Recent Developments in Vitamin D Analogs

Abstract

Within the past decade it has been shown that psoriasis can be treated topically with analogs of vitamin-D3. Impaired differentiation and increased proliferation of keratinocytes are key features in psoriatic lesions together with a local activation of T lymphocytes. Evidence has accumulated showing that analogs of vitamin D3 increase differentiation and inhibit proliferation of keratinocytes. Therefore, analogs of vitamin D3 have been investigated in a number of trials showing improvement of psoriasis. It has been shown that vitamin D analogs are better than their vehicle and show the same potency as potent topical steroids. However, vitamin D analogs have been proven efficacious and without side effects also when used on long term basis. Vitamin D analogs can be used both as monotherapy and in combination topical steroids, UVB, PUVA, retinoids and cysclosporine. The vitamin D3 analog calcipotriol has been investigated in most detail and is available as an ointment, a creme and as a scalp solutation. From clinical studies involving thousands of patients, it can be concluded that calcipotriol is efficacious, safe, well tolerated and can be used on a long term basis. Other analogs are available, however, these analogs have not been studied in greater details yet.

UVB and Vitamin D in Psoriasis

“…Several studies have shown that calcipotriol as well as calcitriol and tacalcitol are efficacious, safe and can be used on a long-term basis for psoriasis (43,(46)(47)(48)(49). Vitamin D3 analogs can be used in combination with phototherapy(50).…”

Mechanisms implicated in the growth regulatory effects of vitamin D in breast cancer.

“…This analogue appears to be equipotent with 1,25(OH) 2 D 3 in inhibiting the growth of MCF-7 breast cancer cells in vitro (Colston et al 1992a), but displays calcaemic activity 100-200 times less than the natural hormone. This profile of activity was subsequently found to be largely due to rapid inactivation of the analogue in vivo and subsequently this compound has been developed and marketed for topical treatment of psoriasis (Binderup & Kragballe 1992, Fogh & Kragballe 2000. With regard to breast cancer, the efficacy of topical treatment of cutaneous nodules with calcipotriol has been investigated (Bower et al 1991).…”

A 1α,25-Dihydroxyvitamin D3 Analog Enhances Regulatory T-Cells and Arrests Autoimmune Diabetes in NOD Mice

“…1,25(OH) 2 D 3 and its analogs have been shown to inhibit autoimmune diseases in animal models, such as experimental allergic encephalomyelitis (14 -16), murine lupus (17), collagen-induced arthritis (18,19), and type 1 diabetes (20). They are clinically used in the treatment of psoriasis, a Th1-mediated autoimmune disease of the skin, where they show efficacy comparable to topical steroids (21). Polymorphisms of the vitamin D receptor gene have been associated with type 1 diabetes in different populations (22,23).…”