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Open Access Research article

Combined treatment with dexamethasone and raloxifene totally abrogates osteoporosis and joint destruction in experimental postmenopausal arthritis

Ulrika Islander*, Caroline Jochems, Alexandra Stubelius, Annica Andersson, Marie K Lagerquist, Claes Ohlsson and Hans Carlsten

Author Affiliations

Centre for Bone and Arthritis Research (CBAR), The Sahlgrenska Academy, University of Gothenburg, Box 480, 405 30 Gothenburg, Sweden

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Arthritis Research & Therapy 2011, 13:R96  doi:10.1186/ar3371

Published: 20 June 2011

Abstract

Introduction

Postmenopausal patients with rheumatoid arthritis (RA) are often treated with corticosteroids. Loss of estrogen, the inflammatory disease and exposure to corticosteroids all contribute to the development of osteoporosis. Therefore, our aim was to investigate if addition of the selective estrogen receptor modulator raloxifene, or estradiol, could prevent loss of bone mineral density in ovariectomized and dexamethasone treated mice with collagen-induced arthritis (CIA).

Methods

Female DBA/1-mice were ovariectomized or sham-operated, and CIA was induced. Treatment with dexamethasone (Dex) (125 μg/d), estradiol (E2) (1 μg/d) or raloxifene (Ral) (120 μg/day) alone, or the combination of Dex + E2 or Dex + Ral, was started after disease onset, and continued until termination of the experiments. Arthritic paws were collected for histology and one of the femoral bones was used for measurement of bone mineral density.

Results

Dex-treatment alone protected against arthritis and joint destruction, but had no effect on osteoporosis in CIA. However, additional treatment with either Ral or E2 resulted in completely preserved bone mineral density.

Conclusions

Addition of raloxifene or estradiol to dexamethasone-treatment in experimental postmenopausal polyarthritis prevents generalized bone loss.

Keywords:
Raloxifene; Estradiol; Dexamethasone; collagen-induced arthritis; bone mineral density