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Homogenized finite element analysis of distal tibia sections: Achievements and limitations 胫骨远端截面的均质化有限元分析:成就与局限
IF 2.5 Q3 ENDOCRINOLOGY & METABOLISM Pub Date : 2024-03-26 DOI: 10.1016/j.bonr.2024.101752
Mathieu Simon , Michael Indermaur , Denis Schenk , Benjamin Voumard , Ivan Zderic , Dominic Mischler , Michael Pretterklieber , Philippe Zysset
<div><p>High-resolution peripheral quantitative computed tomography (HR-pQCT) based micro-finite element (μFE) analysis allows accurate prediction of stiffness and ultimate load of standardised (∼1 cm) distal radius and tibia sections. An alternative homogenized finite element method (hFE) was recently validated to compute the ultimate load of larger (∼2 cm) distal radius sections that include Colles' fracture sites. Since the mechanical integrity of the weight-bearing distal tibia is gaining clinical interest, it has been shown that the same properties can be used to predict the strength of both distal segments of the radius and the tibia. Despite the capacity of hFE to predict structural properties of distal segments of the radius and the tibia, the limitations of such homogenization scheme remain unclear. Therefore, the objective of this study is to build a complete mechanical data set of the compressive behavior of distal segments of the tibia and to compare quantitatively the structural properties with the hFE predictions. As a further aim, it is intended to verify whether hFE is also able to capture the post-yield strain localisation or fracture zones in such a bone section, despite the absence of strain softening in the constitutive model.</p><p>Twenty-five fresh-frozen distal parts of tibias of human donors were used in this study. Sections were cut corresponding to an in-house triple-stack protocol HR-pQCT scan, lapped, and scanned using micro computed tomography (μCT). The sections were tested in compression until failure, unloaded and scanned again in μCT. Volumetric bone mineral density (vBMD) and bone mineral content (BMC) were correlated to compression test results. hFE analysis was performed in order to compare computational predictions (stiffness, yield load and plastic deformation field pattern) with the compressive experiment. Namely, strain localization was assessed based on digital volume correlation (DVC) results and qualitatively compared to hFE predictions by comparing mid-slices patterns.</p><p>Bone mineral content (BMC) showed a good correlation with stiffness (R<sup>2</sup> = 0.92) and yield (R<sup>2</sup> = 0.88). Structural parameters also showed good agreement between the experiment and hFE for both stiffness (R<sup>2</sup> = 0.96, slope = 1.05 with 95 % CI [0.97, 1.14]) and yield (R<sup>2</sup> = 0.95, slope = 1.04 [0.94, 1.13]). The qualitative comparison between hFE and DVC strain localization patterns allowed the classification of the samples into 3 categories: bad (15 sections), semi (8), and good agreement (2).</p><p>The good correlations between BMC or hFE and experiment for structural parameters were similar to those obtained previously for the distal part of the radius. The failure zones determined by hFE corresponded to registration only in 8 % of the cases. We attribute these discrepancies to local elastic/plastic buckling effects that are not captured by the continuum-based FE approach exempt from strain s
基于高分辨率外周定量计算机断层扫描(HR-pQCT)的微有限元(μFE)分析可准确预测标准化(∼1 厘米)桡骨和胫骨远端截面的刚度和极限载荷。最近,一种替代的均质化有限元方法(hFE)经过验证,可以计算包括科林斯骨折部位在内的较大(∼2 厘米)桡骨远端截面的极限载荷。由于负重胫骨远端的机械完整性越来越受到临床关注,因此有研究表明,相同的属性可用于预测桡骨和胫骨远端的强度。尽管 hFE 能够预测桡骨和胫骨远段的结构特性,但这种均质化方案的局限性仍不明确。因此,本研究的目的是建立胫骨远端压缩行为的完整力学数据集,并将结构特性与 hFE 预测进行定量比较。另一个目的是验证 hFE 是否也能捕捉到这种骨切片的屈服后应变定位或断裂带,尽管构成模型中不存在应变软化。根据内部三叠协议 HR-pQCT 扫描结果切割切片,进行搭接,并使用微型计算机断层扫描(μCT)进行扫描。对切片进行压缩测试直至失效,卸载后再次进行μCT扫描。为了将计算预测(刚度、屈服载荷和塑性变形场模式)与压缩实验进行比较,进行了 hFE 分析。也就是说,根据数字体积相关性(DVC)结果评估了应变定位,并通过比较中间切片模式与 hFE 预测进行了定性比较。骨矿物质含量(BMC)与刚度(R2 = 0.92)和屈服(R2 = 0.88)显示出良好的相关性。在刚度(R2 = 0.96,斜率 = 1.05,95 % CI [0.97,1.14])和屈服度(R2 = 0.95,斜率 = 1.04 [0.94,1.13])方面,实验和 hFE 的结构参数也显示出良好的一致性。通过对 hFE 和 DVC 应变定位模式进行定性比较,可将样本分为 3 类:差(15 个部分)、半(8 个部分)和良好一致(2 个部分)。通过 hFE 确定的破坏区仅在 8% 的情况下与登记相符。我们将这些差异归因于局部弹性/塑性屈曲效应,而基于连续体的 FE 方法无法捕捉到这些效应,应变软化除外。改进应变定位 hFE 预测的一种方法是使用具有完整皮质外壳的较长远节段,就像对桡骨所做的那样。总之,所使用的 hFE 方案能可靠地捕捉到胫骨截面的弹性和屈服响应,但不能捕捉到随后的破坏过程。
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引用次数: 0
Fueling recovery: The importance of energy coupling between angiogenesis and osteogenesis during fracture healing 为恢复加油:骨折愈合过程中血管生成和骨生成之间能量耦合的重要性
IF 2.5 Q3 ENDOCRINOLOGY & METABOLISM Pub Date : 2024-03-25 DOI: 10.1016/j.bonr.2024.101757
Fleur van Brakel, Yudong Zhao, Bram C.J. van der Eerden

Approximately half of bone fractures that do not heal properly (non-union) can be accounted to insufficient angiogenesis. The processes of angiogenesis and osteogenesis are spatiotemporally regulated in the complex process of fracture healing that requires a substantial amount of energy. It is thought that a metabolic coupling between angiogenesis and osteogenesis is essential for successful healing. However, how this coupling is achieved remains to be largely elucidated. Here, we will discuss the most recent evidence from literature pointing towards a metabolic coupling between angiogenesis and osteogenesis. We will describe the metabolic profiles of the cell types involved during fracture healing as well as secreted products in the bone microenvironment (such as lactate and nitric oxide) as possible key players in this metabolic crosstalk.

约有一半的骨折愈合不良(不愈合)可归因于血管生成不足。在需要大量能量的复杂骨折愈合过程中,血管生成和骨生成过程受时空调控。人们认为,血管生成和骨生成之间的代谢耦合是成功愈合的关键。然而,如何实现这种耦合在很大程度上仍有待阐明。在此,我们将讨论文献中指向血管生成和成骨之间代谢耦合的最新证据。我们将描述骨折愈合过程中涉及的细胞类型的代谢特征以及骨微环境中的分泌产物(如乳酸和一氧化氮),它们可能是这种代谢串扰的关键参与者。
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引用次数: 0
Protective role of exercise on breast cancer-related osteoporosis in women undergoing aromatase inhibitors: A narrative review 运动对使用芳香化酶抑制剂的女性乳腺癌相关骨质疏松症的保护作用:叙述性综述
IF 2.5 Q3 ENDOCRINOLOGY & METABOLISM Pub Date : 2024-03-25 DOI: 10.1016/j.bonr.2024.101756
Claudia Cerulli , Elisa Moretti , Elisa Grazioli , Gian Pietro Emerenziani , Arianna Murri , Eliana Tranchita , Carlo Minganti , Alessandra Di Cagno , Attilio Parisi

Hormone therapy following surgery reduces the risk of breast cancer (BC) recurrence and progression of hormone-sensitive BC, especially in postmenopausal women. Despite the antitumor efficacy of hormone therapy, particularly of aromatase inhibitors, they cause long-term side effects, mainly bone density reduction. Exercise can slow the rate of bone loss, which reduces the risk of fractures from osteoporosis, and could be an integrative treatment able to mitigate the BC treatment side effects positively impacting bone health. This narrative review aims to discuss studies on the effect of exercise on bone health in BC women undergoing aromatase inhibitors, highlighting the possible role of exercise as complementary to conventional therapies. Additionally, according to the literature revision, exercise practical applications to improve bone health in these patients are summarized.

手术后的激素治疗可降低乳腺癌(BC)复发和激素敏感型BC恶化的风险,尤其是绝经后妇女。尽管激素疗法,尤其是芳香化酶抑制剂具有抗肿瘤功效,但它们会产生长期副作用,主要是骨密度降低。运动可以减缓骨质流失的速度,从而降低因骨质疏松症导致骨折的风险,是一种综合治疗方法,可以减轻乳腺癌治疗的副作用,对骨骼健康产生积极影响。这篇叙述性综述旨在讨论运动对接受芳香化酶抑制剂治疗的BC女性骨健康影响的研究,强调运动作为常规疗法的补充可能发挥的作用。此外,根据文献修订,还总结了运动在改善这些患者骨骼健康方面的实际应用。
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引用次数: 0
High rate of progression to symptomatic multiple myeloma in patients with smoldering myeloma and isolated osteoporotic vertebral fracture 在患有烟雾型骨髓瘤和孤立性骨质疏松性脊椎骨折的患者中,进展为无症状多发性骨髓瘤的比例很高
IF 2.5 Q3 ENDOCRINOLOGY & METABOLISM Pub Date : 2024-03-25 DOI: 10.1016/j.bonr.2024.101755
Kevin Chevalier , Sabrina Hamroun , Samuel Bitoun , Julien Henry , Christian Roux , Karine Briot , Rakiba Belkhir , Xavier Mariette , Raphaèle Seror

Multiple myeloma (MM) frequently causes vertebral fractures (VF). Some are lytic lesions and others have the aspect of benign osteoporotic fractures not requiring anti-myeloma treatment. We explored outcome of these patients with smoldering myeloma (SM) and osteoporotic VF.

In this retrospective bi-centric study, patients were identified using a systematic keyword search on electronic medical records. Patients with SM and isolated VF of osteoporotic aspect without indications for myeloma-specific therapy were included.

Overall, 13 (7 %) of the 184 identified patients had SM and VF confirmed to be osteoporotic (median number of VF was 3). During follow-up, 12 (92 %) patients evolved to symptomatic MM, 7 (54 %) of them within 18 months (early progressors). Myeloma defining events were new lytic bone lesions in 7 patients (53.8 %). The serum calcium level was significantly higher in the early progressor group (median 2.35 IQR [2.31–2.38] and 2.28 IQR [2.21–2.29] respectively, p = 0.003). Early progressors had a higher number of VF at diagnosis (3.0 [2.0–5.5] vs 1.0 [1.0–2.5], p = 0.18) and more frequently evolved to symptomatic MM because of lytic bone lesions (5 [71 %] vs 2 [33 %], p = 0.13) compared to late progressors.

VF of osteoporotic appearance in the context of SM is a rare situation but at high risk of rapid progression to symptomatic MM, suggesting that they may represent bone fragility linked to MM infiltration rather than solely osteoporotic fractures. Further studies are needed to assess if earlier treatment might be beneficial in this population.

多发性骨髓瘤(MM)经常导致脊椎骨折(VF)。有些是溶解性病变,有些则是良性骨质疏松性骨折,不需要抗骨髓瘤治疗。在这项回顾性双中心研究中,我们通过对电子病历进行系统的关键词搜索来确定患者。在184名被确认的患者中,有13人(7%)患有骨髓瘤和骨质疏松性VF(VF的中位数为3)。在随访期间,12 名患者(92%)发展为有症状的骨髓瘤,其中 7 名患者(54%)在 18 个月内(早期进展者)发展为有症状的骨髓瘤。7名患者(53.8%)出现新的溶解性骨病变,这是骨髓瘤的标志性事件。早期进展组的血清钙水平明显更高(中位数分别为 2.35 IQR [2.31-2.38] 和 2.28 IQR [2.21-2.29],P = 0.003)。与晚期进展者相比,早期进展者在确诊时有更多的 VF(3.0 [2.0-5.5] vs 1.0 [1.0-2.5],p = 0.18),并且由于溶解性骨病变而演变为无症状 MM 的频率更高(5 [71 %] vs 2 [33%],p = 0.13)。SM背景下出现骨质疏松的VF是一种罕见的情况,但其快速发展为无症状MM的风险很高,这表明它们可能代表与MM浸润有关的骨脆性,而不仅仅是骨质疏松性骨折。还需要进一步研究,以评估早期治疗是否对这一人群有益。
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引用次数: 0
Lessons learned from the real-world diagnosis and management of hereditary hypophosphatemic rickets 从遗传性低磷血症佝偻病的实际诊断和管理中汲取的经验教训
IF 2.5 Q3 ENDOCRINOLOGY & METABOLISM Pub Date : 2024-03-21 DOI: 10.1016/j.bonr.2024.101753
Deepti Chaturvedi , Taif EmadEldin Mehasi , Assia Benbrahim , Lubna ElDeeb , Asma Deeb

Hypophosphatemic rickets, which is often hereditary, is still under- or misdiagnosed in both children and adults, denying these individuals access to optimal management and genetic counseling. There have been recent calls to compile real-world data and share best practice on these rare conditions to guide clinical decision-making. Here we present eight clinical vignettes of patients with hypophosphatemic rickets encountered in our tertiary pediatric endocrinology practice. We describe the clinical features, genetics, and management of four cases of X-linked hypophosphatemia (PHEX mutations), one each of autosomal recessive hypophosphatemic rickets (DMP1 mutation) and autosomal recessive vitamin D-dependent rickets type 1A (CYP27B1 mutation), and two cases of distal renal tubular acidosis with FOXI1 mutation-associated hypophosphatemic rickets. Our cases prompt consideration of the (i) frequent misdiagnosis of hypophosphatemic rickets in clinical practice and the importance of comprehensive genetic testing; (ii) variable expressivity of the causative mutations; and (iii) a lack of responsiveness and/or compliance to conventional therapy and the value of burosumab in modern management, provided access is equitable. These cases highlight common real-world themes and challenges to managing patients presenting with these diverse conditions, especially the burden of disease hidden by misdiagnosis. In sharing these cases, we hope to raise awareness of these conditions, promote best practice in genetic diagnosis and management, and further advocate for reimbursement equity for the best available therapies.

低磷血症性佝偻病通常具有遗传性,但在儿童和成人中仍然存在诊断不足或误诊的情况,导致这些患者无法获得最佳治疗和遗传咨询。最近,人们呼吁汇编真实世界的数据,分享有关这些罕见病症的最佳实践,以指导临床决策。在此,我们介绍了在三级儿科内分泌科临床实践中遇到的八例低磷血症佝偻病患者的临床案例。我们描述了四例X连锁性低磷血症(PHEX基因突变)、一例常染色体隐性低磷血症佝偻病(DMP1基因突变)和一例常染色体隐性维生素D依赖性佝偻病1A型(CYP27B1基因突变)以及两例远端肾小管酸中毒伴FOXI1基因突变相关性低磷血症佝偻病患者的临床特征、遗传学和处理方法。我们的病例促使人们思考:(i) 低磷血症性佝偻病在临床实践中经常被误诊,以及全面基因检测的重要性;(ii) 致病突变的可变表达性;(iii) 缺乏对常规治疗的反应性和/或依从性,以及在公平可及的条件下布罗单抗在现代治疗中的价值。这些病例凸显了现实世界中常见的主题以及管理这些不同病症患者所面临的挑战,尤其是因误诊而隐藏的疾病负担。通过分享这些病例,我们希望提高人们对这些疾病的认识,推广基因诊断和管理的最佳实践,并进一步倡导公平报销现有最佳疗法的费用。
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引用次数: 0
Microvascular disease not type 2 diabetes is associated with increased cortical porosity: A study of cortical bone microstructure and intracortical vessel characteristics 微血管疾病与 2 型糖尿病皮质孔隙率增加有关:皮质骨微观结构和皮质内血管特征研究
IF 2.5 Q3 ENDOCRINOLOGY & METABOLISM Pub Date : 2024-03-01 DOI: 10.1016/j.bonr.2024.101745
Maximilian T. Löffler , Po-hung Wu , Amir M. Pirmoazen , Gabby B. Joseph , Jay M. Stewart , Isra Saeed , Jing Liu , Anne L. Schafer , Ann V. Schwartz , Thomas M. Link , Galateia J. Kazakia

Introduction

Fracture risk is elevated in type 2 diabetes (T2D) despite normal or even high bone mineral density (BMD). Microvascular disease (MVD) is a diabetic complication, but also associated with other diseases, for example chronic kidney disease. We hypothesize that increased fracture risk in T2D could be due to increased cortical porosity (Ct.Po) driven by expansion of the vascular network in MVD. The purpose of this study was to investigate associations of T2D and MVD with cortical microstructure and intracortical vessel parameters.

Methods

The study group consisted of 75 participants (38 with T2D and 37 without T2D). High-resolution peripheral quantitative CT (HR-pQCT) and dynamic contrast-enhanced MRI (DCE-MRI) of the ultra-distal tibia were performed to assess cortical bone and intracortical vessels (outcomes). MVD was defined as ≥1 manifestation including neuropathy, nephropathy, or retinopathy based on clinical exams in all participants. Adjusted means of outcomes were compared between groups with/without T2D or between participants with/without MVD in both groups using linear regression models adjusting for age, sex, BMI, and T2D as applicable.

Results

MVD was found in 21 (55 %) participants with T2D and in 9 (24 %) participants without T2D. In T2D, cortical pore diameter (Ct.Po.Dm) and diameter distribution (Ct.Po.Dm.SD) were significantly higher by 14.6 μm (3.6 %, 95 % confidence interval [CI]: 2.70, 26.5 μm, p = 0.017) and by 8.73 μm (4.8 %, CI: 0.79, 16.7 μm, p = 0.032), respectively. In MVD, but not in T2D, cortical porosity was significantly higher by 2.25 % (relative increase = 12.9 %, CI: 0.53, 3.97 %, p = 0.011) and cortical BMD (Ct.BMD) was significantly lower by −43.6 mg/cm3 (2.6 %, CI: −77.4, −9.81 mg/cm3, p = 0.012). In T2D, vessel volume and vessel diameter were significantly higher by 0.02 mm3 (13.3 %, CI: 0.004, 0.04 mm3, p = 0.017) and 15.4 μm (2.9 %, CI: 0.42, 30.4 μm, p = 0.044), respectively. In MVD, vessel density was significantly higher by 0.11 mm−3 (17.8 %, CI: 0.01, 0.21 mm−3, p = 0.033) and vessel volume and diameter were significantly lower by −0.02 mm3 (13.7 %, CI: −0.04, −0.004 mm3, p = 0.015) and − 14.6 μm (2.8 %, CI: −29.1, −0.11 μm, p = 0.048), respectively.

Conclusions

The presence of MVD, rather than T2D, was associated with increased cortical porosity. Increased porosity in MVD was coupled with a larger number of smaller vessels, which could indicate upregulation of neovascularization triggered by ischemia. It is unclear why higher variability and average diameters of pores in T2D were accompanied by larger vessels.

导言2型糖尿病(T2D)患者尽管骨质密度(BMD)正常甚至很高,但骨折风险却很高。微血管疾病(MVD)是一种糖尿病并发症,但也与其他疾病有关,例如慢性肾病。我们假设,T2D 患者骨折风险增加的原因可能是 MVD 中血管网络扩张导致皮质孔隙率(Ct.Po)增加。本研究的目的是调查 T2D 和 MVD 与皮质微结构和皮质内血管参数的关系。对胫骨超远端进行了高分辨率外周定量 CT(HR-pQCT)和动态对比增强 MRI(DCE-MRI)检查,以评估骨皮质和皮质内血管(结果)。根据所有参与者的临床检查结果,MVD 的定义为≥1 种表现,包括神经病变、肾病变或视网膜病变。使用线性回归模型比较有/无 T2D 组之间或有/无 MVD 两组参与者之间的调整后结果平均值,并酌情调整年龄、性别、体重指数和 T2D。在 T2D 患者中,皮质孔直径(Ct.Po.Dm)和直径分布(Ct.Po.Dm.SD)分别显著增加了 14.6 μm(3.6%,95% 置信区间 [CI]:2.70, 26.5 μm,p = 0.017)和 8.73 μm(4.8%,CI:0.79, 16.7 μm,p = 0.032)。在 MVD 中,皮质孔隙率显著增加 2.25 %(相对增加 = 12.9 %,CI:0.53,3.97 %,p = 0.011),皮质 BMD(Ct.BMD)显著降低 -43.6 mg/cm3(2.6 %,CI:-77.4,-9.81 mg/cm3,p = 0.012),而在 T2D 中则没有。在 T2D 患者中,血管体积和血管直径分别明显增加了 0.02 mm3(13.3%,CI:0.004,0.04 mm3,p = 0.017)和 15.4 μm(2.9%,CI:0.42,30.4 μm,p = 0.044)。在 MVD 中,血管密度显著增加了 0.11 mm-3 (17.8%,CI:0.01,0.21 mm-3,p = 0.033),血管体积和直径显著减少了 -0.02 mm3 (13.7%,CI:-0.结论 MVD(而非 T2D)的存在与皮质孔隙率增加有关。MVD患者的孔隙率增加与更多的小血管有关,这可能表明缺血引发的新生血管上调。目前还不清楚为什么在 T2D 中孔隙的变异性和平均直径较高的同时血管也较大。
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引用次数: 0
In vivo imaging of bone collagen dynamics in zebrafish 斑马鱼骨胶原动态的活体成像
IF 2.5 Q3 ENDOCRINOLOGY & METABOLISM Pub Date : 2024-03-01 DOI: 10.1016/j.bonr.2024.101748
Hiromu Hino, Shigeru Kondo, Junpei Kuroda

Type I collagen plays a pivotal role in shaping bone morphology and determining its physical properties by serving as a template for ossification. Nevertheless, the mechanisms underlying bone collagen formation, particularly the principles governing its orientation, remain unknown owing to the lack of a method that enables continuous in vivo observations. To address this challenge, we constructed a method to visualize bone collagen by tagging with green fluorescent protein (GFP) in zebrafish and observed the interactions between osteoblasts and collagen fibers during bone formation in vivo. When collagen type I alpha 2 chain (Col1a2)-GFP was expressed under the control of the osteoblast-specific promoters osx or osc in zebrafish, bone collagen was observed clearly enough to identify its localization, whereas collagen from other organs was not. Therefore, we determined that this method was of sufficient quality for the detailed in vivo observation of bone collagen. Next, bone collagen in the scales, fin rays, and opercular bones of zebrafish was observed in detail, when bone formation is more active. High-magnification imaging showed that Col1a2-GFP can visualize collagen sufficiently to analyze the collagen fiber orientation and microstructure of bones.

Furthermore, by simultaneously observation of bone collagen and osteoblasts, we successfully observed dynamic changes in the morphology and position of osteoblasts from the early stages of bone formation. It was also found that the localization pattern and orientation of bone collagen significantly differed depending on the choice of the expression promoter. Both promoters (osx and osc) used in this study are osteoblast-specific, but their Col1a2-GFP localizing regions within the bone were exclusive, with osx region localizing mainly to the outer edge of the bone and osc region localizing to the central area of the bone. This suggests the existence of distinct osteoblast subpopulations with different gene expression profiles, each of which may play a unique role in osteogenesis.

These findings would contribute to a better understanding of the mechanisms governing bone collagen formation by osteoblasts.

I 型胶原蛋白作为骨化的模板,在塑造骨骼形态和决定其物理特性方面发挥着关键作用。然而,由于缺乏可在体内进行连续观察的方法,骨胶原蛋白的形成机制,尤其是其定向原理仍不为人知。为了应对这一挑战,我们在斑马鱼体内构建了一种通过标记绿色荧光蛋白(GFP)来观察骨胶原蛋白的方法,并观察了骨形成过程中成骨细胞与胶原纤维之间的相互作用。在成骨细胞特异性启动子osx或osc的控制下,在斑马鱼体内表达Ⅰ型α2链胶原蛋白(Col1a2)-GFP时,可以清晰地观察到骨胶原蛋白,从而确定其定位,而其他器官的胶原蛋白则不能。因此,我们认为这种方法足以在体内详细观察骨胶原。接下来,我们详细观察了斑马鱼鳞片、鳍条和厣骨中的骨胶原,此时骨形成更为活跃。此外,通过同时观察骨胶原和成骨细胞,我们成功地从骨形成的早期阶段观察到了成骨细胞形态和位置的动态变化。我们还发现,骨胶原蛋白的定位模式和取向因表达启动子的选择而显著不同。本研究中使用的两种启动子(osx 和 osc)都具有成骨细胞特异性,但它们的 Col1a2-GFP 在骨中的定位区域却具有排他性,osx 区域主要定位在骨的外缘,而 osc 区域则定位在骨的中央区域。这些发现有助于更好地理解成骨细胞形成骨胶原的机制。
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引用次数: 0
Disruption of FLNB leads to skeletal malformation by interfering with skeletal segmentation through the HOX gene FLNB 基因的中断会通过 HOX 基因干扰骨骼的分割,从而导致骨骼畸形
IF 2.5 Q3 ENDOCRINOLOGY & METABOLISM Pub Date : 2024-03-01 DOI: 10.1016/j.bonr.2024.101746
Qiming Xu , Lijia Cui , Yude Lin , Leigh-Anne Cui , Weibo Xia

Filamin B (FLNB) plays an important role in skeletal development. Mutations in FLNB can lead to skeletal malformation such as an abnormal number of ossification centers, indicating that the skeletal segmentation in the embryonic period may be interfered with. We established a mouse model with the pathogenic point mutation FLNB NM_001081427.1: c.4756G > A (p.Gly1586Arg) using CRISPR-Cas9 technology. Micro-CT, HE staining and whole skeletal preparation were performed to examine the skeletal malformation. In situ hybridization of embryos was performed to examine the transcription of HOX genes during embryonic development. The expression of FLNB was downregulated in FLNBG1586R/G1586R and FLNBWT/G1586R mice, compared to FLNBWT/WT mice. Fusions in tarsal bones were found in FLNBG1586R/G1586R and FLNBWT/G1586R mice, indicating that the skeletal segmentation was interfered with. In the embryo of FLNBG1586R/G1586R mice (E12.5), the transcription levels of HOXD10 and HOXB2 were downregulated in the carpal region and cervical spine region, respectively. This study indicated that the loss-of-function mutation G1586R in FLNB may lead to abnormal skeletal segmentation, and the mechanism was possibly associated with the downregulation of HOX gene transcription during the embryonic period.

纤 维素 B(FLNB)在骨骼发育过程中发挥着重要作用。FLNB突变可导致骨骼畸形,如骨化中心数量异常,这表明胚胎时期的骨骼分割可能受到干扰。我们利用CRISPR-Cas9技术建立了致病点突变FLNB NM_001081427.1: c.4756G > A (p.Gly1586Arg) 的小鼠模型。为检测骨骼畸形,对胚胎进行了显微 CT、HE 染色和全骨骼制备。对胚胎进行原位杂交以检测胚胎发育过程中HOX基因的转录情况。与FLNBWT/WT小鼠相比,FLNBG1586R/G1586R和FLNBWT/G1586R小鼠中FLNB的表达下调。在FLNBG1586R/G1586R和FLNBWT/G1586R小鼠中发现跗骨融合,这表明骨骼的分割受到了干扰。在FLNBG1586R/G1586R小鼠胚胎(E12.5)中,HOXD10和HOXB2的转录水平分别在腕骨区和颈椎区下调。该研究表明,FLNB功能缺失突变G1586R可能导致骨骼分割异常,其机制可能与胚胎期HOX基因转录下调有关。
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引用次数: 0
The multi-faceted nature of age-associated osteoporosis 老年性骨质疏松症的多面性
IF 2.5 Q3 ENDOCRINOLOGY & METABOLISM Pub Date : 2024-03-01 DOI: 10.1016/j.bonr.2024.101750
A.E. Smit , O.C. Meijer , E.M. Winter

Age-associated osteoporosis (AAOP) poses a significant health burden, characterized by increased fracture risk due to declining bone mass and strength. Effective prevention and early treatment strategies are crucial to mitigate the disease burden and the associated healthcare costs. Current therapeutic approaches effectively target the individual contributing factors to AAOP. Nonetheless, the management of AAOP is complicated by the multitude of variables that affect its development. Main intrinsic and extrinsic factors contributing to AAOP risk are reviewed here, including mechanical unloading, nutrient deficiency, hormonal disbalance, disrupted metabolism, cognitive decline, inflammation and circadian disruption. Furthermore, it is discussed how these can be targeted for prevention and treatment. Although valuable as individual targets for intervention, the interconnectedness of these risk factors result in a unique etiology for every patient. Acknowledgement of the multifaceted nature of AAOP will enable the development of more effective and sustainable management strategies, based on a holistic, patient-centered approach.

年龄相关性骨质疏松症(AAOP)是一种严重的健康负担,其特点是骨量和骨强度下降导致骨折风险增加。有效的预防和早期治疗策略对于减轻疾病负担和相关医疗费用至关重要。目前的治疗方法能有效针对导致 AAOP 的各种因素。然而,由于影响 AAOP 发展的变量众多,其管理也变得十分复杂。本文回顾了导致 AAOP 风险的主要内在和外在因素,包括机械卸载、营养缺乏、荷尔蒙失调、新陈代谢紊乱、认知能力下降、炎症和昼夜节律紊乱。此外,还讨论了如何针对这些因素进行预防和治疗。尽管这些风险因素作为单独的干预目标很有价值,但它们之间的相互联系导致每位患者都有独特的病因。认识到 AAOP 的多面性,就能在以患者为中心的整体方法基础上,制定出更有效、更可持续的管理策略。
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引用次数: 0
Case report: Death caused by multi-organ metastatic calcifications as a result of intramuscular injections with paraffin oil 病例报告:肌肉注射石蜡油导致多器官转移性钙化引发死亡
IF 2.5 Q3 ENDOCRINOLOGY & METABOLISM Pub Date : 2024-03-01 DOI: 10.1016/j.bonr.2024.101749
Søren Reinhold Jakobsen , Marta Diaz-delCastillo , Martin Blomberg Jensen , Thomas Levin Andersen , Ebbe Eldrup , Trine Skov Nielsen

In this forensic case report, we present autopsy findings from a young male in his thirties who had been self-injecting paraffin oil into his upper extremities 8 years prior to death. The injections induced an inflammatory response, leading to granuloma formation. This, in turn, resulted in severe hypercalcemia. The external autopsy examination revealed gross macroscopic ulcerations and enlargement of upper extremities, while calcifications of ligaments, heart, kidneys and dura mater was revealed on postmortem CT-scans. Histopathological examination showed extensive multiorgan metastatic calcifications in several tissues including the lungs, heart and kidney. Cause of death was estimated to be the extensive calcific deposits in the heart likely resulting in cardiac arrest. To our knowledge this is the first case reporting findings from an autopsy in which the cause of death was linked to cosmetic oil injections.

在这份法医案例报告中,我们介绍了一名三十多岁的年轻男性的尸检结果,他在死前 8 年曾自行向上肢注射石蜡油。注射引起了炎症反应,导致肉芽肿形成。这反过来又导致了严重的高钙血症。外部尸检显示他的上肢有大面积溃疡和肿大,死后 CT 扫描显示他的韧带、心脏、肾脏和硬脑膜有钙化。组织病理学检查显示,包括肺、心脏和肾脏在内的多个组织出现了广泛的多器官转移性钙化。据估计,死亡原因是心脏内的广泛钙化沉积可能导致心脏骤停。据我们所知,这是第一例报告死因与注射美容油有关的尸检结果。
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引用次数: 0
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Bone Reports
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