Defining Arthritis

ARTH
(Joint)

IT IS =
(Inflammation)

INFLAMMATION OF THE JOINTS

Arthritis is an umbrella term for over

100 types of rheumatic diseases

Osteoarthritis

Rheumatoid Arthritis

Ankylosing Spondylitis
Fibromyalgia
Lupus
Gout
Bursitis
Juvenile Rheumatoid Arthritis
Osteogenesis Imperfecta
Myositis
Scleroderma
Lyme Disease
Carpel Tunnel
Psioriatic Arthritis

Two Most Common Types

Osteoarthritis

Rheumatoid Arthritis

OSTEOARTHRITIS

Definisi

Merupakan suatu penyakit ditandai dengan

hilangnya keseimbangan normal proses sintesis
dan degradasi makromolekuler yang dibutuhkan
dalam menjaga fungsi dan kemampuan
biomekanikal rawan sendi artikuler.

Merupakan peny sendi degeneratif yang

berkaitan dengan kerusakan kartilago sendi.

Osteoarthritis

Typically affects people over the age of 50

A biologic process which effects cartilage with
subsequent inflammatory component
Characteristically the major component of the
clinical presentation is pain and decreased
function

>75% of people over the age of 75 have x-ray

evidence of disease
> 75% of people over the age of 85 are
symptomatic

Probably affects 16-20,000,000 Americans

Osteoarthritis

Normal Joint

Joint with
Osteoarthritis

Risk Factors

Genetics

Abnormal components of the joint as an organ

Abnormal range of motion
Congenital anomalies

Trauma
Overuse syndromes
Post-infectious
Obesity

Etiology of Osteoarthritis

Disease of the synovial joints

Primary changes of OA begin in the cartilage
Most pronounced in load bearing areas of articular
cartilage
Fibrocartilaginous repair is inferior to original
hyaline cartilage
Other tissues affected include: subchondral bone,
synovium, meniscus, ligaments, muscle

Etiology of Osteoarthritis

Articular cartilage is composed of:

Proteoglycans

Provide compressive stiffness and ability to withstand

load

Collagen

Provides tensile strength and resistance to shear

Etiology of osteoarthritis

Articular cartilage (1-2 mm thick)

Provides a smooth bearing surface

With synovial fluid as a lubricant, the coefficient of

friction for cartilage on cartilage is 15X lower than
rubbing 2 ice cubes together

Prevents the concentration of forces when bones are

loaded

Etiology of Osteoarthritis

Growth of cartilage and bone at the joint

margins leads to osteophytes which can restrict
movement
Chronic synovitis and thickening of the joint
capsule further restrict movement
Periarticular muscle wasting is common and
plays a major role in sx and disability

Conceptual Model of OA
Biochemical changes/ cells and tissue
Structural changes

Pain and other signs and symptoms

Functional limitation

Reduced quality of life

Surgical replacement

Classification of OA

Primary (idiopathic)
unidentified causes

Secondary
precipitating factors

16

Joints affected by OA

Knees (41%)
Hands (30%)
Hips (19%)
Spine (cervical and
lumbar regions)
Toes (first metatarsophalangeal joint)

17

Clinical signs of OA

Crepitus
Restricted joint
movement
Joint instability
Bony swelling
Soft tissue swelling
Joint deformity

Joint tenderness
Increased joint warmth
Muscle atrophy or
weakness
Limp while walking

18

Sources of OA joint pain

Subchondral bone
Nerve endings in periosteum
Stretching of ligaments
Distention of joint capsule
Inflammation of synovium
Periarticular muscle spasm
19

Pain drawings
Mark the area on your body
where you feel the described
sensations
Use the appropriate symbol
Mark the areas of radiation
Include all affected areas
Numbness
====
Pins and needles

Burning
xxxxxxxx
Stabbing
///////

Rating scales
Visual analogue scale

Worst
possible
pain

No
pain

Pain intensity
0
1
2
3
4
5

No pain
Mild
Discomforting
Distressing
Horrible
Excruciating

Clinical Approach to Knee Pain

Valgus Test (MCL)

Varus Test (LCL)

McMurray Maneuver
(menisci)

Lachman Test (ACL)

Duck Waddle
(stability)

Diagnosis of OA

Symptoms
Pain
Decreased function

Due to boney change

Due to soft-tissue change or swelling
Due to alteration of the normal structures

Crepitance or crunching within the joint

Diagnosis of OA

Signs

On physical exam
Asymmetry of findings usually of large joints
Heberdens/Bouchards nodes (may be
symmetrical)

Classic hand involvement: DIP/PIP nodular disease

Some boney swelling

Some swelling and pain out of proportion to
inflammatory findings

Typical OA Hand:
Know It When You See It

Hard boney
enlargements
Heberdens nodes at
the DIP joints
Bouchards nodes at
the PIP joints
Often have squared
first CMC joint due to
osteophytes at that
joint

Diagnosis of Knee OA
Classic Clinical Criteria

established by ACR, 1981

sensitivity 95%, specificity 69%

knee pain plus at least 3 of 6 characteristics:

> 50 yo
Morning stiffness < 30 min
Crepitus
Bony tenderness
Bony enlargement
No palpable warmth 5

Diagnosis of Knee OA
Classification Tree

Clinical symptoms

Synovial fluid
1.
2.
3.

WBC<2000/mm3
Clear color
High Viscosity

No OA

X-rays
1.
2.
3.
4.

Osteophytes
Loss of joint space
Subchondral sclerosis
Subchondral cysts

Confirmed by arthroscopy
(gold standard) 6

Sensitivity 94 %;
Specificity 88 %

Diagnosis of Knee OA

Diagnosis of OA

By imaging

X-ray

Presence of osteophytes (biologic evidence of an attempt to

repair?)
Progressive joint space narrowing which is a surrogate
measure of cartilage thinning

Now known not to be linear and some patients are rapid

progressors while others are slow progressors or somewhere in
between; how to predict which patient falls into which category

Increased sclerotic change in subchondral bone

When significantly progressive might reflect eburnation

OA Hip:

OA Hip: 1997, bilateral, joint space narrowing

(arrows) at the hips that is worse on the left side

Osteoarthritis:
Narrow joint space
Lipping osteophyte
Dislocation
Osteoporosis.

Radiographic Features of the

Knee in OA

Joint space
narrowing
Marginal
osteophytes
Subchondral cysts
Boney sclerosis
Malalignment

Joint space
narrowing

Osteoarthritis: Ankylosis

varus deformity of the

knee and collapse of the
joint space with
destruction of the medial
cartilage and the
subchondral cortex (open
arrowheads).

Osteoarthritis:

Lateral view of the left

knee shows sclerosis
with marked osteophyte
formation (arrows). The
osteophytes are best seen
in this view.

Osteoarthritis:

Subchondral cysts
(solid arrowhead)

OA Fingers:

Diagnosis of OA

Imaging

MRI
Newer technique
Able to provide a 3 D image of the joint as an
organ

Can approximate the volume of cartilage

May be able to identify early change in cartilage
metabolism
Can approximate early bone change (bone edema?)

Laboratory findings in OA

THERE ARE NO DIAGNOSTIC LAB

TESTS FOR OSTEOARTHRITIS
OA is not a systemic disease, therefore:

ESR, Chem 7, CBC, and UA all WNL

Synovial fluid
Mild leukocytosis (<2000 WBC/microliter)
Can be used to exclude gout, CPPD, or septic arthritis if
diagnosis is in doubt

Management: Algorithm
Lifestyle Modifications

NSAIDs PRN

Steroid Injections

Acetaminophen PRN

Celecoxib

Opioids PRN

Hyaluronan Injections

Surgical Referral

Management: Lifestyle

Weight loss

Exercise Program

PT referral
Quadriceps strengthening
ROM exercises
Low impact activities e.g. swimming, biking 7

Ambulatory assist devices

Nutrition referral

Cane
Walker

Insoles
Unloader knee braces

Weight reduction

Increased odds ratio

for knee OA =
1.4 per 10 lb increase
in body weight

44

Thermal modalities

Heat
Relaxes muscles
Stimulates blood flow

Cold
Eases muscle spasms
Blocks pain signals

45

Management: Lifestyle
Varus (bowlegged) vs Valgus (knock-kneed)

G2 Unloader Brace

Exercise

Range of motion

Muscle strengthening

Aerobics

49

Patient education

1-800-283-7800

Education can
improve arthritis
symptoms 15% to
30%
Can last up to 2 years
following intervention

http://www.arthritis.org
50

Management: Medical

Glucosamine/Chondroitin
Acetaminophen
NSAIDs
Cox-2 inhibitors
Opioids
Intraarticular injections

Glucocorticoids
Hyaluronans

Natural Products for Osteoarthritis

Glucosamine sulfate
Most useful, best clinical documentation, and cost effective
Long-term studies now document significant clinical benefit
Meta-analysis shows structural and symptomatic efficacy of
glucosamine and chondroitin in knee osteoarthritis Arch Intern
Med. 2003;163:1515-22
Chondroitin sulfate
Clinical effectiveness documented in 9 double-blind clinical
trials
Controversies remain over quality control issues and
mechanism of action
MSM
Sulfur critically important to cartilage formation, structure and
integrity
MSM + Glucosamine more effective than Glucosamine alone
Clinical Drug Investigation, 2004;24:353-363.

Management: Medical

Glucosamine/Chondroitin

1500 mg/1200 mg daily ($40-50/month)

Glucosamine: building block for glycosaminoglycans
Chondroitin: glycosaminoglycan in articular cartilage
GAIT study, NEJM, Feb 23, 2006

Multicenter, double blind, placebo-controlled, 24 wks, N=1583

Symptomatic mild or moderate-severe knee OA
Infrequent mild side effects e.g. bloating
For mild OA, not better than placebo
For moderate-severe OA, combination showed benefit 8

Patient satisfaction

CHONDROITIN SULFATE ACTION MECHANISMS3-4

STIMULATES:

proteoglycans
HA
EFFECT:
-anti-inflammatory
activity
-Membrane
stabilising action

INHIBITS:
cartilage degradative enzymes
(collagenase,elastase,
proteoglycanase, fosfolipase A2,
N-acetylglucosaminidase, etc.)
cartilage damaging
substances (free radicals)
apoptosis
NO
Stromelysin (MMP-3)
NF-kB

(3) Ronca F et.al. Osteoarthritis Cart (1998) 6, (Supplement A), 14-21. (4) Blanco FJ. et. al. Rev. Esp.
Reumatol 2001; 28, 1: 12-17.

Management: Medical

Acetaminophen

Indication: mild-moderate pain

1000 mg Q6h PRN
Better than placebo but less efficacious than NSAIDs 9
Caution in advanced hepatic disease

NSAIDs

Indication: moderate-severe pain, failed acetaminophen

GI/renal/hepatic toxicity, fluid retention
If risk of GIB, use anti-ulcer agents concurrently
Agents have highly variable efficacy and toxicity

Management: Medical

Cox-2 inhibitors

Indication: mod-severe pain, failed NSAID, risk of GIB

OA pain relief similar to NSAIDs
Fewer GI events e.g. symptomatic ulcers, GIB
Celecoxib 200 mg daily
GI/renal toxicity, fluid retention
Increased risk of CV events?

APC Trial: 700 pts each assigned to placebo, 200 BID, 400 BID
Increased risk at higher doses 11
CLASS Trial: 8,000 pts compared Celecoxib vs Ibuprofen
Similar risk to Ibuprofen 12

Cyclooxygenase (COX)
Two isoenzymes
Cyclooxygenase-1 (COX 1): constitutive
- physiologic production of PG in gastric mucosa,

endothelium, platelet, kidney

Cyclooxygenase-2 (COX 2): inducible
- induced by mitogen, cytokine, endotoxin
- promotes synthesis of pro-inflammatory prostaglandins

Cox-1 vs. Cox-2

What the drug companies wanted us to believe.
Arachidonic acid
COX-1
Constitutive

Good Prostaglandins

GI cytoprotection
Platelet activity
Renal function

COX-2
Inducible

Bad Prostaglandins

Inflammation
Pain
Fever

Cox-1 vs. Cox-2

The reality.
Arachidonic acid
COX-1
Constitutive

Prostaglandins

COX-2
Inducible

Prostaglandins
Pathological

GI cytoprotection
Platelet activity
Renal function

Inflammation
Pain
Fever

Physiological

Renal function
Vascular
Tissue repair

Management: Medical

Opioid Analgesics

Indication:
Moderate-severe pain
Acute exacerbations
NSAIDs/Cox-2 inhibitors failed or contraindicated
Oxycodone synergistic w/ NSAIDs 13
Tramadol/acetaminophen vs codeine/acetaminophen
Similar pain relief 14
Avoid long-term use

Caution in elderly
Confusion, sedation, constipation

Opioids

For moderately severe to

severe pain, opioids can be
used
Tylenol + codeine (T-3)
Tramadol

63

Capsaicin topical cream

Capsaicin derived from

pepper plants
Induces depletion of
substance P involved in
transmitting pain

64

Management: Medical
Intraarticular Injections
Technique

22 gauge 1.5 inch needle

Approach accuracy:

Lateral mid-patellar 93% 18

Patient supine
Leg straight
Manipulate patella
Angle needle slightly posteriorly
Inject after drop in resistance or fluid aspirated

Management: Surgical
When to Refer

Knee pain or functional status

has failed to improve with
non-operative management

Types of Procedures

Arthroscopic Irrigation
Arthroscopic Debridement
High Tibial Osteotomy
Partial Knee Arthroplasty
Total Knee Arthroplasty

Management: Surgical
High Tibial Osteotomy

Indication:

Unicompartmental arthritis
Genu varus or valgus

Realign mechanical axis

Age < 60yo

< 15 degrees deformity19

Management: Surgical
Partial Knee Arthroplasty

Indication:

Unicompartmental arthritis

Ligaments spared

Increased ROM

Faster recovery

Prosthesis 10-yr survival: 84% 20

Arthroplasty

Management: Surgical
Total Knee Arthroplasty

Indication:

Diffuse arthritis
Severe pain
Functional impairment

Pain relief > functional gain

ACL sacrificed
PCL also may be sacrificed
Prosthesis 10-yr survival: 90%

Management option Symptomatic

slow-acting drugs of OA

Symptomatic slow-acting drugs of OA (SYSADOA)

glucosamine
chondroitin
hyaluronic acid

Supported by increasing evidence, although further

research is still required
Given that these agents appear to be well tolerated and
do show some benefit their use should be considered13

Management option 10
Surgery

Refer for orthopaedic evaluation if patient is

disabled by OA or in pain unrelieved by medical
management
Joint replacement can be very effective
Newer techniques such as metal-on-metal
resurfacing are less invasive
Patients should be made aware of the risks and
benefits of surgery

Thank you

Human Cell Membrane

Fatty Acid Metabolism

Omega 6 Fatty Acids Omega 3 Fatty Acids
Most salad oils

Evening primrose oil

LA

ALA

d6d

d6d

GLA

Meat

SDA

el

Mother's milk

DGLA

Flax seed oil

Black currant oil

el
d5d

AA

EPA

cyc

cyc

lip

cyc

PGE1

PGE2

LEUK

PGE3

Fish

Cell Membrane Phospholipids

Phospholipase A2

Arachidonic Acid
Cyclooxygenase

COX -1 - constitutively
expressed
COX -2 - inducible

Prostaglandin H2

Thromboxane A2

TXA2
synthase
isomerase

PGI2
synthase

Prostacyclin (PGI2)

reductase

Prostaglandin D2

Prostaglandin F2
Prostaglandin E2

Metabolic Pathways of
Arachadonic Acid
Membrane Phospholipids

Non-Enzymatic
Lipid Peroxidation
Catalyzed by Free
Radicals

ARACHIDONIC ACID

12-Lipoxygenase

COX

12-HETE, 12-HPETE
- promotes inflammation and
allergic signs/symptoms

Isoprostanes
- Amplifies platelet response
to other agonists.
- Vasoconstrictor
- Plasma levels 1-2 orders
of magnitude > COX
-derived metabolites.

Prostaglandin H2

Thromboxane A2

Prostacyclin

- Platelet Aggregation
- Vasoconstriction

- Platelet Aggregation
- Vasodilation

Thromboxane A2 vs. Prostacyclin

ARACHIDONIC ACID
COX -1

Platelet
TXA2

Vasoconstriction
Platelet Aggregation

COX -2

Endothelial PGI2
(Prostacyclin)

Vasodilation
Anti-Platelet Aggregation

Why do Cox-2 inhibitors increase risk for heart disease?

#1. Because they adversely effect the ratio of thromboxane to prostacyclin

Aspirin
COX-1

COX-2 inhibitors

Prostacyclin Thromboxane

Thromboxane

Decreased
CV events

COX-2

Prostacyclin

Increased
CV events

BIOLOGIC MARKERS

HRQOL / UTILITY

INFLAMMATION

PAIN
PHYSICAL
FUNCTION
PATIENT GLOBAL
IMAGING (1YR)
90%

STIFFNESS
36%

MD GLOBAL
OTHER Eg, Performance based
Flares
Time to Surgery
Analgesic Count

8%

Anti-Inflammatories