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Detailed characterization of bone marrow adipose tissue mesenchymal stem cells in healthy donor, Fanconi anemia, and acute myeloid leukemia

IF 3.5 2区医学 Q2 ENDOCRINOLOGY & METABOLISM

Bone

Pub Date : 2025-02-01 DOI: 10.1016/j.bone.2025.117413

Bihter Muratoğlu , Cansu Özdemir , Cemil Can Eylem , Tuba Reçber , Emirhan Nemutlu , Esin Alpdündar-Bulut , İbrahim Vargel , Duygu Uçkan-Çetinkaya

Bone marrow is a complex tissue featuring distinct cellular organization and diverse cell types. Bone marrow adipose tissue (BMAT) is a dynamic component crucial for tissue function and disease processes. This study explores differences between bone marrow-derived mesenchymal stem cells (BM-MSCs) and BMAT-derived mesenchymal stem cells (BMAT-MSCs), isolated from the same cavity, examining their differentiation potential and secretory profiles. BM-MSCs and BMAT-MSCs both exhibit classical mesenchymal characteristics, with over 90 % positivity for markers such as CD105 and CD29. Notably, BMAT-MSCs display significantly higher differentiation potential than BM-MSCs, with enhanced osteogenic and adipogenic capabilities, as indicated by increased calcium accumulation and lipid storage. In Fanconi anemia (FA) and acute myeloid leukemia (AML), osteogenic potential is limited, indicating impaired differentiation under these pathological conditions. Gene expression analysis of adipogenic molecules and metabolic regulators revealed significant differences in expression profile between BM- and BMAT-MSCs, particularly during adipogenic differentiation, indicating distinct characteristics that were more notable in FAs and AMLs. Furthermore, metabolomic profiling of BM plasma, using GC–MS for in-vivo niche reflection, and lipid analysis via LC-qTOF-MS show significant lipidomic alterations in patient samples, highlighting metabolic dysregulation and lipid remodeling. Lipid-mediated signaling and membrane composition changes appear integral to disease mechanisms. In conclusion, this study highlights the distinctive molecular and metabolomic profiles and adaptive mechanisms of BM- and BMAT-MSCs in bone marrow pathologies.

{"title":"Detailed characterization of bone marrow adipose tissue mesenchymal stem cells in healthy donor, Fanconi anemia, and acute myeloid leukemia","authors":"Bihter Muratoğlu , Cansu Özdemir , Cemil Can Eylem , Tuba Reçber , Emirhan Nemutlu , Esin Alpdündar-Bulut , İbrahim Vargel , Duygu Uçkan-Çetinkaya","doi":"10.1016/j.bone.2025.117413","DOIUrl":"10.1016/j.bone.2025.117413","url":null,"abstract":"<div><div>Bone marrow is a complex tissue featuring distinct cellular organization and diverse cell types. Bone marrow adipose tissue (BMAT) is a dynamic component crucial for tissue function and disease processes. This study explores differences between bone marrow-derived mesenchymal stem cells (BM-MSCs) and BMAT-derived mesenchymal stem cells (BMAT-MSCs), isolated from the same cavity, examining their differentiation potential and secretory profiles. BM-MSCs and BMAT-MSCs both exhibit classical mesenchymal characteristics, with over 90 % positivity for markers such as CD105 and CD29. Notably, BMAT-MSCs display significantly higher differentiation potential than BM-MSCs, with enhanced osteogenic and adipogenic capabilities, as indicated by increased calcium accumulation and lipid storage. In Fanconi anemia (FA) and acute myeloid leukemia (AML), osteogenic potential is limited, indicating impaired differentiation under these pathological conditions. Gene expression analysis of adipogenic molecules and metabolic regulators revealed significant differences in expression profile between BM- and BMAT-MSCs, particularly during adipogenic differentiation, indicating distinct characteristics that were more notable in FAs and AMLs. Furthermore, metabolomic profiling of BM plasma, using GC–MS for in-vivo niche reflection, and lipid analysis via LC-qTOF-MS show significant lipidomic alterations in patient samples, highlighting metabolic dysregulation and lipid remodeling. Lipid-mediated signaling and membrane composition changes appear integral to disease mechanisms. In conclusion, this study highlights the distinctive molecular and metabolomic profiles and adaptive mechanisms of BM- and BMAT-MSCs in bone marrow pathologies.</div></div>","PeriodicalId":9301,"journal":{"name":"Bone","volume":"193 ","pages":"Article 117413"},"PeriodicalIF":3.5,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143082572","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Global epidemiology of lower limb fractures: Trends, burden, and projections from the GBD 2021 study

IF 3.5 2区医学 Q2 ENDOCRINOLOGY & METABOLISM

Bone

Pub Date : 2025-01-31 DOI: 10.1016/j.bone.2025.117420

Yunfa Wang , Zhilin Wang , Bin Chen , Bofan Chen , Ruiying Fang , Haimin Zeng , Jie Peng , Yuan Gao , Liang Hao

Background

Lower limb fractures are a significant global public health issue, imposing considerable social and economic burdens. Despite their prevalence, comprehensive analyses of the global epidemiology of lower limb fractures remain scarce. This study aims to address this gap.

Methods

Using data from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2021, we analyzed four types of lower limb fractures: fractures of foot bones excluding the ankle (FFB), hip fractures (FH), fractures of the patella, tibia or fibula, or ankle (FPTFA), and femur fractures excluding the femoral neck (FF), and conducted a detailed assessment of them.

Results

FPTFA was the most burdensome fracture type, with Slovenia showing the highest age-standardized incidence rate (ASIR), and Saudi Arabia having the highest age-standardized prevalence rate (ASPR) and years lived with disability rate (ASYR). The burden of lower limb fractures increased with age, but FFB and FPTFA showed a “double peak” age distribution, with FFB most common in the 20–24 age group. Lower limb fractures were more prevalent in males among younger individuals and in females among older populations. From 1990 to 2021, the burden of lower limb fractures, excluding FH, decreased (EAPC <1), though the incidence of FF is projected to increase (EAPC = 0.14, 95 % CI 0.1–0.18) over the next decade.

Conclusion

Although the global burden of lower limb fractures, excluding FH, has decreased in recent years, vigilance is still needed. Given the projected rise in FF incidence over the next decade, preventive measures should be implemented early.

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引用次数: 0

Effect of acute performance fatigue on tibial bone strain during basketball maneuvers

IF 3.5 2区医学 Q2 ENDOCRINOLOGY & METABOLISM

Bone

Pub Date : 2025-01-30 DOI: 10.1016/j.bone.2025.117417

Chenxi Yan , Ryan J. Bice , Jeff W. Frame , Mariana E. Kersh , Stuart J. Warden

The tibia is one of the most common sites for bone stress injury (BSI) in active individuals. BSIs are thought to occur in response to damage accumulation from repetitive loading below the tissue's yield limit. The effect of fatigue on musculoskeletal biomechanics and tibial bone strain during athletic movements remains unclear. In this study, participant-specific finite element (FE) and musculoskeletal models in 10 collegiate-basketball players were used to analyze the effect of acute performance fatigue on joint kinematics and torques, ground reaction forces (GRFs), and the magnitude and distribution of tibial bone strains during select basketball maneuvers. Participants were fatigued by performing repeated exercises wearing a weighted vest until their vertical jump height decreased by 20 %. Fatigue reduced the vertical GRF during midstance of a jump task, and lowered hip and knee peak extension torques and ankle plantarflexion. However, fatigue had limited impact on tibial bone strain magnitude and distribution during jumping. In contrast, there was a shift in peak strain timing following fatigue during a lateral cut task and reduced strain at various times of stance during sprinting. The results suggest that fatigue was induced and, if anything, reduced tibial bone strain. As increased bone strain is thought to be associated with increased BSI risk, the reduced strain observed in the current study suggests that fatigue may actually be partly protective, possibly as a result of reduced muscle activation and force production.

{"title":"Effect of acute performance fatigue on tibial bone strain during basketball maneuvers","authors":"Chenxi Yan , Ryan J. Bice , Jeff W. Frame , Mariana E. Kersh , Stuart J. Warden","doi":"10.1016/j.bone.2025.117417","DOIUrl":"10.1016/j.bone.2025.117417","url":null,"abstract":"<div><div>The tibia is one of the most common sites for bone stress injury (BSI) in active individuals. BSIs are thought to occur in response to damage accumulation from repetitive loading below the tissue's yield limit. The effect of fatigue on musculoskeletal biomechanics and tibial bone strain during athletic movements remains unclear. In this study, participant-specific finite element (FE) and musculoskeletal models in 10 collegiate-basketball players were used to analyze the effect of acute performance fatigue on joint kinematics and torques, ground reaction forces (GRFs), and the magnitude and distribution of tibial bone strains during select basketball maneuvers. Participants were fatigued by performing repeated exercises wearing a weighted vest until their vertical jump height decreased by 20 %. Fatigue reduced the vertical GRF during midstance of a jump task, and lowered hip and knee peak extension torques and ankle plantarflexion. However, fatigue had limited impact on tibial bone strain magnitude and distribution during jumping. In contrast, there was a shift in peak strain timing following fatigue during a lateral cut task and reduced strain at various times of stance during sprinting. The results suggest that fatigue was induced and, if anything, reduced tibial bone strain. As increased bone strain is thought to be associated with increased BSI risk, the reduced strain observed in the current study suggests that fatigue may actually be partly protective, possibly as a result of reduced muscle activation and force production.</div></div>","PeriodicalId":9301,"journal":{"name":"Bone","volume":"193 ","pages":"Article 117417"},"PeriodicalIF":3.5,"publicationDate":"2025-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143076715","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

A statistical shape and density model can accurately predict bone morphology and regional femoral bone mineral density variation in children

IF 3.5 2区医学 Q2 ENDOCRINOLOGY & METABOLISM

Bone

Pub Date : 2025-01-30 DOI: 10.1016/j.bone.2025.117419

Yidan Xu , Jannes Brüling , Laura Carman , Ted Yeung , Thor F. Besier , Julie Choisne

Finite element analysis (FEA) is a widely used tool to predict bone biomechanics in orthopaedics for prevention, treatment, and implant design. Subject-specific FEA models are more accurate than generic adult-scaled models, especially for a paediatric population, due to significant differences in bone geometry and bone mineral density. However, creating these models can be time-consuming, costly and requires medical imaging. To address these limitations, population-based models have been successful in characterizing bone shape and density variation in adults. However, children are not small adults and need their own population-based model to generate accurate and accessible musculoskeletal geometry and bone mineral density in a paediatric population. Therefore, this study aimed to create a biomechanical research tool to predict the personalized shape and density of the paediatric femur using a statistical shape and density model for a population of children aged from 4 to 18 years old. Femur morphology and bone mineral density were extracted from 330 CT scans of children. Variations in shape and density were captured using Principal Component Analysis (PCA). Principal components were correlated to demographic and linear bone measurements to create a predictive statistical shape-density model, which was used to predict femoral shape and density. A leave-one-out analysis showed that the shape-density model can predict the femur geometry with a root mean square error (RMSE) of 1.78 ± 0.46 mm and the bone mineral density with a normalized RMSE ranging from 8.9 % to 13.5 % across various femoral regions. These results underscore the model's potential to reflect real-world physiological variations in the paediatric femur. This statistical shape and density model has the potential for clinical application in rapidly generating personalized computational models using partial or no medical imaging data.

{"title":"A statistical shape and density model can accurately predict bone morphology and regional femoral bone mineral density variation in children","authors":"Yidan Xu , Jannes Brüling , Laura Carman , Ted Yeung , Thor F. Besier , Julie Choisne","doi":"10.1016/j.bone.2025.117419","DOIUrl":"10.1016/j.bone.2025.117419","url":null,"abstract":"<div><div>Finite element analysis (FEA) is a widely used tool to predict bone biomechanics in orthopaedics for prevention, treatment, and implant design. Subject-specific FEA models are more accurate than generic adult-scaled models, especially for a paediatric population, due to significant differences in bone geometry and bone mineral density. However, creating these models can be time-consuming, costly and requires medical imaging. To address these limitations, population-based models have been successful in characterizing bone shape and density variation in adults. However, children are not small adults and need their own population-based model to generate accurate and accessible musculoskeletal geometry and bone mineral density in a paediatric population. Therefore, this study aimed to create a biomechanical research tool to predict the personalized shape and density of the paediatric femur using a statistical shape and density model for a population of children aged from 4 to 18 years old. Femur morphology and bone mineral density were extracted from 330 CT scans of children. Variations in shape and density were captured using Principal Component Analysis (PCA). Principal components were correlated to demographic and linear bone measurements to create a predictive statistical shape-density model, which was used to predict femoral shape and density. A leave-one-out analysis showed that the shape-density model can predict the femur geometry with a root mean square error (RMSE) of 1.78 ± 0.46 mm and the bone mineral density with a normalized RMSE ranging from 8.9 % to 13.5 % across various femoral regions. These results underscore the model's potential to reflect real-world physiological variations in the paediatric femur. This statistical shape and density model has the potential for clinical application in rapidly generating personalized computational models using partial or no medical imaging data.</div></div>","PeriodicalId":9301,"journal":{"name":"Bone","volume":"193 ","pages":"Article 117419"},"PeriodicalIF":3.5,"publicationDate":"2025-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143076710","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Global burden of injury due to low bone mineral density in adults aged 55 years and older, 1990 to 2021: A population-based study

IF 3.5 2区医学 Q2 ENDOCRINOLOGY & METABOLISM

Bone

Pub Date : 2025-01-30 DOI: 10.1016/j.bone.2025.117418

Jiansheng Wang , Shaoting Luo , Fuxi Wang , Federico Canavese , Lianyong Li

Objectives

This study aimed to assess the global burden of injuries due to low bone mineral density (BMD) among adults aged 55 and above from 1990 to 2021, focusing on mortality and disability-adjusted life years (DALYs) and analyzing trends across sexes, age groups, and sociodemographic index (SDI) regions.

Methods

Data from the Global Burden of Disease Study 2021, covering 204 countries and territories, were analyzed. Joinpoint regression quantified temporal changes in mortality and DALYs, calculating average annual percentage change (AAPC). Age-period-cohort modeling elucidated demographic influences, and decomposition analysis identified key contributors to mortality changes.

Results

Globally, in 2021, the crude DALY rate for injuries due to low BMD was 900.32 (95 % UI: 742.64 to 1081.51) per 100,000, and the crude mortality rate was 27.04 (95 % UI: 22.49 to 30.75) per 100,000. The age-standardized mortality rate for injuries due to low BMD showed no significant change from 1990 to 2021 (AAPC 0.26 %, P = 0.071), but there was a significant increase in countries with a high SDI (AAPC 0.51 %, P = 0.001). The burden of disease in persons aged 80 years and older remained substantial, with a slight increase. Decomposition analysis identified population growth as the main driver of increasing mortality and DALYs.

Conclusion

Despite the reductions in DALY rates, the mortality has remained stable worldwide; however, has risen significantly in high SDI countries. The substantial and slightly increasing burden of disease in people aged 80 years and older underscores the need for targeted strategies for the prevention and management of low BMD to mitigate the future global impact of these injuries.

{"title":"Global burden of injury due to low bone mineral density in adults aged 55 years and older, 1990 to 2021: A population-based study","authors":"Jiansheng Wang , Shaoting Luo , Fuxi Wang , Federico Canavese , Lianyong Li","doi":"10.1016/j.bone.2025.117418","DOIUrl":"10.1016/j.bone.2025.117418","url":null,"abstract":"<div><h3>Objectives</h3><div>This study aimed to assess the global burden of injuries due to low bone mineral density (BMD) among adults aged 55 and above from 1990 to 2021, focusing on mortality and disability-adjusted life years (DALYs) and analyzing trends across sexes, age groups, and sociodemographic index (SDI) regions.</div></div><div><h3>Methods</h3><div>Data from the Global Burden of Disease Study 2021, covering 204 countries and territories, were analyzed. Joinpoint regression quantified temporal changes in mortality and DALYs, calculating average annual percentage change (AAPC). Age-period-cohort modeling elucidated demographic influences, and decomposition analysis identified key contributors to mortality changes.</div></div><div><h3>Results</h3><div>Globally, in 2021, the crude DALY rate for injuries due to low BMD was 900.32 (95 % UI: 742.64 to 1081.51) per 100,000, and the crude mortality rate was 27.04 (95 % UI: 22.49 to 30.75) per 100,000. The age-standardized mortality rate for injuries due to low BMD showed no significant change from 1990 to 2021 (AAPC 0.26 %, <em>P</em> = 0.071), but there was a significant increase in countries with a high SDI (AAPC 0.51 %, <em>P</em> = 0.001). The burden of disease in persons aged 80 years and older remained substantial, with a slight increase. Decomposition analysis identified population growth as the main driver of increasing mortality and DALYs.</div></div><div><h3>Conclusion</h3><div>Despite the reductions in DALY rates, the mortality has remained stable worldwide; however, has risen significantly in high SDI countries. The substantial and slightly increasing burden of disease in people aged 80 years and older underscores the need for targeted strategies for the prevention and management of low BMD to mitigate the future global impact of these injuries.</div></div>","PeriodicalId":9301,"journal":{"name":"Bone","volume":"193 ","pages":"Article 117418"},"PeriodicalIF":3.5,"publicationDate":"2025-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143076716","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Are balance and lower extremity muscle strength correlated with fracture risk independent of bone mineral density in postmenopausal women?: A cross-sectional study

IF 3.5 2区医学 Q2 ENDOCRINOLOGY & METABOLISM

Bone

Pub Date : 2025-01-29 DOI: 10.1016/j.bone.2025.117414

Büşra Şirin Ahısha , Nurdan Paker

Background

Postmenopausal women are at increased risk of fractures due to reduced bone mineral density (BMD) and impaired physical function. While fracture risk assessment tools like FRAX include clinical factors and BMD, they exclude functional measures such as balance and muscle strength, which are critical for fall prevention. This study aimed to evaluate the correlation between two functional tests- the 30-Second Sit to Stand Test (30STS) and the One Leg Stance Test (OLST)- and fracture risk, independent of BMD in postmenopausal women aged 50–70.

Methods

This cross-sectional study included 156 postmenopausal women aged 50–70. Fracture risk was assessed using FRAX. Postural balance was evaluated using the OLST, while lower extremity muscle strength was measured with the 30STS. Both tests were analyzed for correlations with 10-year risks of major osteoporotic fractures (MOF), hip fractures, femoral neck BMD, and T-score at the lumbar spine and femoral neck. Participants were grouped based on OLST (<10 s) and 30STS (<15 repetitions) cut-offs, and fracture risks were compared.

Results

OLST and 30STS scores were significantly negatively correlated with 10-year hip fracture risk (r = −0.347, p < 0.001 and r = −0.197, p = 0.014, respectively). A significant negative correlation was also observed between OLST scores and 10-year MOF risk (r = −0.245, p = 0.002). Participants with OLST <10 s had significantly higher 10-year hip and MOF risks, while those with 30STS <15 had significantly higher 10-year hip fracture risk only. No correlation was found with femoral neck BMD.

Conclusion

LST and 30STS are associated with fracture risk independent of BMD in postmenopausal women aged 50–70. These practical tests may help identify individuals at higher fracture risk and support early interventions.

{"title":"Are balance and lower extremity muscle strength correlated with fracture risk independent of bone mineral density in postmenopausal women?: A cross-sectional study","authors":"Büşra Şirin Ahısha , Nurdan Paker","doi":"10.1016/j.bone.2025.117414","DOIUrl":"10.1016/j.bone.2025.117414","url":null,"abstract":"<div><h3>Background</h3><div>Postmenopausal women are at increased risk of fractures due to reduced bone mineral density (BMD) and impaired physical function. While fracture risk assessment tools like FRAX include clinical factors and BMD, they exclude functional measures such as balance and muscle strength, which are critical for fall prevention. This study aimed to evaluate the correlation between two functional tests- the 30-Second Sit to Stand Test (30STS) and the One Leg Stance Test (OLST)- and fracture risk, independent of BMD in postmenopausal women aged 50–70.</div></div><div><h3>Methods</h3><div>This cross-sectional study included 156 postmenopausal women aged 50–70. Fracture risk was assessed using FRAX. Postural balance was evaluated using the OLST, while lower extremity muscle strength was measured with the 30STS. Both tests were analyzed for correlations with 10-year risks of major osteoporotic fractures (MOF), hip fractures, femoral neck BMD, and T-score at the lumbar spine and femoral neck. Participants were grouped based on OLST (<10 s) and 30STS (<15 repetitions) cut-offs, and fracture risks were compared.</div></div><div><h3>Results</h3><div>OLST and 30STS scores were significantly negatively correlated with 10-year hip fracture risk (<em>r</em> = −0.347, <em>p</em> < 0.001 and <em>r</em> = −0.197, <em>p</em> = 0.014, respectively). A significant negative correlation was also observed between OLST scores and 10-year MOF risk (<em>r</em> = −0.245, <em>p</em> = 0.002). Participants with OLST <10 s had significantly higher 10-year hip and MOF risks, while those with 30STS <15 had significantly higher 10-year hip fracture risk only. No correlation was found with femoral neck BMD.</div></div><div><h3>Conclusion</h3><div>LST and 30STS are associated with fracture risk independent of BMD in postmenopausal women aged 50–70. These practical tests may help identify individuals at higher fracture risk and support early interventions.</div></div>","PeriodicalId":9301,"journal":{"name":"Bone","volume":"193 ","pages":"Article 117414"},"PeriodicalIF":3.5,"publicationDate":"2025-01-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143076713","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

The protection of nicotinamide riboside against diabetes mellitus-induced bone loss via OXPHOS

IF 3.5 2区医学 Q2 ENDOCRINOLOGY & METABOLISM

Bone

Pub Date : 2025-01-28 DOI: 10.1016/j.bone.2025.117411

Jie Gao , Xiangyuan Meng , Xingxiang Yang , Chenqi Xie , Chunyan Tian , Jianbao Gong , Junwei Zhang , Shiyou Dai , Tianlin Gao

Diabetes mellitus is a global disease that results in various complications, including diabetic osteoporosis. Prior studies have indicated a correlation between low levels of nicotinamide adenine dinucleotide (NAD⁺) and diabetes-related complications. Nicotinamide riboside (NR), a widely utilized precursor vitamin of NAD⁺, has been demonstrated to enhance age-related osteoporosis through the Sirt1/FOXO/β-catenin pathway in osteoblast progenitors. However, the impact of NR on bone health in diabetes mellitus remains unclear. In this study, we assessed the potential effects of NR on bone in diabetic mice. NR was administered to high-fat diet (HFD)/streptozotocin (STZ)-induced type 2 diabetic mice (T2DM), and various parameters, including metabolic indicators, bone quality, bone metabolic markers, and RNA sequences, were measured. Our findings confirmed that HFD/STZ-induced T2DM impaired bone microstructures, resulting in bone loss. NR effectively ameliorated insulin resistance, improved bone microarchitecture, and bone quality, reduced bone resorption, enhanced the Forkhead box O (FOXO) signaling pathway, mitigated the nuclear factor kappa B (NF-kB) signaling pathway, and ameliorated the disorder of the oxidative phosphorylation process (OXPHOS) in diabetic mice. In conclusion, NR demonstrated the capacity to alleviate T2DM-induced bone loss through the modulation of OXPHOS in type 2 diabetic mice. Our results underscore the potential of NR as a therapeutic target for addressing T2DM-related bone metabolism and associated diseases. Further cell-based studies under diabetic conditions, such as in vitro cultures of key cell types (e.g., osteoblasts and osteoclasts), are necessary to validate these findings.

{"title":"The protection of nicotinamide riboside against diabetes mellitus-induced bone loss via OXPHOS","authors":"Jie Gao , Xiangyuan Meng , Xingxiang Yang , Chenqi Xie , Chunyan Tian , Jianbao Gong , Junwei Zhang , Shiyou Dai , Tianlin Gao","doi":"10.1016/j.bone.2025.117411","DOIUrl":"10.1016/j.bone.2025.117411","url":null,"abstract":"<div><div>Diabetes mellitus is a global disease that results in various complications, including diabetic osteoporosis. Prior studies have indicated a correlation between low levels of nicotinamide adenine dinucleotide (NAD<sup>+</sup>) and diabetes-related complications. Nicotinamide riboside (NR), a widely utilized precursor vitamin of NAD<sup>+</sup>, has been demonstrated to enhance age-related osteoporosis through the Sirt1/FOXO/β-catenin pathway in osteoblast progenitors. However, the impact of NR on bone health in diabetes mellitus remains unclear. In this study, we assessed the potential effects of NR on bone in diabetic mice. NR was administered to high-fat diet (HFD)/streptozotocin (STZ)-induced type 2 diabetic mice (T2DM), and various parameters, including metabolic indicators, bone quality, bone metabolic markers, and RNA sequences, were measured. Our findings confirmed that HFD/STZ-induced T2DM impaired bone microstructures, resulting in bone loss. NR effectively ameliorated insulin resistance, improved bone microarchitecture, and bone quality, reduced bone resorption, enhanced the Forkhead box O (FOXO) signaling pathway, mitigated the nuclear factor kappa B (NF-kB) signaling pathway, and ameliorated the disorder of the oxidative phosphorylation process (OXPHOS) in diabetic mice. In conclusion, NR demonstrated the capacity to alleviate T2DM-induced bone loss through the modulation of OXPHOS in type 2 diabetic mice. Our results underscore the potential of NR as a therapeutic target for addressing T2DM-related bone metabolism and associated diseases. Further cell-based studies under diabetic conditions, such as in vitro cultures of key cell types (e.g., osteoblasts and osteoclasts), are necessary to validate these findings.</div></div>","PeriodicalId":9301,"journal":{"name":"Bone","volume":"193 ","pages":"Article 117411"},"PeriodicalIF":3.5,"publicationDate":"2025-01-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143070092","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Type 2 diabetes patients exhibit delayed but coupled bone remodelling, maintaining cortical porosity comparable to healthy controls: A histomorphometric analysis of trans-iliac bone biopsies

IF 3.5 2区医学 Q2 ENDOCRINOLOGY & METABOLISM

Bone

Pub Date : 2025-01-28 DOI: 10.1016/j.bone.2025.117412

C.M. Andreasen , E.M. Wölfel , C. Ejersted , T.L. Andersen , M. Frost

Objective

Fracture risk is increased in longstanding type 2 diabetes (T2D). High-resolution peripheral quantitative CT scans have demonstrated higher cortical porosity in T2D complicated by microvascular disease (MVD). We investigated if cortical bone resorption is followed by inadequate bone formation in individuals with T2D complicated by MVD.

Methods

Thirty-five adult men and women with T2D were recruited from outpatient clinics and through public advertisement. All participants had at least one previous measure of c-peptide >700, a negative GAD antibody test, and 13 had known microvascular disease status. Trans iliac crest bone biopsies were collected for histomorphometric analysis. Glucose control was assessed using HbA1c. Additionally, trans iliac bone specimens from 10 individuals without T2D were included as controls.

Results

Following quality assessment, samples from 30 T2D and 10 controls were used for histomorphometric analyses of cortical bone remodelling. The final study population included 23 men and 7 postmenopausal women with a mean age of 65.8 years for the T2D-MVD group (CI95% 61.2–70.3) and 65.2 years in the T2D + MVD group (CI95% 59.6–70.9), and a mean T2D disease duration of 16.9 years. Seventeen had MVD (57 %). The controls included 5 men and 5 women with a mean age of 64.7 years (CI95% 58.5–70.9). The area, diameter, and density of cortical pores were the same in cases with and without MVD, but the pore diameter was lower than controls. While T2D had significantly more eroded-formative pores compared to controls, there were no significant differences in the proportion of eroded and formative pores between the groups. In quiescent pores/osteons, the osteon diameter and wall thickness were larger in T2D groups than controls.

Conclusion

Cortical bone porosity was not increased in individuals with T2D complicated by MVD. However, an enhanced prevalence of eroded-formative pores and increased osteon diameter concur with a slightly prolonged reversal-resorption phase in T2D irrespective of the presence of MVD.

目的：久治不愈的 2 型糖尿病（T2D）患者骨折风险增加。高分辨率外周定量 CT 扫描显示，并发微血管疾病（MVD）的 T2D 患者皮质孔隙率较高。我们研究了在 T2D 并发 MVD 的患者中，皮质骨吸收是否会导致骨形成不足：我们从门诊和公共广告中招募了 35 名患有 T2D 的成年男性和女性。所有参与者之前至少有一次 c 肽大于 700，GAD 抗体检测呈阴性，13 人有已知的微血管疾病状况。采集经髂嵴骨活检组织进行组织形态分析。使用 HbA1c 评估血糖控制情况。此外，还纳入了 10 名无 T2D 患者的经髂骨标本作为对照：经过质量评估后，来自 30 名 T2D 患者和 10 名对照组的样本被用于皮质骨重塑的组织形态学分析。最终研究对象包括 23 名男性和 7 名绝经后女性，T2D-MVD 组平均年龄为 65.8 岁（CI95% 61.2-70.3），T2D + MVD 组平均年龄为 65.2 岁（CI95% 59.6-70.9），T2D 病程平均为 16.9 年。17人患有中风（57%）。对照组包括 5 名男性和 5 名女性，平均年龄为 64.7 岁（CI95% 58.5-70.9）。有 MVD 和没有 MVD 的病例中，皮质毛孔的面积、直径和密度相同，但毛孔直径低于对照组。与对照组相比，后天性心脏病患者的侵蚀形成孔明显增多，但两组之间侵蚀形成孔的比例没有明显差异。在静止孔隙/骨质中，T2D 组的骨质直径和壁厚大于对照组：结论：并发骨髓增生异常的 T2D 患者的皮质骨孔隙率并没有增加。结论：无论是否存在血管内膜异位症，T2D 患者的皮质骨孔隙率并未增加，但侵蚀形成的孔隙增加，骨小梁直径增大，这与 T2D 患者的逆转-吸收阶段略有延长有关。

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引用次数: 0

The cumulative exposure to triglyceride-glucose index and the risk of onset fragility fractures

IF 3.5 2区医学 Q2 ENDOCRINOLOGY & METABOLISM

Bone

Pub Date : 2025-01-26 DOI: 10.1016/j.bone.2025.117409

Wenchao Yao , Nan Zhang , Lu Guo , Xiaoli Hou , Shuohua Chen , Lei Xing , Xinhao Fan , Yajing Liang , Yixiu Chen , Zhihui Liu , Shouling Wu , Faming Tian

Objective

To investigate the association between the cumulative exposure to triglyceride-glucose index (cumTyG index) and fragility fractures in the general population.

Methods

This prospective cohort study analyzed active and retired employees of Kailuan Group who participated in three consecutive health examinations in 2006, 2008 and 2010, and were followed up until 31st December 2022. The cohort comprised 55,824 participants who met the inclusion and exclusion criteria and were grouped using the cumTyG index quartiles. The outcome event was onset fragility fracture. The cumulative incidence of fragility fracture in each group was calculated by the Kaplan–Meier method, and the incidence curve was plotted. Between-group comparisons were performed using the log-rank test. A Cox regression model was used to analyze the hazard ratio (HR) and 95 % confidence interval (CI) of fragility fractures.

Results

Nine-hundred fragility fractures occurred during a mean follow-up of 11.35 years. After multivariate Cox regression analysis and adjustment for confounders (full model), the HR (95 % CI) of the group with the highest cumTyG index compared with the group with the lowest cumTyG index was 1.30 (1.04–1.61). The risk of fragility fracture was higher in men (HR 1.37, 95 % CI 1.06–1.77) and those taking antihypertensive drugs (HR 2.47, 95 % CI 1.25–4.86). There was a linear association between the cumTyG index and the risk of fragility fracture.

Conclusion

A high cumTyG index is a risk factor for fragility fracture and should be considered in the management of patients with high blood sugar and high cholesterol concentrations.

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引用次数: 0

Pharmacological and non-pharmacological therapies for prevention and treatment of osteoporosis in Duchenne Muscular Dystrophy: A systematic review 预防和治疗杜兴氏肌肉萎缩症患者骨质疏松症的药物和非药物疗法：系统综述。

IF 3.5 2区医学 Q2 ENDOCRINOLOGY & METABOLISM

Bone

Pub Date : 2025-01-24 DOI: 10.1016/j.bone.2025.117410

Sarah McCarrison , Shima Abdelrahman , Ros Quinlivan , Richard Keen , Sze Choong Wong

Background

Long term glucocorticoid treatment in Duchenne Muscular Dystrophy (DMD) is associated with a high incidence of fragility fractures. This systematic review aims to assess the current evidence for pharmacological and non-pharmacological treatment for osteoporosis in children and adults with DMD.

Methods

Three online databases (Embase, Medline, Cochrane Library) were searched for studies that evaluated interventions for treatment or prevention of osteoporosis in DMD. Included studies had to report changes in bone mineral density (BMD) or bone mineral content (BMC) Z-scores or fracture incidence.

Results

Nineteen studies were identified, including twelve that evaluated bisphosphonate, three evaluated testosterone (2 studies of the same patient group), one evaluated vitamin D/calcium, one teriparatide, and two evaluated vibration therapy. Only two randomised-controlled trials were found, one of intravenous bisphosphonate and one of vibration therapy. Changes in lumbar spine BMD ranged from −0.3 to +1.3 in studies of bisphosphonate and − 0.2 to 0.0 with vibration therapy, whereas this was +0.38 with testosterone and + 0.9 with vitamin D/calcium. There was limited information on impact on fracture in all studies. None of the pharmacological studies involved a fracture naïve group at baseline. In addition, none addressed a group of individuals over 18 years at baseline.

Conclusion

This systematic review provides evidence for the effectiveness of bisphosphonate therapy in improving bone density in children and adolescents with DMD. However, there is less information on the impact on fracture. The review did not find studies exclusively in those over 18 years old with DMD and limited information on non-bisphosphonate pharmacological agents.

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引用次数: 0