FGF23 in Pediatric Phosphate Physiology and X-linked Hypophosphatemic Rickets.

FGF23 在小儿磷酸盐生理学和 X 连锁低磷血症性佝偻病中的作用。

• 批准号: 7639753
• 负责人: Erik Allen Imel
• 金额: $ 12.85万
• 依托单位: INDIANA UNIV-PURDUE UNIV AT INDIANAPOLIS
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-07-01 至 2014-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7639753
• 关键词: Abbreviations; Adolescent; Adult; Adverse effects; Affect; Age; Award; Biochemistry; Blood; Body Size; Bone Density; Bone Mineral Contents; Calcinosis; Calcitriol; Child; Childhood; Clinical Research; Cross-Sectional Studies; Data; Development; Diagnosis; Disease; Disease Outcome; Dose; Dual-Energy X-Ray Absorptiometry; Enrollment; Environment; Error Sources; Familial hypophosphatemic bone disease; Fracture; Functional disorder; Future; Goals; Growth; Homeostasis; Hormones; Hyperparathyroidism; Incidence; Kidney; Knowledge; Lead; Measurement; Measures; Mediating; Medical; Mentors; Metabolic; Metabolism; Minerals; Mus; Neck; Nephrocalcinosis; Operative Surgical Procedures; Oral; Osteomalacia; Outcome; Patients; Physiology; Plasma; Play; Principal Investigator; Production; Prospective Studies; Race; Regulation; Research; Research Personnel; Research Technics; Role; Safety; Salts; Sampling; School-Age Population; Serum; Sex Characteristics; Skeleton; Study of serum; Testing; Therapeutic; Training; Tubular formation; Urine; Vertebral column; Vitamin D; Wasting Syndrome; Work; X-Ray Computed Tomography; bone; bone mass; boys; density; dental abscess; fibroblast growth factor 23; girls; inorganic phosphate; peptide hormone; response; sex; skeletal; success; treatment effect; tumor; wasting

DESCRIPTION (provided by applicant): The long term objectives are to establish expertise in metabolic bone research, to characterize the regulation of fibroblast growth factor-23 (FGF23) across the age spectrum of children, and to to explore the pathophysiology of this hormone in phosphate wasting disorders in order to optimize treatment for these disorders. FGF23 is a key regulator of phosphate and vitamin D metabolism, and FGF23 dysregulation is central to X-linked hypophosphatemic rickets (XLH). Serum phosphate concentrations are higher in children than in adults, which may be FGF23 mediated. There is little knowledge concerning the impact of FGF23 on phosphate and skeletal metabolism in healthy children, the effect of treatment of XLH with calcitriol and phosphate on FGF23, or the impact of FGF23 on adverse outcomes of XLH therapy. This lack of knowledge is detrimental to the safety of therapy for XLH. The overall hypothesis is that FGF23 is important in normal phosphate homeostasis in growing children and that FGF23 dysregulation is critical to phosphate wasting syndromes. We hypothesize that FGF23 concentrations vary with age, race, and sex during childhood and are related to parameters of phosphate metabolism and bone mineral content (Aim 1). We will measure serum FGF23, and blood and urine biochemistries on stored samples from healthy black and white boys and girls between the ages of 0 and 16 years (with bone mineral content assessment in a subset). To test the hypothesis that FGF23 levels in XLH are affected by treatment with calcitriol and phosphate and predict disease outcomes (Aim 2), we will enroll subjects with XLH in a prospective study, measuring serial FGF23 concentrations along with clinically important outcomes of XLH treatment, including the major side effects of therapy. These studies will lead to improvements in therapy for XLH. This award will allow the principal investigator to pursue clinical research in a strong mentored environment, while engaging in didactic coursework and specialized training in bone-specific research techniques (including bone histomorphometry and quantitative computed tomography), enhancing his future success as an independent investigator.

描述（由申请人提供）：长期目标是在代谢骨研究中建立专业知识，以表征儿童年龄范围内成纤维细胞生长因子23（FGF23）的调节，以探索这种激素在磷酸盐浪费疾病中的病理生理学，以优化这些疾病的治疗。 FGF23是磷酸盐和维生素D代谢的关键调节剂，FGF23失调对于X连锁的下磷酸rick（XLH）是核心。儿童的血清磷酸盐浓度高于成年人，这可能是FGF23介导的。关于健康儿童对FGF23对磷酸盐和骨骼代谢的影响的知识很少，钙三醇和磷酸盐对FGF23的XLH治疗的影响，或FGF23对XLH治疗不良结果的影响。缺乏知识对XLH治疗的安全有害。总体假设是，FGF23在成长中的儿童正常磷酸盐稳态中很重要，而FGF23失调对于磷酸盐浪费综合征至关重要。我们假设FGF23的浓度随儿童时期的年龄，种族和性别而变化，并且与磷酸盐代谢和骨矿物质含量的参数有关（AIM 1）。我们将测量血清FGF23，以及血液和尿液生物化学的生物化学，从0到16岁之间的健康黑白男孩和女孩的储存样品上（子集中有骨矿物质含量评估）。为了测试XLH中FGF23水平受骨化三醇和磷酸盐治疗的影响并预测疾病预后的假设（AIM 2），我们将在一项前瞻性研究中注册XLH的受试者，测量串行FGF23浓度以及临床上重要的XLH治疗结果，包括治疗的主要副作用。这些研究将导致XLH治疗的改善。该奖项将使首席研究者能够在强大的指导环境中进行临床研究，同时从事教学课程和骨特异性研究技术的专业培训（包括骨骼组织形态和定量计算机断层扫描），从而增强了他作为独立研究者的未来成功。