Exploring the feasibility of pharmacologic management in non-traumatic osteonecrosis: An etiology-based hypothesis

Non-traumatic osteonecrosis is a debilitating condition with a major health burden for the patients. Nevertheless, effective pharmacologic interventions for non-traumatic osteonecrosis are lacking. Increasing evidence suggests a complex interplay between a lipid metabolic disorder and chronic inflammation in the development of osteonecrosis. However, there is no consensus on which of these aberrations initially occurs in the pathogenic sequence of non-traumatic osteonecrosis, as both can mutually and synergistically induce the initiation of each other, perpetuating a recurring process spiraling into the disease state. Furthermore, other pathogenic mechanisms, such as coagulopathy and endothelial dysfunction, have been introduced for non-traumatic osteonecrosis. Understanding the root pathogenic cause of non-traumatic osteonecrosis is important, as therapeutic options should focus on the root cause of the disorder to provide the highest therapeutic impact. Identifying the root pathogenic cause, when feasible, provides a basis for developing pharmacologic strategies tailored to the etiology of osteonecrosis. If the pathogenic sequence originates from a lipid metabolic disorder, pharmacologic interventions should prioritize optimizing lipid metabolism. Conversely, if the primary pathogenic cause is chronic inflammation, anti-inflammatory medications better serve patients. Depending on the underlying mechanisms, additional medications like anti-coagulants could also be considered. In this article, we first provide some clues to determine the root pathogenic cause of non-traumatic osteonecrosis and then suggest an etiology-based pharmacologic intervention based on the potential root pathogenesis.