ReviewVitamin D3 and calcidiol are not equipotent
Introduction
Despite the discussion on the optimal serum threshold of 25-hydroxyvitamin D continues, between 50 nmol/L [1] and 75 nmol/L [2], [3], there is now a general consensus on the fact that post-menopausal and elderly populations have inadequate vitamin D serum levels worldwide [4], [5].
The adjustment of these levels is necessary to improve both bone and general health [6], [7], as it is to optimize bone response to antiresortive treatments [8], [9]. It is recommended, as endorsed by international clinical guidelines, to use Vitamin D3 (cholecalciferol) – the physiological form of Vitamin D – in a dose range between 600–2000 IU. The biological potency of Vitamin D is established as international units (IU), so that 1 μg of cholecalciferol is equivalent to 40 IU [1]. In that context, vitamin D should be administered on a daily basis or on its weekly or monthly equivalents [10].
In some parts of the world, such as Spain, other vitamin D metabolites like calcidiol (25 hydroxyvitamin D3) are available for use in the treatment of osteoporosis [11], [12]. Nevertheless, this metabolite is not an equipotent substitute for adequate vitamin D replacement because all the recommendations have been done with cholecalciferol (Vitamin D3) [13]. Calcidiol compared with cholecalciferol is more hydrophilic, has a shorter half-life, and causes more rapid and sustained increase in serum 25(OH)D concentrations [14], [15].
In Spain, the use of calcidiol at a dose similar to Vitamin D3 is the most extended prescription, notwithstanding the consistent evidence stating that they are not equipotent [16], [17]. This fact may lead to over-dosage and risk of hypervitaminosis D and hypercalcemia induced by calcidiol [18], as evidenced by a review of cases reported to the Spanish Pharmacovigilance System [19].
Based upon the foregoing, in this study we have evaluated the efficacy of calcidiol vs. Vitamin D3 in increasing 25-hydroxyvitamin D -25(OH)D- serum levels, a convenience study in order to provide evidence of the differences between both metabolites prescribed in the common practice posology.
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Patients and methods
This convenience study was conducted, after receiving the informed consent, at the Mineral Metabolism Unit-IMIBIC of the Hospital Universitario “Reina Sofía”, Córdoba (Spain), latitude 36.7°. Forty post-menopausal osteopenic women with general good health, average age 67 years, and deficient in Vitamin D (37.5 ± 5 nmol/L) were studied. The patients were randomized for treatment with vitamin D3 in four groups comparable to each other with respect to all the evaluated characteristics. Each group
Results
Baseline levels, general anthropometrics and biochemical characteristics of the postmenopausal women (PM) enrolled in the study are shown in Table 1. All the PM (100%) had levels of vitamin D below 50 nmol/L at the beginning of the study.
At baseline, there was an inverse correlation between calcium and alkaline phosphatase levels (r: −0.392; p: 0.012). An inverse correlation was also found when levels of PTH were compared to phosphate (r: −0.388; p: 0.013) and 25(OH)D3 (r: −0.768; p: 0.000).
Discussion
Vitamin D status in humans is determined by measuring serum 25(OH)D concentration (2,7). Based upon the increase induced in 25(OH)D levels by calcidiol and cholecalciferol, our data do not support either the proposal stating that both metabolites are equipotent. Contrarily, our data confirm previous reports claiming that they are different molecules with different pharmacological mechanisms, which must be dosed differently to achieve the same target.
Calcidiol is a more polar metabolite than
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