Calcidiol [25(OH)D3]: from diagnostic marker to therapeutical agent

Abstract

Objective:

Osteoporosis is a skeletal disorder characterized by diminished bone strength, which results in an increased risk of fracture. Currently, osteoporosis is a public health priority due to the large number of individuals affected and the detrimental effect on quality of life. Primary osteoporosis, the most common form, usually results from age-related reduction in bone mineral strength. Over time, the individual’s capacity to build bone is impaired, as the synthesis of vitamin D, the hormone responsible for calcium absorption, tends to decline. As serum calcium levels decrease, metabolic control serves to increase the removal of calcium from the skeleton to make up for the deficit. The synthesis of the ‘hormone’ vitamin D and its control therefore become central to intervention in involutional osteoporosis syndromes. In humans, plain vitamin D (cholecalciferol), also called parental or native vitamin D, is photosynthesized in the skin and then hydroxylated in the liver into the vitamin D analog calcidiol [25(OH)D3], which is hydroxylated again in the kidney into the vitamin D analog calcitriol [1,25(OH)2D3]. The advantage of administering vitamin D analogs is that the pro-drug calcidiol avoids the effect of declines in hepatic function, while calcitriol avoids the effect of declines in hepatic and kidney function. A strategy to enhance [25(OH)D3] levels to the optimal threshold of vitamin D is supplementation with the calcidiol metabolite itself. The goal of this paper is to review published studies on the efficacy of the calcidiol metabolite in increasing 25(OH)D3 serum levels and improving skeletal health parameters in humans.

Methods:

A library search of published papers in the area of use of calcidiol in humans from 1967 to 2013 was performed (key words: calcidiol, 25-hydroxy-vitamin D3, vitamin D supplementation, vitamin D metabolism, osteomalacia).

Results and conclusion:

The results of the survey made it possible to conclude that calcidiol is characterized by a number of features that make the compound ideal in conditions that require supplementation with a 25-hydroxylated metabolite.

Keywords::

• Calcidiol
• Vitamin D3
• Vitamin D metabolites
• Vitamin D status
• Vitamin D supplementation
• Vitamin D toxicity

Transparency

Declaration of funding

This work was supported by an unrestricted grant from F.I.R.M.O. Fondazione Raffaella Becagli to M.L.B.

Declaration of financial/other relationships

M.L.B. has disclosed that she has also received grants from Sevier, MSD, Eli Lilly, Roche, Novartis, and Amgen and has been a consultant to Sevier. S.M. has disclosed that he has no significant relationships with or financial interests in any commercial companies related to this study or article.

CMRO peer reviewers on this manuscript have received an honorarium for their review work. Reviewer 1 has disclosed that he has received grants and sponsorship from Servier, Novartis and IBSA; and is a consultant to Rottapharm. Reviewer 2 has disclosed that he is a consultant to Servier, Novartis, Negma, Eli Lilly, Amgen, GlaxoSmithKline, Roche, Merck, Nycomed, NPS, Theramex and UCB. He has received fees for speaking at invited lectures from Merck Sharp and Dohme, Elli Lilly, Rottapharm, IBSA, Genevrier, Novartis, Servier, Roche, GlaxoSmithKline, Teijin, Teva, Ebewee Pharma, Zodiac, Analis, Theramex, Nycomed, Novo-Nordisk and Nolver, and has received grant support from Bristol Myers Squibb, Merck Sharp & Dohme, Rottapharm, Teva, Eli Lilly, Novartis, Roche, GlaxoSmithKline, Amgen, and Servier.