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NAMA :Prof.DR.dr.Harry Isbagio,SpPD K-R,K-GER,FINASIM

TEMPAT/TGL.LAHIR :Magelang, 24 Desember 1948

JABATAN :Guru Besar Divisi Reumatologi Dep. Ilmu Penyakit DalamFKUI/RSUPN Ciptomangunkusumo Jakarta

PENDIDIKAN :

Tamat Dokter 1972 FKUIBrevet Spesialis Penyakit Dalam 1979 FKUIBrevet Subspesialis Reumatologi 1986 FKUIBrevet Subspesialis Geriatri 1996 FKUIDoktor 2004 FKUIGuru Besar 2005 FKUI

ORGANISASI :Ketua Umum, Ikatan Reumatologi Indonesia, 1994 2005President , Rheumatology Association of ASEAN 20012006Ketua Bidang Sp Konsultan, Kolegium Ilmu Penyakit Dalam(KIPD), 2006- 2012

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The Role Diacerein in the

Management of Osteoathrosis

Harry Isbagio

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Pathogenesis of OA

Wear and tear ? It is not necessarily age related

It is asymmetrically distribution/ localized

It is progress steadily

The sign & symptoms of inflammation

Role of inflammation in OA, what is theevidence ?

What are inflammatory factors that couldpossibly be involved in genesis of OAstructural changes?

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Osteoarthritis chondrocyte

Increase functions

Type II collagen and aggrecan synthesis (early OA)

Cell proliferation

Catabolic cytokine production

MMPs, TPA/plasmin

IL-I receptor type 1, NOS/NO, Cox-2/PGE2

Apoptosis,

Decrease functions Type II collagen and aggrecan synthesis (late OA)

IL-1 receptor antagonist

Response to IGF-1

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Chondrocyte metabolism

CatabolismAnabolism

Chondrocyte

Stimulation

IGFs, TGF-beta, PDGF, EGFBone morphogenic protein

Cartilage derived morphogenicprotein

Growth factor

Stimulation

Gamma- Interferon

TNF-alpha

Prostaglandins

Oxygen radicals, NO

IL-1, TNF-alpha, IL-17, FGFs,gamma interferon

Leukemia inhibitory factor

Glucocorticoid

Pro-collagen fragments

Inhibition

TIMP, Plasminogen activatorinhibitor

Calicrein

Inhibition

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Chondrocytes Pro-MMPs Active-MMPs

Extra-cellular

matrixdegradation

Cytokines

IL-1, TNF

+

Growth factors

IGF, TGF-b

+

PKC, NF-KB,

Kinase inhibitors

PA, plasmin

+

+

Thiol, serine proteases,

MT-MMPs

+

TIMPs

-

Heavy metal chelators (Ca,

Zn)

-

Modified from Pelletier JP, Arthritis Rheum 2001;44:1237

NO

NO

+

+

+

+

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Management of Osteoarthritis

Non-pharmacological therapy

Pharmacological therapy

Surgery

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OA KNEE

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Cellmembrane

IL-1

Intracellular

signalling

COX NOSPlasmin

PGs NO Activation of MMPs

Stromelysin

Degrades cartilage

Collagenase

Degrades cartilage

TGF-B

IGF-1

Collagen II

Aggrecans

Hyaluronic acid

Mechanism of action of diacerein

Diacerein

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Conclusion

Non-pharmacological therapy is as important aspharmacological therapy, and should be used in allcases

There are some evidences that SYSADOAs, eg.diacerein is effective in osteoarthritis, and when usedfor a long term period they might be able to modifycartilage structure (disease modifying osteoarthritisdrugs: DMOADs).

Diacerein is as effective as NSAIDs in osteoarthritis,and is well tolerate.

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Thank You