Potential molecular targets for the pharmacologic management of non-traumatic osteonecrosis

Expert Opin Ther Targets. 2024 Nov;28(11):991-1000. doi: 10.1080/14728222.2024.2421755. Epub 2024 Oct 29.

Abstract

Introduction: Non-traumatic osteonecrosis is a debilitating condition marked by bone death, primarily due to reduced blood supply. Currently, no effective pharmacologic intervention is available to manage this condition effectively.

Areas covered: Lipid metabolic disorders, chronic inflammation, vascular dysfunction, coagulopathy, and impaired bone homeostasis are suggested as the key pathogenic mechanisms involved in the development of non-traumatic osteonecrosis. Targeting any of these dysfunctions offers a potential avenue for pharmacologic intervention. However, the potential molecular targets for pharmacologic treatment of non-traumatic osteonecrosis remain underexplored. In this study, we reviewed available databases to compile a comprehensive set of pathogenic mechanisms and corresponding therapeutic targets for non-traumatic osteonecrosis.

Expert opinion: Evidence suggests that a single pathogenic mechanism cannot fully explain the development of osteonecrosis, supporting the adoption of a multi-pathogenic theory. This theory implies that effective management of non-traumatic osteonecrosis requires targeting multiple pathogenic mechanisms simultaneously. Moreover, the same pathogenic mechanisms are unlikely to explain osteonecrosis development in patients with different etiologies. Consequently, a one-size-fits-all approach to medication is unlikely to be effective across all types of non-traumatic osteonecrosis. Future research should, therefore, focus on developing multi-target pharmacologic treatments tailored to the specific etiology of non-traumatic osteonecrosis.

Keywords: Non-traumatic osteonecrosis; etiology; molecular target; pathogenesis; pharmacologic intervention.

Publication types

  • Review

MeSH terms

  • Animals
  • Humans
  • Inflammation / drug therapy
  • Inflammation / physiopathology
  • Lipid Metabolism / drug effects
  • Molecular Targeted Therapy* / methods
  • Osteonecrosis* / drug therapy
  • Osteonecrosis* / etiology
  • Osteonecrosis* / physiopathology