Seminar 30-11-2013 Sarcopenie en osteoporose

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