Approccio multidisciplinare alla gestione del paziente osteoporotico sarcopenico Milano, 12 maggio 2018 Sarcopenia: inquadramento, complicanze Dott. Matteo Longhi

1. Sarcopenia:
inquadramento, complicanze
Matteo Longhi
U.O. di Reumatologia
IRCCS Istituto Ortopedico Galeazzi - Milano
Approccio multidisciplinare alla gestione del
paziente osteoporotico sarcopenico
Milano 12 maggio 2018
Hotel Michelangelo
Responsabile scientifico: Prof.ssa Sabrina Corbetta

2. Frailty: definition
✓ Age-associated frailty in charactherized by a decreased reserve and resistance
to stressors in every organ system
✓ This depletion leads to:
➢ increased vulnerability to diseases with aging
➢ increased suscesptibility to disability with aging

3. Cycle of frailty
Operational definition
of frailty (Fried scale)
Any 3 of the following 5 components:
1. Unintentional weight loss (> 10 lb - 4,5 kg- in the last year)
2. Exhaustion
3. Weakness (grip strength in the lowest quintile for age and sex)
4. Slow gait (walking speed in the lowest quintile for age and sex)
5. Low physical activity ( < 383 Kcal/w for males, < 270 Kcal/w for females)
The presence of 2 of these components defines “pre-frail” subjects
Modified from Fried et al. J Gerontol A Biol Sci Med 2001

4. Sarcopenia
Rosemberg 1989: a condition involving a loss of muscle mass and strength
due to age “ There may be no single feature of age-related decline that could
so drammatically affect ambulation, mobility, indipendence and breathing .
Why have we not given it more attention? Perhaps it needs a name derived
from the Greek. I’’ll suggest sarcomalacia or sarcopenia”
σαρξ = flesh πενία = loss
Evans 1995: “ Age-associated decline in skeletal muscle mass”
Baumgartner et al 1998: standard definition of sarcopenia based on muscle
mass in the contest of New Mexico Aging Process Study by total body
DEXA
Rosemberg IH Am J Clin Nutr 1989
Evans WJ. J Gerontol A Biol Sci Med Sci. 1995
Baumgartner et al. Am J Epidemiol 1998

5. Sarcopenia:
prevalence based on DXA (%)
Age group
(yrs)
Males
(n= 205)
Females
(n= 173)
<70 13.5 23.1
70-74 19.8 33.3
75-80 26.7 35.9
> 80 52.6 43.2
Baumgartner et al. Am J Epidemiol 1998

6. European consensus on definition of sarcopenia
Cruz-Jentoft et al. Age Aging 2010
Sarcopenia is a syndrome characterised by progressive and generalised loss of
skeletal muscle mass and strength with a risk of adverse outcomes such as physical
disability, poor quality of life and death. The EWGSOP recommends using the
presence of both low muscle mass and low muscle function (strength or
performance) for the diagnosis of sarcopenia.
Diagnosis is based on documentation of criterion 1 plus (criterion 2 or criterion 3).
1. Low muscle mass
2. Low muscle strength
3. Low physical performance
The rationale for use of two criteria is: muscle strength does not depend solely on
muscle mass, and the relationship between strength and mass is not linear. Thus,
defining sarcopenia only in terms of muscle mass is too narrow and may be of
limited clinical value. Some have argued that the term dynapenia is better suited to
describe age-associated loss of muscle strength and function. However,
sarcopenia is already a widely recognised term, so replacing it might lead to further
confusion.

7. Adapted from Barry et al J Gerontol A Biol Sci Med Sci. 2004
Muscle mass, strength, power and age

8. Sarcopenia categories by cause
Cruz-Jentoft et al. Age Aging 2010
Primary sarcopenia
Age-related sarcopenia No other cause evident except ageing
Secondary sarcopenia
Activity-related sarcopenia Can result from bed rest,
sedentary lifestyle, deconditioning or zero-
gravity conditions
Disease-related sarcopenia Associated with advanced organ failure
(heart, lung, liver, kidney, brain),
inflammatory diseases, malignancy or
endocrine diseases
Nutrition-related sarcopenia Results from inadequate dietary intake of
energy and/or protein, as with
malabsorption, gastrointestinal disorders or
use of medications that cause anorexia

9. Proposed definitions of Sarcopenia
Dawson-Hughes et al. Osteoporos Int 2016

10. Sarcopenia definitions and assesments
Beaudart et al. Age Clin Exp Res 2018

11. Sarcopenia operational definition
EWGSOP Crutz-Jentoft 2010

12. Measuring muscle mass
Cooper et al. Calcif Tissue Int 2013

13. Body composition by DXA
Messina et al Quant Imag Med Surg 2018

14. Measuring muscle strength
Isokynetic dinamometry
Handgrip strength
(Jamar dynamometer,
Martin vigorimeter)

15. SPPB: Short Physical Performance Battery
• Time 4 meter walk
• Timed repeated chair rise (5 times)
• Standing balance
0-12 score.
Predictive of disability, istitutionalization and mortality (Guralnik et al NEJM 1995, J
Gerontol A BiolSci Med Sci 2000)
It is generally accepted that a total SPPB score < 10 indicates functional
impairment in older population and is strongly predictive of the loss of ability to walk
400 meters
(LIFE study Investigators J Gerontol A BiolSci Med Sci 2006;
Vasunilashorn et al. InCHIANTI study J Gerontol A BiolSci Med Sci 2009)

16. Handgrip strength, walking speed, chair rise
and mortality
Cooper et al. BMJ 2010

17. SARC-F screen for sarcopenia
McKee et al Endocr Pract 2017

18. Emerging biomarkers for cachexia and sarcopenia
Drescher et al J Cachexia Sarcopenia Muscle 2018
• Creatinine
• Neoepitope
• MMP-generated degradation fragment of collagen 6 (C6M)
• Type VI collagen N-terminal globular domain epitope (IC6)
• N-Terminal propeptide of type II procollagen (P3NP)
• C-terminal agrin fragment (CAF)
• Methyl-d3-Methylhistidine (D-3MH)
• Growth differentiating factor-15 (GDF-15)
• Follistatin (FST)
• Irisin
• Ghrelin
• Leptin
• Beta-Dystroglycan
• Dystrophin
• Tartrate-resistant acid phospatase 5a (TRACP5a)

19. Operational definitions for sarcopenia and
prevalence by gender
Dam et al. J Gerontol A Biol Sci Med Sci. 2014

20. Prevalence of sarcopenia in post-acute
impatient rehabilitation: metanalysis
Churilov et al Osteoporos Int 2018
Prevalence of sarcopenia
using muscle mass and function using only muscle mass

21. Sarcopenia, mortality and functional decline
Beaudart et al Plos One 2017

22. Sarcopenia and osteoporosis in women and men
with a hip fracture
Di Monaco et al Arch Gerontol Geriatr 2012
Sarcopenia was present in 340 of 531 women (64%) and 57 of 60
men (95%) and in 21,8% and 86,7% using two different criteria in
defining sarcopenia (Baumgartner 1998, Melton 2000)

23. Sarcopenia in women with vertebral fractures
A pilot study with the purpose to evaluate the prevalence of
sarcopenia in osteoporotic women with vertebral fractures. DXA
was used to measure the whole and regional body composition.
Appendicular lean mass (aLM) was calculated as the sum of lean
mass in arms and legs.
Skeletal muscle mass index (aLM/h2), bone mineral density and T
scores were calculated by DXA scan at total-body and at femoral
neck. Participants were divided according to the number of
vertebral fractures (single or multiple fractures).
A total of 67 women were included. Thirty-five women (52.23 %)
had a vertebral fracture, of them 8 (22.85 %) were sarcopenic and
32 women (47.76 %) had multiple vertebral fractures, of them 14
(43.75 %) were sarcopenic. Our results suggest that sarcopenia is
common among osteoporotic women increasing along with the
number of vertebral fragility fractures.
Iolascon et al Aging Clin Exp Res 2013

24. Sarcopenia and fractures
Zhang et al Osteoporos Int 2018

25. Pathogenenis of sarcopenia
Cruz-Jentoft et al. Age Aging 2010

26. Osteosarcopenia pathophysiology
Adapted from Kawao et al J Cell Biochem 2015

27. Structural and inflammatory changes in muscle
with obesity
Collins et al Frontiers Phisiology 2018

28. Proposed crosstalk between mythocondrial e muscle disfunction
Picca et al Mediators in Inflammation 2018

29. Cederholm et al Eur J Phys Rehabil Med 2013
Palafavacchia et al Nutr Met Cardiovasc Dis 2013
Alway et al. Front Aging Neurosci. 2014
Satellite cells
Satellite cells are miogenic stem cells thet play a maior role in muscle development, manteinence of
muscolar mass and repair damage.
Durig aging satellite cells display reduced proliferative response after damage and reduce
regenerative capacity. In aging muscle, satellite cells may also display a tendency to adopt
alternate lineage, showing fibrogenic potential (muscle fibrosis) and capacity to become adipocites
(miosteatosis). Myostatin inhibits the generation of satellite cells

30. Signalling proteolytic pathways
and crosstalk with protein synthess in skeletal muscle
Polge et al. Nutr Metab Cardiovasc Dis 2013

31. Inflammatory and
molecular mediators in
muscle wastings
Perez Baos et al. Front. Physiol 2018

33. Conclusions
• Osteoporosis and sarcopenia are strongly increasing in geriatric
population and there are growing evidences looking at
osteosarcopenia as a combined syndrome, substantially associated
with a high risk of morbidity and mortality and an elevated health care
cost.
• Although an emerging body of evidence, there is still need for more
high-quality trials from both basic science and clinical research.
• Standardazed clinical and strumental globally shared diagnostic
criteria are still lacking.
• Longitudinal studies will be pivotal to determine which came first, the
chicken or the egg, ie sarcopenia precede osteoporosis or vice versa?
• Future studies should aim to better characterize the communication
between muscle and bone from an autocrine and endocrine
perspective. Theshe new evidence would generate novel potential
therapeutic approaches simultaneosly targeting muscle and bone with
combinated anti-fall and anti-fracture efficacy.