Transcript osteoarthritis

Osteoarthritis (OA)
M90 陳相成 主治醫師
三軍總醫院風溼免疫科
Hsiang-Cheng Chen, MD, PhD, FACR
HCC= Hepatocellular Carcinoma
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以病人為中心!
熱忱!
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Best Medical Schools
(US News & World report)
: 6th Duke University, NC
Campus: 8610 acres
(34.8km2)
Perkins Library, west campus
Duke Chapel, west campus
Center for Human Genetics
East campus
Outline
• OA Definition
• Clinical Features of
OA
• OA Risk Factors
• OA Criteria and
Diagnosis
• Pathogenesis of OA
• Treatment of OA
• Future Direction
– OA biomarkers
– OA genetics
Not so
simple!
Genetics?
I am confused!
Old Age!
(Osteoarthritis
!
Too heavy!
)
Kraus, 2006; Best Practice & Research Clinical Rheumatology, 20, 69-80 (modified)
Background: Osteoarthritis (OA)
People with Arthritis 1990 and 2005
1990
Very common
Causes disability
Aging is a major risk factor
< 15%
15 - 18%
> 18%
2005
Strong genetic component
Most arthritis comes in the form
of OA
Definition of OA (not only cartilage disease)
OA is joint failure, a disease in which all structures of the joint have
undergone pathologic change, often in concert. The pathologic of
disease is hyaline articular cartilage loss. This is accompanied by
increasing thickness and sclerosis of the subchondral bony plate, by
outgrowth of osteophytes at the joint margin, by stretching of the
articular capsule, by mild synovitis in many affected joints, and by
weakness of muscles bridging the joint.
Harrison’s 17th Edition
 OA is a degenerative joint disease, occurring primarily in older
individuals, characterized by erosion of the articular cartilage,
hypertrophy of bone at the margins (ie, osteophytes), subchondroal
sclerosis, and a range of biochemical and morphologic alternations of
the synovial membrane and joint capsule.
Kelley’s Textbook of Rheumatology
Outline
• OA Definition
• Clinical Features of
OA
• OA Risk Factor
• OA Criteria and
Diagnosis
• Pathogenesis of OA
• Treatment of OA
• Future Direction
– OA biomarkers
– OA genetics
Clinical Features of OA
• Pain
• Stiffness
• Loss of movement
and function
• Joint enlargement:
Heberden’s or
Bouchard’s node
Figure 326-1 Harrison’s 17th Edition
Heberden’s node (DIP) and Bouchard’s node (PIP)
Figure 326-2 Harrison’s 17th Edition
Outline
• OA Definition
• Clinical Features of
OA
• OA Risk Factors
• OA Criteria and
Diagnosis
• Pathogenesis of OA
• Treatment of OA
• Future Direction
– OA biomarkers
– OA genetics
Osteoarthritis Risk Factors
•
•
•
•
•
•
Gender
Age
BMI (obesity)
Injury
Joint alignment
Genes
(genetic predisposition)
Kraus, 2006; Best Practice & Research Clinical Rheumatology, 20, 69-80
Osteoarthritis Risk Factors
It is complicated!
It is multi-factorial !
Figure 326-4 Harrison’s 17th Edition
Outline
• OA Definition
• Clinical Features of
OA
• OA Risk Factor
• OA Criteria and
Diagnosis
• Pathogenesis of OA
• Treatment of OA
• Future Direction
– OA biomarkers
– OA genetics
OA Criteria (ACR) and Diagnosis
美國風溼病醫學會 http://www.rheumatology.org/
中華民國風溼病醫學會 http://www.rheumatology.org.tw/
中華民國免疫學會 http://www.immunology.org.tw/
OA Criteria (ACR) and Diagnosis
Definitions of Hand OA : ACR Criteria
ACR clinical hand OA criteria
 Hard tissue enlargement of two or more of 10 selected joints
 Hard tissue enlargement of two or more DIP joints
 Fewer than three swollen MCP joints
Altman RD, 1987; Arthritis Rheum, 30, 1214-25
OA Criteria (ACR) and Diagnosis
Classification of OA
• Primary (Idiopathic)
–
–
–
–
Peripheral Joints
Spine
Subsets
Hereditary
Adapted from: Sharma & Kapoor “Epidemiology of
Osteoarthritis” In: Osteoarthritis, 4th Ed. 2007
• Secondary
– Trauma
– Underlying Joint
disorders
– Systemic Metabolic
disorders
– Crystal deposition
disease
– Neuropathic disorders
(Charcot joints)
– Miscellaneous
Etiologies of Secondary OA
Table 90-1 Kelley’s Textbook of Rheumatology
Joint Hypermobility - Beighton Criteria
(0-9 point scale)
Definition: > 4 points
Hypermobility
Passive
apposition of
the thumb to
the forearm
Passive
dorsiflexion
of the fifth
finger ≧ 900
Hyperextension
of the elbows
≧ 100
Ability to rest the
palms flat on the
floor with
straight knees
Hyperextension of the
knee ≧ 100
Remvig L, 2007; J Rheum, 34, 798-803
OA Biomarkers Vs Joint Hypermobility
Reduced serum COMP in Association with General
Joint Hypermobility in GOGO Cohort (age adjusted)
Non-hand OA
Non- DIP OA: P = 0.007
Non-PIP OA: P = 0.003
Non-Knee OA
Non-CMC1 OA: P = 0.002
Non-Hip OA: P = 0.0008
Chen HC, Kraus VB et al, 2008; Arthritis Rheum,58,3854-64
Differential diagnosis (1)
Figure 325-4 Harrison’s 17th Edition
Prevalence of OA vs RA
From slide collection of Drs. Kuettner and Cole
Rush University Medical Center
Differential diagnosis (2)
Figure 325-5 Harrison’s 17th Edition
Algorithm for helping Differential diagnosis (3)
Figure 325-1 and 325-2 Harrison’s 17th Edition
Interpretation of Synovial Fluid
Aspiration
Figure 325-6 Harrison’s 17th Edition
Typical Radiographic Feature of OA
The plain radiograph remains a key investigation
in the clinical management of OA
the diagnosis of OA
It is useful for:
the assessment of the severity of
structural damage
the search for associated
chondrocalcinosis
The four radiographic features of OA are:
Focal joint space narrowing
Subchondral sclerosis
Marginal osteophyte
Subchondral cyst
Knee OA
- Medial tibiofemoral narrowing in both knees (arrow)
-Note the mild subchondral sclerosis adjacent to the narrowing
in the upper part of the medial tibial plateau, and the absence of well
identified osteophyte.
provided by OARSI
Outline
• OA Definition
• Clinical Features of
OA
• OA Risk Factor
• OA Criteria and
Diagnosis
• Pathogenesis of OA
• Treatment of OA
• Future Direction
– OA biomarkers
– OA genetics
Normal Structure of Joint and
Articular Cartilage
Pathophysiology of OA
Figure 326-3 Harrison’s 17th Edition
Pathological changes of OA
Loss of cartilage
Thickness of the
subchondral bone
ostephyte
Figure 326-6 Harrison’s 17th Edition
Outline
• OA Definition
• Clinical Features of
OA
• OA Risk Factor
• OA Criteria and
Diagnosis
• Pathogenesis of OA
• Treatment of OA
• Future Direction
– OA biomarkers
– OA genetics
Pharmacologic Treatment For OA
• Acetaminophen
• NSAIDs
• Naproxen
• Salsalate
• Ibuprofen
• Cyclooxygenase-2
inhibitors
• Celecoxib
• Opiates
• Capsaicin
• Intra-articular injections
• Hyaluronans
• Steroids
Table 326-1 Harrison’s 17th Edition
* Please see side effects from Harrison’s
Outline
• OA Definition
• Clinical Features of
OA
• OA Risk Factor
• OA Criteria and
Diagnosis
• Pathogenesis of OA
• Treatment of OA
• Future Direction
– OA biomarkers
– OA genetics
Graduation ceremony
Initiation and Progression of OA: a typical
pattern
Chondrocyte proliferation
Collagen synthesis activity ↑
MMP/ADAMTs ↑
Cytokines ↑
Loss of proteoglycans
Collagen degradation ↑
Collagen gene activation
Cell apoptosis
Osteophytes
Joint space ↓
Subchondral
bone sclerosis
Late OA
Genetics
Aging
Injury
Release of matrix fragments (Biomarkers)
OA Progression
Early OA
Imbalance of cartilage matrix
turnover by chondrocytes
Anabolism
Initiation
Catabolism
Background of OA Biomarkers
: Proposed BIPED Classification
BIPED
–
–
–
–
Burden of Disease
Investigative
Prognostic
Efficacy of Therapeutic
Prognostic
Intervention
– Diagnostic
Investigative
Diagnostic
Burden of Disease
Efficacy of Intervention
Bauer, Kraus et al .Osteo Cartilage 2006: 14(8):723-7
Serum PIIANP Decreased with Hand OA
(age-adjusted)
P value
Criteria
Hand OA
Non-Hand OA
Controls
Modified hand
ACR criteria
N=36
N=190
N=45
Ln PIIANP
7.10 + 0.52
7.10 + 0.50
7.36 + 0.51
0.01
Ln HA/ PIIANP
0.53 + 0.12
0.50 + 0.11
0.45 + 0.12
0.01
N=41
N=185
N=45
Ln PIIANP
7.04 + 0.52
7.11 + 0.49
7.36 + 0.51
0.01
Ln HA/ PIIANP
0.52 + 0.12
0.50 + 0.11
0.45 + 0.12
0.02
GOGO hand
criteria
(adjusted
for age)
Chen HC, Kraus VB et al, 2008; Osteo Cartilage:16,1054-9
Concepts of Linkage Study: Look for Chromosomal
Region Linked to Disease (Traits)
Cross over
(recombination) of
chromosomes in
prophase of Meiosis 1
Finding the OA Criminals
Earth
The USA
North Carolina
Duke University
Enemy of the
State (movie)
ACGTGTCGA
23 Chromosomes
1 chromosome
Locus
Gene
Sequence
PIIANP Genome-Wide Linkage Signal
Dr.
PIIANP
Dr. LOD
LOD= Log10 of the Odds
*Chen HC, *Kraus VB et al, Arthritis Rheum, 2010; 62:781-790
Genome-Wide Linkage Signals for 4 Highly
Heritable OA Biomarkers
HA
PIIANP
LOD = 4.3
Suggestive Linkage LOD >1.5
Significant Linkage
COMP
LOD = 3.2
C2C
*Chen HC, *Kraus VB et al, Arthritis Rheum, 2010; 62:781-790
References
• Harrison 17th Edition, pages 2149- 2165
• Kelley’s Textbook of Rheumatology, pages 1525-1577
• 2 Review papers for OA (Steven Abramson and JC Rousseau)
Closing though: Wisdom Quote from Albert
Einstein
Right Drug for the
Right Patient!
OA group
Disease Progressive
but drug useful
Disease Not Progressive
but drug useful
Disease Progressive
and drug Not useful
To Pts: less harmful!
To Drs: more fulfilled!
To Society: more
economical!
Disease Not Progressive
and drug Not useful
“Imagination is more important than knowledge.
For knowledge is limited to all we now know
and understand, while imagination embraces
the entire world, and all there ever will be to
know and understand.”