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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 Dalam FKUI/RSUPN Ciptomangunkusumo Jakarta

PENDIDIKAN : Tamat Dokter Brevet Spesialis Penyakit Dalam Brevet Subspesialis Reumatologi Brevet Subspesialis Geriatri Doktor Guru Besar

1972 FKUI 1979 FKUI 1986 FKUI 1996 FKUI 2004 FKUI 2005 FKUI

ORGANISASI : Ketua Umum, Ikatan Reumatologi Indonesia, 1994 2005 President , Rheumatology Association of ASEAN 2001 2006 Ketua Bidang Sp Konsultan, Kolegium Ilmu Penyakit Dalam (KIPD), 2006- 2012

The Role Diacerein in the Management of Osteoathrosis


Harry Isbagio

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 the evidence ? What are inflammatory factors that could possibly be involved in genesis of OA structural changes?

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

Chondrocyte metabolism
Stimulation IGFs, TGF-beta, PDGF, EGF Bone morphogenic protein Cartilage derived morphogenic protein Growth factor Stimulation Gamma- Interferon TNF-alpha Prostaglandins Oxygen radicals, NO

Chondrocyte Anabolism Catabolism

IL-1, TNF-alpha, IL-17, FGFs, gamma interferon Leukemia inhibitory factor Glucocorticoid Pro-collagen fragments Inhibition

TIMP, Plasminogen activator inhibitor Calicrein Inhibition

Cytokines IL-1, TNF

Growth factors IGF, TGF-b

TIMPs

Heavy metal chelators (Ca, Zn)

PA, plasmin

+
Pro-MMPs

Active-MMPs

Chondrocytes

+
NO +

+
Thiol, serine proteases, MT-MMPs

Extra-cellular matrix degradation

+
NO

PKC, NF-KB, Kinase inhibitors

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

Management of Osteoarthritis

Non-pharmacological therapy

Pharmacological therapy
Surgery

OA KNEE

Mechanism of action of diacerein


IL-1 Cell membrane Diacerein

Intracellular signalling

COX PGs Stromelysin

NOS NO

Plasmin

TGF-B IGF-1

Activation of MMPs

Collagenase

Collagen II Aggrecans

Degrades cartilage Degrades cartilage

Hyaluronic acid

Conclusion

Non-pharmacological therapy is as important as pharmacological therapy, and should be used in all cases There are some evidences that SYSADOAs, eg. diacerein is effective in osteoarthritis, and when used for a long term period they might be able to modify cartilage structure (disease modifying osteoarthritis drugs: DMOADs).

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

Thank You

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