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AB0147 Role of Sclerostin in Rheumatoid Arthritis: New Insights
  1. S.E. Ibrahim1,
  2. A. Louis2,
  3. N. Farouk2
  1. 1Rheumatology
  2. 2Faculty of Medicine, Ain Shams University, Cairo, Egypt

Abstract

Background Rheumatoid arthritis (RA) is an autoimmune-inflammatory disease that may lead to joint destruction and disability Several key molecules are involved in the regulation of osteoclast differentiation, which are induced upon arthritis and play an important role in osteoclast-mediated destruction of the joint architecture. A recent advance in understanding joint remodeling has been the discovery of the role of the wingless (Wnt) pathway in bone formation. Recent studies show that the Wingless (Wnt)/β-catenin signaling pathway may play an important role in the control of bone mass. Sclerostin is a major Wnt antagonist which is secreted by osteocytes. When it binds to one of the low-density lipoprotein receptor–related proteins (LRP), it first inhibits the canonical Wnt/β-catenin signaling pathway and then acts as a negative feedback signal on osteoblasts.

Objectives is to evaluate the serum levels of sclerostin in rheumatoid arthritis patients to explore its potential role in bone affection.

Methods This study was conducted on forty five rheumatoid arthritis patients as well as forty five age and sex matched healthy controls. Assay of serum sclerostin was done for all patients and controls by enzyme linked immunosorbent assay (ELISA). Disease activity of RA patients was assessed using the modified disease activity score. Modified version of Larsen score was used to assess disease severity in RA patients. Magnetic resonance imaging (MRI) of RA wrist and hand was performed to assess synovitis and bone erosion. MRI scoring of RA wrist and hand was performed according to the Outcome Measures in Rheumatology Clinical Trials (OMERACT) group RA-MRI scoring (RAMRIS) system.

Results The serum levels of sclerostin were higher in RA patients than control group. There was a statistically highly significant increase in serum levels of sclerostin in RA patients compared to control as p<0.01. There was a significant positive correlation between serum sclerostin levels in RA patients and each of ESR, CRP, modified DAS, modified Larsen score, MRI synovitis score and MRI erosion score as r=0.655, 0.623, 0.73,0.711, 0.802 and 0.832 respectively as p<0.01.

Conclusions Increased serum levels of sclerostin may play a role in joint damage and bone erosion in RA. blockade of sclerostin, might serve to restore the osteoblast–osteoclast balance and repair bone erosion in RA joints. Such treatments, in combination with anti-inflammatory therapies, could stabilize and repair damaged joints and have the potential to be valuable additions to the armory of RA treatments.

References

  1. de Rooy DP, Yeremenko NG, Wilson AG, et al. Genetic studies on components of the Wnt signalling pathway and the severity of joint destruction in rheumatoid arthritis. Ann Rheum Dis2013;72:769–75.

  2. Chen X, Baum W, Dwyer D, Stock M, Schwabe K, Ke H, etal. Sclerostin inhibition reverses systemic, periarticular and local bone loss in arthritis. Ann Rheum Dis. 2013 October; 72(10): 1732–1736.

  3. van den Broek M, Dirven L, de Vries-Bouwstra JK, et al. Rapid radiological progression in the first year of early rheumatoid arthritis is predictive of disability and joint damage progression during 8 years of follow-up. Ann Rheum Dis2012;71:1530–3.

  4. Heiland GR, Zwerina K, Baum W, et al. Neutralisation of Dkk-1 protects from systemic bone loss during infl ammation and reduces sclerostin expression. Ann Rheum Dis 2010;69:2152–9.

Disclosure of Interest None declared

DOI 10.1136/annrheumdis-2014-eular.2335

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