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

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.