Different Vitamin D Preparations & FGF23 in Humans

Fibroblast growth factor 23 (FGF23) is a novel hormone involved in phosphate and vitamin D
physiology. X-linked hypophosphatemia (XLH), autosomal dominant hypophosphatemic rickets
(ADHR), and tumor induced osteomalacia (TIO) are 3 rare diseases characterized by
rickets/osteomalacia, fractures, and hypophosphatemia secondary to renal phosphate wasting
and inappropriately low levels of activated vitamin D (calcitriol), which are caused by
excess amounts of or mutated FGF23. FGF23 excess also occurs in renal failure, where
elevated FGF23 levels predict increased mortality. Thus, abnormal FGF23 appears to be
central to both rare and common diseases. While FGF23 appears to be regulated by vitamin D,
dietary and serum phosphate, much is still unknown. The effects of different forms of
vitamin D on FGF23 stimulation are not well characterized. Similarly, any racial differences
in the regulation of FGF23 by vitamin D have not been investigated.

To address these knowledge deficits, we will randomize 52 vitamin D deficient (25OHD < or =
24 ng/mL by LC/MS) Caucasian and African-American men and women to treatment with either
dietary vitamin D or activated vitamin D for 12 weeks. Our primary endpoint will be the
change in FGF23 with dietary versus activated vitamin D.