Know Cancer

forgot password

Physiologic Regulation of FGF-23

18 Years
Not Enrolling

Thank you

Trial Information

Physiologic Regulation of FGF-23

Vitamin D and phosphate are central to normal mineral homeostasis and important in many
physiologic functions including skeletal integrity. For several decades parathyroid hormone
(PTH) has been recognized as a central regulator of serum vitamin D and phosphate levels.
Recently, FGF-23 has been identified as central in the regulation of the metabolism of
vitamin D and serum phosphorus. The organ primarily responsible for the physiologic
production of FGF-23 appears to be the skeleton. The study of FGF-23 metabolism and its
direct effect on mineral metabolism is confounded by the classic endocrine feedback loops
that exist among serum calcium, phosphorus, 1,25-(OH)2-vitamin D (1,25-D), and PTH. It is
possible that any of these (phosphorus, calcium, 1,25-D, and/or PTH) are important in the
regulation of serum FGF-23. The goal of this study is to identify what factors regulate
serum FGF-23.

To overcome the confounding effect of PTH, we will study patients deficient in PTH
(hypoparathyroidism) or resistant to PTH at the kidney (pseudohypoparathyroidism type 1B,
PHP1B). The kidney is one of the primary organs responsible for regulating serum phosphorus
and generating 1,25-D. It is the target of PTH and FGF-23. While patients with PHP1B are
resistant to the action of PTH at the kidney, they are sensitive to the action of PTH at the
bone, the tissue that produces FGF-23. Physiologic manipulation of the serum phosphorus,
1,25-D, calcium, and PTH in subjects with hypoparathyroidism or PHP1B will allow for a
nearly complete dissection of the factors that are potential regulators of serum FGF-23.

Inclusion Criteria


Adult hypoparathyroid patients, as defined by low or inappropriately normal PTH levels
despite hypocalcemia, who are on a stable treatment regimen of calcitriol and calcium
supplementation, and who are willing to participate in the study will be eligible.

Adult PHP1B patients as defined by the clinical syndrome of elevated PTH and phosphorus
and confirmed by methylation analysis of the GNAS gene.


Renal insufficiency as evidenced by a creatinine clearance of less than 50 ml/min

Medically unstable patients

Uncontrolled comorbid conditions, e.g., diabetes, coronary artery disease, congestive
heart failure, or cerebrovascular disease.

Digitalis therapy

Patients on diuretic therapy, especially thiazides

Pregnant and lactating women

Patients whose hypoparathyroidism is caused by severe calcium-sensing receptor defects.
These patients begin to have marked symptoms of "hypercalcemia" when the serum calcium is
in the mid-normal range.

Patients under 18 years of age

Patients with history of any bone cancer, skeletal metastases or previous radiotherapy to
the skeleton, unexplained elevations of serum alkaline phosphatase

Type of Study:


Study Design:



United States: Federal Government

Study ID:




Start Date:

July 2006

Completion Date:

Related Keywords:

  • Hypoparathyroidism
  • Phosphate
  • Vitamin D
  • Hypoparathyroidism
  • Phosphatonin
  • Clamp
  • Hypoparathyroidism



National Institutes of Health Clinical Center, 9000 Rockville PikeBethesda, Maryland  20892