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Delineating the nexus between gut-intratumoral microbiome and osteo-immune system in bone metastases 阐明骨转移瘤中肠道-瘤内微生物群与骨免疫系统之间的联系
IF 2.1 Q3 ENDOCRINOLOGY & METABOLISM Pub Date : 2024-10-10 DOI: 10.1016/j.bonr.2024.101809
Shreya Kapoor, Muskan Gupta , Leena Sapra , Taranjeet Kaur, Rupesh K. Srivastava
Emerging insights in osteoimmunology have enabled researchers to explore in depth the role of immune modulation in regulating bone health. Bone is one of the common sites of metastasis notably in case of breast cancer, prostate cancer and several other cancer types. High calcium ion concentration and presence of several factors within the mineralized bone matrix including TGF-β, BMP etc., aid in tumor growth and proliferation. Accumulating evidence has substantiated the role of the gut-microbiota (GM) in tumorigenesis, further providing a strong impetus for the growing “immune-cancer-gut microbiota” relationship. Recent advancements in research further highlight the importance of the intra-tumor microbiota in conjunction with GM in cancer metastasis. Intratumoral microbiota owing to their ability to cause genetic instability, mutations, and epigenetic modifications within the tumor microenvironment, has been recognized to affect cancer cell physiology. The host microbiota and immune system crosstalk shapes the innate and adaptive arms of the immune system, which is the key player in cancer progression. In this review, we aim to decipher the role of microorganisms mediating bone metastasis by shedding light on the immuno-onco-microbiome (IOM) axis. We discussed the feasible cancer therapeutic interventions based on the modulation of the microbiome-immune cell axis which includes prebiotics, probiotics, and postbiotics. Here, we leverage the conceptual framework based on the published articles on microbiota-based therapies to target bone metastases. Understanding this complicated nexus will provide insights into fundamental factors governing bone metastases which will subsequently help in managing this malignancy with better efficacy.
骨免疫学的新进展使研究人员能够深入探讨免疫调节在调节骨骼健康中的作用。骨骼是癌症转移的常见部位之一,尤其是乳腺癌、前列腺癌和其他几种癌症。高钙离子浓度和矿化骨基质中存在的多种因子(包括 TGF-β、BMP 等)有助于肿瘤的生长和增殖。越来越多的证据证实了肠道微生物群(GM)在肿瘤发生中的作用,这进一步有力地推动了 "免疫-癌症-肠道微生物群 "关系的发展。最近的研究进展进一步凸显了肿瘤内微生物群与肠道微生物群在癌症转移中的重要性。肿瘤内微生物群由于能够导致肿瘤微环境中的遗传不稳定性、突变和表观遗传学改变,因此已被公认为会影响癌细胞的生理学。宿主微生物群和免疫系统的相互影响塑造了免疫系统的先天性和适应性臂膀,而先天性和适应性臂膀是癌症进展过程中的关键角色。在这篇综述中,我们旨在通过揭示免疫-生态-微生物组(IOM)轴来解读微生物介导骨转移的作用。我们讨论了基于微生物组-免疫细胞轴(包括益生菌、益生菌和后益生菌)调节的可行癌症治疗干预措施。在此,我们根据已发表的有关基于微生物群的疗法的文章,利用概念框架来治疗骨转移。了解这一复杂的关系将有助于深入了解骨转移的基本因素,从而有助于以更好的疗效控制这种恶性肿瘤。
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引用次数: 0
Administration of low intensity vibration and a RANKL inhibitor, alone or in combination, reduces bone loss after spinal cord injury-induced immobilization in rats 单独或联合使用低强度振动和 RANKL 抑制剂可减少脊髓损伤引起的大鼠固定后的骨质流失
IF 2.1 Q3 ENDOCRINOLOGY & METABOLISM Pub Date : 2024-10-02 DOI: 10.1016/j.bonr.2024.101808
Yuanzhen Peng , Helen M. Bramlett , W. Dalton Dietrich , Alex Marcillo , Juliana Sanchez-Molano , Ofelia Furones-Alonso , Jay J. Cao , Jenney Huang , Andrew A. Li , Jian Q. Feng , William A. Bauman , Weiping Qin
We previously reported an ability of low-intensity vibration (LIV) to improve selected biomarkers of bone turnover and gene expression and reduce osteoclastogenesis but lacking of evident bone accrual. In this study, we demonstrate that a prolonged course of LIV that initiated at 2 weeks post-injury and continued for 8 weeks can protect against bone loss after SCI in rats. LIV stimulates bone formation and improves osteoblast differentiation potential of bone marrow stromal stem cells while inhibiting osteoclast differentiation potential of marrow hematopoietic progenitors to reduce bone resorption. We further demonstrate that the combination of LIV and RANKL antibody reduces SCI-related bone loss more than each intervention alone. Our findings that LIV is efficacious in maintaining sublesional bone mass suggests that such physical-based intervention approach would be a noninvasive, simple, inexpensive and practical intervention to treat bone loss after SCI. Because the combined administration of LIV and RANKL inhibition better preserved sublesional bone after SCI than either intervention alone, this work provides the impetus for the development of future clinical protocols based on the potential greater therapeutic efficacy of combining non-pharmacological (e.g., LIV) and pharmacological (e.g., RANKL inhibitor or other agents) approaches to treat osteoporosis after SCI or other conditions associated with severe immobilization.
我们以前曾报道过低强度振动(LIV)能够改善选定的骨转换生物标志物和基因表达,减少破骨细胞生成,但缺乏明显的骨累积。在这项研究中,我们证明了从受伤后 2 周开始并持续 8 周的长期低强度振动疗法可以防止大鼠在 SCI 后出现骨质流失。LIV 可刺激骨形成,提高骨髓基质干细胞的成骨细胞分化潜能,同时抑制骨髓造血祖细胞的破骨细胞分化潜能,从而减少骨吸收。我们进一步证明,LIV 和 RANKL 抗体的组合比单独使用两种干预措施更能减少 SCI 相关骨质流失。我们的研究结果表明,LIV 能有效维持局部骨量,这表明这种以物理为基础的干预方法是治疗 SCI 后骨质流失的一种无创、简单、廉价且实用的干预方法。由于联合施用 LIV 和 RANKL 抑制剂比单独施用其中一种干预措施能更好地保护 SCI 后的皮下骨质,因此这项研究为未来临床方案的开发提供了动力,而未来的临床方案将基于非药物疗法(如 LIV)和药物疗法(如 RANKL 抑制剂或其他药物)相结合的潜在更大疗效,以治疗 SCI 后或其他与严重固定相关的骨质疏松症。
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引用次数: 0
Utility of ultrasound imaging in monitoring fracture healing in rat femur: Comparison with other imaging modalities 超声成像在监测大鼠股骨骨折愈合中的作用:与其他成像模式的比较
IF 2.1 Q3 ENDOCRINOLOGY & METABOLISM Pub Date : 2024-09-23 DOI: 10.1016/j.bonr.2024.101807
Satoshi Inoue , Michinori Mori , Masaya Yasui , Miwako Matsuki-Fukushima , Kentaro Yoshimura , Naoko Nonaka

Objective

Fractures are common injuries and various imaging modalities are employed to diagnose and monitor bone union. However, the follow-up of fracture healing using ultrasound imaging (US) remains a topic of debate. In this study, we analyzed of fracture healing process and compared US and radiological analyses with histological analyses to clarify the characteristics and limitations of each modality.

Methods

An osteotomy model was created using the femur of Wistar rats, and US, radiological (radiography and micro-computed tomography (micro-CT)), and histological analyses were performed. Radiological assessments were conducted for the evaluation of calcified tissue. The gap between the bony callus and cartilaginous callus was measured.

Results

US effectively captured changes on the fracture surface, potentially reflecting the early healing processes. Both US and radiographic findings showed strong correlation in terms of the decrease in the bony callus gap. US was unable to distinguish cartilaginous callus from the surrounding soft tissue. During the remodeling stage, micro-CT offered a detailed assessment of the internal fracture surface, whereas US was limited to evaluating the outer bone surface and lacked accuracy in visualizing the entire fracture site. Radiography provided a general overview of the fractures. The decrease in the bony callus gap measured using US correlated with the reduction in cartilaginous callus observed histologically.

Conclusion

This study demonstrated that US could be a valuable tool for evaluating fracture healing. Combining fracture management with US and radiological examinations may provide a more accurate assessment of healing progress.
目的骨折是一种常见的损伤,人们采用各种成像模式来诊断和监测骨结合情况。然而,使用超声成像(US)对骨折愈合进行随访仍是一个争论不休的话题。在这项研究中,我们分析了骨折愈合过程,并将超声成像和放射学分析与组织学分析进行了比较,以明确每种成像方式的特点和局限性。放射学评估用于评价钙化组织。结果 超声波有效捕捉了骨折表面的变化,可能反映了早期愈合过程。就骨胼胝体间隙的缩小而言,超声波和放射学检查结果显示出很强的相关性。US 无法区分软骨胼胝和周围软组织。在重塑阶段,显微 CT 可对骨折内部表面进行详细评估,而 US 只能评估骨外表面,无法准确观察整个骨折部位。X 射线照相可提供骨折的总体情况。通过 US 测量到的骨胼胝间隙的减少与组织学观察到的软骨胼胝的减少相关。将骨折处理与 US 和放射学检查相结合,可以更准确地评估愈合进展。
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引用次数: 0
Association between trabecular bone score, 10-year probability risk for fracture, and vertebral fractures in rheumatoid arthritis 类风湿性关节炎患者骨小梁评分、10 年骨折概率风险与脊椎骨折之间的关系
IF 2.1 Q3 ENDOCRINOLOGY & METABOLISM Pub Date : 2024-09-23 DOI: 10.1016/j.bonr.2024.101806
Houssam Boutaibi, Hamida Azzouzi, Fadoua Chennouf, Linda Ichchou

Objectives

The aim was to assess the association and predictive value of trabecular bone score (TBS), fracture risk assessment tool (FRAX), and TBS-adjusted FRAX with prevalent vertebral fractures (VFs) in patients with rheumatoid arthritis (RA).

Methods

Patients diagnosed with RA were included in this cross-sectional study. Clinical data and laboratory tests were collected on the same day as the dual-energy x-ray absorptiometry (DXA) scan. TBS, bone mineral density (BMD), and vertebral fracture assessment (VFA) were obtained from the DXA scan. We used the FRAX tool to assess the 10-year probability of major osteoporotic fracture (MOF-FRAX) and hip fracture (HF-FRAX) with and without BMD. These parameters were further adjusted for TBS. Patients with prevalent VFs were defined as those with moderate to severe VFs from T4 to L4. VFs presence was used as the binary variable in the logistic regressions and receiving operator characteristics (ROC) curves analysis.

Results

Sixty-nine patients were enrolled, with 55.1 % being postmenopausal. The mean TBS was 1.328 ± 0.104. Osteoporosis according to the WHO criteria was present in 39 patients (56.5 %), and six patients (8.7 %) had VFs with thoracic predominance (66.67 %). Univariate and multivariate logistic regression analyses did not show an association between TBS and vertebral fractures, but FRAX scores indicated such an association. The area under the curve (AUC) with 95 % confidence intervals (CI) for the MOF-FRAX score with BMD, MOF-FRAX score without BMD, TBS-adjusted MOF-FRAX score, and TBS were 0.837 [0.686–0.988], 0.795 [0.629–0.961], 0.778 [0.571–0.984], and 0.515 [0.298–0.731], respectively.

Conclusion

In our RA patients, FRAX scores were associated with vertebral fractures (VFs), while TBS was not. The MOF-FRAX score combined with BMD, showed the best AUC for VFs in this population.
目的 评估类风湿关节炎(RA)患者的骨小梁评分(TBS)、骨折风险评估工具(FRAX)和经 TBS 调整的 FRAX 与流行性脊椎骨折(VFs)的相关性和预测价值。临床数据和实验室检查在双能 X 射线吸收仪(DXA)扫描的同一天收集。通过 DXA 扫描获得 TBS、骨矿物质密度 (BMD) 和椎体骨折评估 (VFA)。我们使用 FRAX 工具来评估有无 BMD 的 10 年重大骨质疏松性骨折(MOF-FRAX)和髋部骨折(HF-FRAX)的概率。这些参数根据 TBS 进行了进一步调整。普遍存在VFs的患者被定义为T4至L4存在中度至重度VFs的患者。在逻辑回归和接受操作者特征(ROC)曲线分析中,VFs 的存在被用作二元变量。平均 TBS 为 1.328 ± 0.104。根据世界卫生组织的标准,39 名患者(56.5%)患有骨质疏松症,6 名患者(8.7%)患有 VF,以胸廓为主(66.67%)。单变量和多变量逻辑回归分析未显示 TBS 与椎体骨折之间存在关联,但 FRAX 评分显示两者之间存在关联。有 BMD 的 MOF-FRAX 评分、无 BMD 的 MOF-FRAX 评分、TBS 调整后的 MOF-FRAX 评分和 TBS 的曲线下面积(AUC)和 95 % 置信区间(CI)分别为 0.837 [0.686-0.988], 0.结论在我们的 RA 患者中,FRAX 评分与椎体骨折(VFs)相关,而 TBS 不相关。在该人群中,MOF-FRAX 评分与 BMD 相结合,显示出最佳的 VFs AUC。
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引用次数: 0
Romosuzumab used to treat a 29-year-old patient with anorexia nervosa related osteoporosis – A case report 罗莫单抗用于治疗一名 29 岁神经性厌食症相关骨质疏松症患者--病例报告
IF 2.1 Q3 ENDOCRINOLOGY & METABOLISM Pub Date : 2024-09-01 DOI: 10.1016/j.bonr.2024.101803
Pashija Demolli, Diana Frey

Summary

Osteoporosis and decreased bone density is a frequent complication of anorexia nervosa (AN). As of yet, there have been no studies of accomplished treatment of AN-related osteoporosis with romosuzumab, a monoclonal antibody to sclerostin. We report the first case of a premenopausal, 29-year old patient in Switzerland with decreased bone density and osteoporotic fractures due to anorexia nervosa, who completed the treatment with romosuzumab. There was a significant increase in bone mineral density (BMD) after 12 months of therapy. No serious side effects were reported. To date, only bisphosphonates, denosumab and teriparatide have been evaluated in treatment of AN-related osteoporosis in adolescents and premenopausal individuals respectively. Our report demonstrates that romosuzumab might be an alternative treatment option in patients with anorexia nervosa who are at high risk for osteoporotic fractures. To assess the efficacy and safety of romosuzumab in individuals with AN further studies are needed.

摘要骨质疏松症和骨密度下降是神经性厌食症(AN)的常见并发症。迄今为止,还没有关于使用罗莫珠单抗(一种硬骨素单克隆抗体)治疗神经性厌食症相关骨质疏松症的研究。我们报告了瑞士第一例因神经性厌食症导致骨密度下降和骨质疏松性骨折的 29 岁绝经前患者,她完成了罗莫珠单抗的治疗。治疗 12 个月后,患者的骨密度(BMD)明显增加。无严重副作用报告。迄今为止,只有双膦酸盐、地诺单抗和特立帕肽分别被评估用于治疗青少年和绝经前人群的神经性厌食症相关骨质疏松症。我们的报告表明,对于有骨质疏松性骨折高风险的神经性厌食症患者来说,罗莫珠单抗可能是一种替代治疗方案。要评估罗莫珠单抗对神经性厌食症患者的疗效和安全性,还需要进一步的研究。
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引用次数: 0
A case report of Tumor-Induced Osteomalacia (TIO) caused by central giant cell granuloma 中心巨细胞肉芽肿引起的肿瘤诱发骨软化症(TIO)病例报告
IF 2.1 Q3 ENDOCRINOLOGY & METABOLISM Pub Date : 2024-09-01 DOI: 10.1016/j.bonr.2024.101804
Sevil Ghaffarzadeh Rad , Amir Bahrami , Jalil Houshyar , Nazila Farrin , Farzad Najafipour , Halimeh Amirazad

Introduction

Tumor-induced osteomalacia (TIO) is a rare paraneoplastic syndrome defined by severe hypophosphatemia, bone loss, fractures, and muscle weakness. Identifying of the tumor site is often difficult. The primary treatment for Tumor-induced osteomalacia (TIO) is currently surgical resection. Removing the primary tumor is the most definitive treatment for this disease.

Methods

Here we describe the case of a 32-year-old man who exhibited sever muscle weakness and pain that had continued for three years. The patient has three sisters and one brother, all of whom are completely healthy and free of bone and muscle problems.

Laboratory data indicate low serum phosphorus, normal serum and urine calcium level, besides raised alkaline phosphatase level. Due to elevated phosphorus levels in the urine and the lack of an alternative source for phosphorus excretion, along with the absence of short stature, bone deformities, and a negative family history that might suggest the potential for Tumor-induced osteomalacia (TIO), an octreotide scan was performed to the localized the tumor site. The scan, corroborated by CT and MRI scans, displayed absorption in the right maxillary sinus. Surgical excision of the lesion confirmed it to be a central giant cell granuloma.

Results

Following surgery and without receiving any other treatment, the patient's phosphorus levels and clinical condition improved compared to before the surgical treatment. Subsequently, the symptoms of muscle weakness and skeletal pain significantly diminished, and the patient regained the ability to move.

Conclusion

Tumor enucleation was conducted, and the pathological examination of the maxillary sinus lesion unveiled a central Giant cell granuloma. The patient had clinical and laboratory improvement after surgery. This finding confirmed our diagnosis of a paraneoplastic hypophosphatemia associated with a giant cell granuloma.

导言肿瘤诱发骨软化症(TIO)是一种罕见的副肿瘤综合征,表现为严重的低磷血症、骨质流失、骨折和肌无力。通常很难确定肿瘤部位。目前,治疗肿瘤诱发骨软化症(TIO)的主要方法是手术切除。我们在此描述了一名 32 岁男性的病例,他表现出严重的肌无力和疼痛,并已持续了三年。患者有三个姐妹和一个兄弟,他们都完全健康,没有骨骼和肌肉问题。实验室数据显示,患者血清磷含量低,血清和尿钙水平正常,碱性磷酸酶水平升高。由于尿液中磷含量升高,且缺乏磷排泄的替代来源,加上没有身材矮小、骨骼畸形等症状,以及家族病史阴性,这可能提示存在肿瘤诱发骨质疏松症(TIO)的可能性,因此对患者进行了奥曲肽扫描,以确定肿瘤部位。经 CT 和 MRI 扫描证实,扫描结果显示右侧上颌窦有吸收。手术切除后,患者的血磷水平和临床状况与手术治疗前相比均有所改善。随后,肌无力和骨骼疼痛症状明显减轻,患者恢复了活动能力。结论进行了肿瘤去核手术,上颌窦病变的病理检查显示为中央巨细胞肉芽肿。术后患者的临床和化验指标均有所改善。这一结果证实了我们的诊断:与巨细胞肉芽肿相关的副肿瘤性低磷血症。
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引用次数: 0
Classification of AO/OTA 31A/B femur fractures in X-ray images using YOLOv8 and advanced data augmentation techniques 利用 YOLOv8 和先进的数据增强技术对 X 射线图像中的 AO/OTA 31A/B 股骨骨折进行分类
IF 2.1 Q3 ENDOCRINOLOGY & METABOLISM Pub Date : 2024-09-01 DOI: 10.1016/j.bonr.2024.101801
Giorgia Marullo , Luca Ulrich , Francesca Giada Antonaci , Andrea Audisio , Alessandro Aprato , Alessandro Massè , Enrico Vezzetti

Femur fractures are a significant worldwide public health concern that affects patients as well as their families because of their high frequency, morbidity, and mortality. When employing computer-aided diagnostic (CAD) technologies, promising results have been shown in the efficiency and accuracy of fracture classification, particularly with the growing use of Deep Learning (DL) approaches. Nevertheless, the complexity is further increased by the need to collect enough input data to train these algorithms and the challenge of interpreting the findings. By improving on the results of the most recent deep learning-based Arbeitsgemeinschaft für Osteosynthesefragen and Orthopaedic Trauma Association (AO/OTA) system classification of femur fractures, this study intends to support physicians in making correct and timely decisions regarding patient care. A state-of-the-art architecture, YOLOv8, was used and refined while paying close attention to the interpretability of the model. Furthermore, data augmentation techniques were involved during preprocessing, increasing the dataset samples through image processing alterations. The fine-tuned YOLOv8 model achieved remarkable results, with 0.9 accuracy, 0.85 precision, 0.85 recall, and 0.85 F1-score, computed by averaging the values among all the individual classes for each metric. This study shows the proposed architecture's effectiveness in enhancing the AO/OTA system's classification of femur fractures, assisting physicians in making prompt and accurate diagnoses.

股骨骨折是全球关注的重大公共卫生问题,因其高频率、高发病率和高死亡率而影响着患者及其家庭。在采用计算机辅助诊断(CAD)技术时,骨折分类的效率和准确性方面已经取得了可喜的成果,特别是随着深度学习(DL)方法的使用日益广泛。然而,由于需要收集足够的输入数据来训练这些算法,以及解释研究结果所面临的挑战,其复杂性进一步增加。本研究通过改进基于深度学习的Arbeitsgemeinschaft für Osteosynthesefragen and Orthopaedic Trauma Association(AO/OTA)系统对股骨骨折的最新分类结果,旨在支持医生就患者护理做出正确、及时的决策。研究采用了最先进的架构 YOLOv8,并对其进行了改进,同时密切关注模型的可解释性。此外,在预处理过程中还采用了数据增强技术,通过图像处理改变来增加数据集样本。经过微调的 YOLOv8 模型取得了显著的成果,准确度为 0.9,精确度为 0.85,召回率为 0.85,F1-score 为 0.85(通过计算所有类别中每个指标的平均值得出)。这项研究表明,所提出的架构能有效提高 AO/OTA 系统对股骨骨折的分类能力,帮助医生做出及时准确的诊断。
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引用次数: 0
Delineating the relationship between circulating osteoprotegerin and bone health in women with a pathogenic variant in BRCA1: A cross-sectional analysis 划定 BRCA1 致病变异妇女体内循环骨保护素与骨骼健康之间的关系:横断面分析
IF 2.1 Q3 ENDOCRINOLOGY & METABOLISM Pub Date : 2024-09-01 DOI: 10.1016/j.bonr.2024.101802
Aghaghia Mokhber , Elizabeth Hall , Aleksandra Uzelac , Leonardo Salmena , Angela Cheung , Jan Lubinski , Steven A. Narod , Joanne Kotsopoulos

Purpose

Osteoprotegerin (OPG) plays an important role in the inhibition of osteoclast formation and bone resorption. Studies have reported lower OPG levels among women with a pathogenic variant (mutation) in the BRCA1 gene, and thus, may be at greater risk for skeletal bone loss. Thus, we investigated the association between circulating OPG and two validated markers of bone health: 1) bone fracture risk score (FRAX) and 2) bone mineral density (BMD), among BRCA mutation carriers.

Methods

Women with a blood sample and clinical data were included in this analysis. An enzyme-linked immunosorbent assay (ELISA) was used to quantify serum OPG (pg/mL) and the 10-year risk of major osteoporotic fracture (FRAXmajor) and hip fracture (FRAXhip) (%) was estimated using a web-based algorithm. For a subset of women, lumbar spine BMD was previously assessed by dual x-ray absorptiometry (DXA)(T-score). A Mann–Whitney U test was used to evaluate the association between OPG and FRAX score, while linear regression was used to assess the association of OPG and BMD.

Results

Among 701 women with a BRCA1 mutation, there was a significant (and unexpected) positive association between OPG levels and FRAX score (FRAXmajor: 2.12 (low OPG) vs. 2.53 (high OPG) P < 0.0001; FRAXhip: 0.27 (low OPG) vs. 0.44 (high OPG) P < 0.0001). In a subset with BMD measurement (n = 50), low serum OPG was associated with a significantly lower BMD T-score (−1.069 vs. -0.318; P = 0.04).

Conclusion

Our findings suggest that women with inherently lower OPG may be at risk of lower BMD, the gold standard marker of bone disease. Due to the young age of our cohort, on-going studies are warranted to re-evaluate the association between OPG and FRAX in BRCA mutation carriers.

目的骨保护素(OPG)在抑制破骨细胞形成和骨吸收方面发挥着重要作用。有研究报告称,在 BRCA1 基因有致病变异(突变)的女性中,OPG 水平较低,因此可能面临更大的骨骼骨质流失风险。因此,我们研究了循环 OPG 与骨骼健康的两个有效指标之间的关联:方法本分析纳入了具有血液样本和临床数据的女性。使用酶联免疫吸附测定法(ELISA)对血清 OPG(pg/mL)进行定量,并使用基于网络的算法估算 10 年重大骨质疏松性骨折(FRAXmajor)和髋部骨折(FRAXhip)的风险(%)。对于一部分女性,之前已通过双 X 射线吸收测量法(DXA)评估了腰椎 BMD(T-score)。结果在 701 名 BRCA1 基因突变的女性中,OPG 水平与 FRAX 评分之间存在显著的(意外的)正相关(FRAXmajor:2.12(低 OPG) vs. 2.53(高 OPG)P < 0.0001;FRAXhip:0.27(低 OPG) vs. 2.53(高 OPG)P < 0.0001):0.27(低 OPG)vs. 0.44(高 OPG)P < 0.0001)。我们的研究结果表明,OPG 低的女性可能面临骨密度降低的风险,而骨密度是骨病的金标准指标。由于我们的队列年龄较小,因此有必要继续进行研究,以重新评估 BRCA 基因突变携带者的 OPG 和 FRAX 之间的关联。
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引用次数: 0
A staged approach using machine learning and uncertainty quantification to predict the risk of hip fracture 利用机器学习和不确定性量化的分阶段方法预测髋部骨折风险
IF 2.1 Q3 ENDOCRINOLOGY & METABOLISM Pub Date : 2024-09-01 DOI: 10.1016/j.bonr.2024.101805
Anjum Shaik , Kristoffer Larsen , Nancy E. Lane , Chen Zhao , Kuan-Jui Su , Joyce H. Keyak , Qing Tian , Qiuying Sha , Hui Shen , Hong-Wen Deng , Weihua Zhou

Hip fractures present a significant healthcare challenge, especially within aging populations, where they are often caused by falls. These fractures lead to substantial morbidity and mortality, emphasizing the need for timely surgical intervention. Despite advancements in medical care, hip fractures impose a significant burden on individuals and healthcare systems. This paper focuses on the prediction of hip fracture risk in older and middle-aged adults, where falls and compromised bone quality are predominant factors.

The study cohort included 547 patients, with 94 experiencing hip fracture. To assess the risk of hip fracture, clinical variables and clinical variables combined with hip DXA imaging features were evaluated as predictors, followed by a novel staged approach. Hip DXA imaging features included those extracted by convolutional neural networks (CNNs), shape measurements, and texture features. Two ensemble machine learning models were evaluated: Ensemble 1 (clinical variables only) and Ensemble 2 (clinical variables and imaging features) using the logistic regression as the base classifier and bootstrapping for ensemble learning. The staged approach was developed using uncertainty quantification from Ensemble 1 which was used to decide if hip DXA imaging features were necessary to improve prediction for each subject. Ensemble 2 exhibited the highest performance, achieving an Area Under the Curve (AUC) of 0.95, an accuracy of 0.92, a sensitivity of 0.81, and a specificity of 0.94. The staged model also performed well, with an AUC of 0.85, an accuracy of 0.86, a sensitivity of 0.56, and a specificity of 0.92, outperforming Ensemble 1, which had an AUC of 0.55, an accuracy of 0.73, a sensitivity of 0.20, and a specificity of 0.83. Furthermore, the staged model suggested that 54.49 % of patients did not require DXA scanning, effectively balancing accuracy and specificity, while offering a robust solution when DXA data acquisition is not feasible. Statistical tests confirmed significant differences between the models, highlighting the advantages of advanced modeling strategies.

Our staged approach offers a cost-effective holistic view of patient health. It can identify individuals at risk of hip fracture with a high accuracy while reducing unnecessary DXA scans. This approach has great promise to guide the need for interventions to prevent hip fracture while reducing diagnostic cost and exposure to radiation.

髋部骨折是一项重大的医疗挑战,尤其是在老龄人口中,髋部骨折通常是由跌倒引起的。这些骨折会导致严重的发病率和死亡率,因此需要及时进行手术治疗。尽管医疗保健取得了进步,但髋部骨折仍给个人和医疗保健系统带来了沉重负担。本文的重点是预测中老年人髋部骨折的风险,因为跌倒和骨质受损是中老年人髋部骨折的主要因素。为了评估髋部骨折风险,研究人员采用了一种新颖的分阶段方法,对临床变量和临床变量结合髋部 DXA 成像特征进行了预测评估。髋关节 DXA 成像特征包括卷积神经网络 (CNN) 提取的特征、形状测量和纹理特征。对两种机器学习模型进行了评估:集合 1(仅临床变量)和集合 2(临床变量和成像特征)使用逻辑回归作为基础分类器,并对集合学习进行引导。分阶段方法是利用集合 1 的不确定性量化来开发的,用于决定是否需要髋关节 DXA 成像特征来改进对每个受试者的预测。组合 2 的性能最高,曲线下面积(AUC)达到 0.95,准确率为 0.92,灵敏度为 0.81,特异性为 0.94。分阶段模型也表现出色,AUC 为 0.85,准确度为 0.86,灵敏度为 0.56,特异度为 0.92,优于 AUC 为 0.55,准确度为 0.73,灵敏度为 0.20,特异度为 0.83 的组合 1。此外,分阶段模型还表明 54.49% 的患者不需要进行 DXA 扫描,有效地平衡了准确性和特异性,同时在无法获取 DXA 数据时提供了一个稳健的解决方案。统计测试证实了模型之间的显著差异,凸显了先进建模策略的优势。我们的分阶段方法提供了具有成本效益的患者整体健康视图,它能高精度地识别有髋部骨折风险的个体,同时减少不必要的 DXA 扫描。这种方法有望在降低诊断成本和辐射暴露的同时,指导预防髋部骨折的干预需求。
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引用次数: 0
Evaluation of the age-specific relationship between PTH and vitamin D metabolites 评估 PTH 与维生素 D 代谢物之间的特定年龄关系
IF 2.1 Q3 ENDOCRINOLOGY & METABOLISM Pub Date : 2024-08-26 DOI: 10.1016/j.bonr.2024.101800
Alexandra Povaliaeva , Artem Zhukov , Viktor Bogdanov , Axenia Bondarenko , Oleg Senko , Anna Kuznetsova , Maxim Kodryan , Vitaliy Ioutsi , Ekaterina Pigarova , Liudmila Rozhinskaya , Natalia Mokrysheva

A commonly used method for determining vitamin D sufficiency is the suppression of excess PTH secretion. Conventionally, the main circulating vitamin D metabolite 25(OH)D is used for this assessment, however, the cut-off data for this parameter vary widely in the literature. The role of other metabolites as markers of vitamin D status is actively debated. The aim of our study was to assess the relationship between PTH, age and parameters characterizing vitamin D status, both “classical” – 25(OH)D3, and “non-classical” – 24,25(OH)2D3 and 25(OH)D3/24,25(OH)2D3 (vitamin D metabolite ratio, VMR). This prospective non-controlled cohort study included 162 apparently healthy Caucasian adult volunteers. When PTH was binarized according to the median value, at VMR < 14.9, 25(OH)D3 > 9.7 ng/mL and 24,25(OH)2D3 > 0.64 ng/mL there was a pronounced relationship between PTH and age (p = 0.001, p = 0.023 and p = 0.0134 respectively), with the prevalence of higher PTH levels in older individuals and vice versa. Moreover, at an age of <40.3 years, there was a pronounced relationship between PTH and VMR (p < 0.001), and similarly at an age of <54.5 years, there was a pronounced relationship between PTH and 25(OH)D3 (p = 0.002) as well as between PTH and 24,25(OH)2D3 (p = 0.0038): in younger people, higher PTH values prevailed only in the range of vitamin D insufficiency, while in the older age group this relationship was not demonstrated and PTH values were in general above the median. VMR controlled the correlation between PTH and age more strongly than metabolites 25(OH)D3 and 24,25(OH)2D3 (p = 0.0012 vs. p > 0.05 and p = 0.0385 respectively). The optimal threshold was found equal to 11.7 for VMR such that the relationship between PTH and age in the subset of participants with VMR < 11.7 was characterized by a correlation coefficient of ρ = 0.68 (p < 0.001), while the cohort with VMR > 11.7 was characterized by a very weak correlation coefficient of ρ = 0.12 (p = 0.218), which is non-significant. In summary, our findings suggest that the relationship between PTH and vitamin D is age-dependent, with a greater susceptibility to elevated PTH among older individuals even with preserved renal function, likely due to the resistance to vitamin D function. We propose VMR can be considered as a potential marker of vitamin D status. These findings require confirmation in larger population-based studies.

确定维生素 D 是否充足的常用方法是抑制过多的 PTH 分泌。传统上,主要的循环维生素 D 代谢物 25(OH)D 被用于这一评估,但文献中该参数的临界数据差异很大。关于其他代谢物作为维生素 D 状态标志物的作用,目前还存在激烈的争论。我们的研究旨在评估 PTH、年龄和表征维生素 D 状态的参数之间的关系,包括 "经典"--25(OH)D3 和 "非经典"--24,25(OH)2D3 和 25(OH)D3/24,25(OH)2D3(维生素 D 代谢物比值,VMR)。这项前瞻性非对照队列研究包括 162 名表面健康的高加索成年志愿者。当根据中值对 PTH 进行二值化处理时,VMR 为 14.9,25(OH)D3 为 9.7 纳克/毫升,24,25(OH)2D3 为 0.64 纳克/毫升,PTH 与年龄之间存在明显的关系(分别为 p = 0.001、p = 0.023 和 p = 0.0134),年龄越大,PTH 水平越高,反之亦然。此外,在年龄为 40.3 岁时,PTH 与 VMR 之间存在明显的关系(p = 0.001);同样,在年龄为 54.5 岁时,PTH 与 25(OH)D3 之间存在明显的关系(p = 0.002)以及 PTH 和 24,25(OH)2D3 之间的关系(p = 0.0038):在年轻人中,只有在维生素 D 不足的范围内才会出现较高的 PTH 值,而在老年人群中,这种关系并不明显,PTH 值一般都高于中位数。VMR 比代谢物 25(OH)D3 和 24,25(OH)2D3(分别为 p = 0.0012 vs. p > 0.05 和 p = 0.0385)更能控制 PTH 与年龄之间的相关性。VMR 的最佳阈值为 11.7,因此,在 VMR 为 11.7 的参与者中,PTH 与年龄之间的相关系数为 ρ = 0.68(p = 0.001),而 VMR 为 11.7 的参与者中,PTH 与年龄之间的相关系数为 ρ = 0.12(p = 0.218),相关性很弱,不显著。总之,我们的研究结果表明,PTH 和维生素 D 之间的关系与年龄有关,即使肾功能保持良好,老年人也更容易出现 PTH 升高,这可能是由于维生素 D 功能的阻力所致。我们建议将 VMR 视为维生素 D 状态的潜在标志物。这些发现需要在更大规模的人群研究中得到证实。
{"title":"Evaluation of the age-specific relationship between PTH and vitamin D metabolites","authors":"Alexandra Povaliaeva ,&nbsp;Artem Zhukov ,&nbsp;Viktor Bogdanov ,&nbsp;Axenia Bondarenko ,&nbsp;Oleg Senko ,&nbsp;Anna Kuznetsova ,&nbsp;Maxim Kodryan ,&nbsp;Vitaliy Ioutsi ,&nbsp;Ekaterina Pigarova ,&nbsp;Liudmila Rozhinskaya ,&nbsp;Natalia Mokrysheva","doi":"10.1016/j.bonr.2024.101800","DOIUrl":"10.1016/j.bonr.2024.101800","url":null,"abstract":"<div><p>A commonly used method for determining vitamin D sufficiency is the suppression of excess PTH secretion. Conventionally, the main circulating vitamin D metabolite 25(OH)D is used for this assessment, however, the cut-off data for this parameter vary widely in the literature. The role of other metabolites as markers of vitamin D status is actively debated. The aim of our study was to assess the relationship between PTH, age and parameters characterizing vitamin D status, both “classical” – 25(OH)D<sub>3</sub>, and “non-classical” – 24,25(OH)<sub>2</sub>D<sub>3</sub> and 25(OH)D<sub>3</sub>/24,25(OH)<sub>2</sub>D<sub>3</sub> (vitamin D metabolite ratio, VMR). This prospective non-controlled cohort study included 162 apparently healthy Caucasian adult volunteers. When PTH was binarized according to the median value, at VMR &lt; 14.9, 25(OH)D<sub>3</sub> &gt; 9.7 ng/mL and 24,25(OH)<sub>2</sub>D<sub>3</sub> &gt; 0.64 ng/mL there was a pronounced relationship between PTH and age (<em>p</em> = 0.001, <em>p</em> = 0.023 and <em>p</em> = 0.0134 respectively), with the prevalence of higher PTH levels in older individuals and vice versa. Moreover, at an age of &lt;40.3 years, there was a pronounced relationship between PTH and VMR (<em>p</em> &lt; 0.001), and similarly at an age of &lt;54.5 years, there was a pronounced relationship between PTH and 25(OH)D<sub>3</sub> (<em>p</em> = 0.002) as well as between PTH and 24,25(OH)<sub>2</sub>D<sub>3</sub> (<em>p</em> = 0.0038): in younger people, higher PTH values prevailed only in the range of vitamin D insufficiency, while in the older age group this relationship was not demonstrated and PTH values were in general above the median. VMR controlled the correlation between PTH and age more strongly than metabolites 25(OH)D<sub>3</sub> and 24,25(OH)<sub>2</sub>D<sub>3</sub> (<em>p</em> = 0.0012 vs. <em>p</em> &gt; 0.05 and <em>p</em> = 0.0385 respectively). The optimal threshold was found equal to 11.7 for VMR such that the relationship between PTH and age in the subset of participants with VMR &lt; 11.7 was characterized by a correlation coefficient of ρ = 0.68 (<em>p</em> &lt; 0.001), while the cohort with VMR &gt; 11.7 was characterized by a very weak correlation coefficient of ρ = 0.12 (<em>p</em> = 0.218), which is non-significant. In summary, our findings suggest that the relationship between PTH and vitamin D is age-dependent, with a greater susceptibility to elevated PTH among older individuals even with preserved renal function, likely due to the resistance to vitamin D function. We propose VMR can be considered as a potential marker of vitamin D status. These findings require confirmation in larger population-based studies.</p></div>","PeriodicalId":9043,"journal":{"name":"Bone Reports","volume":"22 ","pages":"Article 101800"},"PeriodicalIF":2.1,"publicationDate":"2024-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2352187224000676/pdfft?md5=b737b6cc70698859989936f8ef803f61&pid=1-s2.0-S2352187224000676-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142088393","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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