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Global 'Conditional' Assurance of Romosozumab Safety: International Consensus on the Uniqueness of Adverse Cardiovascular Events in Japan. 全球 "有条件 "保证 Romosozumab 的安全性:关于日本心血管不良事件独特性的国际共识》。
IF 3.3 3区 医学 Q2 ENDOCRINOLOGY & METABOLISM Pub Date : 2024-10-01 Epub Date: 2024-07-30 DOI: 10.1007/s00223-024-01267-4
Hiroshi Kawaguchi
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引用次数: 0
Muscle Performance as a Predictor of Bone Health: Among Community-Dwelling Postmenopausal Japanese Women from Setagaya-Aoba Study. 肌肉性能是骨骼健康的预测指标:来自世田谷青叶研究的社区绝经后日本妇女。
IF 3.3 3区 医学 Q2 ENDOCRINOLOGY & METABOLISM Pub Date : 2024-10-01 Epub Date: 2024-08-06 DOI: 10.1007/s00223-024-01269-2
Takahisa Ohta, Hiroyuki Sasai, Naoki Kikuchi, Koichi Nakazato, Takanobu Okamoto

Osteoporosis is a significant health concern for postmenopausal women, necessitating efficient screening methods for bone health. This study explores the potential of muscle function, assessed through the 30-s chair stand test (CS-30), as an indicator for low bone stiffness in this demographic, aiming to establish a practical threshold for large-scale fitness surveillance without the need for specialized tools. We analyzed data from 1055 community-dwelling postmenopausal Japanese women, aged 41-89 years, collected between 2016 and 2019. Participants underwent CS-30 to evaluate muscle function alongside quantitative ultrasound (QUS) measurements to assess bone stiffness. The cohort was divided into two groups for the development and validation of a cutoff point for low bone stiffness, defined as a QUS speed of sound less than 1487.3 m/s. The CS-30 cutoff was determined using receiver operating characteristic (ROC) curve analysis and validated through logistic regression, accounting for age, body mass index, and smoking status. Among 577 postmenopausal women, 16.0% exhibited low bone stiffness. In the development group (n = 382), ROC analysis identified a CS-30 cutoff of 25 repetitions for detecting low bone stiffness, with an area under the curve of 0.744 (P < 0.001). In the validation group (n = 195), participants performing ≥ 25 repetitions had a higher risk of low bone stiffness compared to those performing ≤ 24 repetitions. The CS-30 test is an effective preliminary screening tool for identifying postmenopausal women at risk of low bone stiffness, with a threshold of 25 repetitions. This method could facilitate early detection of individuals at higher osteoporosis risk, promoting timely intervention.

骨质疏松症是绝经后妇女的重大健康问题,因此需要有效的骨骼健康筛查方法。本研究探讨了通过 30 秒椅子站立测试(CS-30)评估肌肉功能作为该人群低骨硬度指标的潜力,旨在为无需专业工具的大规模体能监测建立一个实用的阈值。我们分析了 2016 年至 2019 年间收集的 1055 名居住在社区的绝经后日本女性的数据,她们的年龄在 41-89 岁之间。参与者在接受 CS-30 评估肌肉功能的同时,还接受了定量超声波 (QUS) 测量以评估骨硬度。参与者被分为两组,用于开发和验证低骨硬度的临界点,即 QUS 音速小于 1487.3 m/s。CS-30 临界点是通过接收器操作特征(ROC)曲线分析确定的,并通过逻辑回归进行了验证,同时考虑了年龄、体重指数和吸烟状况。在 577 名绝经后妇女中,有 16.0% 的人表现出低骨硬度。在开发组(n = 382)中,ROC 分析确定 CS-30 检测低骨硬度的临界值为重复 25 次,曲线下面积为 0.744(P<0.05)。
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引用次数: 0
Developing Cut-off Values for Low and Very Low Bone Mineral Density at the Thoracic Spine Using Quantitative Computed Tomography. 利用定量计算机断层扫描为胸椎的低骨矿密度和极低骨矿密度制定临界值。
IF 3.3 3区 医学 Q2 ENDOCRINOLOGY & METABOLISM Pub Date : 2024-10-01 Epub Date: 2024-08-16 DOI: 10.1007/s00223-024-01268-3
Andia Cheneymann, Josephine Therkildsen, Laust Dupont Rasmussen, Jesper Thygesen, Christin Isaksen, Ellen-Margrethe Hauge, Simon Winther, Morten Böttcher

Osteoporosis is under-diagnosed while detectable by measuring bone mineral density (BMD) using quantitative computer tomography (QCT). Opportunistic screening for low BMD has previously been suggested using lumbar QCT. However, thoracic QCT also possesses this potential to develop upper and lower cut-off values for low thoracic BMD, corresponding to the current cut-offs for lumbar BMD. In participants referred with chest pain, lumbar and thoracic BMD were measured using non-contrast lumbar- and cardiac CT scans. Lumbar BMD cut-off values for very low (< 80 mg/cm3), low (80-120 mg/cm3), and normal BMD (> 120 mg/cm3) were used to assess the corresponding thoracic values. A linear regression enabled identification of new diagnostic thoracic BMD cut-off values. The 177 participants (mean age 61 [range 31-74] years, 51% women) had a lumbar BMD of 121.6 mg/cm3 (95% CI 115.9-127.3) and a thoracic BMD of 137.0 mg/cm3 (95% CI: 131.5-142.5), p < 0.001. Categorization of lumbar BMD revealed 14%, 35%, and 45% in each BMD category. When applied for the thoracic BMD measurements, 25% of participants were reclassified into a lower group. Linear regression predicted a relationship of Thoracic BMD = 0.85 * Lumbar BMD + 33.5, yielding adjusted thoracic cut-off values of < 102 and > 136 mg/cm3. Significant differences in BMD between lumbar and thoracic regions were found, but a linear relationship enabled the development of thoracic upper and lower cut-off values for low BMD in the thoracic spine. As Thoracic CT scans are frequent, these findings will strengthen the utilization of CT images for opportunistic detection of osteoporosis.

骨质疏松症的诊断率很低,但通过使用计算机断层扫描定量法(QCT)测量骨矿密度(BMD)却能检测出来。以前曾有人建议使用腰部 QCT 对低 BMD 进行机会性筛查。不过,胸腔 QCT 也具有这种潜力,可为胸腔低 BMD 设定上限和下限临界值,与当前的腰椎 BMD 临界值相对应。对于因胸痛而转诊的患者,使用非对比腰椎和心脏 CT 扫描测量腰椎和胸椎 BMD。腰椎 BMD 临界值为极低 (3)、低 (80-120 mg/cm3) 和正常 BMD (>120 mg/cm3),用于评估相应的胸椎值。通过线性回归,确定了新的胸廓 BMD 诊断临界值。177 名参与者(平均年龄 61 [31-74]岁,51% 为女性)的腰椎 BMD 为 121.6 mg/cm3(95% CI 115.9-127.3),胸椎 BMD 为 137.0 mg/cm3(95% CI:131.5-142.5),P 为 136 mg/cm3。腰椎和胸椎区域之间的 BMD 存在显著差异,但由于存在线性关系,因此可为胸椎低 BMD 设定胸椎上下限临界值。由于胸椎 CT 扫描很频繁,这些发现将加强对 CT 图像的利用,以适时检测骨质疏松症。
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引用次数: 0
The Relationship between Sclerostin and Kidney Transplantation Mineral Bone Disorders: A Molecule of Controversies. 硬骨蛋白与肾移植矿物质骨病的关系:充满争议的分子。
IF 3.3 3区 医学 Q2 ENDOCRINOLOGY & METABOLISM Pub Date : 2024-10-01 Epub Date: 2024-07-30 DOI: 10.1007/s00223-024-01261-w
Baris Afsar, Rengin Elsurer Afsar, Yasar Caliskan, Krista L Lentine

Kidney transplantation is the most effective treatment option for most patients with end-stage kidney disease due to reduced mortality, decreased cardiovascular events and increased quality of life compared to patients treated with dialysis. However, kidney transplantation is not devoid of both acute and chronic complications including mineral bone disorders (MBD) which are already present in patients with chronic kidney disease (CKD) before kidney transplantation. The natural history of MBD after kidney transplantation is variable and new markers are needed to define MBD after kidney transplantation. One of these promising molecules is sclerostin. The main action of sclerostin is to inhibit bone formation and mineralization by blocking osteoblast differentiation and function. In kidney transplant recipients (KTRs), various studies have shown that sclerostin is associated with graft function, bone parameters, vascular calcification, and arterial stiffness although non-uniformly. Furthermore, data for inhibition of sclerostin with monoclonal antibody romosozumab for treatment of osteoporosis is available for general population but not in KTRs which osteoporosis is highly prevalent. In this narrative review, we have summarized the studies investigating the change of sclerostin before and after kidney transplantation, the relationship between sclerostin and laboratory parameters, bone metabolism and vascular calcification in the context of kidney transplantation. We also pointed out the uncertainties, explained the causes of divergent findings and suggest further potential study topics regarding sclerostin in kidney transplantation.

与接受透析治疗的患者相比,肾移植可降低死亡率、减少心血管事件并提高生活质量,因此是大多数终末期肾病患者最有效的治疗选择。然而,肾移植并非没有急性和慢性并发症,其中包括肾移植前慢性肾病(CKD)患者已经存在的矿物质骨病(MBD)。肾移植后矿物质骨病的自然史是多变的,因此需要新的标志物来确定肾移植后的矿物质骨病。硬骨蛋白是其中一种很有前景的分子。硬骨素的主要作用是通过阻断成骨细胞的分化和功能来抑制骨形成和矿化。在肾移植受者(KTR)中,各种研究表明,硬骨素与移植物功能、骨参数、血管钙化和动脉僵化有关,但并不一致。此外,使用单克隆抗体罗莫索单抗抑制硬骨蛋白以治疗骨质疏松症的数据适用于普通人群,但不适用于骨质疏松症高发的 KTR。在这篇综述中,我们总结了有关肾移植前后硬骨素变化、硬骨素与实验室指标的关系、肾移植背景下的骨代谢和血管钙化的研究。我们还指出了其中的不确定性,解释了研究结果存在分歧的原因,并就肾移植中硬骨素的潜在研究课题提出了建议。
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引用次数: 0
3D U-Net Neural Network Architecture-Assisted LDCT to Acquire Vertebral Morphology Parameters: A Vertebral Morphology Comprehensive Analysis in a Chinese Population. 三维 U-Net 神经网络架构辅助 LDCT 获取椎体形态参数:中国人群椎体形态综合分析》。
IF 3.3 3区 医学 Q2 ENDOCRINOLOGY & METABOLISM Pub Date : 2024-10-01 Epub Date: 2024-07-17 DOI: 10.1007/s00223-024-01255-8
Duoshan Ma, Yan Wang, Xinxin Zhang, Danyang Su, Mengze Ma, Baoxin Qian, Xiaopeng Yang, Jianbo Gao, Yan Wu

To evaluate the feasibility of acquiring vertebral height from chest low-dose computed tomography (LDCT) images using an artificial intelligence (AI) system based on 3D U-Net vertebral segmentation technology and the correlation and features of vertebral morphology with sex and age of the Chinese population. Patients who underwent chest LDCT between September 2020 and April 2023 were enrolled. The Altman and Pearson's correlation analyses were used to compare the correlation and consistency between the AI software and manual measurement of vertebral height. The anterior height (Ha), middle height (Hm), posterior height (Hp), and vertebral height ratios (VHRs) (Ha/Hp and Hm/Hp) were measured from T1 to L2 using an AI system. The VHR is the ratio of Ha to Hp or the ratio of Hm to Hp of the vertebrae, which can reflect the shape of the anterior wedge and biconcave vertebrae. Changes in these parameters, particularly the VHR, were analysed at different vertebral levels in different age and sex groups. The results of the AI methods were highly consistent and correlated with manual measurements. The Pearson's correlation coefficients were 0.855, 0.919, and 0.846, respectively. The trend of VHRs showed troughs at T7 and T11 and a peak at T9; however, Hm/Hp showed slight fluctuations. Regarding the VHR, significant sex differences were found at L1 and L2 in all age bands. This innovative study focuses on vertebral morphology for opportunistic analysis in the mainland Chinese population and the distribution tendency of vertebral morphology with ageing using a chest LDCT aided by an AI system based on 3D U-Net vertebral segmentation technology. The AI system demonstrates the potential to automatically perform opportunistic vertebral morphology analyses using LDCT scans obtained during lung cancer screening. We advocate the use of age-, sex-, and vertebral level-specific criteria for the morphometric evaluation of vertebral osteoporotic fractures for a more accurate diagnosis of vertebral fractures and spinal pathologies.

目的 评估利用基于三维 U-Net 椎体分割技术的人工智能(AI)系统从胸部低剂量计算机断层扫描(LDCT)图像中获取椎体高度的可行性,以及中国人群椎体形态与性别和年龄的相关性和特征。研究对象为 2020 年 9 月至 2023 年 4 月期间接受胸部 LDCT 检查的患者。采用 Altman 和 Pearson 相关性分析比较人工智能软件和人工测量椎体高度的相关性和一致性。使用人工智能系统测量了从 T1 到 L2 的椎体前高(Ha)、椎体中高(Hm)、椎体后高(Hp)和椎体高度比(VHRs)(Ha/Hp 和 Hm/Hp)。VHR 是椎体 Ha 与 Hp 的比值或 Hm 与 Hp 的比值,可以反映椎体前楔和双凹的形状。这些参数的变化,尤其是 VHR 的变化,在不同年龄和性别组的不同椎体水平上进行了分析。人工智能方法的结果与人工测量结果高度一致和相关。皮尔逊相关系数分别为 0.855、0.919 和 0.846。VHR 的变化趋势在 T7 和 T11 出现低谷,在 T9 出现高峰;但 Hm/Hp 则略有波动。关于 VHR,在所有年龄段的 L1 和 L2 发现了明显的性别差异。这项创新性研究利用胸部 LDCT,在基于三维 U-Net 椎体分割技术的人工智能系统的辅助下,重点研究了中国大陆人群中用于机会分析的椎体形态,以及椎体形态随年龄增长的分布趋势。该人工智能系统展示了利用肺癌筛查中获得的 LDCT 扫描自动执行机会性椎体形态分析的潜力。我们提倡使用年龄、性别和椎体水平特异性标准对椎体骨质疏松性骨折进行形态学评估,以便更准确地诊断椎体骨折和脊柱病变。
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引用次数: 0
Association Between Dietary Acid Load and Grip Strength in Adults 50 Years and Older: A Cross-Sectional Study. 50 岁及以上成年人膳食酸负荷与握力之间的关系:一项横断面研究
IF 3.3 3区 医学 Q2 ENDOCRINOLOGY & METABOLISM Pub Date : 2024-10-01 Epub Date: 2024-07-24 DOI: 10.1007/s00223-024-01258-5
Elsa M Konieczynski, Lisa Ceglia, Elise Reitshamer, Bess Dawson-Hughes

Minimal data exist on whether the acid-base balance of the diet is linked to muscle strength. The aim of this study was to determine if dietary acid load is associated with grip strength in a nationally representative sample of middle- to older-age adults. We examined the cross-sectional association of grip strength with dietary acid load quantified through potential renal acid load (PRAL) and net endogenous acid production (NEAP) in 4,059 adults aged 50 years and older in the 2011-2014 NHANES survey cycles. PRAL and NEAP were estimated from two 24-h recalls and categorized into sex-specific quartiles. Grip strength was measured on a dynamometer. Multiple linear regression models were used to determine the associations of PRAL and NEAP (as quartiles) with grip strength for men and women separately, adjusting for total energy, age, race/ethnicity, weight, physical activity, smoking, serum 25-hydroxyvitamin D, and estimated glomerular filtration rate. Mean grip strength was 26.8 ± 0.2 kg in women and 43.0 ± 0.4 kg in men. Adjusted grip strength was inversely associated with quartiles of PRAL (ptrend = 0.049) and NEAP (ptrend = 0.034) in women with quartile 4 vs 1 differences of - 1.21 and - 1.08 kg (both p < 0.05), respectively. Adjusted grip strength was not associated with PRAL or NEAP in men. Overall, we found inverse associations between dietary acid load and grip strength in middle- and older-age women, suggesting that an alkaline diet may be important in maintaining muscle strength in this population. There was no association between dietary acid load and grip strength in men.

关于饮食酸碱平衡是否与肌肉力量有关的数据极少。本研究旨在确定具有全国代表性的中老年人样本中的膳食酸负荷是否与握力有关。我们研究了 2011-2014 年 NHANES 调查周期中 4059 名 50 岁及以上成年人的握力与膳食酸负荷(通过潜在肾酸负荷(PRAL)和内源性净产酸量(NEAP)量化)之间的横断面关联。PRAL和NEAP是通过两次24小时回忆估算得出的,并按性别分为四等分。握力是通过测力计测量的。采用多元线性回归模型分别确定男性和女性的 PRAL 和 NEAP(作为四分位数)与握力的关系,并对总能量、年龄、种族/民族、体重、体力活动、吸烟、血清 25- 羟维生素 D 和估计肾小球滤过率进行调整。女性的平均握力为 26.8 ± 0.2 千克,男性为 43.0 ± 0.4 千克。调整后的握力与女性的 PRAL 四分位数(ptrend = 0.049)和 NEAP 四分位数(ptrend = 0.034)成反比,四分位数 4 与四分位数 1 的差异分别为 - 1.21 千克和 - 1.08 千克(均为 p
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引用次数: 0
Higher Plasma Copper Exposure was Adversely Associated with Skeletal Muscle Indicators in Chinese Children Aged 6–9 Years: A Cross-Sectional Study 中国 6-9 岁儿童较高的血浆铜暴露量与骨骼肌指标呈负相关:一项横断面研究
IF 4.2 3区 医学 Q2 ENDOCRINOLOGY & METABOLISM Pub Date : 2024-09-18 DOI: 10.1007/s00223-024-01287-0
Jie Xu, Jing Lan, Qiaoting Huang, Abubakar Tarawally, Lan Huang, Zheqing Zhang, Gengdong Chen

It is unclear whether blood concentrations of copper (Cu), magnesium (Mg), and calcium (Ca) influence skeletal muscle mass and strength in children. We aimed to explore the associations between plasma Cu, Mg, and Ca and skeletal muscle indicators in Chinese children. A total of 452 children aged 6 to 9 years old were recruited for this cross-sectional study. Whole body lean soft tissue mass (WLSTM), trunk lean soft tissue mass (TLSTM), and appendicular skeletal muscle mass (ASMM) were measured using dual-energy X-ray absorptiometry. Parameters of these indicators divided by Height2 (Ht2) and Weight (Wt) at the corresponding sites were calculated. Handgrip strength was also measured. Parameters of skeletal muscle indicators and handgrip strength that were below the sex-specific 20th percentile were considered low levels. Plasma concentrations of Cu, Mg, and Ca were measured using ICP-MS. After adjusting for several potential covariates, among the total subjects, for every one standard deviation increase in Cu concentrations, there was a 0.939% decrease in WLSTM/Wt, a 0.415% decrease in TLSTM/Wt, and a 0.47% decrease in ASMM/Wt. For every one standard deviation increase in Cu concentrations, there was a higher odd (OR: 1.36, 95%CI 1.06, 1.75) of low WLSTM/Wt, TLSTM/Wt (OR: 1.33, 95%CI 1.03, 1.71), ASMM/Ht2 (OR: 1.32, 95%CI 1.02, 1.69), as well as ASMM/Wt (OR: 1.56, 95%CI 1.23, 1.99). No significant associations were found between Mg, Ca, and most skeletal muscle indicators. Higher plasma Cu concentrations were adversely associated with skeletal muscle indicators at multiple sites in Chinese children.

目前尚不清楚血液中铜(Cu)、镁(Mg)和钙(Ca)的浓度是否会影响儿童骨骼肌的质量和力量。我们旨在探讨中国儿童血浆中铜、镁和钙与骨骼肌指标之间的关系。这项横断面研究共招募了 452 名 6 至 9 岁的儿童。研究采用双能 X 射线吸收测量法测量了全身瘦软组织质量(WLSTM)、躯干瘦软组织质量(TLSTM)和附属骨骼肌质量(ASMM)。计算出这些指标的参数除以相应部位的身高2(Ht2)和体重(Wt)。此外,还测量了握力。骨骼肌指标和手握力的参数如果低于性别百分位数的 20%,则被视为低水平。使用 ICP-MS 测量了血浆中铜、镁和钙的浓度。在对几个潜在的协变量进行调整后,在所有受试者中,铜浓度每增加一个标准差,WLSTM/Wt 就下降 0.939%,TLSTM/Wt 下降 0.415%,ASMM/Wt 下降 0.47%。铜浓度每增加一个标准差,WLSTM/Wt、TLSTM/Wt(OR:1.33,95%CI 1.03,1.71)、ASMM/Ht2(OR:1.32,95%CI 1.02,1.69)以及 ASMM/Wt (OR:1.56,95%CI 1.23,1.99)偏低的几率就会增加(OR:1.36,95%CI 1.06,1.75)。在镁、钙和大多数骨骼肌指标之间没有发现明显的关联。在中国儿童的多个部位,较高的血浆铜浓度与骨骼肌指标存在不利关系。
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引用次数: 0
Dental Abnormalities in Osteogenesis Imperfecta: A Systematic Review 成骨不全症的牙齿异常:系统综述
IF 4.2 3区 医学 Q2 ENDOCRINOLOGY & METABOLISM Pub Date : 2024-09-18 DOI: 10.1007/s00223-024-01293-2
Laura Ventura, Sara J. E. Verdonk, Lidiia Zhytnik, Angela Ridwan-Pramana, Marjolijn Gilijamse, Willem H. Schreuder, Kirsten A. van Gelderen-Ziesemer, Ton Schoenmaker, Dimitra Micha, Elisabeth M. W. Eekhoff

Osteogenesis imperfecta (OI) is a rare genetic disorder characterized by fragile bones and skeletal deformities. Individuals with OI may have dental abnormalities such as dentinogenesis imperfecta (DI) type I, malocclusions, and unerupted or missing teeth. This review comprehensively examines these dental abnormalities to assess their prevalence among the OI population and explore potential differences across different clinical types of OI and pathogenic variants. In accordance with the PRISMA guidelines, a systematic literature search in PubMed, Embase, and Web of Science was conducted that included articles up to June 2024. Out of 672 articles screened, 34 were included. The included studies confirmed that dental abnormalities are prevalent in OI, with DI prevalence ranging from approximately 20 to 48%. Those with a more severe skeletal phenotype (OI type III/IV) exhibited more dental abnormalities than those with a milder skeletal phenotype (OI type I). Notably, OI type V individuals generally do not have DI, although a few isolated cases have been reported. The prevalence of occlusion types varied: Class I occlusion ranged from 14.8 to 50% and Class II malocclusion ranged from 0 to 37.5%, while Class III malocclusion from 4.1 to 84%. This differs from the general population, where Class III malocclusion is typically the least common. Open bites, cross-bites, and unerupted and missing teeth are also commonly reported, particularly in OI types III and IV. This review emphasizes the need for comprehensive dental examinations in OI due to the high prevalence of dental abnormalities. Additionally, the review draws attention to the lack of clear guidelines for diagnosing DI.

成骨不全症(OI)是一种罕见的遗传性疾病,以骨骼脆弱和骨骼畸形为特征。OI 患者可能有牙科异常,如牙本质发育不全(DI)I 型、畸形、牙齿不齐或缺失。本综述全面研究了这些牙齿异常,以评估其在 OI 患者中的发病率,并探讨不同临床类型的 OI 和致病变体之间的潜在差异。根据 PRISMA 指南,我们在 PubMed、Embase 和 Web of Science 中进行了系统的文献检索,包括截至 2024 年 6 月的文章。在筛选出的 672 篇文章中,有 34 篇被纳入。所纳入的研究证实,牙齿异常在 OI 中很普遍,DI 患病率约为 20% 到 48%。骨骼表型较重(OI III/IV 型)的患者比骨骼表型较轻(OI I 型)的患者表现出更多的牙齿异常。值得注意的是,OI V 型患者一般没有 DI,但也有少数个别病例的报道。闭塞类型的发病率各不相同:I 类咬合从 14.8%到 50%不等,II 类错牙合从 0%到 37.5%不等,III 类错牙合从 4.1%到 84%不等。这与普通人群不同,在普通人群中,III类咬合不正通常是最不常见的。开合咬合、交叉咬合、牙齿未畸形和缺失也是常见报告,尤其是在 OI III 和 IV 型中。本综述强调,由于牙齿畸形的高发率,有必要对 OI 患者进行全面的牙科检查。此外,该综述还提请注意缺乏诊断 DI 的明确指南。
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引用次数: 0
Irisin Ameliorates Muscle Atrophy by Inhibiting the Upregulation of the Ubiquitin‒Proteasome System in Chronic Kidney Disease 鸢尾素通过抑制慢性肾病患者泛素-蛋白酶体系统的上调改善肌肉萎缩状况
IF 4.2 3区 医学 Q2 ENDOCRINOLOGY & METABOLISM Pub Date : 2024-09-16 DOI: 10.1007/s00223-024-01283-4
Shiyuan Wang, Yajing Pan, Qi Pang, Aihua Zhang

Muscle atrophy is a common complication of chronic kidney disease (CKD). Irisin, a novel muscle cytokine, protects against muscle atrophy, but its specific role in CKD-associated muscle atrophy requires further elucidation. Because the ubiquitin–proteasome system (UPS) plays an important role in CKD muscle atrophy, our study will explore whether irisin affects UPS and alleviate CKD-associated muscle atrophy. In this study, an adenine-fed mouse model of CKD and urotension II (UII)-induced C2C12 myotubes were used as in vivo and in vitro models of muscle atrophy. The results showed that renal function, mouse weight, and the cross-sectional area (CSA) of skeletal muscles were significantly improved in CKD mice treated with irisin. Moreover, irisin effectively mitigated the decreases in phosphorylated Forkhead box O 3a (p-FOXO3A) levels and increases in the levels of E3 ubiquitin ligases, such as muscle RING finger 1 (MuRF1) and muscle atrophy F-box (MAFbx/atrogin1), in both the muscles of CKD mice and UII-induced C2C12 myotubes. In addition, irisin significantly increased the expression levels of myogenic differentiation factor D (MyoD) in the muscles of CKD mice. Our study is the first to demonstrate that irisin ameliorates skeletal muscle atrophy by inhibiting UPS upregulation and improving satellite cell differentiation in CKD.

肌肉萎缩是慢性肾脏病(CKD)的常见并发症。鸢尾素是一种新型肌肉细胞因子,能防止肌肉萎缩,但它在 CKD 相关肌肉萎缩中的具体作用还需要进一步阐明。由于泛素-蛋白酶体系统(UPS)在 CKD 肌肉萎缩中发挥着重要作用,我们的研究将探讨鸢尾素是否会影响 UPS 并减轻 CKD 相关肌肉萎缩。本研究采用腺嘌呤喂养的 CKD 小鼠模型和尿张力Ⅱ(UII)诱导的 C2C12 肌管作为肌肉萎缩的体内和体外模型。结果表明,使用鸢尾素治疗的 CKD 小鼠的肾功能、小鼠体重和骨骼肌横截面积(CSA)均有明显改善。此外,鸢尾素还能有效缓解CKD小鼠肌肉和UII诱导的C2C12肌管中磷酸化叉头盒O 3a(p-FOXO3A)水平的下降和E3泛素连接酶(如肌肉RING指1(MuRF1)和肌肉萎缩F-box(MAFbx/atrogin1))水平的升高。此外,鸢尾素还能显著提高 CKD 小鼠肌肉中肌生成分化因子 D(MyoD)的表达水平。我们的研究首次证明了鸢尾素能通过抑制 UPS 上调和改善 CKD 中卫星细胞的分化来改善骨骼肌的萎缩。
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引用次数: 0
Sex-Specific Association of Clinical Parameters and Components of Femoral Bone Quality in Patients Undergoing Total Hip Arthroplasty 全髋关节置换术患者临床参数与股骨骨质成分的性别特异性关联
IF 4.2 3区 医学 Q2 ENDOCRINOLOGY & METABOLISM Pub Date : 2024-09-14 DOI: 10.1007/s00223-024-01286-1
Assil-Ramin Alimy, Maximilian Lenard Thiessen, André Strahl, Christoph Kolja Boese, Simon von Kroge, Frank Timo Beil, Tim Rolvien, Christian Ries

Poor bone quality is a critical factor associated with an increased risk of complications after total hip arthroplasty (THA). However, no consistent recommendations have yet been established for assessing indicators of bone quality preoperatively. Thus, it remains unclear which preoperatively available and readily accessible parameters are most closely associated with femoral bone quality. Here, we obtained femoral neck specimens from 50 patients undergoing THA. Preoperative Dual-energy X-ray absorptiometry (DXA) scans, pelvic radiographs, and laboratory parameters were analyzed. In the obtained specimens, bone microstructure was assessed using micro-CT and histomorphometry. Additionally, matrix mineralization and osteocyte lacunar morphology were evaluated using quantitative backscattered electron imaging. Our analysis revealed that DXA-derived T-scores correlated with trabecular microstructure. Furthermore, radiographic indices and body mass index correlated differentially with aspects of bone quality in women and men. Contrary to previous observations, no correlation was found between serum vitamin D levels and osteoid indices, nor between clinical parameters and matrix mineralization. Age was strongly associated with the number of mineralized osteocyte lacunae, a factor that appeared to be independent of sex. Taken together, our study demonstrates that no single preoperatively available parameter exhibits a strong and consistent association with femoral bone quality. However, DXA remains a reliable preoperative measure for determining the trabecular microstructure of the femoral neck. In clinical practice, surgeons should adopt an individualized approach to preoperative assessments by considering age, sex, BMI, and radiographic indices to enhance their insight into femoral bone quality, particularly when DXA is unavailable.

骨质差是导致全髋关节置换术(THA)后并发症风险增加的关键因素。然而,对于术前评估骨质量指标,目前还没有一致的建议。因此,目前仍不清楚哪些术前可用且容易获得的参数与股骨头质量最密切相关。在此,我们从 50 名接受 THA 的患者身上获取了股骨颈标本。对术前双能 X 射线吸收测量(DXA)扫描、骨盆X光片和实验室参数进行了分析。在获得的标本中,使用显微 CT 和组织形态学评估了骨的微观结构。此外,还使用定量反向散射电子成像技术对基质矿化和骨细胞裂隙形态进行了评估。我们的分析表明,DXA得出的T值与骨小梁微结构相关。此外,放射指数和体重指数与女性和男性骨质的相关性也不同。与之前的观察结果相反,血清维生素 D 水平与骨质指数之间以及临床参数与基质矿化之间均未发现相关性。年龄与矿化骨细胞裂隙的数量密切相关,这一因素似乎与性别无关。综上所述,我们的研究表明,没有一个术前可用的参数与股骨头质量有强烈而一致的关联。然而,DXA仍然是确定股骨颈骨小梁微结构的可靠术前指标。在临床实践中,外科医生应采用个体化的术前评估方法,考虑年龄、性别、体重指数和影像学指标,以提高他们对股骨头质量的洞察力,尤其是在无法使用DXA的情况下。
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Calcified Tissue International
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