This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Vitamin D is very important for bone health. Vitamin D is either formed in the skin after sunlight shines on it or is taken in by mouth as a supplement. Vitamin D then needs to be activated by the kidneys (by the enzyme 1-hydroxylase, 1-OH-ase) to do its job in helping the body to absorb calcium through the intestinal tract, and helping the bone to become hardened (mineralized). In some situations, such as aging and in kidney diseases, the kidneys become less able to activate vitamin D and this can lead to weakened bones. Dr. Streeten has observed, during the course of seeing patients for osteoporosis and other conditions, that some people appear to be unable to adequately activate vitamin D even though they are young and have healthy kidneys. In this situation, to compensate for the lack of activated vitamin D, the hormone from the parathyroid glands (4 glands in the neck that help to control calcium balance), parathyroid hormone, is secreted excessively into the blood. Excessive parathyroid hormone can cause bone loss. These patients have suspected partial 1-OH-ase deficiency. Their elevated parathyroid hormone (PTH) can be corrected by giving them activated vitamin D (1,25-dihydroxyvitamin D, 1,25-D, called calcitriol). Dr. Streeten plans to study 8 patients with suspected partial 1-OH-ase deficiency and 8 controls. We plan to study the function of the 1-OH-ase enzyme in the 8 patients and 8 controls in 3 ways: (1) Stimulating the 1-OH-ase enzyme by giving an intravenous (IV) infusion of PTH, the natural stimulus to the enzyme. We will give Forteo (synthetic PTH, FDA approved for osteoporosis) IV in a dose used by previous researchers, 12 pmol/kg/hr over 8 hours. No side effects and maximal stimulation of 1,25-D have been seen at this dose. Dr. Streeten has obtained an IND from the FDA for use of Forteo in this study (#76,579). (2) We will take blood from each participant, from which we will extract DNA to determine the sequence of the gene for 1-OH-ase. We hope to find a difference in the sequence in the patients compared to controls. (3) A small 4 mm skin punch biopsy will be taken from which we will measure the activity of the 1-hydroxylase enzyme. Although the main source of circulating 1,25-D is by the kidney 1-hydroxylase enxyme, the enzyme is also present in skin. The skin enzyme analysis will be done by Dr. Michael Holick at Boston University

National Institute of Health (NIH)
National Center for Research Resources (NCRR)
General Clinical Research Centers Program (M01)
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University of Maryland Baltimore
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