My Aching Knees

Detection and Prevention

Thomas M. Link M.D., Ph.D.Professor of Radiology

Department of Radiology and Biomedical Imaging, University of California San Francisco

2

Osteoarthritis (OA) is the most frequent joint disease

In the U.S. about 27 million suffer from symptomatic

osteoarthritis1

Affects nearly 50% of patients 75 years and older2

• results in long-term disability • enormous economical health

care cost burden3

Osteoarthritis

1 Lawrence et al. Arthritis and rheumatism 20082 Litwic et al. Br Med Bull. 20133 Kotlarz et al. Arthritis and rheumatism 2009; Illustration from www.healthcare.utah.edu

Disability

National Center for Health Statistics, United States, 2009

75-85 years 65-74 years 55-64 years

Lung

Dia

bete

s

Hea

rt

Bon

es/jo

ints

Life Expectancy

Women Men

Diagnosis with Radiographs

Diagnosis with MRI

Prevention

Risk score

Diagnosis with Radiographs

Diagnosis with MRI

Prevention

Risk score

7

Definition of Osteoarthritis degenerative joint disease

is based on clinical symptoms and on Radiographs/X-rays

knee

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Knee - normal

9

Knee – mild osteoarthritis

10

Knee – mild osteoarthritis

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Knee – moderate osteoarthritis

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Knee – moderate osteoarthritis

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Knee – severe osteoarthritis

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Knee – severe osteoarthritis

Diagnosis with Radiographs

Diagnosis with MRI

Prevention

Risk score

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MRI / Magnetic Resonance Imaging

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MRI / Magnetic Resonance Imaging

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MRI / Magnetic Resonance Imaging

cartilage – bone - meniscus

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MRI / Magnetic Resonance Imaging

cartilage – bone - meniscus

Meniscal tear

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MRI / Magnetic Resonance Imaging

cartilage – bone - meniscus

Meniscal tear

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MRI / Magnetic Resonance Imaging

cartilage – bone - meniscus

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MRI / Magnetic Resonance Imaging

cartilage – bone - meniscus

Collagen Chondrocytes

Cartilage loss

Irreversible

Does not grow back

Leads to osteoarthritis

Evolution of cartilage in OA

23Illustrations from Matzat et al. Quant Imaging Med Surg. 2013

Healthy Cartilage

Proteoglycans

Cartilage loss

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MRI / Magnetic Resonance Imaging

Osteoarthritis – 29 year old man

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MRI / Magnetic Resonance Imaging

Osteoarthritis – ACL degeneration45 yo woman

Diagnosis with Radiographs

Diagnosis with MRI

Prevention

Risk score

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From the Press

Medical News Today 5/2017

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Obesity: modifiable risk factor for OA

Weight loss slows OA1

Improvement of clinical symptoms2

Is a higher degree of weight loss associated with improved cartilage

health?

Obesity and Osteoarthritis (OA)

1 Serebrakian et al. JMRI 2014 2 Edwards et al. Arthritis 2012Illustration from www.clinicaladvisor.com

Early molecular changesCompositional T2 imaging

Molecular T2 Relaxation Time Mapping

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• collagen content • free water

0 70T2 [ms]

Baseline 4 years 8 years

Assessment of molecular cartilage compositionbefore cartilage lesions occur:

Courtesy Zarnowski

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MRI T2 measurements to detect molecular changes before cartilage damage

Obesity and Osteoarthritis (OA)

Do different degrees of weight loss have a different impact on cartilage health?

1 Joseph et al. Arthritis Research & Therapy 2011

Magnetic resonance imaging (MRI)

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Baseline 48-month follow-up

1 Joseph et al. Arthritis Research & Therapy 2011

• Molecular cartilage imaging: T2 relaxation time

Patient selection

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506 patients from the OAIage 62.4±9.3y, 60.6% females

BMI 30.2±3.5 – obese or overweight subjects

patients not loosing weight

253 subjects>10% weight loss

76 subjects

5-10% weight loss 177 subjects

1 Holdsworth et al. Int J Obes Relat Metab Disord. 2004

Results

Magnetic resonance imaging (MRI)

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Baseline 48-month follow-up

1 Joseph et al. Arthritis Research & Therapy 20112 Yu et al. Osteoarthritis Cartilage 2015

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0

0.2

0.4

0.6

0.8

1

1.2

1.4

1.6

Stable weight 5-10% weight loss >10% weight loss5-10%weight loss

>10%weight loss

Cha

nge

ofT2

mea

sure

men

ts(m

s) o

ver4

y

Obese patients withoutweight loss

Cartilage

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Baseline

0 70T2 [ms]

4 year follow-up

Cartilage molecular T2 maps of medial tibiaO

bese

with

>1

0% w

eigh

t los

sO

bese

with

out

wei

ght l

oss

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Progression of defects Baseline 4 year follow-up

Obe

se w

ith

>10%

wei

ght l

oss

Obe

se w

ithou

t w

eigh

t los

s

38

5-10%weight loss

>10%weight loss

Cha

nge

ofkn

eepa

inov

er4y

Obese withoutweight loss

Pain

Obese and overweight patients with risk factors or mild to moderate radiographic evidence for OA:

• protective aspect of weight loss on cartilage

• patients with >10% weight loss benefit significantly more than patients with little or no weight loss

• potentially weight loss can prevent end stage OA

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Conclusion

40

Forbes 10-2017

2017 Mayo Foundation for Medical Education and Research

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Physical Activity and Osteoarthritis WGN-TVChicago

News 11/2009

RSNA Press conference

11/2011

Background

Loading = essential for normal cartilage development If excessive, may lead to degeneration over

time

Association of exercise with OA development is unclear Detrimental, beneficial, no effect on articular

cartilage

1Jones G, et al. 2Vanwanseele B, et al. 3Spector TD, et al. 4Cheng Y, et al. 5Rogers LQ, et al. 6Roos EM, et al. 7Chakravarty EF, et al. (See Reference Page)

Objective

To evaluate the effects of exerciseon knee cartilage

in middle-aged, asymptomatic subjects with and without OA risk factors

PHYSICAL ACTIVITY SCALE FOR THE ELDERLY

3 domains of physical activity over last 7 days Leisure, household, and occupational activities

Leisure ActivitiesSitting, walking, light, moderate, strenuous sport/recreation,

muscle strength training

Sedentary Moderate Exercisers StrenuousExercisers

EXERCISE LEVEL CLASSIFICATION

Color Map

Sedentary Light-moderate StrenuousExerciser Exerciser

Results

Strenuous exercisers = ↑ T2

Associated with more degenerated cartilage

Subjects with knee OA risk factors:

Mild - moderate exercisers = ↓ T2 values

Indicative of healthier cartilage

CONCLUSIONS

In line with American Heart Association Recommendations for Physical Activity in Adults150 minutes per week of moderate exercise or 75 minutes per week of vigorous exercise (or a combination of moderate and vigorous activity). Thirty minutes a day, five times a week is an easy goal to rememberAvoid too much high impact activity !

Recommendations

Diagnosis with Radiographs

Diagnosis with MRI

Prevention

Risk score

Outcome: at any subsequent timepoint (1 year – 8 years) N (%) of 641

KL >= 3 34 (5.31%)WOMAC >=5 at any two subsequent timepoints 53 (8.27%)

Total Knee Replacement 8 (1.25%)ANY OUTCOME 80 (12.48)

J Magnetic Resonance Imaging, 2017, in press

8 year Outcome Variables

Radiographic or clinical osteoarthritis

or total joint replacement

Risk score model

J Magnetic Resonance Imaging, 2017, in press

Risk Score

29.4%

Medial Femur T2 [ms]42.3

Medial Femur T2 [ms]30.8

Medial Femur T2 [ms]37.6

Effects of varying T2 values

0 ms

70 ms

Low risk: 34.1% Med Risk: 57.5% High Risk: 75.1%

Acknowledgments

Acknowledgments

National Institutes of Health U01 AR059507P50 AR060752 R01 AR46905 R01 AG017762, PAR-04-023, NIHNIH BAA-NHLBI-AR-10-06 OAI N01-AR-2-2258; N01-AR-2-2259; N01-AR-2-2260; N01-AR-2-2261; N01-AR-2-2262

GSKUCSF REAC Program

Thank you!