Vitamin D Deficiency in Primary Hyperparathyroidism

原发性甲状旁腺功能亢进症维生素 D 缺乏

• 批准号: 8664370
• 负责人: SHONNI J SILVERBERG
• 金额: $ 56.88万
• 依托单位: COLUMBIA UNIVERSITY HEALTH SCIENCES
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-07-01 至 2017-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8664370
• 关键词: 25-hydroxyvitamin D; Admixture; Area; Biochemical; Biomechanics; Biopsy; Bone Density; Bone Diseases; Bone remodeling; Calcium Metabolism Disorders; Caring; Cholecalciferol; Clinical; Consensus; Data; Disease; Disease of parathyroid glands; Dose; Educational workshop; Endocrine System Diseases; Frequencies; Fright; General Population; Goals; Guidelines; Health; Hypercalcemia; Hyperparathyroidism; Individual; International; Label; Level of Evidence; Measurement; Measures; Methods; Osteitis Fibrosa Cystica; Osteogenesis; Parathyroid gland; Patients; Phenotype; Physicians; Physiological; Population; Publishing; Randomized Clinical Trials; Recommendation; Regimen; Research; Risk; Safety; Secondary Hyperparathyroidism; Severities; Skeleton; Supplementation; System; Testing; Time; Tissues; Vitamin D; Vitamin D Deficiency; Vitamin D2; base; bone; bone imaging; bone strength; bone turnover; clinical decision-making; clinically relevant; hypercalciuria; imaging modality; improved; indexing; skeletal

DESCRIPTION (provided by applicant): Vitamin D deficiency or insufficiency is more common in primary hyperparathyroidism (PHPT) than in the general population. Clinical manifestations of PHPT are more severe in vitamin D deficient patients, and even in those with mild disease, patients with low vitamin D levels have higher PTH concentrations and bone turnover markers. Given the frequency of vitamin D deficiency in the PHPT population, it is likely that our current understanding of the biochemical and skeletal features of PHPT reflects an admixture of these two conditions. The central hypotheses of this proposal are that in patients with PHPT: 1) Vitamin D deficiency worsens the hyperparathyroid state and is associated with its own specific skeletal features; and 2) Repletion of vitamin D will ameliorate those aspects of the disease that are due to vitamin D deficiency, and thus reveal the true biochemical and skeletal phenotype of the underlying disease. To test these hypotheses, this proposal will utilize state-of-the-art biochemical and skeletal imaging methods. The proposal has the following aims: 1. To compare PHPT patients with and without vitamin D deficiency in order to: a) determine the skeletal features of the hyperparathyroid state that are attributable to vitamin D deficiency; and b) to describe the skeleton in PHPT without the confounding effects of co- existing vitamin D deficiency. 2. To investigate the early effects of high dose vitamin D repletion on histomorphometric parameters of bone remodeling (by quadruple labeled bone biopsy). 3. To investigate the effects of three vitamin D repletion regimens on biochemical, denstometric, microarchitectural and biomechanical features of PHPT. This proposal will fulfill a key mandate of the Third International Workshop on Asymptomatic Primary Hyperparathyroidism (2008) to obtain more data on vitamin D deficiency in individuals with PHPT. The recently published International Consensus Guidelines on Asymptomatic PHPT (J Clin Endocrinol Metab 94:335-9, 2009) specifically call for measurement of 25- hydroxyvitamin D in all patients with PHPT, and repletion of low levels (<20 ng/ml). However, no recommendations for repletion were included in the Guidelines, because of limited data upon which to base them. This information is urgently needed, as are data on the effects of vitamin D treatment in PHPT upon clinically relevant endpoints such as bone density, skeletal microarchitecture, bone remodeling and bone strength. This proposal will therefore enhance our understanding of the skeleton in PHPT, while providing information that may help in formulating recommendations for vitamin D repletion, a key research goal of the new Consensus Guidelines, and an imperative for clinicians treating this disorder. The ultimate benefit will be to patients with PHPT, for whom clinical decision-making will be strengthened by data that have heretofore not been available.

描述（由申请人提供）：与普通人群相比，在原发性甲状旁腺功能亢进症（PHPT）中，维生素D缺乏症或不足更为常见。 pHPT的临床表现在维生素D缺乏患者中更为严重，即使在患有轻度疾病的患者中，维生素D水平低的患者的PTH浓度较高和骨转换标记。鉴于PHPT种群中维生素D缺乏症的频率，我们目前对PHPT的生化和骨骼特征的理解可能反映了这两种情况的混合。该提案的中心假设是，在PHPT患者中：1）维生素D缺乏症会恶化甲状旁腺功能亢进状态，并与其自身的特定骨骼特征有关； 2）维生素D的补充将改善由于维生素D缺乏症引起的疾病的那些方面，因此揭示了潜在疾病的真正生化和骨骼表型。为了检验这些假设，该建议将利用最先进的生化和骨骼成像方法。该提案具有以下目的：1。比较患有和没有维生素D缺乏症的PHPT患者： b）描述PHPT中的骨骼，而没有共同现有维生素D缺乏的混杂作用。 2。研究高剂量维生素D的早期对骨重塑的组织形态计量学参数的早期作用（通过标记为骨骼活检的四倍）。 3。研究三种维生素D增生方案对pHPT的生化，固定，微构造和生物力学特征的影响。该提案将履行第三次国际无症状原发性甲状旁腺功能亢进症（2008）的关键任务，以获取有关PHPT患者维生素D缺乏症的更多数据。最近发表的有关无症状PHPT的国际共识指南（J Clin Endocrinol Metab 94：335-9，2009）专门呼吁所有PHPT患者的25-羟基维生素D测量，并呼吁低水平（<20 ng/ml）。但是，指南中未包含补充建议，因为数据基础的数据有限。迫切需要此信息，以及关于PHPT中维生素D处理对临床相关终点的影响的数据，例如骨密度，骨骼微体系结构，骨骼重塑和骨骼强度。因此，该提案将增强我们对PHPT中骨骼的理解，同时提供可能有助于提出维生素D的建议的信息，这是新的共识指南的关键研究目标，以及治疗这种疾病的临床医生的必要性。最终的好处将是对PHPT的患者，迄今无法获得临床决策的数据。