Vitamin D Metabolites and/or Analogs: Which D for Which Patient?

S.      Mazzaferro; D.      Goldsmith; T.E.      Larsson; Z.A.      Massy; M.      Cozzolino

Abstract

Numerous drugs with vitamin D activity are available for clinical use and it may not be easy for the nonspecialist to select the most suitable for the individual patient. In this paper we review the main characteristics of the available drugs and provide evidence about any potential specific clinical indications, with special emphasis on renal patients, in order to facilitate the optimal choice. Natural vitamin D products (i.e. those identical to natural metabolites) are first examined, followed by the most frequently used synthetic molecules (i.e. bioengineered molecules not-existing in nature), which are generally indicated as “ analogs”.

Either cholecalciferol, ergocalciferol or calcifediol can be employed in subjects with normal renal function and in CKD stage 3-5 patients to correct vitamin D deficiency and improve, respectively, age- or growth-related bone disease and secondary hyperparathyroidism. Calcifediol can be considered more rapid and effective. In all cases, especially with increasing doses, the risk of hypercalcemia must be taken into account.

Calcitriol, which can be regarded as the active hormonal form of vitamin D, has the most potent hypercalcemic effect in both normal and renal failure patients. In renal patients calcitriol is a potent inhibitor of parathyroid activity, but the risk of hypercalcemia, now regarded as harmful, is evident whenever pharmacologic doses are used.

Alfacalcidol, requiring 25-hydroxylation to become the active hormonal form of vitamin D₃, is prescribed in normal subjects to treat osteoporosis and in renal patients to cure hyperparathyroidism and renal bone disease. Doxercalciferol, transformed into the active hormonal form of vitamin D₂ following 25-hydroxylation, is mostly studied in renal patients in whom it cures secondary hyperparathyroidism, possibly with a lower calcemic effect than calcitriol.

Paricalcitol, a vitamin D₂ analog not requiring activation, has been specifically developed to suppress PTH in renal patients with a limited calcemic effect. As such it is now regarded as a powerful drug useful to treat even severe cases of secondary hyperparathyroidism. Importantly, reno-protective and cardio-protective effects of this analog have been recently evaluated by means of randomized clinical trials in renal patients with partially positive renal effects and negative cardiac results, thus additional studies are needed for confirmation.

22-oxacalcitriol, a vitamin D₃ analog with a limited calcemic effect available in Japan, is mostly used in renal patients affected by secondary hyperparathyroidism.

The clinical activity of some vitamin D analogs is such that they can be employed in diseases like cancer and autoimmunity.

The clinical activity of some vitamin D analogs is such that they can be employed in diseases like cancer and autoimmunity. In summary, available drugs with vitamin D like activity are not all the same either in terms of pharmacological actions, and side-effects. They have specific characteristics that may be useful to know in order to operate the best choice in the individual patient.

Keywords: Alphacalcidol, calcifediol, calcitriol, cholecalciferol, doxercalciferol, ergocalciferol, oxacalcitriol, paricalcitol.

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