FUTURE TREATMENTS FOR OSTEONECROSIS: FROM BEDSIDE TO BENCH

Osteonecrosis is a chronic inflammatory disease of bone in which the marrow contents die, leading to progressive collapse of bone and subsequent degenerative arthritis. The condition afflicts younger individuals during their working years; osteonecrosis of the femoral head (ONFH) is the most common anatomical site. The two most common etiologies for developing ONFH include corticosteroid use and excessive alcohol intake. Early identification of the condition, i.e., when the femoral head (FH) is still round and without collapse, provides a unique opportunity for preserving the hip joint, rather than performing a joint sacrificing procedure such as total joint arthroplasty. However, approximately 75% of patients seen in our orthopaedic clinics are first diagnosed at the late stages of ONFH, in which collapse of the FH ± degenerative arthritis has made retention of the FH untenable. Thus, we have concentrated our research efforts on several key areas to mitigate these adverse clinical events. These endeavors include the following: Providing algorithms and clinical pathways for earlier diagnosis and treatment of patients who are at increased risk for developing ONFH and ON in multiple other anatomical areas (multifocal ON). Several clinical examples include patients who will undergo chemotherapy for leukemia, after organ transplantation, and for diseases such as lupus erythematosus, during which high dose corticosteroids are prescribed. Understanding the pathophysiology and timeline of corticosteroid associated ON so that appropriate interventions can be delivered to preserve the FH and other affected anatomical locations. The potential interventions could include modulating the pathologic events that lead to progression of the condition via pharmacologic treatments or minimally invasive surgical procedures. Developing rigorous and validated in vitro, in vivo and in silico models that simulate the events associated with ON authentically, so that potential novel methods for diagnosis and intervention can be assessed. In this respect, the identification of specific biomarkers of disease and high throughput assays for assessment of treatments are highly desired. The basic, translational and clinical activities of our laboratory will be described in the above areas in the hope that ON of the FH and other locations can be prevented, mitigated or even reversed.