Elsevier

The Lancet

Volume 365, Issue 9471, 7–13 May 2005, Pages 1621-1628
The Lancet

Articles
Oral vitamin D3 and calcium for secondary prevention of low-trauma fractures in elderly people (Randomised Evaluation of Calcium Or vitamin D, RECORD): a randomised placebo-controlled trial

https://doi.org/10.1016/S0140-6736(05)63013-9Get rights and content

Summary

Background

Elderly people who have a fracture are at high risk of another. Vitamin D and calcium supplements are often recommended for fracture prevention. We aimed to assess whether vitamin D3 and calcium, either alone or in combination, were effective in prevention of secondary fractures.

Methods

In a factorial-design trial, 5292 people aged 70 years or older (4481 [85%] of whom were women) who were mobile before developing a low-trauma fracture were randomly assigned 800 IU daily oral vitamin D3, 1000 mg calcium, oral vitamin D3 (800 IU per day) combined with calcium (1000 mg per day), or placebo. Participants who were recruited in 21 UK hospitals were followed up for between 24 months and 62 months. Analysis was by intention-to-treat and the primary outcome was new low-energy fractures.

Findings

698 (13%) of 5292 participants had a new low-trauma fracture, 183 (26%) of which were of the hip. The incidence of new, low-trauma fractures did not differ significantly between participants allocated calcium and those who were not (331 [12·6%] of 2617 vs 367 [13·7%] of 2675; hazard ratio (HR) 0·94 [95% CI 0·81–1·09]); between participants allocated vitamin D3 and those who were not (353 [13·3%] of 2649 vs 345 [13·1%] of 2643; 1·02 [0·88–1·19]); or between those allocated combination treatment and those assigned placebo (165 [12·6%] of 1306 vs 179 [13·4%] of 1332; HR for interaction term 1·01 [0·75–1·36]). The groups did not differ in the incidence of all-new fractures, fractures confirmed by radiography, hip fractures, death, number of falls, or quality of life. By 24 months, 2886 (54·5%) of 5292 were still taking tablets, 451 (8·5%) had died, 58 (1·1%) had withdrawn, and 1897 (35·8%) had stopped taking tablets but were still providing data for at least the main outcomes. Compliance with tablets containing calcium was significantly lower (difference: 9·4% [95% CI 6·6–12·2]), partly because of gastrointestinal symptoms. However, potentially serious adverse events were rare and did not differ between groups.

Interpretation

The findings do not support routine oral supplementation with calcium and vitamin D3, either alone or in combination, for the prevention of further fractures in previously mobile elderly people.

Published online April 28, 2005 DOI 10.1016/S0140-6736(05)63013-9

Introduction

Low-trauma fractures in elderly people are a substantial and increasing burden of ill health,1, 2 and those who have a low-trauma fracture are at high risk of another.3 Low serum concentrations of vitamin D metabolites are widespread in elderly people in the UK,4 especially in those with low-trauma fractures.5 Vitamin D and calcium, alone or in combination, are often recommended for prevention of osteoporotic fractures. Inadequate vitamin D status, exacerbated by low calcium intake, might raise the risk of these fractures by increasing bone resorption and loss from secondary hyperparathyroidism. Vitamin D might also protect against falls that lead to fracture.6 Evidence from randomised trials favours the combination of calcium and vitamin D.7 In this secondary-prevention study we aimed to test whether calcium and vitamin D, alone or in combination compared with placebo, would lead to one less person per 100 having a fracture every year over a median of 3 years.

Section snippets

Participants

15 024 people age 70 years or older who had had a low-trauma, osteoporotic fracture in the previous 10 years were assessed between Feb 1, 1999, and March 31, 2002. The trial was based in 21 hospitals in the UK. Ethics approval was obtained from the Multicentre Research Ethics Committee for Scotland and from the local research ethics committee of each hospital, and participants gave written informed consent.

Study nurses identified potential participants from hospital notes of patients seen in a

Results

Figure 1 shows the trial profile. Of 15 024 people assessed, about a third joined the trial and about 3500 of those who were eligible did not participate. Those recruited were younger (mean age 77 years [SD 6]) than were those who declined (80 years [6]) or who were ineligible (82 years [7]). The main reasons for ineligibility were cognitive impairment (2666 [43·0%]), current antiosteoporotic treatment (2103 [33·9%]), and previous excluding cancer (680 [11·0%]); this group also had a higher

Discussion

In this trial of secondary-fracture prevention, incidence of fractures did not differ between those allocated any calcium versus no calcium, between those allocated any vitamin D3 versus no vitamin D3, or between those allocated combination treatment versus placebo.

As expected, the rate of further low-trauma fracture was high (one in eight). However, there were fewer hip fractures than anticipated, which was related to the tendency for older people to be ineligible because of cognitive

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