What is osteonecrosis?

Osteonecrosis, also known as avascular necrosis or aseptic necrosis, is a medical condition characterized by the death of bone tissue due to the loss of blood supply to the affected area. This lack of blood flow deprives the bone cells of oxygen and nutrients, leading to their death and eventual collapse of the bone structure. Osteonecrosis can occur in any bone in the body, but it most commonly affects the hip joint, followed by the knee, shoulder, and ankle joints. It can affect one or multiple joints simultaneously.


Osteonecrosis can be caused by various factors that disrupt the blood supply to the bone. These include trauma or injury to the bone, excessive pressure or stress on the bone, use of corticosteroid medications, alcohol abuse, certain medical conditions (such as sickle cell disease, lupus, and diabetes), radiation therapy, and excessive use of certain types of medications (such as bisphosphonates used to treat osteoporosis).


What is the relationship between osteonecrosis and oxidative stress?

The relationship between osteonecrosis and oxidative stress involves the interplay of several mechanisms that contribute to the pathogenesis and progression of the condition:


  • Ischemia-Reperfusion Injury: The initial insult in osteonecrosis is the loss of blood supply to the affected bone, resulting in ischemia (lack of oxygen and nutrients) and subsequent tissue death. When blood flow is restored, either spontaneously or through interventions such as surgical decompression, reperfusion occurs, leading to the generation of reactive oxygen species (ROS). This process, known as ischemia-reperfusion injury, contributes to oxidative stress and further damage to the bone tissue.


  • Mitochondrial Dysfunction: Ischemia-induced oxidative stress can impair mitochondrial function in bone cells, particularly osteocytes and osteoblasts. Mitochondria are the cellular organelles responsible for energy production and play a critical role in maintaining cellular homeostasis. Oxidative damage to mitochondria disrupts energy metabolism, increases ROS production, and triggers apoptotic pathways, leading to cell death and tissue necrosis.


  • Inflammatory Response: Oxidative stress activates inflammatory pathways in the affected bone, leading to the recruitment of immune cells and the production of pro-inflammatory cytokines and chemokines. Chronic inflammation further exacerbates tissue damage and promotes osteoclast-mediated bone resorption, contributing to the collapse of the bone structure in osteonecrosis.


  • Antioxidant Defenses: The body’s antioxidant defense mechanisms play a crucial role in counteracting oxidative stress and protecting tissues from damage. However, in conditions such as osteonecrosis, the balance between ROS production and antioxidant defenses is disrupted, leading to oxidative stress overload. Reduced levels of antioxidants, such as superoxide dismutase (SOD), catalase, and glutathione, have been observed in the bone tissue of individuals with osteonecrosis.


  • Cellular Damage: Oxidative stress-induced damage to cellular components, including lipids, proteins, and DNA, contributes to the pathogenesis of osteonecrosis. Lipid peroxidation, protein carbonylation, and DNA oxidation are common markers of oxidative stress observed in osteonecrotic tissues. These molecular alterations compromise cellular function, promote inflammation, and contribute to tissue necrosis and bone collapse.


Overall, oxidative stress plays a significant role in the development and progression of osteonecrosis by inducing cellular damage, inflammation, mitochondrial dysfunction, and impaired antioxidant defenses in the affected bone tissue.