Is There a Role for BMPs in the Treatment of Osteonecrosis?

The cause for osteonecrosis (ON) is still largely unknown and might in fact be multifactorial [1–3]. Multiple theories exist and almost all lead to impaired osseous blood flow with subsequent bone and marrow cell death. In cases of steroid- and alcohol-induced ON, current research points towards a predominance of adipogenic over osteogenic differentiation of mesenchymal stem cells, leading to osteocyte death and impaired remodeling with fatty atrophy of the subchondral bone [4, 5]. The foundation for the vascular insult theory is thought to be either from a traumatic disruption of the vasculature, from stenosis (i.e., compression), or from occlusion (i.e., thromboembolic event) [6]. After the initial ischemic event, necrosis of the cancellous bone and adjacent bone marrow ensues. This leads to an activation of signaling pathways that cumulate in an inflammatory response. Macrophages and osteoclasts home to the site of acute necrosis and initiate a resorption phase. In cases where only a small area of bone is involved, creeping substitution will replace the necrotic bone and the process will likely resolve without any clinically significant sequelae. If, however, the area of necrosis exceeds the size that can be regenerated through creeping substitution, then osteoclastic resorption can lead to structural compromise with the detrimental result of collapse. At this final stage of osteonecrosis, regenerative treatment options are futile and replacement of the involved joint is most commonly the last option. It is estimated that about 5–12% of total hip arthroplasties are performed for sequelae of osteonecrosis of the femoral head [7, 8]. Current research focuses on the development of regenerative strategies that could lead to an osteogenic response during the pre-collapse state. Growth factors are the main target of this research. If we understand how to control the choice between proliferation and differentiation, then theoretically we will have the ability to expand what might be a limited population of progenitor cells within the site of osteonecrosis, induce their timely differentiation, and thus restore the function of the involved bone segment.