背景:观察性研究表明他汀类药物可能对骨密度具有保护作用,这使其成为潜在的骨质疏松症治疗药物之一。目的:通过孟德尔随机化方法来评估药物靶点介导的脂质表型与骨密度之间的因果关系。方法:从IEU Open GWAS数据库获取了与他汀类药物...背景:观察性研究表明他汀类药物可能对骨密度具有保护作用,这使其成为潜在的骨质疏松症治疗药物之一。目的:通过孟德尔随机化方法来评估药物靶点介导的脂质表型与骨密度之间的因果关系。方法:从IEU Open GWAS数据库获取了与他汀类药物相关的单核苷酸多态性以及骨密度相关数据。主要分析方法是逆方差加权法,同时也使用了加权中位数法、简单中位数法、加权中值方法和MR-Egger回归法。使用β值和95%CI来评估他汀类药物与骨密度之间的因果关系;另外,进行敏感性分析以验证结果的可靠性,使用Cochran’s Q检验来评估异质性,使用MR-Egger截距检验是否存在水平多效性。使用留一法分析确定是否有单个或多个单核苷酸多态性影响了结果。结果与结论:他汀类药物作用靶点——3-羟基-3-甲基戊二酰辅酶A还原酶介导的低密度脂蛋白胆固醇与足跟定量超声骨密度(β=-0.086,95%CI:-0.117至-0.055,P=5.42×10^(-8))和全身骨密度(β=-0.193,95%CI:-0.288至-0.098,P=7.35×10^(-5))呈显著相关。该研究结果支持了他汀类药物对骨密度的保护作用。这些发现不仅加深了对胆固醇相关基因和骨骼健康关系的理解,还揭示了改善骨密度的潜在治疗靶点。展开更多
2型糖尿病肾病(Type 2 diabetic nephropathy, DKD)的基本机制是活性氧(reactive oxygen, ROS)和晚期糖基化终产物(advanced glycation end product, AGEs)的积累。除此之外持续和长期暴露于高血糖环境中,和其他危险因素,如肥胖、血脂...2型糖尿病肾病(Type 2 diabetic nephropathy, DKD)的基本机制是活性氧(reactive oxygen, ROS)和晚期糖基化终产物(advanced glycation end product, AGEs)的积累。除此之外持续和长期暴露于高血糖环境中,和其他危险因素,如肥胖、血脂异常和胰岛素抵抗都会导致2型糖尿病肾病。中医认为肾为先天之本,脾为后天之本,二者相互充养才能使机体维持正常的生命活动,脾胃虚弱是糖尿病肾病发病的病机之一。另外由于高血糖,炎性反应和胰岛素抵抗等因素可能导致2型糖尿病肾病患者继发骨质疏松。应监测骨代谢标志物包括骨吸收标志物[β-胶原降解产物测定(Beta-collagen degradation products, β-CTX)]和骨形成标志物[总I型胶原氨基端延长肽(Elongation of amino end of total type Ⅰ collagen, PINP)]和骨密度,做到早发现早治疗,减轻患者痛苦。临床应用降糖药物时应该关注其额外的降糖作用,注意降糖药物对患者肾脏和骨质疏松的影响。该文总结研究了2型糖尿病肾病患者继发骨质疏松的病因病机和降糖药物的额外作用,对今后的临床研究具有指导作用。展开更多
The risk of fracture is increased in both type 1 diabetes mellitus(T1DM)and type 2 diabetes mellitus(T2DM).However,in contrast to the former,patients with T2DM usually possess higher bone mineral density.Thus,there is...The risk of fracture is increased in both type 1 diabetes mellitus(T1DM)and type 2 diabetes mellitus(T2DM).However,in contrast to the former,patients with T2DM usually possess higher bone mineral density.Thus,there is a considerable difference in the pathophysiological basis of poor bone health between the two types of diabetes.Impaired bone strength due to poor bone microarchitecture and low bone turnover along with increased risk of fall are among the major factors behind elevated fracture risk.Moreover,some antidiabetic medications further enhance the fragility of the bone.On the other hand,antiosteoporosis medications can affect the glucose homeostasis in these patients.It is also difficult to predict the fracture risk in these patients because conventional tools such as bone mineral density and Fracture Risk Assessment Tool score assessment can underestimate the risk.Evidence-based recommendations for risk evaluation and management of poor bone health in diabetes are sparse in the literature.With the advancement in imaging technology,newer modalities are available to evaluate the bone quality and risk assessment in patients with diabetes.The purpose of this review is to explore the patho-physiology behind poor bone health in diabetic patients.Approach to the fracture risk evaluation in both T1DM and T2DM as well as the pragmatic use and efficacy of the available treatment options have been discussed in depth.展开更多
Objective： The aim of our meta-analysis was to assess the effects of antiepileptic drugs on bone mineral density and bone metabolism in epileptic children. Methods： Searches of Pub Med and Web of Science were undert...Objective： The aim of our meta-analysis was to assess the effects of antiepileptic drugs on bone mineral density and bone metabolism in epileptic children. Methods： Searches of Pub Med and Web of Science were undertaken to identify studies evaluating the association between antiepileptic drugs and bone mineral density and bone metabolism. Results： A total of 22 studies with 1492 subjects were included in our research. We identified：（1） a reduction in bone mineral density at lumbar spine（standardized mean difference（SMD）=-0.30, 95% confidence interval（CI） [-0.61,-0.05]）, trochanter（mean difference（MD）=-0.07, 95% CI [-0.10,-0.05]）, femoral neck（MD=-0.05, 95% CI [-0.09,-0.02]）, and total body bone mineral density（MD=-0.33, 95% CI [-0.51,-0.15]）;（2） a reduction in 25-hydroxyvitamin D（MD=-3.37, 95% CI [-5.94,-0.80]） and an increase in serum alkaline phosphatase（SMD=0.71, 95% CI [0.38, 1.05]）;（3） no significant changes in serum parathyroid hormone, calcium, or phosphorus. Conclusions： Our meta-analysis suggests that treatment with antiepileptic drugs may be associated with decreased bone mineral density in epileptic children.展开更多
1概述1.1定义和分类骨质疏松症(osteoporosis)是一种以骨量低下、骨组织微结构损坏,导致骨脆性增加,易发生骨折为特征的全身性骨病[1]。2001年美国国立卫生研究院(National Institutes of Health,NIH)将其定义为骨强度下降和骨折风险增...1概述1.1定义和分类骨质疏松症(osteoporosis)是一种以骨量低下、骨组织微结构损坏,导致骨脆性增加,易发生骨折为特征的全身性骨病[1]。2001年美国国立卫生研究院(National Institutes of Health,NIH)将其定义为骨强度下降和骨折风险增加为特征的骨骼疾病[2]。骨质疏松症可发生于任何年龄,但多见于绝经后女性和老年男性。展开更多
背景:中医药可有效防治糖皮质激素性骨质疏松,但其防治机制尚不明确。DKK1是Wnt/β-catenin信号通路的抑制剂,糖皮质激素可诱导其上调。因此,DKK1蛋白是防治糖皮质激素性骨质疏松的重要靶点。目的:探讨左归丸防治糖皮质激素性骨质疏松中...背景:中医药可有效防治糖皮质激素性骨质疏松,但其防治机制尚不明确。DKK1是Wnt/β-catenin信号通路的抑制剂,糖皮质激素可诱导其上调。因此,DKK1蛋白是防治糖皮质激素性骨质疏松的重要靶点。目的:探讨左归丸防治糖皮质激素性骨质疏松中对DKK1的调控作用。方法:18只3月龄雌性SD大鼠随机均分为3组:空白组、模型组和左归丸组。模型组和左归丸组大鼠皮下注射地塞米松建立糖皮质激素性骨质疏松模型;空白组给予等体积生理盐水;左归丸组皮下注射地塞米松同时给予左归丸水提液灌胃。1个月后取大鼠腰椎进行micro-CT检测骨量及骨微细结构、压缩试验检测生物力学性能,q PCR测定腰椎DKK1、Runx2和CTSK m RNA表达;血清检测碱性磷酸酶活性。结果与结论:(1)与空白组比较,模型组体积骨密度、相对骨体积、骨小梁数量和骨小梁厚度显著降低(P<0.05),骨小梁间距和结构模型指数较空白组显著增大(P<0.05),血清碱性磷酸酶活性较空白组呈降低趋势,DKK1 m RNA表达显著上调(P<0.05),成骨相关因子Runx2 m RNA表达呈下调趋势,破骨相关因子CTSK m RNA呈上调趋势;(2)与模型组比较,左归丸组体积骨密度、相对骨体积和骨小梁数量显著提升(P<0.05),结构模型指数显著降低(P<0.05),骨小梁间距有减小趋势但差异无显著性意义,血清碱性磷酸酶活性较模型组呈升高趋势,DKK1 m RNA表达显著下调(P<0.05),Runx2 m RNA表达呈上调趋势,CTSK m RNA呈下调趋势;(3)与模型组比较,左归丸组椎体压缩强度显著提升(P<0.05);(4)结果说明,左归丸可能通过下调DKK1的表达防治糖皮质激素性骨质疏松。展开更多
文摘背景:观察性研究表明他汀类药物可能对骨密度具有保护作用,这使其成为潜在的骨质疏松症治疗药物之一。目的:通过孟德尔随机化方法来评估药物靶点介导的脂质表型与骨密度之间的因果关系。方法:从IEU Open GWAS数据库获取了与他汀类药物相关的单核苷酸多态性以及骨密度相关数据。主要分析方法是逆方差加权法,同时也使用了加权中位数法、简单中位数法、加权中值方法和MR-Egger回归法。使用β值和95%CI来评估他汀类药物与骨密度之间的因果关系;另外,进行敏感性分析以验证结果的可靠性,使用Cochran’s Q检验来评估异质性,使用MR-Egger截距检验是否存在水平多效性。使用留一法分析确定是否有单个或多个单核苷酸多态性影响了结果。结果与结论:他汀类药物作用靶点——3-羟基-3-甲基戊二酰辅酶A还原酶介导的低密度脂蛋白胆固醇与足跟定量超声骨密度(β=-0.086,95%CI:-0.117至-0.055,P=5.42×10^(-8))和全身骨密度(β=-0.193,95%CI:-0.288至-0.098,P=7.35×10^(-5))呈显著相关。该研究结果支持了他汀类药物对骨密度的保护作用。这些发现不仅加深了对胆固醇相关基因和骨骼健康关系的理解,还揭示了改善骨密度的潜在治疗靶点。
文摘2型糖尿病肾病(Type 2 diabetic nephropathy, DKD)的基本机制是活性氧(reactive oxygen, ROS)和晚期糖基化终产物(advanced glycation end product, AGEs)的积累。除此之外持续和长期暴露于高血糖环境中,和其他危险因素,如肥胖、血脂异常和胰岛素抵抗都会导致2型糖尿病肾病。中医认为肾为先天之本,脾为后天之本,二者相互充养才能使机体维持正常的生命活动,脾胃虚弱是糖尿病肾病发病的病机之一。另外由于高血糖,炎性反应和胰岛素抵抗等因素可能导致2型糖尿病肾病患者继发骨质疏松。应监测骨代谢标志物包括骨吸收标志物[β-胶原降解产物测定(Beta-collagen degradation products, β-CTX)]和骨形成标志物[总I型胶原氨基端延长肽(Elongation of amino end of total type Ⅰ collagen, PINP)]和骨密度,做到早发现早治疗,减轻患者痛苦。临床应用降糖药物时应该关注其额外的降糖作用,注意降糖药物对患者肾脏和骨质疏松的影响。该文总结研究了2型糖尿病肾病患者继发骨质疏松的病因病机和降糖药物的额外作用,对今后的临床研究具有指导作用。
文摘The risk of fracture is increased in both type 1 diabetes mellitus(T1DM)and type 2 diabetes mellitus(T2DM).However,in contrast to the former,patients with T2DM usually possess higher bone mineral density.Thus,there is a considerable difference in the pathophysiological basis of poor bone health between the two types of diabetes.Impaired bone strength due to poor bone microarchitecture and low bone turnover along with increased risk of fall are among the major factors behind elevated fracture risk.Moreover,some antidiabetic medications further enhance the fragility of the bone.On the other hand,antiosteoporosis medications can affect the glucose homeostasis in these patients.It is also difficult to predict the fracture risk in these patients because conventional tools such as bone mineral density and Fracture Risk Assessment Tool score assessment can underestimate the risk.Evidence-based recommendations for risk evaluation and management of poor bone health in diabetes are sparse in the literature.With the advancement in imaging technology,newer modalities are available to evaluate the bone quality and risk assessment in patients with diabetes.The purpose of this review is to explore the patho-physiology behind poor bone health in diabetic patients.Approach to the fracture risk evaluation in both T1DM and T2DM as well as the pragmatic use and efficacy of the available treatment options have been discussed in depth.
基金Project supported by the National High-Tech R&D Program(863)of China(No.2012AA020408)the Medical and Health General Research Plan of Zhejiang Province(No.2014KYA103),China
文摘Objective： The aim of our meta-analysis was to assess the effects of antiepileptic drugs on bone mineral density and bone metabolism in epileptic children. Methods： Searches of Pub Med and Web of Science were undertaken to identify studies evaluating the association between antiepileptic drugs and bone mineral density and bone metabolism. Results： A total of 22 studies with 1492 subjects were included in our research. We identified：（1） a reduction in bone mineral density at lumbar spine（standardized mean difference（SMD）=-0.30, 95% confidence interval（CI） [-0.61,-0.05]）, trochanter（mean difference（MD）=-0.07, 95% CI [-0.10,-0.05]）, femoral neck（MD=-0.05, 95% CI [-0.09,-0.02]）, and total body bone mineral density（MD=-0.33, 95% CI [-0.51,-0.15]）;（2） a reduction in 25-hydroxyvitamin D（MD=-3.37, 95% CI [-5.94,-0.80]） and an increase in serum alkaline phosphatase（SMD=0.71, 95% CI [0.38, 1.05]）;（3） no significant changes in serum parathyroid hormone, calcium, or phosphorus. Conclusions： Our meta-analysis suggests that treatment with antiepileptic drugs may be associated with decreased bone mineral density in epileptic children.
文摘1概述1.1定义和分类骨质疏松症(osteoporosis)是一种以骨量低下、骨组织微结构损坏,导致骨脆性增加,易发生骨折为特征的全身性骨病[1]。2001年美国国立卫生研究院(National Institutes of Health,NIH)将其定义为骨强度下降和骨折风险增加为特征的骨骼疾病[2]。骨质疏松症可发生于任何年龄,但多见于绝经后女性和老年男性。
文摘背景:中医药可有效防治糖皮质激素性骨质疏松,但其防治机制尚不明确。DKK1是Wnt/β-catenin信号通路的抑制剂,糖皮质激素可诱导其上调。因此,DKK1蛋白是防治糖皮质激素性骨质疏松的重要靶点。目的:探讨左归丸防治糖皮质激素性骨质疏松中对DKK1的调控作用。方法:18只3月龄雌性SD大鼠随机均分为3组:空白组、模型组和左归丸组。模型组和左归丸组大鼠皮下注射地塞米松建立糖皮质激素性骨质疏松模型;空白组给予等体积生理盐水;左归丸组皮下注射地塞米松同时给予左归丸水提液灌胃。1个月后取大鼠腰椎进行micro-CT检测骨量及骨微细结构、压缩试验检测生物力学性能,q PCR测定腰椎DKK1、Runx2和CTSK m RNA表达;血清检测碱性磷酸酶活性。结果与结论:(1)与空白组比较,模型组体积骨密度、相对骨体积、骨小梁数量和骨小梁厚度显著降低(P<0.05),骨小梁间距和结构模型指数较空白组显著增大(P<0.05),血清碱性磷酸酶活性较空白组呈降低趋势,DKK1 m RNA表达显著上调(P<0.05),成骨相关因子Runx2 m RNA表达呈下调趋势,破骨相关因子CTSK m RNA呈上调趋势;(2)与模型组比较,左归丸组体积骨密度、相对骨体积和骨小梁数量显著提升(P<0.05),结构模型指数显著降低(P<0.05),骨小梁间距有减小趋势但差异无显著性意义,血清碱性磷酸酶活性较模型组呈升高趋势,DKK1 m RNA表达显著下调(P<0.05),Runx2 m RNA表达呈上调趋势,CTSK m RNA呈下调趋势;(3)与模型组比较,左归丸组椎体压缩强度显著提升(P<0.05);(4)结果说明,左归丸可能通过下调DKK1的表达防治糖皮质激素性骨质疏松。
