Sarcopenia &
osteoporosis
Andrea Maier
VUmc
Prof. dr. A
.B. Maier
Bijlsma et al. J. Age Res Rev, 2012Prof. d
r. A.B. Maier
Bijlsma et al. J. Age Res Rev, 2012Prof. d
r. A.B. Maier
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. Maier
Risk factors for falls
Prof. dr. A
.B. Maier
640 muscles
contraction = movement
glucose metabolisme
protein storage
Modifyable!Vesalius
Muscle
Prof. dr. A
.B. Maier
sarx flesh penia deminished
•
•
low skeletal muscle mass
Sarcopenia
Prof. dr. A
.B. Maier
FP7, MYOAGEProf. d
r. A.B. Maier
Morgan Int J Biochem Cell Bio, 2003Prof. d
r. A.B. Maier
21 jr 63 jr
Prof. dr. A
.B. Maier
= ==
Muscle mass Muscle strength Movement
Prof. dr. A
.B. Maier
Muscle mass
45-90% lean mass
10-40% fat mass
Ling et al., J Nutr 2011; Ling et al., Age 2011Prof. dr. A
.B. Maier
Muscle strength
Grip strength
Quadriceps strengthProf. dr. A
.B. Maier
Beenakker et al., Ageing Res Rev, 2010meta-regression lines with 95% confidence
band (adjusted to 50% female)
General population
20 40 60 80 1000
10
20
30
40
50
60
Age (years)
Gri
p s
tren
gth
(k
g)
Prof. dr. A
.B. Maier
30 50-70
Prof. dr. A
.B. Maier
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. Maier
Physical
performanceMobility
Physical performance
Prof. dr. A
.B. Maier
Andreas Vesalius 1514-1564Prof. d
r. A.B. Maier
Prof. dr. A
.B. Maier
15
17
19
21
23
25
27
Mea
n ha
ndgr
ip s
tren
gth
[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. Maier
21Taekema et al. J. Hypertension, 2010
Muscle strength and blood pressure
Prof. dr. A
.B. Maier
Muscle strenght
Muscle strength and bone mineral density
Bijlsma et al. Osteoporos Int, 2013Prof. d
r. A.B. Maier
SARCOPENIA
MUSCLE
MOBILITY
HEALTH
Interrelations
Ageing x Disease
Prof. dr. A
.B. Maier
Sarcopenia Mobility
Cluster 1
Cluster n
Sarcopenia treatment
Prof. dr. A
.B. Maier
- Sarcopenia predicts physical, psychological and social outcome, interrelated
with organ systems.
Prof. dr. A
.B. Maier
Muscle strength and age
General population
20 40 60 80 1000
10
20
30
40
50
60
Age (years)
Gri
p s
tren
gth
(k
g)
Beenakker et al., Age Res Rev 2010
?
Prof. dr. A
.B. Maier
CodeFormula 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, AgeProf. d
r. A.B. Maier
‘Concordance’ sarcopenia
Bijlsma et al. 2012, AgeProf. d
r. A.B. Maier
CodeFormula 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, AgeProf. d
r. A.B. Maier
European consensus
Cruz-Jentoft et al., Age Ageing 2010Prof. d
r. A.B. Maier
“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. Maier
• 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. Maier
ddddd
ddddd
ddd
JAGS 2006
‘Concordance’ frailty
Prof. dr. A
.B. Maier
- 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. Maier
• 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. Maier
16 weeks 3 x /week
Sipila et al., 1994 Am Physiol SocProf. d
r. A.B. Maier
Leg press after intervention
Peterson, Age Res Rev 2010Prof. d
r. A.B. Maier
Osteoporos Int, 2013
Physical exercise 3/week, 65+ yrsProf. dr. A
.B. Maier
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. Maier
Elderly general population:
Undernutrition: 10% (NL)Prof. dr. A
.B. Maier
Houston et al., 2008 Am J Clin Nutr
3 y
ea
rs
low protein intake high
Prof. dr. A
.B. Maier
12 g amino acids / d3 month
Cognamiglio et al., 2005 GerontologyProf. d
r. A.B. Maier
N=154, 75y+
Exercise AND amino acid supplementation, exercise, amino acid
supplementation, health education
Prof. dr. A
.B. Maier
Prof. dr. A
.B. Maier
old onset
monkeys
young onset
monkeys
Caloric restriction - lifespan30% decrease ad libitum feeding without malnutrition (mech via oxidative damage, mitochondrial function)
Mattison et al., Nature 2012Prof. dr. A
.B. Maier
Caloric restriction - healthspan30% 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. Maier
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. Maier
Murphy et al., 2010 FASEB
- TGF-b superfamily
- inhibition of muscle growth
- associated with low BMD
Prof. dr. A
.B. Maier
Prof. dr. A
.B. Maier
Prof. dr. A
.B. Maier
Elimination of
senescent cells
Aging stopped
Biological young
Biological old
Baker et al.,Nature, 2011
Target: senescent cells
Prof. dr. A
.B. Maier
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. Maier
- 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. Maier
Prof. dr. A
.B. Maier
Prof. dr. A
.B. Maier