1. Bone Health EPI 254 May 25, 2011

2. Bone health: Something to worry about in old age?

3. Outline Functions of bone Bone composition & structure Measuring bone Bone density and osteoporosis Determinants of bone health –genes, hormones physical activity, diet Prevalence of osteoporosis Promoting bone health

4. Functions of Bone Provides structural support for the body Protects vital organs Attachment sites for muscles Acts as a mineral reservoir for calcium homeostasis in the body Provides an environment for marrow Trap for some dangerous minerals

5. Bone composition The matrix –40% organic Type 1 collagen (tensile strength) Proteoglycans (compressive strength) Osteocalcin/Osteonectin Growth factors/Cytokines/Osteoid –60% inorganic Calcium hydroxyapatite The cells –osteo-clast/blast/cyte/progenitor

6. Structure of collagen molecule from National Center for Biotechnology Information Bone composition & structure Organic Matrix (40%): collagen & other proteins Mineral (60%): Calcium hydroxyapatite Ca 10 (PO 4 ) 6 (OH) 2

7. Bone strength is determined by bone microarchitecture and bone mass but clinically indicated by bone mass

8. 70% of bone fragility is accounted for by bone mass

9. Measuring Bone Mass Different expressions of bone mass Most common expression is: B one M ineral D ensity (g/cm 2 ) as measured by dual-energy x-ray absorptiometry

10. DPX-NT, GE Medical Systems Spine Hip Whole body Dual-energy x-ray absorptiometry (DXA)

11. Limitation of BMD BMD = Bone Mineral Content (g)/Bone Area (cm 2 ) So BMD is an areal estimate of bone density Therefore, it gives biased comparisons when bone size is different

12. How are BMD values interpreted? WHO definitions BMD (young adult as reference) -2.5 osteopenia

13. An example of a DXA scan

14. Definition Osteoporosis is defined as a skeletal disorder characterized by compromised bone strength predisposing to an increased risk of fracture. NIH Consensus Development Conference. Osteoporosis Prevention, Diagnosis, and Therapy. March 27-29, 2000.

15. 33 yr old55 yr old 72 yr old Vertebra sample from women using Computed Microtomography (CMT) Salome, et al, Creatis, INSA, Lyons, France European Synchrotron Radiation Facility (ESRF) Bone micro-architecture

16. Determinants of bone density 1.Genes 2.Hormones 3. Diet 4. Physical Activity

17. Changes in bone mass with age Adolescence Premenopause Postmenopause Age (years) BMD, g/cm 2 Peak bone mass

18. Bone acquisition

19. Diet  BMD: calcium, phosphorus, vitamin D, vitamin C, vitamin K, phytoestrogens, protein  BMD: sodium, animal protein, phosphorus, caffeine, alcohol (?)

20. Calcium & Vitamin D play critical roles in osteoporosis prevention

21. Calcium requirements 19972010 0-6 months 210 mg 200 6-12 270 mg 260 1-3 yr 500 mg 700 4-9 yr 800 mg1000 9-13 1300 mg1300 14-181300 mg1300 19-301000 mg1000 31-501000 mg1000 51-701200 mg1200 > 701200 mg1200 Source: Food & Nutrition Board, IOM

22. Mean calcium intake CSFII, 1994-95 Age (years) mg

23. 9 out of 10 teenage girls do not get enough calcium 7 out of 10 teenage boys do not get enough calcium

24. How does calcium affect bone mass? 99% of total body calcium (1000-1200g) is found in bone –needed for bone formation, maintenance and repair Bone acts as a reserve for calcium –to maintain calcium homeostasis

25. What are the effects of other dietary components on calcium metabolism 1.Calcium excretion 2.Calcium absorption

26. Calcium Excretion Sodium Protein

27. Sodium increases urinary calcium loss Sodium and calcium share the same transport system in the proximal tubule 2300 mg Na excreted 20-60 mg Ca loss Massey L and Whiting S (1996). J Bone Miner Res 11:731

28. Protein increases urinary calcium loss? Acid generated by diet is excreted in the urine. Meat and fish have a high potential renal acid load. Because calcium acts as a buffer, a diet high in animal protein may lead to increased urinary loss of calcium. Every gram of protein metabolized in adults causes an additional 1 mg calcium to be lost in the urine.

29. Protein associated with decreased bone loss in older women? Framingham Study Higher protein intakes were associated with lower bone losses in over 600 men and women, aged 70-90 years. Hannan, et al (2000). J Bone Miner Res 5(12):2504-12.

30. Calcium absorption  Vitamin D (sunlight)  Fiber (wheat bran)  Oxylate (spinach, rhubarb, beans)  Phytate (beans)  Caffeine (by ~ 3 mg Ca per cup of coffee)   Phosphorus Heaney RP (1996). Nutrition and risk for osteoporosis. In: Marcus R, Feldman D & Kelsey JL (eds) Osteoporosis. Academic Press, New York, pp 483-510.

31. Are some sources of calcium better absorbed than others? Serving size (g) Calcium (mg) Est. Fr Absorp. (%) Absorb. calcium (mg) Needed to equal 1 cup milk Milk (1 c)24030032961.0 Beans288021175.7 Broccoli713553185.2 Pak-Choy857964422.3 Kale65459283.5 Spinach901225.16.215.5 Soy milk1205311.660.4 Tofu12625831801.2 Weaver, C. Purdue University

32. Phosphorus decreases calcium absorption? In animal studies, phosphorus shown to result in changes in calcium-regulating hormones (decreasing serum 1,25 (OH) 2 D 3 ) that may compromise bone health. Calvo, M.(1993). J. Nutr. 123:1627- 33. In 460 high school females, cola consumption associated with bone fractures. OR = 3.1 (1.5,6.8) Wyshak, G. (2000). Arch Pediatr Adol Med. 154:610-3.

33. Vitamin D Aids in absorption and utilization of Ca Sunlight converts precursors in skin Vitamin D status measured by serum 25-hydroxy vitamin D Vitamin D levels  with age

34. Are Americans deficient in Vitamin D? Recent IOM Report (2010): Majority of North Americans receive adequate Vitamin D. The majority receive significant levels from sun exposure. Some subgroups are at risk of receiving inadequate levels. E.g. The elderly living in institutions or people with darker pigmentation.

35. How do we determine dietary adequacy?

36. Dietary Reference Intakes 1. EAR (Estimated Average Requirement) 2. RDA (Recommended Dietary Allowance) 3. AI (Adequate Intake) 4. UL (Tolerable Upper Intake Level)

37. EAR RISK OF INADEQUACY ADVERSE EFFECTS RDA AI UL 1.0 0.5 0 Increasing intakes

38. Vitamin D: Dietary Reference Intakes Vitamin D intake may come from diet or sun exposure. RDA recently increased (previously, no RDA, just AI) People age 71 and above may require up to 800 IUs/day due to potential body changes while aging.

40. Vitamin D: Dietary Reference Intakes Vitamin D intake surpassing 4,000 IUs per day increases the risk for harm. Very high levels of Vitamin D (above 10,000 IUs per day) are known to cause tissue and kidney damage. Limited evidence on potential risks for low levels of Vitamin D intake, but preliminary studies suggests adverse health effects.

41. Modulation of cell growth Neuromuscular Immune Reduction of inflammation Other functions of Vitamin D

42. Serum 25-hydroxy vitamin D & Health From: http://ods.od.nih.gov/factsheets/VitaminD-HealthProfessional/

43. From Kaye, 2007. JADA 138:619

44. Other nutrients affect bone formation, maintenance, and repair Vitamin C needed for collagen synthesis Vitamin K needed for gamma-carboxylation of some of the proteins in bone matrix Magnesium Phytoestrogens Fluoride Boron Nutritional effects are small (hard to measure)

45. Prevalence of Osteopenia & Osteoporosis (Total Hip) for Men and Women Ages 50+ Osteopenia * Osteoporosis * 1988-19942005-20061988-19942005-2006 Women 40%36%16%7% Men 33%12%4%-- * Using sex-specific cutoffs Looker AC, et al (1997). J Bone Miner Res. 12:1761-1768. Looker AC, et al (2010). J Bone Miner Res. 25: 64-71

46. Prevalence of Osteopenia & Osteoporosis for Women Ages 50+ by race/ethnicity Looker AC, et al (1997). J Bone Miner Res. 12:1761-1768. Looker AC, et al (2010). J Bone Miner Res. 25: 64-71 WomenOsteopeniaOsteoporosis 1988-19942005-20061988-19942005-2006 NH Whites41%39%16%8 NH Blacks28%25%10%8 Mexican American 38%22%18%8 Total 39%37%16%8

47. Economic Burden of Osteoporosis 2005: $17 billion in health care expenditures due to osteoporotic fractures Projected to increase to $ 25 billion in 2025 Burge R, Dawson-Hughes B, Solomon DH, et al. (2007) Incidence and economic burden of osteoporosis-related fractures in the United States, 2005-2025. J Bone Miner Res 22:465.

48. Promoting bone health - lifestyle Adequate calcium intake (from food and then supplements) http://depts.washington.edu/bonebio/ASBMRed/exercise/calcium.html Adequate fruits and vegetables Weight-bearing exercise http://depts.washington.edu/bonebio/ASBMRed/exercise.html

49. Some Resources International Osteoporosis Foundation: www.iofbonehealth.orgwww.iofbonehealth.org National Osteoporosis Foundation: www.nof.orgwww.nof.org Osteoporosis Society of Canada: www.osteoporosis.cawww.osteoporosis.ca Powerful Bones. Powerful Girls: www.cdc.gov/powerfulboneswww.cdc.gov/powerfulbones The National Women's Health Information Center: www.4woman.govwww.4woman.gov National Dairy Council: http://www.nationaldairycouncil.org/Pages/Home.aspxhttp://www.nationaldairycouncil.org/Pages/Home.aspx Dairy Council of California: www.dairycouncilofca.orgwww.dairycouncilofca.org Foundation for Osteoporosis Research & Education: www.fore.orgwww.fore.org IOM Report on calcium and Vitamin D: http://www.iom.edu/~/media/Files/Report%20Files/2010/Dietary- Reference-Intakes-for-Calcium-and-Vitamin- D/Vitamin%20D%20and%20Calcium%202010%20Report%20Brief.pdfhttp://www.iom.edu/~/media/Files/Report%20Files/2010/Dietary- Reference-Intakes-for-Calcium-and-Vitamin- D/Vitamin%20D%20and%20Calcium%202010%20Report%20Brief.pdf