Effects of vitamin D derivatives on soft tissue calcification in neonatal and calcium mobilization in adult rats

Kistler, Andreas D.; Galli, Brigitta; Horst, Ronald L.; Truitt, Gary A.; Uskoković, Milan R.

doi:10.1007/bf00303129

Cited by 10 publications

(2 citation statements)

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“…Most cases of vitamin D intoxication are thought to occur as a result of high plasma levels of 25(OH)D rather than high plasma 1a,25(OH) 2 D 3 levels. 33 Excess sensitivity to high normal vitamin D/25(OH)D levels also occurs when the normal feedback system by (renal) 1a-hydroxylase is compromised. This is especially the case in patients with chronic inflammation and ectopic activation of monocytic 1a-hydroxylase (e.g.…”

Section: Safety and Vitamin D Intakementioning

confidence: 99%

Vitamin D nutritional policy needs a vision for the future

Norman

Bouillon

2010

Exp Biol Med (Maywood)

202

147

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Historically vitamin D is known to be essential for normal bone growth and quality, and thus appropriate dietary vitamin D supplementation can eliminate vitamin D deficiency childhood rickets and adult osteomalacia. In spite of many government and medical associations' worldwide guidelines for the reference daily intake (RDI) of vitamin D, scientists and nutritionists from many countries agree that at present about half of elderly North Americans and Western Europeans and probably also of the rest of the world are not receiving enough vitamin D to maintain healthy bone. In addition, over the past decade there has been a dramatic increase in our understanding of the many biological actions that result from vitamin D acting through its daughter steroid hormone, 1alpha,25-dihydroxyvitamin D(3) [1alpha,25(OH)(2)D(3)] in collaboration with its cognate vitamin D receptor (VDR). Consequently, evidence has accumulated that beside intestine and bone, there are five additional physiological systems where the VDR with 1alpha,25(OH)(2)D generates biological responses. These include the immune system (both the innate and adaptive), pancreas and metabolic homeostasis, heart-cardiovascular, muscle and brain systems as well as the control of the cell cycle, and thus of the disease process of cancer. Acting through the VDR, 1alpha,25(OH)(2)D(3) can produce a wide array of favorable biological effects that collectively are projected to contribute to the improvement of human health. Responsible medicine demands that worldwide vitamin D nutritional guidelines reflect current scientific knowledge about vitamin D's spectrum of activities. Thus, worldwide vitamin D nutritional policy is now at a crossroads. This paper presents several proposed policy changes with regard to the amount of vitamin D daily intake that if implemented will maximize vitamin D's contribution to reducing the frequency of many diseases, which would then increase the quality and longevity of life and significantly reduce the cost of medical care worldwide.

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Section: Safety and Vitamin D Intakementioning

confidence: 99%

Vitamin D nutritional policy needs a vision for the future

Norman

Bouillon

2010

Exp Biol Med (Maywood)

202

147

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“…When exogenous calcitriol was administered systemically at high‐dose levels in animals, e.g. oral treatment in rats and dogs, plasma calcitriol levels increased considerably in excess of normal endogenous values, resulting in hypercalcaemia, hypercalciuria, hyper‐phosphaturia and ectopic calcification in the soft tissues 23 , 24…”

Section: Animal Studiesmentioning

confidence: 99%

Topical calcitriol - studies on local tolerance and systemic safety

Rizova

Corroller

2001

Br J Dermatol

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Calcitriol 3 microg g(-1) ointment (Silkis ointment, Galderma Laboratories) is a new treatment for psoriasis. Calcitriol is the biologically active metabolite of vitamin D3. It induces keratinocyte differentiation, inhibits keratinocyte, T-cell and fibroblast proliferation, and inhibits the production of some inflammatory mediators, all contributors to the pathogenesis of psoriasis. Preclinical studies have shown an effect of topical calcitriol on calcium homeostasis at doses higher than those in clinical use. No adverse local events were observed when calcitriol was applied to animal skin. Phase I clinical studies confirmed that calcitriol 3 microg g(-1) ointment is well tolerated in humans. These studies have demonstrated that at the minimal effective concentration of 3 microg g(-1), calcitriol ointment has no discernible photosensitizing or phototoxic potential and no skin irritant or allergic potential in healthy volunteers. Its low systemic absorption through human skin is unlikely to significantly affect calcium homeostasis. This paper summarizes the findings of the preclinical and early clinical studies that provided the foundation of the later Phase II and III clinical trials on efficacy and safety with topical calcitriol 3 microg g(-1) ointment for the treatment of plaque psoriasis.

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