM … +1 more , Caird MS
Bone · 2026 Mar · PMID 41407176 · Full text
BACKGROUND: Osteogenesis imperfecta (OI) is an inherited connective tissue disease characterized by lifelong skeletal fragility and recurrent fractures. While most prior research has focused on long bone fractures in sel...
BACKGROUND: Osteogenesis imperfecta (OI) is an inherited connective tissue disease characterized by lifelong skeletal fragility and recurrent fractures. While most prior research has focused on long bone fractures in selected clinical cohorts, population-based estimates of craniofacial and site-specific fracture risk in OI remain largely limited. This study used insurance claims data to quantify the period prevalence, anatomical distribution, and predictors of fractures in individuals with versus without OI. METHODS: A retrospective cohort study was conducted using the IBM® MarketScan® Multi-State Medicaid (2016-2022, all ages) and Commercial Databases (2016-2022, < 65 years old). Diagnosis of OI and all fractures were identified using ICD and CPT codes recorded during healthcare encounters. The first full year of enrollment was used to determine 1-year period prevalence and counts of fractures overall and by site, stratified by age (<5, 6-9, 10-13, 14-18, 19-25, ten-year intervals to >55). Differences between cohorts were estimated using relative risk (RR). Associations with demographic and clinical factors were assessed via logistic regression. Proxy measures of OI severity and medical device use were applied, as clinical classification and exposure to treatments could not be directly adjudicated. RESULTS: Among 4294 individuals with OI and approximately 54.8 million controls, the overall fracture prevalence was 33.9 % in the OI cohort versus 2.5 % in controls (RR 13.6), with elevated rates observed at all anatomical sites. Jaw (craniofacial) fractures were nearly seven times more frequent in OI (0.40 % vs. 0.06 %; RR 6.7), while femur fractures showed the greatest disparity (RR 119.4). Age-specific analysis revealed the highest fracture risk for individuals with OI in early childhood, particularly at craniofacial and axial sites, with risk increasing further in those with greater proxy-measured disease severity. Female was associated with lower odds of fracture compared to males, and Medicaid coverage correlated with increased risk at select skeletal sites. Limitations include inability to distinguish fracture etiology (spontaneous, traumatic, or iatrogenic), unmeasured exposure to treatments, inability to apply clinical OI classifications, and exclusion of uninsured individuals. CONCLUSIONS: Individuals with OI face a markedly greater and distinctive burden of fractures, including craniofacial involvement, than the general population. This work provides the first large-scale, population-based estimates of craniofacial fracture burden in OI, highlighting distinct age- and site-specific risk patterns. These findings reinforce the importance of ongoing, site-specific monitoring and integrated multidisciplinary care for individuals with OI, supporting clinicians in anticipatory guidance and tailored prevention strategies.
Predicting skeletal age from HR-pQCT imaging.
Bugbird AR, Boyd SK
Bone · 2026 Mar · PMID 41391644 · Publisher ↗
INTRODUCTION: High-resolution peripheral quantitative computed tomography (HR-pQCT) provides detailed bone microarchitecture assessments, but the interpretability of its many complex parameters remains challenging. This...
INTRODUCTION: High-resolution peripheral quantitative computed tomography (HR-pQCT) provides detailed bone microarchitecture assessments, but the interpretability of its many complex parameters remains challenging. This study aimed to develop a deep learning model to estimate skeletal age from HR-pQCT scans, offering an interpretable, quantitative summary of bone health relative to chronological age. METHODS: The training dataset included 1236 adults (62.1% female) from a normative cohort, and an independent test set of 460 adults (69.3% female). HR-pQCT scans of the distal radius and tibia were acquired for all participants. Five models were trained: 2D models using a single radius (2DRad) and tibia (2DTib) slice from the middle of the scan; 3D models using full volumetric radius (3DRad) and tibia (3DTib); and a combined 2D model (2DRadTib) applying linear regression to the 2D outputs. RESULTS: The 2DRadTib model achieved the best performance, with a validation mean absolute error (MAE) of 5.29 ± 4.60 years (R = 0.85) and test MAE of 5.34 ± 4.38 years (R = 0.85). Saliency maps revealed cortical bone was most influential in younger individuals, while both cortical and trabecular features contributed in older participants. Predicted skeletal age was strongly correlated with established HR-pQCT parameters, particularly cortical and density measures (ρ = -0.51 to 0.85), indicating the model relies on key bone features. CONCLUSION: We present a novel deep learning framework for skeletal age prediction from HR-pQCT, providing a concise and interpretable summary measure of bone health. This approach may enhance the clinical utility of HR-pQCT by improving interpretability and supporting early identification of accelerated skeletal aging. LAY SUMMARY: High-resolution peripheral quantitative computed tomography (HR-pQCT) provides detailed images of bone structure, but the volume and complexity of data can make interpretation difficult. In this study, we developed a deep learning model to estimate skeletal age from HR-pQCT scans, offering a simplified and interpretable measure of bone health. By translating complex imaging data into an age-based summary, this approach may enhance clinical use of HR-pQCT, support early identification of individuals at risk of accelerated bone loss, and improve patient understanding by providing a relatable measure of skeletal integrity.
Evaluation of trabecular and subentheseal bone volume density in calcaneus with dual-echo ultrashort echo time magnetic resonance imaging: In vivo feasibility study.
Doi K, Moazamian D, Wu Y … +7 more , Yamamoto T, Leu A, Alenezi S, Flint JH, Cheng KY, Ma Y, Jerban S
Bone · 2026 Mar · PMID 41391643 · Publisher ↗
Trabecular and entheseal bone quantity in the calcaneus may relate to general bone health and physical activity levels of patients. Magnetic resonance imaging (MRI) has been increasingly used for bone evaluation, to avoi...
Trabecular and entheseal bone quantity in the calcaneus may relate to general bone health and physical activity levels of patients. Magnetic resonance imaging (MRI) has been increasingly used for bone evaluation, to avoid ionizing radiation and enable simultaneous evaluation of surrounding soft tissue. A rapid quantitative MRI-based method to estimate bone volume to total volume (BV/TV), solving eatures, has been developed utilizing a dual echo ultrashort echo time (UTE) sequence that can directly acquire bone and free water signal for further quantification. This nvestigated the feasibility of using dual echo UTE for trabecular and subentheseal BV/TV evaluation in the calcaneus. Ankle joints of 32 healthy subjects (12 women and 20 men, 35.0 ± 6.8years old) were scanned in the sagittal plane using dual echo UTE with 3 min scan time. BV/TV was measured in four regions of interest (ROIs); proximal calcaneal crescent (ROI 1), plantar calcaneal crescent (ROI 2), deep calcaneal bone (ROI 3), and subentheseal bone (ROI 4). Differences were examined with Kruskal Wallis test. Spearman's correlations of BV/TV with age, weight, height, and BMI were calculated. BVTV was significantly different (p < 0.05) between regions (mean ± SD of 42.8 ± 4.3, 41.7 ± 3.2,38.4 ± 3.3, and 37.8 ± 3.2 for subentheseal bone, proximal calcaneal crescent, plantar calcaneal crescent, and deep trabecular regions, respectively). BV/TV showed significant positive correlations with age and weight in all regions. This study highlights the lity of dual echo UTE technique for rapid MRI-based evaluation of BV/TV in patients.
Association of body fat distribution with bone mineral density: evidence from observational and mendelian randomization analyses.
Sun Q, Cui L, Liu Y … +9 more , Pang Q, Chi Y, Jiajue R, Liu W, Jiang Y, Wang O, Li M, Xing X, Xia W
Bone · 2026 Mar · PMID 41386581 · Publisher ↗
BACKGROUND: Although higher body weight is generally considered protective against low bone mineral density (BMD), the influence of body fat distribution on BMD remains unclear. We aimed to investigate whether specific a...
BACKGROUND: Although higher body weight is generally considered protective against low bone mineral density (BMD), the influence of body fat distribution on BMD remains unclear. We aimed to investigate whether specific adipose tissue depots have differential associations with BMD and to assess causality using Mendelian randomization (MR). METHODS: We conducted a cross-sectional analysis using National Health and Nutrition Examination Survey (NHANES) data to evaluate associations between regional fat depots (gynoid, android, visceral, abdominal subcutaneous fat, and total fat percentage) and BMD at total body, femoral neck, and lumbar spine. Multivariable linear regression was used to evaluate these relationships. To assess potential causal effects, we performed two-sample MR using genome-wide association study summary statistics for fat distribution traits and BMD. RESULTS: Gynoid fat was positively associated with BMD at the total body, femoral neck, and lumbar spine, while visceral and total body fat showed consistent inverse associations across these regions. Two-sample MR analysis supported a causal effect of gynoid fat on BMD but found no evidence of causality for visceral or total body fat. CONCLUSIONS: Gynoid fat shows a beneficial and causal effect on BMD, whereas the inverse associations observed for visceral and total body fat appear to be non-causal. These findings underscore the importance of considering fat distribution, not merely total body fat or weight, when evaluating bone health.
Region-specific variation in trapeziometacarpal joint bone microarchitecture in females with osteoarthritis assessed using HR-pQCT.
Kuczynski MT, Hasselaar C, Dhaliwal G … +4 more , Hiscox C, White NJ, Whittier DE, Manske SL
Bone · 2026 Mar · PMID 41380947 · Publisher ↗
The trapeziometacarpal (TMC) joint is commonly affected by osteoarthritis (OA), and its unique morphology creates localized loading patterns that cause regional bone adaption. Radiographic OA is more prevalent than sympt...
The trapeziometacarpal (TMC) joint is commonly affected by osteoarthritis (OA), and its unique morphology creates localized loading patterns that cause regional bone adaption. Radiographic OA is more prevalent than symptomatic OA, highlighting the disconnect between structural features and clinical disease. Ex vivo studies have demonstrated regional changes in trapezial bone microarchitecture but are limited to cadaveric specimen with advanced disease. In vivo studies are needed to characterize regional bone microarchitecture in symptomatic TMC OA. We investigated regional bone microarchitecture in females with TMC OA using high-resolution peripheral quantitative computed tomography (HR-pQCT), and whether these changes differed from those associated with ageing. HR-pQCT scans of the TMC joint were acquired from 13 females with TMC OA, 12 controls matched groupwise by age and sex, and 15 sex-matched young controls. Total bone mineral density, bone volume fraction (Tt.BV/TV), thickness, and separation were quantified by quadrant in the first metacarpal and trapezium. A mixed ANOVA assessed group, quadrant, and group-by-quadrant effects. Significant interaction effects were observed for all parameters in the trapezium and separation in the first metacarpal (p < 0.001). In OA, trapezial separation was higher, and Tt.BV/TV was lower in the ulnar-volar quadrant, while separation was lower in the radial-volar quadrant compared to young controls (p < 0.05). In the first metacarpal, radial-volar separation was lower in OA than young controls (p < 0.05). These results suggest that OA may disrupt the normal variation in first metacarpal and trapezial bone microarchitecture, highlighting the utility of HR-pQCT in early detection of structural bone changes in hand OA.
Fermented mealworm extract prevents concurrent bone and muscle loss by modulating RANKL-NFκB/MAPK signaling in ovariectomized mice.
Choi SY, Lee MK
Bone · 2026 Mar · PMID 41371429 · Publisher ↗
This study investigated whether fermented mealworms extract (FME) can simultaneously improve postmenopausal osteoporosis and muscle atrophy, along with the underlying mechanisms. Female C57BL/6 N mice were divided into f...
This study investigated whether fermented mealworms extract (FME) can simultaneously improve postmenopausal osteoporosis and muscle atrophy, along with the underlying mechanisms. Female C57BL/6 N mice were divided into five groups: sham-operated, ovariectomized (OVX), OVX treated with two doses of FME (200 and 500 mg/kg, oral), and OVX treated with alendronate (Alen, 500 μg/kg, oral) as a positive control, for 15 weeks. FME500 significantly increased grip strength, whereas FME200 showed no significant improvement compared to the OVX group. Muscle cross-sectional area significantly increased in both FME groups compared to the OVX group. FME500 also enhanced muscle protein synthesis markers (MyoD1 and MHC) and more effectively suppressed muscle degradation markers (MuRF-1, atrogin-1, myostatin, and polyubiquitinated proteins) than FME200. In bone, both FME doses improved bone density and serum levels of RANKL and CTX-1 compared to the OVX group. FME500 more effectively downregulated RANKL, IL-6, and TNF-α expression in both bone and muscle than FME200 in OVX group. Mechanistic analyses were performed mainly in the FME500 group, which downregulated NFκB/MAPK and upregulated IGF-1-PI3K-Akt in both bone and muscle. These results indicate that FME suppresses the postmenopausal concurrent bone and muscle loss by regulating RANKL-NFκB/MAPK and IGF-1-PI3K-Akt signaling pathways.
Expression of proteins secreted by osteocytes in bone biopsies of patients with chronic kidney disease and iron overload, before and after treatment with deferoxamine.
Machado HKAG, Dos Reis LM, Nunes LA … +7 more , Oliveira IB, Silva C, Dominguez WV, Elias RM, Moysés RM, Custódio M, Jorgetti V
Bone · 2026 Mar · PMID 41352648 · Publisher ↗
INTRODUCTION: Individuals with CKD can develop anemia, as well as mineral and bone disorder. Anemia is treated with recombinant erythropoietin and iron supplementation, which can result iron overload in various organs. L...
INTRODUCTION: Individuals with CKD can develop anemia, as well as mineral and bone disorder. Anemia is treated with recombinant erythropoietin and iron supplementation, which can result iron overload in various organs. Little is known about the effects of iron overload and its treatment on bone remodeling and osteocyte expression of relevant proteins. The objective of this study was to evaluate the effects that iron overload and treatment with the iron chelator deferoxamine have on parameters of iron metabolism in bone tissue and on osteocyte protein expression. METHODS: This was an observational study of individuals with CKD and iron overload who underwent bone biopsy and were treated with deferoxamine. Biochemical analysis, histomorphometry, and immunohistochemistry were performed. The results were compared with those obtained for controls. RESULTS: Deferoxamine treatment reduced all parameters of iron metabolism decreased calcium, increased alkaline phosphatase, and decreased (intact and c-terminal) fibroblast growth factor 23 levels. After treatment, trabecular separation increased, and osteoblast surface decreased. DFO treatment increased the expression of DMP-1, decreased the expression of DKK-1, PHEX and the RAGE proteins involved in bone remodeling and oxidative stress. Comparison of the expression of osteocyte proteins before and after DFO treatment with their expression in normal bone tissue, there was also increased expression of proteins that act in the formation of dendrites and cytoskeleton, such as E11 and CD44. CONCLUSION: In patients with CKD and iron overload, deferoxamine treatment modulates bone remodeling and expression of osteocyte proteins, which also play a role in the process.
Does irradiation adversely impact bone forming properties of demineralized bone matrix and allograft bone? A systematic review of the literature.
Tabbaa SM, Davidson EA, Miclau T … +1 more , El Naga A
Bone · 2026 Mar · PMID 41349634 · Publisher ↗
Abstract loading — click title to view on PubMed.
Pro-osteogenic effects of green Rooibos (Aspalathus linearis) against different dietary backgrounds in male Wistar rats.
Khan J, Sadie-Van Gijsen H, Kotzé-Hörstmann LM … +4 more , Kotze SH, Windvogel SL, Brink TN, Layman-Lemphane JI
Bone · 2026 Mar · PMID 41344408 · Publisher ↗
Previous in vitro studies have demonstrated direct effects of Rooibos (Aspalathus linearis) on bone cell populations, notably osteoblasts and osteoclasts, but in vivo evidence of Rooibos effects on bone remain scant. Her...
Previous in vitro studies have demonstrated direct effects of Rooibos (Aspalathus linearis) on bone cell populations, notably osteoblasts and osteoclasts, but in vivo evidence of Rooibos effects on bone remain scant. Here, we compared the effects of a green (minimally oxidized) Rooibos extract (GRT) on the femora of male Wistar rats, against the background of a medium-fat/high-sugar (MF/HS) and a high-fat/high-fructose (HF/Fr) diet. Male Wistar rats were maintained for 17 weeks on one of three diets: control (CON), MF/HS (OB1) or HF/Fr (OB2) (n = 24 each). From weeks 11-17, n = 12 animals in each group received oral GRT supplementation (60 mg/kg body weight daily). Femoral bone mineral content and density (BMC, BMD) were analysed by densitometry; cortical and cancellous bone microarchitecture was assessed using micro-computed tomography (μCT); and osteoblast (N.Ob), osteoclast (N.Oc), adipocyte (N.Ad) and chondrocyte numbers (N.Ch) were quantified histomorphometrically. GRT supplementation did not affect femur weight, BMC or BMD, but improved trabecular measurements were observed in the CON-GRT group, compared to all other groups. GRT increased N.Ob/mm and decreased N.Oc/mm in the CON and OB2 dietary groups. Notably, GRT reversed the OB2 diet-associated increase in N.Oc/mm in both cortical and cancellous bone. Although GRT had no effect on serum malondialdehyde (MDA) levels as a measure of systemic oxidative stress status, serum MDA levels were nevertheless positively correlated with cortical and cancellous N.Oc/mm and negatively correlated with cortical N.Ob/mm. Overall, GRT supplementation had pro-osteogenic and anti-osteoclastogenic effects in vivo, indicating that green Rooibos should be further explored as a bone-supporting nutraceutical.
Development of an explainable machine learning model to reproduce and interpret expert pharmacological decisions in osteoporosis treatment.
Sugawara Y, Shimizu T, Ishizu H … +6 more , Arita K, Ohashi Y, Yamazaki S, Kokabu T, Yamada K, Iwasaki N
Bone · 2026 Mar · PMID 41338331 · Publisher ↗
The management of osteoporosis in real-world clinical practice is highly heterogeneous, reflecting the complexity and variability inherent in therapeutic decision-making. Although artificial intelligence (AI)-based tools...
The management of osteoporosis in real-world clinical practice is highly heterogeneous, reflecting the complexity and variability inherent in therapeutic decision-making. Although artificial intelligence (AI)-based tools have been developed to support diagnosis, limited research has investigated their potential to elucidate the rationale underlying treatment choices. This study applied explainable machine learning to replicate and interpret pharmacological treatment decisions made by two board-certified osteoporosis specialists. We retrospectively analyzed 1481 patients who underwent dual-energy X-ray absorptiometry (DXA) and lateral spine radiography between 2020 and 2023 at Hokkaido University Hospital and two affiliated institutions. Two specialists independently assigned patients to one of five non-overlapping treatment categories. External validation was performed in 372 outpatients from three independent hospitals in 2024. The LightGBM model demonstrated the highest predictive performance. To interpret this model, we analyzed feature importance and applied SHapley Additive exPlanations (SHAP) to identify the most influential clinical factors driving treatment decisions. The LightGBM model achieved an accuracy of 0.90 and an F1-score of 0.90 in external validation. SHAP analysis revealed that femoral neck bone mineral density (BMD) and severity of vertebral fractures (especially grade 3) were the most influential factors in treatment selection. These patterns mirrored the expert reasoning, highlighting the prioritization of objective imaging data in therapeutic decisions. This study demonstrated that explainable AI can clarify the clinical reasoning behind osteoporosis treatment decisions. Bone mineral density and vertebral fracture severity are key determinants, supporting a transparent and reproducible framework for future decision support tools that assist clinicians in making consistent therapeutic decisions.
Genetic contributors to osteoporosis in pregnancy and lactation associated osteoporosis (PLO).
Lynch L, Shea PR, Vena N … +10 more , Chung WK, Shane E, Kamanda-Kosseh M, Barry J, El-Najjar D, Agarwal S, Kondapalli A, Colon I, Bucovsky M, Cohen A
Bone · 2026 Mar · PMID 41330509 · Full text
Pregnancy- and lactation-associated osteoporosis (PLO) describes a fragility fracture presentation around pregnancy/lactation. Presentation often includes multiple vertebral fractures, but can also involve hip, sacral/pe...
Pregnancy- and lactation-associated osteoporosis (PLO) describes a fragility fracture presentation around pregnancy/lactation. Presentation often includes multiple vertebral fractures, but can also involve hip, sacral/pelvic, or other fractures. Substantial bone structural deficits and low bone formation rate have been documented. Most have no known secondary cause. Many have a history of childhood fracture and/or family history of osteoporosis. These characteristics, together with early onset and disease severity, lead to the hypothesis that genetic factors may contribute to PLO. We enrolled 110 women with PLO (mean #fractures = 6, vertebral fractures in 88 %) in an exome sequencing (ES) study. Analyses identified rare (<1 % allele frequency in gnomAD) predicted deleterious variants (RPDV) in 33/110 (30 %) women. All were heterozygous; two participants had multiple RPDV. No RPDV in COL1A1/COL1A2 were identified. 28/110 (25 %) had RPDV in genes related to WNT signaling, critical to bone formation: LRP5 (n = 19), LRP6 (n = 6), WNT1 (n = 2) or WNT1&LRP5 (n = 1). Seven had RPDV related to renal/calcium handling (SLC34A1, SLC34A3, SLC9A3), or other osteoporosis mechanisms (PLS3 (n = 3), HGD (n = 1)). Those with RPDV did not differ from those without in terms of BMD, fracture characteristics, and most clinical characteristics. Among 110 PLO women, exome sequencing analyses identified a potential genetic osteoporosis contribution in 30 %, suggesting that many genetic contributors to PLO have yet to be elucidated. The finding of variants related to WNT signaling in 25 % of the cohort is consistent with the predominantly low bone formation phenotype of PLO and may have implications for prognosis and treatment response.
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