In a double blind placebo controlled 3-year osteoporosis study in elderly women, we collected prospective data on falls. The study population comprised 489 normal elderly women aged 65-77 years randomized to four groups: placebo, calcitriol 0.25 mcg b.i.d., conjugated equine estrogens (0.625 mg/day) and calcitriol+estrogen. Falls occurred in 57% of all women. Using a Poisson regression model, the placebo group with low GFR-creatinine clearance (CrCl<60 ml/min) had 60% more falls compared to the group with CrCl> or =60 ml/min. Further sub group analyses showed that there is no increased risk of falls with CrCl 60-70, 70-80 and >90 ml/min. Calcitriol treatment significantly reduced the number of falls by 50% (OR=0.5, 95% CI: 0.4-0.9, p=0.010) compared to placebo in the low CrCl group. The group with lower CrCl had lower calcium absorption (p<0.001), lower serum 1,25-dihydroxyvitamin D (1,25(OH)(2)D) (p<0.001) and normal serum 25OHD suggesting that there is decreased conversion of 25OHD to 1,25(OH)(2)D by the aging kidney. It is postulated that the decrease in falls on calcitriol therapy is related to an increase in serum 1,25(OH)(2)D, upregulation of VDR and improvement in muscle strength although one cannot exclude an effect on the central nervous system.