Influence of Vitamin D Binding Protein on Clinical Measures of Vitamin D Status and Bone Health

维生素 D 结合蛋白对维生素 D 状态和骨骼健康临床指标的影响

基本信息

批准号：
10394279
负责人：
CHARLES GINSBERG
金额：
$ 20.31万
依托单位：
UNIVERSITY OF CALIFORNIA, SAN DIEGO
依托单位国家：
美国
项目类别：
财政年份：
2018
资助国家：
美国
起止时间：
2018-07-03 至 2024-04-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10394279
关键词：
25-hydroxyvitamin D Accounting Affect Affinity Aging American Binding Proteins Biological Availability Biological Markers Biopsy Body Composition Bone Density Bone Diseases California Catabolism Chronic Kidney Failure Clinical Conduct Clinical Trials Conflict (Psychology)Dihydroxycholecalciferols Educational workshop Elderly Fracture General Population Goals Health Hip Fractures Hormones Individual Lead Learning Link Literature Measurement Measures Mentors Mentorship Metabolism Minerals Osteoid Osteomalacia Pathologic Pathology Patients Performance Persons Physiologic calcification Positioning Attribute Renal function Research Research Personnel Rickets Risk Scientist Serum Tissues Toxic effect Training Universities Vitamin D Vitamin D Deficiency Vitamin D supplementation Vitamin D-Binding Protein Work bone bone health career cohort community living fracture risk multidisciplinary novel prevent skills

项目摘要

PROJECT SUMMARY This is an initial submission of a K23 application by Dr. Charles Ginsberg, under the mentorship of Dr. Joachim Ix at the University of California San Diego (UCSD). Through this proposal Dr. Ginsberg intends to establish himself as an independent investigator studying the chronic kidney disease-mineral bone disorder (CKD-MBD). Candidate: Dr. Ginsberg's training objectives in this proposal include; 1)become proficient in the performance of bone biopsies, 2)the interpretation of bone histomorphometry and 3)learn the necessary skills to develop a research team and conduct clinical trials. Dr. Ginsberg will accomplish these objectives through mentorship, coursework, and participation in workshops and steering committees. He has assembled a multidisciplinary team of scientists including his primary mentor Dr. Joachim Ix, an expert in the CKD-MBD, Dr. Florin Vaida, an expert biostatistician at UCSD, and Dr. Isidro Salusky a leader in bone biopsy performance and interpretation. Research: Vitamin D deficiency is common among Americans and is known to lead to osteomalacia, rickets, and fractures. Serum 25-hydroxyvitamin D [25(OH)D], the recommended clinical parameter to assess for vitamin D deficiency, is flawed as there is conflicting evidence of association between 25(OH)D with bone density and fracture risk. Dr. Ginsberg hypothesizes that the weakness of 25(OH)D as a marker for bone health is, in part, due to variability in vitamin D binding protein (DBP). In Dr. Ginsberg's preliminary work he demonstrated that the ratio of 24,25-dihydroxyvitamin D to 25(OH)D [the vitamin D metabolite ratio (VMR)] is a superior marker of fracture risk in older adults, compared to 25(OH)D alone. The VMR is hypothesized to be a marker of vitamin D status that is independent of DBP concentrations. In Aim 1, Dr. Ginsberg will evaluate the relationship between 25(OH)D, other vitamin D metabolites, and the VMR with serum DBP concentrations among 1,142 older adults in the Health, Aging and Body Composition (Health ABC) Study; an observational cohort comprised of individuals with and without CKD. This will establish if the VMR is in fact independent of differences in DBP concentrations. In Aim 2, Dr. Ginsberg will evaluate the associations between 25(OH)D, other vitamin D metabolites, and the VMR with longitudinal change in bone density in the Health ABC Study and will determine if accounting for differences in DBP influences these relationships. In Aim 3, Dr. Ginsberg will evaluate the associations of 25(OH)D, other vitamin D metabolites, and the VMR with the degree of unmineralized bone in patients with CKD undergoing bone biopsies. This will provide a direct pathological correlate of bone disease and will determine the degree to which these relationships are influenced by DBP concentrations. This will not only allow for a better understanding of the variability in bone pathology seen across the spectrum of CKD but will also identify valuable biomarkers of the CKD-MBD and may ultimately provide a more rational approach to measurement and treatment of vitamin D insufficiency.

项目摘要这是查尔斯·金斯伯格（Charles Ginsberg）博士在Joachim博士的指导下的K23申请的初步提交。加州大学圣地亚哥分校（UCSD）的IX。通过这项建议，金斯伯格博士打算建立他本人是研究慢性肾脏病矿物质骨病（CKD-MBD）的独立研究者。候选人：本提案中金斯伯格博士的培训目标包括： 1）精通表演骨骼活检，2）解释骨骼组态法和3）学习开发的必要技能研究团队并进行临床试验。金斯伯格博士将通过指导实现这些目标，课程工作，并参加研讨会和转向委员会。他已经组建了一个多学科科学家团队包括他的主要导师Joachim IX博士，CKD-MBD专家Florin Vaida博士， UCSD的专家生物统计学家和Isidro Salusky博士是骨骼活检和解释领域的领导者。研究：维生素D缺乏症在美国人中很常见，众所周知会导致骨质核酸，rick骨，rick。和骨折。血清25-羟基维生素D [25（OH）D]，建议评估的临床参数维生素D缺乏症存在缺陷，因为有25（OH）D与骨头之间有关联的证据相互矛盾密度和断裂风险。金斯伯格博士假设25（OH）D的弱点是骨头的标记健康部分是由于维生素D结合蛋白（DBP）的变异性。在金斯伯格博士的初步工作中证明24,25-二羟基维生素D与25（OH）D的比率[维生素D代谢物比（VMR）]是一个老年人骨折风险的出色标记，而仅25（OH）D。 VMR被认为是维生素D状态的标记与DBP浓度无关。在AIM 1中，金斯伯格博士将评估 25（OH）D，其他维生素D代谢物与血清DBP浓度的VMR之间的关系在健康，衰老和身体成分（健康ABC）研究中的1,142名老年人中；观察性队列由有和没有CKD的个体组成。这将确定VMR是否实际上独立于 DBP浓度的差异。在AIM 2中，金斯伯格博士将评估25（OH）D之间的关联在健康ABC研究中，其他维生素D代谢产物和具有纵向变化的VMR 并将确定DBP差异是否会影响这些关系。在AIM 3中，金斯伯格博士将评估25（OH）D的关联，其他维生素D代谢产物和VMR的关联程度 CKD患者的无矿化骨骼正在进行骨活检。这将提供直接的病理骨骼疾病的相关性，并将确定这些关系受DBP影响的程度浓度。这不仅可以更好地了解所见骨病理学的变异性跨CKD范围，但还将确定CKD-MBD的有价值的生物标志物，最终可能提供了一种更合理的方法来测量和治疗维生素D功能不全。

项目成果

期刊论文数量（10）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Effect of Lanthanum Carbonate on Blood Pressure in CKD.

DOI：
10.1053/j.ajkd.2020.12.012
发表时间：
2021-08
期刊：
American journal of kidney diseases : the official journal of the National Kidney Foundation
影响因子：
0
作者：
通讯作者：

New Insights into the Effects of Etelcalcetide on Bone Health.

关于 Etelcalcetide 对骨骼健康影响的新见解。

DOI：
10.2215/cjn.0000000000000316
发表时间：
2023
期刊：
Clinical journal of the American Society of Nephrology : CJASN
影响因子：
0
作者：
Ginsberg,Charles;Ix,JoachimH
通讯作者：
Ix,JoachimH

The Effects of Intensive Blood Pressure Lowering on Markers of Mineral Metabolism in Persons with CKD in SPRINT.

SPRINT 中强化降压对 CKD 患者矿物质代谢标志物的影响。

DOI：
10.2215/cjn.01400220
发表时间：
2020
期刊：
Clinical journal of the American Society of Nephrology : CJASN
影响因子：
0
作者：
Ginsberg,Charles;Katz,Ronit;Chonchol,MichelB;Bullen,AlexanderL;Raphael,KalaniL;Zhang,WilliamR;Ambrosius,WalterT;Bates,JeffreyT;Neyra,JavierA;Killeen,AnthonyA;Punzi,Henry;Shlipak,MichaelG;Ix,JoachimH
通讯作者：
Ix,JoachimH

Vitamin D Metabolite Ratio and Coronary Artery Calcification in the Multi-Ethnic Study of Atherosclerosis.

动脉粥样硬化多种族研究中的维生素 D 代谢比和冠状动脉钙化。

DOI：
10.1161/circimaging.122.015055
发表时间：
2023
期刊：
Circulation. Cardiovascular imaging
影响因子：
0
作者：
Ginsberg,Charles;Hoofnagle,AndrewN;Katz,Ronit;Cheng,JonathanH;Hsu,Simon;Budoff,MatthewJ;Kado,DeborahM;Kestenbaum,Bryan;Siscovick,DavidS;Michos,ErinD;Ix,JoachimH;deBoer,IanH
通讯作者：
deBoer,IanH

The Influence of Medical School Debt on Career Choices in Nephrology.

医学院债务对肾脏病学职业选择的影响。