Over the last 30 years, several clinical trials have reported the efficacy of D-hormone analogs to treat primary and secondary osteoporosis, and their genomic and nongenomic mode of action have been demonstrated with the progress of biochemical research technologies. Recent metaanalyses reviewed the preventive effect on falls and fractures of "vitamin D3" in the elderly population, mainly based on studies with alfacalcidol and calcitriol. In future a clear differentiation must be made between calcium and plain vitamin D supplementation in very old, vitamin D-deficient women and men (> 75 years) and the pharmacological treatment of patients with established osteoporosis using D-hormone analogs, independent of a patient's vitamin D status. The dual action of D-hormone analogs on bone and muscle is unique, and differentiates them from all other, bone-specific antiosteoporotic drugs. Based on its efficacy in preventing falls, alfacalcidol is an excellent partner for combination therapy to improve the antifracture efficacy, especially in elderly patients. Further research is required to elucidate the mechanism of new actions of D-hormone analogs on muscle, nerves, brain, and on the immune system, to determine their application in different diseases.
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