MRONJ Stages: Radiological and Clinical Classification

Medication-related osteonecrosis of the jaw (MRONJ) is a serious condition linked to certain antiresorptive and antiangiogenic medications. It can cause persistent bone exposure, pain, and secondary infections, significantly affecting a patient’s quality of life. Early identification and classification are essential for guiding treatment and preventing complications.

A structured approach using clinical and radiological criteria helps categorize MRONJ into distinct stages, aiding diagnosis and management.

Key Mechanisms Of Progression

MRONJ develops due to impaired bone remodeling, vascular compromise, and microbial colonization. Antiresorptive agents like bisphosphonates and denosumab disrupt the balance between osteoclast-mediated resorption and osteoblast-driven formation. Suppressed osteoclastic activity leads to microdamage accumulation, reducing the jawbone’s ability to repair itself after minor trauma, such as tooth extractions or ill-fitting dentures. This compromised remodeling allows necrotic bone to persist, increasing the risk of complications.

Vascular impairment worsens the condition by limiting oxygen and nutrient delivery to affected bone tissue. Antiangiogenic medications, often used in oncology, inhibit new blood vessel formation, which is particularly detrimental in the jaw due to its high remodeling rate. Reduced angiogenesis correlates with a higher incidence of MRONJ, as diminished blood supply hinders necrotic bone clearance and delays healing. This ischemic environment fosters progressive bone degradation, making the condition harder to reverse.

Microbial colonization introduces chronic inflammation and infection into necrotic bone. Exposed bone provides an entry point for oral bacteria, leading to biofilm formation and persistent infection. Actinomyces species are frequently present in MRONJ lesions, contributing to a chronic inflammatory response that further impairs healing. Bacterial biofilms complicate treatment by creating a barrier against immune responses and antimicrobial therapies, allowing infection to persist and spread.

Clinical Classification Criteria

MRONJ staging relies on observable symptoms and patient history to assess disease severity and guide treatment. Diagnosis is based on exposed bone or fistulas probing to bone for more than eight weeks in a patient with a history of antiresorptive or antiangiogenic therapy, without prior radiation therapy to the jaw or obvious metastatic disease in the region. This framework helps distinguish between early, asymptomatic cases and advanced stages with infection, necrosis, and pathological fractures.

Early signs include mucosal breakdown, which may appear as ulceration or mild discomfort. Many patients remain asymptomatic initially, delaying diagnosis. As the disease progresses, pain, inflammation, purulent drainage, and halitosis become more pronounced due to bacterial colonization. The extent of necrosis and infection determines disease stage, with advanced cases showing widespread inflammation and extraoral fistula formation.

Systemic involvement becomes a concern in later stages. Extensive bone exposure and secondary infection may lead to regional lymphadenopathy, fever, and malaise. Severe cases involve osteolysis extending beyond the alveolar bone, compromising structures like the inferior border of the mandible or the maxillary sinus. These complications increase morbidity and complicate surgical management, as debridement or resection may be necessary to control infection and prevent further deterioration.

Radiological Indicators

Imaging is crucial for identifying MRONJ, especially in cases with subtle or absent clinical signs. Panoramic and periapical X-rays are first-line imaging tools, revealing early changes like increased bone density and trabecular alterations. These findings may precede overt bone exposure, aiding early detection. As the disease progresses, radiographs show irregular lytic areas, sequestra, and cortical disruptions. However, standard X-rays have limitations in visualizing the full extent of osseous involvement.

Computed tomography (CT), particularly cone-beam CT (CBCT), offers three-dimensional reconstructions that enhance visualization of bone architecture. CBCT scans reveal sclerosis surrounding radiolucent zones, indicating necrotic bone encapsulated by reactive remodeling. They also delineate the transition between viable and nonviable bone, crucial for surgical planning. In severe cases, CBCT detects pathological fractures, sinus involvement, and periosteal reactions, which are less discernible on conventional radiographs.

Magnetic resonance imaging (MRI) provides additional insights by assessing marrow involvement, a feature not readily apparent on X-rays or CT scans. T1-weighted sequences show hypointense regions corresponding to necrotic bone, while T2-weighted and short tau inversion recovery (STIR) sequences highlight inflammatory changes. MRI helps differentiate MRONJ from osteomyelitis or metastatic disease by identifying patterns of bone edema and soft tissue extension. This modality is particularly useful for detecting early-stage MRONJ before bone exposure occurs.

Stage Descriptions

MRONJ is classified into distinct stages based on clinical and radiological findings. Each stage reflects disease progression and informs treatment strategies.

Stage 0

This stage lacks visible bone exposure, making diagnosis challenging. Patients may report jaw pain, altered sensation, or mild swelling, which can be mistaken for temporomandibular joint disorders or odontogenic infections. Radiological findings may include subtle osteosclerosis, thickened lamina dura, or early trabecular changes. Management focuses on symptom relief and close monitoring. Antimicrobial mouth rinses and conservative pain management are recommended while avoiding invasive dental procedures that could worsen the condition. Early identification at this stage improves long-term outcomes.

Stage 1

Exposed necrotic bone is present, but patients typically do not experience significant pain or infection. The exposed bone may appear as a small, asymptomatic lesion, often discovered incidentally during routine dental exams. Radiographic findings may show localized increased bone density or early cortical irregularities without significant osteolysis. Treatment focuses on maintaining oral hygiene and preventing secondary infection. Chlorhexidine mouth rinses are commonly recommended, and patients should avoid trauma to the affected area. While surgical intervention is not usually needed, regular follow-ups are essential to monitor for progression.

Stage 2

Exposed necrotic bone is accompanied by pain and infection, with symptoms like erythema, swelling, and purulent discharge. Patients often report discomfort that worsens with chewing or palpation. Radiographs show cortical erosion, sequestrum formation, and increased radiolucency. Infection accelerates bone destruction, increasing the risk of complications. Management includes systemic antibiotics such as penicillin or clindamycin to control infection and reduce inflammation. Antiseptic mouth rinses remain essential, and pain management may involve NSAIDs or mild opioids. Conservative surgical debridement may be considered for loose sequestra contributing to infection. Close monitoring ensures effective treatment and prevents further progression.

Stage 3

This is the most advanced stage, characterized by extensive bone necrosis, severe infection, and complications such as pathological fractures, extraoral fistula formation, or maxillary sinus involvement. Patients experience significant pain, swelling, and difficulty with oral function. Radiographic imaging reveals widespread osteolysis, sequestration, and, in some cases, pathological fractures compromising jaw stability.

Treatment requires aggressive intervention, including surgical resection of necrotic bone, ranging from segmental resection to hemimandibulectomy in extreme cases. Long-term antibiotic therapy is often necessary, and reconstructive procedures may be considered to restore function and aesthetics. Due to the complexity of stage 3 MRONJ, a multidisciplinary approach involving oral surgeons, infectious disease specialists, and prosthodontists is crucial for optimal patient outcomes.