Muscle weakness, neuro-muscular deficits, balance and gait disorders are manifestations of mobility impairment and increase the risk of "intrinsic"falls. Fallings in old age break bones, fear of falling reduces self-esteem and physical activities and this initiates a vicious circle of de-conditioning. Fractures are also the relevant outcome of osteoporoses, but more than 90 % of hip fractures are fall-related. D-hormone (1,25[OH](2) D; calcitriol), the active vitamin D metabolite, and its receptor (VDR) play an important role in muscle development. Older age is significantly associated with decreased VDR expression in human skeletal muscle tissue as well as with D-hormone dependent changes in muscle fibre type and muscle cell differentiation and metabolism. A positive correlation was found between femoral muscle power and -function and D-hormone serum levels in elderly women and men. This interaction was strongly supported by the recently shown fact, that higher D-hormone serum levels are correlated with lower fall rates in elderly women. All these results together suggest that the age-related increase of falls seemed in part to be explained by a decrease of Dhormone and VDR.Impaired renal function is detrimental to the activation of D-hormone and may be in future a diagnostic tool for identifying patients with decreased bone mineral density and muscle power, increased risk of falls and fractures. Histochemical classification based on muscle biopsies revealed that a six months treatment with 1 ug alfacalcidol daily increased the number and the diameter of fast-twitch type II A fibres. In elderly osteopenic women calcitriol was able to delay the decline of physical performance tests. A significant decrease in the fall rate after three years of treatment with 0.5 ug calcitriol daily in communitydwelling osteopenic women without vitamin D deficiency and especially with reduced kidney function has been described. Alfacalcidol, an advantageous pro-drug of calcitriol, has demonstrated after nine months therapy the reduction of falls by 50-70% in elderly, community-dwelling women and men with normal vitamin D levels in serum and who have taken more than 500 mg calcium daily from diet or had a creatinine clearance of less than 65 ml/min. Metaanalyses on the basis of controlled, randomised clinical trials with alfacalcidol and calcitriol have shown the higher reduction of falls, vertebral and non-vertebral fractures versus plain vitamin D.The pleiotropic effects of alfacalcidol on reduced calcium metabolism in muscles, on the regulation on muscle fibre composition, on decreased muscle function and neuro-muscular co-ordination are unique, and thus differentiate this form of therapy from all other anti-osteoporotic drugs. The rationale of the advantage of alfacalcidol versus plain vitamin D is the fact that this drug is acting without metabolic activation in the kidney which results in higher concentrations of D-hormone at the target organs, e. g. muscles, nerves, brain, and in more local expression of VDR. Plain vitamin D seemed to be active mainly in vitamin D deficient patients with normal kidney function.
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