Modulation of RANKL and osteoprotegerin expression in synovial tissue from patients with rheumatoid arthritis in response to disease-modifying antirheumatic drug treatment and correlation with radiologic outcome.
OBJECTIVE
To demonstrate the effect of treatment with disease-modifying agents on the expression of osteoprotegerin (OPG) and RANKL in the synovial tissue from rheumatoid arthritis (RA) patients and to correlate these changes with radiologic damage measured on sequential radiographs of the hands and feet.


METHODS
Synovial biopsy specimens were obtained at arthroscopy from 25 patients with active RA (16 of whom had a disease duration <12 months) before and at 3-6-month intervals after starting treatment with a disease-modifying agent. Immunohistologic analysis was performed using monoclonal antibodies to detect OPG and RANKL expression, with staining quantitated using computer-assisted image analysis and semiquantitative analysis techniques. Serial radiographs of the hands and feet were analyzed independently by 2 radiologists and a rheumatologist using the van der Heide modification of the Sharp scoring method.


RESULTS
Thirteen patients achieved a low disease state as defined by a disease activity score <2.6 while 19 patients achieved an American College of Rheumatology response >20% after disease-modifying antirheumatic drug (DMARD) treatment. Successful DMARD treatment resulted in an increase in OPG expression and a decrease in RANKL expression at the synovial tissue level, which correlated with a reduction in erosion scores measured on annual radiographs of the hands and feet.


CONCLUSIONS
Successful treatment-induced modulation of OPG and RANKL expression at the synovial tissue level, resulting in a reduction in the RANKL:OPG ratio, is likely to have a significant impact on osteoclast formation and joint damage in patients with active RA.
Haynes
David
D
University of Adelaide, Adelaide, South Australia, Australia.
Crotti
Tania
T
Weedon
Helen
H
Slavotinek
John
J
Au
Virginia
V
Coleman
Mark
M
Roberts-Thomson
Peter J
PJ
Ahern
Michael
M
Smith
Malcolm D
MD
D000368:Aged; D000369:Aged, 80 and over; D018501:Antirheumatic Agents / Q000627:therapeutic use*; D001172:Arthritis, Rheumatoid / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000378:metabolism; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007719:Knee Joint / Q000187:drug effects* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D053244:Osteoprotegerin / Q000378:metabolism*; D053245:RANK Ligand / Q000378:metabolism*; D011859:Radiography; D012720:Severity of Illness Index; D013583:Synovial Membrane / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology
D018501:Antirheumatic Agents; D053244:Osteoprotegerin; D053245:RANK Ligand; C505688:TNFSF11 protein, human