Beyond the Break Role of Vitamin D in Nutrition, Bone health and Osteoporosis Clinical: updates & practical considerations
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1 Beyond the Break Role of Vitamin D in Nutrition, Bone health and Osteoporosis Clinical: updates & practical considerations Presenter: Hope Weiler, RD(CDO), PhD Date: March 4, 2016
2 Disclosures OC Consultant ; OC Knowledge Transfer Committee Research funding CIHR, NSERC, CFI, Canada Research Chair , ESAC DFC Participated in systematic reviews for IOM: Cranney et al 2007, Evid Rep Technol Assess (Full Rep) as co-author Chung et al 2009, Evid Rep Technol Assess (Full Rep) as content reviewer Euro-pharm International Canada Inc., has provided in-kind product (Gallo et al, JAMA 2013)
3 Learning Objectives By attending this workshop, physicians and health care professionals will have a strong understanding of: Epidemiology of osteoporosis, falls and fractures in Canada Practice guidelines in Canada for prevention and management of osteoporosis The physiology of vitamin D Measurement of vitamin D status and definitions Evidence behind recommendations focus on vitamin D New concepts in vitamin D nutrition falls and fracture prevention, lean body mass
4 Community residents Osteoporosis in Canada Risk factors: female, aboriginal, income below 5 th quintile, underweight. Garriguet, Health Reports 2011;22:3. Men > 50 y overall - may be under-diagnosed - 6.6% Tenenhouse et al, Osteoporos Int 2000.
5 Canadians are living longer Life expectancy continues to increase Year Men (y) Women (y) Year 3 % 65 y % 80 y Life expectancy at birth 1 Statistics Canada, CANSIM, table and Catalogue no XIE. Last modified: Canada s Aging Population, Health Canada, 2002, p The Daily, Statistics Canada, Sept 17, 2014 (based on medium growth)
6 Osteoporosis/Fracture 57,413 osteoporosisrelated fractures 2007/ d mean hospital stay Hip fractures accounted for half of the hospitalized d 112,740 emergency visits, 85% wrist fx 3433 same day surgeries 30% wrist 23% hip 30% other fractures $1.2 billion Highest cost for multiple fractures and hip fractures ($20,163/hospitalization) 53% of total costs hip fractures Continuing care 91 additional days Estimated $245 million in home care 41% hip fractures Tarride et al, Osteoporos Int, 2012
7 Injuries and Falls Fracture Those 85 y or over Major Causes of Fracture 70% more likely to have an injury 60% more common in women Falls are the main cause Falls 65% of all injuries 84% of injury-related admissions 58% of injury-related deaths Annual health care costs due to falls $1.2 billion (50% due to hip fractures) Canada s Aging Population, Health Canada, 2002, p
8 Falls and Osteoporosis in Canada CCHS community surveillance CANSIM Database Statistics Canada
9 Life after fracture? Tarride et al, Osteoporos Int, 2012
10 Prevention of osteoporosis and fractures: Canadian Guidelines Prevention & management of osteoporosis lifestyle including diet, supplements and exercise Exercise resistance &/or weight bearing activity Improves physical function, pain, strength and balance Nutrition to build or preserve mineral mass Before age 50 y: High risk 800 to 2000 IU vitamin D/d Over age 50 y: Calcium 1200 mg/d total Vitamin D IU/d; IU/d if high risk Papaioannou et al, CMAJ 2010
11 Diagnosis: With or without BMD Assessments Diagnosis of Osteoporosis: > 50 y T-score below -2.5 = osteoporosis Papaioannou et al, CMAJ 2010
12 Vitamin D + Ca for preventing fractures 800 IU g Ca 400 vs 800 IU +1.2 g Ca 700 IU mg Ca 800 IU mg Ca 400 IU D mg Ca Avenell et al, Cochrane Database of Systematic Reviews; 14 APR 2014 DOI: /
13 Vitamin D plus Calcium Avenell et al, Cochrane Review 2014
14 Vitamin D, Bone and Skeletal Muscle Terminology Cholecalciferol or vitamin D 3 Ergocalciferol or vitamin D 2 Vitamin D 1 µg = 40 IU vitamin D 25-hydroxyvitamin D or calcidiol 1 ng/ml =~ 2.5 nmol/l 1,25(OH) 2 D or calcitriol
15 Vitamin D 25(OH)D Dietary Sources 37 Chemically characterized metabolites UVB 7-Dehydrocholesterol (present in the skin) [25(OH)D] = status indicator Sun, diet and supplements 50 nmol/l Health Canada/IOM 75 nmol/l Osteoporosis Canada Modified from Norman, A. W Am J Clin Nutr 2008;88:
16 Dietary Reference Intakes IOM 2011 Age Vitamin D RDA g (IU) Vitamin D UL g (IU) 0-6 mo (AI: 400 IU) mo (AI: 400 IU) y y y y y > 70 y
17 74% 61% 27% 20%
18 Seru 25 h dro vita i D a d risk of ajor osteoporotic fractures in older U.S. adults RR Looker et al, 2013 JBMR Journal of Bone and Mineral Research Volume 28, Issue 5, pages , 17 APR 2013 DOI: /jbmr
19 Who to Test or NOT to Test? Tests are now indicated only for individuals with specific conditions: Osteoporosis, rickets, osteomalacia, malabsorption syndromes, renal disease and if taking medications that may affect vitamin D status
20 Risk Factors for Low or Deficient Vitamin D Status Endogenous Synthesis Moderately fair-skinned 6 to 7 min/d mid-morning to mid-afternoon on most days to maintain vitamin D status Risk of low status: Housebound, communitydwelling older people Disabled people Residential care Dark-skinned people Clothing coverage Regular avoidance of sun Indoor workers Exogenous Intakes In countries with no fortification policy, most adults are likely to achieve 5 to 10 % of needs by food If sun exposure is minimal 600 IU/d people < 70 y 800 IU/d people > 70 y High risk may require higher dosages Vita i D a d health i adults i Australia a d Ne Zeala d: a positio state e t Nowson et al, 2014 MJA
21 Ca ada s Food Guide Potential contribution to dietary vitamin D intake Fluid milk (~100 IU or 2.5 g/250 ml) y: 2 servings ~200 IU or 5 g/d 51+ y: 3 servings ~300 IU or 7.5 g/d > 50 y: 3 servings IU/10 g supplement = 700 IU or >15 g/d
22 Dietary Patterns: It is possible to achieve intakes mostly from food as long as compliance to food and supplements is high. May be feasible at most ages from childhood to aging Food Milk 3 cups/d Orange juice 0.5 cup/d 50 Egg whole/d 25 Pink Salmon 7 oz/wk 171 Yoghurt 175 g made with fortified milk Vitamin D (IU) 300 (or 2 enriched) 44 Margarine 4 tsp/d 100 Supplement 400 Total=1090 IU
23 Vitamin D Intakes of Canadians from Food (CCHS; mean g/d) Age (y) Males and Females Age (y) Males Females (188 IU) (208 IU) (284 IU) 5.0 (200 IU) > (252 IU) 5.3 (212 IU) 5 g = 200 IU 10 g = 400 IU 15 g = 600 IU Milk products intake y: <1.4 servings >70 y: <1.4 servings Canadian seniors on average meet less than ¼ of the recommended servings of milk products.
24 Milk Intakes by Canadians Percentage below recommended minimum number of servings of milk products, by age group and sex, household population ages 4 or older, Canada excluding territories, % of vitamin D intake from food is derived from milk
25 Men & Women 69 to 83 y Total Vitamin D intake ( g/d) % 4.6 g 184 IU 48% 8.7 g 348 IU 45% 14.1 g 564 IU < >75 Vitamin D Status Category (nmol/l) Sources of Vitamin D: 6x24 h recalls (n=404) 6 g Supplements Response of 25(OH)D to 1 g or 40 IU: Supplementation: elevates by 1.4 nmol/l Food: elevates by 3.1 nmol/l Summer: 14 nmol/l higher Barake et al, J Nutr g Milk 0.8 g Margarine 0.7 g Fish 0.6 g Meat 0.4 g Other 0.1 g Eggs
26 Supplement Isoform Random-effects meta-analysis comparing the effects of daily and bolus supplementation of D3 with that of D2 on net changes in serum 25(OH)D concentrations. mean difference D 3 over D 2 : 15.23; 95% CI: 6.12, 24.34; P = by American Society for Nutrition Source: Tripkovic L et al. Am J Clin Nutr 2012;95:
27 Supplements with Food 50,000 IU tablet every 3 mo. Like letters indicate different P 0.04 Taking the same vitamin D with the largest meal improves absorption and higher serum levels of 25 h dro vita i D Journal of Bone and Mineral Research Volume 25, Issue 4, pages , 8 FEB 2010 DOI: /jbmr.67 Meal conditions affect absorption of vitamin D 3 but not status response Journal of Bone and Mineral Research Volume 28, Issue 8, pages , 18 JUL 2013 DOI: /jbmr
28 2008 by American Society for Nutrition, Norman A W Am J Clin Nutr 2008;88:
29 Muscle and Vitamin D Muscle strength Standardized mean difference 0.17 (P=0.02). >65 y standardized mean difference of 0.25 (0.01 to 0.48) vs younger 0.03 (-0.08 to 0.14) Muscle Mass NS Muscle Power NS Std Diff in means and 95%CI Beaudart et al 2014 Favors control Favors vitamin D
30 Falls in community Vitamin D supplementation helps if low status 600,000 IU D IU mg Ca Gillespie et al 2012 Rate of falls: RaR 0.57 ( ); Risk of falls: RR 0.70 ( ) O erall ita i D did ot redu e rate of falls or risk of falli g; ut ay do so i people ith lo er ita i D le els efore treat e t
31 Vitamin D and Falls 800 IU D 3, 1200 mg Ca 1000 D 2 /d or IU/wk mg Ca 800 IUD 2 /d 2.5 mg D 2 /2mo (1100 IU/d) 400 IU D mg CaCO3 Cameron et al, 2012
32 Vitamin D in Skeletal Muscle Sheath Skeletal Muscle Blood vessel 25(OH)D Blood vessel 1,25(OH) 2 D VDR Single muscle fibre myofilament Single myofibril Non-genomic effects RXR VDR Gene transcription: IGF-1, VDR, calmodulin, type 2 muscle CSA VDRE CYP27B1 Mitochondria Skeletal Muscle Cell (Myocyte)
33 Skeletal Muscle Cell Vitamin D Metabolism C2C12 muscle cell 1α-hydroxylase With authors per issio ; Girgis et al, Endocrinology 2014
34 Skeletal Muscle Cell Vitamin D Metabolism C2C12 muscle cell - functional 1α-hydroxylase - less proliferation and greater myotube diameter With authors per issio ; Girgis et al, Endocrinology 2014
35 Skeletal Muscle Cell Vitamin D Metabolism Vitamin D supplementation elevates VDR in muscle biopsies 1,25(OH) 2 D dosedependently elevates VDR mrna expression ( 36%) in human primary myoblasts from healthy young adults Pojednic et al, Calcif Tissue Int, 2014
36 Skeletal Muscle Cell Vitamin D Metabolism Vitamin D supplementation elevates VDR in muscle biopsies 16 wk trial of 4000 IU/D vs placebo in 8 older men and 12 women elevates VDR gene expression in muscle biopsies. VDR protein higher if vitamin D sufficient p=0.02, regardless of trial group. Pojednic et al, Calcif Tissue Int, 2014
37 Skeletal Muscle Cell Vitamin D Metabolism Vitamin D supplementation elevates muscle VDR and fibre size 4 mo trial Women > 65 y 4000 IU vitamin D vs placebo 25(OH)D 43.6 to 80.0 nmol/l in treatment group; NS change in placebo. Ceglia et al, JCEM 2013
38 Skeletal Muscle Cell Vitamin D Metabolism Vitamin D supplementation trial after stroke 2-y trial of 1000 IU vitamin D 2 vs placebo Women (n=96) after stroke Baseline 25(OH)D < 25 nmol/l Treatment: relative number and size of type II muscle fibres Improved muscle strength 59% reduction in falls (95% CI, 28-81, p=0.03) Fewer hip fractures (4/48 vs 0/48, p=0.049) Sato et al Cerebrovasc Dis 2005
39 From: Exercise and Vitamin D in Fall Prevention Among Older Women: A Randomized Clinical Trial JAMA Intern Med. 2015;175(5): doi: /jamainternmed y double blind RCT 800 IU/d with and without exercise vs placebo Women y, home-dwelling, Finland 25(OH)D > 65 nmol/l at baseline Primary outcome: falls Vitamin D maintained femoral neck BMD and increased tibial trabecular BMD, but did not alter muscle strength or balance. Figure Legend: Hazard Ratios (95% CIs) for Fallers, Injured Fallers, and Multiple Fallers Using the Placebo Without Exercise Group as the ReferenceCumulative hazard is presented for the injured fallers. a P <.05 compared with the placebo without exercise group. Date of download: 10/13/2015 Copyright 2015 American Medical Association. All rights reserved.
40 Summary: Vitamin D, Muscle, Falls and Fractures Osteoporosis and falls are similarly common in Canadian women > 65 y; dx in men is less common Osteoporosis Canada recommends calcium, vitamin D and activity in the prevention and management of osteoporosis Most Canadians have good vitamin D status For those with low vitamin D status Benefits of achieving good vitamin D status may realized as improved: musculoskeletal health, bone density, muscle mass, falls prevention
41 Acknowledgements CRC Tier I, Nutrition and Health Across the Lifespan
42 Vitamin D Food Policy in Canada Mandated fortification Milk ~100 IU/cup Margarine ~25 IU/tsp Food label panels Nutritional Facts 1983 recommendations 200 IU/d RNI vs 2011 recommendations 600 to 800 IU/d RDA
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