Prolia (denosumab) is a medication used to treat osteoporosis and prevent skeletal complications in certain cancers by targeting bone breakdown. While effective at strengthening bone, it is associated with a rare but serious side effect: osteonecrosis of the jaw (ONJ). This article details the incidence rates of ONJ observed with denosumab use, outlining the variables that determine an individual’s risk profile. The risk varies dramatically based on the condition being treated and the patient’s individual health factors.
Understanding Osteonecrosis of the Jaw
Osteonecrosis of the jaw (ONJ) is characterized by the breakdown and poor healing of bone tissue in the jaw. Formally, it involves exposed bone in the maxillofacial region that persists without healing for more than eight weeks. Denosumab is an anti-resorptive agent that inhibits the cells that dissolve old bone. By inhibiting this bone remodeling process, the medication impairs the jaw’s ability to repair itself after trauma. Common signs of ONJ include pain, swelling, infection, or exposed bone, often triggered by an invasive dental procedure like a tooth extraction.
Statistical Frequency of Prolia-Associated ONJ
The statistical frequency of osteonecrosis of the jaw associated with denosumab varies significantly based on the dose and the underlying condition being treated. Denosumab is administered at two different doses, which correspond to vastly different risk profiles. The lower dose, 60 mg every six months, is marketed as Prolia for osteoporosis treatment, while the higher dose, 120 mg every four weeks, is marketed as Xgeva for cancer-related bone issues.
For patients receiving Prolia for osteoporosis, the risk of ONJ is very low, though it increases with the duration of use. Data from the FREEDOM extension trial, which tracked patients for up to ten years, showed an exposure-adjusted incidence rate of approximately 5.2 cases per 10,000 patient-years of exposure. This low rate translates to a risk of roughly 0.05% in patients who do not undergo any invasive dental procedures.
However, the cumulative risk rises over time, starting at a very low rate of about 0.04% after three years and climbing to approximately 0.44% after ten years of continuous treatment. When an invasive oral procedure is performed, the risk for patients on the osteoporosis dose temporarily increases to about 0.68%.
The risk is substantially higher for patients receiving the higher-dose Xgeva for cancer treatment. This dose is 10 to 12 times greater than the osteoporosis dose and is given more frequently. In this oncology setting, the incidence of ONJ ranges from 0.7% to 2.4% (or 70 to 240 cases per 10,000 patients). This marked difference is due to the higher cumulative dose of the drug and the patients’ often compromised underlying health.
Patient-Specific Factors That Modify Risk
Beyond the dosage, several individual health and dental factors can shift a patient to a higher susceptibility level for ONJ. The duration of denosumab therapy is one of the strongest systemic factors, as the risk increases with the total cumulative drug exposure over many years. Similarly, the use of other medications, such as concurrent chemotherapy or systemic corticosteroids, can further heighten the risk profile.
Certain co-morbidities are also associated with an increased likelihood of developing ONJ. Patients with diabetes mellitus or hypertension have a greater risk of this complication. These conditions impair the body’s natural healing processes and affect blood flow to the jawbone, making it more vulnerable to necrosis.
Local oral factors are frequently the direct trigger for ONJ, with invasive dental procedures being the most common inciting event. Tooth extractions carry the highest risk, but other factors also increase the chances of ONJ:
- Poor oral hygiene.
- Pre-existing periodontal disease.
- Ill-fitting dentures that cause chronic mucosal irritation.
Addressing these modifiable local issues is a primary strategy in risk mitigation.
Proactive Dental Care and Management
Patients beginning or currently on Prolia should take proactive steps to minimize their risk of developing ONJ, starting with a comprehensive dental evaluation. All necessary invasive dental procedures, such as extractions or the placement of implants, should ideally be completed and fully healed before beginning denosumab therapy. Healing time of four to eight weeks is generally recommended before the first injection.
Maintaining excellent oral hygiene and attending regular dental checkups are fundamental to prevention, as this helps control periodontal disease and dental infections, which are known risk factors. Should an invasive procedure become necessary while on the medication, both the dentist and the prescribing physician must be informed about the denosumab treatment.
For a necessary tooth extraction, the dental procedure should be performed with meticulous technique, often utilizing prophylactic antibiotics and primary wound closure to encourage healing. Some physicians may suggest scheduling the procedure during a “window of opportunity” in the dosing cycle, ideally five to six months after the last injection and at least one month before the next scheduled dose. A “drug holiday” or temporary cessation of denosumab is controversial and lacks consensus, so this decision requires careful consultation between the patient’s physician and dentist.