Falls are associated with decreased renal function and insufficient calcitriol production by the kidney

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Abstract

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  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)2D) (p < 0.001) and normal serum 25OHD suggesting that there is decreased conversion of 25OHD to 1,25(OH)2D 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)2D, upregulation of VDR and improvement in muscle strength although one cannot exclude an effect on the central nervous system.

Introduction

Falls in elderly people represent a serious public health problem in United States. Approximately 30% of people over age of 65 and 50% over age 80 years fall each year and 10% of falls cause fractures. There is increasing data relating falls and decreased muscle strength to changes in vitamin D metabolism and decreasing renal function. A possible link between these two observations is that the decrease in renal function with age measured by creatinine clearance (CrCl) is associated with a decrease in production of 1,25-dihydroxyvitamin D together with a decrease in vitamin D receptors (VDR) in muscle.

We showed earlier that treatment with 1,25-dihydroxyvitamin D (calcitriol) vitamin D significantly reduced the risk of falls in elderly women [1], [2] and now this has been confirmed in men and women using alphacalcidol [3], [4].

A creatinine clearance of <65 ml/min has been recently reported as a significant risk factor for falls and increased risk of vertebral, hip and radial fractures in elderly men and women treated for osteoporosis [5], [6]. Treatment with alphacalcidol significantly reduced the number of fallers and falls in a group with low CrCl (<65 ml/min) [4].

In an osteoporosis intervention trial primarily designed to test the efficacy of conjugated estrogens and calcitriol given alone or in combination on bone loss, we had the opportunity to collect prospective data on the incidence of falls and the effect of estrogen, calcitriol and combination (calcitriol + estrogen) therapies on fall incidence. We have shown that a CrCl <60 ml/min is associated with a 60% increase in falls. In this paper we examine different levels of CrCl in relation to falls.

Section snippets

Materials and methods

Four hundred and eighty-nine elderly women aged 65–77 years were enrolled into a prospective double blind randomized placebo controlled clinical trial (STOP IT) lasting 3 years to test the efficacy of conjugated equine estrogens and calcitriol given individually or in combination, on bone loss [1]. Women were excluded if they had severe chronic illness (chronic liver or kidney disease, severe COPD, severe rheumatoid arthritis, serious heart failure), had primary hyperparathyroidism or active

Results

The distribution of low CrCl by age is shown in Fig. 1. Most values for the low CrCl group are distributed equally over the age span of the study population.

Discussion

In this study of normal elderly women, we previously originally noted that a low 24 h CrCl (<60 ml/min) was associated with an increase in the number of falls but not in the number of fallers. We explored the data further by comparing fall incidence in sub groups of CrCl. There was no evidence that falls were increased in the groups with CrCl of 60–70 or 70–80 or >90 ml/min, so it would seem that this fall effect is associated only in the women with CrCl < 60 ml/min or stage III chronic renal

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    Citation Excerpt :

    The two studies that identified CKD as a predictor of falls were subgroup analyses from randomized controlled trials of Vitamin D therapy that enrolled independent older adults (age range = 65–77 years) who had few severe chronic illnesses.7,8 One study enrolled women with osteoporosis (those with severe chronic illnesses were excluded) and, after 36 months of follow-up, 24-hr urine creatinine clearance (CrCl) was a significant predictor of incident falls in the placebo arm.8 In the other study, a relatively healthy cohort of older adults (average albumin was 42.3 g/L) was followed for 36 weeks, and those with a serum CrCl < 65 ml/min had at least threefold greater risk of incident falls (Odds ratio 3.68, 95% CI, 1.38–9.82) than those with CrCl ≥ 65 ml/min.7

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