Osteonecrosis of the jaw (ONJ) is a severe condition defined by the progressive death of bone tissue in the upper or lower jaw. This results in exposed, necrotic bone in the mouth that fails to heal over at least eight weeks. ONJ causes significant pain, swelling, infection, and impaired function. While historically rare, its incidence has increased dramatically due to the widespread use of certain medical treatments. Understanding the causes requires examining the systemic and local factors that compromise the jaw’s natural ability to repair itself.
The Primary Role of Specific Medications
The most common cause of ONJ is exposure to certain drug classes, leading to Medication-Related Osteonecrosis of the Jaw (MRONJ). The primary culprits are antiresorptive agents, which reduce the breakdown of bone tissue. These drugs are prescribed for osteoporosis and for cancer patients with multiple myeloma or bone metastases to prevent skeletal-related events.
The two main antiresorptive types are Bisphosphonates (e.g., zoledronic acid and pamidronate) and the RANK ligand inhibitor, Denosumab. The risk of MRONJ depends heavily on the administration method and the underlying disease. Patients receiving high-dose intravenous formulations for cancer treatment face a substantially higher risk (up to 15%) compared to those taking lower-dose oral formulations for osteoporosis (around 0.001% to 0.01%).
Anti-angiogenic agents and tyrosine kinase inhibitors, specialized cancer treatments, also contribute to MRONJ. These medications interfere with angiogenesis, the formation of new blood vessels. The nomenclature shifted from BRONJ to MRONJ to include these non-bisphosphonate drugs, reflecting the growing list of systemic therapies that compromise jawbone health.
Underlying Biological Mechanisms of Necrosis
The medications associated with MRONJ disrupt the complex biological processes that keep the jawbone healthy and able to heal. A leading theory centers on the suppression of bone remodeling, the body’s natural cycle of removing old, micro-damaged bone and replacing it with new tissue. Antiresorptive drugs slow the activity of osteoclasts, the cells responsible for breaking down bone.
This suppression prevents the removal of damaged bone, leading to a buildup of micro-damage and nonviable bone cells. Because the jawbone experiences constant, high mechanical stress from chewing, it has a higher rate of remodeling than other bones, making it uniquely vulnerable when this process is impaired. When the jawbone cannot repair itself, damage accumulates, leading to necrosis.
Impaired angiogenesis, the failure to form new blood vessels, is another significant mechanism. The jawbone relies on a rich blood supply for oxygen and nutrients, especially during healing following an injury like a tooth extraction. When new blood vessel formation is inhibited, the bone tissue becomes ischemic (starved of blood), leading to cell death.
The jaw’s unique environment also plays a role, as the bone is constantly exposed to the microbial load of the oral cavity. When repair mechanisms are suppressed, the bone cannot effectively ward off localized infection or inflammation following minor trauma or dental procedures. This combination of suppressed repair, reduced blood supply, and microbial invasion results in the exposed, infected, and necrotic bone characteristic of ONJ.
Contributing Local and Systemic Risk Factors
Beyond primary drug exposure, several local and systemic factors significantly increase the likelihood of developing ONJ. The most common local risk factor is dental trauma or invasive procedures that breach the gum tissue and expose the bone. Tooth extractions are the most frequent precipitating event, though the placement of dental implants or periodontal surgery can also act as a trigger. Pre-existing dental disease also heightens the risk, as these conditions introduce a microbial burden directly to the bone surface.
Local Risk Factors
Local factors that increase risk include:
- Poor oral hygiene.
- Periodontitis.
- Periapical inflammation.
- Poorly fitting dentures that cause chronic irritation.
These factors provide an entry point for bacteria and create a wound that the compromised bone healing mechanism cannot close.
Systemic Risk Factors
Systemic health issues act as co-factors by further impairing the body’s ability to heal. Conditions such as diabetes mellitus affect blood vessel health and immune function, both necessary for bone repair. Other medications, including systemic corticosteroids and chemotherapy drugs, are associated with increased risk by compromising the immune system and affecting cell turnover. Furthermore, a history of radiation therapy to the head and neck area can independently damage the jaw’s blood supply, making it susceptible to necrosis.