Vitamin D and Bone Health

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  • Vitamin D and Bone Health

    1. 1. Changing Horizon of Vitamin D Requirements and Replacements
    2. 2. Ca absorption Vitamin D Insufficiency Muscle mass PTH Muscle strength Falls Bone TO and loss Fractures
    3. 3. Skeletal Muscle Microanatomy
    4. 4. Muscle Fiber Characteristics Fiber Type Contraction time Duration of use Force production I slow hrs low IIa moderate < 30 min medium IIx fast < 5 min high
    5. 5. Muscle Tissue Changes with Aging and Vitamin D Deficiency <ul><li>Sarcopenia of Aging </li></ul><ul><li>- ↓ lean mass by ~ 2 kg/decade </li></ul><ul><li>- ↓ muscle VDR number </li></ul><ul><li>- ↓ fiber number </li></ul><ul><li>- fiber size and proportion(I/II) are stable </li></ul><ul><li>Severe vitamin D deficiency </li></ul><ul><li>- ↓ Type II fiber proportion (area) </li></ul>Vandervoort 2002; Frontera 2008
    6. 6. Effect of Treatment with Vitamin D on Muscle Fibers <ul><li>In 9 elderly women, treatment with 1-α-hydroxyvitamin D (1-2 μg daily) for 3 months increased the cross-sectional area and relative number (proportion) of type IIa muscle fibers (Sorensen 1979). </li></ul><ul><li>In RCT of stroke survivors, treatment with ergocalciferol (1000 IU/day) for 2 years increased the diameter and relative number (proportion) of type II muscle fibers (Sato 2005). </li></ul>
    7. 7. HANES III – Serum 25(OH)D and Walk Time Bischoff-Ferrari HA. Am J Clin Nutr 2004:80:752-8.
    8. 8. HANES III – Serum 25(OH)D and Time to Stand Bischoff-Ferrari HA. Am J Clin Nutr 2004;80:752-8.
    9. 9. Meta-Analysis of Vitamin D and Falls Bischoff-Ferrari HA. JAMA 2004; 291: 1999-2006.
    10. 10. RCT:Vitamin D 2 (1,200 IU/d) and Risk of Falling (625 assisted living residents, mean age 83.4, 2-yr follow-up) Flicker L et al. JAGS 2005. 53:1881-1888. Outcome (N) All subjects Compliant (>50%) N 625 540 First fall (355) 0.82 [0.59-1.12] 0.70 [0.50-0.99] All falls (1555) 0.73 [0.57-0.95] 0.63 [0.48-0.82]
    11. 11. Effect of Vitamin D 3 on Falls ( 124 nursing home residents, mean age 89 years, 5 mo follow-up) 44 58 60 60 20 Broe KE. JAGS 2007;55:234-9. Proportion of fallers
    12. 12. Calcium/Vitamin D and Falls 3-yr RCT in 389 men and women age 65+ (Bischoff-Ferrari, Dawson-Hughes. Arch Int Med 2006;166:424-30) Men Women Fallers, % 45 55 Mean 25(OH)D, ng/ml 33.2 ±14.2 26.6 ±12.7 OR on Ca/D (vs placebo) [CI] NS 0.54 [0.30, 0.97] OR on Ca/D (vs placebo) [CI] in inactive subjects NS 0.35 [0.15, 0.81]
    13. 13. RCTs: Vitamin D, muscle performance and falls Trial Dose Duration 25(OH)D Outcome PERF Sato 1000 D 2 3 yr 84 + Bischoff 800 D 2 3 mo 66 + Pfeiffer 800 D 3 2 mo 66 + FALLS Bischoff 700 D 3 3 yr 99 + Broe 800 D 2 5 mo 75 + Grant 800 D 3 5 yr 62 null Prince 1000 D 1 yr 59 + Flicker 800 D 2 2 yr N/A +
    14. 14. Serum 25(OH)D and Calcium Absorption in Postmenopausal Women Devine A. AJCN:2002;283-288
    15. 15. Associations of 25OHD with 1,25(OH) 2 D and Calcium Absorption (319 patients , mean 68 yrs, with 25OHD < 40 nmol/L) Need AG. JBMR 2008;23:1859-63 .
    16. 16. Thomas MK. N Eng J Med 1998; 338: 777-83. Vitamin D and PTH Levels in Hospitalized Patients
    17. 17. Calcium and Vitamin D Intakes and Serum PTH Icelandic population, males (58 ± 14 yrs) and females (54 ± 16 yrs) Steingrimsdottir, JAMA 2005; 294:2336-2341
    18. 18. Effect of Season on Vitamin D and PTH Levels Krall EA. N Eng J Med 1989; 321: 1777-83.
    19. 19. BMD Response to Vitamin D by Season and Overall Dawson-Hughes B. Ann Int Med 1991;115:505-12 . -2.0 -1.5 -1.0 -0.5 0.0 0.5 1.0 1.5 2.0 Summer/Fall Winter/Spring Net Placebo Vitamin D Spine
    20. 20. Vitamin D and Hip Fracture Vitamin D 700-800 IU/d Chapuy et al, 2002 Chapuy et al, 1994 Trivedi et al, 2003 Pooled Bischoff-Ferrari HA. JAMA 2005;293:2257-2264 Favors Vitamin D Favors Control Vitamin D 400 IU/d Meyer et al, 2002 Lips et al, 1996 Pooled
    21. 21. Vitamin D and Nonvertebral Fracture Favors Vitamin D Favors Control Vitamin D 700-800 IU/d Pfeifer et al, 2000 Chapuy et al, 2002 Chapuy et al, 1994 Dawson-Hughes et al, 1997 Trivedi et al, 2003 Pooled Vitamin D 400 IU/d Meyer et al, 2002 Lips et al, 1996 Pooled Bischoff-Ferrari HA. JAMA 2005;293:2257-2264 Relative Risk (95% CI)
    22. 22. Hip and Nonvertebral Fracture Efficacy by 25(OH)D level Bischoff-Ferrari HA. JAMA 2005;293:2257-2264
    23. 23. The RECORD GROUP Trial The RECORD Trial Group. Lancet 2005; on-line April 28
    24. 24. WHI – 400 IU Vitamin D 3 + 1000 mg Ca vs Placebo on Fractures (36,282 women, 62.4 yrs, 7 yr trial) <ul><li>Site Fractures HR </li></ul><ul><li>(N) </li></ul><ul><li>Hip 374 0.88 (0.72 – 1.08) </li></ul><ul><li>Clinical 378 0.90 (0.74 – 1.10) </li></ul><ul><li>Vertebral </li></ul><ul><li>Forearm 1122 1.01 (0.90 – 1.14) </li></ul><ul><li>All 4260 0.96 (0.91 – 1.02) </li></ul>Jackson RD. NEJM 2006;354:669-683.
    25. 25. Fracture Efficacy by achieved 25(OH)D levels Hip fracture Bischoff-Ferrari HA et al. JAMA 2005 Any non-vertebral fracture Meta-regression: p = 0.02 Meta-regression: p = 0.03 RECORD WHI WHI RECORD
    26. 26. Serum 25(OH)D, PTH and Fracture Responses to Supplemental Vitamin D 3 or D 2 Study Dose (IU) 25(OH)D (nmol/L) ∆ PTH (%) Effect on non-vert fx Dawson-Hughes 700 112 -28 + Chapuy 800 100 47 + Chapuy 800 100 -33 + Trivedi 820 74 + Law 933 74 -14 NS Grant 800 63 -13 NS Meyer 400 64 -6 NS Jackson 400 59 NS Lips 400 54 NS Larsen (open) 400 47 +
    27. 27. Calcium and Vitamin D Intakes and Risk of Type 2 Diabetes Mellitus in Nurses Health Study Pittas A, Diabetes Care 2006; 29(3): 650-656.
    28. 28. Serum 25(OH)D and Diabetes in NHANES III (OR of fasting glu >7.0 mmol/l in high vs low quintile of 25(OH)D) <ul><li>Group (diabetes- Yes, No) </li></ul><ul><li>Caucasian (26, 1086) </li></ul><ul><li>Hispanic (6, 302) </li></ul><ul><li>Blacks (7, 124) </li></ul><ul><li>OR [CI] </li></ul><ul><li>0.25 0.11-0.60 </li></ul><ul><li>0.17 0.08-0.37 </li></ul><ul><li>3.40 1.07-10.86 </li></ul>25(OH)D Quintile 1 < 43.9 nmol/l; Quintile 5 > 81 nmol/l Scragg R. Diabetes Care 2004;27:2813-8.
    29. 29. Serum 25(OH)D and Colon Cancer Risk in Women Feskanich D. 2004 Cancer Epid Biom Prev;13:1502-8.
    30. 30. Solar Radiation and Cancer Mortality in Japan (correlation coefficients) Adjusted for income (all), fat intake (colon, ovary), or salt (stomach) *P < 0.05. Mizoue T. Health Phys 2004;87:532-8. Cancer site Men Women Esophagus -0.45* -0.41* Stomach -0.44* -0.35* Colon -0.41* -0.33 Prostate or ovary -0.07 -0.04
    31. 31. Serum 25(OH)D and Risk of Multiple Health Outcomes Bischoff-Ferrari HA et al. Am J Clin Nutr 2006; 84:18-28.
    32. 32. Quartile of 25OHD and Cardiovascular and All- Cause Mortality (in 3258 patients scheduled for coronary angiography; 25OHD quartile means:19, 33, 47, and 71 nmol/L, Diasorin) Dobnig H. Arch Intern Med 2008;168:1340-9
    33. 33. Both 25OHD and 1,25(OH) 2 D Contribute to Mortality Risk Dobnig H. Arch Intern Med 2008;168:1340-9.
    34. 34. What is the vitamin D status in the US? NHANES III and Now
    35. 35. NHANES 25OHD sample <ul><li>NHANES III age 12+ 18,158 </li></ul><ul><li>(1988-1994) </li></ul><ul><li>NHANES Now age 1+ 20,289 </li></ul><ul><li>(2000-2004) </li></ul><ul><li>NHANES Now ongoing </li></ul>Yetley EA. Am J Clin Nutr 2008;88(suppl):558S-64S.
    36. 36. Data collection and season <ul><li>75% of data collected at latitude <35 was collected in winter (Nov – Mar) </li></ul><ul><li>86% of data collected at latitude > 35 was collected in summer (Apr – Oct) </li></ul>Yetley EA. Am J Clin Nutr 2008;88(suppl):558S-64S.
    37. 37. NH White NH Black Mex Am Age (y) Mean serum 25OHD* in males NHANES 2000-2004 **Data for age 1-5 available from NHANES 2003-04 only nmol/L *Adjusted for season Yetley EA. Am J Clin Nutr 2008;88(suppl):558S-64S. 0
    38. 38. NH White NH Black Mex Am Age (y) Mean serum 25OHD* in females NHANES 2000-2004 nmol/L **Data for age 1-5 available from NHANES 2003-04 only *Adjusted for season Yetley EA. Am J Clin Nutr 2008;88(suppl):558S-64S. 0
    39. 39. Men with serum 25(OH)D < selected cut-points NHANES 2000-2004 Yetley EA. Am J Clin Nutr 2008;88(suppl):558S-64S.
    40. 40. Women with 25(OH)D levels < selected cut-points NHANES 2000-2004 Yetley EA. Am J Clin Nutr 2008;88(suppl):558S-64S.
    41. 41. Age-adjusted mean 25(OH)D in whites NHANES 1988-1994 vs 2000-2004 Yetley EA. Am J Clin Nutr 2008;88(suppl):558S-64S.
    42. 42. Global Prevalence of 25(OH)D Levels < 75 nmol/L Study Design: Observational, cross-sectional study of 1285 community-dwelling women with osteoporosis from 18 countries to evaluate serum 25(OH)D distribution. Adapted from Lim S-K et al. Poster presented at ISCD, February 16–19, New Orleans, LA; Heaney RP Osteoporos Int 2000;11:553–555. Prevalence (%) 0 10 30 40 60 80 90 Latin America 51% 63% Asia All 59% Australia 59% Europe 52% Regions N=1285 81% Middle East 50 70 20 In a cross-sectional observational international study in 1285 postmenopausal women with osteoporosis
    43. 43. Effective Sun Exposure Minutes needed to face, hands and arms (or arms and legs) between 11am and 3pm 3pm Holick, The UV Advantage , 2003. Boston (42 ºN ) Miami (26 ºN) Nov-Feb Jun-Aug Nov-Feb Jun-Aug Skin Type: Lightest -- 8 2-8 10-15 -15 1-5 1-5 Darkest -- 25-35 -35 40-60 20-30 -30
    44. 44. Serum 25(OH)D Responses to 1000 (A) and 4000 (B) IU/d of Vitamin D 3 Vieth R. Am J Clin Nutr 2001; 73: 288-94. A B
    45. 45. Mean Increment in 25(OH)D for a Given Increase in Intake of Vitamin D Intake 25(OH)D Increment 1 microgram/d 1 nmol/L 100 IU/d 1 ng/ml
    46. 46. Effects of Vitamin D 2 and D 3 on 25(OH)D Levels (4000 IU/d for 2 weeks; N=17 (D 2 ) and 55 (D 3 ); mean age 38 yrs) Trang HM. Am J Clin Nutr 1998; 68: 854-8. Serum 25(OH)D, nmol/L Vit D 2 Vit D 3 Controls Baseline 44 41 40 Final 57 65 43 Change 14 24* 3 *Greater change than for D 2 , P=003
    47. 47. Vitamin D 2 and D 3 Effects on 25OHD Levels (68 young adults, 1000 IU/d X 11 wks in winter) Holick MF 2008 JCEM 93:677-681.
    48. 48. Ish-Shalom, S. et al. J Clin Endocrinol Metab 2008;93:3430-3435 Effects of the same cumulative dose of vitamin D 3 , equivalent to 1500 IU/d, but given once daily, once weekly, or once monthly, on serum 25(OH)D
    49. 49. Conclusions <ul><li>The mean level of 25(OH)D needed for optimal muscle performance is unclear but appears to be no lower than 60 nmol/L. </li></ul><ul><li>If older persons maintain a 25(OH)D level at 75 nmol/l or higher, they will be at reduced risk of fracture and likely reduce risk of other chronic diseases. </li></ul><ul><li>An intake of 800 IU to 1000 IU/d of vitamin D 3 will bring a group mean 25(OH)D level to about 75 nmol/L. . </li></ul>

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