How Common Is Osteonecrosis of the Jaw With Prolia?

Prolia (denosumab) treats osteoporosis by inhibiting bone resorption. While effective, it has been linked to a rare but serious side effect: osteonecrosis of the jaw (ONJ), where jawbone tissue fails to heal properly after minor trauma or dental procedures.

Biological Processes Linked to Jaw Osteonecrosis

ONJ associated with Prolia results from disruptions in bone remodeling, a process essential for skeletal integrity. Denosumab inhibits RANKL, a protein necessary for osteoclast differentiation. While this reduces bone resorption and strengthens bone density, it also impairs the natural turnover needed for repairing microdamage and maintaining blood supply in the jawbone. Unlike bisphosphonates, which integrate into bone and have long-term effects, denosumab’s impact is reversible upon discontinuation. However, its suppression of osteoclast function can still predispose patients to ONJ, particularly after dental extractions or prolonged use.

The jawbone is especially vulnerable due to its high remodeling rate and constant exposure to mechanical stress and oral bacteria. In healthy bone, osteoclasts resorb old tissue while osteoblasts deposit new bone. Denosumab disrupts this balance, leading to microfractures and reduced capacity for renewal. The mandible, with its lower vascular density, is particularly at risk. Studies indicate prolonged RANKL inhibition can lead to avascular necrosis, where bone deteriorates due to poor blood flow.

Exposure to oral bacteria further increases ONJ risk. The alveolar bone, which supports teeth, is in direct contact with the oral environment, making it more susceptible to infection when healing is impaired. Minor trauma from dental procedures, such as extractions or implants, can allow bacteria to infiltrate compromised bone. Without proper remodeling, these infections persist, leading to chronic inflammation and further necrosis. Research published in the Journal of Bone and Mineral Research shows patients on denosumab who undergo invasive dental procedures face a significantly higher risk of ONJ, particularly if they have periodontal disease or poor oral hygiene.

Incidence Rates in Osteoporotic Populations

ONJ in Prolia users remains rare but is closely monitored. Large studies and post-marketing data estimate incidence rates between 0.01% and 0.3% per year in osteoporotic patients. A systematic review in Osteoporosis International found ONJ in about 0.1% of patients treated with denosumab over three years. In contrast, oncology patients receiving higher doses for bone metastases experience rates exceeding 1%. The lower incidence in osteoporosis patients is due to reduced dosage and less aggressive bone turnover suppression.

Longitudinal studies indicate risk increases with longer treatment. A Journal of Bone and Mineral Research cohort study of over 50,000 postmenopausal women found ONJ incidence rose with prolonged denosumab use. Patients on the drug for more than five years had rates nearing 0.2%, while shorter treatment durations showed lower occurrences. This suggests a time-dependent effect, where extended suppression of bone resorption heightens ONJ risk, especially after invasive dental procedures or in those with poor oral health.

Comparative analyses show slightly higher ONJ rates in denosumab users than in those taking bisphosphonates. A Lancet Diabetes & Endocrinology meta-analysis found ONJ rates at 0.02% to 0.1% annually for bisphosphonates, compared to 0.05% to 0.3% for denosumab. While the difference is small, some clinicians consider bisphosphonates a lower-risk alternative for patients with significant dental concerns.

Signs and Symptoms of Osteonecrosis

Early ONJ symptoms in Prolia users can be subtle, making detection challenging. Initial signs include jaw discomfort, mild swelling, or a sensation of heaviness. As the condition progresses, persistent pain develops, often unrelated to recent dental work. Unlike typical toothaches, ONJ pain worsens over time, particularly when chewing or applying pressure. Some patients report tingling or numbness in the gums before visible changes appear.

As necrosis advances, exposed bone may become visible along the gum line. Initially small, these areas can enlarge if healing remains impaired. The affected bone may take on a yellowish or grayish hue, indicating poor vitality. Secondary bacterial infections are common, leading to purulent drainage, foul breath, and inflammation. Teeth near necrotic areas may loosen due to progressive bone loss.

Severe ONJ cases can cause fistulas—abnormal channels connecting necrotic bone to the skin or sinuses—resulting in persistent drainage and increased infection risk. Swelling may extend beyond the oral cavity, affecting the lower face and neck, sometimes limiting mouth opening (trismus). In extreme cases, weakened jawbone structure leads to spontaneous fractures, often requiring surgical intervention.

Diagnostic Criteria and Imaging Methods

Diagnosing ONJ in Prolia users involves clinical evaluation and imaging. The American Association of Oral and Maxillofacial Surgeons (AAOMS) defines ONJ as exposed jawbone persisting for more than eight weeks in a patient with antiresorptive therapy history and no prior head or neck radiation. This helps distinguish ONJ from conditions like osteomyelitis or periodontitis. A thorough patient history is crucial to identify contributing factors, including recent dental extractions, ill-fitting dentures, or persistent oral infections.

Clinical examination may reveal exposed or necrotic bone, but imaging is essential for assessing disease extent and detecting early-stage cases. Panoramic radiography (orthopantomogram) is a common initial screening tool, offering a broad jawbone view to identify sclerosis, bone resorption, or fractures. However, early ONJ changes may not be visible on standard X-rays, necessitating advanced imaging. Cone-beam computed tomography (CBCT) provides high-resolution images for detailed trabecular bone and cortical integrity assessment, useful for detecting subtle bone changes before symptoms appear.

Magnetic resonance imaging (MRI) offers additional insights, particularly for soft tissue involvement or marrow edema. MRI detects early inflammatory changes, making it valuable for assessing disease progression. Nuclear medicine techniques, such as technetium-99m bone scintigraphy, can highlight altered bone metabolism but are generally reserved for complex cases where conventional imaging is inconclusive.