Vitamin D and Fall prevention


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Evidence base in Vitamin D and Fall prevention

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Vitamin D and Fall prevention

  1. 1. Prevention of Falls in Older Adults: Evidence Based Medicine Wisit Cheungpasitporn, MD. Bassett Medical Center PGY -1, Internal Medicine
  2. 2. Leading Causes of Death: 65+ <ul><li>1. Heart Disease </li></ul><ul><li>2. Cancer </li></ul><ul><li>3. Stroke </li></ul><ul><li>4. COPD/Pulmonary disease </li></ul><ul><li>5. UNINTENTIONAL INJURIES </li></ul>
  3. 3. Facts About Falling… <ul><li>1/3 of community dwelling older adults fall annually </li></ul><ul><li>95% of hip fractures result from a fall. </li></ul><ul><li>Of those who fall, 25% suffer injuries that reduce mobility and independence. </li></ul><ul><li>50% of those who sustain injury from a fall can no longer live independently. </li></ul>
  4. 4. Facts About Hip Fractures <ul><li>1 in 7 women will break hip. </li></ul><ul><li>25% will regain full functional ability. </li></ul><ul><li>50% will end up in nursing home. </li></ul><ul><li>25% will die within one year. </li></ul><ul><li>Risk of dying from osteoporosis = </li></ul><ul><li>Risk of dying from breast cancer </li></ul>
  5. 5. Why Do People Fall? summary of 12 studies <ul><li>Accident/environment- 31% </li></ul><ul><li>Gait/balance problem – 17% </li></ul><ul><li>Dizziness/vertigo – 10% </li></ul><ul><li>Confusion – 4% </li></ul><ul><li>Postural hypo-tension –3% </li></ul><ul><li>Vision –3% </li></ul><ul><li>Other and unknown –20% </li></ul>
  6. 6. Where do people fall? <ul><li>For those 65+ </li></ul><ul><ul><li>- 60% happen at home </li></ul></ul><ul><ul><li>- 30% occur in public places </li></ul></ul><ul><ul><li>- 10% in health care institutions </li></ul></ul>
  7. 7. Facts About Falls and Hospitals <ul><li>. 6 –2.9 falls per bed annually in hospitals; ( Rubenstein 2000) </li></ul><ul><li>14% of d/c pts. fall the first month after discharge; </li></ul><ul><li>falls are the BEST predictor of nursing home placement; </li></ul><ul><li>40% of nursing home placements due in some way related to a fall. </li></ul>
  8. 8. Cost of falls <ul><li>8% of those over 70 visit ER annually for a fall. </li></ul><ul><li>1/3 of these are hospitalized. </li></ul><ul><li>5.3% of hospitalizations of those over 65 are directly due to falls. </li></ul><ul><li>Ave. cost per fall for 65+= $19,440 (excluding MD). Rizzo 1998 </li></ul><ul><li>Cost to US-estimate: $20B 1995 2020 $32B. </li></ul>
  9. 9. Falls are Predictable: Risk Factors for Falls <ul><li>Impairments in… </li></ul><ul><ul><li>Cognition. </li></ul></ul><ul><ul><li>Vision or hearing. </li></ul></ul><ul><ul><li>Feet. </li></ul></ul><ul><ul><li>Lower extremity strength. </li></ul></ul><ul><ul><li>Balance or gait. </li></ul></ul><ul><ul><li>Postural hypo-tension. </li></ul></ul><ul><ul><li>Syncope and arrhythmia. </li></ul></ul>
  10. 10. Risk Factors for falls, cont. <ul><li>Medication use </li></ul><ul><li>Total number over 4 AND/OR </li></ul><ul><li>- Sedatives: confusion, motor dysfunction </li></ul><ul><li>- Anti-psychotics: hypotension </li></ul><ul><li>- Anti-depressants: hypotension </li></ul><ul><li>- Anti-hypertensives: postural hypo-tension </li></ul><ul><li>- Anti-anxiety: Confusion </li></ul><ul><li>- Diuretics: Urinary urgency resulting in a </li></ul><ul><li>fall </li></ul>
  11. 11. Risk Factors for Falls, cont. <ul><li>Alcohol intake. </li></ul><ul><li>Dehydration. </li></ul><ul><li>Poor Nutrition. </li></ul><ul><li>- Vitamin D </li></ul><ul><li>- Calcium </li></ul>
  12. 12. ED Assessment of falls ( Aannals of internal meds 1997 <ul><li>Things to consider in the History & Physical </li></ul><ul><li> Elder abuse </li></ul><ul><li> Alcohol abuse </li></ul><ul><li> Medication review </li></ul><ul><li>Falls in preceding months </li></ul><ul><li>Hydration </li></ul><ul><li>Malnutrition </li></ul><ul><li>Eye exams in past year </li></ul><ul><li>Gait, strength and balance </li></ul><ul><li>Environmental hazards </li></ul>
  13. 13. J Am Geriatr Soc .  2010;58 ( 7 ): 1299-1310
  14. 14. Introduction <ul><li>Recent studies have suggested that vitamin D supplementation is a safe, well - tolerated approach to improve muscle strength and function, leading to fewer falls . </li></ul><ul><li>Older adults may be at greater risk for vitamin D deficiency for many reasons, including lower cutaneous synthesis of vitamin D </li></ul><ul><li>The most commonly available forms are native vitamin D ( cholecalciferol or vitamin D3, ergocalciferol or vitamin D2, 25-hydroxyvitamin D ) and active vitamin D ( calcitriol, alfacalcidol or 1,25-dihydroxyvitamin D ). </li></ul>
  15. 15. <ul><li>Muscle biopsies in patients who are deficient in vitamin D demonstrate atrophy of type II fibers, which are recruited first to prevent a fall . </li></ul><ul><li>Binding of the vitamin D receptor ( VDR ) in muscle affects transcription of genes that modulate calcium and phosphate uptake, phospholipid metabolism, and muscle cell proliferation and differentiation . </li></ul><ul><li>In VDR knockout mice, impaired motor coordination is observed . </li></ul><ul><li>Clinical vitamin D deficiency is associated with a proximal myopathy that improves with treatment . </li></ul>
  16. 16. <ul><li>Body sway improved more with vitamin D and calcium than with calcium alone in elderly ambulatory women . 18 Improvements in muscle strength, and subsequent gait stability, may explain the association between vitamin D therapy and fall prevention . </li></ul><ul><li>Although previous reviews have found insufficient evidence to conclude that vitamin D supplementation reduces the risk of falling 5,19–21 or greater benefit with active vitamin D, 22,23 one study 24 reported a significant 22% fewer falls with any type of vitamin D . In a recent meta - analysis of eight randomized controlled trials, 25 native vitamin D treatment reduced falls by 13%, although there was significant heterogeneity of studies . Only high - dose vitamin D ( 700–1,000 IU ) , achieved serum 25-hydroxyvitamin D concentrations greater than 24 ng / mL, and active vitamin D treatment significantly reduced fall risk by 19% to 23% . Most previous meta - analyses were underpowered or did not examine specific subgroups of patients in whom vitamin D may have differential effects . In recent years, additional randomized controlled trials using various fall ascertainment techniques have been published reporting the potential benefits of vitamin D in the prevention of falls; therefore, an updated meta - analysis is warranted . </li></ul><ul><li>The objective of the current study was to perform a comprehensive, updated systematic review and meta - analysis of randomized controlled trials that have evaluated the effectiveness of vitamin D therapy on fall prevention in older adults ( mean age ≥60 ) , adding to recent findings 25 by investigating if progressively higher doses of vitamin D are associated with greater benefits in fall risk . Whether beneficial effects of vitamin D treatment extend to hospitalized patients and whether particular patient factors ( e . g . , history of prior fracture or fall ) or treatment regimens ( e . g . , adjunctive calcium use ) contribute to the effect of vitamin D was also explored . Formal quality assessment of included studies was also undertaken to identify possible sources of systematic biases . </li></ul>
  17. 17. METHODS <ul><li>Data Sources and Selection </li></ul><ul><li>A standardized protocol was developed and followed for all steps of the review . Investigators searched MEDLINE, CENTRAL, EMBASE, CINAHL, Web of Science, and LILACS and hand - searched bibliographies of selected articles and previous systematic reviews to identify articles that potentially met the inclusion criteria . Medical subject headings, keywords, and truncated word vocabulary were used in the search strategies . The search strategy combined terms for the intervention of vitamin D ( 1,25-dihydroxycholecalciferol, 25-hydroxycholecalciferol, 1,25-dihydroxyvitamin D, 25-hydroxyvitamin D, vitamin D, ergocalciferol, cholecalciferol, calcitriol, hydroxycholecalciferol, dihydroxycholecalciferol, calcifediol, vitamin D 2 , vitamin D 3 , paricalcitol, vitamin D analogs and derivatives ) , outcome of falls ( accidental falls, body sway, gait ) , and study design of randomized clinical trials using the Cochrane highly sensitive search strategy ( MEDLINE only ). 26 For smaller databases, to maximize the yield, the search strategy did not include syntax for study design . All electronic databases were accessed on February 9, 2009 . </li></ul>
  18. 18. <ul><li>Study Selection </li></ul><ul><li>Two investigators independently reviewed the titles, abstracts, or full - text manuscripts of relevant articles identified through the literature search to determine whether they met eligibility criteria ( Figure 1 ). A study was eligible for inclusion if it was a randomized, controlled trial; the mean age of study participants was 60 and older; the study compared vitamin D treatment with calcium therapy, placebo, or no treatment; the number of participants with one or more falls according to treatment arm was given; and an explicit fall definition was provided along with a description of how falls were ascertained . Falls were defined as “unintentionally coming to rest on the ground, floor, or other lower level . ” 27 Studies that did not have an explicit fall definition were included in a post hoc analysis . To examine potential subgroup effects, all eligible studies were included, regardless of dwelling ( community, nursing institution, or hospital ) ; participants' history of fracture or fall; vitamin D levels; adjunctive calcium therapy; or dose, type, and duration of vitamin D therapy . Studies that used only intramuscular vitamin D were excluded because this route is not as effective as oral . 28 Studies restricted to participants with significant neurological disabilities, such as Parkinson's disease or stroke with hemiplegia, in whom the independent effects of vitamin D on fall risk may be unclear, were also excluded . There were no restrictions on year or language, although at least one author had to be able to translate the study . Disagreements regarding inclusion and exclusion of studies were resolved according to group consensus and by referring to the original reports . </li></ul>
  19. 19. <ul><li>Data Extraction and Quality Assessment </li></ul><ul><li>Study investigators independently abstracted data in duplicate using a standardized form . The abstracted data were then entered into Microsoft Excel ( Microsoft Corp, Redmond, WA ) , and a second reviewer verified them . Abstracted data included study design ( date and location of study, sample size ) , patient characteristics ( risk factors for falling, such as history of previous fracture or fall and comorbidities ) , study methodology ( eligibility criteria, method of randomization, blinding ) , intervention ( type, dose, duration of therapy ) , adverse events, and main results . Authors were not contacted directly for missing data . Methodological quality of included studies was investigated by collecting data on sources of systematic bias using published guidelines . 29 Collected data included information regarding sequence generation, allocation concealment, assessor blinding, incomplete outcome data, selective reporting, eligibility criteria, therapies, excluded patients, and reliability of fall ascertainment . Sources of funding were documented . </li></ul><ul><li>The primary outcome of the meta - analysis was the number of participants with one or more falls during follow - up . Studies in which only the relative risk of falling in each treatment arm was reported, but not the number of fallers, were included . Total number of falls was not analyzed because individuals with recurrent falls may have other significant risk factors for falling . </li></ul>
  20. 20. <ul><li>Data Synthesis and Analysis </li></ul><ul><li>A summary relative risk ( RR ) was calculated for the primary ( dichotomous ) outcome of number of participants with one or more falls during follow - up . The planned analysis was vitamin D arm ( with or without calcium ) versus comparator arm ( placebo, calcium, or no treatment ). For studies that tested multiple doses of vitamin D in separate intervention arms, a pooled effect estimate from all arms with vitamin D were compared with a pooled effect estimate from all arms without vitamin D for the main analysis . </li></ul><ul><li>The presence of heterogeneity was evaluated using the I 2 statistic for pooled study-level data. An I 2 statistic greater than 50% suggested moderate heterogeneity . 30 The a priori hypothesis was that there would be heterogeneity between and within studies, so a random effects model was used . The following a priori subgroup analyses were conducted to explore potential heterogeneity between studies : type, dose, and duration of vitamin D; use of adjunctive calcium in treatment arm; type of dwelling; history of fall or fracture in majority of participants; and mean baseline vitamin D level of 30 ng / mL or less ( vitamin D insufficiency ). For studies with arms that used multiple doses of vitamin D, each arm was compared with the control arm to derive a RR of falling for the relevant subgroup analyses . A meta - regression analysis examining the linear association between dose and duration of vitamin D treatment and the RR of falling was also performed . Sensitivity analysis was performed on studies with similar baseline characteristics between intervention and control groups . Publication bias was assessed using Begg's funnel plot and the Begg's and Egger's statistical tests . 31,32 All analyses were performed using Stata version 10.0 ( StataCorp, College Station, TX ). </li></ul>
  21. 22. Result <ul><li>Search Results and Study Characteristics </li></ul><ul><li>A total of 1,679 unique titles and abstracts were retrieved from the search ( Figure 1 ) ; 1,543 studies were excluded after title and abstract review because they did not satisfy the inclusion criteria . Subsequently, 136 articles underwent full text review, with 126 studies excluded . ( Seven of these articles without an explicit fall definition were later examined in post hoc analysis .) Ultimately, 10 randomized controlled trials met inclusion criteria for primary analysis . </li></ul><ul><li>The mean ages of participants ranged from 71 to 92 ( Table 1 ) , and the majority were women . The included studies spanned eight countries; three were multicenter trials . 33–35 One study 36 included only hospitalized patients, four included institutionalized participants, 33,34,37,38 and five evaluated community - dwelling adults . 18,35,39–41 All studies in community - dwelling adults had a mean age younger than 80 . Four studies specified that the majority of participants had a history of previous fracture or fall, 36–39 whereas four specified that most participants did not have history of fractures or falls . 18,34,35,40 In all studies in which baseline mean 25-hydroxyvitamin D levels were reported, the level in at least one treatment arm was less than 30 ng / mL . </li></ul>
  22. 25. <ul><li>All intervention arms were compared with placebo or calcium . All studies were parallel group design and had two arms ( intervention and control ) except for one 38 that randomized patients to five treatment arms based on vitamin D dose ( 200–800 IU ) and a placebo arm . Seven studies had intervention arms that included adjunctive calcium supplementation ( 500–1,200 mg ) ; 18,34–37,39,41 although most of these also included calcium supplementation in the control arm, one used placebo in the control arm . 41 The remaining three trials compared vitamin D with placebo . 33,38,40 Three types of vitamin D ( cholecalciferol, ergocalciferol, alfacalcidol ) were used . Treatment duration ranged between 1 and 36 months, and native vitamin D dosage ranged between 200 and 1,000 IU . Adherence ranged from 86% to 98% for most studies in which this information was reported . 18,34,36,38 The follow - up rate was greater than 85% in studies that reported completion rates . 18,34,36,38–40 Two studies reported involvement with industry sponsorship . 18,35 </li></ul><ul><li>Falls were a primary outcome in all included studies and were ascertained according to direct observation in three studies, 36–38 questionnaire alone in two studies, 18,39 and fall diaries in three studies. 34,35,40 Two studies used a combination of methods, including questionnaire and postcard 41 and questionnaire and diary. 33 </li></ul>
  23. 26. <ul><li>Assessment of Methodological Quality </li></ul><ul><li>In general, methodological quality of included studies was good ( Table 2 ). All studies had clearly defined eligibility criteria and therapies and reliable fall ascertainment . All studies were double - blind except for one, 33 which did not clearly mention the method of blinding and may have been subject to detection bias; in this study, a subgroup of participants was followed as part of a larger, observational study and randomized to vitamin D treatment . Sequence generation was adequately described in all studies except four . 18,33,35,41 In three of these studies, 18,33,35 there was insufficient information on allocation concealment, which may have made them vulnerable to selection bias . At least one of the following was absent or unclear in three studies 33,35,41 —incomplete outcome data addressed, similar rates of follow - up, and reasons for loss to follow - up—rendering these studies vulnerable to attrition bias . Reasons for exclusion were described in all studies except one . 33 Baseline characteristics were dissimilar between study arms in two studies because of differences in previous fracture rate 34 or anticoagulant use 40 and were unclear in two studies . 33,36 </li></ul><ul><li>Statistical methods were described in all studies . Prospective sample size justification was not clearly stated in three studies, 33,38,41 whereas intention - to - treat analysis was clearly stated in all but one study . 33 </li></ul>