Pub Date : 2025-11-10DOI: 10.1016/j.bone.2025.117707
Sharvani Patil , Nikhil Shah , Alex Ireland , Vivek Patwardhan , Neha Sanwalka , Neha Kajale , Chidvilas More , Ketan Gondhalekar , Anuradha Khadilkar
{"title":"Corrigendum to “Familial determinants of bone health parameters – a dual X-ray absorptiometry (DXA) and peripheral quantitative computed tomography (pQCT)-based parent and offspring study in rural Indian children” [Bone (2026), volume 202, article 117685]","authors":"Sharvani Patil , Nikhil Shah , Alex Ireland , Vivek Patwardhan , Neha Sanwalka , Neha Kajale , Chidvilas More , Ketan Gondhalekar , Anuradha Khadilkar","doi":"10.1016/j.bone.2025.117707","DOIUrl":"10.1016/j.bone.2025.117707","url":null,"abstract":"","PeriodicalId":9301,"journal":{"name":"Bone","volume":"203 ","pages":"Article 117707"},"PeriodicalIF":3.6,"publicationDate":"2025-11-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145491022","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}
Pub Date : 2025-11-09DOI: 10.1016/j.bone.2025.117711
Alibek Zhakubayev , Kathleen A. Grant , Lara H. Sattgast , Russell T. Turner , Urszula T. Iwaniec , Mary Lauren Benton
Alcohol abuse is a risk factor for atraumatic fractures. Our previous work using a non-human primate model of voluntary ethanol consumption showed that chronic ethanol intake for 6 months to 2.5 years decreased global bone turnover and tibial cortical porosity but did not result in changes in distal tibia cancellous architecture. However, bone remodeling varies among skeletal sites. Here, we extended this analysis to include 3 additional cancellous bone compartments (distal femur metaphysis, distal femur epiphysis, lumbar vertebra). Specifically, we applied a machine learning framework to data from 155 monkeys (100 ethanol and 55 controls) to identify the bone features associated with chronic ethanol use. In concordance with our prior findings, we did not find that ethanol consumption resulted in population-level changes in cancellous bone architecture. These findings support the concept that ethanol consumption similarly decreases bone formation and bone resorption across sites, resulting in minimal changes in bone remodeling balance.
{"title":"Ethanol consumption has minimal effects on cancellous bone architecture in femur and lumbar vertebra in two species of non-human primates","authors":"Alibek Zhakubayev , Kathleen A. Grant , Lara H. Sattgast , Russell T. Turner , Urszula T. Iwaniec , Mary Lauren Benton","doi":"10.1016/j.bone.2025.117711","DOIUrl":"10.1016/j.bone.2025.117711","url":null,"abstract":"<div><div>Alcohol abuse is a risk factor for atraumatic fractures. Our previous work using a non-human primate model of voluntary ethanol consumption showed that chronic ethanol intake for 6 months to 2.5 years decreased global bone turnover and tibial cortical porosity but did not result in changes in distal tibia cancellous architecture. However, bone remodeling varies among skeletal sites. Here, we extended this analysis to include 3 additional cancellous bone compartments (distal femur metaphysis, distal femur epiphysis, lumbar vertebra). Specifically, we applied a machine learning framework to data from 155 monkeys (100 ethanol and 55 controls) to identify the bone features associated with chronic ethanol use. In concordance with our prior findings, we did not find that ethanol consumption resulted in population-level changes in cancellous bone architecture. These findings support the concept that ethanol consumption similarly decreases bone formation and bone resorption across sites, resulting in minimal changes in bone remodeling balance.</div></div>","PeriodicalId":9301,"journal":{"name":"Bone","volume":"203 ","pages":"Article 117711"},"PeriodicalIF":3.6,"publicationDate":"2025-11-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145497864","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}
Pub Date : 2025-11-08DOI: 10.1016/j.bone.2025.117720
Anna Maria Markarian , Dennis R. Taaffe , Daniel A. Galvão , Jodie Cochrane Wilkie , Carolyn J. Peddle-McIntyre , Mark Markarian , Daniel J. Schiferl , Robert U. Newton
Background
Assessing bone mineral density (BMD) in children and adolescents is essential for detecting skeletal deficits and fracture risk. Peripheral quantitative computed tomography (pQCT) has gained increasing attention as a valuable imaging tool due to its ability to assess bone quality. Unlike dual-energy x-ray absorptiometry, pQCT provides volumetric BMD measurements and distinguishes between cortical and trabecular compartments. Despite these advantages, its clinical adoption remains limited due to the lack of reference data and standardized protocols.
Methods
A systematic search was conducted in CINAHL, Embase, PubMed, SPORTDiscus, and Web of Science from inception to November 2024. Studies reporting pQCT-derived tibial BMD in healthy children and adolescents (<19 years old) were included. Meta-regression models using natural cubic splines were applied to estimate age-specific BMD values for trabecular and cortical bone. Potential moderators, such as sex, race, reference line location, limb, and pQCT device, were evaluated to assess their influence on BMD outcomes.
Results
Eighty-three studies (18,531 participants) were included in this review. The meta-regression models demonstrated a non-linear relationship between BMD and age, best described using natural cubic splines. Moderator analysis indicated that sex, race, and reference line location significantly influenced cortical BMD, while trabecular BMD was affected by reference line location and pQCT device. The choice of limb assessed (dominant vs non-dominant) had minimal impact on BMD outcomes.
Conclusion
We present pQCT-derived BMD estimates from a diverse cohort of healthy children and adolescents and identify key moderators. Our findings provide a foundation for improved understanding and future standardization, laying the groundwork for enhancing the clinical utility of pQCT.
背景:评估儿童和青少年的骨密度(BMD)对于发现骨骼缺陷和骨折风险至关重要。外周定量计算机断层扫描(pQCT)作为一种有价值的成像工具,由于其评估骨质量的能力而受到越来越多的关注。与双能x线吸收仪不同,pQCT提供了体积骨密度测量,并区分了皮质和小梁间室。尽管有这些优势,但由于缺乏参考数据和标准化方案,其临床应用仍然有限。方法:系统检索CINAHL、Embase、PubMed、SPORTDiscus、Web of Science自建站至2024年11月。报告pqct衍生的健康儿童和青少年胫骨骨密度的研究(结果:83项研究(18,531名受试者)纳入本综述。meta回归模型显示BMD与年龄之间存在非线性关系,最好使用自然三次样条来描述。调节分析表明,性别、种族和参考线位置显著影响皮质骨密度,而参考线位置和pQCT设备影响小梁骨密度。评估肢体的选择(优势与非优势)对骨密度结果的影响最小。结论:我们从不同的健康儿童和青少年队列中提出了pqct衍生的BMD估计值,并确定了关键的调节因素。我们的研究结果为进一步了解和规范pQCT奠定了基础,为提高pQCT的临床应用奠定了基础。
{"title":"Pediatric pQCT-derived tibial bone mineral density estimates: A systematic review and meta-regression","authors":"Anna Maria Markarian , Dennis R. Taaffe , Daniel A. Galvão , Jodie Cochrane Wilkie , Carolyn J. Peddle-McIntyre , Mark Markarian , Daniel J. Schiferl , Robert U. Newton","doi":"10.1016/j.bone.2025.117720","DOIUrl":"10.1016/j.bone.2025.117720","url":null,"abstract":"<div><h3>Background</h3><div>Assessing bone mineral density (BMD) in children and adolescents is essential for detecting skeletal deficits and fracture risk. Peripheral quantitative computed tomography (pQCT) has gained increasing attention as a valuable imaging tool due to its ability to assess bone quality. Unlike dual-energy x-ray absorptiometry, pQCT provides volumetric BMD measurements and distinguishes between cortical and trabecular compartments. Despite these advantages, its clinical adoption remains limited due to the lack of reference data and standardized protocols.</div></div><div><h3>Methods</h3><div>A systematic search was conducted in CINAHL, Embase, PubMed, SPORTDiscus, and Web of Science from inception to November 2024. Studies reporting pQCT-derived tibial BMD in healthy children and adolescents (<19 years old) were included. Meta-regression models using natural cubic splines were applied to estimate age-specific BMD values for trabecular and cortical bone. Potential moderators, such as sex, race, reference line location, limb, and pQCT device, were evaluated to assess their influence on BMD outcomes.</div></div><div><h3>Results</h3><div>Eighty-three studies (18,531 participants) were included in this review. The meta-regression models demonstrated a non-linear relationship between BMD and age, best described using natural cubic splines. Moderator analysis indicated that sex, race, and reference line location significantly influenced cortical BMD, while trabecular BMD was affected by reference line location and pQCT device. The choice of limb assessed (dominant vs non-dominant) had minimal impact on BMD outcomes.</div></div><div><h3>Conclusion</h3><div>We present pQCT-derived BMD estimates from a diverse cohort of healthy children and adolescents and identify key moderators. Our findings provide a foundation for improved understanding and future standardization, laying the groundwork for enhancing the clinical utility of pQCT.</div></div>","PeriodicalId":9301,"journal":{"name":"Bone","volume":"203 ","pages":"Article 117720"},"PeriodicalIF":3.6,"publicationDate":"2025-11-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145484267","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}
This study aimed to investigate the age-related bone mineral density (BMD) response to romosozumab. A prospective cohort study was conducted on 221 treatment-naïve women aged 55–100 years with primary osteoporosis who initiated a 12-month romosozumab therapy. Percent changes in lumbar spine (LS), total hip (TH), and femoral neck (FN) BMD and bone turnover markers were assessed at 6 and 12 months. Associations between age and treatment efficacy were analyzed using multivariate regression, adjusting for potential confounders. Sensitivity analyses were conducted according to the baseline 25-hydroxyvitamin D (25OHD) status (<20 vs. ≥20 ng/mL). Restricted cubic spline curves were applied to assess the potential non-linear associations between age and the BMD response, adjusting for the same covariates. Multivariate regression showed that younger age is independently associated with higher percent changes in LS BMD at 6 (regression coefficient [β], −0.31; 95 % confidence interval [CI], −0.45 to −0.18) and 12 months (β, −0.19; 95 % CI, −0.36 to −0.02). Sensitivity analyses confirmed the association between age and percent gains in the LS BMD at 6 months but not at 12 months. No evidence of non-linearity was found at 6 (p for non-linearity = 0.874) and 12 months (p for non-linearity = 0.686). No significant associations were observed for TH or FN BMD or the bone turnover markers. An inverse linear relationship was observed between age and percent change of the LS BMD at 6 months; however, the relationship was not robust at 12 months.
{"title":"Age-related response to 12-month romosozumab in treatment-naïve Japanese women aged 55–100 years with primary osteoporosis","authors":"Takaomi Kobayashi , Tomonori Kobayakawa , Yukio Nakamura","doi":"10.1016/j.bone.2025.117708","DOIUrl":"10.1016/j.bone.2025.117708","url":null,"abstract":"<div><div>This study aimed to investigate the age-related bone mineral density (BMD) response to romosozumab. A prospective cohort study was conducted on 221 treatment-naïve women aged 55–100 years with primary osteoporosis who initiated a 12-month romosozumab therapy. Percent changes in lumbar spine (LS), total hip (TH), and femoral neck (FN) BMD and bone turnover markers were assessed at 6 and 12 months. Associations between age and treatment efficacy were analyzed using multivariate regression, adjusting for potential confounders. Sensitivity analyses were conducted according to the baseline 25-hydroxyvitamin D (25OHD) status (<20 vs. ≥20 ng/mL). Restricted cubic spline curves were applied to assess the potential non-linear associations between age and the BMD response, adjusting for the same covariates. Multivariate regression showed that younger age is independently associated with higher percent changes in LS BMD at 6 (regression coefficient [<em>β</em>], −0.31; 95 % confidence interval [CI], −0.45 to −0.18) and 12 months (<em>β</em>, −0.19; 95 % CI, −0.36 to −0.02). Sensitivity analyses confirmed the association between age and percent gains in the LS BMD at 6 months but not at 12 months. No evidence of non-linearity was found at 6 (<em>p</em> for non-linearity = 0.874) and 12 months (<em>p</em> for non-linearity = 0.686). No significant associations were observed for TH or FN BMD or the bone turnover markers. An inverse linear relationship was observed between age and percent change of the LS BMD at 6 months; however, the relationship was not robust at 12 months.</div></div>","PeriodicalId":9301,"journal":{"name":"Bone","volume":"203 ","pages":"Article 117708"},"PeriodicalIF":3.6,"publicationDate":"2025-11-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145477112","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}
Pub Date : 2025-11-06DOI: 10.1016/j.bone.2025.117719
Tao Han , Yang Qu , Jiangbo Zhu , Linna Sha , Bowen Lei , Rong Xiang , Xunying Zhao , Jiaojiao Hou , Qin Deng , Sirui Zheng , Jinyu Zhou , Ting Yu , Xin Song , Bin Yang , Yangdan Zhong , Maoyao Xia , Douglas P. Kiel , Xia Jiang
Objectives
Subclinical atherosclerosis and osteoporosis are often present together in the same individual, but their common mechanisms remain unclear. This study aims to investigate the pleiotropic relationship underlying coronary artery calcification (CAC) and estimated calcaneal bone mineral density (eBMD), providing molecular insights into their observed phenotypic associations.
Methods
Genetic correlation between CAC and eBMD was estimated based on genome-wide summary statistics. Shared loci were examined at the levels of single-nucleotide polymorphism (SNP), multi-SNP, and gene expressions to provide insights into genetic pleiotropy. Sensitivity analyses using data of DXA-derived BMD at femoral neck and lumbar spine were performed to validate key findings. Pathway enrichment analyses were conducted on significant shared loci to explore potential biological mechanisms.
Results
Despite an absence of a global genetic correlation, partitioning the genome into independent regions revealed five significant signals. Through subsequent multi-layered analysis, we identified 211 non-overlapping significant shared genes, including 190 from single-SNP-level, 27 from multi-SNP-level, and 3 from gene expression level, underscoring the widespread pleiotropy across CAC and eBMD. Notably, the shared signals were predominantly concentrated on chromosome 17, with SMG6 and PAFAH1B1 highlighted as crucial pleiotropic genes, and both were further confirmed by sensitivity analyses. Pathway enrichment analyses revealed oxidative stress regulation and the ubiquitin-proteasome system as critical biological mechanisms potentially linking the two traits.
Conclusion
Our study demonstrates that the observed association between CAC and eBMD is mainly driven by pleiotropic associations.
{"title":"A comprehensive multi-layered analysis reveals genetic pleiotropy underlying coronary artery calcification and bone mineral density","authors":"Tao Han , Yang Qu , Jiangbo Zhu , Linna Sha , Bowen Lei , Rong Xiang , Xunying Zhao , Jiaojiao Hou , Qin Deng , Sirui Zheng , Jinyu Zhou , Ting Yu , Xin Song , Bin Yang , Yangdan Zhong , Maoyao Xia , Douglas P. Kiel , Xia Jiang","doi":"10.1016/j.bone.2025.117719","DOIUrl":"10.1016/j.bone.2025.117719","url":null,"abstract":"<div><h3>Objectives</h3><div>Subclinical atherosclerosis and osteoporosis are often present together in the same individual, but their common mechanisms remain unclear. This study aims to investigate the pleiotropic relationship underlying coronary artery calcification (CAC) and estimated calcaneal bone mineral density (eBMD), providing molecular insights into their observed phenotypic associations.</div></div><div><h3>Methods</h3><div>Genetic correlation between CAC and eBMD was estimated based on genome-wide summary statistics. Shared loci were examined at the levels of single-nucleotide polymorphism (SNP), multi-SNP, and gene expressions to provide insights into genetic pleiotropy. Sensitivity analyses using data of DXA-derived BMD at femoral neck and lumbar spine were performed to validate key findings. Pathway enrichment analyses were conducted on significant shared loci to explore potential biological mechanisms.</div></div><div><h3>Results</h3><div>Despite an absence of a global genetic correlation, partitioning the genome into independent regions revealed five significant signals. Through subsequent multi-layered analysis, we identified 211 non-overlapping significant shared genes, including 190 from single-SNP-level, 27 from multi-SNP-level, and 3 from gene expression level, underscoring the widespread pleiotropy across CAC and eBMD. Notably, the shared signals were predominantly concentrated on chromosome 17, with <em>SMG6</em> and <em>PAFAH1B1</em> highlighted as crucial pleiotropic genes, and both were further confirmed by sensitivity analyses. Pathway enrichment analyses revealed oxidative stress regulation and the ubiquitin-proteasome system as critical biological mechanisms potentially linking the two traits.</div></div><div><h3>Conclusion</h3><div>Our study demonstrates that the observed association between CAC and eBMD is mainly driven by pleiotropic associations.</div></div>","PeriodicalId":9301,"journal":{"name":"Bone","volume":"203 ","pages":"Article 117719"},"PeriodicalIF":3.6,"publicationDate":"2025-11-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145476841","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}
Pub Date : 2025-11-05DOI: 10.1016/j.bone.2025.117710
Donal Fitzpatrick , Eamon Laird , Mary Ward , Leane Hoey , Catherine F. Hughes , Liadhan McAnena , J.J. Strain , Conal Cunningham , Anne M. Molloy , Helene McNulty , Rosaleen Lannon , Kevin McCarroll
Introduction
The renin-angiotensin system (RAS) is implicated in osteoclast activation and bone loss. We investigated the relationship of angiotensin receptor blockers (ARBs) or angiotensin-converting enzyme inhibitors (ACE-Is) usage with bone turnover markers (BTM) and bone mineral density (BMD).
Methods
Participants were from the TUDA cohort of Irish adults aged ≥60 years not receiving osteoporosis treatment. BMD at the total hip, femoral neck and lumbar spine, and BTMs were compared between users of ARBs or ACE-Is and non-users of either medication, adjusting for age, sex, BMI, Timed-Up-and-Go, vitamin D status, eGFR, parathyroid hormone, lifestyle factors, socioeconomic status, comorbidities and other medications.
Results
In the ARB analysis (n = 1516; mean age 70.2 years; 64 % female; 33 % users), ARB use vs non-use was associated with higher adjusted BMD at the femoral neck 0.856 g/cm2 (95 % CI 0.830–0.882) vs 0.837 (0.812–0.863), p = 0.005; total hip 0.937 g/cm2 (0.909–0.965) vs 0.913 (0.886–0.941), p = 0.002; and lumbar spine 1.122 g/cm2 (1.082–1.162) vs 1.087 (1.047–1.126), p < 0.001. In the ACE-I analysis (n = 1692; mean age 70.1 years; 59 % female; 40 % users), ACE-I usage was not associated with BMD. In a subsample with available BTM (n = 1613), ARB users versus non-users had lower serum adjusted tartrate-resistant acid phosphatase 3.14 units/l (2.87–3.41) vs 3.28 (3.01–3.55), p = 0.040. No association was found between ACE-I usage and TRACP5b.
Discussion
ARB use was associated with higher BMD and lower TRACP5b, a marker of osteoclast activity, with no corresponding associations for ACE-Is. This pattern suggests a possible differential effect between ARBs and ACE-Is on bone that merits evaluation in prospective cohorts and randomised trials.
肾素-血管紧张素系统(RAS)与破骨细胞活化和骨质流失有关。我们研究了血管紧张素受体阻滞剂(ARBs)或血管紧张素转换酶抑制剂(ACE-Is)的使用与骨转换标志物(BTM)和骨矿物质密度(BMD)的关系。方法参与者来自TUDA队列,年龄≥60岁,未接受骨质疏松治疗的爱尔兰成年人。在调整年龄、性别、BMI、time - upand - go、维生素D状态、eGFR、甲状旁腺激素、生活方式因素、社会经济状况、合并症和其他药物后,比较arb或ACE-Is使用者与非arb或ACE-Is使用者的全髋关节、股骨颈和腰椎的骨密度以及btm。结果在ARB分析中(n = 1516例,平均年龄70.2岁,女性占64%,使用ARB者占33%),使用ARB者与不使用ARB者股骨颈校正骨密度较高(0.856 g/cm2)相关(95% CI 0.830-0.882) vs 0.837 (0.812-0.863), p = 0.005;总臀围0.937 g/cm2 (0.909-0.965) vs 0.913 (0.886-0.941), p = 0.002;腰椎1.122 g/cm2 (1.082-1.162) vs 1.087 (1.047-1.126), p < 0.001。在ACE-I分析中(n = 1692,平均年龄70.1岁,59%为女性,40%为使用者),ACE-I的使用与BMD无关。在具有可用BTM的子样本中(n = 1613), ARB使用者与非使用者的血清调整酒石酸耐受性酸性磷酸酶较低,分别为3.14单位/升(2.87-3.41)和3.28单位/升(3.01-3.55),p = 0.040。ACE-I的使用与TRACP5b之间没有关联。arb的使用与较高的骨密度和较低的TRACP5b(一种破骨细胞活性的标志物)相关,而与ACE-Is没有相应的关联。这种模式表明arb和ACE-Is对骨骼可能有不同的影响,值得在前瞻性队列和随机试验中进行评估。
{"title":"Angiotensin receptor blockers (ARBs) but not angiotensin converting enzyme inhibitors (ACE-Is) are associated with lower osteoclast activity and higher bone mineral density: Results from the TUDA study","authors":"Donal Fitzpatrick , Eamon Laird , Mary Ward , Leane Hoey , Catherine F. Hughes , Liadhan McAnena , J.J. Strain , Conal Cunningham , Anne M. Molloy , Helene McNulty , Rosaleen Lannon , Kevin McCarroll","doi":"10.1016/j.bone.2025.117710","DOIUrl":"10.1016/j.bone.2025.117710","url":null,"abstract":"<div><h3>Introduction</h3><div>The renin-angiotensin system (RAS) is implicated in osteoclast activation and bone loss. We investigated the relationship of angiotensin receptor blockers (ARBs) or angiotensin-converting enzyme inhibitors (ACE-Is) usage with bone turnover markers (BTM) and bone mineral density (BMD).</div></div><div><h3>Methods</h3><div>Participants were from the TUDA cohort of Irish adults aged ≥60 years not receiving osteoporosis treatment. BMD at the total hip, femoral neck and lumbar spine, and BTMs were compared between users of ARBs or ACE-Is and non-users of either medication, adjusting for age, sex, BMI, Timed-Up-and-Go, vitamin D status, eGFR, parathyroid hormone, lifestyle factors, socioeconomic status, comorbidities and other medications.</div></div><div><h3>Results</h3><div>In the ARB analysis (<em>n</em> = 1516; mean age 70.2 years; 64 % female; 33 % users), ARB use vs non-use was associated with higher adjusted BMD at the femoral neck 0.856 g/cm<sup>2</sup> (95 % CI 0.830–0.882) vs 0.837 (0.812–0.863), <em>p</em> = 0.005; total hip 0.937 g/cm<sup>2</sup> (0.909–0.965) vs 0.913 (0.886–0.941), <em>p</em> = 0.002; and lumbar spine 1.122 g/cm<sup>2</sup> (1.082–1.162) vs 1.087 (1.047–1.126), <em>p</em> < 0.001. In the ACE-I analysis (<em>n</em> = 1692; mean age 70.1 years; 59 % female; 40 % users), ACE-I usage was not associated with BMD. In a subsample with available BTM (<em>n</em> = 1613), ARB users versus non-users had lower serum adjusted tartrate-resistant acid phosphatase 3.14 units/l (2.87–3.41) vs 3.28 (3.01–3.55), <em>p</em> = 0.040. No association was found between ACE-I usage and TRACP5b.</div></div><div><h3>Discussion</h3><div>ARB use was associated with higher BMD and lower TRACP5b, a marker of osteoclast activity, with no corresponding associations for ACE-Is. This pattern suggests a possible differential effect between ARBs and ACE-Is on bone that merits evaluation in prospective cohorts and randomised trials.</div></div>","PeriodicalId":9301,"journal":{"name":"Bone","volume":"203 ","pages":"Article 117710"},"PeriodicalIF":3.6,"publicationDate":"2025-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145464740","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}
Pub Date : 2025-11-05DOI: 10.1016/j.bone.2025.117706
Costas Glavas , Jakub Mesinovic , Peter R. Ebeling , Surbhi Sood , Elena S. George , Melkamu Tamir Hunegnaw , Ayse Zengin , Robin M. Daly , Paul Jansons , David Scott
{"title":"Corrigendum to “Comparing bone and muscle parameters in community-dwelling older adults with obesity, with or without type 2 diabetes mellitus” [Bone 202 (2026) 117680]","authors":"Costas Glavas , Jakub Mesinovic , Peter R. Ebeling , Surbhi Sood , Elena S. George , Melkamu Tamir Hunegnaw , Ayse Zengin , Robin M. Daly , Paul Jansons , David Scott","doi":"10.1016/j.bone.2025.117706","DOIUrl":"10.1016/j.bone.2025.117706","url":null,"abstract":"","PeriodicalId":9301,"journal":{"name":"Bone","volume":"202 ","pages":"Article 117706"},"PeriodicalIF":3.6,"publicationDate":"2025-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145454190","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}
Pub Date : 2025-11-04DOI: 10.1016/j.bone.2025.117709
Annabel R. Bugbird , Lauren A. Burt , Danielle E. Whittier , Steven K. Boyd
<div><h3>Introduction:</h3><div>A previously developed <em>phenotyping</em> model groups common combinations of bone characteristics into three primary phenotypes: <em>healthy</em>, <em>low volume</em>, and <em>low density</em> from high resolution peripheral quantitative computed tomography (HR-pQCT). While these phenotypes have been characterized in cross-sectional cohorts, their longitudinal progression and transitions with aging remains unknown. Therefore, the aim of this study was to investigate how bone microarchitecture phenotypes evolves over time, identify common transitional patterns, and examine their association with fracture risk.</div></div><div><h3>Methods:</h3><div>Our cohort included 606 adult male and female participants from a longitudinal population study. HR-pQCT scans of the distal radius and tibia were acquired at two visits. Bone phenotypes, defined as <em>healthy</em>, <em>low volume</em>, and <em>low density</em>, were determined at baseline and follow-up. Transitional patterns in phenotypes were examined by age group and sex, and further analyzed in relation to average bone size based on cross-sectional area. The relative contributions of sex and bone size to phenotype transitions were evaluated using nested linear regression models.</div></div><div><h3>Results:</h3><div>The average age of participants was 60.4 ± 16.2 years, with a mean follow-up duration of 6.76 ± 1.78 years. Phenotype membership remained relatively stable over the follow-up time but exhibited an average transitional pattern from the <em>healthy</em> phenotype in younger adults (18–40 years), to <em>low volume</em> (40–60 years), and eventually to <em>low density</em> (60+ years), particularly among females. When stratified by bone size, individuals with larger bones tended to follow an average trajectory from <em>healthy</em> to <em>low density</em>, whereas those with smaller bones typically transitioned from <em>healthy</em> to <em>low volume</em> to <em>low density</em>. Although sex and bone size were strongly correlated (R<span><math><mrow><msup><mrow></mrow><mrow><mn>2</mn></mrow></msup><mo>=</mo></mrow></math></span> 0.43), and showed similar transitional patterns, sex remained a significant predictor of phenotype membership even after adjusting for bone size (p <span><math><mo><</mo></math></span> 0.001).</div></div><div><h3>Conclusion:</h3><div>These findings demonstrate that the bone phenotype model provides a dynamic, interpretable framework for monitoring skeletal health over time, capturing age-, sex-, and size-related trajectories, and offering potential for individualized bone health assessment.</div></div><div><h3>Lay Summary:</h3><div>We investigated the longitudinal progression of bone phenotypes, categorized as <em>healthy</em>, <em>low volume</em>, and <em>low density</em>, in adult males and females. Phenotype transitions were analyzed by age, sex, and average bone size. Most individuals followed an average trajectory from <em>
{"title":"Bone size and sex are key determinants of the longitudinal bone phenotype trajectory in aging males and females","authors":"Annabel R. Bugbird , Lauren A. Burt , Danielle E. Whittier , Steven K. Boyd","doi":"10.1016/j.bone.2025.117709","DOIUrl":"10.1016/j.bone.2025.117709","url":null,"abstract":"<div><h3>Introduction:</h3><div>A previously developed <em>phenotyping</em> model groups common combinations of bone characteristics into three primary phenotypes: <em>healthy</em>, <em>low volume</em>, and <em>low density</em> from high resolution peripheral quantitative computed tomography (HR-pQCT). While these phenotypes have been characterized in cross-sectional cohorts, their longitudinal progression and transitions with aging remains unknown. Therefore, the aim of this study was to investigate how bone microarchitecture phenotypes evolves over time, identify common transitional patterns, and examine their association with fracture risk.</div></div><div><h3>Methods:</h3><div>Our cohort included 606 adult male and female participants from a longitudinal population study. HR-pQCT scans of the distal radius and tibia were acquired at two visits. Bone phenotypes, defined as <em>healthy</em>, <em>low volume</em>, and <em>low density</em>, were determined at baseline and follow-up. Transitional patterns in phenotypes were examined by age group and sex, and further analyzed in relation to average bone size based on cross-sectional area. The relative contributions of sex and bone size to phenotype transitions were evaluated using nested linear regression models.</div></div><div><h3>Results:</h3><div>The average age of participants was 60.4 ± 16.2 years, with a mean follow-up duration of 6.76 ± 1.78 years. Phenotype membership remained relatively stable over the follow-up time but exhibited an average transitional pattern from the <em>healthy</em> phenotype in younger adults (18–40 years), to <em>low volume</em> (40–60 years), and eventually to <em>low density</em> (60+ years), particularly among females. When stratified by bone size, individuals with larger bones tended to follow an average trajectory from <em>healthy</em> to <em>low density</em>, whereas those with smaller bones typically transitioned from <em>healthy</em> to <em>low volume</em> to <em>low density</em>. Although sex and bone size were strongly correlated (R<span><math><mrow><msup><mrow></mrow><mrow><mn>2</mn></mrow></msup><mo>=</mo></mrow></math></span> 0.43), and showed similar transitional patterns, sex remained a significant predictor of phenotype membership even after adjusting for bone size (p <span><math><mo><</mo></math></span> 0.001).</div></div><div><h3>Conclusion:</h3><div>These findings demonstrate that the bone phenotype model provides a dynamic, interpretable framework for monitoring skeletal health over time, capturing age-, sex-, and size-related trajectories, and offering potential for individualized bone health assessment.</div></div><div><h3>Lay Summary:</h3><div>We investigated the longitudinal progression of bone phenotypes, categorized as <em>healthy</em>, <em>low volume</em>, and <em>low density</em>, in adult males and females. Phenotype transitions were analyzed by age, sex, and average bone size. Most individuals followed an average trajectory from <em>","PeriodicalId":9301,"journal":{"name":"Bone","volume":"203 ","pages":"Article 117709"},"PeriodicalIF":3.6,"publicationDate":"2025-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145460844","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}
Pub Date : 2025-11-04DOI: 10.1016/j.bone.2025.117700
Costas Glavas , Jakub Mesinovic , Peter R. Ebeling , Surbhi Sood , Elena S. George , Melkamu Tamir Hunegnaw , Ayse Zengin , Robin M. Daly , Paul Jansons , David Scott
{"title":"Response to ‘reconsidering bone-muscle interactions in obese older adults with type 2 diabetes: Methodological limitations and future directions’","authors":"Costas Glavas , Jakub Mesinovic , Peter R. Ebeling , Surbhi Sood , Elena S. George , Melkamu Tamir Hunegnaw , Ayse Zengin , Robin M. Daly , Paul Jansons , David Scott","doi":"10.1016/j.bone.2025.117700","DOIUrl":"10.1016/j.bone.2025.117700","url":null,"abstract":"","PeriodicalId":9301,"journal":{"name":"Bone","volume":"203 ","pages":"Article 117700"},"PeriodicalIF":3.6,"publicationDate":"2025-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145460842","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}
Pub Date : 2025-11-03DOI: 10.1016/j.bone.2025.117691
Yubo Shi , Jianzhou Yu , Yanqing Wu , Hao Fang , Bo Yang
An effective approach for treating osteoporosis (OP) is to focus on restoring the osteogenic ability of bone marrow-derived mesenchymal stem cells (BMSCs). Melatonin (MEL) has been found to possess the capability to enhance osteogenesis. Nevertheless, the precise mechanisms through which MEL regulates the differentiation of BMSCs and the development of OP are still not well understood. In the present study, circZFAND1 characterization was validated using Sanger sequencing, RNase R treatment, and RNA fluorescence in situ hybridization assay. To investigate the relationship between circZFAND1, DKK1 and miR-433-3p, we performed a series of experiments including the luciferase reporter assay, RNA immunoprecipitation assay, and rescue experiments. In addition, the MEL-mediated m6A modification of circZFAND1 was evaluated using dot-blot assay and Methylated RNA immunoprecipitation (Me-RIP) assay. Finally, the osteogenic differentiation of BMSCs was detected through function assays, including immunofluorescence staining, 5-ethynyl-20-deoxyuridine (EdU) assay, western blotting, and staining with alkaline phosphatase and alizarin red. The results showed that MEL promoted osteogenic differentiation of BMSCs by regulating circZFAND1/miR-433-3p/DKK1 pathway through melatonin receptor 2 (MT2) -dependent m6A modification of circZFAND1. These findings offer novel biomarkers for managing OP and may lay the theoretical foundation for applying MEL for OP management in the clinical setting.
{"title":"Melatonin promotes osteogenic differentiation of BMSCs by regulating circZFAND1/miR-433-3p/DKK1 pathway through melatonin receptor-dependent m6A modification of circZFAND1","authors":"Yubo Shi , Jianzhou Yu , Yanqing Wu , Hao Fang , Bo Yang","doi":"10.1016/j.bone.2025.117691","DOIUrl":"10.1016/j.bone.2025.117691","url":null,"abstract":"<div><div>An effective approach for treating osteoporosis (OP) is to focus on restoring the osteogenic ability of bone marrow-derived mesenchymal stem cells (BMSCs). Melatonin (MEL) has been found to possess the capability to enhance osteogenesis. Nevertheless, the precise mechanisms through which MEL regulates the differentiation of BMSCs and the development of OP are still not well understood. In the present study, circZFAND1 characterization was validated using Sanger sequencing, RNase R treatment, and RNA fluorescence in situ hybridization assay. To investigate the relationship between circZFAND1, DKK1 and miR-433-3p, we performed a series of experiments including the luciferase reporter assay, RNA immunoprecipitation assay, and rescue experiments. In addition, the MEL-mediated m6A modification of circZFAND1 was evaluated using dot-blot assay and Methylated RNA immunoprecipitation (Me-RIP) assay. Finally, the osteogenic differentiation of BMSCs was detected through function assays, including immunofluorescence staining, 5-ethynyl-20-deoxyuridine (EdU) assay, western blotting, and staining with alkaline phosphatase and alizarin red. The results showed that MEL promoted osteogenic differentiation of BMSCs by regulating circZFAND1/miR-433-3p/DKK1 pathway through melatonin receptor 2 (MT2) -dependent m6A modification of circZFAND1. These findings offer novel biomarkers for managing OP and may lay the theoretical foundation for applying MEL for OP management in the clinical setting.</div></div>","PeriodicalId":9301,"journal":{"name":"Bone","volume":"202 ","pages":"Article 117691"},"PeriodicalIF":3.6,"publicationDate":"2025-11-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145454174","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}