Effect of four monthly oral vitamin D3 (cholecalciferol) supplementation on fractures and mortality in men and women living in the community: randomised double blind controlled trial

doi:10.1136/bmj.326.7387.469

BMJ 2003;326:469 ( 1 March )

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Effect of four monthly oral vitamin D₃ (cholecalciferol) supplementation on fractures and mortality in men and women living in the community: randomised double blind controlled trial

Daksha P Trivedi, research fellow, ^a Richard Doll, emeritus professor, ^b Kay Tee Khaw, professor of clinical gerontology. ^a

^a Clinical Gerontology Unit, University of Cambridge School of Clinical Medicine, Addenbrooke's Hospital, Cambridge CB2 2QQ, ^b Clinical Trial Service Unit and Epidemiological Studies Unit, University of Oxford

Correspondence to: K T Khaw kk101{at}medschl.cam.ac.uk

Objective: To determine the effect of four monthly vitaminD supplementation on the rate of fractures in men and women aged65 years and over living in thecommunity.
Design: Randomised double blind controlled trial of100 000 IU oral vitamin D₃ (cholecalciferol) supplementation ormatching placebo every four months over fiveyears.
Setting and participants: 2686 people (2037 men and 649 women) aged65-85 years living in the general community, recruited from theBritish doctors register and a general practice register inSuffolk.
Main outcome measures: Fracture incidence and total mortality bycause.
Results: After five years 268 men and women had incidentfractures, of whom 147 had fractures in common osteoporotic sites(hip, wrist or forearm, or vertebrae). Relative risks in the vitaminD group compared with the placebo group were 0.78 (95% confidenceinterval 0.61 to 0.99, P=0.04) for any first fracture and 0.67(0.48 to 0.93, P=0.02) for first hip, wrist or forearm, or vertebralfracture. 471 participants died. The relative risk for total mortalityin the vitamin D group compared with the placebo group was 0.88(0.74 to 1.06, P=0.18). Findings were consistent in men and womenand in doctors and the general practicepopulation.
Conclusion: Four monthly supplementation with 100 000IU oral vitamin D may prevent fractures without adverse effectsin men and women living in the generalcommunity.

What is already known in this topic
Vitamin D and calcium supplements are effective in preventing fractures in elderly women

Whether isolated vitamin D supplementation prevents fractures is not clear

What this paper adds
Four monthly oral supplementation with 100 000 IU vitamin D reduces fractures in men and women aged over 65 living in the general community

Total fracture incidence was reduced by 22% and fractures in major osteoporotic sites by 33%

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Randomised controlled trial of calcium and supplementation with cholecalciferol (vitamin D₃) for prevention of fractures in primary care: Jill Porthouse, Sarah Cockayne, Christine King, Lucy Saxon, Elizabeth Steele, Terry Aspray, Mike Baverstock, Yvonne Birks, Jo Dumville, Roger Francis, Cynthia Iglesias, Suezann Puffer, Anne Sutcliffe, Ian Watt, and David J Torgerson
BMJ 2005 330: 1003. [Abstract] [Full Text] [PDF]

Vitamin D three times a year can prevent fractures
BMJ 2003 326: 0. [Full Text] [PDF]

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Gordon, J. (2003). OSTEOPOROSIS: TRANSLATING RESEARCH INTO CLINICAL PRACTICE. Gerontologist 43: 939-944 [Full text]
Heaney, R. P (2003). Long-latency deficiency disease: insights from calcium and vitamin D. Am. J. Clin. Nutr. 78: 912-919 [Abstract] [Full text]
Heaney, R. P. (2003). Vitamin D, Nutritional Deficiency, and the Medical Paradigm. J. Clin. Endocrinol. Metab. 88: 5107-5108 [Full text]
Forbes, D. (2003). Oral vitamin D3 supplementation reduced fractures in community dwelling elderly people. Evid. Based Nurs. 6: 113-113 [Full text]
Woolf, A. D, Akesson, K. (2003). Preventing fractures in elderly people. BMJ 327: 89-95 [Full text]
(2003). Robin Goodfellow (42-6). Rheumatology (Oxford) 42: 813-813 [Full text]
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(2003). Vitamin D: A Simple Way to Prevent Fractures. JWatch General 2003: 2-2 [Full text]
Heaney, R. P., Dowell, M. S., Hale, C. A., Bendich, A. (2003). Calcium Absorption Varies within the Reference Range for Serum 25-Hydroxyvitamin D. J. Am. Coll. Nutr. 22: 142-146 [Abstract] [Full text]

Rapid Responses:

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Vitamin D deficiency, lack of sunlight, multiple sclerosis: Peter K. Tun
bmj.com, 1 Mar 2003 [Full text]
Level of vitamin D (3) supplementation 100,000IU: Anne Woo
bmj.com, 1 Mar 2003 [Full text]
Re: Level of vitamin D (3) supplementation 100,000IU: Robert D Toon
bmj.com, 2 Mar 2003 [Full text]
Why no funding for a community trial?: Jim Page
bmj.com, 2 Mar 2003 [Full text]
100,000 IU of Vitamin D is a Lethal Dose for Many in our Community: Trevor G Marshall, PhD
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A Therapy is Only Safe if it "Does No Harm": Trevor G Marshall, PhD
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Re: How can Trivedi et al, Overlook the Possibility of Hypervitaminosis-D?: Reinhold Vieth
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