CLINICAL COUNTERPOINT: Vitamin D: New Actions, New Analogs, New Therapeutic Potential*

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Abstract
Introduction AN EXCITING new era has developed in the vitamin D field with the discovery of new target tissues, mechanisms of action, and selective analogs. As a clinical counterpoint article, this review will emphasize the potential clinical applications of these new discoveries. Many of the applications to be discussed remain untested, whereas others remain in their infancy. A major reason for optimism in predicting an expanding list of therapeutic applications for the vitamin D metabolites and analogs stems from the development of analogs of calcitriol that differ in their biological effects. In particular, analogs are now available that appear to separate the effects of calcitriol on growth and differentiation from effects on intestinal calcium absorption or bone mobilization. This apparent selectivity may reflect altered pharmacokinetic properties or may involve mechanistic differences at the cellular level as well. Regardless, the development of these drugs is likely to lead to clinical applications in which raising serum calcium need not accompany other actions. The initial portion of this review is devoted to a discussion of these analogs. The main goal of this article is to review those areas in which calcitriol and its analogs are being used in new ways and to describe potential applications that are suggested by the newly discovered actions of calcitriol. Thus, new concepts in vitamin D action have led to clinical trials of calcitriol and its analogs in the management of hyperparathyroidism and psoriasis, and trials of these drugs in certain malignancies or immunological disorders may not be far off. None of the clinical applications discussed are approved applications for these drugs. Rather, this review is intended to link the laboratory observations of the past decade with the bedside of the next decade.

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