Pub Date : 2026-01-01Epub Date: 2025-10-21DOI: 10.1016/j.bone.2025.117688
Lunjian Li , Minoo Patel , Lihai Zhang
Despite standard rehabilitation protocols, many patients still suffer from limited mobility, delayed union, or even non-union. This underscores the need for personalized rehabilitation protocols. Fracture healing is a dynamic process governed by the interplay of mechanical stimuli and biochemical signalling pathways. This review first summarizes current understanding of the biological and mechanobiological mechanisms that regulate bone repair. It also discusses different simulation models, including the finite element method (FEM), agent-based models (ABM), reaction–diffusion models (RDM), and machine learning (ML), and evaluates their respective strengths. Recent advances in patient-specific models are also reviewed, particularly those integrating CT-derived geometry, bone properties, and musculoskeletal (MSK) loading. These approaches enable individualized predictions of healing and can inform clinical rehabilitation strategies. Finally, the key challenges and future priorities for implementing these technologies in clinical practice are discussed, providing insights to support the development of more precise and patient-specific fracture care.
{"title":"A review of bone fracture healing modelling: from mechanobiological theory to personalized rehabilitation protocols","authors":"Lunjian Li , Minoo Patel , Lihai Zhang","doi":"10.1016/j.bone.2025.117688","DOIUrl":"10.1016/j.bone.2025.117688","url":null,"abstract":"<div><div>Despite standard rehabilitation protocols, many patients still suffer from limited mobility, delayed union, or even non-union. This underscores the need for personalized rehabilitation protocols. Fracture healing is a dynamic process governed by the interplay of mechanical stimuli and biochemical signalling pathways. This review first summarizes current understanding of the biological and mechanobiological mechanisms that regulate bone repair. It also discusses different simulation models, including the finite element method (FEM), agent-based models (ABM), reaction–diffusion models (RDM), and machine learning (ML), and evaluates their respective strengths. Recent advances in patient-specific models are also reviewed, particularly those integrating CT-derived geometry, bone properties, and musculoskeletal (MSK) loading. These approaches enable individualized predictions of healing and can inform clinical rehabilitation strategies. Finally, the key challenges and future priorities for implementing these technologies in clinical practice are discussed, providing insights to support the development of more precise and patient-specific fracture care.</div></div>","PeriodicalId":9301,"journal":{"name":"Bone","volume":"202 ","pages":"Article 117688"},"PeriodicalIF":3.6,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145356963","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 : 2026-01-01Epub Date: 2025-09-11DOI: 10.1016/j.bone.2025.117641
Giulia Montagna , Stephanie Lee , Austin Baacke , Matthew L. Warman , Christina M. Jacobsen
Increased fracture is a hallmark feature of the skeletal disorder Osteogenesis Imperfecta (OI). A neutralizing antibody against sclerostin, an endogenous Wnt signaling inhibitor, has been FDA-approved for osteoporosis and is now in clinical trials for OI. This anti-sclerostin antibody increased bone mass and skeletal strength in several preclinical models of OI.
Because in vivo fracture incidence is the primary outcome measure in human OI clinical trials, we examined the effect of enhancing Wnt signaling in a preclinical mouse model of severe, autosomal dominant OI (the Col1a1Aga2/+ mouse). We genetically enhanced Wnt signaling using the Lrp5A214V allele, which makes the Wnt co-receptor LRP5 resistant to sclerostin inhibition. By crossing Col1a1Aga2/+ sires with Lrp5A214V/+ dams, we generated pups with OI alone and pups with OI plus enhanced Wnt signaling. We radiographically examined these animals for fractures at 5, 9, and 13 weeks of age and also measured their mobility using a Holeboard assay.
We found that enhanced Wnt signaling significantly reduced fracture numbers in this OI model by 30 % at each age but did not significantly affect mobility. These data indicate that an enhanced Wnt signaling decreases fracture incidence in a preclinical model of severe OI and suggest that lower fracture rates could be achieved by administering anti-sclerostin antibodies to OI patients.
{"title":"Enhancing Wnt signaling lowers fracture incidence in a severe mouse model of Osteogenesis Imperfecta","authors":"Giulia Montagna , Stephanie Lee , Austin Baacke , Matthew L. Warman , Christina M. Jacobsen","doi":"10.1016/j.bone.2025.117641","DOIUrl":"10.1016/j.bone.2025.117641","url":null,"abstract":"<div><div>Increased fracture is a hallmark feature of the skeletal disorder Osteogenesis Imperfecta (OI). A neutralizing antibody against sclerostin, an endogenous Wnt signaling inhibitor, has been FDA-approved for osteoporosis and is now in clinical trials for OI. This anti-sclerostin antibody increased bone mass and skeletal strength in several preclinical models of OI.</div><div>Because <em>in vivo</em> fracture incidence is the primary outcome measure in human OI clinical trials, we examined the effect of enhancing Wnt signaling in a preclinical mouse model of severe, autosomal dominant OI (the <em>Col1a1<sup>Aga2/+</sup></em> mouse). We genetically enhanced Wnt signaling using the <em>Lrp5<sup>A214V</sup></em> allele, which makes the Wnt co-receptor LRP5 resistant to sclerostin inhibition. By crossing <em>Col1a1<sup>Aga2/+</sup></em> sires with <em>Lrp5<sup>A214V/+</sup></em> dams, we generated pups with OI alone and pups with OI plus enhanced Wnt signaling. We radiographically examined these animals for fractures at 5, 9, and 13 weeks of age and also measured their mobility using a Holeboard assay.</div><div>We found that enhanced Wnt signaling significantly reduced fracture numbers in this OI model by 30 % at each age but did not significantly affect mobility. These data indicate that an enhanced Wnt signaling decreases fracture incidence in a preclinical model of severe OI and suggest that lower fracture rates could be achieved by administering anti-sclerostin antibodies to OI patients.</div></div>","PeriodicalId":9301,"journal":{"name":"Bone","volume":"202 ","pages":"Article 117641"},"PeriodicalIF":3.6,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145058838","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 : 2026-01-01Epub Date: 2025-10-04DOI: 10.1016/j.bone.2025.117676
Mengyuan Cai , Jinluan Chen , Jiawei Li , Katerina Trajanoska , Evert F.S. van Velsen , M. Carola Zillikens
Background
Advanced glycation end products (AGEs), formed through non-enzymatic glycation of, e.g., proteins in collagen have been associated with prevalent fractures, but their relation with bone mineral density (BMD) and trabecular bone score (TBS) is unclear.
Objectives
To assess the association of skin AGEs with BMD and TBS changes over time.
Methods
In the Rotterdam Study, skin AGEs were assessed as skin autofluorescence (SAF) using the AGE Reader®. Total body (TB), femoral neck (FN) and lumbar spine (LS) BMD were assessed using dual-energy X-ray absorptiometry (DXA). SAF was analyzed with baseline and follow-up BMD and TBS, employing a linear mixed effects model adjusted for clinical and lifestyle confounders, with interaction analysis for sex, prevalent type 2 diabetes mellitus (T2DM), chronic kidney disease, and bisphosphonate use.
Results
Longitudinal analyses between SAF and TB BMD were performed in 2553 participants (mean follow-up time 4.9 years), and between SAF and LS BMD, FN BMD and TBS in 851 participants (mean follow-up 5.6 years). SAF was not associated with BMD nor with TBS changes over time. Significant interactions were observed with sex (TB and FN BMD) and with diabetes (FN BMD), but stratified analysis revealed no significant associations.
Conclusion
We did not observe a longitudinal association between SAF and BMD at multiple sites or TBS, which is consistent with our earlier findings that associations of SAF with prevalent fractures were not explained by BMD or TBS. Other aspects of bone quality or muscle characteristics including fall risk may be involved.
{"title":"Skin Advanced Glycation End Products (AGEs) are not associated with bone mineral density longitudinally: The Rotterdam Study","authors":"Mengyuan Cai , Jinluan Chen , Jiawei Li , Katerina Trajanoska , Evert F.S. van Velsen , M. Carola Zillikens","doi":"10.1016/j.bone.2025.117676","DOIUrl":"10.1016/j.bone.2025.117676","url":null,"abstract":"<div><h3>Background</h3><div>Advanced glycation end products (AGEs), formed through non-enzymatic glycation of, e.g., proteins in collagen have been associated with prevalent fractures, but their relation with bone mineral density (BMD) and trabecular bone score (TBS) is unclear.</div></div><div><h3>Objectives</h3><div>To assess the association of skin AGEs with BMD and TBS changes over time.</div></div><div><h3>Methods</h3><div>In the Rotterdam Study, skin AGEs were assessed as skin autofluorescence (SAF) using the AGE Reader®. Total body (TB), femoral neck (FN) and lumbar spine (LS) BMD were assessed using dual-energy X-ray absorptiometry (DXA). SAF was analyzed with baseline and follow-up BMD and TBS, employing a linear mixed effects model adjusted for clinical and lifestyle confounders, with interaction analysis for sex, prevalent type 2 diabetes mellitus (T2DM), chronic kidney disease, and bisphosphonate use.</div></div><div><h3>Results</h3><div>Longitudinal analyses between SAF and TB BMD were performed in 2553 participants (mean follow-up time 4.9 years), and between SAF and LS BMD, FN BMD and TBS in 851 participants (mean follow-up 5.6 years). SAF was not associated with BMD nor with TBS changes over time. Significant interactions were observed with sex (TB and FN BMD) and with diabetes (FN BMD), but stratified analysis revealed no significant associations.</div></div><div><h3>Conclusion</h3><div>We did not observe a longitudinal association between SAF and BMD at multiple sites or TBS, which is consistent with our earlier findings that associations of SAF with prevalent fractures were not explained by BMD or TBS. Other aspects of bone quality or muscle characteristics including fall risk may be involved.</div></div>","PeriodicalId":9301,"journal":{"name":"Bone","volume":"202 ","pages":"Article 117676"},"PeriodicalIF":3.6,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145240659","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}
Hereditary hypophosphatemia (HH) are rare diseases, characterized by excessive renal phosphate wasting, rickets and osteomalacia in growing children, and osteomalacia in adults. There are several types of HH caused by pathogenic variants in a number of different genes. We present a large Danish family consisting of 19 family members with clinically and biochemically hypophosphatamia caused by a previously unreported deep intronic splice variant in PHEX: c.1080-687 A > G (p.?). The affected family members displayed a milder HH phenotype compared with a larger group of individuals with other disease causing PHEX variants. We were able to genetically confirm a diagnosis of X-linked hypophosphatemia (XLH) by genome sequencing intron analysis and in vitro analysis consisting of an exon trapping assay. Our findings emphasize the phenotypic variability of XLH, where this family in general displays a milder phenotype. Furthermore, our findings demonstrate that XLH can be caused by intron variants in PHEX.
遗传性低磷血症（HH）是一种罕见的疾病，其特征是过度的肾磷酸盐消耗、佝偻病和成长期儿童骨软化症以及成人骨软化症。有几种类型的HH是由许多不同基因的致病变异引起的。我们提出了一个由19个家庭成员组成的丹麦大家庭，其临床和生化低磷血症是由先前未报道的PHEX深内含子剪接变异引起的：c.1080-687 a > G （p.?）。与其他疾病引起的PHEX变异个体相比，受影响的家庭成员表现出较轻的HH表型。通过基因组测序内含子分析和体外外显子捕获分析，我们能够从遗传学上确认x连锁低磷血症（XLH）的诊断。我们的研究结果强调了XLH的表型变异性，这个家族通常表现出较温和的表型。此外，我们的研究结果表明XLH可能是由PHEX的内含子变异引起的。
{"title":"A deep intronic PHEX variant in a large Danish family with hereditary hypophosphatemia and a milder skeletal, but more severe dental phenotype","authors":"Jenny Blechingberg , Kristian Alsbjerg Skipper , Signe Sparre Beck-Nielsen , Pernille Axél Gregersen","doi":"10.1016/j.bone.2025.117666","DOIUrl":"10.1016/j.bone.2025.117666","url":null,"abstract":"<div><div>Hereditary hypophosphatemia (HH) are rare diseases, characterized by excessive renal phosphate wasting, rickets and osteomalacia in growing children, and osteomalacia in adults. There are several types of HH caused by pathogenic variants in a number of different genes. We present a large Danish family consisting of 19 family members with clinically and biochemically hypophosphatamia caused by a previously unreported deep intronic splice variant in <em>PHEX</em>: c.1080-687 A > G (p.?). The affected family members displayed a milder HH phenotype compared with a larger group of individuals with other disease causing <em>PHEX</em> variants. We were able to genetically confirm a diagnosis of X-linked hypophosphatemia (XLH) by genome sequencing intron analysis and in vitro analysis consisting of an exon trapping assay. Our findings emphasize the phenotypic variability of XLH, where this family in general displays a milder phenotype. Furthermore, our findings demonstrate that XLH can be caused by intron variants in <em>PHEX</em>.</div></div>","PeriodicalId":9301,"journal":{"name":"Bone","volume":"202 ","pages":"Article 117666"},"PeriodicalIF":3.6,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145226488","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 : 2026-01-01Epub Date: 2025-10-15DOI: 10.1016/j.bone.2025.117678
Tse-Yu Chen , Ya-Lian Deng , I-Chieh Chen , Ching-Heng Lin , Jun-Fu Lin , Yi-Ming Chen , Hsu-Tung Lee , Hui-Chih Hung
Introduction
Medication-related osteonecrosis of the jaw (MRONJ) was first reported in cancer patients receiving high-dose intravenous bisphosphonates and later linked to other anti-resorptive agents such as denosumab and romosozumab. However, large-scale real-world data on MRONJ risk following these therapies remain limited. This study focuses on the widely used parenteral anti-resorptive agents—ibandronate, denosumab, and zoledronic acid—chosen for their clinical popularity, cost-effectiveness, and convenient dosing. We aimed to assess the risk of MRONJ associated with each agent using real-world data from a global healthcare network.
Methods
This retrospective cohort study was conducted using the TriNetX network. To clarify the causal relationship, cohorts were created to include patients treated with only one anti-resorptive medication. Propensity score matching was applied to adjust for known risk factors associated with MRONJ. Additionally, subgroup analyses were performed for cancer and non-cancer patient populations.
Results
Propensity score matching yielded balanced cohorts (n = 36,983 each) for comparing MRONJ risk. Among matched patients, 106 denosumab users and 41 zoledronic acid users developed MRONJ (HR: 0.378; 95 % CI: 0.264–0.543). No case occurred in the ibandronate group (n = 11,405), which showed substantially lower risk compared to zoledronic acid and denosumab. The incidence of inflammatory condition of jaws share similar trends compared to those of MRONJ among the three groups. In cancer patients, MRONJ risk was 0.294 % with denosumab and 0.525 % with zoledronic acid. Non-cancer patients had much lower risk.
Conclusions
This study used real-world data from the TriNetX platform to evaluate the risk of MRONJ associated with various anti-osteoporosis medications, excluding combination therapies for clarity. Our findings indicate that among the commonly used parenteral anti-resorptive agents, denosumab has been associated with the highest risk of MRONJ, followed by zoledronic acid, with ibandronate showing the lowest risk.
{"title":"Medication-related osteonecrosis of the jaw following osteoporosis therapy: A real-world retrospective cohort study using the TriNetX global collaborative network","authors":"Tse-Yu Chen , Ya-Lian Deng , I-Chieh Chen , Ching-Heng Lin , Jun-Fu Lin , Yi-Ming Chen , Hsu-Tung Lee , Hui-Chih Hung","doi":"10.1016/j.bone.2025.117678","DOIUrl":"10.1016/j.bone.2025.117678","url":null,"abstract":"<div><h3>Introduction</h3><div>Medication-related osteonecrosis of the jaw (MRONJ) was first reported in cancer patients receiving high-dose intravenous bisphosphonates and later linked to other anti-resorptive agents such as denosumab and romosozumab. However, large-scale real-world data on MRONJ risk following these therapies remain limited. This study focuses on the widely used parenteral anti-resorptive agents—ibandronate, denosumab, and zoledronic acid—chosen for their clinical popularity, cost-effectiveness, and convenient dosing. We aimed to assess the risk of MRONJ associated with each agent using real-world data from a global healthcare network.</div></div><div><h3>Methods</h3><div>This retrospective cohort study was conducted using the TriNetX network. To clarify the causal relationship, cohorts were created to include patients treated with only one anti-resorptive medication. Propensity score matching was applied to adjust for known risk factors associated with MRONJ. Additionally, subgroup analyses were performed for cancer and non-cancer patient populations.</div></div><div><h3>Results</h3><div>Propensity score matching yielded balanced cohorts (<em>n</em> = 36,983 each) for comparing MRONJ risk. Among matched patients, 106 denosumab users and 41 zoledronic acid users developed MRONJ (HR: 0.378; 95 % CI: 0.264–0.543). No case occurred in the ibandronate group (<em>n</em> = 11,405), which showed substantially lower risk compared to zoledronic acid and denosumab. The incidence of inflammatory condition of jaws share similar trends compared to those of MRONJ among the three groups. In cancer patients, MRONJ risk was 0.294 % with denosumab and 0.525 % with zoledronic acid. Non-cancer patients had much lower risk.</div></div><div><h3>Conclusions</h3><div>This study used real-world data from the TriNetX platform to evaluate the risk of MRONJ associated with various anti-osteoporosis medications, excluding combination therapies for clarity. Our findings indicate that among the commonly used parenteral anti-resorptive agents, denosumab has been associated with the highest risk of MRONJ, followed by zoledronic acid, with ibandronate showing the lowest risk.</div></div>","PeriodicalId":9301,"journal":{"name":"Bone","volume":"202 ","pages":"Article 117678"},"PeriodicalIF":3.6,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145314287","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 : 2026-01-01Epub Date: 2025-10-27DOI: 10.1016/j.bone.2025.117687
Han Liu , Zihui Li , Catherine E. Davey , Kathryn S. Stok
Osteoarthritis (OA) is the most prevalent joint disorder affecting millions of people worldwide, and involves deterioration to subchondral bone. This study aims to reveal the early bone microstructural changes at high temporal resolution in a small animal model of OA with joint laxity and inflammation.
Seventy-five male C57BI/10 mice aged nine weeks were recruited and assigned to three cross-sectional cohorts, baseline, control, and OA. Of these, forty-seven ten-week-old mice assigned to the OA cohort received intra-articular injection of collagenase on the right knee to destabilize the right tibiofemoral joint. Micro-computed tomography (microCT) scan was performed after humanely killing the mice at nine time points (eight weeks in total). Quantitative morphometric analysis (QMA) was performed to measure structure of subchondral cortical and epiphyseal femoral and tibial bone, and osteophyte activity.
Early pathological changes caused by collagenase-injection were characterized by bone morphometry measures and osteophyte detection. Compared to control joints, bone loss, lower bone volume fraction, thinner trabeculae, larger trabecular spacing, smaller trabecular number, thinner cortical bone, and osteophyte formation were observed in osteoarthritic joints at multiple time points, with changes detectable as early as one week post disease induction. Additionally, a non-linear pattern of structural changes was observed throughout the experiment, with a critical transition occurring within three weeks after disease induction. These findings underscore the necessity of early and frequent quantification to capture rapidly changing bone microstructure alterations in early stage of OA, potentially enabling earlier diagnosis, intervention, and treatment of OA.
{"title":"Revealing early subchondral bone structural changes in osteoarthritis progression in a collagenase-induced mouse model using microCT","authors":"Han Liu , Zihui Li , Catherine E. Davey , Kathryn S. Stok","doi":"10.1016/j.bone.2025.117687","DOIUrl":"10.1016/j.bone.2025.117687","url":null,"abstract":"<div><div>Osteoarthritis (OA) is the most prevalent joint disorder affecting millions of people worldwide, and involves deterioration to subchondral bone. This study aims to reveal the early bone microstructural changes at high temporal resolution in a small animal model of OA with joint laxity and inflammation.</div><div>Seventy-five male C57BI/10 mice aged nine weeks were recruited and assigned to three cross-sectional cohorts, baseline, control, and OA. Of these, forty-seven ten-week-old mice assigned to the OA cohort received intra-articular injection of collagenase on the right knee to destabilize the right tibiofemoral joint. Micro-computed tomography (microCT) scan was performed after humanely killing the mice at nine time points (eight weeks in total). Quantitative morphometric analysis (QMA) was performed to measure structure of subchondral cortical and epiphyseal femoral and tibial bone, and osteophyte activity.</div><div>Early pathological changes caused by collagenase-injection were characterized by bone morphometry measures and osteophyte detection. Compared to control joints, bone loss, lower bone volume fraction, thinner trabeculae, larger trabecular spacing, smaller trabecular number, thinner cortical bone, and osteophyte formation were observed in osteoarthritic joints at multiple time points, with changes detectable as early as one week post disease induction. Additionally, a non-linear pattern of structural changes was observed throughout the experiment, with a critical transition occurring within three weeks after disease induction. These findings underscore the necessity of early and frequent quantification to capture rapidly changing bone microstructure alterations in early stage of OA, potentially enabling earlier diagnosis, intervention, and treatment of OA.</div></div>","PeriodicalId":9301,"journal":{"name":"Bone","volume":"202 ","pages":"Article 117687"},"PeriodicalIF":3.6,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145403212","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}
{"title":"Comment on “Impact of baseline PINP on the BMD increase with romosozumab, teriparatide, and denosumab in treatment-naïve primary osteoporosis: A retrospective cohort study”","authors":"Daquan Liao , Xuezheng Zhu , Shiye Huang , Yubin Feng , Ziye Zhuang","doi":"10.1016/j.bone.2025.117667","DOIUrl":"10.1016/j.bone.2025.117667","url":null,"abstract":"","PeriodicalId":9301,"journal":{"name":"Bone","volume":"202 ","pages":"Article 117667"},"PeriodicalIF":3.6,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145260095","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 : 2026-01-01Epub Date: 2025-09-25DOI: 10.1016/j.bone.2025.117646
Lyan Abdul Wadood , Victoria McHugh , Kristin K. Clemens , Mary E. Jenkins , Jeffrey D. Holmes , Jamie L. Fleet
Background
Parkinson's Disease (PD) is a progressive neurodegenerative disorder that primarily affects the dopaminergic neurons in the basal ganglia. It leads to a range of motor symptoms such as tremors, bradykinesia, rigidity, and gait instability. A significant, but often overlooked, sequela of PD is osteoporosis, which contributes to a higher incidence of fractures. This risk is exacerbated by both PD itself as well as the medications used to manage PD. Despite the heightened risk of fragility fractures, osteoporosis in PD is frequently under-recognized and inadequately managed.
Objective
This review aimed to explore the current literature on osteoporosis management strategies specifically for individuals with PD.
Methods
MEDLINE, Scopus, and EMBASE were searched from database inception to August 10, 2025.
Results
Following a two-stage review process conducted by two independent reviewers, 18 relevant articles were identified. Of these, 17 were review articles and one was an interventional study. The literature most commonly identified lifestyle modifications, pharmacological treatments, and surgical interventions as management strategies for osteoporosis in PD. However, most of the recommendations were based on research conducted in the general population, raising concerns about their effectiveness for individuals with PD, who may have unique clinical needs.
Conclusions
We note a significant gap in research focused on osteoporosis management in PD patients. Research efforts should prioritize developing tailored strategies to manage osteoporosis in individuals with PD.
{"title":"Management of osteoporosis in Parkinson's disease: A scoping review","authors":"Lyan Abdul Wadood , Victoria McHugh , Kristin K. Clemens , Mary E. Jenkins , Jeffrey D. Holmes , Jamie L. Fleet","doi":"10.1016/j.bone.2025.117646","DOIUrl":"10.1016/j.bone.2025.117646","url":null,"abstract":"<div><h3>Background</h3><div>Parkinson's Disease (PD) is a progressive neurodegenerative disorder that primarily affects the dopaminergic neurons in the basal ganglia. It leads to a range of motor symptoms such as tremors, bradykinesia, rigidity, and gait instability. A significant, but often overlooked, sequela of PD is osteoporosis, which contributes to a higher incidence of fractures. This risk is exacerbated by both PD itself as well as the medications used to manage PD. Despite the heightened risk of fragility fractures, osteoporosis in PD is frequently under-recognized and inadequately managed.</div></div><div><h3>Objective</h3><div>This review aimed to explore the current literature on osteoporosis management strategies specifically for individuals with PD.</div></div><div><h3>Methods</h3><div>MEDLINE, Scopus, and EMBASE were searched from database inception to August 10, 2025.</div></div><div><h3>Results</h3><div>Following a two-stage review process conducted by two independent reviewers, 18 relevant articles were identified. Of these, 17 were review articles and one was an interventional study. The literature most commonly identified lifestyle modifications, pharmacological treatments, and surgical interventions as management strategies for osteoporosis in PD. However, most of the recommendations were based on research conducted in the general population, raising concerns about their effectiveness for individuals with PD, who may have unique clinical needs.</div></div><div><h3>Conclusions</h3><div>We note a significant gap in research focused on osteoporosis management in PD patients. Research efforts should prioritize developing tailored strategies to manage osteoporosis in individuals with PD.</div></div>","PeriodicalId":9301,"journal":{"name":"Bone","volume":"202 ","pages":"Article 117646"},"PeriodicalIF":3.6,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145182393","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 : 2026-01-01Epub Date: 2025-10-14DOI: 10.1016/j.bone.2025.117684
Peng Luo , Zeyang Miao , Mengyao Guo , Lingdi Qin , Run Xu , Li Lu , Ying Wang , Guanwu Li
Objective
To investigate the relationship between body roundness index (BRI) and lumbar marrow proton density fat fraction (PDFF) in postmenopausal women, with emphasis on potential nonlinear associations.
Methods
In this retrospective cross-sectional study of 186 postmenopausal women, lumbar PDFF was quantified using T2-corrected magnetic resonance spectroscopy (L3 vertebra), and bone mineral density (BMD) was assessed via dual-energy X-ray absorptiometry. Multivariable-adjusted linear regression and nonlinear analyses (smooth curve fitting, two-segment linear models) were employed to evaluate BRI-PDFF relationships, adjusting for age, menopause duration, physical activity, and BMD.
Results
Both BRI and lumbar BMD exhibited significant inverse correlations with PDFF (BRI: r = −0.513; BMD: r = −0.462; both P < 0.001). Higher BRI quartiles were associated with elevated BMD at total hip, femoral neck, and lumbar spine (P < 0.05, Q4 vs. Q1–Q3) and a progressive reduction in adjusted PDFF (Ptrend < 0.05). Linear regression confirmed dose-dependent inverse associations between BRI (continuous/quartile) and PDFF (adjusted β = −1.870 to −11.098, P < 0.05 for Q3–Q4 vs. Q1; Ptrend < 0.001). Nonlinear analysis identified a threshold at BRI = 2.58: below this point, BRI strongly predicted PDFF reduction (β = −26.048, P < 0.001), whereas the association attenuated above it (β = −1.086, P = 0.024).
Conclusions
Increased BRI independently correlates with reduced marrow adiposity in postmenopausal women, with a nonlinear threshold effect (BRI = 2.58) suggesting distinct biological mechanisms at lower versus higher adiposity levels. These findings highlight BRI as a potential biomarker for marrow fat dynamics and a target for metabolic bone disease interventions.
目的：探讨绝经后妇女体圆度指数（BRI）与腰椎骨髓质子密度脂肪分数（PDFF）之间的关系，重点探讨潜在的非线性关联。方法：在这项对186名绝经后妇女的回顾性横断面研究中，腰椎PDFF使用t2校正磁共振波谱（L3椎体）进行量化，骨密度（BMD）通过双能x线吸收仪进行评估。采用多变量调整线性回归和非线性分析（光滑曲线拟合，两段线性模型）来评估BRI-PDFF关系，调整年龄，更年期持续时间，身体活动和BMD。结果:砖和腰椎BMD与PDFF表现出显著负相关性(BRI: r = -0.513;BMD: r = -0.462;两个P 趋势 趋势 结论:增加BRI独立与减少骨髓肥胖症在绝经后妇女,用非线性阈值效应(BRI = 2.58)显示不同的生物学机制和更高的肥胖水平较低。这些发现强调BRI是骨髓脂肪动态的潜在生物标志物和代谢性骨病干预的靶标。
{"title":"The association between body roundness index and lumbar marrow fat content in postmenopausal women","authors":"Peng Luo , Zeyang Miao , Mengyao Guo , Lingdi Qin , Run Xu , Li Lu , Ying Wang , Guanwu Li","doi":"10.1016/j.bone.2025.117684","DOIUrl":"10.1016/j.bone.2025.117684","url":null,"abstract":"<div><h3>Objective</h3><div>To investigate the relationship between body roundness index (BRI) and lumbar marrow proton density fat fraction (PDFF) in postmenopausal women, with emphasis on potential nonlinear associations.</div></div><div><h3>Methods</h3><div>In this retrospective cross-sectional study of 186 postmenopausal women, lumbar PDFF was quantified using T2-corrected magnetic resonance spectroscopy (L3 vertebra), and bone mineral density (BMD) was assessed via dual-energy X-ray absorptiometry. Multivariable-adjusted linear regression and nonlinear analyses (smooth curve fitting, two-segment linear models) were employed to evaluate BRI-PDFF relationships, adjusting for age, menopause duration, physical activity, and BMD.</div></div><div><h3>Results</h3><div>Both BRI and lumbar BMD exhibited significant inverse correlations with PDFF (BRI: <em>r</em> = −0.513; BMD: <em>r</em> = −0.462; both <em>P</em> < 0.001). Higher BRI quartiles were associated with elevated BMD at total hip, femoral neck, and lumbar spine (<em>P</em> < 0.05, Q4 vs. Q1–Q3) and a progressive reduction in adjusted PDFF (<em>P</em><sub>trend</sub> < 0.05). Linear regression confirmed dose-dependent inverse associations between BRI (continuous/quartile) and PDFF (adjusted β = −1.870 to −11.098, <em>P</em> < 0.05 for Q3–Q4 vs. Q1; <em>P</em><sub>trend</sub> < 0.001). Nonlinear analysis identified a threshold at BRI = 2.58: below this point, BRI strongly predicted PDFF reduction (β = −26.048, <em>P</em> < 0.001), whereas the association attenuated above it (β = −1.086, <em>P</em> = 0.024).</div></div><div><h3>Conclusions</h3><div>Increased BRI independently correlates with reduced marrow adiposity in postmenopausal women, with a nonlinear threshold effect (BRI = 2.58) suggesting distinct biological mechanisms at lower versus higher adiposity levels. These findings highlight BRI as a potential biomarker for marrow fat dynamics and a target for metabolic bone disease interventions.</div></div>","PeriodicalId":9301,"journal":{"name":"Bone","volume":"202 ","pages":"Article 117684"},"PeriodicalIF":3.6,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145310144","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}
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