Stefan Lohmander Odense 2016-01-28
osteoarthritis as illness
and disease:
the road map
•
•
•
•
•
•
•
a few facts
what is OA?
who gets it and why?
what happens in the OA joint?
management of OA
”early” OA
how will we ever get there?
Stefan Lohmander, MD, PhD
a few facts
• by far the most common joint disease
• accounts for more functional limitation & disability
than any other chronic disease among the elderly
• 90% of indications for total joint replacement
• costs ~ 2% of GNP in developed countries
• OA has multiple outcomes for joint and patient,
but pain is dominant driver of seeking healthcare
for OA
• there is a link between joint structure and pain,
but variable and tenous
osteoarthritis
what is
osteoarthritis
and who gets it?
osteoarthritis?
pain
loss of
participation
impairment
1
Stefan Lohmander Odense 2016-01-28
osteoarthritis?
osteoarthritis?
• are you over 50?
• have you had pain in
your knee for most
days of the month
during the last year?
• have you ..
OA criteria?
symptoms
(pain,
both
impairment,
structural
loss of
changes
participation)
(X-ray, MRI)
who gets OA
and why?
who gets OA and why?
• age
– prevalence increases markedly over age 50
• heritability
– genetic and non-genetic
life style(s)
• lifestyle
– diet & exercise
– use and abuse of joints at work / leisure
overweight & obesity
2
Stefan Lohmander Odense 2016-01-28
obesity is associated
with high OA risk
• biomechanics
– dynamic load on knee joint x2.5 body weight
– joint overload every step, millions x years
life style(s)
• metabolic stress
joint injury
– obesity is associated with chronic inflammation,
adipokines from adipocytes and macrophages in
adipose tissue suggested to be a metabolic link
between obesity and OA
knee injury leads to OA
at 10-20 y after
cruciate ligament or
meniscus lesions,
some 50% have
OA
what happens in
the OA joint?
“young patients
with old knees”
Lohmander et al. Am J Sports Med 2007
cartilage thickness maps
4.0mm
0.25mm
0.25mm
-0.25 mm
-0.25 mm
0.0mm
MRI morphometry
bone curvature
bone surface area
Baseline
2Y Change
5Y Change
KANON study, images José Tamez, QImaging
3
Stefan Lohmander Odense 2016-01-28
MRI morphometry (qMRI)
cartilage thickness increase after ACL tear
N=107
***
***
95% CI
**
n.s.
*
Eckstein, Wirth, Lohmander, Hudelmaier, Frobell. Arthritis Rheum 2014
Eckstein et al. 2013
cartilage thickness increase after ACL tear
Total Femorotibial Joint (FTJ)
baseline
bone curvature measurement
• average of the mean curvature of the surface
• a measure of degree and direction of bending of object
• can be used to measure the degree of bone
remodeling as OA progresses
Year 2
(ACL tear)
n.s.
Year 5
Negative curvature
Zero curvature
Small positive curvature
Large positive curvature
Example
-0.2
0.2
Eckstein et al. 2013
KANON bone curvature change over 5y
2 Year Change
Baseline
change in medial femur bone area
5 Year Change
+0.01mm-1
Raw
Change
Trochlea
-0.01mm-1
Femur
+1.0 z
Medial
Lateral
Concave
Convex
-0.1 mm-1
+0.1 mm-1
0.0
SRM
-1.0 z
+0.01mm-1
Trochlea
Raw
Change
-0.01mm-1
Tibia
+1.0 z
Medial
-0.1 mm-1
SRM
Lateral
+0.1 mm-1
-1.0 z
Hunter, Lohmander, Makovey, Tamez-Pena, Totterman, Schreyer, Frobell. Osteoarthritis Cartilage 2014
Frobell, Lohmander, Wolstenholme, Vincent, Bowes. 2014
4
Stefan Lohmander Odense 2016-01-28
bone changes in single fastprogressing individual
•
•
•
Video shows addition of bone to
baseline shape with time
Subsequent time-points are coloured
with increasingly dark green to show
progression
In the femur, bone is primarily added
around the cartilage plate
(osteophyte region), but central
articulating region also flattens
emerging understanding of
disease mechanisms can
identify novel targets for
intervention
– this way of displaying data cannot
show areas of bone which shrink with
time, but major effect was addition of
bone
Frobell, Lohmander, Wolstenholme, Vincent, Bowes. 2014
how do we manage OA?
managing OA
few
surgery
some
drugs,
walking aids
information,
exercise, weightloss,
self-management
all
in summary
core set of treatments for OA
•
•
•
•
all except TJR have small-modest ES
many OA drugs have significant AEs
exercise+weight loss as effective as drugs
there is no disease-modifying treatment
• in general, our current management
of OA is reactive
• we need to change into a proactive
management of earlier stages of
disease
• compare with our current attitudes for
managing early diabetes,
cardiovascular disease
5
Stefan Lohmander Odense 2016-01-28
knee without OA
“early” OA
when does
the ”real”
OA begin?
knee with OA
should we treat
or should we treat
?
when should we
best intervene?
no illness
no disease
preclinical
clinical
no illness
disease+
illness+
disease+
eOA?
no illness
no disease
preradiographic
clinical
illness+
no? disease
illness+
disease+
eOA?
image from Hayashi et al. Osteoarthritis Cartilage 2014
6
Stefan Lohmander Odense 2016-01-28
preclinical
no illness
no illness
disease+
no disease
preradiographic
illness+
do early structural joint
changes predict later
symptomatic OA?
clinical
illness+
disease+
no? disease
lifestyle promotion
detect and treat early
reduce damage
eOA?
prospective population-based study
does radiographic OA predict THR?
N~1,500
Colon radiography
1980-97
Mean age 60 years
?
More
OA
Incidence of THR for
OA by linkage with the
national Icelandic TJR
register
Insult Acute
Franklin J et al. 2011 AC&R
Chronic
OA
Time
Age
Hazard Ratios for getting THR
Cox multivariate regression adj for age & sex
MJS (mm)
HR (95%ci)
K&L grade
HR (95%ci)
<=2.5
13.2 (8.1-21)
1 4
12.9 (7.9-21)
3.0
1.7 (0.87-3.3) 1
1.8 (0.81-3.8)
2.5
3.7 (1.1-12)
2
8.5 (4.4-16)
1.5-2.0
9.5 (4.1-22)
3
33 (16-68)
0-1.0
51 (28-93)
4
49 (17-141)
only 17% of those with
radiographic hip OA at
baseline had undergone THR
for OA at the end of the 11-28
year study
*ref JS>3.5mm or K&L 0
Franklin J et al. 2011 AC&R
7
Stefan Lohmander Odense 2016-01-28
positive & negative predictive
values of radiographic hip OA
radiographic OA:
diagnostic criterion or risk factor?
• PPV 0.40
• NPV 0.96
overdiagnosis
treating those at risk of being at risk?
8