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

• 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
• 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

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 这是由Charles Ginsberg博士在Joachim博士的指导下首次提交的K23申请 在加州圣地亚哥大学（UCSD）的IX。通过这项提案，金斯伯格博士打算建立 他自己作为一名独立的研究者，研究慢性肾脏疾病-矿物质骨疾病（CKD-MBD）。 候选人：金斯伯格博士的培训目标在这个建议包括：1）成为熟练的性能 2）骨组织形态计量学的解释和3）学习必要的技能，以制定一个 研究团队并进行临床试验。金斯伯格博士将通过指导来实现这些目标， 课程，并参加讲习班和指导委员会。他组建了一个多学科的 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的生物统计学专家Isidro Salusky博士是骨活检性能和解释的领导者。 研究：维生素D缺乏在美国人中很常见，已知会导致骨软化症，佝偻病， 和骨折血清25-羟基维生素D [25（OH）D]，推荐用于评估 维生素D缺乏症是有缺陷的，因为25（OH）D与骨骼之间存在相互矛盾的证据 密度和断裂风险。Ginsberg博士假设，25（OH）D作为骨标记的弱点 健康的部分原因是维生素D结合蛋白（DBP）的变异性。在金斯伯格博士的初步工作中， 证明了24，25-二羟维生素D与25（OH）D的比率[维生素D代谢物比率（VMR）]是一个 老年人骨折风险的上级标志物，与单用25（OH）D相比。VMR被假设为 维生素D状态的标志物，与DBP浓度无关。在目标1中，金斯伯格博士将评估 25（OH）D、其他维生素D代谢产物和VMR与血清DBP浓度之间的关系 在健康，衰老和身体组成（健康ABC）研究中，1，142名老年人中进行了一项观察性研究。 队列由患有和不患有CKD的个体组成。这将确定VMR实际上是否独立于 DBP浓度的差异。在目标2中，Ginsberg博士将评估25（OH）D， 其他维生素D代谢物，以及健康ABC研究中骨密度纵向变化的VMR 并将确定考虑DBP的差异是否影响这些关系。在目标3中，金斯伯格博士 将评估25（OH）D，其他维生素D代谢物和VMR与 接受骨活检的CKD患者的未矿化骨。这将提供一个直接的病理 与骨疾病相关，并将确定这些关系受DBP影响的程度 浓度的这不仅可以更好地了解骨病理学的变化， 但也将识别CKD-MBD的有价值的生物标志物，并可能最终 为维生素D缺乏的测量和治疗提供了更合理的方法。

项目成果

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
• 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
• 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

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。

• DOI: 10.2215/cjn.14260920
• 发表时间: 2021
• 期刊: Clinical journal of the American Society of Nephrology : CJASN
• 作者: Ginsberg,Charles

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
• 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