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Elevated sclerostin levels contribute to reduced bone mineral density in non-ambulatory stroke patients 硬骨蛋白水平升高导致无法行走的中风患者骨质密度降低
IF 2.1 Q3 ENDOCRINOLOGY & METABOLISM Pub Date : 2025-02-11 DOI: 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.
中风后骨质疏松症是患者康复的重要障碍。中风患者瘫痪后机械负荷和运动减少,尤其是那些不能走动的患者,对骨质流失有很大的影响。硬化蛋白是一种由SOST基因编码的蛋白质,由于机械负荷减少而积累,并抑制骨形成。本研究利用三个队列探讨脑卒中患者机械卸荷、硬化蛋白水平和骨密度(BMD)之间的关系。队列1的分析,包括可用的硬化蛋白水平测量的患者,发现非门诊患者的硬化蛋白水平明显高于门诊患者,表明门诊状态对硬化蛋白调节的影响。队列2,由骨密度测量的患者组成,证明非门诊患者长时间的机械卸载导致骨密度随时间的更大下降。在队列3患者中,有双侧骨密度测量结果的分析显示,与非偏瘫侧相比,机械负荷减少的偏瘫侧骨密度较低。这些发现共同证实了减少机械负荷会提高硬化蛋白水平并加速骨质流失的假设。通过整合三个队列的数据,本研究强调了机械卸载对骨骼健康的关键影响,特别是对行动能力有限的慢性中风患者。我们的研究为综合动态状态、硬化蛋白水平和慢性脑卒中患者骨密度的治疗提供了临床见解,并强调了对针对机械负荷途径和硬化蛋白积累的治疗方法的需求增加,这些治疗方法可以用于治疗脑卒中后慢性骨质疏松症。
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引用次数: 0
Heterotopic ossification (HO) prophylaxis in total hip arthroplasty (THA): A systematic review of level I and level II evidence since 2000 全髋关节置换术(THA)中异位骨化(HO)预防:自2000年以来I级和II级证据的系统回顾
IF 2.1 Q3 ENDOCRINOLOGY & METABOLISM Pub Date : 2025-01-25 DOI: 10.1016/j.bonr.2025.101828
Troy B. Puga , McKenna W. Box , Vincent M. Dieu , Charles R. Marchese , John T. Riehl

Introduction

Heterotopic ossification (HO) is a somewhat common occurrence after total hip arthroplasty (THA), particularly with certain approaches. This complication can be detrimental to the success of the surgical outcome. Indomethacin and radiotherapy remain common treatment modalities; however, no true gold-standard treatment is universally agreed upon. This study aims to evaluate Level I and Level II evidence for treatment practices of HO prophylaxis since 2000.

Methods

To evaluate HO prophylaxis in total hip arthroplasty, a search was conducted across MEDLINE/Pubmed, Cochrane, and Embase databases using keywords and Medical Subject Heading (MeSH) terms. Titles and abstracts were screened for eligibility for inclusion criteria. Full texts were screened and included if they met eligibility criteria.

Results

HO chemical prophylaxis was more effective than no HO prophylaxis, except for aspirin. Multiple NSAIDs showed equivalence and better side effect profiles than indomethacin. No one superior NSAID was found, and numerous modalities showed efficacy. The most effective dosages of radiation therapy and combination therapy remain unclear. Additionally, both etidronate and salmon calcitonin showed benefit in preventing HO in one study each.

Conclusion

Radiation, NSAIDs, and combination therapy all showed efficacy as HO prophylaxis modalities. HO prophylaxis treatment and modalities should be guided upon patient and surgical factors such as surgical approach, side effects and tolerability of modalities, comorbidities, and available facility resources to optimize the prevention of HO.
Level of evidence: Level IV Therapeutic.
异位骨化(HO)是全髋关节置换术(THA)后的常见现象,特别是在某些入路中。这种并发症对手术结果的成功是不利的。吲哚美辛和放疗仍然是常见的治疗方式;然而,没有一种真正的黄金标准治疗方法得到普遍认可。本研究旨在评估自2000年以来HO预防治疗实践的I级和II级证据。方法为了评估全髋关节置换术中HO的预防作用,使用关键词和医学主题标题(MeSH)在MEDLINE/Pubmed、Cochrane和Embase数据库中进行了检索。筛选标题和摘要是否符合纳入标准。如果全文符合资格标准,则对其进行筛选并纳入。结果除阿司匹林外,HO化学预防比无HO预防更有效。多种非甾体抗炎药表现出与吲哚美辛等效且副作用更好的特点。没有一种更好的非甾体抗炎药被发现,许多治疗方式显示出疗效。放射治疗和联合治疗的最有效剂量尚不清楚。此外,在一项研究中,依地膦酸盐和鲑鱼降钙素都显示出预防HO的益处。结论放疗、非甾体抗炎药及联合治疗均可作为HO的预防方式。HO预防治疗和模式应根据患者和手术因素,如手术方式、副作用和模式的耐受性、合并症和现有设施资源来指导,以优化HO的预防。证据等级:IV级治疗性。
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引用次数: 0
Long-term effects of infrapatellar fat pad SVF infiltration in knee osteoarthritis management: A prospective cohort study 髌下脂肪垫SVF浸润对膝关节骨关节炎治疗的长期影响:一项前瞻性队列研究
IF 2.1 Q3 ENDOCRINOLOGY & METABOLISM Pub Date : 2025-01-24 DOI: 10.1016/j.bonr.2025.101827
Klaus Werner Labarre, Gerald Zimmermann
<div><h3>Background</h3><div>Knee osteoarthritis (OA) is a prevalent and debilitating condition that significantly impacts patients' quality of life and poses a substantial socioeconomic burden. Current treatments, including nonsteroidal anti-inflammatory drugs (NSAIDs) and physical therapy, often provide only temporary relief and fail to halt disease progression, particularly in advanced stages where knee replacement surgery becomes the primary option. Regenerative cell therapies, particularly those utilizing mesenchymal stem cells (MSCs), have emerged as promising alternatives due to their anti-inflammatory and regenerative properties. This study investigates the efficacy of stromal vascular fraction (SVF) derived from autologous adipose tissue when injected into the infrapatellar (Hoffa's) fat pad, an approach that leverages the rich vascular and stem cell environment of the fat pad to potentially modulate inflammation and promote tissue repair.</div></div><div><h3>Methods</h3><div>Patients receiving therapy with SVF were invited to participate in the study. Inclusion criteria encompassed male and female patients aged 18 years or older with a Kellgren-Lawrence score up to 4, while exclusion criteria included malignant tumors, sepsis, or skin lesions at the site of collection or injection. A total of 25 patients were included in the study cohort, with two patients receiving bilateral treatment, resulting in 27 knees analyzed.</div><div>For the correlation analysis, an additional four patients who had only completed the six-month follow-up were included, one of whom underwent bilateral treatment. This extended the correlation analysis cohort to 29 patients and 32 knees. However, these four patients were excluded from the final study analysis as they had not completed the two-year follow-up. Consequently, the final analysis focused exclusively on the 25 patients (27 knees) who completed the full two-year follow-up.</div></div><div><h3>Results</h3><div>Significant improvements were observed in VAS pain scores and KOOS subscales for pain, activities of daily living (ADL), and quality of life (QOL) at 6 and 24 months (<em>p</em> < 0.05). The correlation between the number of injected cells and functional improvements was significant for ADL at 6 months (Spearman's rho = 0.31, <em>p</em> = 0.044). This time point was prioritized to evaluate early therapeutic responses, as it represents a critical window when cellular activity and therapeutic effects are believed to peak. Focusing on the six-month follow-up allowed for a detailed assessment of these early impacts while minimizing potential confounding factors observed in later stages. No major complications were reported.</div></div><div><h3>Conclusion</h3><div>SVF infiltration into the infrapatellar fat pad shows promising long-term benefits in pain relief and functional improvement for knee OA patients. Despite the lack of blinding and a control group, these findings suggest that SVF therapy coul
膝关节骨性关节炎(OA)是一种普遍且使人衰弱的疾病,严重影响患者的生活质量,并造成严重的社会经济负担。目前的治疗方法,包括非甾体抗炎药(NSAIDs)和物理治疗,通常只能提供暂时的缓解,不能阻止疾病的进展,特别是在膝关节置换手术成为主要选择的晚期。再生细胞疗法,特别是利用间充质干细胞(MSCs)的疗法,由于其抗炎和再生特性而成为有希望的替代疗法。本研究研究了自体脂肪组织衍生的基质血管组分(SVF)注射到髌下(Hoffa’s)脂肪垫后的疗效,这种方法利用脂肪垫丰富的血管和干细胞环境来调节炎症和促进组织修复。方法邀请接受SVF治疗的患者参与研究。纳入标准包括年龄≥18岁且kelgren - lawrence评分≥4的男性和女性患者,排除标准包括恶性肿瘤、败血症或采集或注射部位的皮肤病变。研究队列共纳入25例患者,其中2例患者接受双侧治疗,共分析27个膝关节。为了进行相关性分析,另外4名患者只完成了6个月的随访,其中1名接受了双侧治疗。这将相关分析队列扩展到29名患者和32个膝关节。然而,这4例患者因未完成2年随访而被排除在最终研究分析之外。因此,最终的分析集中在25名患者(27个膝关节),他们完成了为期两年的随访。结果在6个月和24个月时,两组患者的VAS疼痛评分和kos疼痛亚量表、日常生活活动(ADL)和生活质量(QOL)均有显著改善(p <;0.05)。注射细胞数与6个月时ADL功能改善之间的相关性显著(Spearman’s rho = 0.31, p = 0.044)。这个时间点被优先用于评估早期治疗反应,因为它代表了细胞活动和治疗效果达到峰值的关键窗口。关注六个月的随访可以详细评估这些早期影响,同时最大限度地减少后期观察到的潜在混杂因素。无重大并发症报道。结论svf浸润髌下脂肪垫对膝关节OA患者的疼痛缓解和功能改善具有远期疗效。尽管缺乏盲法和对照组,这些研究结果表明,SVF治疗可能是一种可行的微创替代更具侵入性的手术干预。
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引用次数: 0
A simple and user-friendly machine learning model to detect osteoporosis in health examination populations in Southern Taiwan 一个简单易用的机器学习模型来检测台湾南部健康检查人群中的骨质疏松症。
IF 2.1 Q3 ENDOCRINOLOGY & METABOLISM Pub Date : 2025-01-11 DOI: 10.1016/j.bonr.2025.101826
Wei-Chin Huang , I-Shu Chen , Hsien-Chung Yu , Chi-Shen Chen , Fu-Zong Wu , Chiao-Lin Hsu , Pin-Chieh Wu

Background

Osteoporosis is a growing public health concern in aging populations such as Taiwan, where limited utilization of dual-energy X-ray absorptiometry (DXA) often leads to underdiagnosis and even delayed treatment. Therefore, we leveraged machine learning (ML) and aimed to develop a simple and easily accessible model that effectively identifies individuals at high risk of osteoporosis.

Methods

This retrospective analysis enrolled 5510 men aged ≥50 years and 4720 postmenopausal women who underwent DXA at the Kaohsiung Veterans General Hospital, with another cohort of 610 men and 523 women for validation. We developed separate models for men and women using decision trees, random forests, support vector machines, k-nearest neighbors, extreme gradient boosting, and artificial neural networks (ANNs) to predict osteoporosis. Furthermore, we compared each model with the traditional Osteoporosis Self-Assessment Tool for Asians (OSTA) model.

Results

We identified age, height, weight, and BMI as variables for our prediction model and evaluated the model's performance using the area under the receiver operating characteristic curve (AUC). The ANN model significantly outperformed the OSTA model and all the other ML models for both men and women (AUC: 0.67 for men; 0.77 for women). The validation data for the ANN model showed similar AUCs for both men and women.

Conclusion

This study developed ML models to help identify individuals at high risk of osteoporosis in postmenopausal women and men aged ≥50 years in southern Taiwan. Our ML models, especially the ANN model, surpassed the OSTA model and consistently performed well across different populations.
背景:骨质疏松症是台湾等老龄化人口日益关注的公共卫生问题,双能x线吸收仪(DXA)的有限使用经常导致诊断不足甚至延误治疗。因此,我们利用机器学习(ML),旨在开发一种简单易用的模型,有效识别骨质疏松症高风险个体。方法:本回顾性分析纳入5510名年龄≥50岁的男性和4720名绝经后妇女,并在高雄退伍军人总医院接受DXA治疗,另一队列为610名男性和523名女性进行验证。我们使用决策树、随机森林、支持向量机、k近邻、极端梯度增强和人工神经网络(ann)为男性和女性开发了单独的模型来预测骨质疏松症。此外,我们将每个模型与传统的骨质疏松自我评估工具(OSTA)模型进行了比较。结果:我们确定了年龄、身高、体重和BMI作为预测模型的变量,并使用受试者工作特征曲线下面积(AUC)评估模型的性能。ANN模型在男性和女性上都明显优于OSTA模型和所有其他ML模型(AUC: 0.67;女性0.77)。人工神经网络模型的验证数据显示,男性和女性的auc相似。结论:本研究建立了ML模型,以帮助识别台湾南部年龄≥50岁的绝经后女性和男性骨质疏松症的高危个体。我们的机器学习模型,尤其是人工神经网络模型,超越了OSTA模型,并在不同的人群中始终表现良好。
{"title":"A simple and user-friendly machine learning model to detect osteoporosis in health examination populations in Southern Taiwan","authors":"Wei-Chin Huang ,&nbsp;I-Shu Chen ,&nbsp;Hsien-Chung Yu ,&nbsp;Chi-Shen Chen ,&nbsp;Fu-Zong Wu ,&nbsp;Chiao-Lin Hsu ,&nbsp;Pin-Chieh Wu","doi":"10.1016/j.bonr.2025.101826","DOIUrl":"10.1016/j.bonr.2025.101826","url":null,"abstract":"<div><h3>Background</h3><div>Osteoporosis is a growing public health concern in aging populations such as Taiwan, where limited utilization of dual-energy X-ray absorptiometry (DXA) often leads to underdiagnosis and even delayed treatment. Therefore, we leveraged machine learning (ML) and aimed to develop a simple and easily accessible model that effectively identifies individuals at high risk of osteoporosis.</div></div><div><h3>Methods</h3><div>This retrospective analysis enrolled 5510 men aged ≥50 years and 4720 postmenopausal women who underwent DXA at the Kaohsiung Veterans General Hospital, with another cohort of 610 men and 523 women for validation. We developed separate models for men and women using decision trees, random forests, support vector machines, k-nearest neighbors, extreme gradient boosting, and artificial neural networks (ANNs) to predict osteoporosis. Furthermore, we compared each model with the traditional Osteoporosis Self-Assessment Tool for Asians (OSTA) model.</div></div><div><h3>Results</h3><div>We identified age, height, weight, and BMI as variables for our prediction model and evaluated the model's performance using the area under the receiver operating characteristic curve (AUC). The ANN model significantly outperformed the OSTA model and all the other ML models for both men and women (AUC: 0.67 for men; 0.77 for women). The validation data for the ANN model showed similar AUCs for both men and women.</div></div><div><h3>Conclusion</h3><div>This study developed ML models to help identify individuals at high risk of osteoporosis in postmenopausal women and men aged ≥50 years in southern Taiwan. Our ML models, especially the ANN model, surpassed the OSTA model and consistently performed well across different populations.</div></div>","PeriodicalId":9043,"journal":{"name":"Bone Reports","volume":"24 ","pages":"Article 101826"},"PeriodicalIF":2.1,"publicationDate":"2025-01-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11783436/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143078586","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}
引用次数: 0
Ano5Cys360Tyr mutation leads to bone dysfunction of gnathodiaphyseal dysplasia via disturbing Akt signaling Ano5Cys360Tyr突变通过干扰Akt信号导致颌骨干发育不良的骨功能障碍。
IF 2.1 Q3 ENDOCRINOLOGY & METABOLISM Pub Date : 2025-01-06 DOI: 10.1016/j.bonr.2025.101825
Hongyu Li, Shengnan Wang, Shuai Zhang, Rui Dong, Congcong Miao, Zhenchuan Tian, Ying Hu

Background

Gnathodiaphyseal dysplasia (GDD) is a rare autosomal dominant genetic disease characterized by osteosclerosis of the tubular bones and cemento-osseous lesions of the mandibles. Anoctamin 5 (ANO5) is the pathogenic gene, however, the specific molecular mechanism of GDD remains unclear. Herein, a knockin (Ano5KI/KI) mouse model expressing the human mutation p.Cys360Tyr was used to investigate the role of Akt signaling in enhanced osteogenesis and decreased osteoclastogenesis in GDD.

Methods

Bone marrow-derived macrophages (BMMs) and mouse calvarial osteoblasts (mCOBs) were isolated from homozygous Ano5KI/KI mice and treated with SC79, a specific Akt activator. The differentiation and F-actin ring formation of osteoclasts were examined by TRAP and phalloidin staining, respectively. Osteoblast differentiation and mineralization were examined by ALP and alizarin red staining. The expression of bone remodeling-related factors was measured by qRT-PCR.

Results

Akt activation promoted the generation of TRAP-positive multinucleated osteoclasts and the formation of actin rings in Ano5KI/KI BMMs cultures, accompanied by increased expression of Nfatc1, Trap, Dc-stamp, Mmp9, Ctsk, and Atp6v0d2. Additionally, Ano5Cys360Tyr mutation down-regulated the Akt phosphorylation level in osteoblast. ALP activity and matrix mineralization capacity in Ano5KI/KI osteoblast cultures were inhibited after SC79 stimulation, with reduced expression of Runx2, Opn, Col1a1, and Ocn.

Conclusion

Akt activation by SC79 stimulation can obviously rescue abnormal increased osteogenesis and decreased osteoclastogenesis in Ano5KI/KI mouse model, which demonstrated that disturbed Akt signaling pathway may play a pivotal role in the pathogenesis of GDD, and an Akt activator is probable a therapeutic target for GDD.
背景:颌骨干发育不良(GDD)是一种罕见的常染色体显性遗传病,其特征是下颌骨管状骨硬化和骨水泥病变。ANO5是致病基因,但GDD的具体分子机制尚不清楚。本研究采用表达人类突变p.Cys360Tyr的敲入蛋白(Ano5 KI/KI)小鼠模型,研究Akt信号在GDD中促进成骨和降低破骨细胞生成中的作用。方法:从纯合子Ano5 KI/KI小鼠中分离骨髓源性巨噬细胞(BMMs)和小鼠颅骨成骨细胞(mCOBs),并用特异性Akt激活剂SC79处理。分别用TRAP和phalloidin染色检测破骨细胞的分化和F-actin环的形成。ALP和茜素红染色检测成骨细胞分化和矿化。采用qRT-PCR检测骨重塑相关因子的表达。结果:Akt激活促进Ano5 KI/KI BMMs培养中Trap阳性多核破骨细胞的产生和肌动蛋白环的形成,同时Nfatc1、Trap、Dc-stamp、Mmp9、Ctsk和Atp6v0d2的表达增加。此外,Ano5 Cys360Tyr突变下调了成骨细胞中Akt磷酸化水平。SC79刺激后,Ano5 KI/KI成骨细胞ALP活性和基质矿化能力受到抑制,Runx2、Opn、Col1a1和Ocn的表达降低。结论:在Ano5 KI/KI小鼠模型中,SC79刺激激活Akt可明显恢复异常的成骨增加和破骨细胞减少,这表明Akt信号通路紊乱可能在GDD发病中起关键作用,Akt激活剂可能是GDD的治疗靶点。
{"title":"Ano5Cys360Tyr mutation leads to bone dysfunction of gnathodiaphyseal dysplasia via disturbing Akt signaling","authors":"Hongyu Li,&nbsp;Shengnan Wang,&nbsp;Shuai Zhang,&nbsp;Rui Dong,&nbsp;Congcong Miao,&nbsp;Zhenchuan Tian,&nbsp;Ying Hu","doi":"10.1016/j.bonr.2025.101825","DOIUrl":"10.1016/j.bonr.2025.101825","url":null,"abstract":"<div><h3>Background</h3><div>Gnathodiaphyseal dysplasia (GDD) is a rare autosomal dominant genetic disease characterized by osteosclerosis of the tubular bones and cemento-osseous lesions of the mandibles. <em>Anoctamin 5</em> (<em>ANO5</em>) is the pathogenic gene, however, the specific molecular mechanism of GDD remains unclear. Herein, a knockin (<em>Ano5</em><sup><em>KI/KI</em></sup>) mouse model expressing the human mutation p.Cys360Tyr was used to investigate the role of Akt signaling in enhanced osteogenesis and decreased osteoclastogenesis in GDD.</div></div><div><h3>Methods</h3><div>Bone marrow-derived macrophages (BMMs) and mouse calvarial osteoblasts (mCOBs) were isolated from homozygous <em>Ano5</em><sup><em>KI/KI</em></sup> mice and treated with SC79, a specific Akt activator. The differentiation and F-actin ring formation of osteoclasts were examined by TRAP and phalloidin staining, respectively. Osteoblast differentiation and mineralization were examined by ALP and alizarin red staining. The expression of bone remodeling-related factors was measured by qRT-PCR.</div></div><div><h3>Results</h3><div>Akt activation promoted the generation of TRAP-positive multinucleated osteoclasts and the formation of actin rings in <em>Ano5</em><sup><em>KI/KI</em></sup> BMMs cultures, accompanied by increased expression of <em>Nfatc1</em>, <em>Trap</em>, <em>Dc-stamp</em>, <em>Mmp9</em>, <em>Ctsk</em>, and <em>Atp6v0d2</em>. Additionally, <em>Ano5</em><sup><em>Cys360Tyr</em></sup> mutation down-regulated the Akt phosphorylation level in osteoblast. ALP activity and matrix mineralization capacity in <em>Ano5</em><sup><em>KI/KI</em></sup> osteoblast cultures were inhibited after SC79 stimulation, with reduced expression of <em>Runx2, Opn, Col1a1</em>, <em>and Ocn</em>.</div></div><div><h3>Conclusion</h3><div>Akt activation by SC79 stimulation can obviously rescue abnormal increased osteogenesis and decreased osteoclastogenesis in <em>Ano5</em><sup><em>KI/KI</em></sup> mouse model, which demonstrated that disturbed Akt signaling pathway may play a pivotal role in the pathogenesis of GDD, and an Akt activator is probable a therapeutic target for GDD.</div></div>","PeriodicalId":9043,"journal":{"name":"Bone Reports","volume":"24 ","pages":"Article 101825"},"PeriodicalIF":2.1,"publicationDate":"2025-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11763220/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143045635","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}
引用次数: 0
Ischemic stroke reduces bone perfusion and alters osteovascular structure 缺血性中风减少骨灌注,改变骨血管结构。
IF 2.1 Q3 ENDOCRINOLOGY & METABOLISM Pub Date : 2025-01-04 DOI: 10.1016/j.bonr.2025.101824
Nicholas J. Hanne , Andrew J. Steward , Carla Geeroms , Elizabeth D. Easter , Hannah T. Gensch , Greet Kerckhofs , Tatjana N. Parac-Vogt , Huaxin Sheng , Jacqueline H. Cole
Stroke patients lose bone mass and experience fracture at an elevated rate. Although functional intraosseous vasculature is necessary for skeletal maintenance, the effect of stroke on osteovasculature is unknown. In this study we characterized changes to osteovascular perfusion, structure, and composition following mild-to-moderate stroke severity in mice, both with and without exercise therapy. Twelve-week-old male mice (n = 27) received either an ischemic stroke (middle cerebral artery occlusion) or sham procedure, followed by a four-week recovery with either moderate daily treadmill or sedentary activity. Intraosseous perfusion, measured weekly in the proximal tibial metaphysis with laser Doppler flowmetry, was reduced for two weeks in the stroke group relative to the sham group. After four weeks, osteovascular structure was assessed in the distal femoral metaphysis with contrast-enhanced computed tomography. Increased osteovascular volume and branching, decreased number of smaller vessels (6–22 μm), and increased number of larger vessels (>66 μm) were observed in the stroke groups compared to sham groups, which may be a compensatory response to early perfusion deficits. Although moderate exercise mitigated the impact of stroke on osteovascular perfusion and volume, it tended to reduce the amount of osteogenic type H vasculature quantified with immunofluorescence microscopy and, exacerbated by stroke effects, produced fewer vessels in close proximity to bone and thus may have detrimental effects on bone remodeling during early stroke recovery. Since results were similar in both limbs, the effects of ischemic stroke on osteovascular perfusion and structure were primarily systemic, rather than resulting from paresis or disuse, providing new insight for future studies on the pathogenesis and treatment of skeletal fragility in stroke patients.
中风患者骨量减少,骨折发生率升高。虽然骨内血管系统的功能是骨骼维持所必需的,但中风对骨内血管系统的影响尚不清楚。在这项研究中,我们描述了在小鼠轻度至中度中风严重程度后,无论是否进行运动治疗,骨血管灌注、结构和组成的变化。12周大的雄性小鼠(n = 27)接受缺血性中风(大脑中动脉闭塞)或假手术,随后进行为期四周的恢复,每天进行适度的跑步机或久坐活动。用激光多普勒血流仪每周测量胫骨近端干骺端骨内灌注,与假手术组相比,中风组的骨内灌注减少了两周。四周后,通过增强计算机断层扫描评估股骨远端干骺端骨血管结构。与假手术组相比,中风组骨血管体积和分支增加,小血管(6-22 μm)数量减少,大血管(> - 66 μm)数量增加,这可能是对早期灌注缺陷的代偿反应。虽然适度运动减轻了中风对骨血管灌注和体积的影响,但它倾向于减少免疫荧光显微镜量化的成骨H型血管的数量,并且由于中风的影响而加剧,在靠近骨骼的地方产生更少的血管,因此可能对早期中风恢复期间的骨重塑产生不利影响。由于两肢结果相似,缺血性脑卒中对骨血管灌注和结构的影响主要是全身性的,而不是由轻瘫或废用引起的,这为未来脑卒中患者骨骼脆性的发病机制和治疗研究提供了新的思路。
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引用次数: 0
The association between dietary inflammatory index and bone health in US adolescents: Analysis of the NHANES data 美国青少年饮食炎症指数与骨骼健康之间的关系:NHANES数据分析
IF 2.1 Q3 ENDOCRINOLOGY & METABOLISM Pub Date : 2025-01-03 DOI: 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.
简介峰值骨矿物质密度(BMD)和骨矿物质含量(BMC)较低的青少年成年后患骨质疏松症的风险较高。饮食对骨骼健康的影响,尤其是饮食在控制炎症(骨骼健康的关键因素)方面的作用,正得到越来越广泛的认可。尽管有证据表明,抗炎饮食可增强骨骼健康,但对美国青少年的饮食炎症指数(DII)与骨骼健康之间的联系尚未进行深入研究。本研究旨在评估该人群中 DII 分数与骨骼健康之间的相关性:这项横断面研究使用了美国国家健康与营养调查(NHANES)的数据,调查对象为 12-18 岁的美国青少年,调查时间跨度为 2001 年至 2018 年。DII 是通过问卷访问获得的饮食回忆数据得出的。骨骼健康通过全身减去头部(TBLH)的骨密度(BMD)和骨密度表观密度(BMC)z-分数以及腰椎骨矿物质表观密度(BMADa)进行评估:研究对象包括 8773 名青少年,平均年龄为(14.94 ± 1.97)岁,其中 52.2% 为男性。多变量线性回归分析显示,DII与腰椎BMADa呈负相关(β = -0.000003,95%置信区间[CI],-0.000005至-0.000001;P = 0.001)。在男性、非黑人、教育程度较高、家庭收入较高、体重不足至正常的参与者中,与四分位 1(Q1)的 DII 分数(-3.71 至 1.04)相比,四分位 4(3.37 至 5.04)的 BMADa 较低,回归系数为-0.00002(95 % CI,-0.00003 至 -0.000007,P a 和 TBLH BMC z 分数)。我们发现 DII 与 TBLH BMD z 分数之间没有明显关联:这项横断面分析的结果表明,美国青少年的 DII 与骨骼健康之间存在显著关联,对男性和非黑人的影响尤为明显。这些见解强调了采用饮食模式减轻炎症、支持最佳骨骼健康和新陈代谢的重要性。
{"title":"The association between dietary inflammatory index and bone health in US adolescents: Analysis of the NHANES data","authors":"Yuanyuan Zhang,&nbsp;Xuejing Wang,&nbsp;Shiguang Huo,&nbsp;Li Hong,&nbsp;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> &lt; 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":"2025-01-03","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}
引用次数: 0
Clinical features and treatment of hypophosphatemia and associated complications induced by Phosphaturic mesenchymal tumors: A case series of six patients 6例含磷间充质肿瘤所致低磷血症及相关并发症的临床特点及治疗
IF 2.1 Q3 ENDOCRINOLOGY & METABOLISM Pub Date : 2024-12-31 DOI: 10.1016/j.bonr.2024.101822
Guoqiang Lai , Wangsheng Zuo , Runmin Tang , Zengbo Lu , Dehai Shi
Phosphaturic mesenchymal tumor (PMT) is a rare benign mesenchymal tumor characterized by excessive secretion of fibroblast growth factor 23 (FGF23), leading to phosphate loss and systemic osteomalacia. Despite recent progress in PMT research, no consensus on diagnosis and treatment guidelines has been established. This case series describes the clinical and pathological features of six pathologically confirmed PMT patients treated at the Third Affiliated Hospital of Sun Yat-sen University from 2010 to 2024, aiming to provide new insights for the management of this condition. The patients, consisting of three males and three females with an average age of 44 years and follow-up periods of 0.5 to 4.5 years, presented primarily with muscle pain and lower limb weakness. One patient experienced loose teeth, and two had palpable, painless masses. One case developed hyperphosphatemia, tertiary hyperparathyroidism, and renal impairment after prolonged phosphate supplementation. Tumor localization was achieved using 18F-FDG or 68Ga-DOTATATE Positron Emission Tomography-Computed Tomography(PET/CT) and MRI, followed by complete surgical resection. Pathological examination confirmed PMT, and postoperative recovery was marked by significant symptom relief and normalization of serum phosphate levels. Two patients experienced recurrence within three years but showed no further recurrence following repeat surgery by the last follow-up. The diagnosis of PMT is challenging and may take years, potentially leading to complications due to inadequate treatment. Complete tumor resection remains the primary treatment, generally resulting in a favorable prognosis; however, long-term monitoring is essential to detect potential recurrences and initiate timely interventions.
磷酸盐间质瘤(PMT)是一种罕见的良性间质瘤,其特点是成纤维细胞生长因子23(FGF23)分泌过多,导致磷酸盐流失和全身性骨软化症。尽管近年来 PMT 的研究取得了进展,但在诊断和治疗指南方面尚未达成共识。本病例系列描述了中山大学附属第三医院自2010年至2024年收治的6例经病理证实的PMT患者的临床和病理特征,旨在为该病的治疗提供新的见解。这些患者包括三男三女,平均年龄为44岁,随访时间为0.5至4.5年,主要表现为肌肉疼痛和下肢无力。一名患者牙齿松动,两名患者可触及无痛性肿块。其中一例患者在长期补充磷酸盐后出现了高磷血症、三级甲状旁腺功能亢进症和肾功能损害。通过18F-FDG或68Ga-DOTATATE正电子发射计算机断层扫描(PET/CT)和磁共振成像确定了肿瘤的位置,随后进行了彻底的手术切除。病理检查证实为 PMT,术后症状明显缓解,血清磷酸盐水平恢复正常。两名患者在三年内复发,但在最后一次随访时,再次手术后未再复发。PMT 的诊断具有挑战性,可能需要数年时间,并可能因治疗不当而导致并发症。完全切除肿瘤仍是主要的治疗方法,一般来说预后较好;但是,长期监测对发现潜在复发和及时启动干预措施至关重要。
{"title":"Clinical features and treatment of hypophosphatemia and associated complications induced by Phosphaturic mesenchymal tumors: A case series of six patients","authors":"Guoqiang Lai ,&nbsp;Wangsheng Zuo ,&nbsp;Runmin Tang ,&nbsp;Zengbo Lu ,&nbsp;Dehai Shi","doi":"10.1016/j.bonr.2024.101822","DOIUrl":"10.1016/j.bonr.2024.101822","url":null,"abstract":"<div><div>Phosphaturic mesenchymal tumor (PMT) is a rare benign mesenchymal tumor characterized by excessive secretion of fibroblast growth factor 23 (FGF23), leading to phosphate loss and systemic osteomalacia. Despite recent progress in PMT research, no consensus on diagnosis and treatment guidelines has been established. This case series describes the clinical and pathological features of six pathologically confirmed PMT patients treated at the Third Affiliated Hospital of Sun Yat-sen University from 2010 to 2024, aiming to provide new insights for the management of this condition. The patients, consisting of three males and three females with an average age of 44 years and follow-up periods of 0.5 to 4.5 years, presented primarily with muscle pain and lower limb weakness. One patient experienced loose teeth, and two had palpable, painless masses. One case developed hyperphosphatemia, tertiary hyperparathyroidism, and renal impairment after prolonged phosphate supplementation. Tumor localization was achieved using 18F-FDG or 68Ga-DOTATATE Positron Emission Tomography-Computed Tomography(PET/CT) and MRI, followed by complete surgical resection. Pathological examination confirmed PMT, and postoperative recovery was marked by significant symptom relief and normalization of serum phosphate levels. Two patients experienced recurrence within three years but showed no further recurrence following repeat surgery by the last follow-up. The diagnosis of PMT is challenging and may take years, potentially leading to complications due to inadequate treatment. Complete tumor resection remains the primary treatment, generally resulting in a favorable prognosis; however, long-term monitoring is essential to detect potential recurrences and initiate timely interventions.</div></div>","PeriodicalId":9043,"journal":{"name":"Bone Reports","volume":"24 ","pages":"Article 101822"},"PeriodicalIF":2.1,"publicationDate":"2024-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11760829/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143045636","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}
引用次数: 0
Integrating deep learning and machine learning for improved CKD-related cortical bone assessment in HRpQCT images: A pilot study 整合深度学习和机器学习以改善HRpQCT图像中ckd相关皮质骨评估:一项试点研究。
IF 2.1 Q3 ENDOCRINOLOGY & METABOLISM Pub Date : 2024-12-26 DOI: 10.1016/j.bonr.2024.101821
Youngjun Lee , Wikum R. Bandara , Sangjun Park , Miran Lee , Choongboem Seo , Sunwoo Yang , Kenneth J. Lim , Sharon M. Moe , Stuart J. Warden , Rachel K. Surowiec
High resolution peripheral quantitative computed tomography (HRpQCT) offers detailed bone geometry and microarchitecture assessment, including cortical porosity, but assessing chronic kidney disease (CKD) bone images remains challenging. This proof-of-concept study merges deep learning and machine learning to 1) improve automatic segmentation, particularly in cases with severe cortical porosity and trabeculated endosteal surfaces, and 2) maximize image information using machine learning feature extraction to classify CKD-related skeletal abnormalities, surpassing conventional DXA and CT measures.
We included 30 individuals (20 non-CKD, 10 stage 3 to 5D CKD) who underwent HRpQCT of the distal and diaphyseal radius and tibia and contributed data to develop and validate four different AI models for each anatomical site. Manually annotated cortical bone was used to train each segmentation deep-learning model. Textural features were extracted via Gray-Level Co-occurrence Matrix (GLCM) and classified as CKD or non-CKD using XGBoost with each segmentation model. For comparison, manufacturer-supplied segmentation was used to extract cortical geometry, microarchitecture, and finite element analysis (FEA) outcomes. Model performance was confirmed using the test dataset and a separate independent validation cohort which included HRpQCT imaging from 42 additional individuals (18 non-CKD, 24 CKD stage 5D).
For segmentation, the diaphyseal location showed strong performance on test datasets, with Mean IoUs of 0.96 and 0.95, and accuracies of 0.97 for both radius and tibia sites in CKD. Model 4 developed from the diaphyseal tibia region excelled in classifying test and independent validation datasets, achieving F1 scores of 0.99 and 0.96, AUCs of 0.99 and 0.94, sensitivities of 0.99, and specificities of 0.99 and 0.92. No single parameter, including BMD and cortical porosity, among conventional CT outcomes consistently differentiated CKD from non-CKD across all anatomical sites.
Integrating HRpQCT with deep and machine learning, this innovative approach enables precise automatic segmentation of severely deteriorated endocortical surfaces and enhances sensitivity to CKD-related cortical bone changes compared to standard DXA and HRpQCT outcomes.
高分辨率外周定量计算机断层扫描(HRpQCT)提供了详细的骨骼几何和微结构评估,包括皮质孔隙度,但评估慢性肾脏疾病(CKD)骨骼图像仍然具有挑战性。这项概念验证研究融合了深度学习和机器学习,以1)改善自动分割,特别是在皮质孔隙度严重和骨膜表面小梁的情况下;2)利用机器学习特征提取最大化图像信息,对ckd相关的骨骼异常进行分类,超越传统的DXA和CT测量。我们纳入了30名患者(20名非CKD, 10名3至5D CKD),他们接受了远端和骨干桡骨和胫骨的HRpQCT检查,并提供了数据,用于开发和验证每个解剖部位的四种不同的AI模型。使用人工标注的皮质骨来训练每个分割深度学习模型。通过灰度共生矩阵(GLCM)提取纹理特征,并使用XGBoost对每个分割模型进行CKD和非CKD分类。为了比较,使用制造商提供的分割来提取皮质几何形状、微结构和有限元分析(FEA)结果。使用测试数据集和一个单独的独立验证队列来确认模型的性能,该队列包括来自42个额外个体(18个非CKD, 24个CKD阶段5D)的HRpQCT成像。对于分割,骨干定位在测试数据集上表现出很强的性能,CKD的桡骨和胫骨部位的平均IoUs分别为0.96和0.95,准确率为0.97。从胫骨骨干区开发的模型4在分类测试和独立验证数据集上表现优异,F1得分分别为0.99和0.96,auc分别为0.99和0.94,灵敏度为0.99,特异性为0.99和0.92。在常规CT结果中,没有单一参数(包括骨密度和皮质孔隙度)能在所有解剖部位一致地区分CKD和非CKD。与标准的DXA和HRpQCT结果相比,这种创新的方法将HRpQCT与深度学习和机器学习相结合,可以精确地自动分割严重恶化的皮质内表面,提高对ckd相关皮质骨变化的敏感性。
{"title":"Integrating deep learning and machine learning for improved CKD-related cortical bone assessment in HRpQCT images: A pilot study","authors":"Youngjun Lee ,&nbsp;Wikum R. Bandara ,&nbsp;Sangjun Park ,&nbsp;Miran Lee ,&nbsp;Choongboem Seo ,&nbsp;Sunwoo Yang ,&nbsp;Kenneth J. Lim ,&nbsp;Sharon M. Moe ,&nbsp;Stuart J. Warden ,&nbsp;Rachel K. Surowiec","doi":"10.1016/j.bonr.2024.101821","DOIUrl":"10.1016/j.bonr.2024.101821","url":null,"abstract":"<div><div>High resolution peripheral quantitative computed tomography (HRpQCT) offers detailed bone geometry and microarchitecture assessment, including cortical porosity, but assessing chronic kidney disease (CKD) bone images remains challenging. This proof-of-concept study merges deep learning and machine learning to 1) improve automatic segmentation, particularly in cases with severe cortical porosity and trabeculated endosteal surfaces, and 2) maximize image information using machine learning feature extraction to classify CKD-related skeletal abnormalities, surpassing conventional DXA and CT measures.</div><div>We included 30 individuals (20 non-CKD, 10 stage 3 to 5D CKD) who underwent HRpQCT of the distal and diaphyseal radius and tibia and contributed data to develop and validate four different AI models for each anatomical site. Manually annotated cortical bone was used to train each segmentation deep-learning model. Textural features were extracted via Gray-Level Co-occurrence Matrix (GLCM) and classified as CKD or non-CKD using XGBoost with each segmentation model. For comparison, manufacturer-supplied segmentation was used to extract cortical geometry, microarchitecture, and finite element analysis (FEA) outcomes. Model performance was confirmed using the test dataset and a separate independent validation cohort which included HRpQCT imaging from 42 additional individuals (18 non-CKD, 24 CKD stage 5D).</div><div>For segmentation, the diaphyseal location showed strong performance on test datasets, with Mean IoUs of 0.96 and 0.95, and accuracies of 0.97 for both radius and tibia sites in CKD. Model 4 developed from the diaphyseal tibia region excelled in classifying test and independent validation datasets, achieving F1 scores of 0.99 and 0.96, AUCs of 0.99 and 0.94, sensitivities of 0.99, and specificities of 0.99 and 0.92. No single parameter, including BMD and cortical porosity, among conventional CT outcomes consistently differentiated CKD from non-CKD across all anatomical sites.</div><div>Integrating HRpQCT with deep and machine learning, this innovative approach enables precise automatic segmentation of severely deteriorated endocortical surfaces and enhances sensitivity to CKD-related cortical bone changes compared to standard DXA and HRpQCT outcomes.</div></div>","PeriodicalId":9043,"journal":{"name":"Bone Reports","volume":"24 ","pages":"Article 101821"},"PeriodicalIF":2.1,"publicationDate":"2024-12-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11763521/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143045637","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}
引用次数: 0
“Cellularity as a predictive tool for mesenchymal stem cell concentration in bone marrow concentrates: Implications for regenerative medicine” 细胞结构作为骨髓浓缩物中间充质干细胞浓度的预测工具:对再生医学的影响
IF 2.1 Q3 ENDOCRINOLOGY & METABOLISM Pub Date : 2024-11-26 DOI: 10.1016/j.bonr.2024.101820
Klaus Werner Labarre, Peter Ansgar Grathwol, Gerald Zimmermann

Background

Mesenchymal stem cells (MSCs) derived from bone marrow play an increasingly important role in regenerative medicine due to their capacity to promote tissue regeneration in various clinical contexts. Applications include the treatment of osteoarthritis, bone regeneration post-injury, and the management of conditions such as Crohn's disease, alopecia, and nervous system reconstruction. Accurate quantification of MSCs within Bone Marrow Concentrates (BMCs) is essential for ensuring the quality and efficacy of these cell therapy products in clinical settings.

Objective

This study aims to quantify the population of CD271+ and CD45 cells in BMCs prepared using the method we have selected and to provide a basis for comparing these results with other BMC products. Additionally, we seek to determine whether the total cell count in BMCs can serve as a reliable indicator of MSC numbers and if cellularity (the number of cells per ml) can predict a higher percentage of MSCs within the population.

Methods

Bone Marrow Aspirates (BMA) were collected from 41 patients undergoing knee or hip arthroplasty. Aspirates were processed using density gradient centrifugation and positive selection of CD271+ cells. Flow cytometry was applied to analyze cell subsets, and cell counts were determined with a NucleoCounter. The relationships between BMA cellularity (total cells per ml), MSC concentration (MSC count per ml), and MSC percentage (the proportion of MSCs within the total cell population) were assessed.

Results

The mean percentage of CD271+ CD45 cells in bone marrow samples was 0.03 % (SD 0.03 %). Cellularity varied significantly among samples, with a mean of 6 million cells/ml (SD 8.7 million cells/ml). A strong correlation was observed between BMC cellularity and MSC concentration (p < 0.05), although no correlation was found between cellularity and the MSC percentage.

Conclusion

Despite high variability in cellularity, the concentration of MSCs correlated strongly with BMC cellularity, suggesting that total cell counts can be used to estimate MSC numbers in BMCs. However, cellularity is not an indicator of a particularly high MSC content. This study supports the use of cell counts as a measure for estimating MSC concentration in BMCs. Future research should focus on establishing direct comparisons with other BMC products and exploring factors influencing cellularity and MSC percentages to enhance BMC quality for clinical applications.
来源于骨髓的间充质干细胞(MSCs)由于其在各种临床环境中促进组织再生的能力,在再生医学中发挥着越来越重要的作用。应用包括骨关节炎的治疗,损伤后的骨再生,以及克罗恩病、脱发和神经系统重建等疾病的治疗。骨髓浓缩物(BMCs)中MSCs的准确定量对于确保这些细胞治疗产品在临床环境中的质量和疗效至关重要。目的定量分析采用本方法制备的BMC中CD271+和CD45−细胞的数量,并为与其他BMC产品进行比较提供依据。此外,我们试图确定骨髓间充质干细胞的总细胞计数是否可以作为骨髓间充质干细胞数量的可靠指标,以及细胞含量(每毫升细胞数量)是否可以预测人群中较高的骨髓间充质干细胞百分比。方法收集41例膝关节或髋关节置换术患者的骨髓抽吸液(BMA)。抽吸液采用密度梯度离心和CD271+细胞阳性选择处理。流式细胞术分析细胞亚群,核计数仪测定细胞计数。评估BMA细胞数量(每ml总细胞数)、MSC浓度(每ml MSC计数)和MSC百分比(总细胞群中MSC的比例)之间的关系。结果骨髓标本中CD271+ CD45−细胞的平均百分比为0.03% (SD为0.03%)。不同样品的细胞数量差异显著,平均为600万个细胞/ml (SD为870万个细胞/ml)。BMC细胞数量与MSC浓度之间存在很强的相关性(p <;0.05),但细胞数量与间充质干细胞百分比之间没有相关性。结论:尽管骨髓间充质干细胞的细胞数量存在很大差异,但骨髓间充质干细胞的浓度与骨髓间充质干细胞的细胞数量密切相关,这表明骨髓间充质干细胞的总细胞计数可以用来估计骨髓间充质干细胞的数量。然而,细胞性并不是MSC含量特别高的指标。本研究支持使用细胞计数作为估计骨髓间充质干细胞浓度的一种措施。未来的研究应侧重于建立与其他BMC产品的直接比较,并探索影响细胞含量和MSC百分比的因素,以提高BMC的临床应用质量。
{"title":"“Cellularity as a predictive tool for mesenchymal stem cell concentration in bone marrow concentrates: Implications for regenerative medicine”","authors":"Klaus Werner Labarre,&nbsp;Peter Ansgar Grathwol,&nbsp;Gerald Zimmermann","doi":"10.1016/j.bonr.2024.101820","DOIUrl":"10.1016/j.bonr.2024.101820","url":null,"abstract":"<div><h3>Background</h3><div>Mesenchymal stem cells (MSCs) derived from bone marrow play an increasingly important role in regenerative medicine due to their capacity to promote tissue regeneration in various clinical contexts. Applications include the treatment of osteoarthritis, bone regeneration post-injury, and the management of conditions such as Crohn's disease, alopecia, and nervous system reconstruction. Accurate quantification of MSCs within Bone Marrow Concentrates (BMCs) is essential for ensuring the quality and efficacy of these cell therapy products in clinical settings.</div></div><div><h3>Objective</h3><div>This study aims to quantify the population of CD271<sup>+</sup> and CD45<sup>−</sup> cells in BMCs prepared using the method we have selected and to provide a basis for comparing these results with other BMC products. Additionally, we seek to determine whether the total cell count in BMCs can serve as a reliable indicator of MSC numbers and if cellularity (the number of cells per ml) can predict a higher percentage of MSCs within the population.</div></div><div><h3>Methods</h3><div>Bone Marrow Aspirates (BMA) were collected from 41 patients undergoing knee or hip arthroplasty. Aspirates were processed using density gradient centrifugation and positive selection of CD271<sup>+</sup> cells. Flow cytometry was applied to analyze cell subsets, and cell counts were determined with a NucleoCounter. The relationships between BMA cellularity (total cells per ml), MSC concentration (MSC count per ml), and MSC percentage (the proportion of MSCs within the total cell population) were assessed.</div></div><div><h3>Results</h3><div>The mean percentage of CD271<sup>+</sup> CD45<sup>−</sup> cells in bone marrow samples was 0.03 % (SD 0.03 %). Cellularity varied significantly among samples, with a mean of 6 million cells/ml (SD 8.7 million cells/ml). A strong correlation was observed between BMC cellularity and MSC concentration (<em>p</em> &lt; 0.05), although no correlation was found between cellularity and the MSC percentage.</div></div><div><h3>Conclusion</h3><div>Despite high variability in cellularity, the concentration of MSCs correlated strongly with BMC cellularity, suggesting that total cell counts can be used to estimate MSC numbers in BMCs. However, cellularity is not an indicator of a particularly high MSC content. This study supports the use of cell counts as a measure for estimating MSC concentration in BMCs. Future research should focus on establishing direct comparisons with other BMC products and exploring factors influencing cellularity and MSC percentages to enhance BMC quality for clinical applications.</div></div>","PeriodicalId":9043,"journal":{"name":"Bone Reports","volume":"24 ","pages":"Article 101820"},"PeriodicalIF":2.1,"publicationDate":"2024-11-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142757590","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}
引用次数: 0
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