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Bone quality analysis of the mandible in alcoholic liver cirrhosis: Anatomical, microstructural, and microhardness evaluation 酒精性肝硬化下颌骨骨质量分析:解剖、显微结构和显微硬度评估。
IF 3.5 2区 医学 Q2 ENDOCRINOLOGY & METABOLISM Pub Date : 2024-12-19 DOI: 10.1016/j.bone.2024.117378
Teodora Rodic , Eva M. Wölfel , Imke A.K. Fiedler , Danica Cvetkovic , Katharina Jähn-Rickert , Jelena Sopta , Slobodan Nikolic , Vladimir Zivkovic , Björn Busse , Marija Djuric , Petar Milovanovic

Objectives

Alcoholic bone disease has been recognized in contemporary literature as a systemic effect of chronic ethanol consumption. However, evidence about the specific influence of alcoholic liver cirrhosis (ALC) on mandible bone quality is scarce. The aim of this study was to explore microstructural, compositional, cellular, and mechanical properties of the mandible in ALC individuals compared with a healthy control group.

Materials and methods

Mandible bone cores of mаle individuаls with ALC (n = 6; age: 70.8 ± 2.5 yeаrs) and age-matched healthy controls (n = 11; age: 71.5 ± 3.8 yeаrs) were obtаined postmortem during аutopsy from the edentulous аlveolаr bone in the mandibular first molаr region аnd the mаndibulаr аngulus region of each individual. Micro-computed tomogrаphy wаs used to аssess bone microstructure. Analyses based on quаntitаtive bаckscаttered electron microscopy included the characterization of osteon morphology, osteocyte lаcunаr properties, and bone mаtrix minerаlizаtion. Composition of bone minerаl аnd collаgen phаses was assessed by Rаmаn spectroscopy. Histomorphometry wаs used to determine cellulаr аnd tissue chаrаcteristics of bone specimens. Vickers microhardness test was used to evaluate cortical bone mechanical properties.

Results

The ALC group showed higher closed cortical porosity (volume of pores thаt do not communicаte with the sаmple surfаce) (p = 0.003) and smaller lacunar area in the trabecular bone of the molar region (p = 0.002) compared with the Control group. The trabecular bone of the angulus region showed lower osteoclast number (p = 0.032) in the ALC group. There were higher carbonate content in the buccal cortex of the molar region (p = 0.008) and lower calcium content in the trabecular bone of the angulus region (p = 0.042) in the ALC group. The cortical bone showed inferior mechanical properties in the ALC cortical bony sites (p < 0.001), except for the buccal cortex of the molar region (p = 0.063). There was no significant difference in cortical thickness between the groups.

Conclusions

Bone quality is differentially altered in ALC in two bony sites and compartments of the mandible, which leads to impaired mechanical properties.

Clinical relevance

Altered mandible bone tissue characteristics in patients with ALC should be considered by dental medicine professionals prior to oral interventions in these patients. Knowledge about mandible bone quality alterations in ALC is valuable for determining diagnosis, treatment plan, indications for oral rehabilitation procedures, and follow-up procedures for this group of patients.
目的:在当代文献中,酒精性骨病已被认为是慢性酒精消费的系统性影响。然而,关于酒精性肝硬化(ALC)对下颌骨质量的具体影响的证据很少。本研究的目的是探讨ALC个体下颌骨的显微结构、组成、细胞和力学特性,并与健康对照组进行比较。材料与方法:ALC患者的下颌骨核(n = 6;年龄:70.8 ± 2.5岁)和年龄匹配的健康对照(n = 11;年龄:71.5 ± 3.8岁,在死后的尸检中从每个个体的下颌第一磨牙区和下颌第二磨牙区无牙的骨中获得。微计算机断层扫描(Micro-computed tomography)用于评估骨的微观结构。基于定量扫描电子显微镜的分析包括骨细胞形态学,骨细胞lintel特性和骨基质矿化的表征。骨矿物质和胶原蛋白的组成采用红外光谱法测定。组织形态测定法用于测定骨标本的细胞和组织特征。采用维氏显微硬度试验评价皮质骨力学性能。结果:与对照组相比,ALC组具有更高的皮质封闭孔隙率(与样本表面不相通的孔隙体积)(p = 0.003)和更小的磨牙区骨小梁腔隙面积(p = 0.002)。ALC组骨角区骨小梁破骨细胞数量明显减少(p = 0.032)。ALC组磨牙区颊皮质钙含量较高(p = 0.008),牙角区小梁骨钙含量较低(p = 0.042)。结论:ALC在下颌骨的两个骨区和骨室中骨质量发生了不同程度的改变,导致骨力学性能受损。临床相关性:在对ALC患者进行口腔干预之前,牙科医学专业人员应考虑其下颌骨组织特征的改变。了解ALC的下颌骨质量改变对确定诊断、治疗计划、口腔康复手术的指征和这组患者的随访程序是有价值的。
{"title":"Bone quality analysis of the mandible in alcoholic liver cirrhosis: Anatomical, microstructural, and microhardness evaluation","authors":"Teodora Rodic ,&nbsp;Eva M. Wölfel ,&nbsp;Imke A.K. Fiedler ,&nbsp;Danica Cvetkovic ,&nbsp;Katharina Jähn-Rickert ,&nbsp;Jelena Sopta ,&nbsp;Slobodan Nikolic ,&nbsp;Vladimir Zivkovic ,&nbsp;Björn Busse ,&nbsp;Marija Djuric ,&nbsp;Petar Milovanovic","doi":"10.1016/j.bone.2024.117378","DOIUrl":"10.1016/j.bone.2024.117378","url":null,"abstract":"<div><h3>Objectives</h3><div>Alcoholic bone disease has been recognized in contemporary literature as a systemic effect of chronic ethanol consumption. However, evidence about the specific influence of alcoholic liver cirrhosis (ALC) on mandible bone quality is scarce. The aim of this study was to explore microstructural, compositional, cellular, and mechanical properties of the mandible in ALC individuals compared with a healthy control group.</div></div><div><h3>Materials and methods</h3><div>Mandible bone cores of mаle individuаls with ALC (<em>n</em> = 6; age: 70.8 ± 2.5 yeаrs) and age-matched healthy controls (<em>n</em> = 11; age: 71.5 ± 3.8 yeаrs) were obtаined <em>postmortem</em> during аutopsy from the edentulous аlveolаr bone in the mandibular first molаr region аnd the mаndibulаr аngulus region of each individual. Micro-computed tomogrаphy wаs used to аssess bone microstructure. Analyses based on quаntitаtive bаckscаttered electron microscopy included the characterization of osteon morphology, osteocyte lаcunаr properties, and bone mаtrix minerаlizаtion. Composition of bone minerаl аnd collаgen phаses was assessed by Rаmаn spectroscopy. Histomorphometry wаs used to determine cellulаr аnd tissue chаrаcteristics of bone specimens. Vickers microhardness test was used to evaluate cortical bone mechanical properties.</div></div><div><h3>Results</h3><div>The ALC group showed higher closed cortical porosity (volume of pores thаt do not communicаte with the sаmple surfаce) (<em>p</em> = 0.003) and smaller lacunar area in the trabecular bone of the molar region (<em>p</em> = 0.002) compared with the Control group. The trabecular bone of the angulus region showed lower osteoclast number (<em>p</em> = 0.032) in the ALC group. There were higher carbonate content in the buccal cortex of the molar region (<em>p</em> = 0.008) and lower calcium content in the trabecular bone of the angulus region (<em>p</em> = 0.042) in the ALC group. The cortical bone showed inferior mechanical properties in the ALC cortical bony sites (<em>p</em> &lt; 0.001), except for the buccal cortex of the molar region (<em>p</em> = 0.063). There was no significant difference in cortical thickness between the groups.</div></div><div><h3>Conclusions</h3><div>Bone quality is differentially altered in ALC in two bony sites and compartments of the mandible, which leads to impaired mechanical properties.</div></div><div><h3>Clinical relevance</h3><div>Altered mandible bone tissue characteristics in patients with ALC should be considered by dental medicine professionals prior to oral interventions in these patients. Knowledge about mandible bone quality alterations in ALC is valuable for determining diagnosis, treatment plan, indications for oral rehabilitation procedures, and follow-up procedures for this group of patients.</div></div>","PeriodicalId":9301,"journal":{"name":"Bone","volume":"192 ","pages":"Article 117378"},"PeriodicalIF":3.5,"publicationDate":"2024-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142873717","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Hormones synthesized by the adrenal reticulum protect bone density in premenopausal women with Cushing syndrome 肾上腺网合成的激素保护绝经前库欣综合征妇女的骨密度。
IF 3.5 2区 医学 Q2 ENDOCRINOLOGY & METABOLISM Pub Date : 2024-12-19 DOI: 10.1016/j.bone.2024.117379
Keyang Wu , Siyu Yan , Jieying Wan , Yuanyuan Ye , Yian Gu , Hequn Sang , Shuo Li , Li Ding , Hengjie Yuan , Lina Chang , Ming Liu , Qing He

Background

Differences in bone metabolism between patients with adrenal Cushing's syndrome (ACS) and Cushing's disease (CD) have been noted, but the impact of steroid hormones on bone metabolism remains underexplored. The purpose of this study is to explore the differences in bone metabolism between the two subtypes of Cushing's syndrome and the correlation between hormones synthesized by the adrenal reticulum and bone metabolism.

Method

This retrospective study included 75 premenopausal women, consisting of 33 patients with CD and 42 patients with ACS. The clinical characteristics, laboratory examination and bone metabolism differences between the two groups were analyzed. Then, 16 patients with ACS and 12 patients with CD underwent comparison of blood steroid hormone levels. Additionally, the relationship between bone mineral density (BMD) values and steroid hormone variables was analyzed.

Results

The serum and urinary cortisol and serum ACTH concentrations were significantly higher in patients with CD compared to those with ACS. Conversely, lumbar and femoral BMD were lower, and osteocalcin (OC) levels were elevated in the ACS group. Dehydroepiandrosterone (DHEA) and dehydroepiandrosterone-sulphate (DHEAS) had a significant positive correlation with Z-score in lumbar spine in both CD and ACS group. However, Z-score in femoral neck had a significant positive correlation with DHEA and DHEAS only in the ACS group.

Conclusion

Bone loss is more pronounced in ACS than in CD, despite higher cortisol levels in CD patients. High levels of hormones synthesized by the adrenal reticulum might be protective for bone density in premenopausal women with hypercortisolism.
背景:肾上腺库欣综合征(ACS)和库欣病(CD)患者骨代谢的差异已被注意到,但类固醇激素对骨代谢的影响仍未得到充分探讨。本研究旨在探讨两种库欣综合征亚型骨代谢的差异以及肾上腺网合成的激素与骨代谢的相关性。方法:回顾性研究75例绝经前妇女,其中33例为CD, 42例为ACS。分析两组患者的临床特点、实验室检查及骨代谢差异。然后,比较16例ACS患者和12例CD患者的血液类固醇激素水平。此外,还分析了骨密度(BMD)值与类固醇激素变量之间的关系。结果:CD患者血清、尿皮质醇和血清ACTH浓度明显高于ACS患者。相反,ACS组腰椎和股骨骨密度较低,骨钙素(OC)水平升高。脱氢表雄酮(DHEA)和硫酸脱氢表雄酮(DHEAS)与CD组和ACS组腰椎Z-score均有显著正相关。而股骨颈z评分与DHEA呈正相关,仅ACS组与DHEAS呈正相关。结论:骨质流失在ACS患者中比在CD患者中更为明显,尽管在CD患者中皮质醇水平较高。肾上腺网合成的高水平激素可能对绝经前高皮质醇血症妇女的骨密度有保护作用。
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引用次数: 0
Corrigendum to “Macrophage migration inhibitory factor promotes heterotopic ossification by mediating ROS/HIF-1α positive feedback loop and activating Wnt/β-catenin signaling pathway” [Bone 190 (2025) 117331] 巨噬细胞迁移抑制因子通过介导ROS/HIF-1α正反馈回路和激活Wnt/β-catenin信号通路促进异位骨化[Bone 190(2025) 117331]。
IF 3.5 2区 医学 Q2 ENDOCRINOLOGY & METABOLISM Pub Date : 2024-12-18 DOI: 10.1016/j.bone.2024.117365
Ping Li , Wensheng Zhang , Jie Zhang , Jie Liu , Jiaming Fu , Zhengnong Wei , Shiyong Le , Jiajia Xu , Liang Wang , Zhongmin Zhang
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引用次数: 0
Multi-scale inferomedial femoral neck bone quality in type 2 diabetes patients with fragility fracture 2型糖尿病合并脆性骨折患者股骨颈内侧间段骨质量分析。
IF 3.5 2区 医学 Q2 ENDOCRINOLOGY & METABOLISM Pub Date : 2024-12-16 DOI: 10.1016/j.bone.2024.117375
Praveer Sihota , Saroj Kumar , Ruban Dhaliwal , Piyush Uniyal , Ram Naresh Yadav , Vandana Dhiman , Deepak Neradi , Shailesh Karn , Mohin Sapara , Sidhartha Sharma , Sameer Aggarwal , Vijay G. Goni , Vishwajeet Mehandia , Björn Busse , Deepak Vashishth , Sanjay Kumar Bhadada , Navin Kumar
Both trabecular and cortical bone undergo changes at multiple scales. We previously demonstrated the multi-scale changes in trabecular bone quality that contribute to bone fragility in type 2 diabetes (T2D). The link between increased fragility in T2D and multi-scale changes in cortical bone and their interaction with glycation remains unclear. This study presents, first-ever, multi-scale cortical bone quality parameters in T2D patients after their first hip fracture. The study objective was to determine the association between cortical porosity (Ct.Po.), mechanical, material, and bone compositional properties in T2D. Inferomedial femoral neck (FN) bone tissue specimens were collected from patients (n = 10 with T2D, n = 25 age- and sex-matched non-diabetes controls) who underwent hip replacement surgery following the first hip fragility fracture. Bone mineral density at FN was found to be similar between groups. In T2D, Ct.Po was higher (p = 0.038), while ultimate stress (p = 0.021), ultimate strain (p = 0.040), post-yield strain (p = 0.011), toughness (p = 0.005), yield energy (p = 0.003), and post-yield energy (p = 0.004) were notably lower. Tissue compositional differences included lower gravimetric mineral/matrix (p = 0.017), higher non-enzymatic collagen cross-link ratio (NE-xLR) (p = 0.049) and higher sugar/matrix ratio (p = 0.042) in T2D. Fluorescent advanced glycation end-products (fAGEs) content was higher in T2D bone (p = 0.043). At the mesoscale, the fAGEs in the bone matrix are inversely related to the yield- and ultimate strain of T2D bone, and NE-xLR is negatively correlated with yield- and ultimate- stress in the T2D group. In conclusion, study findings demonstrate that elevated glycation weakens the mechanical integrity of cortical bone by reducing its ability to absorb energy and resist deformation, thereby contributing to bone fragility in T2D. The strong association of fAGEs with lower yield strain, along with the association of NE-xLR with lower yield- and ultimate stress, establishes a causal link between AGEs and the deterioration of cortical bone mechanical properties. These findings underscore the need for strategies targeting glycation and collagen quality to mitigate fracture risk in T2D patients.
骨小梁和骨皮质都会发生多尺度的变化。我们曾证实,骨小梁质量的多尺度变化会导致 2 型糖尿病(T2D)患者骨质脆弱。2 型糖尿病患者骨脆性增加与皮质骨的多尺度变化及其与糖化的相互作用之间的联系仍不清楚。本研究首次对首次髋部骨折后的 T2D 患者的多尺度皮质骨质量参数进行了研究。研究目的是确定 T2D 患者骨皮质孔隙率(Ct.Po.)、机械、材料和骨成分特性之间的关联。研究收集了首次髋部脆性骨折后接受髋关节置换手术的患者(10 名 T2D 患者,25 名年龄和性别匹配的非糖尿病对照组患者)的股骨颈内侧(FN)骨组织标本。结果发现,各组患者髋关节脆性骨折时的骨矿物质密度相似。在 T2D 组中,Ct.Po 较高(p = 0.038),而极限应力(p = 0.021)、极限应变(p = 0.040)、屈服后应变(p = 0.011)、韧性(p = 0.005)、屈服能量(p = 0.003)和屈服后能量(p = 0.004)明显较低。组织成分差异包括:T2D患者的重力矿物质/基质比率较低(p = 0.017),非酶胶原交联比率(NE-xLR)较高(p = 0.049),糖/基质比率较高(p = 0.042)。T2D 骨中的荧光高级糖化终产物(fAGEs)含量更高(p = 0.043)。在中观尺度上,骨基质中的 fAGEs 与 T2D 骨的屈服应力和极限应变成反比,而 NE-xLR 与 T2D 组的屈服应力和极限应变成负相关。总之,研究结果表明,糖化程度升高会削弱皮质骨的机械完整性,降低其吸收能量和抵抗变形的能力,从而导致 T2D 患者骨质脆弱。fAGEs与较低屈服应变的密切关系,以及NE-xLR与较低屈服应力和极限应力的关系,确定了AGEs与骨皮质机械性能恶化之间的因果关系。这些发现强调了针对糖化和胶原蛋白质量的策略以降低 T2D 患者骨折风险的必要性。
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引用次数: 0
Craniofacial fibrous dysplasia: A review of current literature 颅面纤维发育不良:当前文献综述。
IF 3.5 2区 医学 Q2 ENDOCRINOLOGY & METABOLISM Pub Date : 2024-12-14 DOI: 10.1016/j.bone.2024.117377
Sara Tuompo , Riikka E. Mäkitie , Mikko T. Nieminen

Introduction

Fibrous dysplasia (FD) is a rare genetic disease, in which normal bone is replaced by fibro-osseus tissue. Disease severity varies greatly from single monostotic lesions to widespread polyostotic disease. Craniofacial lesions are common and, due to the complex anatomy, can cause several disabling symptoms and local extra-skeletal complications. Since relatively rare, reported cases of craniofacial FD (CFD), specifically, are few and the appropriate management remains incompletely defined.

Methodology

We performed a systematic literature review following the PRISMA guidelines for articles considering CFD in the years 2010–2023. The search was conducted in the PubMed and OVID Medline libraries. Altogether 193 articles were retrieved and reviewed.

Results

Overall, the clinical presentation of CFD is highly variable depending on site and extent of lesion, with pain, deformity or impairment of function being most common. Diagnoses are often incidental and primarily based on CT imaging, while more extensive imaging, genetic studies and lesion biopsies are reserved for unclear cases. Asymptomatic patients are suitable for observation, while symptomatic or widespread disease may require more active approach with medical or surgical treatment. Follow-up is encouraged in all patients to observe possible lesion reactivation, late-stage complications and, though rarely, malignant transformation. Management should be individually tailored with a multidisciplinary team and wholesome consideration of individual needs.

Conclusions

This review provides an updated discussion on craniofacial FD with focus on improved understanding of disease pathophysiology, appropriate line of surgical management, and new potential means of medical treatment.
简介:纤维性发育不良(FD)是一种罕见的遗传性疾病,患者的正常骨被纤维性骨组织所取代。疾病的严重程度差别很大,从单一的单一病变到广泛的多骨病变。颅面病变是常见的,由于复杂的解剖结构,可引起几种致残症状和局部骨骼外并发症。由于报道的颅面FD (CFD)病例相对罕见,特别是很少,适当的治疗仍然不完全明确。方法:我们按照PRISMA指南对2010-2023年间考虑CFD的文章进行了系统的文献综述。搜索是在PubMed和OVID Medline图书馆进行的。共检索和审查了193篇文章。结果:总体而言,CFD的临床表现随病变部位和程度的不同而变化很大,最常见的是疼痛、畸形或功能障碍。诊断通常是偶然的,主要基于CT成像,而更广泛的成像,遗传研究和病变活检是为不明确的病例保留的。无症状的患者适合观察,而有症状或广泛传播的疾病可能需要更积极的药物或手术治疗。鼓励对所有患者进行随访,观察可能的病变再激活、晚期并发症以及恶性转化(虽然很少)。管理应由一个多学科的团队和对个人需要的全面考虑量身定制。结论:这篇综述提供了关于颅面FD的最新讨论,重点是提高对疾病病理生理学的理解,适当的外科治疗方法,以及新的潜在医学治疗手段。
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引用次数: 0
Combining systemic and local osteoporosis treatments: A longitudinal in vivo microCT study in ovariectomized rats 结合全身和局部骨质疏松症治疗:卵巢切除大鼠体内显微 CT 纵向研究。
IF 3.5 2区 医学 Q2 ENDOCRINOLOGY & METABOLISM Pub Date : 2024-12-13 DOI: 10.1016/j.bone.2024.117373
Vincent A. Stadelmann , Estelle Gerossier , Ulrike Kettenberger , Dominique P. Pioletti

Introduction

Managing osteoporotic patients at immediate fracture risk is challenging, in part due to the slow and localized effects of anti-osteoporotic drugs. Combining systemic anti-osteoporotic therapies with local bone augmentation techniques offers a promising strategy, but little is known about potential interactions. We hypothesized that integrating systemic treatments with local bone-strengthening biomaterials would have an additive effect on bone density and structure. This study investigated interactions and synergies between systemic therapies and injectable biomaterials, HA2 and HA2-ZOL, designed for local bone strengthening. HA2-ZOL incorporates Zoledronate, a bisphosphonate, to enhance anti-resorptive effects. These materials were tested in an in vivo rat model of osteoporosis using microCT and histology.

Methods

Thirty-six ovariectomized Wistar rats were treated systemically with vehicle (VEH), alendronate (ALN), or parathyroid hormone (PTH). One week later, their tibiae were randomly assigned to local treatment groups: HA2, HA2-ZOL, or NaCl control. Bilateral injections targeted metaphyseal trabecular bone, with microCT scans tracking changes over 8 weeks. Regions of interest (ROIs) were identified and analyzed for bone volume fraction (BV/TV), tissue mineral density (TMD), and trabecular morphology. Histological analyses were performed at week 8 to assess bone structure and mineral inclusions.

Results

VEH animals with NaCl injections experienced marked bone loss, partially mitigated by ALN and PTH. HA2 injections increased BV/TV by factors of 2.5 to 3.4 across treatments compared to baseline, with effects confined to the injected material. HA2-ZOL amplified this response, with BV/TV increases up to 4.8-fold, particularly in VEH and PTH animals. The effects peaked at 2–4 weeks post-injection, followed by remodeling and restoration. Both local treatments increased trabecular thickness, with HA2-ZOL showing slower post-peak resorption.

Discussion

HA2 injections significantly densified bone, independent of systemic therapy. Zoledronate in HA2-ZOL enhanced bone formation and delayed resorption in control and PTH animals, but offered no additional benefit when combined with systemic bisphosphonate. These findings support the hypothesis of an additive effect, suggesting that injectable hydrogels with localized drug delivery can complement systemic therapies by rapidly increasing local bone density, thereby potentially preventing fractures in high-risk osteoporotic patients.
导言:治疗有直接骨折风险的骨质疏松症患者具有挑战性,部分原因是抗骨质疏松药物的作用缓慢且局限于局部。将全身性抗骨质疏松疗法与局部骨质增强技术相结合是一种很有前景的策略,但人们对潜在的相互作用知之甚少。我们假设,将全身治疗与局部骨强化生物材料相结合将对骨密度和骨结构产生叠加效应。本研究调查了全身治疗与注射用生物材料 HA2 和 HA2-ZOL(用于局部骨强化)之间的相互作用和协同作用。HA2-ZOL 加入了双膦酸唑来增强抗骨质吸收效果。这些材料在体内骨质疏松症大鼠模型中使用显微 CT 和组织学方法进行了测试:方法:36 只卵巢切除的 Wistar 大鼠分别接受了载体(VEH)、阿仑膦酸盐(ALN)或甲状旁腺激素(PTH)的全身治疗。一周后,大鼠的胫骨被随机分配到局部治疗组:HA2、HA2-ZOL 或氯化钠对照组。双侧注射针对骨骺小梁,显微CT扫描跟踪8周内的变化。确定感兴趣区(ROI)并分析骨体积分数(BV/TV)、组织矿物质密度(TMD)和骨小梁形态。第 8 周时进行组织学分析,以评估骨结构和矿物质内含物:结果:注射NaCl的VEH动物出现明显的骨质流失,ALN和PTH可部分缓解骨质流失。与基线相比,HA2注射可使各处理的BV/TV增加2.5至3.4倍,效果仅限于注射材料。HA2-ZOL扩大了这种反应,BV/TV增加高达4.8倍,尤其是在VEH和PTH动物中。这种效应在注射后 2-4 周达到顶峰,随后出现重塑和恢复。两种局部治疗方法都能增加骨小梁厚度,而HA2-ZOL的峰值后吸收速度较慢:讨论:HA2注射能明显增加骨密度,与全身治疗无关。HA2-ZOL中的唑来膦酸盐可增强对照组和PTH组动物的骨形成并延缓骨吸收,但与全身性双膦酸盐联合使用时并无额外益处。这些研究结果支持了 "相加效应 "的假设,表明局部给药的可注射水凝胶可以通过快速增加局部骨密度来补充全身疗法,从而有可能预防高危骨质疏松症患者的骨折。
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引用次数: 0
Male Down syndrome Ts65Dn mice have impaired bone regeneration 雄性唐氏综合症小鼠Ts65Dn骨再生受损。
IF 3.5 2区 医学 Q2 ENDOCRINOLOGY & METABOLISM Pub Date : 2024-12-13 DOI: 10.1016/j.bone.2024.117374
Kirby M. Sherman , Catrina J. Silveira , Mingquan Yan , Ling Yu , Abigail Leon , Kasey Klages , Lauren G. White , Hannah M. Smith , Sarah M. Wolff , Alyssa Falck , Ken Muneoka , Regina Brunauer , Dana Gaddy , Larry J. Suva , Lindsay A. Dawson
Trisomy of human chromosome 21 (Ts21) individuals present with a spectrum of low bone mineral density (BMD) that predisposes this vulnerable group to skeletal injuries. To determine the bone regenerative capacity of Down syndrome (DS) mice, male and female Dp16 and Ts65Dn DS mice underwent amputation of the digit tip (the terminal phalanx (P3)). This is a well-established mammalian model of bone regeneration that restores the amputated skeletal segment and all associated soft tissues. P3 amputation was performed in 8-week-old male and female DS mice and WT controls and followed by in vivo μCT, histology and immunofluorescence. Following P3 amputation, the bone degradation phase was attenuated in both Dp16 and Ts65Dn males. In Dp16 males, P3 regeneration was delayed but complete by 63 days post amputation (DPA); however, male Ts65Dn exhibited attenuated regeneration by 63 DPA. In both Dp16 and Ts65Dn female DS mice, P3 regenerates were indistinguishable from WT by 42 DPA. In Ts65Dn males, osteoclasts and eroded bone surface were significantly reduced, and osteoblast number significantly decreased in the regenerating digit. In Ts65Dn females, no significant differences were observed in any osteoclast or osteoblast parameter. Like Ts21 individuals and DS mice with sex differences in bone mass, these data expand the characteristic sexually dimorphism to include bone resorption and regeneration in response to skeletal injury in Ts65Dn mice. These observations suggest that sex differences contribute to the poor bone healing of DS and compound the increased risk of bone injury in the Ts21 population.
人类21号染色体三体(Ts21)个体存在低骨矿物质密度(BMD)谱,易使这一脆弱群体遭受骨骼损伤。为了确定唐氏综合征(DS)小鼠的骨再生能力,我们将雄性和雌性Dp16和Ts65Dn DS小鼠的趾尖(末梢指骨(P3))截肢。这是一种成熟的哺乳动物骨再生模型,可以恢复被截肢的骨段和所有相关的软组织。对8周龄雄性、雌性DS小鼠和WT对照组进行P3截肢,并进行体内μCT、组织学和免疫荧光检查。P3切除后,Dp16和Ts65Dn雄性骨降解期均减弱。在Dp16雄性中,P3再生延迟,但在截肢后63 天完成;而雄性Ts65Dn则表现出63 DPA的衰减再生。在Dp16和Ts65Dn雌性DS小鼠中,P3再生与WT没有42 DPA的区别。Ts65Dn雄性再生趾破骨细胞和侵蚀骨面明显减少,成骨细胞数量明显减少。在Ts65Dn女性中,任何破骨细胞和成骨细胞参数均无显著差异。与骨量存在性别差异的Ts21个体和DS小鼠一样,这些数据将性别二态性特征扩展到Ts65Dn小鼠骨骼损伤后的骨吸收和再生。这些观察结果表明,性别差异导致退行性椎体滑移的骨愈合不良,并增加了Ts21人群骨损伤的风险。
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引用次数: 0
Deficiency of EXT1 and FGFR3 genes promotes chondrocyte differentiation, leading to the induction of osteochondroma formation 缺乏EXT1和FGFR3基因可促进软骨细胞分化,导致骨软骨瘤的形成。
IF 3.5 2区 医学 Q2 ENDOCRINOLOGY & METABOLISM Pub Date : 2024-12-13 DOI: 10.1016/j.bone.2024.117370
Hongrong Zhang , Zhencun Tang , Shiying Shen , Lei Feng , Yunfa Qin , Liangchong Huang , Yanyan Chen , Yu Liu , Weihong Wang

Objective

This study aims to investigate the roles of the EXT1 and FGFR3 genes in the development of osteochondromas, focusing specifically on their potential interactions in chondrocyte proliferation, differentiation, and tumor formation.

Methods

In vitro, the ATDC5 chondroprogenitor cell line was used to examine the effects of inactivation of both EXT1 and FGFR3. In vivo, a mouse model with dual gene knockout of Ext1 and Fgfr3 was constructed to further explore these genes' roles in tumor formation by observing the incidence and distribution patterns of osteochondromas.

Results

The in vitro experiments demonstrated that ATDC5 cells with reduced expression of EXT1 and FGFR3 genes exhibited enhanced chondrogenic differentiation. In vivo, Fgfr3+/−;Ext1+/− mice showed a significant incidence of osteochondromas (72.7 %), primarily located in the humerus, fibula, and tibia, while mice with a single heterozygous deletion did not display notable lesions.

Conclusion

The EXT1 and FGFR3 genes play crucial regulatory roles in the development of osteochondromas. Deficiencies in Ext1 and Fgfr3 can induce the formation of osteochondromas.
目的:本研究旨在探讨EXT1和FGFR3基因在骨软骨瘤发生中的作用,特别关注它们在软骨细胞增殖、分化和肿瘤形成中的潜在相互作用。方法:在体外,使用ATDC5软骨祖细胞系来检测EXT1和FGFR3失活的影响。在体内,我们构建了Ext1和Fgfr3双基因敲除的小鼠模型,通过观察骨软骨瘤的发病率和分布规律,进一步探索这些基因在肿瘤形成中的作用。结果:体外实验表明,EXT1和FGFR3基因表达降低的ATDC5细胞表现出增强的软骨分化。在体内,Fgfr3+/-;Ext1+/-小鼠表现出显著的骨软骨瘤发生率(72.7 %),主要位于肱骨、腓骨和胫骨,而具有单一杂合缺失的小鼠没有表现出显著的病变。结论:EXT1和FGFR3基因在骨软骨瘤的发生发展中起着重要的调控作用。缺乏Ext1和Fgfr3可诱导骨软骨瘤的形成。
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引用次数: 0
Potassium bicarbonate, not sodium bicarbonate, maintains acidosis-mediated bone dissolution 维持酸中毒介导的骨溶解的是碳酸氢钾,而不是碳酸氢钠。
IF 3.5 2区 医学 Q2 ENDOCRINOLOGY & METABOLISM Pub Date : 2024-12-12 DOI: 10.1016/j.bone.2024.117369
Mikayla Moody , Nayara Zainadine , Trey Doktorski , Ruchir Trivedi , Tannin A. Schmidt , Alix Deymier
Treatments for metabolic acidosis are not well studied; however, one treatment that is commonly used is sodium bicarbonate administration. Sodium bicarbonate has been shown to help reduce symptoms of metabolic acidosis, but its benefits for bone health remain uncertain. Potassium bicarbonate has become a potential new treatment due to its reduction in bone resorption markers, unlike sodium bicarbonate. However, very few studies have looked at the connection between bone functionality and potassium bicarbonate supplementation, especially under the influence of an acidic challenge. To determine the impact of potassium bicarbonate and sodium bicarbonate on the mechanical, structural, compositional, and cellular properties of bone, acidotic mice were given either potassium bicarbonate or sodium bicarbonate for seven days. Blood gas analysis was conducted to evaluate their acidotic states throughout the study. After experimentation, the mice were euthanized, and their femurs excised for further analysis. Before bicarbonate supplementation, the acidotic mice given sodium bicarbonate were in acidosis while the acidotic mice given potassium bicarbonate were in acidemia. The bicarbonate treatment somewhat rescued the blood gas parameters in both acidosis groups, but acidemia and bone dissolution continued occurring in the acidotic mice given potassium bicarbonate, as made evident by the continuous elevation in blood sodium levels compared to the control. The acidosis group given potassium bicarbonate group also had worsened composition and structure, while the acidosis group given sodium bicarbonate had no changes in bone metrics. In this study, potassium bicarbonate was not effective at reducing bone dissolution under acidotic conditions.
代谢性酸中毒的治疗方法尚未得到很好的研究;然而,一种常用的治疗方法是使用碳酸氢钠。碳酸氢钠已被证明有助于减轻代谢性酸中毒的症状,但其对骨骼健康的益处仍不确定。与碳酸氢钠不同,碳酸氢钾因其减少骨吸收标志物而成为一种潜在的新治疗方法。然而,很少有研究关注骨功能和补充碳酸氢钾之间的联系,特别是在酸性挑战的影响下。为了确定碳酸氢钾和碳酸氢钠对骨的力学、结构、组成和细胞特性的影响,对酸中毒小鼠分别给予碳酸氢钾或碳酸氢钠7天。在整个研究过程中进行血气分析以评估他们的酸中毒状态。实验结束后,这些老鼠被安乐死,它们的股骨被切除以作进一步分析。补充碳酸氢钠前,给予碳酸氢钠的小鼠出现酸中毒,给予碳酸氢钾的小鼠出现酸血症。碳酸氢盐治疗在一定程度上挽救了两个酸中毒组的血气参数,但在给予碳酸氢钾的酸中毒小鼠中,酸血症和骨溶解继续发生,与对照组相比,血钠水平持续升高表明这一点。给予碳酸氢钾的酸中毒组的骨组成和结构也出现了恶化,而给予碳酸氢钠的酸中毒组的骨指标没有变化。在这项研究中,碳酸氢钾在酸性条件下不能有效地减少骨溶解。
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引用次数: 0
Strength and strain distributions obtained from digital wrist tomosynthesis discriminate patients with and without a history of fragility fracture 从数字腕部断层合成获得的强度和应变分布可区分有无脆性骨折史的患者。
IF 3.5 2区 医学 Q2 ENDOCRINOLOGY & METABOLISM Pub Date : 2024-12-12 DOI: 10.1016/j.bone.2024.117368
Ram N. Yadav , Daniel J. Oravec , Terra Cushman , Sudhaker D. Rao , Yener N. Yeni
Bone fractures due to osteoporosis are a significant problem. Limited accuracy of standard bone mineral density (BMD) for fracture risk assessment, combined with low adherence to bone health screening precludes identification of those at risk of fracture. Because of the wide availability of digital breast tomosynthesis (DBT) imaging, bone screening using a DBT scanner at the time of breast screening has been proposed. Earlier studies have shown that BMD, microstructure, and stiffness of the distal radius can be calculated using digital tomosynthesis imaging of the wrist (DWT). However, strength and stress/strain parameters, which are more relevant to structural failure, and have the potential to enhance the utility of DWT, were not examined previously. Therefore, this study aimed to examine the ability of DWT to discriminate patients with and without fragility fracture using DWT based finite element (DWT-FE) derived strength and stress/strain distribution properties, and to determine in vivo repeatability of these biomechanical properties.
Twenty-two postmenopausal women with any fragility fracture (included spine, hip, distal radius, humerus and tibia fractures) and 68 without were recruited. Each participant's nondominant arm (dominant arm if history of fracture in the nondominant arm) was scanned with DWT and compressive loading was simulated using FE modeling. Six additional patients were DWT-scanned thrice, with repositioning, to determine the repeatability of the study variables.
Age and T-score were not different between fracture and nonfracture groups (p > 0.1), but strength and stress/strain parameters were significant predictors of fracture status (AUC = 0.64–0.74). Standard deviation of tensile strain was the most discriminatory variable for fracture status (AUC = 0.74) and was independent from stiffness. Repeatability error of DWT biomechanical properties was 0.7 % to 5.8 %.
This study demonstrated that DWT-FE based strength and standard deviation of tensile strain were reproducible and predict fracture status independent from BMD and stiffness. The results suggest that the accuracy of fracture risk screening can be improved in the highly accessible environment of mammographic imaging.
骨质疏松导致的骨折是一个重要的问题。用于骨折风险评估的标准骨密度(BMD)准确性有限,加上对骨骼健康筛查的依从性较低,妨碍了对有骨折风险者的识别。由于数字乳腺断层合成(DBT)成像的广泛应用,在乳腺筛查时使用DBT扫描仪进行骨筛查已被提出。早期的研究表明,可以使用腕部数字断层合成成像(DWT)计算骨密度、微观结构和桡骨远端刚度。然而,强度和应力/应变参数,更相关的结构破坏,并有可能提高DWT的效用,以前没有研究过。因此,本研究旨在通过基于DWT的有限元(DWT- fe)导出的强度和应力/应变分布特性来检验DWT区分脆性骨折患者和非脆性骨折患者的能力,并确定这些生物力学特性在体内的可重复性。22名绝经后妇女有任何脆性骨折(包括脊柱、髋部、桡骨远端、肱骨和胫骨骨折),68名没有。每个参与者的非优势臂(如果有非优势臂骨折史的优势臂)用DWT扫描,并使用有限元模型模拟压缩载荷。另外6名患者进行了三次dwt扫描,重新定位,以确定研究变量的可重复性。年龄和t评分在骨折组和非骨折组之间没有差异(p > 0.1),但强度和应力/应变参数是骨折状态的显著预测因子(AUC = 0.64-0.74)。拉伸应变的标准差是断裂状态最具歧视性的变量(AUC = 0.74),与刚度无关。DWT生物力学性能的重复性误差为0.7 % ~ 5.8 %。该研究表明,基于DWT-FE的强度和拉伸应变的标准偏差是可重复的,并且可以独立于BMD和刚度预测断裂状态。结果表明,在高度可及的乳房x线摄影环境下,骨折风险筛查的准确性可以得到提高。
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引用次数: 0
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Bone
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