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Osteoporosis and Nutrition Module 4 Speaking of Bones Osteoporosis For Health Professionals Susan J Whiting University of Saskatchewan Learning Objectives • Understand the 3 critical nutrients for bone: calcium, vitamin D and protein – Recommendations for these have recently changed • Appreciate bone is a living tissue and other nutrients are needed – Their impact depends on one’s baseline diet • Intend to use dietary recommendations such as CFG or DASH as these are bone healthy except vitamin D – A vitamin D supplement always necessary – These diets are low sodium, high potassium Acknowledgments and Conflict of Interest • This presentation is mainly based upon a slide kit* in development through funding by Yoplait France, and the following experts have reviewed its content: – Pr. Jean-Philippe Bonjour, Division of Bone Diseases, Departement of Internal Medicine, University Hospital, Genève, Suisse – Pr. Marius Kraenzlin, Division of Endocrinology, Diabetes, and Clinical Nutrition, University Hospital, Bale, Suisse – Dr. Régis Levasseur, Service de Rhumatologie et Pôle Ostéoarticulaire, CHU Angers, France – Pr. Michelle Warren, Department of Obstetrics and Gynecology Columbia University Medical Center, New York, USA – Pr. Susan Whiting, College of Pharmacy and Nutrition, University of Saskatchewan, Canada *Updates by S. Whiting have not been vetted by the group of experts Definition of Osteoporosis « …a skeletal disease characterized by low bone mass and microarchitectural deterioration of bone tissue with a consequent increase in bone fragility and susceptibility to fracture » Consequences: fractures Wrist Spine Hip WHO 1994 Photos: Dempster DW et al., J Bone Miner Res 1986; 1:15. Copyright 1986 © Wiley Pathophysiology of fragility fracture risk in elderly Undernutrition + Low level of physical activity Bone formation - Balance - Muscle mass - Neuro-muscular function Bone resorption Bone mass and strength Risk of falls Fracture risk Protective response Importance of essential nutrients Calcium Vitamin D Protein Vitamin D metabolism Skin UVB light 7-dehydrocholesterol Vitamin D Diet Inactive form Kidney 1,25(OH)2D Active form 25(OH)D + 1-hydroxylase Stimulation of intestinal calcium absorption Circulating and measured form Status indicator PTH Hypocalcemia Hypophosphatemia IGF-I 25α-hydroxylase Vitamin D metabolism Skin UVB light 7-dehydrocholesterol Vitamin D Diet Inactive form Kidney 1,25(OH)2D Active form 25(OH)D + Circulating form 1-hydroxylase Stimulation of intestinal calcium absorption Status indicator 25α-hydroxylase 1,25 is made intracellularly Stimulation of cell growth and differentiation in other tissues Vitamin D metabolism Skin UVB light 7-dehydrocholesterol Vitamin D Diet Inactive form Kidney 1,25(OH)2D Active form 25(OH)D + Circulating form 1-hydroxylase Status indicator Stimulation of intestinal calcium absorption Endocrine pathway 25α-hydroxylase 1,25 is made intracellularly Autocrine pathway Stimulation of cell growth and differentiation in other tissues Vitamin D deficiency in elderly 45 25(OH)D (ng/ml) Serum (ng/ml) Serul 25(OH)D 40 35 Osteoporosis Canada 75 nmol/L 30 25 IOM 50 nmol/L 20 15 10 5 Double cause of deficiency with age: Reduced skin synthesis of vitamin D Insufficient sun exposure 0 Adults Independent Elderly in Hip f racture elderly institutions patients Adapted from Lips P et al., Endocr Rev 2001; 22:477 Recent Meta-Analysis of Fracture Risk: NEJM July 5, 2012 • In 11 RCTs involving over 31,000 people, a dose response is seen • To achieve a significantly reduced HR for fracture reduction, 25(OH)D levels must be over 60 nmol/L Recent MetaAnalysis of Fracture Risk: NEJM July 5, 2012 Only when sufficient vitamin D is given ( > 792 IU) to raise levels of 25(OH)D is there a significant effect on fracture risk. Effect of vitamin D on the risk of falls Fall prevention by 1000 IU vitamin D2 supplementation in women with a history of falling in the previous year p<0.05 35.8 % Percentage of subjects 40 27.2 % 27.8 % 25.2 % 30 Placebo++calcium calciumcitrate (1g/d) Placebo 20 Vitamin D2 (1 000 IU) Ergocalciferol + calcium citrate + calcium citrate (1g/d) 10 0 First fall in summer/autumn First fall in winter/spring In 2011 the European Food Safety Authority has approved a health claim for 800 IU of vitamin D for falls prevention in persons > 60 y Prince RL et al., Arch Int Med 2008; 168:103 2010 Osteoporosis Canada Recommendations for Vitamin D Recommended intake for low-risk and younger adults are 10-25 μg (400–1000 IU) daily Recommended intake for high-risk and older adults are 20–50 μg (800–2000 IU) daily For individuals being treated for osteoporosis, vitamin D status should be assessed by serum measurement of 25hydroxyvitamin D after 3 months of vitamin D supplementation To ensure levels are at or above 75 nmol/L How to reach these recommendations ? 3 sources of vitamin D Diet Sun exposure Supplementation Independent and cumulative effect Foods with vitamin D salmon liver sardines in oil meat eggs Butter or margarine Unlike calcium, few foods contain vitamin D in significant amounts Difficult to reach daily recommended intake via diet alone Decline in previtamin D3 synthesis in skin with age Godar et al., Dermato-Endocrinology 3:4, 243-250; October/November/December 2011 Importance of essential nutrients Calcium Vitamin D Protein Calcium during growth Genetics Spontaneous calcium intake Gender Menarcheal age Bone gain Physical activity Other nutrients Pubertal stage Skeletal sites Bonjour JP et al., Le Rhumatologue 2009; 70:19 Calcium attenuates bone loss in women Lumbar BMD Mean % change ( 1 SEM) 6 3 controls 0 1000 mg Ca supplements / day -3 2000 mg Ca supplements / day -6 -9 Early peri Late peri Early post Late post Methodology: 248 women 46-55 y 25(OH)D levels similar ~ 18 ng/ml) menopause Elders P et al., J Clin Endocrinol Metab 1991; 73:533 2010 Osteoporosis Canada Recommendations for calcium Recommended intake for younger adults is 1000 mg daily Recommended intake for older adults is 1200 mg daily – New evidence suggests intake does not need to be higher than these recommendations – Excess intake may lead to kidney stones Examples of equivalence for 300 mg of calcium 300 g of soft white cheese 1 cabbage of 850 g 1 kg of oranges 30 g of Emmental 50 g of Saint Nectaire 5 baguettes 2 yogurts 4 kg of beef 250 ml of milk 2010 Osteoporosis Canada Recommendations for calcium Recommended intake for younger adults is 1000 mg daily Recommended intake for older adults is 1200 mg daily – New evidence suggests intake does not need to be higher than these recommendations – Excess intake may lead to kidney stones Keep total intake below Upper Level of 2000 mg Calcium and Heart Disease Risk What is the evidence? In the journal Heart 2012: data from ~24,000 men and women in Germany, 35-64 y, tracked for an average of 11 years as part of a European cancer and nutrition study. What was reported in Abstract (underlining added): Associations for stroke risk and CVD mortality were overall null. In comparison with non-users of any supplements, users of calcium supplements had a statistically significantly increased MI risk (HR:1.86 95% CI 1.17 - 2.96), which was more pronounced for calcium supplement only users (HR: 2.39; 95% CI 1.12-5.12) Kuanrong Li et al. Heart 98:920-925 Calcium Supplements and Heart Disease? What was reported: Calcium Is a Threshold Nutrient: More than adequate is not better Response (c) to increasing intake from C to D is almost immeasurable compared to (b) D Supplementation is effective up to an intake threshold Example in prepubertal girls with high and low calcium intake year) peryear) (% per BMD (% inBMDs Changes Change in Duration: 48 weeks 6 Spontaneous calcium intake Spontaneous Ca intake Median:855 855mg/d mg/d > < Median: < > * 5 4 Placebo 3 Ca supplement 2 36 36 * p < 0.01 31 41 1 0 805 694 1 238 1 175 11805 54 16 56 64 Total Ca consumed (mg/d) SEM Bonjour JP et al., J Clin Invest ; 99:1287 Importance of essential nutrients Calcium Vitamin D Protein Protein intake reduces fracture risk Protein intake and hip fracture in postmenopausal women of hip RRRR hip fracture of fracture Quartiles of total protein intake 1.2 1.0 0.8 0.6 0.4 0.2 0.0 Q1 Low intake Low intake Q2 Q3 Q4 HighHigh intake intake Quartiles of total protein intakes Munger et al., Am J Clin Nutr 1999; 69:147 Patients with recent hip fracture Methodology: (%) (%) femurfemur of proximal in BMD ange of proximal in BMD Change Mean age: 80.7 7.4 years Duration: 6 months 0 Placebo and treatment: 550 mg Ca/d 0 + 200 -1 000 IU vit D (one time) -1 -2 p=0.029 Change in BMD of proximal femur (%) Protein attenuates proximal femur bone loss p=0.029 -2 -3 -3 -4 -4 Number-5of hospital stays reduced by 21 days 0 -1 p=0.029 -2 -3 -4 -5 -6 0 6 12 -1 Proteinsupplements supplements(20 (20 g.d ) Protein Time (months) + calcium + vit D g.d-1) + calcium + vit D Protein supplements (20 g.d Protein supplement(20 (20 g/d)-1)+ calcium + vit D Protein supplements + calcium + vit D g.d-1) + calcium + vit D Isocaloric placebo (calcium + vit D only) Placebo Placebo (calcium + vit D (calcium + vit D only) only) Placebo Placebo (calcium + vit D (calcium + vit D only) only) -5 -6 0 6 12 Schürch M et al., Ann Intern Med 1998; 128:801 Prote Prote (20 g g.d-1) + cal Plac Placeb (calc only) Negative consequences of insufficient protein intake in the elderly Functional consequences of sarcopenia on bone Decreased mobility Protein balance Anabolism Catabolism Increased risk of falling Increased risk of fracture Adapted from Rosenberg IH, Am J Clin Nutr 1989; 50:1231 Increased milk consumption improves bone biomarkers in women Change in bone biomarkers (%) 10 5 0 -5 -10 *** *** *** -15 -20 PTH *** CTX P1NP OC BAP IGF-1 ***p < 0.01 Methodology: Duration: 2 x 6 weeks 2 groups in cross-over: Ca intake 600 mg vs.1 200 mg (600 mg + ½ l of milk) Bonjour JP et al., Brit J Nutr 2008;1 Protein Recommendations • For bone, intake should be at least 1 g/kg • In 2002, OC Guidelines were ““Maintain adequate protein” • OC is willing to accept the recommendation of 1 g/kg (compared to RDA of 0.8 g/kg) • Protein is not the “bad” nutrient for bone unless calcium intakes are low No effect of diet acid-ash on calcium balance Change of calcium balance (mmol/d) Change of calcium balance (mmol/day) There is no relationship between a change in net acid 2 excretion and a net loss of whole body calcium. 11 Roughead 05 00 Kerstetter 06 -1 -1 Roughead 03 Dahl 95 Kerstetter 06 Kerstetter 06 Kerstetter 06 -2 -2 R² = 0.003 p = 0.38 Spence 05 -3 -3 -50 -50 -25 -25 0 0 25 25 50 50 Change of net acid excretion (mEq/d) Change of net acid excretion (mEq/day) Promotion of an “alkaline diet” to prevent calcium loss is not justified Fenton TR and al., J Bone Miner Res 2009;24:1835-1840 Vegetarian, vegan diets and bone health Vegetarian diets Lacto-vegetarian diets provide sufficient calcium and protein Vegan diets Vegans diets, lacking milk products or appropriate alternatives, are low in calcium, protein, and vitamin D as well as other nutrients important for bone growth and bone maintenance The vegan diet requires a plant-based milk substitute or a supplement in order to provide sufficient calcium Protein may be limited and of poor quality unless there is an effort to select pulses (beans), nuts, and other protein foods Ho-Pham LT et al., Am J Clin Nutr 2009; 90:943 Janelle KC, Barr SI. J Am Diet Assoc 1995; 95:180 New SA, Osteoporos Int 2004; 15:679 There are potential benefits of many nutrients and food constituents Magnesium Phosphorus Zinc Manganese Vitamin C Vitamin K Vitamin B12 Carotenes Phytoestrogens Polyphenols Potassium Fibre 5 nutrients have received a positive opinion from EFSA on having evidence for a causeeffect relationship related to bone Magnesium Manganese* Phosphorus* Zinc* Vitamin K * EFSA ruled No current evidence for a deficiency in the population – no health claim approved Some nutrients and food constituents, in excess, may be harmful to bone health • Nutrients behave in a U-shape manner, giving rise to deficiencies when not present in sufficient amounts and to toxicities when present in excess. • This concept is illustrated in the following figure, where the risk of adverse effects is zero when intakes are below the Upper level (UL). 39 When ingested in excess, these otherwise beneficial components appear to affect bone metabolism Vitamin A# Sodium* Alcohol # UL =3000 mcg retinol Caffeine * UL = 2300 mg Na 40 Some populations are at risk of deficiencies in nutrients that may affect bone health • Strict vegans: in addition to calcium, vitamin D and protein – B12, zinc • People on restrictive diet: in addition to calcium, vitamin D and protein – B12, zinc (if restrict meat), vitamin C, carotenes, potassium if restrict fruit & vegetables. • Frail elderly people with low appetite: potentially low in all bone healthy nutrients • Those with an alcohol problem: potentially low in all bone healthy nutrients All of the food groups are needed to provide all of the bone healthy nutrients Nutrient Fruit & Vegetables Calcium √ Whole Grains Dairy √ Vitamin D √ Protein √ Vitamin K √ Magnesium √ √ Zinc √ Phosphorus √ Vitamin C √ Carotenes √ √ √ Manganese B12 Meat & Alternatives √ √ √ √ √ Dietary pattern research: consume a bone healthy diet • A study of dietary patterns in Canadian men and women over 50 y indicated that a nutrient dense diet was protective against incident low-trauma fractures in women: whole grains) * Langsetmo et al., Am J Clin Nutr2011;93:192–9 Following the Food Guide Ensures Bone Health Canada’s Food Guide ensures adequate calcium and protein, and most other nutrients + recommends a vitamin D supplement