Vitamin D plays an important role in muscle function and strength. Low vitamin D levels are associated with sarcopenia, or the loss of muscle mass and strength that occurs with aging. A study of over 800 men found that lower vitamin D levels were a significant determinant of lower relative appendicular skeletal muscle mass, even after adjusting for other factors. Another study of nearly 1,000 older adults found that lower vitamin D levels were associated with poorer performance on physical tests of mobility and strength. Maintaining adequate vitamin D levels may help reduce the risk of sarcopenia and falls in older adults.

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 Π0.2). Androstenedi- mone was not a significant deter
MINOS Cohort one and SHBG were not associated with RASM (P Π0.2). 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
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