The D-hormone analog alfacalcidol: the pioneer beyond the horizon of osteoporosis treatment.

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.

Prevention and therapy of osteoporosis: the roles of plain vitamin D and alfacalcidol.

Severe vitamin D deficiency was identified only in the first decades of the last century as the most common aetiology of rickets in children and osteomalacia in adults. It was later shown that vitamin D is not, as had been supposed, the biologically active principle for healing bone disease but must be hydroxylated in the liver and then finally in the kidney to become 1alpha,25-dihydroxy-cholecalciferol, a biologically highly active renal hormone. This study reviews the various principles, mechanisms, and approaches to the treatment of different forms of osteoporosis using vitamin D, alfacalcidol, and calcitriol therapy regimens.

Alfacalcidol reduces the number of fallers in a community-dwelling elderly population with a minimum calcium intake of more than 500 mg daily.

OBJECTIVES: To study the effect of alfacalcidol (1alpha(OH)D3) on fall risk in community-dwelling elderly men and women. DESIGN: Randomized, double-blind, placebo-controlled intervention trial. SETTING: Basel, Switzerland. PARTICIPANTS: Three hundred seventy-eight community-dwelling elderly (191 women/187 men). INTERVENTION: Participants were randomly assigned to receive 1 microg of alfacalcidol or matched placebo daily for 36 weeks. MEASUREMENTS: Serum 25-hydoxyvitamin D3 (25(OH) D,1,25-dihydroxyvitamin D3 (D-hormone), and intact parathormone (iPTH) levels were measured using radioimmunoassay at baseline and every 12 weeks. Numbers of fallers and falls were assessed using a questionnaire during each study site visit. Dietary calcium intake was assessed at baseline using a food frequency questionnaire. RESULTS: At baseline, participants had, on average, normal vitamin D and D-hormone serum levels. Over 36 weeks, alfacalcidol treatment was associated with fewer fallers (odds ratio (OR)=0.69, 95% confidence interval (CI)=0.41-1.16) than placebo. In a post hoc subgroups analysis by medians of total calcium intake, this reduction reached significance in alfacalcidol-treated subjects with a total calcium intake of more than 512 mg/d (OR=0.45, 95% CI=0.21-0.97, P=.042) but not in those who consumed less than 512 mg/d (OR=1.00, 95% CI= 0.47-2.11, P=.998). Alfacalcidol treatment was also, independent of total calcium intake, associated with a significant 37.9% reduction in iPTH serum levels (P<.0001). No cases of clinically relevant hypercalcemia were observed. CONCLUSION: Provided a minimal calcium intake of more than 512 mg/d, alfacalcidol treatment significantly and safely reduces number of fallers in an elderly community dwelling population.