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Combined Romosozumab and Raloxifene treatment targets impaired bone quality in a male murine model of diabetic kidney disease.
Pub Date : 2025-01-28 DOI: 10.1016/j.bone.2025.117415
Rachel Kohler, Dyann M Segvich, Olivia Reul, Corinne E Metzger, Matthew R Allen, Joseph M Wallace

Comorbid diabetes and chronic kidney disease create a complex disease state with multi-faceted impacts on bone health, primarily reduced bone mass and tissue quality. To reduce fracture risk in this growing population, interventions are needed that target both bone mass and quality. Romosozumab (Romo) is an FDA-approved sclerostin inhibitor that has been shown to increase bone mass and strength in a murine model of combined diabetes and CKD (DKD), while Raloxifene (RAL) is a mild anti-resorptive used to treat osteoporosis that has also been shown to increase bone mechanical properties by increasing bone bound water content. We aimed to test whether combined RAL and Romo treatment could improve bone quality in our murine model of DKD more than either treatment alone. Using a previously established streptozotocin- and adenine-diet-induced model, male, C57BL/6J mice were randomly divided into four treatment groups and given daily subcutaneous injections of 100 μL vehicle (phosphorus buffered saline, PBS) or 0.5 mg/kg RAL. In addition, two groups were also given a weekly dose of Romo (10 mg/kg). Overall, Romo increased whole-bone strength and RAL improved tissue-level mechanical properties. Combined RAL-Romo treatment led to significantly higher cortical and trabecular bone mass compared to untreated controls. These morphological improvements created corresponding improvements in cortical bending strength and vertebral trabecular compression strength. These results suggest that combined RAL-Romo treatment provides both mass and quality improvements to DKD bone.

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引用次数: 0
Comment on 'Automatic AI tool for opportunistic screening of vertebral compression fractures on chest frontal radiographs: A multicenter study'. 对“在胸正位x线片上进行椎体压缩性骨折机会筛查的自动人工智能工具:一项多中心研究”的评论。
Pub Date : 2024-12-17 DOI: 10.1016/j.bone.2024.117372
Yanxia Jia, Weibo Wang, Guodong Luo, Chengqiang Jin
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引用次数: 0
Letter to the editor concerning 'The association of waist circumference with bone mineral density and risk of osteoporosis in US adult: National health and nutrition examination survey'. 致编辑的信,内容涉及 "美国成年人腰围与骨矿物质密度和骨质疏松症风险的关系:全国健康与营养状况调查"。
Pub Date : 2024-11-01 DOI: 10.1016/j.bone.2024.117312
Shangxian Pan, Kuangyang Yang
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引用次数: 0
Letter to the editor concerning 'Impact of diabetes on the risk of subsequent fractures in 92,600 patients with an incident hip fracture: A Danish nationwide cohort study 2004-2018'. 致编辑的信,内容涉及 "糖尿病对9.26万名髋部骨折患者后续骨折风险的影响:2004-2018年丹麦全国性队列研究"。
Pub Date : 2024-05-01 DOI: 10.1016/j.bone.2024.117124
Junqing Miao, Xiaole Kong, Jingzhi Wang
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引用次数: 0
Swim training induces distinct osseous gene expression pattern in anosteocytic and osteocytic teleost fish. 游泳训练在无骨细胞和有骨细胞的远洋鱼类中诱导不同的骨质基因表达模式。
Pub Date : 2024-05-01 DOI: 10.1016/j.bone.2024.117125
Josephine T Tauer, Tobias Thiele, Catherine Julien, Lior Ofer, P. Zaslansky, Ron Shahar, Bettina M. Willie
{"title":"Swim training induces distinct osseous gene expression pattern in anosteocytic and osteocytic teleost fish.","authors":"Josephine T Tauer, Tobias Thiele, Catherine Julien, Lior Ofer, P. Zaslansky, Ron Shahar, Bettina M. Willie","doi":"10.1016/j.bone.2024.117125","DOIUrl":"https://doi.org/10.1016/j.bone.2024.117125","url":null,"abstract":"","PeriodicalId":93913,"journal":{"name":"Bone","volume":"210 S650","pages":"117125"},"PeriodicalIF":0.0,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141040215","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
The effects of synbiotics-glyconutrients on growth performance, nutrient digestibility, gas emission, meat quality, and fatty acid profile of finishing pigs. 合生素-甘氨酸营养素对育成猪生长性能、营养消化率、气体排放、肉质和脂肪酸谱的影响。
IF 2.3 Pub Date : 2024-03-01 Epub Date: 2024-03-31 DOI: 10.5187/jast.2023.e52
Olivier Munezero, Sungbo Cho, In Ho Kim

Glyconutrients help in the body's cell communication. Glyconutrients and synbiotics are promising options for improving immune function. Therefore, we hypothesized that combining synbiotics and glyconutrients will enhance pig nutrient utilization. 150 pigs (Landrace × Yorkshire × Duroc), initially weighing 58.85 ± 3.30 kg of live body weight (BW) were utilized to determine the effects of synbiotics-glyconutrients (SGN) on the pigs' performance, feed efficiency, gas emission, pork traits, and composition of fatty acids. The pigs were matched by BW and sex and chosen at random to 1 of 3 diet treatments: control = Basal diet; TRT1 = Basal diet + SGN 0.15%; TRT2 = Basal diet + SGN 0.30%%. The trials were conducted in two phases (weeks 1-5 and weeks 5-10). The average daily gain was increased in pigs fed a basal diet with SGN (p = 0.036) in weeks 5-10. However, the apparent total tract digestibility of dry matter, nitrogen, and gross energy did not differ among the treatments (p > 0.05). Dietary treatments had no effect on NH3, H2S, methyl mercaptans, acetic acids, and CO2 emissions (p > 0.05). Improvement in drip loss on day 7 (p = 0.053) and tendency in the cooking loss were observed (p = 0.070) in a group fed basal diets and SGN at 0.30% inclusion level. The group supplemented with 0.30% of SGN had higher levels of palmitoleic acid (C16:1), margaric acid (C17:0), omega-3 fatty acid, omega-6 fatty acid, and ω-6: ω-3 ratio (p = 0.034, 0.020, 0.025, 0.007, and 0.003, respectively) in the fat of finishing pigs. Furthermore, group supplemented with 0.30% of SGN improved margaric acid (C17:0), linoleic acid (C18:2n6c), arachidic acid (C20:0), omega 6 fatty acid, omega-6 to omega-3 ratio, unsaturated fatty acid, and monounsaturated fatty acid (p = 0.037, 0.05, 0.0142, 0.036, 0.033, 0.020, and 0.045, respectively) in the lean tissues of finishing pigs compared to pigs fed with the control diets. In conclusion, the combination of probiotics, prebiotics, and glyconutrients led to higher average daily gain, improved the quality of pork, and more favorable fatty acid composition. Therefore, these results contributed to a better understanding of the potential of SGN combinations as a feed additive for pigs.

糖营养素有助于人体细胞的交流。糖营养素和合生素是改善免疫功能的有前途的选择。因此,我们假设将合生素和糖营养素结合使用将提高猪的营养利用率。我们利用 150 头最初体重为 58.85 ± 3.30 千克的猪(Landrace × Yorkshire × Duroc)来测定合生素-糖营养素(SGN)对猪的生产性能、饲料效率、气体排放、猪肉性状和脂肪酸组成的影响。试验猪的体重和性别均匹配,并从 3 种日粮处理中随机选择一种:对照组 = 基础日粮;TRT1 = 基础日粮 + SGN 0.15%;TRT2 = 基础日粮 + SGN 0.30%%。试验分两个阶段进行(第 1-5 周和第 5-10 周)。在第 5-10 周,饲喂添加 SGN 的基础日粮的猪的平均日增重提高了(p = 0.036)。然而,干物质、氮和总能的表观总消化率在不同处理间没有差异(p > 0.05)。日粮处理对 NH3、H2S、甲硫醇、乙酸和 CO2 排放量没有影响(p > 0.05)。在饲喂基础日粮和添加量为 0.30% 的 SGN 的组别中,第 7 天的滴水损失有所改善(p = 0.053),蒸煮损失呈下降趋势(p = 0.070)。添加 0.30% SGN 的组别在育成猪脂肪中的棕榈油酸(C16:1)、人造黄油酸(C17:0)、ω-3 脂肪酸、ω-6 脂肪酸和 ω-6: ω-3 比率(p = 0.034、0.020、0.025、0.007 和 0.003)的含量更高。此外,添加 0.30% SGN 的组改善了人造黄油酸(C17:0)、亚油酸(C18:2n6c)、花生四烯酸(C20:0)、ω-6 脂肪酸、ω-6 与ω-3 比率、不饱和脂肪酸和单不饱和脂肪酸(p = 0.037、0.05、0.0142、0.036、0.033、0.020 和 0.045)。总之,益生菌、益生元和糖营养素的组合提高了平均日增重,改善了猪肉的质量,并使脂肪酸组成更加有利。因此,这些结果有助于更好地了解 SGN 组合作为猪饲料添加剂的潜力。
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引用次数: 0
TNF-α promotes osteocyte necroptosis by upregulating TLR4 in postmenopausal osteoporosis TNF-α 在绝经后骨质疏松症中通过上调 TLR4 促进骨细胞坏死
Pub Date : 2024-02-01 DOI: 10.1016/j.bone.2024.117050
Hongwang Cui, Ji Li, Xiangtao Li, Tian Su, Peng Wen, Chuanling Wang, Xiaozhong Deng, Yonghua Fu, Weijie Zhao, Changjia Li, Pengbing Hua, Yongjun Zhu, Wei Wan
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引用次数: 0
Bone intrinsic material and compositional properties in postmenopausal women diagnosed with long-term Type-1 diabetes. 诊断为长期1型糖尿病的绝经后妇女的骨内在物质和组成特性
Pub Date : 2023-06-27 DOI: 10.2139/ssrn.4328036
W. Qian, S. Gamsjaeger, E. Paschalis, Laura A Graeff-Armas, S. Bare, J. Turner, J. Lappe, R. Recker, M. Akhter
The incidence of diabetes mellitus and the associated complications are growing worldwide, affecting the patients' quality of life and exerting a considerable burden on health systems. Yet, the increase in fracture risk in type 1 diabetes (T1D) patients is not fully captured by bone mineral density (BMD), leading to the hypothesis that alterations in bone quality are responsible for the increased risk. Material/compositional properties are important aspects of bone quality, yet information on human bone material/compositional properties in T1D is rather sparse. The purpose of the present study is to measure both the intrinsic material behaviour by nanoindentation, and material compositional properties by Raman spectroscopy as a function of tissue age and microanatomical location (cement lines) in bone tissue from iliac crest biopsies from postmenopausal women diagnosed with long-term T1D (N = 8), and appropriate sex-, age-, BMD- and clinically-matched controls (postmenopausal women; N = 5). The results suggest elevation of advanced glycation endproducts (AGE) content in the T1D and show significant differences in mineral maturity / crystallinity (MMC) and glycosaminoglycan (GAG) content between the T1D and control groups. Furthermore, both hardness and modulus by nanoindentation are greater in T1D. These data suggest a significant deterioration of material strength properties (toughness) and compositional properties in T1D compared with controls.
糖尿病及其相关并发症的发病率在全球范围内不断增长,影响了患者的生活质量,并给卫生系统带来了相当大的负担。然而,骨密度(BMD)并不能完全反映1型糖尿病(T1D)患者骨折风险的增加,这导致了骨质量变化是风险增加的原因的假设。材料/成分特性是骨骼质量的重要方面,但T1D中关于人类骨骼材料/成分性质的信息相当稀少。本研究的目的是通过纳米压痕测量固有材料行为,并通过拉曼光谱测量材料成分特性,作为组织年龄和骨组织显微解剖位置(水泥线)的函数 = 8) ,以及适当的性别、年龄、骨密度和临床匹配的对照组(绝经后妇女;N = 5) 。结果表明,T1D组和对照组的晚期糖基化终产物(AGE)含量升高,矿物质成熟度/结晶度(MMC)和糖胺聚糖(GAG)含量存在显著差异。此外,在T1D中,纳米压痕的硬度和模量都更大。这些数据表明,与对照组相比,T1D中的材料强度特性(韧性)和成分特性显著恶化。
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引用次数: 1
Pediatric reference values of alkaline phosphatase: Analysis from a German population-based cohort and influence of anthropometric and blood parameters. 儿童碱性磷酸酶参考值:来自德国人群的队列分析以及人体测量和血液参数的影响。
Pub Date : 2023-05-01 DOI: 10.2139/ssrn.4358797
Jacqueline-Michéle Strauch, M. Vogel, C. Meigen, U. Ceglarek, J. Kratzsch, A. Willenberg, W. Kiess
BACKGROUNDDue to different growth and metabolic processes, reference values of alkaline phosphatase (AP) for children aged 3 month to 18 years are dependent on age and sex. They are not constant and differ from those of adults due to the growth processes taking place. Accordingly, reference levels of AP continuous across these ages were generated for boys and girls based on of a large German health- and population-based study, LIFE Child. We considered AP at different growth and Tanner stages and additionally its association with other anthropometric parameters. The association between AP and BMI was of particulary great interest due to controversial literature on this topic. The role of AP in liver metabolism was investigated by examining ALAT, ASAT, and GGT.METHODS3976 healthy children (12,093 visits) were included from the LIFE Child study from 2011 to 2020. The subjects´ age ranged from 3 months to 18 years. Serum samples from 3704 subjects (10,272 cases, 1952 boys and 1753 girls) were analysed for AP after applying specific exclusion criteria. After calculating of reference percentiles, associations between AP and height-SDS, growth velocity, BMI-SDS, Tanner stage and the liver enzymes ALAT, ASAT and GGT were examined via linear regression models.RESULTSIn the continuous reference levels, AP showed a first peak during the first year of life, followed by a plateau at a lower level until the start of puberty. In girls, AP increased beginning at the age 8, with a peak around 11 years, in boys beginning at the age 9, with a peak around age 13. Afterwards, AP values decreased continuously until age 18. In Tanner stages 1 and 2, AP levels did not differ between the two sexes. We found a strong positive association between AP-SDS and BMI-SDS. We also observed a significantly positive association between AP-SDS and height-SDS, which was stronger in boys than in girls. We found different intensities in the associations of AP with growth velocity depending on age group and sex. Furthermore, we found a significantly positive association between ALAT and AP in girls but not in boys, whereas ASAT-SDS and GGT-SDS were significantly positively associated with AP-SDS in both sexes.CONCLUSIONSex and age, but also BMI may act as confounding factors for AP reference ranges. Our data confirm the remarkable association between AP and growth velocity (or height-SDS, respectively) during infancy and puberty. In addition, we were able to specify the associations between AP and ALAT, ASAT, and GGT and their differences in both sexes. These relations should be considered when evaluating liver and bone metabolism markers, especially in infancy.
背景由于不同的生长和代谢过程,3岁儿童碱性磷酸酶(AP)的参考值 月至18 年龄取决于年龄和性别。它们不是恒定的,并且由于发生的生长过程而与成年人不同。因此,根据德国一项大型健康和人群研究LIFE Child,为男孩和女孩生成了这些年龄段持续的AP参考水平。我们考虑了AP在不同生长和Tanner阶段的情况,以及它与其他人体测量参数的关系。AP和BMI之间的联系特别令人感兴趣,因为这方面的文献存在争议。通过检查ALAT、ASAT和GGT来研究AP在肝脏代谢中的作用。方法2011年至2020年,LIFE Child研究纳入了976名健康儿童(12093次访问)。受试者的年龄范围为3岁 月至18 年。在应用特定的排除标准后,对3704名受试者(10272例,1952名男孩和1753名女孩)的血清样本进行了AP分析。在计算参考百分位数后,通过线性回归模型检验AP与身高SDS、生长速度、BMI-SDS、Tanner阶段以及肝酶ALAT、ASAT和GGT之间的相关性。结果在连续参考水平下,AP在出生的第一年出现第一个峰值,随后在青春期开始前一直处于较低水平。在女孩中,AP从8岁开始增加,在11岁左右达到峰值 年,男孩从9岁开始,在13岁左右达到峰值。之后,AP值持续下降,直到18岁。在Tanner阶段1和2,AP水平在两性之间没有差异。我们发现AP-SDS和BMI-SDS之间有很强的正相关。我们还观察到AP-SDS和身高SDS之间存在显著的正相关,男孩的这种相关性比女孩更强。我们发现AP与生长速度的关联强度因年龄组和性别而异。此外,我们发现ALAT和AP在女孩中显著正相关,但在男孩中没有,而ASAT-SDS和GGT-SDS在两性中都与AP-SDS显著正相关。结论性别和年龄以及BMI可能是AP参考范围的混杂因素。我们的数据证实了AP与婴儿期和青春期的生长速度(或身高SDS)之间的显著相关性。此外,我们能够明确AP和ALAT、ASAT和GGT之间的关联以及它们在两性中的差异。在评估肝脏和骨骼代谢标志物时,尤其是在婴儿期,应考虑这些关系。
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引用次数: 0
Muscle strength and physical performance contribute to and improve fracture risk prediction in older people: A narrative review. 肌肉力量和身体表现有助于并改善老年人骨折风险预测:一篇叙述性综述。
Pub Date : 2023-04-05 DOI: 10.2139/ssrn.4281657
Dima A Alajlouni, D. Bliuc, Thach Tran, R. Blank, J. Center
Osteoporotic fractures present a major health problem with an increasing prevalence in older people. Fractures are associated with premature mortality, reduced quality of life, subsequent fracture, and increased costs. Hence, it is crucial to identify those at higher risk of fracture. Fracture risk assessment tools incorporated clinical risk factors to improve fracture predictive power over BMD alone. However, fracture risk prediction using these algorithms remains suboptimal, warranting further improvement. Muscle strength and physical performance measurements have been associated with fracture risk. In contrast, the contribution of sarcopenia, the composite condition of low muscle mass, muscle strength and/or physical performance, to fracture risk is unclear. It is uncertain whether this is due to the problematic definition of sarcopenia per se or limitations of the diagnostic tools and cut-off points of the muscle mass component. The recent position statement from the Sarcopenia Definition and Outcomes Consortium confirmed the inclusion of muscle strength and performance in the definition of sarcopenia but not DXA-assessed lean mass. Therefore, clinicians should focus on functional assessment (muscle strength and performance) rather than muscle mass, at least as assessed by DXA, as predictors of fractures. Muscle strength and performance are modifiable risk factors. Resistance exercise improves muscle parameters in the elderly, potentially leading to reduced risk of falls and fractures in the general population and in those who sustained a fracture. Therapists may consider exercise intervention to improve muscle parameters and potentially reduce the risk of fractures. The aim of this review was to explore 1) the contribution of muscle parameters (i.e., muscle mass, strength, and physical performance) to fracture risk in older adults, and 2) the added predictive accuracy of these parameters beyond the existing fracture assessment tools. These topics provide the rationale for investigating strength and physical performance interventions to reduce fracture risk. Most of the included publications showed that muscle mass is not a good predictor of fracture risk, while poor muscle strength and performance are associated with an increased risk of fracture, particularly in men, independent of age, BMD, and other risk factors for fractures. Muscle strength and performance can potentially improve the predictive accuracy in men beyond that obtained by the fracture risk assessment tools, Garvan FRC and FRAX.
骨质疏松性骨折是一个主要的健康问题,在老年人中患病率越来越高。骨折与过早死亡、生活质量下降、后续骨折和成本增加有关。因此,识别那些骨折风险较高的人是至关重要的。骨折风险评估工具结合了临床风险因素,以提高单独BMD对骨折的预测能力。然而,使用这些算法进行骨折风险预测仍然是次优的,需要进一步改进。肌肉力量和身体表现测量与骨折风险有关。相比之下,少肌症,即低肌肉量、肌肉力量和/或身体表现的综合状况,对骨折风险的贡献尚不清楚。目前尚不确定这是由于少肌症本身的定义存在问题,还是由于诊断工具和肌肉质量成分分界点的局限性。肌肉减少症定义和结果联合会最近的立场声明证实,肌肉减少症的定义中包括了肌肉力量和表现,但没有包括DXA评估的瘦质量。因此,临床医生应该专注于功能评估(肌肉力量和性能),而不是肌肉质量,至少根据DXA的评估,作为骨折的预测因素。肌肉力量和表现是可改变的风险因素。阻力运动可以改善老年人的肌肉参数,有可能降低普通人群和骨折患者跌倒和骨折的风险。治疗师可能会考虑进行运动干预,以改善肌肉参数,并潜在地降低骨折风险。这篇综述的目的是探讨1)肌肉参数(即肌肉质量、力量和身体表现)对老年人骨折风险的贡献,以及2)这些参数在现有骨折评估工具之外增加的预测准确性。这些主题为研究强度和物理性能干预措施以降低骨折风险提供了基本原理。大多数纳入的出版物表明,肌肉质量不是骨折风险的良好预测指标,而肌肉力量和表现不佳与骨折风险增加有关,尤其是在男性中,与年龄、BMD和其他骨折风险因素无关。肌肉力量和表现可以潜在地提高男性的预测准确性,超过骨折风险评估工具Garvan FRC和FRAX的预测准确性。
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引用次数: 4
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Bone
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