title: Treatment with alfacalcidol in elderly people significantly decreases the high risk of falls associated with a low creatinine clearance of <65 ml/min.
abstract: We previously observed that a creatinine clearance (CrCl) of <65 ml/min is a significant and independent risk factor for the number of fallers and falls in a community-dwelling elderly population and postulated that this increased risk is due to the associated significant lower D-hormone serum levels. To test our hypothesis, we investigated in a post hoc analysis of a double-blind randomized study whether treatment with alfacalcidol, a synthetic prodrug of the D-hormone, can reduce the high incidence of fallers and the high risk of falls associated with low CrCl. Of 378 Swiss community-dwelling women (n=191) and men (n=187), aged 70 years and older, 191 received randomly 1 microg capsules of alfacalcidol (AlphaD3: Teva), and 187 received one capsule of placebo daily. With the help of questionnaires we regularly assessed the incidence and frequency of falls. The risk of becoming a faller and the risk of falling were assessed in multivariate-controlled logistic regression models according to treatment groups and according to a CrCl cut-off of 65 ml/min. The presented results are from ITT analyses. In participants with a CrCl of <65 ml/min, the 36 weeks of treatment with alfacalcidol was, compared with placebo, associated with a significant reduction in the number of fallers (14/72 versus 25/70; OR 0.26, 95% CI 0.08-0.80, P=0.019), and a significant reduction of the number of falls (16/72 versus 28/70; OR 0.29, 95% CI 0.09-0.88, P=0.028). No such association was observed in participants with a CrCl of >or=65 ml/min (for fallers 26/120 versus 21/116; OR 0.92 95% CI 0.34-2.52, P=0.875; for falls 32/120 versus 23/116; OR 0.93 95% CI 0.34-2.54, P=0.885). In the placebo group frequency of falls was dependent on CrCl (P=0.006), whereas in the alfacalcidol treatment group frequency of falls was independent of CrCl (P=0.494). No cases of clinically relevant hypercalcemia were observed. In a community-dwelling population of elderly men and women with a CrCl of <65 ml/min, treatment with alfacalcidol can significantly and safely reduce the low CrCl associated increased number of fallers and the high risk of falls.
authors.affiliation: Geriatric University Clinic, Kantonsspital, Basel, Switzerland. l.d@gmx.net <l.d@gmx.net>
authors.forename: Laurent
authors.initials: L
authors.lastname: Dukas
authors.forename: Erich
authors.initials: E
authors.lastname: Schacht
authors.forename: Ze'ev
authors.initials: Z
authors.lastname: Mazor
authors.forename: Hannes B
authors.initials: HB
authors.lastname: Stähelin
mesh_terms: D000058:Accidental Falls / Q000517:prevention & control*; D000367:Age Factors; D000368:Aged; D015992:Body Mass Index; D002118:Calcium / Q000097:blood; D002136:Calcium, Dietary / Q000008:administration & dosage; D003404:Creatinine / Q000378:metabolism*; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D006887:Hydroxycholecalciferols / Q000009:adverse effects / Q000097:blood / Q000627:therapeutic use*; D008297:Male; D011355:Prodrugs / Q000008:administration & dosage* / Q000009:adverse effects; D012307:Risk Factors
chemical_list: D002136:Calcium, Dietary; D006887:Hydroxycholecalciferols; D011355:Prodrugs; D003404:Creatinine; D002118:Calcium; C008088:alfacalcidol