Osteonecrosis of the femoral head: Potential treatment with growth and differentiation factors

Basic and clinical research have shown the efficacy of various cellular mediators (bone morphogenetic proteins, interleukins, angiogenic growth factors) in healing bone defects. The potential application of these growth and differentiation factors to other musculoskeletal conditions, including osteonecrosis of the femoral head, only recently has been explored. Osteonecrosis is a disease of unknown pathogenesis that usually progresses to hip joint destruction necessitating total hip arthroplasty. The pathology involves ischemic events followed by death of bone and marrow elements. A process of repair then is initiated, but unless the lesion is small (less than 15% of the femoral head involved), this repair process is usually ineffective. The net result is weakening of subchondral bone with subsequent collapse of the articular surface. Because the results of hip arthroplasty in patients with osteonecrosis are relatively poor, much focus has been on modalities aimed at femoral head preservation. The surgical alternatives may include core decompression, osteotomy, nonvascularized, and vascularized bone grafting, which might be enhanced with the use of growth and differentiation factors. At least three of these factors are potential candidates as therapeutic modalities: cytokines (such as interleukins, tumor necrosis factors, and signaling molecules such as fibroblast growth factors, platelet derived growth factors, insulinlike growth factors, and transforming growth factor betas), bone morphogenetic proteins, and angiogenic factors. Despite considerable effort, evaluation of these growth and differentiation factors has been hampered by the lack of an animal model that adequately simulates the pathology of osteonecrosis in humans. Therefore, investigators have attempted to model certain aspects of the disease process. Recently, several investigators have attempted to mimic osteonecrosis in the femoral head of large mammals by combinations of devascularization, freezing, osteotomy of the femoral neck, or creation of a head defect. Results from some of these studies have confirmed the potential for growth and differentiation factors to effect more rapid healing and filling of defects with biomechanically competent and viable bone. The application of this therapy shows promise, and clinical studies on efficacy and safety are ongoing.