The vitamin D endocrine system was originally discovered for its critical role in calcium and
phosphate homeostasis. The active form of vitamin D, 1,25-dihydroxyvitamin D3 (calcitriol), promotes
intestinal absorption of calcium and phosphate, but actions on bone, kidney and the parathyroids also
contribute to the control of mineral metabolism. Subsequently, the vitamin D receptor (VDR) was
detected in many other target tissues where calcitriol exerts pleiotropic effects, often in an
autocrine/paracrine fashion. These non-classical activities of calcitriol have suggested therapeutic
applications of calcitriol for the treatment of hyperproliferative disorders (e.g. cancer and psoriasis),
immune dysfunction (autoimmune diseases), and endocrine disorders (e.g. hyperparathyroidism). In
many cases, however, the effective therapeutic doses of calcitriol are hypercalcemic, a limitation that
has spurred the development of vitamin D analogs that retain the therapeutically useful actions of
calcitriol, but with reduced calcemic activity. Analogs with wider therapeutic windows are available for
treatment of psoriasis and secondary hyperparathyroidism in chronic kidney disease, and research on
even more effective analogs for these indications continues. Pre-clinical and clinical trials of analogs for
treatment of several types of cancer, autoimmune disorders, and many other diseases are underway.
Newer analogs show promise in various cellular models, but this review will focus on analogs currently
in use and those with documented efficacy in animal models or in clinical trials.
Keywords: Autoimmune diseases, breast cancer, colon cancer, leukemia, osteoporosis, pancreatic cancer,
prostate cancer, psoriasis, secondary hyperparathyroidism, skin cancer, transplant rejection.
