Opportunistic screening of sarcopenia, osteoporosis, and dysmobility syndrome using CT-based machine learning algorithm
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Medical Korea 2021
Session 8: 포스트 코로나 시대 비대면 의료혁신기술의 현재와 미래
Opportunistic screening of sarcopenia,
osteoporosis, and dysmobility syndrome
using CT-based machine learning algorithm
Namki Hong, M.D.,M.P.H.
Department of Internal Medicine,
Yonsei University College of Medicine,
Seoul, Korea
Disclosure • This research was supported by a fund (2013- E63007-01, 2013-E63007-02) from Research of Korea Centers for Disease Control and Prevention.
Post COVID-19 era and
Untact Medicine
• Increased awareness of health
?
• Untact
• Expandability
• Cost-effectiveness
Yoon Sup Choi, 2020.05.20 Korea Biomedical Review
Metabolic syndrome and COVID-19 mortality:
underlying metabolic health in the spotlight
Diabetes Care 2020 Aug; dc20171
New threats to metabolic hea Reduced physical activity Increased dietary intake
Aging…
Bone loss [https://courses.washington.edu/bonephys/opclin.html]
Muscle loss
206 500
AFTER COVID-19: Musculoskeletal perspectives Accelerated bone loss Accelerated muscle loss Impaired mobility Increased comorbidities
BURDEN OF OSTEOPOROTIC FRACTURES IN ASIA-PACIFIC REGION
Incidence of fragility fractures
1 year incidence
GLOW study: 50,461 women (a prospective, multinational, observational cohort study)
1822 fractures/year
Osteoporos Int. 2012 Dec; 23(12): 2863–2871.Impact of fragility fractures
Osteoporos Int. 2012 Dec; 23(12): 2863–2871.Mortality after fragility fractures
Lancet. 1999 Mar 13;353(9156):878-82.Survival according to types of
fracture and age groups in women
DUBBO cohort (1989-2007), 4005 individuals (2244, women; 1760, me
aged 60 or older
Age < 75 Age 75 or higher
JAMA. 2009 Feb 4;301(5):513-21.Survival according to types of
fracture and age groups in men
DUBBO cohort (1989-2007), 4005 individuals (2244, women; 1760, men)
aged 60 or older; fractured: 1295 (952, women; 343, men)
Age < 75 Age 75 or higher
JAMA. 2009 Feb 4;301(5):513-2Increased risk for subsequent fractures according
to initial fracture types
JAMA. 2007 Jan 24;297(4):387-9Fragility fractures are not benign conditions
Countries with the largest percentage
point increase in the share of older
persons aged 65 years or over between
2019 and 2050
Estimated and projected prospective old-
age dependency ratios (65+/20-64)
by region, 1990-2050
Rapid ageing in Asian countries
United Nations. World Population Ageing 2019: HighlightsSecular trends in hip fracture incidence
rates in Japan from 2010 and 2018
Increased femoral neck fracture incidence in men in 2016-2018
compared to 2004-2006
Archives of Osteoporosis (2020) 15:152Changes in age-specific incidence of hip fracture in
Beijing, China from 1990-1992 to 2002-2006
J Bone Miner Res. 2012 Jan;27(1):125-9.Changes in age-specific incidence of hip fracture in South
Korea
from 2002 to 2011
J Korean Med Sci. 2015 Apr; 30(4): 483–488.Increasing societal costs of fragility
fractures in Korea between 2007 to 2011
VALUE IN HEALTH REGIONAL ISSUES 9C (2016) 36–41Key statistics for Asia
• It is projected that more than about 50% of all
osteoporotic hip fractures will occur in Asia by the year
2050
• In a systematic review of hip fracture incidence worldwide,
age-standardised hip fracture rates in women were high
in Hong Kong, Singapore and Taiwan, i.e. an incidence
above 300/100,000 persons.
• In China, the incidence of hip fracture will raise from
411,000 in 2015 to an estimate of more than 1 million
hip fractures in 2050.
https://www.osteoporosis.foundation/facts-statistics/key-statistic-for-asiaBone & Muscle
• Associations between bone and muscle
– Quantitatively : BMD and Muscle Mass
• Caucasian 313 women with hip fractures(79.7 years)
• DXA (QDR 4500w, Hologic, Inc)
M. Di Monaco et al. Archives of Gerontology and Geriatrics 2011Aging of Bone & Muscle
(g/cm2)
Men Women
Femur Neck BMD
Bone
Fracture
30s 90s 30s 90s
(years) (years)
(Kg)
Men Women
Appendicular skeletal
Muscle
muscle mass
Frailty
30s 90s 30s 90s
(years) (years)
Modified from Kim KM et al. J Bone Miner Metab 2012 Modified from Kim KM & Lim S et al., IJC Metabolic & Endocrine 2014Multifactorial factors of aging skeletal muscles
• Physical activity • Genetics
• Nutrition • Hormones
• Low-grade
inflammation
• Fear of falling, psychological resilience, self-efficacy, loneliness
[Journal of Cachexia, Sarcopenia and Muscle 2018; 9: 3–19The concept is not SIMPLE!
Definitions
Term Definition Assessment
Sarcopenia Loss of muscle mass DXA, MRI, CT, US, BIA,
Anthropometry(circumfere
nce)
Kratopenia Loss of force (strength) Isometric(dynamometry)/Is
otonic
Dynapenia Loss of power (force X velocity) Walking speed/distance,
stair climbing, Jepsen hand
function
Frailty Weight loss/weakness/fatigue/slow CHS, FRAIL
walking speed/low physical activity
Disability Loss of activities of daily living(ADLs) Katz ADLs, Barthel index
Locomotive Sarcopenia+Osteoarthritis+Osteoporosis
syndrome
Dysmobility Osteoporosis/Falls/Sarcopenia/Slow gait
syndrome speed/Low grip strength/ObesityThe age-related loss of muscle strength is
weakly associated with the loss of muscle mass
[Delmonico MJ et al. Longitudinal study of muscle strength, quality,
and adipose tissue infiltration. Am J Clin Nutr. 2009; 90:1579]Concepts of Words
Muscle Force
Muscle Quality
Absolute
(Force/mass)
Relative/BWt
Muscle Composition
Muscle Power = Force X VelocityClinical importance of physical function
• Compared to muscle mass, “muscle function and physical
performance” is associated more strongly with
– Risk of falls and fractures
J Bone Miner Res 2008;23:1037-44.
– Mortality and disability Age Ageing 2010;39:412-23.
Lancet 2015; 386: 266–73.Handgrip Force/Functional tests
Jamar Martin-
hydraulic Vigorimeter
dynamometer (pneumatic
dynamometer)
• Isometric
assessment
• 16-20 kg(Women)
• 26-30 kg(Men)
• Limitation of traditional assessments [grip strength(upper limb)/gait speed,
TUG(lower limb)]
– Yes/no determinations
– Timing variability from tester subjectivity
– Requiring some level of disability to be considered abnormal
– Testing only single muscle group, low intensity, or simple tasks
Osteoporos Int 2015;26:819-25.
J Musculoskelet Neuronal Interact 2015; 15(4):301-308Objective measurement of muscle function
(Jumping Mechanography)
• Quantification of individual anaerobe peak power output
• Parameters: force, acceleration, power, counter movement, mass,
Esslinger Fitness Index (E.F.I.), efficiency of movement, etc.
The jump was performed as a counter-
movement jump with freely moving arms, and
the subjects were instructed to jump as high as
possible with the head and chest. Subjects
jumped using both feet and landed on both feet.
[Buehring B et al. J Clin Densitom. 2010]Korean Urban Rural Elderly (KURE) cohort
▪ Study Design
▪ Community-based, Cross-sectional study
▪ Study subjects
▪ healthy elderly aged 64 to 87 years from the Korean Urban
Rural Elderly (KURE) cohort study, 2014~
▪ Assessment
▪ Bone mineral density by dual X-ray absorptiometry
▪ Skeletal muscle mass and index (kg/m2) by bioimpedence
▪ Muscle function by jumping mechanography[single 2-legged
jumps, S2LJ]
▪ Vertebral fracture assessmentLower migration out rate
Incorrect weight shifting while standing and turning
Incorrect weight shifting while walking forward
Trip while walking and turning
Trip while walking forward
Loss of support with external object while sitting down
Lancet 2013; 381: 47–54Self-induced shifting of
body weight, causing
center of gravity to move
outside the base of support
Hip extension (gluteus
maximus, long-head of biceps
femoris..)
Knee extension (quadriceps
femoris)
Ankle plantarflexion
(gastrocnemius, soleus)
Lancet 2013; 381: 47–54Growing interest in assessing jump power in elderly
“How much work
can be done within a
limited time?”
f=ma; Δv=at
distance = v x t
Power = Work/t
= f x d/t
=fxv
Strength
✓ Physiologically
complex
✓ High intensity
✓ Reproducible &
safe
✓ No learning
effect
Journal of Clinical Densitometry: Assessment of Skeletal Health, vol. 13, no. 3, 283e291, 2010
Osteoporos Int 2015; 26:819-25.; Eur J Appl Physiol 2001;84:206-12.Osteoporosis and fracture prevalence
according to muscle mass
Osteoporosis at hip Vertebral fractures
Lee EY, Rhee Y et al., Calcif Tissue Int (2017) 100:585–594Osteoporosis and fracture prevalence
according to Pmax/mass
Osteoporosis at hip Vertebral fractures
Max. Peak Power Max. Peak Power
Lee EY, Rhee Y et al., Calcif Tissue Int (2017) 100:585–594Regression analysis for vertebral
fracture
Model1 Model2
OR (95% CI) P OR (95% CI) P
Quartile 1 1.06 (0.70-1.61) 0.770 0.66 (0.42-1.03) 0.068
Quartile 2 1.35 (0.90-2.02) 0.144 1.00 (0.66-1.53) 0.997
Muscle mass
by SMI Quartile 3 1.24 (0.82-1.87) 0.301 1.04 (0.68-1.58) 0.883
Quartile 4 1.00 (reference) 1.00 (reference)
Quartile 1 2.80 (1.79-4.36)[Binkely N et al., Osteoporos Int. 2013 Dec;24(12):2955]
Dysmobility syndrome
• Calls for moving beyond simple concepts to
focus on ‘elevated fracture risk’
• Identification of individuals at risk of impaired
mobility, fractures, and falls
• Combination of
– Sarcopenia “Unification of osteoporosis,
sarcopenia, and sarcopenic
– Obesity obesity” like metabolic
– Mobility impairment syndrome in cardiovascular
field
– Osteoporosis
[Osteoporos Int. 2013 Dec;24(12):2955]Dysmobility syndrome and mortality risk in US
men and women age 50 years and older
[Osteoporos Int. 2015 Jan; 26(1): 93]Prevalence of morphometric vertebral or
nonvertebral fracture according to
dysmobility scores
50
Nonvertebral fracture P for trend < 0.001 for all
Morphometric vertebral fracture
Any fracture
40
30
20
10
0
0 1 2 3 4 5 or 6
Number of dysmobility components
Hong N et al., Archives of Osteoporosis 2018Odds of any fracture or morphometric
vertebral fracture according to presence
of dysmobility syndrome
Hong N et al., Archives of Osteoporosis 2018Detection of dysmobility
syndrome in post COVID-19 era
• Bunch of tests with direct contacts
• Frequent visit to hospital
?
• Limited extension
(limited DXA machine)
• Difficulties in physical
function testing…
DXA, BIA, handgrip strength, jump, etc….POTENTIAL STRATEGY CT-BASED OPPORTUNISTIC SCREENING OF SARCOPENIA AND DYSMOBILITY SYNDROME
Why CT-based opportunistic screening of dysmobility
syndrome or sarcopenia in post COVID-19 era?
• Increased awareness of health
– Increasing burden of sarcopenia and dysmobility syndrome in aged society
– Early detection can lead to improvement of treatment outcome
• Untact
– Diagnosis can be made solely on CT images taken for other clinical purposes
• Expandability
– Korea: 25 CT scanners/million (next to US, JPN)
– High accessibility; more than million scans worldwide; better than DXA
• Cost-effectiveness
– Secondary use of ‘already taken’ image resources
– Maximize the information gain from routine clinical CTSkeletal muscle quality beyond mass
Skeletal muscle radiodensity (SMD,
muscle attenuation; HU)
• Indicator of myosteatosis
• Decreased HU: correlate with
ageing, poor physical function,
insulin resistance, and higher
intramyocellular TG contents
SMA: 104.0 cm2 SMA: 107.0 cm2
SMD: 43.0 HU SMD: 36.9 HU
Acta Physiol 2014, 210, 489–497[Heewon Choi, Namki Hong, Narae Park, Yumie Rhee, SSBH, 2019]
Participants characteristics according
to handgrip strength
Choi HW, Hong N, Rhee Y, et al. Calcified tissue internationalIndependent association of SMD with
low grip strength
Choi HW, Hong N, Rhee Y, et al. Calcified tissue internationalAge-related trajectory of (A) L3SMA, (B) SMI, (C)
SMD, and (D) L1 trabecular attenuationPrevalence of presarcopenia or sarcopenia according to the age SMA (mass) SMD (quality)
Comparison of discriminative performance of
L3SMA, L3SMI and L3SMD for L1 trabecular
attenuation < 110 HU
1.00 P < 0.001
0.75
Sensitivity
0.50
0.25
L3SMA: 0.6856
L3SMI: 0.6825
L3SMD: 0.8551
Reference
0.00
0.00 0.25 0.50 0.75 1.00
1-Specificity3D Deep neural
network-based semi-
automatic
segmentation서울시 인공지능 기술사업화 과제 2020
Diagnostic thresholds equivalent to
standard diagnostic modalities
40 cm2/m2 and 35 cm2/m2 in men and women for defining sarcopenia
4.7 cm2/kg and 5.8 cm2/kg in men and women for high fat mass
Yoon SH, Hong N et al., SubmittedImproved diagnostic performance for
sarcopenia and dysmobility syndrome
Yoon SH, Hong N et al., SubmittedFUTURE: AI-empowered, untact Fracture Liaison Service
Enhancing secondary prevention of fracture
https://capturethefracture.org/fracture-liaison-servicesThanks to Pf. Yumie Rhee,
KURE team, and Medical IP
1Internal Medicine, Yonsei University College of Medicine, Seoul, Korea,
2Division of Endocrinology and Metabolism, Department, of Internal Medicine,
Seoul St. Mary’s Hospital, College of Medicine, The Catholic University of Korea,
Seoul, Republic of Korea, 3Internal Medicine, Seoul National University Bundang
Hospital, Seongnam, Korea, 4Sociology, Yonsei University, Seoul, Korea,
5Preventive Medicine, Yonsei University College of Medicine, Seoul, Korea
6Department of Internal Medicine, National Health Insurance Service Ilsan
Hospital, Goyang, Korea, 7Department of Endocrinology and Metabolism, Inha
University School of Medicine, Incheon, KoreaThank you for your attention!
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