Pub Date : 2025-06-01Epub Date: 2025-05-20DOI: 10.1016/j.bonr.2025.101852
Sema Ertan Birsel , Ekrem Demirci , Ali Seker , Kadriye Yasemin Usta Ayanoğlu , Emir Oncu , Fatih Ciftci
Hip displacement is a significant concern in children with cerebral palsy (CP), necessitating accurate and timely assessment to prevent long-term complications. This study developed a support vector machine (SVM) model to classify hip conditions using migration percentage (MP) measurements obtained from 176 hips across 88 anteroposterior pelvic radiographs. MP values were categorized into three groups: normal (MP ≤ 30 %), risky (30 % < MP ≤ 60 %), and dislocated (MP > 60 %). The SVM model was evaluated using stratified k-fold cross-validation, with accuracy, precision, recall, and F1-scores as key metrics. Its classifications were compared to manual evaluations performed by an orthopedic resident and a pediatric orthopedic surgeon. The model achieved an overall accuracy of 92.898 %, surpassing the consistency and reliability of manual assessments, particularly in identifying dislocated hips. Statistical analysis showed no significant differences between the model's MP measurements and those of the clinicians, validating its effectiveness. This study highlights the potential of SVM models to enhance diagnostic accuracy, reduce variability in evaluations, and support clinical decision-making. Future research should expand the dataset and incorporate advanced machine learning models to further improve diagnostic precision.
{"title":"Machine learning-assisted classification of hip conditions in pediatric cerebral palsy patients using migration percentage measurements","authors":"Sema Ertan Birsel , Ekrem Demirci , Ali Seker , Kadriye Yasemin Usta Ayanoğlu , Emir Oncu , Fatih Ciftci","doi":"10.1016/j.bonr.2025.101852","DOIUrl":"10.1016/j.bonr.2025.101852","url":null,"abstract":"<div><div>Hip displacement is a significant concern in children with cerebral palsy (CP), necessitating accurate and timely assessment to prevent long-term complications. This study developed a support vector machine (SVM) model to classify hip conditions using migration percentage (MP) measurements obtained from 176 hips across 88 anteroposterior pelvic radiographs. MP values were categorized into three groups: normal (MP ≤ 30 %), risky (30 % < MP ≤ 60 %), and dislocated (MP > 60 %). The SVM model was evaluated using stratified k-fold cross-validation, with accuracy, precision, recall, and F1-scores as key metrics. Its classifications were compared to manual evaluations performed by an orthopedic resident and a pediatric orthopedic surgeon. The model achieved an overall accuracy of 92.898 %, surpassing the consistency and reliability of manual assessments, particularly in identifying dislocated hips. Statistical analysis showed no significant differences between the model's MP measurements and those of the clinicians, validating its effectiveness. This study highlights the potential of SVM models to enhance diagnostic accuracy, reduce variability in evaluations, and support clinical decision-making. Future research should expand the dataset and incorporate advanced machine learning models to further improve diagnostic precision.</div></div>","PeriodicalId":9043,"journal":{"name":"Bone Reports","volume":"25 ","pages":"Article 101852"},"PeriodicalIF":2.1,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144099602","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-06-01Epub Date: 2025-03-10DOI: 10.1016/j.bonr.2025.101834
Yu-ling Liu , Yue-ming Mei , Jing-qiong Xun , Zhuo-yue Lv , Qian He , Zhou-bo-ran Liu , Lin Li , Fen Xie , Ru-chun Dai
Bone remodeling process is the basis for maintaining normal bone microstructure and promoting fracture repair. Recent studies have proven that integrins can promote bone formation and fracture repair. Integrin-linked kinase (ILK), as the proximal effector of the integrin receptor, is a key protein factor linking integrin and cytoskeleton. It is involved in crucial cellular processes including proliferation, survival, differentiation, migration, invasion, and angiogenesis reflects on systemic changes in the kidney, heart, muscle, skin, and vascular system. At present, the regulation effect of ILK in bone formation attracts the attention of researchers. This review emphasizes that ILK as a key molecule affects the functions of bone marrow stromal cells (BMSCs) and osteoblasts, and regulates bone formation. Additionally, ILK plays a key role in the process of“angiogenic–osteogenic coupling ”. The present role of ILK in the pathogenesis of osteoporosis is also described. Strategies that target ILK may as a new prospective treatment for osteoporosis (OP).
{"title":"The biological function of integrin-linked kinase on bone formation","authors":"Yu-ling Liu , Yue-ming Mei , Jing-qiong Xun , Zhuo-yue Lv , Qian He , Zhou-bo-ran Liu , Lin Li , Fen Xie , Ru-chun Dai","doi":"10.1016/j.bonr.2025.101834","DOIUrl":"10.1016/j.bonr.2025.101834","url":null,"abstract":"<div><div>Bone remodeling process is the basis for maintaining normal bone microstructure and promoting fracture repair. Recent studies have proven that integrins can promote bone formation and fracture repair. Integrin-linked kinase (ILK), as the proximal effector of the integrin receptor, is a key protein factor linking integrin and cytoskeleton. It is involved in crucial cellular processes including proliferation, survival, differentiation, migration, invasion, and angiogenesis reflects on systemic changes in the kidney, heart, muscle, skin, and vascular system. At present, the regulation effect of ILK in bone formation attracts the attention of researchers. This review emphasizes that ILK as a key molecule affects the functions of bone marrow stromal cells (BMSCs) and osteoblasts, and regulates bone formation. Additionally, ILK plays a key role in the process of“angiogenic–osteogenic coupling ”. The present role of ILK in the pathogenesis of osteoporosis is also described. Strategies that target ILK may as a new prospective treatment for osteoporosis (OP).</div></div>","PeriodicalId":9043,"journal":{"name":"Bone Reports","volume":"25 ","pages":"Article 101834"},"PeriodicalIF":2.1,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143609277","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-06-01Epub Date: 2025-02-11DOI: 10.1016/j.bonr.2025.101829
Hye Kyoung Lee , Geneva Rose Notario , Sun Young Won , Jung Hwan Kim , Su Min Lee , Ha Seong Kim , Sung-Rae Cho
Osteoporosis following stroke is a significant impediment to patient recovery. Decreased mechanical loading and locomotion following the onset of paralysis in stroke patients, especially those who are non-ambulatory, contributes greatly to bone loss. Sclerostin, a protein encoded by the SOST gene, accumulates as a result of reduced mechanical loading and inhibits bone formation. This study explores the relationship between mechanical unloading, sclerostin levels, and bone mineral density (BMD) in stroke patients, utilizing three cohorts. Analysis of Cohort 1, consisting of patients with available sclerostin level measurements, found significantly elevated sclerostin levels in non-ambulatory patients compared to ambulatory patients, indicating the influence of ambulatory status on sclerostin regulation. Cohort 2, consisting of patients with BMD measurements, demonstrated that prolonged mechanical unloading in non-ambulatory patients resulted in a greater decline in BMD over time. Analysis in Cohort 3 patients, who had bilateral BMD measurements available, revealed that hemiplegic sides subjected to reduced mechanical loading exhibited lower BMD compared to non-hemiplegic sides. These findings collectively confirm the hypothesis that reduced mechanical loading elevates sclerostin levels and accelerates bone loss. By integrating data across the three cohorts, this study underscores the critical impact of mechanical unloading on bone health, particularly in chronic stroke patients with limited mobility. Our study provides clinical insights for treatments integrating ambulatory status, sclerostin levels, and BMD in chronic stroke patients and highlights an increased need for therapeutics targeting mechanical loading pathways and sclerostin accumulation which can be administered to treat chronic osteoporosis following stroke.
{"title":"Elevated sclerostin levels contribute to reduced bone mineral density in non-ambulatory stroke patients","authors":"Hye Kyoung Lee , Geneva Rose Notario , Sun Young Won , Jung Hwan Kim , Su Min Lee , Ha Seong Kim , Sung-Rae Cho","doi":"10.1016/j.bonr.2025.101829","DOIUrl":"10.1016/j.bonr.2025.101829","url":null,"abstract":"<div><div>Osteoporosis following stroke is a significant impediment to patient recovery. Decreased mechanical loading and locomotion following the onset of paralysis in stroke patients, especially those who are non-ambulatory, contributes greatly to bone loss. Sclerostin, a protein encoded by the SOST gene, accumulates as a result of reduced mechanical loading and inhibits bone formation. This study explores the relationship between mechanical unloading, sclerostin levels, and bone mineral density (BMD) in stroke patients, utilizing three cohorts. Analysis of Cohort 1, consisting of patients with available sclerostin level measurements, found significantly elevated sclerostin levels in non-ambulatory patients compared to ambulatory patients, indicating the influence of ambulatory status on sclerostin regulation. Cohort 2, consisting of patients with BMD measurements, demonstrated that prolonged mechanical unloading in non-ambulatory patients resulted in a greater decline in BMD over time. Analysis in Cohort 3 patients, who had bilateral BMD measurements available, revealed that hemiplegic sides subjected to reduced mechanical loading exhibited lower BMD compared to non-hemiplegic sides. These findings collectively confirm the hypothesis that reduced mechanical loading elevates sclerostin levels and accelerates bone loss. By integrating data across the three cohorts, this study underscores the critical impact of mechanical unloading on bone health, particularly in chronic stroke patients with limited mobility. Our study provides clinical insights for treatments integrating ambulatory status, sclerostin levels, and BMD in chronic stroke patients and highlights an increased need for therapeutics targeting mechanical loading pathways and sclerostin accumulation which can be administered to treat chronic osteoporosis following stroke.</div></div>","PeriodicalId":9043,"journal":{"name":"Bone Reports","volume":"25 ","pages":"Article 101829"},"PeriodicalIF":2.1,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143685344","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-06-01Epub Date: 2025-03-24DOI: 10.1016/j.bonr.2025.101838
André Silva Franco , Valeria de Falco Caparbo , Elieser Hitoshi Watanabe , Rosa Maria Rodrigues Pereira , Luiz Fernando Onuchic
Introduction
Osteoporosis, typically seen in postmenopausal women, can also affect younger individuals, a condition known as Early-Onset Osteoporosis (EOOP). EOOP may be secondary to various conditions or arise from rare genetic disorders such as Hajdu-Cheney Syndrome (HCS), characterized by systemic bone involvement and fragility fractures.
Case Report
A 14-year-old male presented with a distal left femur fragility fracture. His medical history included spina bifida and bilateral tarsal coalition, with no family history of osteoporosis, and polycystic kidneys associated with a positive family history of autosomal dominant polycystic kidney disease (ADPKD). Laboratory tests were unremarkable, but dual X-ray absorptiometry (DXA) revealed low bone mineral density (BMD), and high resolution peripheral quantitative computed tomography (HR-pQCT) showed decreased volumetric bone density (vBMD), particularly in the cortical bone. At age 17, his kidneys were cystic and mildly enlarged. Whole exome sequencing revealed a pathogenic variant in NOTCH2, confirming the diagnosis of HCS, and a very likely causative variant in PKD1, supporting the diagnosis of ADPKD.
The treatment regimen included weekly alendronate, impact exercise, a calcium-rich diet, and vitamin D supplementation. After 3 years, follow-up DXA and HR-pQCT demonstrated significant improvements in BMD and vBMD, mainly in the cortical bone.
Discussion
This case highlights the effectiveness of alendronate in managing osteoporosis in a patient with HCS and ADPKD, despite the current lack of strong supportive evidence. Long-term monitoring revealed substantial improvements in bone density and microarchitecture, underscoring the importance of early diagnosis and intervention for genetic causes of osteoporosis to prevent fracture-related morbidity.
{"title":"Bone mineral density and microarchitecture improvement in a young patient with Hajdu-Cheney syndrome and autosomal dominant polycystic kidney disease treated with alendronate","authors":"André Silva Franco , Valeria de Falco Caparbo , Elieser Hitoshi Watanabe , Rosa Maria Rodrigues Pereira , Luiz Fernando Onuchic","doi":"10.1016/j.bonr.2025.101838","DOIUrl":"10.1016/j.bonr.2025.101838","url":null,"abstract":"<div><h3>Introduction</h3><div>Osteoporosis, typically seen in postmenopausal women, can also affect younger individuals, a condition known as Early-Onset Osteoporosis (EOOP). EOOP may be secondary to various conditions or arise from rare genetic disorders such as Hajdu-Cheney Syndrome (HCS), characterized by systemic bone involvement and fragility fractures.</div></div><div><h3>Case Report</h3><div>A 14-year-old male presented with a distal left femur fragility fracture. His medical history included spina bifida and bilateral tarsal coalition, with no family history of osteoporosis, and polycystic kidneys associated with a positive family history of autosomal dominant polycystic kidney disease (ADPKD). Laboratory tests were unremarkable, but dual X-ray absorptiometry (DXA) revealed low bone mineral density (BMD), and high resolution peripheral quantitative computed tomography (HR-pQCT) showed decreased volumetric bone density (vBMD), particularly in the cortical bone. At age 17, his kidneys were cystic and mildly enlarged. Whole exome sequencing revealed a pathogenic variant in <em>NOTCH2</em>, confirming the diagnosis of HCS, and a very likely causative variant in <em>PKD1</em>, supporting the diagnosis of ADPKD.</div><div>The treatment regimen included weekly alendronate, impact exercise, a calcium-rich diet, and vitamin D supplementation. After 3 years, follow-up DXA and HR-pQCT demonstrated significant improvements in BMD and vBMD, mainly in the cortical bone.</div></div><div><h3>Discussion</h3><div>This case highlights the effectiveness of alendronate in managing osteoporosis in a patient with HCS and ADPKD, despite the current lack of strong supportive evidence. Long-term monitoring revealed substantial improvements in bone density and microarchitecture, underscoring the importance of early diagnosis and intervention for genetic causes of osteoporosis to prevent fracture-related morbidity.</div></div>","PeriodicalId":9043,"journal":{"name":"Bone Reports","volume":"25 ","pages":"Article 101838"},"PeriodicalIF":2.1,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143697921","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-06-01Epub Date: 2025-03-12DOI: 10.1016/j.bonr.2025.101836
Russell T. Turner , Amida F. Kuah , Cynthia H. Trevisiol , Kathy S. Howe , Adam J. Branscum , Urszula T. Iwaniec
Allografts play an important role in treatment of complex bone fractures and deformities. The purpose of this study was to test the hypothesis that alcohol consumption impairs graft incorporation and bone healing by two mechanisms: (1) by lowering osteoinductive capacity and (2) by suppressing bone formation. We performed experiments using a demineralized allogeneic bone matrix (DBM) model in which DBM harvested from donor rats fed control or ethanol diet was implanted subcutaneously into recipient rats fed control or ethanol diet. We also evaluated the efficacy of intermittent parathyroid hormone (PTH) on bone graft incorporation (DBM from donor rats fed alcohol or control diet) using a critical size defect model. Bone formed during osteoinduction was measured by micro-computed tomography. Experiment 1: Bone volume was lower in DBM harvested from ethanol-consuming donors 6 weeks following implantation into recipients fed control diet, indicating that exposure of the donor rats to ethanol lowered osteoinductive capacity. Experiment 2: Bone volume was lower in DBM harvested 3 weeks following implantation from ethanol-consuming donors into ethanol-consuming recipients compared to DBM harvested from control donors implanted into control recipients or DBM harvested from control donors implanted into ethanol-consuming recipients. Experiment 3: Ethanol consumption by donors resulted in a tendency for lower DBM bone volume (p = 0.085) whereas PTH treatment resulted in higher DBM bone volume in the critical size defect model. Our results suggest that chronic heavy alcohol consumption by allograft donors may impair osteoinduction and this negative outcome may be worsened by alcohol intake during bone healing. Additionally, PTH has the potential to increase osteoinduction in DBM harvested from both abstinent and alcohol-consuming donors.
{"title":"Chronic heavy alcohol consumption impairs the ability of demineralized allogenic bone matrix to support osteoinduction in alcohol-naïve rats","authors":"Russell T. Turner , Amida F. Kuah , Cynthia H. Trevisiol , Kathy S. Howe , Adam J. Branscum , Urszula T. Iwaniec","doi":"10.1016/j.bonr.2025.101836","DOIUrl":"10.1016/j.bonr.2025.101836","url":null,"abstract":"<div><div>Allografts play an important role in treatment of complex bone fractures and deformities. The purpose of this study was to test the hypothesis that alcohol consumption impairs graft incorporation and bone healing by two mechanisms: (1) by lowering osteoinductive capacity and (2) by suppressing bone formation. We performed experiments using a demineralized allogeneic bone matrix (DBM) model in which DBM harvested from donor rats fed control or ethanol diet was implanted subcutaneously into recipient rats fed control or ethanol diet. We also evaluated the efficacy of intermittent parathyroid hormone (PTH) on bone graft incorporation (DBM from donor rats fed alcohol or control diet) using a critical size defect model. Bone formed during osteoinduction was measured by micro-computed tomography. <u>Experiment 1</u>: Bone volume was lower in DBM harvested from ethanol-consuming donors 6 weeks following implantation into recipients fed control diet, indicating that exposure of the donor rats to ethanol lowered osteoinductive capacity. <u>Experiment 2</u>: Bone volume was lower in DBM harvested 3 weeks following implantation from ethanol-consuming donors into ethanol-consuming recipients compared to DBM harvested from control donors implanted into control recipients or DBM harvested from control donors implanted into ethanol-consuming recipients. <u>Experiment 3</u>: Ethanol consumption by donors resulted in a tendency for lower DBM bone volume (<em>p</em> = 0.085) whereas PTH treatment resulted in higher DBM bone volume in the critical size defect model. Our results suggest that chronic heavy alcohol consumption by allograft donors may impair osteoinduction and this negative outcome may be worsened by alcohol intake during bone healing. Additionally, PTH has the potential to increase osteoinduction in DBM harvested from both abstinent and alcohol-consuming donors.</div></div>","PeriodicalId":9043,"journal":{"name":"Bone Reports","volume":"25 ","pages":"Article 101836"},"PeriodicalIF":2.1,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143632198","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-06-01Epub Date: 2025-05-05DOI: 10.1016/j.bonr.2025.101848
Nicola Veronese , Francesco Saverio Ragusa , Shaun Sabico , Ligia Juliana Dominguez , Mario Barbagallo , Gustavo Duque , Lee Smith , Nasser Al-Daghri
Background
Osteosarcopenia (i.e., the co-existence of osteoporosis and sarcopenia) and depression are highly prevalent among older people. However, the association between osteosarcopenia and depression in older people is largely unknown. Therefore, the present study aims to investigate this possible association in a representative sample of the older adult population in Europe and Israel.
Methods
Osteosarcopenia was defined as the concomitant presence of osteoporosis and sarcopenia; depressive symptoms in the SHARE study were self-reported using the EURO-D scale. The association between the presence of osteosarcopenia at baseline in people free from depression and incident depression during 12 years of follow-up was analyzed using a Cox's regression analysis, adjusting for several baseline covariates.
Results
16,452 participants were included (mean age 63.7, SD 9.6; females 50.6 %). During the follow-up period, 5056 participants (31.1 % of the initial population) became depressed. People affected by osteosarcopenia became depressed in more than half of the cases compared to a quarter of controls. After adjusting for several potential baseline confounding variables, only sarcopenia (HR, hazard ratio = 1.17; 95 % CI, confidence intervals 1.04–1.32; p = 0.009) and osteosarcopenia (HR = 1.27; CI 95 % 1.12–1.58; p = 0.003) were significantly associated with a higher risk of depression.
Limitations
Definition of sarcopenia using an anthropometric equation; definition of depression using the EURO-D scale.
Conclusions
The present study identified a significant association between osteosarcopenia and depression over 12 years of follow-up, mainly driven by sarcopenia. If future research confirms the present findings, it may then be prudent to target those with osteosarcopenia to aid in the prevention of onset depression.
{"title":"Osteosarcopenia as a risk factor for depression: Longitudinal findings from the SHARE study","authors":"Nicola Veronese , Francesco Saverio Ragusa , Shaun Sabico , Ligia Juliana Dominguez , Mario Barbagallo , Gustavo Duque , Lee Smith , Nasser Al-Daghri","doi":"10.1016/j.bonr.2025.101848","DOIUrl":"10.1016/j.bonr.2025.101848","url":null,"abstract":"<div><h3>Background</h3><div>Osteosarcopenia (i.e., the co-existence of osteoporosis and sarcopenia) and depression are highly prevalent among older people. However, the association between osteosarcopenia and depression in older people is largely unknown. Therefore, the present study aims to investigate this possible association in a representative sample of the older adult population in Europe and Israel.</div></div><div><h3>Methods</h3><div>Osteosarcopenia was defined as the concomitant presence of osteoporosis and sarcopenia; depressive symptoms in the SHARE study were self-reported using the EURO-D scale. The association between the presence of osteosarcopenia at baseline in people free from depression and incident depression during 12 years of follow-up was analyzed using a Cox's regression analysis, adjusting for several baseline covariates.</div></div><div><h3>Results</h3><div>16,452 participants were included (mean age 63.7, SD 9.6; females 50.6 %). During the follow-up period, 5056 participants (31.1 % of the initial population) became depressed. People affected by osteosarcopenia became depressed in more than half of the cases compared to a quarter of controls. After adjusting for several potential baseline confounding variables, only sarcopenia (HR, hazard ratio = 1.17; 95 % CI, confidence intervals 1.04–1.32; <em>p</em> = 0.009) and osteosarcopenia (HR = 1.27; CI 95 % 1.12–1.58; <em>p</em> = 0.003) were significantly associated with a higher risk of depression.</div></div><div><h3>Limitations</h3><div>Definition of sarcopenia using an anthropometric equation; definition of depression using the EURO-D scale.</div></div><div><h3>Conclusions</h3><div>The present study identified a significant association between osteosarcopenia and depression over 12 years of follow-up, mainly driven by sarcopenia. If future research confirms the present findings, it may then be prudent to target those with osteosarcopenia to aid in the prevention of onset depression.</div></div>","PeriodicalId":9043,"journal":{"name":"Bone Reports","volume":"25 ","pages":"Article 101848"},"PeriodicalIF":2.1,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144105355","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Medication-Related-Osteonecrosis-of-the-Jaw (MRONJ) is an adverse event linked to antiresorptives such as bisphosphonates and denosumab. While MRONJ predominantly affects cancer patients treated with these agents, it has been less frequently reported in cancer patients receiving angiogenesis inhibitors (AgIs) like bevacizumab and sunitinib, even without concurrent use of antiresorptives. We hypothesized that certain AgIs exhibit antiresorptive activity in addition to their antiangiogenic effects, potentially influencing the pathophysiology of MRONJ.
52 five-week-old SD rats were randomized to receive vehicle (VEH), an oncologic dose of zoledronic acid (ZOL), or low (LD) and high doses (HD) of either an anti-VEGFA antibody or sunitinib (SU) for 10 days. We used the Schenk assay to assess the in vivo antiresorptive properties of these drugs/agents. We evaluated serum biomarkers of bone resorption (TRACP 5b) and formation (P1NP), pQCT variables of the femurs/tibias, and bone resorption/formation variables by bone histomorphometry at the distal femur metaphysis.
ZOL reduced TRACP-5b levels, osteoclast number, and BFR while increasing vBMD, mineralized tissue volume, calcified cartilage volume, and bone volume. Both anti-VEGFA and SU decreased osteoclast number and increased calcified cartilage volume relative to total mineralized tissue volume, though to a lesser extent than ZOL. Anti-VEGFA (HD) also reduced TRACP-5b levels. Furthermore, both AgIs decreased P1NP levels, MAR, and bone elongation rate but increased growth cartilage thickness and induced physeal dysplasia.
In conclusion, AgIs, particularly anti-VEGFA, exhibit significant yet milder antiresorptive activity compared to ZOL. They also affect bone formation, suggesting a complex mechanism that may play a role in the pathophysiology of MRONJ.
{"title":"Mild antiresorptive activity of an anti-vascular endothelial growth factor A antibody and sunitinib in a rat model of bone resorption","authors":"J.I. Aguirre, S.M. Croft, E.J. Castillo, C.J. Cruz-Camacho, D.B. Kimmel","doi":"10.1016/j.bonr.2025.101837","DOIUrl":"10.1016/j.bonr.2025.101837","url":null,"abstract":"<div><div>Medication-Related-Osteonecrosis-of-the-Jaw (MRONJ) is an adverse event linked to antiresorptives such as bisphosphonates and denosumab. While MRONJ predominantly affects cancer patients treated with these agents, it has been less frequently reported in cancer patients receiving angiogenesis inhibitors (AgIs) like bevacizumab and sunitinib, even without concurrent use of antiresorptives. We <em>hypothesized</em> that certain AgIs exhibit antiresorptive activity in addition to their antiangiogenic effects, potentially influencing the pathophysiology of MRONJ.</div><div>52 five-week-old SD rats were randomized to receive vehicle (VEH), an oncologic dose of zoledronic acid (ZOL), or low (LD) and high doses (HD) of either an anti-VEGFA antibody or sunitinib (SU) for 10 days. We used the Schenk assay to assess the <em>in vivo</em> antiresorptive properties of these drugs/agents. We evaluated serum biomarkers of bone resorption (TRACP 5b) and formation (P1NP), pQCT variables of the femurs/tibias, and bone resorption/formation variables by bone histomorphometry at the distal femur metaphysis.</div><div>ZOL reduced TRACP-5b levels, osteoclast number, and BFR while increasing vBMD, mineralized tissue volume, calcified cartilage volume, and bone volume. Both anti-VEGFA and SU decreased osteoclast number and increased calcified cartilage volume relative to total mineralized tissue volume, though to a lesser extent than ZOL. Anti-VEGFA (HD) also reduced TRACP-5b levels. Furthermore, both AgIs decreased P1NP levels, MAR, and bone elongation rate but increased growth cartilage thickness and induced physeal dysplasia.</div><div>In conclusion, AgIs, particularly anti-VEGFA, exhibit significant yet milder antiresorptive activity compared to ZOL. They also affect bone formation, suggesting a complex mechanism that may play a role in the pathophysiology of MRONJ.</div></div>","PeriodicalId":9043,"journal":{"name":"Bone Reports","volume":"25 ","pages":"Article 101837"},"PeriodicalIF":2.1,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143642223","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-06-01Epub Date: 2025-05-29DOI: 10.1016/j.bonr.2025.101853
Lothar Seefried, Franca Genest
Purpose
Hypophosphatasia (HPP) is a rare disease characterized by skeletal and nonskeletal manifestations that can increase patient disability. The 6-Minute Walk Test (6MWT) is frequently used to assess mobility in patients with HPP, although the test is laborious to conduct in clinical practice. The purpose of the current study was to determine correlations between time to complete the 6MWT, time to complete the Chair-Rise Test (CRT), and scores on the Lower Extremity Functional Scale (LEFS) in adults with HPP.
Methods
Pearson correlations between time to complete outcomes on the 6MWT and CRT, time to complete the 6MWT and scores on the LEFS, and time to complete the CRT and scores on the LEFS were calculated using de-identified data from adults with HPP who had first onset of symptoms in childhood. All patients were enrolled in the previously conducted, observational EmPATHY study.
Results
Pearson correlation analyses showed inverse correlations between 6MWT and CRT outcomes (r = −0.584) and between CRT and LEFS outcomes (r = −0.596) and a direct correlation between 6MWT and LEFS outcomes (r = 0.808).
Conclusions
Time to complete the 6MWT was correlated with time to complete the CRT and scores on the LEFS in adults with HPP. CRT and LEFS may be suitable, expeditious options to amend or substitute 6MWT when assessing functional status in patients with HPP.
{"title":"Correlations between 6-minute walk test, chair-rise test, and lower extremity functional scale among patients with hypophosphatasia","authors":"Lothar Seefried, Franca Genest","doi":"10.1016/j.bonr.2025.101853","DOIUrl":"10.1016/j.bonr.2025.101853","url":null,"abstract":"<div><h3>Purpose</h3><div>Hypophosphatasia (HPP) is a rare disease characterized by skeletal and nonskeletal manifestations that can increase patient disability. The 6-Minute Walk Test (6MWT) is frequently used to assess mobility in patients with HPP, although the test is laborious to conduct in clinical practice. The purpose of the current study was to determine correlations between time to complete the 6MWT, time to complete the Chair-Rise Test (CRT), and scores on the Lower Extremity Functional Scale (LEFS) in adults with HPP.</div></div><div><h3>Methods</h3><div>Pearson correlations between time to complete outcomes on the 6MWT and CRT, time to complete the 6MWT and scores on the LEFS, and time to complete the CRT and scores on the LEFS were calculated using de-identified data from adults with HPP who had first onset of symptoms in childhood. All patients were enrolled in the previously conducted, observational EmPATHY study.</div></div><div><h3>Results</h3><div>Pearson correlation analyses showed inverse correlations between 6MWT and CRT outcomes (<em>r</em> = −0.584) and between CRT and LEFS outcomes (<em>r</em> = −0.596) and a direct correlation between 6MWT and LEFS outcomes (<em>r</em> = 0.808).</div></div><div><h3>Conclusions</h3><div>Time to complete the 6MWT was correlated with time to complete the CRT and scores on the LEFS in adults with HPP. CRT and LEFS may be suitable, expeditious options to amend or substitute 6MWT when assessing functional status in patients with HPP.</div></div>","PeriodicalId":9043,"journal":{"name":"Bone Reports","volume":"25 ","pages":"Article 101853"},"PeriodicalIF":2.1,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144167867","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-03-01Epub Date: 2025-01-03DOI: 10.1016/j.bonr.2024.101823
Yuanyuan Zhang, Xuejing Wang, Shiguang Huo, Li Hong, Feifei Li
Introduction
Adolescents with a lower peak bone mineral density (BMD) and bone mineral content (BMC) have an elevated risk of osteoporosis in adulthood. The impact of diet on bone health, particularly its role in managing inflammation, which is a key factor in bone health, is gaining wider recognition. Despite evidence that anti-inflammatory diets can enhance bone health, the link between the dietary inflammatory index (DII) and bone health among US adolescents has not been thoroughly investigated. This study aimed to evaluate the correlation between DII score and bone health in this population.
Methods
This cross-sectional study used data from the National Health and Nutrition Examination Survey (NHANES) of US adolescents aged 12–18 years, spanning surveys from 2001 to 2018. The DII was derived from dietary recall data obtained through questionnaire interviews. Bone health was assessed through total body less head (TBLH) BMD and BMC z-scores and lumbar spine bone mineral apparent density for age (BMADa).
Results
The study comprised 8773 adolescents with a mean age of 14.94 ± 1.97 years, 52.2 % were male. Multivariate linear regression analysis revealed a negative correlation between DII and lumbar spine BMADa (β = −0.000003, 95 % confidence interval [CI], −0.000005 to −0.000001; P = 0.001).This significant association remained robust when DII was treated as a categorical variable. Compared with individuals in quartile 1(Q1) DII scores (−3.71 to 1.04), those in Q4 (3.37 to 5.04) had lower BMADa, with a regression coefficient of −0.00002 (95 % CI, −0.00003 to −0.000007, P < 0.001). DII was negatively correlated with TBLH BMC z-scores; however, the difference was not statistically significant. Subgroup analyses showed that DII was associated with lumbar spine BMADa and TBLH BMC z-scores in participants who were male, non-black, with a higher educational level, with a high family income, and underweight to normal weight. We found no significant association between DII and TBLH BMD z-scores.
Conclusion
The findings from this cross-sectional analysis indicate a significant association between the DII and bone health among adolescents in the US, with a notable impact in males and non-black. These insights underscore the importance of adopting dietary patterns to mitigate inflammation and to support optimal bone health and metabolism.
{"title":"The association between dietary inflammatory index and bone health in US adolescents: Analysis of the NHANES data","authors":"Yuanyuan Zhang, Xuejing Wang, Shiguang Huo, Li Hong, Feifei Li","doi":"10.1016/j.bonr.2024.101823","DOIUrl":"10.1016/j.bonr.2024.101823","url":null,"abstract":"<div><h3>Introduction</h3><div>Adolescents with a lower peak bone mineral density (BMD) and bone mineral content (BMC) have an elevated risk of osteoporosis in adulthood. The impact of diet on bone health, particularly its role in managing inflammation, which is a key factor in bone health, is gaining wider recognition. Despite evidence that anti-inflammatory diets can enhance bone health, the link between the dietary inflammatory index (DII) and bone health among US adolescents has not been thoroughly investigated. This study aimed to evaluate the correlation between DII score and bone health in this population.</div></div><div><h3>Methods</h3><div>This cross-sectional study used data from the National Health and Nutrition Examination Survey (NHANES) of US adolescents aged 12–18 years, spanning surveys from 2001 to 2018. The DII was derived from dietary recall data obtained through questionnaire interviews. Bone health was assessed through total body less head (TBLH) BMD and BMC z-scores and lumbar spine bone mineral apparent density for age (BMAD<sub>a</sub>).</div></div><div><h3>Results</h3><div>The study comprised 8773 adolescents with a mean age of 14.94 ± 1.97 years, 52.2 % were male. Multivariate linear regression analysis revealed a negative correlation between DII and lumbar spine BMAD<sub>a</sub> (β = −0.000003, 95 % confidence interval [CI], −0.000005 to −0.000001; <em>P</em> = 0.001).This significant association remained robust when DII was treated as a categorical variable. Compared with individuals in quartile 1(Q1) DII scores (−3.71 to 1.04), those in Q4 (3.37 to 5.04) had lower BMAD<sub>a</sub>, with a regression coefficient of −0.00002 (95 % CI, −0.00003 to −0.000007, <em>P</em> < 0.001). DII was negatively correlated with TBLH BMC z-scores; however, the difference was not statistically significant. Subgroup analyses showed that DII was associated with lumbar spine BMAD<sub>a</sub> and TBLH BMC z-scores in participants who were male, non-black, with a higher educational level, with a high family income, and underweight to normal weight. We found no significant association between DII and TBLH BMD z-scores.</div></div><div><h3>Conclusion</h3><div>The findings from this cross-sectional analysis indicate a significant association between the DII and bone health among adolescents in the US, with a notable impact in males and non-black. These insights underscore the importance of adopting dietary patterns to mitigate inflammation and to support optimal bone health and metabolism.</div></div>","PeriodicalId":9043,"journal":{"name":"Bone Reports","volume":"24 ","pages":"Article 101823"},"PeriodicalIF":2.1,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11758120/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143045638","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-03-01Epub Date: 2025-02-20DOI: 10.1016/j.bonr.2025.101831
Tongxin Zhu, Zhangyan Xu, Dan Liu, Wei Zeng, Yongliang Pu, Haitao Yang
Objectives
To investigate the effect of lumbosacral transitional vertebra (LSTV) on the biomechanical properties of adjacent discs and facet joints based on geometrically 3D personalized FEA.
Methods
A total of 45 individuals who underwent low dose whole body CT scans were retrospectively included and equally divided into 23, 24, and 25 presacral vertebrae (PSV) groups. Three-dimensional Finite Element computational models of normal and number-variant sub-types of LSTV were created. The biomechanical parameters, including the range of motion (ROM), the intervertebral disc pressure (IDP), and facet joint forces (FJF), were all evaluated to determine the biomechanical effects. IDP was equally divided into anterior (AIDP), middle (MIDP) and posterior (PIDP) parts along the short axis of the intervertebral disc.
Results
During extension, the 23 PSV group exhibited significantly higher von Meiss stress in the upper intervertebral disc compared to the 24 and 25 PSV groups (P = 0.003), indicating concentrated stress in the upper lumbar region and an increased the likelihood of localized disc degeneration over time. Furthermore, the 23 PSV group exhibited a larger ROM (3.28°) than the 25 PSV group (1.40°) (P = 0.011), implying greater segmental mobility and possible instability in the transitional segment. During flexion, the 25 PSV group showed higher stress in the lower intervertebral disc and a larger ROM than the 23 and 24 PSV groups; however, the differences were not significant (P > 0.05).
Conclusions
The increased stress distribution and ROM in the upper disc of the transitional segment were only found in the 23 PSV sub-type of Castellvi type I LSTVs during extension, but not in the 25 PSV sub-type, which may help to further understand the impact of LSTV on the surrounding structures.
{"title":"Biomechanical influence of numerical variants of lumbosacral transitional vertebra with Castellvi type I on adjacent discs and facet joints based on 3D finite element analysis","authors":"Tongxin Zhu, Zhangyan Xu, Dan Liu, Wei Zeng, Yongliang Pu, Haitao Yang","doi":"10.1016/j.bonr.2025.101831","DOIUrl":"10.1016/j.bonr.2025.101831","url":null,"abstract":"<div><h3>Objectives</h3><div>To investigate the effect of lumbosacral transitional vertebra (LSTV) on the biomechanical properties of adjacent discs and facet joints based on geometrically 3D personalized FEA.</div></div><div><h3>Methods</h3><div>A total of 45 individuals who underwent low dose whole body CT scans were retrospectively included and equally divided into 23, 24, and 25 presacral vertebrae (PSV) groups. Three-dimensional Finite Element computational models of normal and number-variant sub-types of LSTV were created. The biomechanical parameters, including the range of motion (ROM), the intervertebral disc pressure (IDP), and facet joint forces (FJF), were all evaluated to determine the biomechanical effects. IDP was equally divided into anterior (AIDP), middle (MIDP) and posterior (PIDP) parts along the short axis of the intervertebral disc.</div></div><div><h3>Results</h3><div>During extension, the 23 PSV group exhibited significantly higher von Meiss stress in the upper intervertebral disc compared to the 24 and 25 PSV groups (<em>P</em> = 0.003), indicating concentrated stress in the upper lumbar region and an increased the likelihood of localized disc degeneration over time. Furthermore, the 23 PSV group exhibited a larger ROM (3.28°) than the 25 PSV group (1.40°) (<em>P</em> = 0.011), implying greater segmental mobility and possible instability in the transitional segment. During flexion, the 25 PSV group showed higher stress in the lower intervertebral disc and a larger ROM than the 23 and 24 PSV groups; however, the differences were not significant (<em>P</em> > 0.05).</div></div><div><h3>Conclusions</h3><div>The increased stress distribution and ROM in the upper disc of the transitional segment were only found in the 23 PSV sub-type of Castellvi type I LSTVs during extension, but not in the 25 PSV sub-type, which may help to further understand the impact of LSTV on the surrounding structures.</div></div>","PeriodicalId":9043,"journal":{"name":"Bone Reports","volume":"24 ","pages":"Article 101831"},"PeriodicalIF":2.1,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143480616","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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