Osteoporosis and Nutrition Module 4 Speaking of Bones Osteoporosis For Health Professionals. Susan J Whiting University of Saskatchewan

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2 Osteoporosis and Nutrition Module 4 Speaking of Bones Osteoporosis For Health Professionals Susan J Whiting University of Saskatchewan

3 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

4 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

$in bone fragility and susceptibility to fracture»$ $Consequences: fractures Wrist Spine Hip WHO 1994$

5 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

$Pathophysiology of fragility fracture risk in elderly Undernutrition + Low level of physical activity Bone formation Bone$

6 Pathophysiology of fragility fracture risk in elderly Undernutrition + Low level of physical activity Bone formation Bone resorption - Balance - Muscle mass - Neuro-muscular function Bone mass and strength Risk of falls Protective response Fracture risk

7 Importance of essential nutrients Calcium Vitamin D Protein

Circulating and measured form Status indicator 25α-hydroxylase

8 Vitamin D metabolism UVB light Diet Skin 7-dehydrocholesterol Vitamin D Inactive form Kidney 1,25(OH) 2 D Active form + 1-hydroxylase 25(OH)D Circulating and measured form Status indicator 25α-hydroxylase Stimulation of intestinal calcium absorption PTH Hypocalcemia Hypophosphatemia IGF-I

Status indicator 25α-hydroxylase Stimulation of intestinal calcium absorption 1,25

9 Vitamin D metabolism UVB light Diet Skin 7-dehydrocholesterol Vitamin D Inactive form Kidney 1,25(OH) 2 D Active form + 1-hydroxylase 25(OH)D Circulating form Status indicator 25α-hydroxylase Stimulation of intestinal calcium absorption 1,25 is made intracellularly Stimulation of cell growth and differentiation in other tissues

25α-hydroxylase Stimulation of intestinal calcium absorption Endocrine pathway Autocrine

10 Vitamin D metabolism UVB light Diet Skin 7-dehydrocholesterol Vitamin D Inactive form Kidney 1,25(OH) 2 D Active form + 1-hydroxylase 25(OH)D Circulating form Status indicator 25α-hydroxylase Stimulation of intestinal calcium absorption Endocrine pathway Autocrine pathway 1,25 is made intracellularly Stimulation of cell growth and differentiation in other tissues

11 Serul 25(OH)D (ng/ml) Serum 25(OH)D (ng/ml) Vitamin D deficiency in elderly Osteoporosis Canada 75 nmol/l IOM 50 nmol/l Double cause of deficiency with age: Reduced skin synthesis of vitamin D Insufficient sun exposure 0 Adults Independent elderly Elderly in institutions Hip fracture patients Adapted from Lips P et al., Endocr Rev 2001; 22:477

12 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

$given ( > 792 IU) to raise levels of 25(OH)D is there a significant effect on fracture risk.$

13 Recent Meta- Analysis 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.

Percentage of subjects Effect of vitamin D on the risk of falls Fall prevention by 1000 IU

citrate + calcium citrate (1g/d) 0 First fall in summer/autumn First fall in winter/spring In

14 Percentage of subjects Effect of vitamin D on the risk of falls Fall prevention by 1000 IU vitamin D 2 supplementation in women with a history of falling in the previous year p< % % 27.8 % 25.2 % Placebo + calcium citrate (1g/d) Ergocalciferol Vitamin D 2 ( calcium IU) citrate + calcium citrate (1g/d) 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

15 2010 Osteoporosis Canada Recommendations for Vitamin D Recommended intake for low-risk and younger adults are μg ( IU) daily Recommended intake for high-risk and older adults are μg ( IU) daily For individuals being treated for osteoporosis, vitamin D status should be assessed by serum measurement of 25- hydroxyvitamin D after 3 months of vitamin D supplementation To ensure levels are at or above 75 nmol/l

16 How to reach these recommendations? 3 sources of vitamin D Diet Sun exposure Supplementation Independent and cumulative effect

17 Foods with vitamin D salmon sardines in oil meat eggs liver Butter or margarine Unlike calcium, few foods contain vitamin D in significant amounts Difficult to reach daily recommended intake via diet alone

18 Decline in previtamin D3 synthesis in skin with age Godar et al., Dermato-Endocrinology 3:4, ; October/November/December 2011

19 Importance of essential nutrients Calcium Vitamin D Protein

20 Calcium during growth Genetics Gender Spontaneous calcium intake Menarcheal age Bone gain Physical activity Pubertal stage Skeletal sites Other nutrients Bonjour JP et al., Le Rhumatologue 2009; 70:19

21 Mean % change ( 1 SEM) Calcium attenuates bone loss in women 6 Lumbar BMD controls 1000 mg Ca supplements / day 2000 mg Ca supplements / day -6-9 Early peri Late peri Early post Late post menopause Methodology: 248 women y 25(OH)D levels similar ~ 18 ng/ml) Elders P et al., J Clin Endocrinol Metab 1991; 73:533

22 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

23 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 250 ml of milk 50 g of Saint Nectaire 5 baguettes 4 kg of beef 2 yogurts

24 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

25 Calcium and Heart Disease Risk What is the evidence? In the journal Heart 2012: data from ~24,000 men and women in Germany, 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: % CI ), which was more pronounced for calcium supplement only users (HR: 2.39; 95% CI ) Kuanrong Li et al. Heart 98:

26 Calcium Supplements and Heart Disease? What was reported:

27 Calcium Is a Threshold Nutrient: More than adequate is not better D Response (c) to increasing intake from C to D is almost immeasurable compared to (b)

28 Changes in in BMDs (% per per year) year) Supplementation is effective up to an intake threshold Example in prepubertal girls with high and low calcium intake Duration: 48 weeks 6 5 Spontaneous calcium Ca intake intake < Median: 855 mg/d > < > * 4 Placebo Ca supplement * p < Total Ca consumed (mg/d) SEM Bonjour JP et al., J Clin Invest ; 99:1287

29 Importance of essential nutrients Calcium Vitamin D Protein

$RR of hip fracture RR of hip fracture$ $Protein intake and hip fracture in$ protein intake 1.2 1.0 0.8 0.6 0.4 0.2 0.

30 RR of hip fracture RR of hip fracture Protein intake reduces fracture risk Protein intake and hip fracture in postmenopausal women Quartiles of total protein intake Q1 Q2 Q3 Q4 Low Low intake intake High High intake intake Quartiles of total protein intakes Munger et al., Am J Clin Nutr 1999; 69:147

31 ange Change in BMD in BMD of proximal of proximal femur femur (%) (%) Change in BMD of proximal femur (%) Protein attenuates proximal femur bone loss 0 Patients with recent hip fracture Methodology: Mean age: years Duration: 0 6 months Placebo and treatment: 550 mg Ca/d IU vit D (one time) p=0.029 p=0.029 Number of hospital stays reduced by 21 days p= Protein supplements (20 (20 g.d -1 ) Time (months) g.d-1) + calcium + calcium + vit D+ vit D Protein supplements (20 g.d g/d) -1 ) + calcium + vit D g.d-1) + calcium + calcium + vit D+ vit D Isocaloric Placebo (calcium placebo + vit (calcium D + vit D only) only) (calcium + vit D only) Placebo (calcium + vit D only) (calcium + vit D only) Schürch M et al., Ann Intern Med 1998; 128:801 Prote g.d-1) (20 g + cal Placeb only) (calc

$falling Increased risk of fracture$

32 Negative consequences of insufficient protein intake in the elderly Functional consequences of sarcopenia on bone Protein balance Decreased mobility Anabolism Catabolism Increased risk of falling Increased risk of fracture Adapted from Rosenberg IH, Am J Clin Nutr 1989; 50:1231

33 Change in bone biomarkers (%) Increased milk consumption improves bone biomarkers in women *** *** *** 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 mg (600 mg + ½ l of milk) Bonjour JP et al., Brit J Nutr 2008;1

34 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

35 Change of calcium balance (mmol/day) Change of calcium balance (mmol/d) No effect of diet acid-ash on calcium balance There is no relationship between a change in net acid 2 excretion and a net loss of whole body calcium Roughead 05 Roughead 03 Kerstetter 06 Dahl 95 Kerstetter 06 Kerstetter 06 Kerstetter Spence Change of net acid excretion (meq/d) Change of net acid excretion (meq/day) R² = p = 0.38 Promotion of an alkaline diet to prevent calcium loss is not justified Fenton TR and al., J Bone Miner Res 2009;24:

Vegetarian diets Vegetarian, vegan diets Lacto-vegetarian diets provide sufficient calcium and protein and bone health Vegan diets Vegans diets, lacking milk products or

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

36 Vegetarian diets Vegetarian, vegan diets Lacto-vegetarian diets provide sufficient calcium and protein and bone health 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

37 There are potential benefits of many nutrients and food constituents Magnesium Phosphorus Manganese Zinc Vitamin K Vitamin C Vitamin B12 Carotenes Phytoestrogens Polyphenols Fibre Potassium

38 5 nutrients have received a positive opinion from EFSA on having evidence for a causeeffect relationship related to bone Magnesium Phosphorus* Manganese* Zinc* Vitamin K * EFSA ruled No current evidence for a deficiency in the population no health claim approved

39 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

40 When ingested in excess, these otherwise beneficial components appear to affect bone metabolism Vitamin A# Sodium* Alcohol Caffeine # UL =3000 mcg retinol * UL = 2300 mg Na 40

Some populations are at risk of deficiencies in nutrients

calcium, vitamin D and protein B12, zinc People on

protein B12, zinc (if restrict meat), vitamin C, carotenes,

Frail elderly people with low appetite: potentially low in

41 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

42 All of the food groups are needed to provide all of the bone healthy nutrients Nutrient Fruit & Vegetables Calcium Vitamin D Whole Grains Dairy Meat & Alternatives Protein Vitamin K Magnesium Manganese Zinc Phosphorus Vitamin C Carotenes B12

$fractures in women: whole grains) * Langsetmo et al.$

43 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

44 Canada s Food Guide ensures adequate calcium and protein, and most other nutrients + recommends a vitamin D supplement Following the Food Guide Ensures Bone Health

Osteoporosis and Nutrition Module 4 Speaking of Bones Osteoporosis For Health Professionals. Susan J Whiting University of Saskatchewan

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: