Disease and Vitamin D
The figure to the right presents a schematic
diagram of the metabolic processing of vitamin D via its endocrine system.
Listed under each of the various metabolic or regulatory sites are disease
states that are known to be clinically focused at that particular locus.
Conceptually, human clinical disorders related to vitamin D can be considered
as those arising because of (a) altered availability of vitamin D; (b) altered
conversion of vitamin D3 to 25(OH)D3; (c) altered
conversion of 25(OH)D3 to
1a,25(OH)2D3 and/or
24R,25(OH)2D3; (d) variations in end organ responsiveness
to 1a,25(OH)2D3 or
possibly 24R,25(OH)2D3; and (e) other conditions of
uncertain relation to vitamin D. Thus, the clinician/nutritionist/biochemist is
faced with a problem, in a diagnostic sense, of identifying parameters of
hypersensitivity, antagonism, or resistance (including genetic aberrations) to
vitamin D or one of its metabolites as well as identifying perturbations of
metabolism that result in problems in production and/or delivery of the
hormonally active form,
1a,25(OH)2D3. A detailed
consideration of this area is beyond the scope of this presentation. There are
many scientific publications and only a few recent summary articles are listed
at the end of this presentation.
Drug Forms of 1a,25(OH)2D3
As a consequence of the significant scientific advances in the understanding of
how vitamin D generates biological responses [principally via
1a,25(OH)2D3], a number
of new drug forms of
1a,25(OH)2D3 have been
generated by pharmaceutical companies. The table below
summarizes these new drugs and the relevant pharmaceutical company, and
identifies the clinical circumstance for which their use has been authorized.
DRUG FORMS OF VITAMIN D METABOLITES
|
COMMERCIAL NAME | (COMPANY) | COMPOUND | EFFECTIVE DAILY DOSE (micrograms)
|
|---|
|
CALDEROL | (ORGANON Inc.-USA) | 25(OH)D3 | 50-500
|
|
ONE-ALPHA | (LEO-DENMARK) | 1a-OH-D3 | 1-2
|
|
ALPHA-D3 | (TEVA-ISRAEL) | 1a-OH-D3 | 0.25-1.0
|
|
ONEALFA | (TEIJIN LTD-JAPAN) | 1a-OH-D3 | 0.25-1.0
|
|
ALFAROL | (CHUGAI-JAPAN) | 1a-OH-D3 | 0.25-1.0
|
|
ROCALTROL | (ROCHE PHARMACEUTICALS) | 1a,25(OH)2D3 | 0.5-1.0
|
|
ZEMPLAR | (ABBOTT LABORATORIES) | 1a,25(OH)219-nor-D2 | 3-7
|
|
CALCIJEX | (ABBOT LABORATORIES) | 1a,25(OH)2D3 | 0.5 (i.v.)
|
|
DOVONEX | (WESTWOOD SQUIBB) | Calcipotriol | (only external)
|
|
TACALCITOL | (TEIJIN LTD-JAPAN) | 1a,24R(OH)2D3 | (only external)
|
References:
Jones, G. and Calverley, M.J. A dialogue of analogues: Newer vitamin D drugs for use in bone disease, psoriasis and cancer. Trends in Endocrinol. Metab. 4:297-303 (1993).
Bikle, D.D. Clinical counterpoint: Vitamin D: New actions, new analogs, new therapeutic potential. Endocr. Rev. 13:765-784 (1992).
Binderup, L. and Kragballe, K. Origin of the use of calcipotriol in psoriasis treatment. Rev. Contemp. Pharmacother. 3:357-365 (1992).
Pols, H.A.P., Birkenhäger, J.C., Foekens, J.A. and van Leeuwen, J.P.T.M. Vitamin D: A modulator of cell proliferation and differentiation. J. Steroid Biochem. Mol. Biol. 37:873-876 (1990).
Reichel, H. Koeffler, H.P. and Norman, A.W. The role of the vitamin D endocrine system in health and disease. New Engl. J. Med. 320:980-991 (1989).
The figure to the right presents a schematic
diagram of the metabolic processing of vitamin D via its endocrine system.
Listed under each of the various metabolic or regulatory sites are disease
states that are known to be clinically focused at that particular locus.
Conceptually, human clinical disorders related to vitamin D can be considered
as those arising because of (a) altered availability of vitamin D; (b) altered
conversion of vitamin D3 to 25(OH)D3; (c) altered
conversion of 25(OH)D3 to
1a,25(OH)2D3 and/or
24R,25(OH)2D3; (d) variations in end organ responsiveness
to 1a,25(OH)2D3 or
possibly 24R,25(OH)2D3; and (e) other conditions of
uncertain relation to vitamin D. Thus, the clinician/nutritionist/biochemist is
faced with a problem, in a diagnostic sense, of identifying parameters of
hypersensitivity, antagonism, or resistance (including genetic aberrations) to
vitamin D or one of its metabolites as well as identifying perturbations of
metabolism that result in problems in production and/or delivery of the
hormonally active form,
1a,25(OH)2D3. A detailed
consideration of this area is beyond the scope of this presentation. There are
many scientific publications and only a few recent summary articles are listed
at the end of this presentation.