Clinical Management of

Sarcopenia: from Medical to

Orthopedic Problems

Dr David Dai

Geriatrician

14/4/2016

www.no-fa

ll.hk

Frailty and Fragility

Sarco-osteopenia

Nutrition, Vitamins and Exercise

Pharmacological treatment

Frailty, Falls and Fracture

Ageing Bone

www.no-fa

ll.hk

Osteoporosis P5www.no-fa

ll.hk

www.no-fa

ll.hk

Figure 1. Incidence of vertebral fractures in women and men, (Reprinted withPermission from [5]

The American Journal of Medicine Vol 98 (suppl 2A):76S-87S J of Gerontology Medical Sciences Vol 11(4):M107-M111www.no-fa

ll.hk

NIH Consensus Development on Osteoporosis 2001

• Bone quality( micro-architectural deterioration)

• Systemic skeletal disease• Insufficient bone strength: bone

density• ↑Fracture risk

質與量www.no-fa

ll.hk

The importance of bone microarchitecture.

Brandi M L Rheumatology 2009;48:iv3-iv8Bone 39 (2006) 1173-1181www.no

-fall.h

k

Frailty (Fried 2001)

•Sarcopenia • Neuroendocrine dysfunction • Immune dysfunction • Weight loss• Low grip strength • Low energy (exhaustion) • Slow gait speed • Low physical activity

失肌症www.no-fa

ll.hk

Muscle Quality:Type IIB fibers positively correlate with BMD

( CMJ 2010; 123(21): 3009-3014)

23 yr old 83 yr old

IIA

IIB

I

N=16 Male, 24 Female, Age 53±20 years (22-82)www.no-fa

ll.hk

• Type IIB positive relationship with hip BMD irrespective of age

• Type II fibers critical for postural control and maintain bone quality

• Impact loading increases BMD; high impact (running, hockey, tennis, weight lifting)

• Whole body Vibration 30-50Hz may compensate for loss of firing rate due to type II fibers

www.no-fa

ll.hk

Fried Phenotype model( Aus J Age 2015; 34(1): 68-73)

3 or more of:1) Wt loss2) Exhaustion3) Weak grip4) Strength5) Slow walking speed and low physical

activity

體能表現www.no-fa

ll.hk

Frailty

Function

Hospitalization

Institutionalization

Death

Mobility

Fall Osteopenia

Hip Fracture

Fear of

Falling

Social

Activity

Incontinence

Stroke

Adverse Outcomes

不良後果www.no-fa

ll.hk

Gavrilov theory

• Progressive accumulation of random damage to a complex system of redundant parts

• Ageing organism losses redundancy• System loses resilience and vulnerable to

external and internal stressors

儲備透支www.no-fa

ll.hk

Fall

摔跌www.no-fa

ll.hk

Hip Fracture: Frailty

www.no-fa

ll.hk

Frailty, Falls and Fracture( J Morley JAMDA 2013; 149-151)

FatigueResistance (can you walk up one

flight ?)Aerobic ( can you walk more than a

block?)Illness ( > 5)Loss of weight (> 5% in 6 months)www.no

-fall.h

k

FRAILTY

• Physical• Cognitive• Psychosocial

體能

認知 社倫

www.no-fa

ll.hk

Old AgeFrailty (Reserve) and VulnerabilityOsteopeniaSarcopeniaFallsPre-mobid multiple co-morbiditiesPerioperative medical instability Hospitalization syndrome (Delirium, infection, polypharmacy)Functional declinePsychosocial issuesPost-discharge support

Fragility FractureSyndrome

Post discharge period“I year”www.no-fa

ll.hk

Declining Physiological Reserves( Crit Care Med 2004; 32(suppl): S92-S101)

• Cardiac• Respiratory• Renal• GI• Hepatobiliary• Body composition and energy use

• CNS (Delirium)

• Pain • Immune function• Haemopoietic

Hip Fracture and Hospitalization as Stress Agent

儲備透支

www.no-fa

ll.hk

The Stressor: Hospitalization

Dementia

Hospitalization Complications:

RestraintsMedicationsFunctional

decline

BPSDBladderInfections

Acute illness

Gait/Falls

www.no-fa

ll.hk

(24% discharged to OAH)older age ( ↑1.6 risk for 10 yrs increase age)dementialow mobility scoreslow basic and instrumental ADL

( Asian J Gerontol Geriatr 2007; 2: 69-77)

Predictors for old age home placement in HK:

www.no-fa

ll.hk

Declining Physiological Reserves( Crit Care Med 2004; 32(suppl): S92-S101)

• Cardiac• Respiratory• Renal• GI• Hepatobiliary• Body composition and energy use• CNS

• Pain • Immune function• Haemopoietic

Hip Fracture and Hospitalization as Stress Agentwww.no-fa

ll.hk

Ortho-geriatric Co-managementat PWHwww.no

-fall.h

k

Geriatric Clinical Assessment1) Greet patient (mental state, cognition,mood)2) Raise your arms ( stroke, parkinsonism, local

injury)3) Neurovascular examination ( CVS and fluid

status, AF, carotid bruit, reflexes )4) Respiration ( SaO2, chest, CXR)5) Abdomen ( bladder, bladder scan, bowel,

Foley’s)

6) Legs (edema, ? DVT) www.no-fa

ll.hk

Independent Nurse Assessmentwww.no-fa

ll.hk

Ortho-geriatric Roundwww.no-fa

ll.hk

Expected benefits of acute orthogeriatric care(Curr Anae & Critical Care 2005, 16:2-10)

Superior medical careOptimal scheduling of fracture surgeryBetter communication with patients and

their relativesBetter communication within the

multidisciplinary teamInitiation of research, education and auditReduction in adverse eventsEarlier initiation of rehabilitation and more

effective use of discharge resourceswww.no-fa

ll.hk

Probability of patient survival after hip fracture

according to geriatric and medical intervention

Time, days

0 50 100 150 200 250

Cu

mu

lativ

e s

urviv

al fr

ee o

f p

atie

nt

aft

er h

ip f

ractu

re

0.0

0.2

0.4

0.6

0.8

1.0

Geriatric Intervention

Conventional Care without Medical Consultation

Conventional Care with Medical Consultation

Log-rank: P < 0.0001

www.no-fa

ll.hk

Ambulatory Status – at 3 months

P value <0.01 www.no-fa

ll.hk

Ambulatory Status – at 12 months

P value <0.01 www.no-fa

ll.hk

Osteoporosis Case Manager( Arch Intern Med 2009; 169(1): 25-31)

• Rates of appropriate osteoporosis treatment are less than 10-20% in the year after hip fracture

• A hospital-based osteoporosis case manager could lead to 51% rate of bisphosphonate treatment within 6 months of fracture ( vs 22% for controls)

護理統籌www.no-fa

ll.hk

J of Clin Densitometry: Assessment of Skeletal HealthVol (12); 4:413-416, 2009www.no-fa

ll.hk

Sarcopenia in Hip Fracture( Archives of Geron & Geriatrics 2011; 52:71-74)

• 313 women within 3 weeks of hip fracture

• DXA• 58% sarcopenic• 74% osteoporotic

www.no-fa

ll.hk

Gerontology 2014;60:294-305www.no-fa

ll.hk

Translational Neuroscience 2015;6:103-110www.no-fa

ll.hk

Muscle Wasting Disease( J Cach Sarc Mus 2014; 5: 83-87)

• Muscle Wasting Disease: myopenia, sarcopenia, cachexia

Sarcopenia: primarily neurodegenerationCachexia: inflammatory muscle disorder

• Gold standard: Exercise

www.no-fa

ll.hk

Sarcopenia: Measurement

• Muscle mass• Muscle strength• Gait speed

量質功能

www.no-fa

ll.hk

Int J Evid Based Healthc 2014;12:227-243www.no

-fall.h

k

Int J Evid Based Healthc 2014;12:227-243www.no

-fall.h

k

J Musculoskelet Neuronal Interact 2014;14(4):425-431www.no-fa

ll.hk

Treatment

• Exercise• Nutritional supplementation: the evidence

grows ( JAMDA 2015; 16: 717-719)

• Pharmacological

運動, 營養, 藥物

www.no-fa

ll.hk

2 Birds with 1 Stone( Curr Osteo Rep 2014, March 16)

• Muscle and Bone development:coordinated unitcommon mesenchymal progenitor

• Mechanostat Theory:mechanical force drives periosteal growth, bone density andgeometryGH/IGF-1 axis

• Paracrine or endocrine cross talk:skeletal muscle “ second periosteum”

trophic factors, morphogens, cells bidirectional

一石二鳥, 骨肉同根生www.no-fa

ll.hk

Exercise

• Enhance protein metabolism• Improve motor unit function• Stimulate non-satellite stem cells and• Release growth factors resulting in• Satellite cell proliferation and

differentiation

運動www.no-fa

ll.hk

Sarcopenia in Older People( Int J Evid Based Healthc 2014; 12: 227-243)

• Physical activity• Aerobic/ endurance: lower intensity for frail

older persons; 30 mins, 2 times/week, incremental over 9 weeks

• Progressive resistance: 2 non-consecutive days/ wek; 8-10 exercises , 10-15 repetitions, 2 min rest in between

• Flexibility• Balancewww.no

-fall.h

k

www.no-fa

ll.hk

www.no-fa

ll.hk

www.no-fa

ll.hk

Nutrition

• Protein supplementation increase muscle synthesis in conjunction with exercise

• PROTAGE: 1-1.5kg of high quality protein ( leucine-enriched, balanced aas)

• INTERCOM: copd, heart failure, hospitalisation

• Cochrane: weight gain and reduce mortality

營養www.no-fa

ll.hk

Feeding strategies( Int J Evid Based Healthc 2014; 12:227-243)

• Protein provided with a meal: anabolic • Spread evenly across the day/ pulse

feeding• Immediately after resistance training• Whey protein, fast protein• EAAs: leucine• Β-HMB

進食策略www.no-fa

ll.hk

Kobe 2013(International Cachexic Conference)

1)Orexigenics ( ghrelin-like agents): enchance food intake, GH secretion, capromelin, MK-0677, anamorelin, OHR118

2) Megestrol plus thalidomide3) Cannabinoid-like drugs4) Testosterone5) Androgen receptor molecules (SARMS)www.no

-fall.h

k

6) Activin receptor antibody:myostatin inhibitor; bimagrumab

7) Cardiological: perindopril, espindolol8) Fast skeletal muscle troponin activitor:

amplify response to motor neuron input; tirasemtiv, CK-2127101)

9) Mitrochondrial enhancer: bendavia

www.no-fa

ll.hk

Vitamin D

• Biologically active 1,25(OH)2D binds to VDR

• Muscle and bone osteoblasts and osteoclasts express VDR

• Severe Vit D deficiency causes type II atrophy

• Reduction of VDR in aging muscle• IOM and US Endo Soc: target 25OHD 50-

75 nmol/Lwww.no-fa

ll.hk

Vitamin D and Myogenesis( Biomed Res Int 2014)

• VDR in muscle fibres, myoblastic proliferation and differentiation

• 1α, 25(OH)2D3 induce c-Src tyrosine kinase

• Vitamin D increase cell proliferation and inhibit apoptosis; satellite cells

• Vitamin D beneficial effects among patients with glucose intolerance and insulin resistancewww.no

-fall.h

k

Amer J Med 2006;119:1019-1026www.no-fa

ll.hk

Vibration Therapy( Curr Opin Endo Diab Obes 2014; 21(6):447-453)

• Skeletal disuse leads to consequences in musculoskeletal system

• Anabolic mechanical signals to mimic exercise in bone

• Mesenchymal stem cells, progenitors for bone and muscle growth

高頻率, 低幅度www.no-fa

ll.hk

www.no-fa

ll.hk

Fig 1. Cellular targets of vibration. The physiological effects of vibration are mediated by individual cellular actions. Low-magnitude mechanical signals target many cell types including mesenchymal stem cells, osteoblasts, osteocytes, adipocytes, osteoclasts, myocytes, and neurons. Curr Opin Endocrinol Diabetes Obes 2014; 21(6):447-453www.no

-fall.h

k

Fig 2. Physiological responses of whole-body vibration. Delivery of low-magnitude mechanical signals mimic aspects of loading exercise, providing direct benefits to the skeleton, but also indirectly improves musculoskeletal outcomes including balance, posture, and muscle strength. These additional benefits feed back to further enhance skeletal strength.

Curr Opin Endocrinol Diabetes Obes 2014; 21(6):447-453www.no-fa

ll.hk

www.no-fa

ll.hk