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Sarcopenia and Vitamin D

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Presented at the 2010 Philippine Society for the Study of the Aging Male annual convention.

Presented at the 2010 Philippine Society for the Study of the Aging Male annual convention.

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  • 1. Nanghihina Dahil Di Naarawan? Sarcopenia and Vitamin D Iris Thiele Isip Tan MD, FPCP, FPSEM Clinical Associate Professor, University of the Philippines College of Medicine Section of Endocrinology, Diabetes & Metabolism Department of Medicine, Philippine General Hospital
  • 2. Disclosure Merck Sharp & Dohme (MSD) Honoraria as RTD speaker Hotel accommodation to attend convention Travel grant for regional endocrine meeting
  • 3. Sarcopenia Greek, ‘lack of flesh’ Loss of muscle mass and strength with aging
  • 4. Sarcopenia Disease or normal aging? A Life Course Model of Sarcopenia Sayer et al J Nutr Health Aging 2008;12(7):427-432
  • 5. Sarcopenia What It is Not Sarcopenia: loss of skeletal muscle and strength with aging Wasting: loss of weight driven by inadequate nutrition Cachexia: loss of fat-free mass from hypermetabolism and hypercatabolism Acute disuse atrophy: muscle mass is reduced but fiber number and specific force maintained with shift toward fast fiber types Bross et al JCEM 1999;84(10):3420-30
  • 6. Sarcopenia No consensus on threshold of muscle loss to be used in definition Absolute appendicular skeletal mass >2 SDs below mean of young adults Skeletal muscle index (SMI) 1-2 SDs (Class 1) or >2 SDs (Class 2) of young adults SMI = muscle mass/body mass X 100 Baumgartner at al Am J Epidemiol 1998;147:755-63 Melton at al J Am Geriatr Soc 2000;48:625-30 Janssen at al J Am Geriatr Soc 2002;50:889-96
  • 7. Two-compartment Model of Body Composition Body weight = fat mass + fat-free mass Aging-associated Changes in Body Composition ↑ adiposity (more central distribution) ↓ fat-free mass (loss of muscle mass) 35-40% cumulative decline between 20-80 yr of age No weight loss: muscle depletion with fat accumulation Bross et al JCEM 1999;84(10):3420-30
  • 8. Sarcopenia Changes in Muscle Anatomy Preferential atrophy of fast-twitch type II fibers (reduced reinnervation capacity vs type I fibers) Reduced contractile tissue volume for locomotion and metabolism Increase in intramuscular fat and connective tissue Friction brake to slow contractile velocity STEVE G SCHEISSNER/SPL Scanning electron micrograph of skeletal muscle fibres Bross et al JCEM 1999;84(10):3420-30
  • 9. Sarcopenia Changes in Muscle Function Preferential loss of type II fibers → less strength and power-generating capacity Walking, stair climbing, rising from a chair and load carrying deteriorate Increased risk of falls Decreased oxidative capacity of skeletal muscle → decline in maximal aerobic capacity Bross et al JCEM 1999;84(10):3420-30
  • 10. Is there a link How much vitamin Does supplemental between vitamin D D is enough? vitamin D reduce and sarcopenia? falls?
  • 11. Is there a link between vitamin D and sarcopenia?
  • 12. Role of Vit D in Muscle Function VDR in skeletal muscles cells that specifically bind 1,25(OH)D3 Regulation of calcium transport Uptake of inorganic phosphate for production of energy-rich phosphate compounds Protein synthesis Vit D deficiency → secondary hyperparathyroidism Affect predominantly the weight-bearing anti-gravity lower limb muscles Janssen et al Am J Clin Nutr 2002:75:611-5 Houston et al J Gerontol A Biol Sci Med Sci 2007;62(4):440-46
  • 13. Determinants of Appendicular Skeletal Muscle Mass in Men The MINOS Study P: 845 men age 45-85 y in France I: Lifestyle factors, relative appendicular skeletal muscle mass (RASM), 25(OH)D O: Multivariate analysis to identify determinants of RASM M: Cross-sectional data from prospective population-based study Szulc et al. Am J Clin Nutr 2004;80:496-503
  • 14. in the men who had AFTC or FTI values Œ3 SDs below the which corresponded to 2 SDs belo respective means. Neither total testosterone nor total 17 - in those who had a concentration estradiol were determinants of RASM (P Œ 0.2). Androstenedi- mone was not a significant deter MINOS Cohort one and SHBG were not associated with RASM (P Œ 0.2). of men (P 0.66). After adjustment for confounding variables, 25(OH)D was a 25(OH)D: Significant Determinant of RASM significant determinant of RASM (partial F 2.84, P  0.04) (Figure 4). RASM values were significantly lower in the men Characteristics of men with sa Sarcopenia was defined as the studied cohort (6.32 kg/m2.3). p<0.04 the 3 upper quartiles of RASM, significantly older (Table 2). Th significantly lower body weight mass and fat mass. In contrast, th * * fat mass did not differ significan Relative men with sarcopenia were signifi with normal RASM values to be c appendicular compared with 66%; P 0.03). skeletal had significantly lower levels o activity. After adjustment for co muscle mass with sarcopenia had significantl index (RASM) the men with normal RASM val of total testosterone, 17 -estradi and parathyroid hormone did not 2 groups. DISCUSSION Our results show that, in elde tobacco smoking, thinness, low tion of testosterone, and posssibl trations are risk factors for sarco FIGURE 4. Adjusted mean ( SEM) values for relative appendicular eral methods have been sugges 25(OH)D skeletal muscle mass index (RASM) according to 25-hydroxycholecalciferol results are correlated; however, concentration expressed in SDs from the mean value in youngSzulc et al. Am J Clin Nutr 2004;80:496-503 healthy men. n 845, P  0.04. Bars with different letters are significantly different, P  26 –28). Each method has spec 0.05 (ANCOVA and Tukey’s test). n values in parentheses. assumption of constant density o
  • 15. Association between Vit D status and Physical Performance The InCHIANTI Study P: 976 persons age >65 y at baseline I: Short physical performance battery (SPPB) and handgrip strength O: Multiple linear regression to examine association between serum 25(OH)D, PTH and physical performance (adjusted for sociodemographic variables, behavioral characteristics, BMI, season, cognition, health conditions, creatinine, Hb and albumin) M: Cross-sectional data from prospective population- based study Houston et al J Gerontol A Biol Sci Med Sci 2007;62(4):440-46
  • 16. Short Physical Performance Battery (SPPB) Used in the Established Populations for the Epidemiology Studies of the Elderly (EPESE) 5 Highest performance level 0 Unable to do test Walking Ability to stand Standing speed from a chair balance test Three measures added from 0 (worst) to 12 (best) Houston et al J Gerontol A Biol Sci Med Sci 2007;62(4):440-46
  • 17. Selected Participant Characteristics The InCHIANTI Study 100 Men Women 75 % 50 46 49 38 25 29 25 14 0 <25 25 to <50 >=50 Serum 25(OH)D (mmol/L) Serum 25(OH)D Men p <25 25 to <50 >50 Age 79.8 (0.8) 74.5 (0.5) 72.2 (0.4) <0.0001 Season (Nov-Feb, %) 69.4 54.5 33.9 <0.0001 PTH, ng/L 40.5 (3.2) 27.7 (1.8) 20.6 (1.6) <0.0001 Houston et al J Gerontol A Biol Sci Med Sci 2007;62(4):440-46
  • 18. Vit D Status and Adjusted Physical Performance Measures The InCHIANTI Study Serum 25(OH)D Physical (nmol/L) p value for p value for p Performance Measure 25 to <25 vs >25 <50 vs >50 for trend <25 >50 <50 Men 10.15 10.73 10.94 SPPB score* 0.03 0.10 0.04 (0.29) (0.15) (0.14) 36.28 36.37 38.80 Handgrip strength* 0.42 0.009 0.01 (1.40) (0.71) (0.62) Women 9.29 9.85 9.59 SPPB score* 0.03 0.74 0.58 (0.19) (0.14) (0.20) 20.58 21.52 22.83 Handgrip strength* 0.06 0.02 0.009 (0.60) (0.41) (0.57) * Adjusted for sociodemographic variables, smoking status, physical activity, BMI, total energy intake, season, cognition, CHF, COPD, CVD and levels of creatinine, Hb and albumin Houston et al J Gerontol A Biol Sci Med Sci 2007;62(4):440-46
  • 19. PTH Status and Adjusted Physical Performance Measures The InCHIANTI Study PTH Status p value for p value 1st Physical (ng/L) 1st tertile vs and 2nd p Performance Measure 1st 2nd 3rd 2nd & 3rd tertiles vs for trend tertile tertile tertile tertiles 3rd tertile Men 10.79 10.76 10.75 SPPB score* 0.86 0.89 0.86 (0.16) (0.16) (0.19) 38.31 38.73 34.75 Handgrip strength* 0.28 0.003 0.002 (0.68) (0.71) (0.90) Women 9.58 9.73 9.60 SPPB score* 0.69 0.82 0.44 (0.18) (0.18) (0.16) 22.29 21.69 21.00 Handgrip strength* 0.14 0.12 0.08 (0.51) (0.52) (0.51) * Adjusted for sociodemographic variables, smoking status, physical activity, BMI, total energy intake, season, cognition, CHF, COPD, CVD and levels of creatinine, Hb and albumin Houston et al J Gerontol A Biol Sci Med Sci 2007;62(4):440-46
  • 20. Association between Vit D status and Physical Performance The InCHIANTI Study Low vitamin D status was associated with poor physical performance among elderly men and women (cross-sectional data) Houston et al J Gerontol A Biol Sci Med Sci 2007;62(4):440-46
  • 21. Low Vit D/High PTH and Sarcopenia The Longitudinal Aging Study Amsterdam P: 1509 persons age >65 y in LASA cohort I: Grip strength (n=1008) and appendicular skeletal muscle mass (n=331, DXA) O: Multiple linear regression to examine association between serum 25(OH)D, PTH and grip strength and appendicular skeletal muscle mass M: Baseline and 3-y data from prospective population- based study Visser et al JCEM 2003;88:5766-72
  • 22. % (sd 23.9%). ers. Higher 25-OHD concentration was protective of sar- defined as a copenia. Per unit increase in ln(25-OHD), the risk of sar- experiencedVit Low copenia was 0.55 (95%Sarcopeniabased on grip strength D/High PTH and CI 0.36 – 0.83) The Longitudinal Aging Study Amsterdam ge in ASMM and 0.59 (95% CI 0.29 –1.20) based on ASMM after adjustment %). A decline ondents, and f sarcopenia efinition of a (5), was ob- re vitamin D r 1.3% of the ol/liter) was participants ble 1. Partici- hed less, had roke and ar- d were more ifferences in n those with 5-OHD cate- FIG. 1. Prevalence of grip strength loss (defined as loss 40%, study wer 25-OHD sample n 1,008) and appendicular muscle mass loss (defined as loss grip strength 3%, study sample n 331) during 3-yr follow-up according to cat- ASMM (P egories of baseline serum 25-OHD concentration. P value of 2 test. Visser et al JCEM 2003;88:5766-72
  • 23. still had an increased risk of sarcopenia. High PTH status was ASMM loss [ 0.5 also associated with loss of grip strength. After adjustment additionally adjus Low Vit D/High PTH confounders, participants in the highest ter- for all potential and Sarcopenia gistic regression m attenuated. For ex The Longitudinal Aging Study Amsterdam tile of PTH (4.0 pmol/liter) were 1.71 times more likely to less than 25 nmol/ (95%CI 0.76 – 6.66 also did not chan with loss of grip We also invest bined categories high PTH concen OHD concentratio 1.12–5.62) times strength and 2.38 experience loss of PTH and a high 2 The results of concentration and risk of sarcopenia dicular muscle m present after care FIG. 2. Prevalence of grip strength loss (defined as loss 40%, study sample n 1,008) and appendicular muscle mass loss (defined as loss style factors, inclu 3%, study sample n 331) during 3-yr follow-up according to tertiles more striking wh of baseline serum PTH concentration. P value of 2 test. ulation-based coh Visser et al JCEM 2003;88:5766-72 TABLE 2. Adjusted odds ratios (95% confidence interval) for loss of grip strength and loss
  • 24. Low Vit D/High PTH and Sarcopenia The Longitudinal Aging Study Amsterdam Lower 25OHD and higher PTH levels increase the risk of sarcopenia in older men and women. Visser et al JCEM 2003;88:5766-72
  • 25. How much vitamin D is enough?
  • 26. Vitamin D and Bone Metabolism Balanced System Low Levels of Vitamin D Calcium absorption meets metabolic demands Calcium reservoir of bone is depleted to Normal bone mineralization is maintained correct for low calcium absorption in gut Dietary calcium 4 Mobilization of calcium GUT from bone 1 VITAMIN D CIRCULATION VITAMIN D PTH 3 In vitamin D- 2 Calcium PTH deficient state, PARATHYROID reabsorption calcium absorption RENAL DISTAL decreases Low calcium causes TUBULE increase in PTH secretion Adapted from Holick M. Curr Opin Endocrinol Diabetes. 2002;9:87–98; DeLuca HF. Am J Clin Nutr. 2004;80(suppl 1):1689S–1696S; Lips P. Endocr Rev. 2001;22:477–501; Holick MF. J Nutr. 2005;135:2739S–2748S.
  • 27. Threshold Effect Calcium Absorption Vitamin D metabolic utilization 4,000 IU/day 32 ng/dL Heaney R. Clin J Am Soc Nephrol 2008;3:1535-41
  • 28. Chief Dietary Sources of Vit D Vitamin D-fortified milk (400 IU/quart) Cereals (40-50 IU/serving) Egg yolks Saltwater fish Liver Clinician’s Guide to the Prevention & Treatment of Osteoporosis National Osteoporosis Foundation, 2008
  • 29. Vitamin D: Recommended daily intake Recommended Vitamin D Calcium daily intake Under age 50 400-800 IU at least 1,000 mg Over age 50 800-1,000 IU at least 1,200 mg The Hormone Foundation 2009
  • 30. Rule of Thumb Patient with a starting serum 25(OH)D of 15 ng/mL would require 1,500 IU/d to + 100 IU oral bring his level to 30 ng/mL vitamin D intake = + 1 ng/mL (2.5 nmol/L) serum 25(OH)D Heaney R. Clin J Am Soc Nephrol 2008;3:1535-41
  • 31. Individualize requirements for vit D supplementation Brown S, Alternative Medicine Review 2008 Base Sunlight vitam line Intestinal exposure in D absorption Skin level rates pigmentation Age Gene tic (reduc ed photo- Type of vit D varia f tion i co nversion o vitam n rocholeste rol supplement in D 7-dehyd recep to vit D) (D3 is 3x tor more potent activ than D2) ity
  • 32. Vitamin D Supplementation Toxicity Trial characteristics 22 vitamin D trials with AE outcomes Most frequently reported 19 trials: adults only Hypercalcemia Many too short to observe AEs Hypercalciuria 400-4,000 IU/d vit D3 (n=19) More events in vit D 5,000-10,000 IU/d vit D2 (n=2) group but difference with placebo group NS Asymptomatic Cranney et al, Am J Clin Nutri 2008;88(suppl):513S-9S
  • 33. Vitamin D Supplementation Toxicity Trial characteristics 7 trials reported kidney stone incidence Women’s Health Initiative 5 trials had no cases n = 36,282 1 trial reported NS difference 400 IU vitamin D3 + 1 reported increase in stones 1000 mg Ca vs Ca alone (WHI) 5.7 events/10,000 women-years exposure Cranney et al, Am J Clin Nutri 2008;88(suppl):513S-9S
  • 34. Institute of Medicine Tolerable Upper No-observed-adverse- Intake Level (TUIL) effect-level (NOAEL) 2,000 IU/day 10,000 IU/day Serum 25(OH)D 32 ng/mL = minimum daily intake of 2,600 IU vitamin D (US residents) Heaney R. J Musculoskelet Neuronal Interact 2006:6(4):334-
  • 35. Limited by age higher latitudes working indoors use of sunscreen skin pigmentation 80-90% of vitamin D is cultural practices cutaneously produced precluding skin exposure from sunlight
  • 36. Bathing suit exposure during summer until skin just begins to turn pink skin production of 10,000 - 50,000 IU of vitamin D3 Adams et al. NEJM 1982;306:772-775
  • 37. Effect on serum 25(OH)D Nursing home residents with 4 RCTs using artificial low baseline 25(OH)D UVB light source Suberythemal UV light 4 RCTs using solar exposure = 25(OH)D 28-42 exposure nmol/L after 3 mos. Cranney et al, Am J Clin Nutri 2008;88(suppl):513S-9S
  • 38. “Fair evidence to suggest that artificial and solar exposure increases 25(OH)D levels in vitamin D- deficient and replete persons, including the elderly.” Brannon et al, Am J Nutr 2008;88:483S-90S
  • 39. Sun Exposure Toxicity “Is a specific level of sunlight exposure sufficient to maintain adequate vitamin D levels without increasing the risk of non-melanoma skin cancer or melanoma?” No studies! Cranney et al, Am J Clin Nutri 2008;88(suppl):513S-9S
  • 40. Does supplemental vitamin D reduce falls?
  • 41. “Muscle Bone Unit” No fall, no fracture! Parallel to ↓ bone strength, a loss of muscle and performance (sarcopenia), neuromuscular deficiencies, deterioration in gait and postural stability occur. ALENDRONATE/ CHOLECALCIFEROL FOSAVANCE™ Schact et al, J Musculoskelet Neuronal Interact 2005;5(3):273-284
  • 42. Is Vitamin D insufficiency common? Rationale for Vitamin D Prescribing in a Falls Clinic P: 400 consecutive patients in a falls clinic >65 y and have fallen at least once in preceding 8 weeks I: Serum 25(OH)D O: Multivariate analysis to determine independent variables for vitamin D status M: Prospective observational descriptive study Dhesi et al Age and Ageing 2002;31:257-71
  • 43. Is Vitamin D insufficiency common? Rationale for Vitamin D Prescribing in a Falls Clinic 50.0 40.7 72.5% had 37.5 hypovitaminosis D 31.8 (25OHD <20 ug/L) Percentage 26.2 25.0 12.5 1.3 0 <12.0 21.1-20.0 20.1-40.0 >40.1 25OHD ug/L Dhesi et al Age and Ageing 2002;31:257-71
  • 44. Meta-analysis Vitamin D and the Risk of Falls Objective Data Source Study Selection MEDLINE, To test the efficacy r D2 or oral EMBASE, BIOSIS Vit D3 o of supplemental and Cochrane active vit D vit D + Ca in database up to Aug Age >65 preventing falls 2008 Minimum ff-up 3 mos among older 8 RCTs (n=2426) individuals Falls as primary or seconda ry endpoint Bischoff-Ferrari et al, BMJ 2009;339:b3692
  • 45. o analysis was performed with STATA version 8.0 (Stata- Meta-analysis Corp, College Station, TX, USA). Vitamin D and the Risk of Falls High dose vitamin D Relative risk (95% CI) 700-1000 IU/day Prince et alw3 w1 Vit D2 Broe et al Flicker et alw4 w2 Bischoff-Ferrari et al Pfeifer et alw5 Vit D3 Bischoff et alw6 w7 Pfeifer et al d Pooled relative d. risk (95% CI) Combined 0.81 (0.71 to 0.92) Bischoff-Ferrari et al, BMJ 2009;339:b3692 Low dose vitamin D
  • 46. Pfeifer et alw7 ed Pooled relative d. Meta-analysis risk (95% CI) Vitamin D and the Risk of Falls Combined 0.81 (0.71 to 0.92) Low dose vitamin D 200-600 IU/day Broe et alw1 (200 IU D2/day) n, Broe et alw1 Vit D2 (400 IU D2/day) Broe et alw1 (600 IU D2/day) Graafmans et alw8 Vit D3 ce; Pooled relative risk (95% CI) ble Combined 1.10 (0.89 to 1.35) be 0.1 0.5 0 5 10 ials Favours Favours ded supplemental control vitamin D Bischoff-Ferrari et al, BMJ 2009;339:b3692 Fig 2 |Fall prevention with high dose (700-1000 IU a day) and
  • 47. at a 25 abstracts of the American Society for Bone and Meta-regression for fall w12 Mineral Research (table 4). Three of these trials Vit D dose and risk of >1 fall med by als did d a sig- Fall prevention by dose of vitamin D 2.5 Relative risk (95% CI) serum one fall 2.0 nmol/l 1.5 h doses 1.0 a high 0.5 U), the w1 w1 w8 w1 w2 w1 w5,w6,w7 w3,w4 0 als that 2 2 2 2 3 2 3 2 D D D3 D D D D D 0 0 0 0 0 0 00 ls that 20 40 0 60 70 80 80 40 10 mbined Dose of vitamin D2 or vitamin D3 (IU) th pla- tion of level Fall prevention by 25-hydroxyvitamin D3Bischoff-Ferrari et al, BMJ 2009;339:b3692 2.5 I)
  • 48. ), the w1 w1 w8 w1 w2 w1 w5,w6,w7 w3,w4 0 s thatMeta-regression 2 2 2 2 3 2 3 2 D D D3 D D D D D Serum 25OHD and risk of >1 fall 0 0 0 0 0 0 00 that 20 40 0 60 70 80 80 40 10 bined Dose of vitamin D2 or vitamin D3 (IU) h pla- on of Fall prevention by 25-hydroxyvitamin D3 level 2.5 Relative risk (95% CI) min D 25OHD >60 nmol/L cium pooled RR 0.77, 95% CI 0.65-0.90) 2.0 udies. udies 1.5 thus, addi- 1.0 amin 0.5 which pared 0 w1(400) w1(200,600) w1(800),w3 w6,w7 w5 w2 men 44 48 60 66 85 95 ment 25-hydroxyvitamin D3 serum concentration (nmol/l) D sig- Fig 3 |Fall prevention by dose and achieved 25(OH)D et al, BMJ 2009;339:b3692 Bischoff-Ferrari ment
  • 49. Some observations Vitamin D and Risk of Falls Presence of nursing staff Trials assessing More accurate impact of vit D on ascertainment of falls falling more likely Higher supplement compliance to have positive results when conducted in institutions Dawson-Hughes, Am J Clin Nutr 2008;88(suppl):573S-40S
  • 50. Risk of Falls in Elderly High-risk Women Effect of Ergocalciferol added to Calcium P: 302 community-dwelling ambulatory older women aged 70-90 y living in Perth, Australia Serum 25(OH)D <24.0 ng/mL History of falling in the previous year I: Ergocalciferol (Vit D2) 1000 IU/d + Calcium Citrate 1000 mg/d vs Calcium Citrate 1000 mg/d + placebo O: Risk of having at least one fall over 1 year M: Population-based, double-blind RCT Prince et al Arch Intern Med 2008;168(1):103-108
  • 51. Faller : OR, 0.66 (95% CI, 0.41-1.06)∗ Faller baseline height adjusted: OR, 0.61 (95% CI, 0.37-0.99)∗ Winter/spring: OR, 0.55 (95% CI, 0.32-0.96)† Summer/autumn: OR, 0.81 (95% CI, 0.46-1.42)† 1 Fall: n = 83 (47%) OR, 0.50 (95% CI, 0.28-0.88)† 2 or more falls: n = 92 (53%) OR, 0.86 (95% CI, 0.50-1.49)† 0.00 0.25 0.50 0.75 1.00 1.25 1.50 53% (n=80) of Vit D group vs 62.9% Odds Ratio (n=95) of control group had falls Figure 2. Effects of treatment on falls. “Faller” refers to participant who had at least 1 fall during the study period; CI indicates confidence interval; OR, odds ratio; asterisk, logistic regression analysis; dagger, multinomial logistic regression analysis; error bars, 95% CIs. Prince et al Arch Intern Med 2008;168(1):103-108
  • 52. P <.05 Ergocalciferol + calcium citrate 40 Placebo + calcium citrate 35.8% 30 27.8% 27.2% Percentage of Subjects 25.2% 20 10 0 First Fall in First Fall in Summer/Autumn Winter/Spring Prince at al Arch Intern Med 2008;168(1):103-108 Figure 3. Percentages of subjects who had at least 1 fall, by season of first fall. Percentages of fallers were compared using 2 testing.
  • 53. Baseline P <.001 P <.001 Summer/autumn Winter/spring 80 Serum 25OHD Concentration, nmol/L 70 60 50 40 30 20 10 0 Ergocalciferol + Placebo + Calcium Citrate Calcium Citrate Figure 4. Effect of season and treatment on the 25-hydroxyvitamin D (25OHD) status during the study. Error bars represent standard deviations. Means were compared using 1-factor repeated-measures analysis of variance. To convert serum 25OHD to nanograms per milliliter, divide by 2.496. Prince et al Arch Intern Med 2008;168(1):103-108
  • 54. Risk of Falls in Ambulatory Older Men and Women Effect of Cholecalciferol and Calcium P: 199 men and 246 women >65 y and living at home I: 700 IU of cholecalciferol + 500 mg calcium citrate malate or placebo O: Risk of falling at least once during follow-up (3 y) M: Double-blind placebo-controlled randomized trial Bischoff-Ferrari et al Arch Intern Med 2006;166:424-30
  • 55. Sex difference in response to Vit D3-calcium? ↓Risk of falling in women but not in men A Women B Men 80 80 70 OR 0.54 (95% CI 0.30,0.97) 70 OR 0.93 (95% CI 0.50,1.72) Cumulative % of Subjects Who Fell Cumulative % of Subjects Who Fell 60 60 50 50 40 40 30 30 20 20 10 Cholecalciferol-Calcium (n = 77) 10 Cholecalciferol-Calcium (n = 71) Placebo (n = 93) Placebo (n = 77) 0 0 0 6 12 18 24 30 36 0 6 12 18 24 30 36 Time, mo Time, mo Figure 1. Cumulative percentage of falls by treatment group and sex. A, The women who received cholecalciferol (vitamin D) plus calcium citrate malate had lower rates of falls starting after 12 months and then throughout the follow-up compared with women in the placebo group. B, In men, both groups had similar rates of falls throughout the study. Baseline 25OHD level did not modulate the treatment effect. A B 80 Bischoff-Ferrari et al Arch Intern Med 2006;166:424-30 80 70 70 Fell Fell
  • 56. Some observations Vitamin D and Risk of Falls Trials indicate mean values Research has not of 75 nmol/L and 99 nmol/L identified the ? higher values might confer minimum 25(OH)D benefit level for maximal benefit in fall prevention Dawson-Hughes, Am J Clin Nutr 2008;88(suppl):573S-40S
  • 57. Randomized controlled trials Vitamin D and the Risk of Falls Vit D dose/ 25(OH)D level Duration Trial preparation achieved Outcome of trial ug (IU)/d nmol/L Muscle performance Sato 25(1000) D2 3y 84 + Pfeiffer 20 (800) D3 2 mo 66 + Bischoff 20 (800) D3 3 mo 66 + Falls Bischoff 17.5 (700) D3 3y 99 + Broe 20 (800) D2 5 mo 75 + Flicker 20 (800) D2 2y NA + Grant 20 (800) D3 5y 62 Null Dawson-Hughes, Am J Clin Nutr 2008;88(suppl):573S-40S
  • 58. Potential candidates as functional indicators Setting the EAR* for Vitamin D Indicator Indicator of Suboptimal Status Calciotropic function Parathyroid hormone Stimulated level of PTH Percentage absorption of Ca improves Calcium absorption when Vit D provided Increase in fracture risk relative to Fracture risk adequate Vit D status Muscle strength Muscle strength tests Serum calcium and Relative hypocalcemia and phosphorus hypophosphatemia Increased bone resorption and decreased Bone turnover markers bone formation * Estimated Average Requirement Whiting & Calvo, J Nutr 2005;135:304-9
  • 59. What cut-off value defines low vit D status? Serum 25(OH)D <25 nmol/L 25-75 nmol/L >75 nmol/L Deficiency Insufficiency Sufficiency Optimal level of Variability of vit D concentration 25(OH)D 30 ng/mL by geographical location determined in a Differences in assay methodology Caucasian population Dawson-Hughes B, Am J Clin Nutr 2008:88(suppl);537S-40S
  • 60. Goal of vit D supplementation? Serum 25(OH)D greater than an accepted cutpoint (e.g. 30 ng/ml) Upper limit of normal (a value that varies between laboratories) Binkley et al, JCEM 2008; 92;2130-5
  • 61. Is there a link How much vitamin Does supplemental between vitamin D D is enough? vitamin D reduce and sarcopenia? falls?
  • 62. Thank You http://www.endocrine-witch.info