Targeted therapies in

Osteoarthritis.
By
Prof. Samir Elbadawy.
 OA in History
• While evidence of primary ankle osteoarthritis has been
discovered in dinosaurs, the first known traces of human
arthritis date back as far as 4500 BC.

• Evidence of arthritis has been found throughout history, as

from the mummy of an Egyptian lady (circa 3000 BC).
O.A burden
• WHO report indicates that knee OA is
– The 4th most important global cause of disability
in women
– The 8th most important global cause of disability
in men.

• Prevalence is projected to increase to 18.2% by 2020

due to aging population. (statistics from 2003)
That is why OA, is a major public health problem
throughout the world.

Deborah Symmons, Colin Mathers, Bruce Pfleger. Global burden of osteoarthritis in the year 2000.
ww.who.int/entity/healthinfo/statistics/bod_osteoarthritis.pdf
Lawrence, et al. 1998; Woolf, et al. 2003
 Epidemiology of OA

• 80% of people over 30 years, have radiographic

evidence of OA.

• Only 25-30% of those are symptomatic.

• Among the elderly, knee OA is the most common

cause of disability.

“Despite its prevalence, the precise

etiology, pathogenesis, and progression of
OA remain beyond our understanding…”
Deborah Symmons, Colin Mathers, Bruce Pfleger. Global burden of osteoarthritis in the year 2000.
ww.who.int/entity/healthinfo/statistics/bod_osteoarthritis.pdf
 Definition of OA
• The pathological definition is
of a condition characterized by
focal areas of loss of articular
cartilage within synovial joints,
associated with hypertrophy of
bone (osteophytes and
subchondral bone sclerosis)
and thickening of the capsule.

Exercise and osteoarthritis, D. J. Hunter and F. Eckstein. J. Anat. (2009) 214, pp197–207
 Risk factors for OA
Age
Obesity Gender

Occupation Bone injury

OA
Family history Joint injury
Genetics
Joint
Trauma
dysplasia

Solomon L. 1997
 Joint involvement in OA

Solomon L. Clinical features of osteoarthritis. Textbook Rheum 1997;2:1383–1393.

 Presentation overview

1- Biochemical changes in OA.

2- IL-1 in pathogenesis of OA.
3- Treatment of OA.
4- NSAID’s & Arthrofast in OA.
5-Disease Modifying OsteoArthritic
Drugs (DMAOD)- Osteocerin.
 Presentation overview

1- Biochemical changes in OA.

2- IL-1 in pathogenesis of OA.
3- Treatment of OA.
4- NSAID’s & Arthrofast in OA.
5-Disease Modifying OsteoArthritic
Drugs (DMAOD)- Osteocerin.
.
Imbalance between injury & repair in
O.A
 Presentation overview

1- Biochemical changes in OA.

2- IL-1 in pathogenesis of OA.
3- Treatment of OA.
4- NSAID’s & Arthrofast in OA.
5-Disease Modifying OsteoArthritic
Drugs (DMAOD)- Osteocerin.
WHAT ARE CYTOKINES?
Cytokines are peptides that have a
fundamental role in communication
within the immune system and in
allowing the immune system and host
tissues cells to exchange information.
They are small glycoprotein
messengers.
RA: IMPACT, PATHOGENESIS, AND TREATMENT

Cytokine disequilibrium

M A TO RY
TI- IN FLAM
AN
R
sTNF
M AT O RY IL-4 sIL-1R
NF L AM
PR O I IL-10 IL - 1R a
IL-8 TGF 
TN F IFN-
IL-1 L T
IL-6

Adapted from Feldmann M et al. Cell 85:307-310, 1996 and Moreland LW et al. Arthritis Rheum 40:397-409, 1997.
 Role of IL-1 in normal & OA joints

• In the normal joint, IL -1α controlled

cytokine activation mediates normal tissue
turnover and repair.

• However, in osteoarthritic joints, excessive

IL-1β production and activity can lead to
extracellular matrix degradation,
chondrocyte apoptosis, subchondral bone
remodeling, down-regulation of anabolic
pathways and inflammation in the joint.
Cytokines Mechanical Stress

Trauma
IL1, IL6
IL10, IL17 Obesity
TNF-α, IFN-γ Altered loading

Cellular COX Activation Cellular NOS2 Activation

PGE2 NO
O2
ONOO , NO2, etc.
-

Inflammation, Cartilage degradation

In knees with excessive ADAMTS5

Guilak: Clin Orthop, Vol 423. June 2004. 17-26

 IL-1 levels are increased in
osteoarthritic joint

• The levels of this cytokine are increased in the synovial fluids of OA

patients. 3-5

• It was demonstrated that a cytokine, now termed interleukin-1 (IL-1),

was playing a crucial role in OA physiopathology. 1,2

• Furthermore, it can be locally produced by both the synovial cells

and articular chondrocytes. 5

1. Dingle, J.T. (1981). Catabolin—a cartilage catabolic factor from synovium. Clin. Orthop. Relat. Res., 156, 219–231.
2. Pujol, J.P., and Loyau, G. (1987). Interleukin-1 and osteoarthritis. Life Sci., 41, 1187–1198.
3. Wood, D.D., Ihrie, E.J., Dinarello, C.A., and Cohen, P.L. (1983). Isolation of an interleukin-1 like factor from human joint effusions. Arthr. Rheum., 26, 975–
983.
4. Pelletier, J.P., andMartel-Pelletier, J. (1989). Evidence for the involvement of interleukin-1 in human osteoarthritic cartilage degradation: protective effect of
NSAID. J. Rheumatol., 16, 19–27.
5. Farahat, M.N., Yanni, G., Poston, R., and Panayi, G.S. (1993). Cytokine expression in synovial membranes of patients with rheumatoid arthritis and
ostoarthritis. Ann. Rheum. Dis., 52, 870–875.
Role of IL1 in pathogenesis of O.A

• It is known that in O.A joint there are raised levels of degradative

enzymes.

• Cartilage degradation is a multistep process based on the release of

matrix-degrading enzymes such as
• Aggrecanases (ADAMTS)
• Matrix metalloproteinase (MMPs) ,
• Collagenase
• Stromelysin

• with subsequent degradation of extra cellular matrix (ECM)

1.C. M. Davies et.al Reactive nitrogen and oxygen species in interleukin-1-mediated DNA damage associated with
osteoarthritis, Osteoarthritis and Cartilage (2008) 16, 624e630
2.Marc Fajardo et.al Disease-Modifying Therapies for Osteoarthritis Drugs Aging 2005; 22 (2): 141-161
3.Bruce et.al ,Interleukin- 1, immune activation pathways, and different mechanisms in osteoarthritis, Annals of
rheumatic diseases 1991;50:395-400
 IL-1 stimulate the release of degrading
enzymes

• An important activator of these enzymes Interleukin-1 has many

properties, such as stimulation of stromelysin, collagenase and
plasminogen activator secretion as well as direct bone resorbing
activities, that might account for many of these changes.

• Synovial fibroblasts start producing matrix-degrading enzymes

and invade cartilage when activated by cytokines such as tumour-
necrosis factor (TNF) and IL-1.

1. Martel-Pelletier, J., Zafarullah, M., Kodama, S., and Pelletier, J.P. (1991). In vitro effects of interleukin-1 on the synthesis of metalloproteases, TIMP,
plasminogen activators and inhibitors in human articular cartilage. J. Rheumatol., 18, 80–84.
2. Martel-Pelletier, J. (2004). Pathophysiology of osteoarthritis. Osteoarthr. Cart., 12 Suppl A, S31–S33.
3. Pasternak, R.D., Hubbs, S.J., Caccese, RG, Marks, R.L, Conaty, J.M., and DiPasquale, G. (1986). Interleukin-1 stimulates the secretion of proteoglycan- and
collagen-degrading proteases by rabbit articular chondrocytes. Clin. Immunol. Immunopathol., 41, 351–367.
4. Bocquet, J., Daireaux, M., Langris, M., Jouis, V., Pujol, J.P., B´eliard, R., and Loyau,G. (1986). Effect of a interleukin-1 like factor (mononuclear cell
5. factor) on proteoglycan synthesis in cultured human articular chondrocytes. Biochem. Biophys. Res. Commun., 134, 539–549.
6. Goldring, M.B., Birkead, J., Kimura, T., and Krane, S.M. (1988). Interleukin-1 suppresses expression of cartilage-specific types II and IX collagens and
increases types I and III collagens in human chondrocytes. J. Clin. Invest., 82, 2026–2037.
7. Lefebvre, V., Peeters-Joris, C., and Vaes, G. (1990). Modulation by interleukin-1 and tumor necrosis factor alpha of production of collagenase, tissue
inhibitor of metalloproteinases and collagen types in differentiated and dedifferentiated articular chondrocytes. Biochim. Biophys. Acta, 1052, 366–378.

Nature Reviews Immunology 7, 429-442 (June 2007)

 IL-1 Interferes with the Matrix synthesis
enzymes as follows

• Up-regulation of proinflammatory mediators like

– Nitric oxide (NO)
– Inducible NO synthase (iNOS)
– Plasminogen activator secretion
– Matrix degrading enzymes
• Matrix metalloproteinase-1 (MMP-1)
• Aggrecanases (ADAMTS)
• Collagenase & stromelysin

• Down-regulation of
– Matrix proteins like proteoglycans
– Inhibiting enzymes like tissue inhibitors of metalloprotinases
(TIMP)

Am J Physiol Cell Physiol 290:1610-1615, 2006

 Role of IL1 in Matrix degradation
and cartilage degeneration

• IL-1 is implicated in the degeneration of cartilage due to its induction

of proteoglycan loss and matrix degradation

• Elevated levels of IL-1 occur in the synovial fluid and cartilage tissue
of patients with OA compared to healthy individuals implying a role
in disease pathogenesis.

• OA cartilage had significantly more DNA damage than non-OA

cartilage , IL-1 caused an increase in DNA damage which was
associated with increased NO production.

1.C. M. Davies et.al Reactive nitrogen and oxygen species in interleukin-1-mediated DNA damage associated with
osteoarthritis, Osteoarthritis and Cartilage (2008) 16, 624e630
2.Marc Fajardo et.al Disease-Modifying Therapies for Osteoarthritis Drugs Aging 2005; 22 (2): 141-161
3. Bruce et.al ,Interleukin- 1, immune activation pathways, and different mechanisms in osteoarthritis, Annals of rheumatic
diseases 1991;50:395-400
 IL-1 Role in Cartilage Damage
• IL 1 induce a switch in the synthesis pattern of chondrocytes
from matrix molecules to matrix-degrading enzymes.

• The cytokine inhibits also the synthesis of enzyme inhibitors, the

TIMPs (tissue inhibitors of metalloproteinases).

• Chondrocyte death is another feature of cartilage damage, it

leads to the formation of empty lacunae and deprives cartilage
from the ability to replenish matrix.

1. Martel-Pelletier, J., Zafarullah, M., Kodama, S., and Pelletier, J.P. (1991). In vitro effects of interleukin-1 on the synthesis of metalloproteases, TIMP, plasminogen
activators and inhibitors in human articular cartilage. J. Rheumatol., 18, 80–84.
2. Martel-Pelletier, J. (2004). Pathophysiology of osteoarthritis. Osteoarthr. Cart., 12 Suppl A, S31–S33.
3. Pasternak, R.D., Hubbs, S.J., Caccese, RG, Marks, R.L, Conaty, J.M., and DiPasquale, G. (1986). Interleukin-1 stimulates the secretion of proteoglycan- and collagen-
degrading proteases by rabbit articular chondrocytes. Clin. Immunol. Immunopathol., 41, 351–367.
4. Bocquet, J., Daireaux, M., Langris, M., Jouis, V., Pujol, J.P., B´eliard, R., and Loyau,G. (1986). Effect of a interleukin-1 like factor (mononuclear cell
5. factor) on proteoglycan synthesis in cultured human articular chondrocytes. Biochem. Biophys. Res. Commun., 134, 539–549.
6. Goldring, M.B., Birkead, J., Kimura, T., and Krane, S.M. (1988). Interleukin-1 suppresses expression of cartilage-specific types II and IX collagens and increases types
I and III collagens in human chondrocytes. J. Clin. Invest., 82, 2026–2037.
7. Lefebvre, V., Peeters-Joris, C., and Vaes, G. (1990). Modulation by interleukin-1 and tumor necrosis factor alpha of production of collagenase, tissue inhibitor of
metalloproteinases and collagen types in differentiated and dedifferentiated articular chondrocytes. Biochim. Biophys. Acta, 1052, 366–378.
Role of IL-1β in Cartilage Destruction

• The cytokine IL-1 plays a crucial role in triggering the

cascade of events leading to cartilage breakdown and
joint inflammation.

• Modulation of the production and/or physiological

effects of this cytokine by pharmacological agents is
beneficial in the treatment of OA.

• Blocking IL-1 or its activity has been shown to be very

effective in preventing cartilage destruction.

1- Pelletier JP, Mineau F, Ranger P,Tardiff G, Martel-Pelletier J.The increased synthesis of inducible nitric oxide inhibits IL-1ra synthesis by human articular
chondrocytes: possible role in osteoarthritic cartilage degradation. Osteo Cart 1996; 4(1): 77–84.
2- van de Loo FA, Joosten LA, van Lent PL, Arntz OJ, van den Berg WB. Role of interleukin-1, tumour necrosis factor alpha, and interleukin-6 in cartilage proteoglycan
metabolism and destruction: effect of in situ blocking in murine antigen- and zymosan-induced arthritis. Arthritis Rheum 1995; 38(2): 164–72.
 Role of IL-1β in OA

1. Cartilage degradation

2. Inflammation in the synovial membrane

3. Chondrocyte and synoviocyte apoptosis

4. Subchondral bone changes

5. Stimulation of further IL-1 production

 Presentation overview

1- Biochemical changes in OA.

2- IL-1 in pathogenesis of OA.
3- Treatment of OA.
4- NSAID’s & Arthrofast in OA.
5-Disease Modifying OsteoArthritic
Drugs (DMAOD)- Osteocerin.
Goals of The Treatment

• Relief pain, swelling and inflammation.

• Inhibit joint degeneration.

• Improve quality of life.

Osteoarthritis and Cartilage (2008) 16, 624e630

 Non- pharmacological
treatments
1- Self management, education and
information.
2- Exercises.
3- Weight reduction.
4- Acupuncture.
5- Electromagnetic therapy.
Pharmacological treatments
1- Acetaminophen (paracetamol).
2- Non-steroidal anti-inflammatory
drugs (NSAID’s).
3- Topical NSAID’s.
4- Opioids.
5- Intra-articular (IA) corticosteroids.
6- IA hyaluronic acid (IAHA).
7- Glucosamine.
8- Chondritin sulphate (CS).
9- Avocado soyabean unsaponifables
(ASU).
10- Vitamin E.
11- Other nutritional supplements.
12- Other herbal remedies.
13- Diacerhin.
14- Anti-resorptive bone acting agents.
 Surgical treatments
1- Lavage / debridement.
2- Other surgical therapies.
= Correction osteotomy.
= High tibial osteotomy (HTO).
= Unicompartmental knee
arthroplasty (UKA).
= Total knee arthroplasty (TKA).
 Presentation overview

1- Biochemical changes in OA.

2- IL-1 in pathogenesis of OA.
3- Treatment of OA.
4- NSAID’s & Arthrofast in OA.
5-Disease Modifying OsteoArthritic
Drugs (DMAOD)- Osteocerin.
 Treatment of Osteoarthritis
Pharmacological approaches

Osteoarthritis therapy has evolved in the

past few decades from symptomatic
treatment to possible disease-modifying
solutions
 Analgesics

• Clinical Benefits
– Reducing pain

• Limitations
– Does not interfere with the disease pathogenesis
– No anti inflammatory effect

Rashad S, Revell P, Hemingway A, Low F, Rainsford K, Walker F. Effect of non-steroidal

anti-inflammatory drugs on the course of osteoarthritis. Lancet 1989; 2(8662): 519–22.
 NSAIDS
• Clinical Benefits
– Reducing pain and inflammation

• Limitations
– Limitation for long term use due to
safety issues
_ Does not interfere with the
pathogenesis of the disease and
thus has no impact on slowing
disease progression

Rashad S, Revell P, Hemingway A, Low F, Rainsford K, Walker F. Effect of non-steroidal

anti-inflammatory drugs on the course of osteoarthritis. Lancet 1989; 2(8662): 519–22.
 Strong evidences among different guidelines for the use
of NSAIDs in management of arthritis

George Nuki, MB, FRCP Queen’s Medical Research Institute, University of Edinburgh,
UK Chair of the OARSI Guidelines Committee, Dec 2007
 Full dose of diclofenac is recommended for
management of inflammation of arthritis

Nazli Conway et al ,Diagnosis&Management of acute gout, Medicine&Health, vol.92,

no 11, novemb. 2009
 What is Arthrofast

• Arthrofast is 150mg Diclofenac sodium in a

modified release formulation

• Arthrofast is the optimal once daily modified

release NSAID that provides fast & lasting
pain relief for patients suffering from flare-ups
of both arthritis & spondylosis through it’s
bilayer technology
Arthrofast unique technology provides
Immediate release within 15 minutes
Sustained effective concentration for 24 hours

Mean + s.d. diclofenac plasma concentrations measured after single oral administration of
150 mg diclofenac as one new slow-release tablet
Arthrofast Provides 76% reduction of
arthritis inflammation

Assessed by symptoms regression on 4 point scale

(where 0 = nil and 3 = severe)
R. Bakshi, S.P.Sane,et al. Current therapeutic research 1989 October; 46(4): 709-716
Overall safety profile
More than 92% overall safety as rated by patients & physicians

Arthrofast GIT tolerability is comparable to that of

diclofenac
sodium enteric coated tablets 3 times daily

*Over all safety evaluation as rated by patients and physicians as very good-fair
Novartis data on file
 Presentation overview

1- Biochemical changes in OA.

2- IL-1 in pathogenesis of OA.
3- Treatment of OA.
4- NSAID’s & Arthrofast in OA.
5-Disease Modifying OsteoArthritic
Drugs (DMAOD)- Osteocerin.
Osteocerein a Novel
Target
Treatment
 Chemistry of Osteocerein
• Osteocerein is the acetylated form of rhein and is obtained from
rhein by esterification (Di-Acetyl Rhein).
• This process increases the lipophilicity of the molecule, which
increases absorption by the intestinal mucosa.
• It works by inhibiting the production and activity of
IL-1, a novel mode of action that differentiates it
from NSAIDs and other drugs used in OA.

• Based on World Health Organization (WHO)

guidelines, Osteocerein is classified as a slow-
acting drug in osteoarthritis as its beneficial effects
become apparent 2–4 weeks after the start of
treatment, with clinically relevant differences from
placebo after 4–6 weeks.
• Osteocerein is well absorbed following oral
dosing. Once absorbed, it is rapidly broken
down and completely de-acetylated into its
active metabolite, Rhein (extracted from
Rhubarb), which is distributed to all tissues.

• Peak plasma concentration of rhein was

reached 15–30 minutes after dosing.

• Binding of rhein to plasma proteins is >99%

• Rhein is eliminated mainly by the kidneys

• Dose adjustment is not normally required in patients with

mild-to-moderate renal or hepatic impairment

• In severe renal damage, ( creatinine clearance <30

ml/min) dose adjustments are recommended

• When Osteocerein is taken with food, there is an

increase (about 24%) in its absorption. Thus, it is
recommended that Osteocerein be taken with meals.
 MOA of
1- Anti-Catabolic Effects
• Osteocerein has a unique mode of action that distinguishes it from
other drugs used in OA.

• The effects of Osteocerein are primarily due to potent inhibition of

the production and activity of IL-1 and other catabolic cytokines
(NO,MMPs as stromelysin) expressed in OA.

• This in turn prevents cytokine-induced connective tissue destruction

and inhibition of cartilage repair.

• The effects of Osteocerein on IL-1 concentration and activity occur at

the cell membrane (pre-membrane effects) and also within the cell
(post-membrane effects).
 MOA of
2- Anti-Inflammatory Effects

Effect of Osteocereinon the inflammatory cascade

Summary of MOA
 Study Design

• 9 months treatment by standard therapy

(selection of physiotherapy and/or NSAIDs
and/or analgesics and/or Neutraceuticals)

• Other arm, Osteocerein was added on

standard therapy for 6 months , followed by 3
months of follow up period.

Standard O.A therapy in Osteocerein arm= NSAIDs+other analgesics+ physiotherapy +Osteocerein

O.A therapy in other arm=NSAIDs+other analgesics + physiotherapy any other O.A drug except Osteocerein
Delaying OA Progression by 32 %
Improves Function by 83% , with 3
Months of Carryover
Enhances Pain Relief by 69% when used with
NSAIDs, with 3 Months of Carryover
 Results
• Adding Osteocerein to standard OA regimens

–Significantly decreased NSAIDs and analgesic

consumption

–Improved function by 83 % as per Lequesne’s

functional index

–Enhanced pain control by 69% when given with

NSAIDs

Francis Fagnani et.al ,Medico-Economic Analysis, Pharmacoeconomics 1998 Jan; 13 (1 Pt 2): 135-146
Components of Multimodal Osteoarthritis Treatment

Surgery

Intra-articular Injection
Hyaluronic acids
Corticosteroids
Pharmacological Therapy
NSAIDs Topical
DMAs

Non-pharmacological Therapy
Education Physical therapy Exercise
Occupational therapy Weight Control Assistive
devices Nutraceuticals

Osteoarthritis and Cartilage (2008) 16, 624e630

 CONCLUSIONS.
• OSTEOCEREIN is a novel target treatment for OA
with a different MOA than other drugs.
• OSTEOCERE is a Disease Modifying OsteoArthritis
Drug (DMOAD) that slows disease progression by
32%.
• OSTEOCEREIN’s inhibition of IL-1 and other
inflammatory mediators related to it  it is neither
similar to NSAIDs nor Neutraceuticals.
• Adding to current treatments will improve function
and decrease pain with a carryover effect of 3
months.
What is Arthritis?
• Arthritis-related joint problems include:
– Pain, stiffness, inflammation and damage to
the joint .
• Such damage can lead to joint weakness,
instability and visible deformities that can
interfere with the most basic daily activities.
– In some forms of arthritis ,Systemic
involvement , might affect the whole body e.g
heart, lungs, kidneys, blood vessels and skin.

Adapted from The Arthritis Foundation's Guide to Good Living with Rheumatoid
Arthritis.2010
Definition of Arthritis flare ups
• Some forms of arthritis go through
cycles of getting better and worse.
• A flare-up means the disease is more
active.
– increased morning stiffness
– more pain and swelling in the joints
– involvement of other joint
– increased tiredness and fatigue.
M. Marty et al. / Joint Bone Spine 76 (2009) 268e272
 Symptoms of Flare-ups
• Symptom intensity varies over time, and patients
experience intermittent flare-ups during which the
pain and functional impairment worsen. 1
• The pathological concomitant of osteoarthritis flare-
ups is the development of inflammatory lesions
within the synovial membrane. 2

• The pain becomes more severe and responds less to

rest, tending to become continuous. 2

• A joint effusion and warmth may be noted. 2

1.Dieppe PA. et al. J Rheumatol 2004;70(31 Suppl.):50e3.

2. Spector T, Hart DJ, Nandra D, et al. Arthritis Rheum 1997;40:723e7.
 PGs & OA

• A major role of PGE2 in the

pathogenesis of OA is supported by in
vitro data :

– Chondrocytes isolated from patients

with OA produce 50-fold more PGE2
than chondrocytes from patients
without OA.
CLEVELAND CLINIC JOURNAL OF MEDICINE, VOLUME 69 , SUPPLEMENT, SI-6
PGs & OA
• High concentrations of prostaglandins
can:

– Inhibit collagen synthesis

– Enhance the inhibitory effects of
interleukin 1 (IL-1) on collagen
transcription

CLEVELAND CLINIC JOURNAL OF MEDICINE, VOLUME 69 , SUPPLEMENT, SI-6

 A Multifactorial Disease
O.A is a Combination of predisposing factors & joint
biomechanics which triggers biochemical Changes.
1
2

3
.

Adapted from The Lancet, Vol 365, Dieppe PA, Lohmander S. Pathogenesis and management of
pain in osteoarthritis, Pages 965-973, Copyright 2005, with permission from Elsevier
 MOA of
3- Pro-Anabolic Effects

TGF-β Collagen II and HA

production Proteoglycan synthesis synthesis

Stimulation of Matrix Restore the Synovial

Chondrocytes proliferation Components Fluid properties
Components of Multimodal OA Treatment

Surgery
(osteotomy, TKR)

Opioid Analgesics

Intra Articular Injections

(corticosteroids & hyaluronic
acid)
Pharmacologic Therapy
Acetaminophen
NSAIDS / COX2
Adjunctive analgesics
Topical agents / Nutritional supplements
DMOADs

Non Pharmacological
Education/ Exercise / Weight control / Physical therapy /
Occupational therapy / Assistive devices
Osteoarthritis pathogenesis
(Biochemical)
• OA results from an imbalance in catabolic and anabolic
processes that lead to progressive cartilage damage and
destruction.

• Initially anabolic process such as proteoglycan synthesis

maintain balance with catabolic processes and damage to
cartilage is repaired. However with time and age ,anabolic
processes decline and progressive damage ensues.

Osteoarthritis and Cartilage (2008) 16, 624e630

Role of IL-1 In
Osteoarthritis
pathogenesis