TITLE: Vitamin D Supplementation in the Elderly and Long-Term Care Residents: Clinical Effectiveness and Guidelines for Use DATE: 20 March 2009 RESEARCH QUESTIONS: 1. What is the clinical effectiveness of Vitamin D supplementation in the elderly and longterm care residents? 2. What are the guidelines associated with use of Vitamin D supplementation in the elderly and long-term care residents? METHODS: A limited literature search was conducted on key health technology assessment resources, including PubMed, the Cochrane Library (Issue 4, 2008), University of York Centre for Reviews and Dissemination (CRD) databases, ECRI, EuroScan, international HTA agencies, and a focused Internet search. Results include articles published between 2004 and March 2009 and are limited to English language publications only. Filters were applied to limit the retrieval to health technology assessments, systematic reviews, meta-analyses, randomized controlled trials, and guidelines. Internet links are provided, where available. The summary of findings was prepared from the abstracts of the relevant information. Please note that data contained in abstracts may not always be an accurate reflection of the data contained within the full article. RESULTS: HTIS reports are organized so that the higher quality evidence is presented first. Therefore, health technology assessment reports, systematic reviews, and meta-analyses are presented first. These are followed by randomized controlled trials (RCTs), and evidence-based guidelines. Disclaimer: The Health Technology Inquiry Service (HTIS) is an information service for those involved in planning and providing health care in Canada. HTIS responses are based on a limited literature search and are not comprehensive, systematic reviews. The intent is to provide a list of sources of the best evidence on the topic that CADTH could identify using all reasonable efforts within the time allowed. HTIS responses should be considered along with other types of information and health care considerations. The information included in this response is not intended to replace professional medical advice, nor should it be construed as a recommendation for or against the use of a particular health technology. Readers are also cautioned that a lack of good quality evidence does not necessarily mean a lack of effectiveness particularly in the case of new and emerging health technologies, for which little information can be found, but which may in future prove to be effective. While CADTH has taken care in the preparation of the report to ensure that its contents are accurate, complete and up to date, CADTH does not make any guarantee to that effect. CADTH is not liable for any loss or damages resulting from use of the information in the report. Copyright: This report contains CADTH copyright material and may contain material in which a third party owns copyright. This report may be used for the purposes of research or private study only. It may not be copied, posted on a web site, redistributed by email or stored on an electronic system without the prior written permission of CADTH or applicable copyright owner. Links: This report may contain links to other information on available on the websites of third parties on the Internet. CADTH does not have control over the content of such sites. Use of third party sites is governed by the owners own terms and conditions.
Two meta-analyses, eight RCTs, and two guidelines were identified pertaining to the use of Vitamin D supplementation in the elderly and long-term care residents. No health technology assessments were identified. The main body of the report includes systematic reviews, RCTs, and evidence-based guidelines wherein the mean age of participants was clearly reported as being 60 years or older. Studies with mixed-age populations or where the age of the participants was not reported are included in the appendix. Also included in the appendix are additional articles that may be of interest. OVERALL SUMMARY OF FINDINGS: Systematic reviews and meta-analyses Two meta-analyses pertaining to the use of vitamin D supplementation in older adults were identified; one to prevent fractures and the other to prevent falls. With regard to fracture prevention, authors analyzed trials in which patients 60 years were supplemented with oral vitamin D (cholecalciferol) with and without calcium supplementation. 1 Vitamin D doses of 700-800 IU per day reduced the relative risk of hip fractures and any nonvertebral fractures compared to calcium or placebo alone. No clinical benefit was observed when vitamin D supplementation of 400 IU per day was administered. Authors concluded that in an ambulatory or institutionalized elderly population, 700-800 IU per day vitamin D supplementation appears to reduce the risk of hip and non-vertebral fracture. A meta-analysis by the same authors assessed the effectiveness of vitamin D in preventing falls in older adults ( 60 years). 2 No dosing range was reported in the abstract, but vitamin D reduced the risk of falls compared to patients taking either placebo or calcium. They found that in order to prevent one fall, 15 patients would need to be treated with vitamin D supplements. Authors concluded that in an ambulatory or institutionalized elderly population, vitamin D reduces the risk of falling by more than 20%. Randomized controlled trials Of the eight RCTs identified, six evaluated the effectiveness of vitamin D supplementation for the reduction of falls 3-7, 10 and four for the reduction of fractures. 6,8-10 A vitamin D dose of 1000 IU per day was found to be effective in preventing falls in two studies. 3,7 The first study included older women aged 70 to 90 years who lived in the community and who received either 1000 IU of ergocalciferol per day or placebo. Follow-up data were collected every 6 weeks for one year. Vitamin D therapy reduced the risk of having at least one fall over one year but did not reduce the risk of falling more than once. In the second study, both men and women in residential care (mean age 83.4) were supplemented with 1000 IU of ergocalciferol per day or placebo and were followed for two years. 7 Authors found that two years of vitamin D supplementation resulted in reduced incidence of falls in older adults in residential care. One trial studied the effect of vitamin D supplementation at a dose of 700 IU per day on reducing falls in men and women 65 years who were living at home. 5 Participants were randomized to vitamin D (cholecalciferol) plus calcium or placebo and were followed up for three years. Vitamin D supplementation reduced the odds of falling in women, but not in men. Longterm supplementation reduced the odds of falling by 46% in ambulatory older women and by 65% in less active ambulatory women. Vitamin D Supplementation in the Elderly and Long-term Care Residents 2
Once study reported mixed conclusions regarding the effect vitamin D supplementation on fall prevention in older adults. 10 This study differed from other included studies in that investigators studied the use of a single intramuscular injection of either 600,000 IU vitamin D (ergocalciferol) or placebo in ambulatory subjects 65 years with a history of falling. 10 Although there was no significant difference in the number of falls or people falling in the two groups, the authors concluded that vitamin D supplementation has a beneficial effect on functional performance and reaction time, and that this improvement might reduce falls. This was not tested. Two studies found that vitamin D supplementation had no effect on reducing falls in older adults. 4,6 The first study found that vitamin D at a dose of 800 IU per day did not significantly reduce the number of falls or fallers in a group of geriatric inpatients. 4 The second study took place in residential care units and administered vitamin D doses of 1,100 IU per day (administered as 2.5mg every three months). 7 Patients were followed for 10 months and authors found no evidence that the vitamin D supplementation prevented falls in elderly people in care homes. None of the included RCTs found vitamin D supplementation to be effective in preventing fractures in elderly populations. 6,8-10 Doses used in these studies were 2.5mg every 3 months (equivalent to 1,100 IU per day), 6 800 IU per day, 8,9 and a single intramuscular injection of 600,000 IU per day. The duration of the studies ranged from 6 months 10 to just over 5 years, 8 and took place both in the community 8-10 and in residential care. 6 No study pertaining to either fractures or falls reported any adverse effects of vitamin D supplementation. Guidelines and recommendations Two guidelines were identified that issued recommendations on vitamin D supplementation to prevent falls and fractures. 11,12 The recommendation statement from the Canadian Task Force on Preventative Health states that for women without osteoporosis, there is fair evidence that vitamin D supplementation prevents osteoporotic fractures. 12 Supplementation of 400-800 IU per day is recommended for all postmenopausal women (see Figure 1 in the guideline). The National Institute for Health and Clinical Excellence guideline states that the combination of vitamin D3 and calcium supplementation has been found to reduce fracture rates in older people residing in assisted care. 11 They state that although there is emerging evidence that vitamin D may reduce the risk of falling, there is still some uncertainty (especially about route of administration and dosing) and thus they cannot make a firm recommendation about the indication. Overall, there is mixed evidence regarding the vitamin D supplementation for the reduction of falls and fractures in older adults. Long-term supplementation with dose of 1000 IU per day seems to be beneficial in preventing falls in both community dwelling 3 and residential care 7 populations. Supplementation in doses of 700-800 IU per day may reduce the risk of hip and non-vertebral fracture in an elderly residential population according to the included metaanalysis, 1 but none of the included RCTs found evidence to support vitamin D supplementation to reduce the incidence of fractures in the elderly. 6,8-10 Both guidelines, however, recommended vitamin D supplementation to reduce fractures. 11,12 Although only one abstract reported any safety information, 8 safety data may have been recorded in other studies and may be available in the full text reports. Vitamin D Supplementation in the Elderly and Long-term Care Residents 3
REFERENCES SUMMARIZED: Health technology assessments No literature identified Systematic reviews and meta-analyses 1. Bischoff-Ferrari HA, Willett WC, Wong JB, Giovannucci E, Dietrich T, wson-hughes B. Fracture prevention with vitamin D supplementation: a meta-analysis of randomized controlled trials. JAMA 2005;293(18):2257-64. PubMed: PM15886381 2. Bischoff-Ferrari HA, wson-hughes B, Willett WC, Staehelin HB, Bazemore MG, Zee RY, et al. Effect of Vitamin D on falls: a meta-analysis. JAMA 2004;291(16):1999-2006. PubMed: PM15113819 Randomized controlled trials 3. Prince RL, Austin N, Devine A, Dick IM, Bruce D, Zhu K. Effects of ergocalciferol added to calcium on the risk of falls in elderly high-risk women. Arch Intern Med 2008;168(1):103-8. PubMed: PM18195202 4. Burleigh E, McColl J, Potter J. Does vitamin D stop inpatients falling? A randomised controlled trial. Age Ageing 2007;36(5):507-13. PubMed: PM17656420 5. Bischoff-Ferrari HA, Orav EJ, wson-hughes B. Effect of cholecalciferol plus calcium on falling in ambulatory older men and women: a 3-year randomized controlled trial. Arch Intern Med 2006;166(4):424-30. PubMed: PM16505262 6. Law M, Withers H, Morris J, Anderson F. Vitamin D supplementation and the prevention of fractures and falls: results of a randomised trial in elderly people in residential accommodation. Age Ageing 2006;35(5):482-6. PubMed: PM16641143 7. Flicker L, MacInnis RJ, Stein MS, Scherer SC, Mead KE, Nowson CA, et al. Should older people in residential care receive vitamin D to prevent falls? Results of a randomized trial. J Am Geriatr Soc 2005;53(11):1881-8. PubMed: PM16274368 8. Grant AM, Avenell A, Campbell MK, McDonald AM, Maclennan GS, McPherson GC, et al. 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. Lancet 2005;365(9471):1621-8. PubMed: PM15885294 9. Porthouse J, Cockayne S, King C, Saxon L, Steele E, Aspray T, et al. Randomised controlled trial of calcium and supplementation with cholecalciferol (vitamin D3) for prevention of fractures in primary care. BMJ 2005;330(7498):1003. PubMed: PM15860827 10. Dhesi JK, Jackson SH, Bearne LM, Moniz C, Hurley MV, Swift CG, et al. Vitamin D supplementation improves neuromuscular function in older people who fall. Age Ageing 2004;33(6):589-95. PubMed: PM15501836 Vitamin D Supplementation in the Elderly and Long-term Care Residents 4
Guidelines and recommendations 11. Falls: The assessment and prevention of falls in older people. London: National Institute for Health and Clinical Excellence (NICE). NHS; 2004 Nov. Clinical Guideline 21. Available: http://www.nice.org.uk/nicemedia/pdf/cg021niceguideline.pdf (accessed 2009 Mar 20). See pg 13 section 1.12.5 12. Cheung AM, Feig DS, Kapral M, az-granados N, Dodin S. Prevention of osteoporosis and osteoporotic fractures in postmenopausal women: recommendation statement from the Canadian Task Force on Preventive Health Care. CMAJ 2004;170(11):1665-7. Available: http://www.cmaj.ca/cgi/content/full/170/11/1665 (accessed 2009 Mar 19). PREPARED BY: Kristen Moulton, BA, Research Assistant Emmanuel Nkansah, MLS, MA, Information Specialist Health Technology Inquiry Service Email: htis@cadth.ca Tel: 1-866-898-8439 Vitamin D Supplementation in the Elderly and Long-term Care Residents 5
APPENDIX FURTHER INFORMATION: Guidelines 13. Vitamin D and adult bone health in Australia and New Zealand: a position statement. Med J Aust 2005;182(6):281-5. PubMed: PM15777143 Studies in which the mean age was not reported 14. Avenell A, Gillespie WJ, Gillespie LD, O'Connell DL. Vitamin D and vitamin D analogues for preventing fractures associated with involutional and post-menopausal osteoporosis. Cochrane Database Syst Rev 2005;(3):CD000227. PubMed: PM16034849 15. Lyons RA, Johansen A, Brophy S, Newcombe RG, Phillips CJ, Lervy B, et al. Preventing fractures among older people living in institutional care: a pragmatic randomised double blind placebo controlled trial of vitamin D supplementation. Osteoporos Int 2007;18(6):811-8. PubMed: PM17473911 16. Sato Y, Iwamoto J, Kanoko T, Satoh K. Low-dose vitamin D prevents muscular atrophy and reduces falls and hip fractures in women after stroke: a randomized controlled trial. Cerebrovasc Dis 2005;20(3):187-92. PubMed: PM16088114 Studies investigating a mixed-age population 17. Cranney A, Horsley T, O'Donnell S, Weiler H, Puil L, Ooi D, et al. Effectiveness and safety of vitamin D in relation to bone health. Evid Rep Technol Assess (Full Rep) 2007;(158):1-235. PubMed: PM18088161 Available: http://www.ahrq.gov/downloads/pub/evidence/pdf/vitamind/vitad.pdf (accessed 2009 Mar 19). 18. Jackson RD, LaCroix AZ, Gass M, Wallace RB, Robbins J, Lewis CE, et al. Calcium plus vitamin D supplementation and the risk of fractures. N Engl J Med 2006;354(7):669-83. PubMed: PM16481635 Studies in which outcomes are ambiguous 19. Autier P, Gandini S. Vitamin D supplementation and total mortality: a meta-analysis of randomized controlled trials. Arch Intern Med 2007;167(16):1730-7. Available: http://www.crd.york.ac.uk/crdweb/showrecord.asp?id=12007008358 Secondary analyses 20. Broe KE, Chen TC, Weinberg J, Bischoff-Ferrari HA, Holick MF, Kiel DP. A higher dose of vitamin d reduces the risk of falls in nursing home residents: a randomized, multiple-dose study. J Am Geriatr Soc 2007;55(2):234-9. PubMed: PM17302660 21. Bischoff-Ferrari HA, Conzelmann M, Stahelin HB, Dick W, Carpenter MG, Adkin AL, et al. Is fall prevention by vitamin D mediated by a change in postural or dynamic balance? Osteoporos Int 2006;17(5):656-63. PubMed: PM16508700 Vitamin D Supplementation in the Elderly and Long-term Care Residents 6