An age-related decrease in creatinine clearance is associated with an increase in number of falls in untreated women but not in women receiving calcitriol treatment

Abstract

Context: Decreased calcitriol production due to impaired renal function may be a significant risk factor for falls in normal aging population.

Objective: The objective of the study was to examine the association between creatinine clearance (CrCl) and the incidence of falls and fallers in groups treated with placebo, calcitriol, estrogen therapy (ET)/estrogen + progestin therapy (HT), and calcitriol + ET/HT.

Design: This was a 3-yr, double-blind, placebo-controlled study designed to test the efficacy of calcitriol and ET/HT on bone loss and falls with analysis by intention to treat and post hoc.

Setting: The study was conducted at an academic outpatient center.

Participants: Four hundred eighty-nine normal elderly women aged 65-77 yr; 415 women completed the study.

Intervention: Subjects were randomized to placebo, calcitriol 0.25 mug twice a day, ET daily (conjugated equine estrogens 0.625 mg), HT (conjugated equine estrogen 0.625 mg + medroxyprogesterone acetate 2.5 mg) and calcitriol + ET/HT.

Main outcome measures: Cumulative number of falls and fallers were compared between groups with 24-h urine CrCl less than 60 and 60 ml/min or greater.

Results: Calcitriol treatment decreased the number of fallers and falls. Low CrCl less than 60 ml/min was a predictor of the number of falls per person but not fallers in the placebo group (P = 0.007). In the low CrCl group (<60 ml/min), the rate of falls decreased on calcitriol by 53% [95% confidence interval (CI) -71% to -22%; P = 0.003], calcitriol + ET/HT by 61% (95% CI -76% to -37%; P = 0.001), and ET/HT by 25% (95% CI: -55% to +24%; not significant). Calcitriol reduced the rate of falls by 30% (95% CI -49% to -4%; P = 0.027) in the CrCl 60 ml/min or greater group.

Conclusion: Calcitriol treatment decreases falls in all subjects but especially in elderly women with decreased renal function (<60 ml/min) and frequent fallers.

Fig. 1

Correlation graph between measured CrCl and serum 1,25(OH)₂D₃.

Fig. 2

Cumulative number of falls per person in the placebo and calcitriol groups (A); placebo and ET/HT + calcitriol groups (B); and placebo and ET/ HT groups (C) over the treatment period in women with CrCl less than 60 and more than 60 ml/min. The data were adjusted for significant covariates: number of comorbid conditions, smoking status, and PASE score. *, P < 0.05, compared with placebo CrCl greater than 60 ml/min; †, P < 0.05, compared with calcitriol CrCl less than 60 ml/min; ‡, P < 0.05, compared with calcitriol + ET/HT CrCl less than 60 ml/min.