Rheumatology Advance Access originally published online on July 7, 2008
Rheumatology 2008 47(9):1432-1433; doi:10.1093/rheumatology/ken243
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Repairing erosions in rheumatoid arthritis. A realistic goal
1Department of Rheumatology, Puerta de Hierro University Hospital, Madrid, Spain
Correspondence to: J.-L. Andreu, Servicio de Reumatología, Hospital Universitario Puerta de Hierro San Martín de Porres 4, 28035, Madrid. E-mail: jlandreu{at}arrakis.es
SIR, Persistent inflammation in RA is an osteodestructive process, which leads to an accumulation of joint damage over time. Bone loss in RA occurs both in the joints and throughout the skeleton as a result of the multifactorial increase in bone resorption. Bone erosion starts early in disease and progresses most rapidly during the first year. The structural joint damage that is evident on conventional radiographs is strongly associated with poor functional outcome in patients with RA. These findings have fostered the concepts that retardation, arrest or even repair of structural damage should be considered central goals in the treatment of RA. We report a case of a woman with a long-evolution RA, in whom erosion repairing was achieved.
The patient was a 65-yr-old woman who had been diagnosed with a positive RF RA in 1985. Since then, she had received multiple DMARDs (aurothiomalate, chloroquine, MTX, SSZ, HCQ, LEF and infliximab) without achieving a satisfactory clinical response. Radiographs taken during those years revealed disease progression, as illustrated by the serial images of her left first MCP joint (Fig. 1). In 2004, etanercept plus low-dose weekly MTX was initiated, obtaining an excellent clinical response, with the 28-joint disease activity score persistently under 3.2. Radiographs taken after 2 and 3 yrs with etanercept plus MTX showed repair of the erosions (Fig. 1).
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RA results in extensive bone resorption as evidenced by focal bone erosions, juxta-articular osteopenia and systemic osteoporosis. Osteoclasts, specialized bone resorbing cells regulated by RANK ligand (RANKL) and monocyte colony-stimulating factor, are implicated in RA joint erosion [1]. Blockade of RANKL does not inhibit inflammation, but can prevent the structural damage progression that often occurs despite use of disease-modifying drugs, preserving joint architecture and function in RA patients. Anti-TNF agents (infliximab, etanercept and adalimumab) have shown the potential to arrest radiological damage in patients with active RA [2–4]. In this sense, the results from the Trial of Etanercept and Methotrexate with Radiographic Patient Outcomes (TEMPO) study suggest that etanercept in combination with MTX slows the radiographic progression in RA [5]. In this study, more patients receiving combination therapy had negative scores in the radiographic measurement after 1 and 2 yrs, compared with patients in either of the monotherapy groups, which could mean an effective repair of structural damage [5,6]. The exact mechanism by which this protection occurs has not been fully determined, but it is thought that TNF-
antagonists modulate the osteoprotegerin (OPG)/RANKL system. In fact, increased expression of OPG, and subsequent decrease in the RANKL : OPG ratio, in synovial tissue have been seen in patients following therapy with an anti-TNF- agent [7]. But the ambitious goal to repair bone erosions in RA could be achieved not only with the control of the inflammation, since new powerful agents are being developed to inhibit osteoclast function. Denosumab, a fully human neutralizing antibody directed against RANKL, has been demonstrated to increase bone mass at both axial and peripheral skeletal sites, as well as in trabecular and cortical areas of bone [8]. It can probably prevent not only the generalized bone loss in RA, but also the joint destruction inhibiting the bone erosion [9]. On the other hand, zoledronic acid is a potent third-generation aminobisphosphonate that is thought to act by inhibiting the osteoclast lifespan. It has been suggested that, added to MTX, it reduces the number of bone erosions in RA [10].
It seems clear that the new challenge in the treatment of RA should be not only to arrest the structural damage, but also to repair the previous erosions. Anti-TNF- therapy, zoledronic acid and denosumab, alone or in combined therapy, are among the potential candidates to achieve that ambitious but, we think, realistic goal.
Disclosure statement: The authors have declared no conflicts of interest.
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