RESEARCH - Studies find no evidence that vitamin D and calcium prevent fractures

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Studies find no evidence that vitamin D and calcium prevent fractures

Rheumawire

Apr 28, 2005

Gandey

Aberdeen, UK - Two new studies are casting doubt on the benefit of vitamin D

and calcium supplementation to prevent bone fractures in the elderly. The

studies are available online April 28, 2005 in the Lancet and published in

the upcoming issue of the BMJ [1,2]. " The benefits of calcium and vitamin D

as a treatment option to prevent further fractures are uncertain, " Jackie

Parrington, a spokesperson for the National Osteoporosis Society, said in a

statement to the press. Parrington noted that other treatment options for

people with osteoporosis who are not old and frail include antiresorptive

drugs such as the bisphosphonates.

The UK Medical Research Council funded the Randomized Evaluation of Calcium

or Vitamin D (RECORD) trial, and the Northern and Yorkshire NHS research and

development healthy aging program funded the BMJ study. Shire

Pharmaceuticals and Nycomed provided the drugs for both studies, and some of

the authors have financial ties to the companies.

In an accompanying Comment in the Lancet, Dr Philip Sambrook (Royal North

Shore Hospital, Sydney, Australia) points out that vitamin-D deficiency is

generally considered to be a major contributor to falls and fractures in

older people [3]. He writes that since the landmark study by Chapuy and

colleagues, it has been assumed that treatment with calcium and vitamin D

reduces the risk of osteoporotic fractures in the elderly [4]. Sambrook

notes, " The RECORD study, a large randomized trial of participants with a

recent low-trauma fracture, failed to show any benefit of calcium or vitamin

D on fracture. "

Sambrook argues that despite this new finding, overall the data are still

consistent with a therapeutic benefit of vitamin D on fractures in people

deficient in vitamin D. " But the effect of vitamin-D supplementation in

vitamin-D-replete individuals living in the community is less clear. Indeed,

given uncertainties about the efficacy of vitamin D alone or in combination

with calcium on falls, more studies in older people with suboptimum

vitamin-D levels are appropriate to establish benefit on both falls and

fracture end points. "

In the BMJ study, lead author Dr Jill Porthouse (University of York, UK) and

colleagues came to a similar conclusion: " We found no evidence that

supplementation with calcium and vitamin D3 affects fracture rates over two

years in women aged 70 or over. " The researchers point out, however, that

their population was generally healthy and living in the community. " People

in sheltered accommodation or nursing homes may be at more risk of a low

calcium and vitamin-D intake and at higher risk of fracture. "

The studies also did not address the benefit of supplementation in the

prevention of bone loss in the young to offset the risk of osteoporosis. The

present findings merely suggest that treating patients with vitamin D and

calcium who have already suffered a fracture and therefore by definition

have osteoporosis is not sufficient.

RECORD finds calcium and vitamin D either alone or in combination

ineffective

" Our trial indicates that routine supplementation with calcium and vitamin

D3, either alone or in combination, is not effective in the prevention of

further fractures in people who had a recent low-trauma fracture, " lead

author Prof Grant (University of Aberdeen, UK) told the press.

" Policies for secondary prevention should therefore consider other

strategies. "

The RECORD trial group sought to assess whether vitamin D and calcium,

either alone or in combination, were effective in the prevention of

secondary fractures. Using a factorial design, the investigators looked at

more than 5200 people aged 70 years or older recruited from 21 hospitals in

the UK. Most of the cohort were women (85%4481 subjects). The researchers

randomly assigned patients who were mobile before developing a low-trauma

fracture to 800 IU daily of oral vitamin D3, 1000-mg calcium, a combination

of the oral vitamin D3 with calcium, or placebo. They followed participants

for between 24 and 62 months. Analysis was by intention to treat, and their

primary outcome was new low-energy fractures.

Grant and colleagues found that 13% of participants had a new low-trauma

fracture. Of those, 26% were fractures of the hip. 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.

After 24 months, 54.5% of subjects were still taking tablets, 8.5% had died,

1.1% had withdrawn, and 35.8% had stopped taking tablets but were still

providing data for at least the main outcomes. " As expected, " Grant and

colleagues write, " it was difficult to maintain compliance with allocated

tablets; participants were elderly, usually taking other medications, and

comorbidity was common. " Compliance with tablets containing calcium was

significantly lower, they point out, partly because of gastrointestinal

symptoms. The researchers report the difference was 9.4% (95% CI 6.6-12.2).

They note that potentially serious adverse events were rare and did not

differ between groups.

In his accompanying article, Sambrook points out that compliance might have

been as low as 45% when nonresponders to the questionnaire about compliance

were included. " On this basis, it is difficult to see how the authors can be

sure there was 'no evidence that true differences may have been obscured by

poor compliance.' "

Sambrook adds that the study perpetuates the limitations of most previous

studies by measuring 25-hydroxyvitamin D in only a small sample (n=60just

1.1% of the study population). " Thus the vitamin-D status of the trial

population at baseline remains largely unknown. Although, because the

patients were younger than in other studies, ambulatory, and living in the

community, they were less likely to have vitamin-D deficiency. "

BMJ study finds supplementation does not reduce fractures or incidence of

falls

In this open, randomized, controlled trial, Porthouse and colleagues

assessed whether giving calcium and vitamin-D supplements to

community-dwelling older women at increased risk of hip fracture would

reduce their risk of fractures either through reductions in bone loss or by

reducing falls.

They looked at more than 3300 women from nurse-led clinics in primary care.

They focused on women aged 70 and over with 1 or more risk factors for hip

fracture. Like the RECORD trial group, the investigators initiated daily

oral supplementation of 800 IU of vitamin D3 and 1000 mg of calcium. For the

control group, they distributed information leaflets about dietary calcium

intake and prevention of falls.

They found that 69% of the women who completed the follow-up questionnaire

at 24 months were still taking supplements. This number dropped to 55% when

they included randomized participants known to be alive. After a median

follow-up of 25 months, clinical fracture rates were lower than expected in

both groups but did not significantly differ for all clinical fractures.

Porthouse and colleagues point out that their results do not apply to men,

those in residential care, or those with dementia. They also did not use a

placebo in the control group, and they note that this could have biased the

results. " Fewer fractures occurred than we anticipated, " they write, " thus

reducing the power of our study to observe modest differences between

groups. This was, however, offset to some degree by our exceeding our

planned sample size. "

The National Osteoporosis Society is advising that older patients at risk of

breaking a bone because of osteoporosis focus on consuming a healthy diet

that includes a full range of vitamins and minerals. The organization is

recommending that vital nutrients be consumed from food rather than from

commercial supplements.

Sources

a. Grant AM, FH, Avenell A, et al. On behalf of the

RECORD trial group. Oral vitamin D3 and calcium for secondary prevention of

low-trauma fractures in elderly peoplerandomised evaluation of calcium or

vitamin D (RECORD): a randomised placebo-controlled trial. Lancet 2005; DOI:

10.1016/S0140-6736(05)63013-9. Available at: http://www.lancet.com.

b. Porthouse J, Cockayne S, King C, et al. Randomised

controlled trial of supplementation with calcium and cholecalciferol

(vitamin D3) for prevention of fractures in primary care. BMJ 2005;

330:1003-1006.

c. Sambrook P. Vitamin D and fractures: quo vadis? Lancet

2005; DOI: 10.1016/S0140-6736(05)66385-4. Available at:

http://www.lancet.com.

d. Chapuy MC, Arlot ME, Duboeuf F, et al. Vitamin D3 and

calcium to prevent hip fractures in the elderly women. N Engl J Med 1992;

327:1637-1642.

Not an MD

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Mayo Clinic in Rochester

http://www.mayoclinic.org/rochester

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