Definition and Diagnosis of Sarcopenia for Asian the Basic Science

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1 Definition and Diagnosis of Sarcopenia for Asian the Basic Science Simon Chow Educational Workshop on Sarcopenia and its Related Orthopaedic Problems February 13th, Prince of Wales Hospital.

2 Sarcopenia Greek (σάρξ sarx), "flesh" and πενία penia, "poverty" Age associated loss of skeletal muscle mass and strength. Appendicular lean/fat mass 2 SD less than that of mean of young adults Decrease in gait speed Type II muscle fibers show faster decline ( disuse: mostly decrease number of type I fibers) Leads to deterioration in physical function, strength or overall health Force Mass

3 Sarcopenia Type I fibers, Slow, % increase with age Type II fibers, Fast, % decrease with age [Lee, et al., Clin Orthop Relat Res, 2006.]

4 Legend: Type IIA Type IIB Type I Changes in Muscle Fibres [Lee, et al., Clin Orthop Relat Res, 2006.] 27 versus 77 TYPE I TYPE IIA/B CONNECTIVE n=65

5 Primary sarcopenia (1 ) Age related Secondary sarcopenia (2 ) Activity related Disease related Nutrition related Types and Causes [Cruz-Jentoft AJ et al. Age Ageing. 2010] Age related Pathophyiological changes [Tarantino U et al, J Bone Joint Surg Am 2015.]

Sex hormones Alteration in cellular turnover Muscle Denervation,

6 Age related Etiology of Sarcopenia Hormone Synthesis Anabolic hormones: GH, IGF 1 Oxidative stress & Mitrochondrial dysfunction IL 1, IL 6, TNF Sex hormones Alteration in cellular turnover Muscle Denervation, Apoptosis & Satellite cells Nutrition and Metabolism Protein intake Inflammation

Oxidative stress & Mitrochondrial dysfunction Muscle Denervation,

intake and metabolism Inflammation [2] IL 1, IL 6, TNF [1] 1.

7 Age related Etiology of Sarcopenia Hormone Synthesis Anabolic hormones: GH, IGF 1 Sex hormones Alteration in cellular turnover Oxidative stress & Mitrochondrial dysfunction Muscle Denervation, Apoptosis & Satellite cells Nutrition and Metabolism Protein intake and metabolism Inflammation [2] IL 1, IL 6, TNF [1] 1. Hepple, R.T., Front Aging Neurosci, Sousa-Victor, P., et al., Nature, 2014.

Increasing Oxidative stress & Mitrochondrial dysfunction Age related changes in mitochondria Reduced capacity to generate cellular energy in form of ATP Progressive decline in muscle aerobic function

8 Increasing Oxidative stress & Mitrochondrial dysfunction Age related changes in mitochondria Reduced capacity to generate cellular energy in form of ATP Progressive decline in muscle aerobic function Increased susceptibility to apoptosis Increased Reactive Oxygen Species (ROS) production Greater oxidative damage Greater vulnerability to apoptosis Induce protein degradation by proteasome activity Decreased mitochondrial turnover Normally high turnover rate in 2 7 days ROS may impair enzyme function, thus requiring continual renewal of mitochondrial proteins

9 Muscle Denervation & Decrease in Satellite Cells Age related changes Neuromuscular Junctions (NMJ) innervation < denervation age related denervation occurs before myofiber atrophy [1]. Age related changes in Satellite Cells Reduced population [2]. [2. Siu et al. Am J Physiol Cell Physiol. 2005] [image from Pre-synaptic branches and post-synaptic acetylcholine receptor of the same NMJ. [1. Deschenes MR et al. Exp Gerontol May]

Age related Etiology of Sarcopenia Hormone Synthesis Anabolic hormones: GH, IGF 1 Sex hormones Alteration in cellular turnover Oxidative stress & Mitrochondrial

10 Age related Etiology of Sarcopenia Hormone Synthesis Anabolic hormones: GH, IGF 1 Sex hormones Alteration in cellular turnover Oxidative stress & Mitrochondrial dysfunction Muscle Denervation, Apoptosis & Satellite cells Nutrition and Metabolism Protein intake and metabolism Inflammation IL 1, IL 6, TNF [Bauer, J Am Med Dir Assoc, 2013.]

11 Age related Etiology of Sarcopenia Hormone Synthesis Anabolic hormones: GH, IGF 1 Sex hormones Alteration in cellular turnover Oxidative stress & Mitrochondrial dysfunction Muscle Denervation, Apoptosis & Satellite cells Nutrition and Metabolism Protein intake and metabolism Inflammation IL 1, IL 6, TNF

12 Age related Etiology of Sarcopenia [Tarantino U et al, J Bone Joint Surg Am 2015.]

13 Diagnosis of Sarcopenia Strength Functional Muscle Mass [Cruz-Jentoft AJ et al. Age Ageing. 2010]

14 Strength Functional Muscle Mass Diagnosis of Sarcopenia [Chen, L.K., et al., J Am Med Dir Assoc, 2014]

15 Diagnosis of Sarcopenia European/Asian Consensus on definition and diagnosis [Cruz-Jentoft AJ et al. Age Ageing, Chen LK et al, J Am Med Dir Assoc, 2014] Criterion European Asian 1 MuscleMass 2 Muscle Strength 3 Physical Performance DXA Men: 7.26 kg/m 2 Women: 5.5 kg/m 2 Handgrip Men: < 30 kg Women: < 20 kg Gait speed < 0.8 m/s DXA Men: 7.0 kg/m 2 Women: 5.4 kg/m 2 Handgrip Men: < 26 kg Women: < 18 kg Gait speed < 0.8 m/s European Working Group on Sarcopenia in Older People (EWGSOP) Asian Working Group for Sarcopenia (AWGS)

Methods to Assess Muscle Mass Golden Standard Widely Used Measures

tomography (CT) Creatinine excretion Dual energy X-ray

Anthropometry Peripheral quantitative computerized tomography (pqct)

16 Methods to Assess Muscle Mass Golden Standard Widely Used Measures Other Measures Method Magnetic resonance imaging (MRI) Computerized tomography (CT) Creatinine excretion Dual energy X-ray absorptiometry (DXA) Bioelectrical impedance analysis (BIA) Anthropometry Peripheral quantitative computerized tomography (pqct) Ultrasound Neutron activation [Pahor et al. J Nutr Health Aging Oct; 13(8): ]

$mechanical force to stimulate growth of bone Osteoporosis and sarcopenia together increases risk of fracture!! 1. Crepaldi G and Maggi S. J Endocrinol Invest. 2005] 2. Novotny et al.$

17 Sarcopenia in Orthopaedics Sarcopenia and Osteoporosis: A Harzardous Duet [1] The Muscle-bone unit [2] Biochemical cross-talk between muscle and bone Mechanostat Theory Muscle exerts the required mechanical force to stimulate growth of bone Osteoporosis and sarcopenia together increases risk of fracture!! 1. Crepaldi G and Maggi S. J Endocrinol Invest. 2005] 2. Novotny et al. Physiology, 2015]

18 Screening of Sarcopenia in Community Elderly n = 119 (23%) n = 525, mean age=75.46 [Range:58 to 96] n = 406 (77%) n = 89 (participants) n = 24 (27%) n = 65 (73%)

19 Screening of Sarcopenia in Community Elderly Preliminary results suggests that subjects with osteoporosis have 33% higher chance (OR: 1.33) of suffering sarcopenia. Osteoporosis + osteopenic subjects have 176% higher chance (OR: 2.76) have suffering sarcopenia DXA Sarcopenia Normal Osteoporosis 23 (26%) 7 (8%) 30 Osteopenia 35 (39%) 11 (12%) 46 Normal 7 (8%) 6 (7%) (73%) 24 (27%) 89

$Sarcopenia and Muscle Typing in Fractured Patients Lower extremities fractured patients are recruited for sarcopenia assessments 71% 29% Normal Sarcopenia 57% (n = 44, mean$

20 Sarcopenia and Muscle Typing in Fractured Patients Lower extremities fractured patients are recruited for sarcopenia assessments 71% 29% Normal Sarcopenia 57% (n = 44, mean age=63 [63 to 101] 9% 34% Normal Osteopenia Osteoporosis Representative muscle histology of osteoporosis & sarcopenia patient at age 89, dominated by 54.8% of type-i myofibres.

21 Take home message Sarcopenia is age related decline in muscle mass and strength. Diagnosis can be performed by 1) 6-m walk, 2) hand-grip, and 3) DXA/BIA. The age-related causes of sarcopenia include altered hormonal balance, decreased muscle fibre regeneration, changes in nutrition, chronic pro-inflammatory factors A strong association exists between sarcopenia and fragility fracture.

22 Thank you for your attention!

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