THE PATHOGENESIS OF OSTEONECROSIS

Abstract

Introduction: Osteonecrosis continues to be a challenging problem in orthopaedic practice. Etiology is multi-factorial but steroid- and alcohol-associated osteonecrosis contributed to more than two thirds of all the cases. While the pathogenesis of the disease is still unknown, many new insights have emerged from research in the last decade. Studies have demonstrated that both steroids and alcohol promote adipogenesis and inhibit osteogenesis, in vitro and in vivo, leading to osteonecrosis and osteoporosis. It has been found that Dexamethasone can turn on adipogenic transcription factor PPARy2 but suppress osteogenic transcription factor Cbfa1/Runx2. Steroids also decrease VEGF production resulting in inhibition of angiogenesis by osteoprogenitor cells. However, alcohol produces adipogenesis through a different mechanism at a point downstream in the fatty acid metabolism pathway, but it does inhibit osteogenesis by decreasing osteocalcin gene expression. Increased adipogenesis and osteoporosis, together with decreased osteogenesis and angiogenesis, will eventually lead to the final pathway of osteonecrosis.