1 Muscle matters! Andrea Maier, MD PhD Professor of Medicine – Gerontology VU University Medical Center, Amsterdam, NL 640 muscles contraction = movement glucose metabolisme protein storage Modifyable! Vesalius Muscle sarx flesh penia deminished • • low skeletal muscle mass Sarcopenia 21 jr 63 jr = = = Muscle mass Muscle strength Movement 45-90% lean mass 10-40% fat mass Ling et al., J Nutr 2011; Ling et al., Age 2011 Muscle mass
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1
Muscle matters!
Andrea Maier, MD PhD
Professor of Medicine – Gerontology
VU University Medical Center, Amsterdam, NL
640 muscles
contraction = movement
glucose metabolisme
protein storage
Modifyable!
Vesalius
Muscle
sarx flesh penia deminished
•
•
low skeletal muscle mass
Sarcopenia
21 jr 63 jr
= ==
Muscle mass Muscle strength Movement
45-90% lean mass
10-40% fat mass
Ling et al., J Nutr 2011; Ling et al., Age 2011
Muscle mass
2
Grip strength
Quadriceps strength
Muscle strength
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)
30 50-70
Life trajectories
89 years
HR 3.7, CI 2.5-5.7
HR 2.6, CI 1.6-4.4
Muscle strength and survival
Ling et al., CMAJ 2009
Physical performance
Mobility
Physical performance
Andreas Vesalius 1514-1564
3
15
17
19
21
23
25
27
Me
an
ha
nd
gri
p s
tre
ng
th [
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
SARCOPENIA
MUSCLE
MOBILITY
HEALTH
Ageing x Disease
Interrelations
Sarcopenia interrelates with
organ systems.
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
?
Muscle strength and age
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, Age; Reijnierse et al. under review
4
Bijlsma et al. 2012, Age; Reijnierse et al. under review
‘Concordance’ sarcopenia
Middle aged ElderlyCode
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; Reijnierse et al. under review
Cruz-Jentoft et al., Age Ageing 2010
European consensus
“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
Sarcopenia interrelates with
organ systems.
Urgent need for a consensus
definition of sarcopenia.
5
Harimoto., Brit J Surg 2013
196 pt hepatocellular carcinoma undergoing
hepatectomy, CT L3, 40% sarcopenic
Hepatocellular carcinoma - survival
Iritani, J Gastroenterol 2014
217 pt hepatocellular cancer, any treatment,
CT L3
Hepatocellular carcinoma - survival
Iritani, J Gastroenterol 2014
Hepatocellular carcinoma - survival
217 pt hepatocellular cancer, any treatment,
CT L3
Psutka, Cancer 2014
205 pt bladder cancer, radical cystectomy, CT L3,
69% sarcopenic
Bladder cancer - survival
122 pt endometrial cancer, L3 CT, 50% sarcopenic
Kuroki, Ann Surg Oncol 2014
Endomentrial cancer - survival
6
55 pt metastatic renal cell cancer, L3 CT
Antoun, Annals Oncol 2010
Renal cancer - dose limiting toxicity
Barret, Nutr Cancer 2014
51 pt mCRC, CT L3,
71% sarcopenic
Metastatic colorectal cancer - toxicity
Sarcopenia interrelates with
organ systems.
Urgent need for a consensus
definition of sarcopenia.
Sarcopenia associates strongly
with detrimental outcome in
cancer patients.
Targeted intervention!
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