Presentatie Sarcopenie en osteoporose

1. Sarcopenia &
osteoporosis
Andrea Maier
VUmc
Prof. dr. A.B. Maie

2. Bijlsma et al. J. Age Res Rev, 2012
Prof. dr. A.B. Maie

3. Bijlsma et al. J. Age Res Rev, 2012
Prof. dr. A.B. Maie

4. Falls
• 30% of the elderly 65+ years fall at least once a year
• Increased risk to fall again
• 1% of falls hip fracture
• 10% of falls  fracture
• Increased mortalityProf. dr. A.B. Maie

5. Risk factors for falls
Prof. dr. A.B. Maie

6. 640 muscles
contraction =
movement
glucose metabolisme
protein storage
Modifyable!
Vesalius
Muscle
Prof. dr. A.B. Maie

7. sarx flesh penia deminished
•
•
low skeletal muscle mass
Sarcopenia
Prof. dr. A.B. Maie

8. FP7, MYOAGE
Prof. dr. A.B. Maie

9. Morgan Int J Biochem Cell Bio, 2003
Prof. dr. A.B. Maie

10. 21 jr 63 jr
Prof. dr. A.B. Maie

11. = ==
Muscle mass Muscle strength Movement
Prof. dr. A.B. Maie

12. Muscle mass
45-90% lean mass
10-40% fat mass
Ling et al., J Nutr 2011; Ling et al., Age 2011Prof. dr. A.B. Maie

13. Muscle strength
Grip strength
Quadriceps strength
Prof. dr. A.B. Maie

14. Beenakker et al., Ageing Res Rev, 2010
meta-regression lines with 95% confidence
band (adjusted to 50% female)
General population
20 40 60 80 100
0
10
20
30
40
50
60
Age (years)
Gripstrength(kg)
Prof. dr. A.B. Maie

15. 30 50-70
Prof. dr. A.B. Maie

16. 89 years
HR 3.7, CI 2.5-5.7
HR 2.6, CI 1.6-4.4Ling et al. Ling et al., CMAJ 2009
Survival and muscle strength
Prof. dr. A.B. Maie

17. Physical
performance
Mobility
Physical performance
Prof. dr. A.B. Maie

18. Andreas Vesalius 1514-1564Prof. dr. A.B. Maie

19. Prof. dr. A.B. Maie

20. 15
17
19
21
23
25
27
Meanhandgripstrength[kg]
Lowest tertile Middle tertile Highest tertile
MMSE 85 years MMSE 89 years
both p for trend < 0.001
Taekema et al. 2011
Muscle strength and cognition
Prof. dr. A.B. Maie

21. 21Taekema et al. J. Hypertension, 2010
Muscle strength and blood pressure
Prof. dr. A.B. Maie

22. Muscle strenght
Muscle strength and bone mineral density
Bijlsma et al. Osteoporos Int, 2013
Prof. dr. A.B. Maie

23. SARCOPENIA
MUSCLE
MOBILITY
HEALTH
Interrelations
Ageing x Disease
Prof. dr. A.B. Maie

24. Sarcopenia Mobility
Cluster 1
Cluster n
Sarcopenia treatment
Prof. dr. A.B. Maie

25. - Sarcopenia predicts physical, psychological and social outcome, interrelated
with organ systems.
Prof. dr. A.B. Maie

26. Muscle strength and age
General population
20 40 60 80 100
0
10
20
30
40
50
60
Age (years)
Gripstrength(kg)
Beenakker et al., Age Res Rev 2010
?
Prof. dr. A.B. Maie

27. Code
Formula Cut-off point Cohort used as reference population Reference†
Sarcopenia present Men Women
A ALM/height2 > 2 SD below RP 7.26 kg/m2 5.45 kg/m2 Rosetta Study (1986-1992) non-Hispanic
white men and women aged 18-40 years
Baumgartner
1998
B ALM/height2 Under 20th percentile 7.25 kg/m2 5.67 kg/m2 Health ABC Study (1997/1998), 2976 men
and women 70-79 years old black and white,
Pittsburgh, Pennsylvania and Memphis,
Tenessee
Delmonico
2007
C ALM/height2 > 2 SD below RP 6.19 kg/m2 4.73 kg/m2 NHANES survey (1999 - 2004) white men
and women aged 20 years
Kelly 2009
D ALM with height
and fat mass
Under 20th percentile NA NA NA Delmonico
2007
E Skeletal lean
mass/body mass
* 100%
>2 SD below RP is class II
sarcopenia
1-2 SD below RP is class I
sarcopenia
31%
37%
22%
28%
NHANES III (1988-1994), 6414 men and
women aged 18-39 years non-Hispanic
white, non-Hispanic black and
Mexican-American
Janssen 2002
F Skeletal lean
mass/ height2
ROC analysis 8.50
10.75 kg/m2
5.75
6.75 kg/m2
NHANES III (1988-1994), 60 years plus,
non-Hispanic white, black and Mexican-
American
Janssen 2004
G Optimal cutpoint
for grip strength,
walking slower
than 0.8 m/s
Below optimal cutpoint 30.3 kg 19.3 kg InCHIANTI (1998-2000), 1030 subjects aged
20 - 102 years, ,
Lauretani
2003
Used definitions
Bijlsma et al. 2012, Age
Prof. dr. A.B. Maie

28. ‘Concordance’ sarcopenia
Bijlsma et al. 2012, Age
Prof. dr. A.B. Maie

29. Code
Formula Cut-off point Cohort used as reference population Reference†
Sarcopenia present Men Women
A ALM/height2 > 2 SD below RP 7.26 kg/m2 5.45 kg/m2 Rosetta Study (1986-1992) non-Hispanic
white men and women aged 18-40 years
Baumgartner
1998
B ALM/height2 Under 20th percentile 7.25 kg/m2 5.67 kg/m2 Health ABC Study (1997/1998), 2976 men
and women 70-79 years old black and white,
Pittsburgh, Pennsylvania and Memphis,
Tenessee
Delmonico
2007
C ALM/height2 > 2 SD below RP 6.19 kg/m2 4.73 kg/m2 NHANES survey (1999 - 2004) white men
and women aged 20 years
Kelly 2009
D ALM with height
and fat mass
Under 20th percentile NA NA NA Delmonico
2007
E Skeletal lean
mass/body mass
* 100%
>2 SD below RP is class II
sarcopenia
1-2 SD below RP is class I
sarcopenia
31%
37%
22%
28%
NHANES III (1988-1994), 6414 men and
women aged 18-39 years non-Hispanic
white, non-Hispanic black and
Mexican-American
Janssen 2002
F Skeletal lean
mass/ height2
ROC analysis 8.50
10.75 kg/m2
5.75
6.75 kg/m2
NHANES III (1988-1994), 60 years plus,
non-Hispanic white, black and Mexican-
American
Janssen 2004
G Optimal cutpoint
for grip strength,
walking slower
than 0.8 m/s
Below optimal cutpoint 30.3 kg 19.3 kg InCHIANTI (1998-2000), 1030 subjects aged
20 - 102 years, ,
Lauretani
2003
Used definitions-no concordance
Bijlsma et al. 2012, Age
Prof. dr. A.B. Maie

30. European consensus
Cruz-Jentoft et al., Age Ageing 2010
Prof. dr. A.B. Maie

31. “Sarcopenia with limited mobility” is defined as a person with
muscle loss whose walking speed is equal to or less than 1
m/s or who walks less than 400 m during a 6-minute walk, and
who has a lean appendicular mass corrected for height
squared of 2 standard deviations or more below the mean of
healthy persons between 20 and 30 years of age of the same
ethnic group.
Morley et al. JAMDA 2011
International consensus
Prof. dr. A.B. Maie

32. • Rockwood: 2 items of cognitive decline or disabilities
in activities of daily living or urinary incontinence
• Fried: 3 items of exhaustion, weight loss, slow gait
speed, low handgrip strength, low physical activity
• low handgrip strength (women <17.5 kg; men <30
kg)
• Gait speed less than 1.0 m/s
Frailty definitions
Prof. dr. A.B. Maie

33. ddddd
ddddd
ddd
JAGS 2006
‘Concordance’ frailty
Prof. dr. A.B. Maie

34. - Sarcopenia predicts physical, psychological and social outcome, interrelated
with other organ systems.
- Sarcopenia has become a syndrome / disease. No clear definition yet.
Prof. dr. A.B. Maie

35. • resistance, endurance,
balance training
• Prevent inactivity!
• Diet, amino acids, vitamins
• Prevent catabolic state!
• Phase II trails (Wnt
signalling, hormons etc)
Sarcopenia interventions
Prof. dr. A.B. Maie

36. 16 weeks
3 x /week
Sipila et al., 1994 Am Physiol Soc
Prof. dr. A.B. Maie

37. Leg press after intervention
Peterson, Age Res Rev 2010
Prof. dr. A.B. Maie

38. Osteoporos Int, 2013
Physical exercise 3/week, 65+ yrs
Prof. dr. A.B. Maie

39. Sarcopenia interventions
• resistance, endurance,
balance training
• Prevent inactivity!
• Diet, amino acids, vitamins
• Prevent catabolic state!
• Phase II trails (Wnt
signalling, hormons etc)
Prof. dr. A.B. Maie

40. Elderly general population:
Undernutrition: 10% (NL)
Prof. dr. A.B. Maie

41. Houston et al., 2008 Am J Clin Nutr
3years
low protein intake high
Prof. dr. A.B. Maie

42. 12 g amino acids / d
3 month
Cognamiglio et al., 2005 Gerontology
Prof. dr. A.B. Maie

43. N=154, 75y+
Exercise AND amino acid supplementation, exercise, amino acid
supplementation, health education
Prof. dr. A.B. Maie

44. Prof. dr. A.B. Maie

45. old onset
monkeys
young onset
monkeys
Caloric restriction - lifespan
30% decrease ad libitum feeding without malnutrition (mech via oxidative damage,
mitochondrial function)
Mattison et al., Nature 2012Prof. dr. A.B. Maie

46. Caloric restriction - healthspan
30% decrease ad libitum feeding without malnutrition (mech via oxidative damage,
mitochondrial function)
young onset
monkeys
CVD, DM,
cancer
Mattison et al., Nature 2012Prof. dr. A.B. Maie

47. Sarcopenia interventions
• resistance, endurance,
balance training
• Prevent inactivity!
• Diet, amino acids, vitamins
• Prevent catabolic state!
• Phase II/III trails (Wnt
signalling, hormons,
myostatin inhibition etc)
Prof. dr. A.B. Maie

48. Murphy et al., 2010 FASEB
- TGF-b superfamily
- inhibition of muscle growth
- associated with low BMD
Prof. dr. A.B. Maie

49. Prof. dr. A.B. Maie

50. Prof. dr. A.B. Maie

51. Elimination of
senescent cells
Aging stopped
Biological
young
Biological
old
Baker et al.,Nature, 2011
Target: senescent cells
Prof. dr. A.B. Maie

52. Regeneration capacity muscle / heart
pre + + + - - -
post + + + + - -
Influence of factor x en y in blood
Loffredo et al., Cell 2013, Conboy et al., Nature 2007Prof. dr. A.B. Maie

53. - Sarcopenia predicts physical, psychological and social outcome, interrelated
with other organ systems.
- Sarcopenia has become a disease. No clear definition yet.
-Prevent decline of muscle mass in early stages and increase muscle mass
by targeted intervention. Drug therapy will be available next years.Prof. dr. A.B. Maie

54. Prof. dr. A.B. Maie

55. Prof. dr. A.B. Maie