The effects of calcitriol on falls and fractures and physical performance tests☆
Introduction
Elderly people fall more often as they age. Falls occur in 30% of people over the age of 65 years and in 50% of people over age 80 years [1], [2], [3]. Increased falling is associated with subsequent admission to a nursing home [4]. About 20% of fall incidents require medical attention, and approximately 10% result in fractures [1], [4], [5], [6], [7], [8], [9]. About 50% of osteoporotic fractures are non-vertebral, and falls appear to be the biggest contributor to a non-vertebral fracture [10]. The most serious fracture due to a fall is hip fracture because it results in a mortality of 15–20% of patients and as many as 50% of hip fracture patients are so physically impaired that they never leave the nursing homes. There are several risk factors for falls in elderly people such as poor general health, diabetes, poor vision, urinary incontinence, a previous history of stroke, Parkinson’s disease, dementia, poor cognitive function, depression, poor balance, decreased muscle strength, difficulty with the activities of daily living, medication use (particularly sedatives and anticonvulsants) and environmental obstacles and barriers [1]. Some of these risk factors are modifiable. A meta-analysis of several studies showed that different types of interventions could reduce the number of falls and multiple targeted interventions were shown to reduce the incidence of falls by about 10% [11]. In the present double blind randomized trial we examined prospectively the effect of calcitriol or estrogen therapy on bone mineral density and the incidence of falls and fractures.
Section snippets
Materials and methods
489 subjects were randomly assigned to one of the following four groups: conjugated equine estrogens (Premarin) 0.625 mg daily plus medroxyprogesterone acetate (Provera) 2.5 mg daily (HT); calcitriol (Rocaltrol) 0.25 μg twice daily; the combination of HT plus calcitriol; or placebo. Hysterectomized women (n=290) assigned to estrogen were not given the progestin, but received estrogen alone (ET) [12]. Calcium intake was maintained at or below 1000 mg per day. On entry into the study, women underwent
Results
The mean age of the women was 72 years at baseline and 75 years at the end of study. Mean serum 25OHD was 80 nmol/L (31 ng/ml), mean serum PTH was 37 pg/ml (normal <60). The effects of the therapy on BMD have previously been described [12].
The cumulative number of fallers was 64% in the placebo group versus 50% on calcitriol (P<0.0382), 58% on ET/HT and 57% on ET/HT + calcitriol. Because of the multiple comparisons test the difference between placebo and calcitriol was not significant.
However, the
Discussion
The results of this study raise questions about the present approach to fracture prevention in the elderly which focuses on the effects of pharmacological agents that increase bone mineral density (BMD). An analysis of the MORE trial showed that an increase in BMD could account for only 4% of the reduction in vertebral fractures [16]. Another analysis of all the large osteoporosis trials showed that only 16% of the decrease in vertebral fracture reduction could be accounted for by an increase
Acknowledgements
This study was primarily supported by the National Institutes of Health (UO1-AG10373 and RO1 AG10373). Other support was provided by Wyeth Pharmaceuticals, Hoffman La Roche and Pharmacia Upjohn.
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Presented at the 12th Workshop on Vitamin D (Maastricht, The Netherlands, 6–10 July 2003).