Osteonecrosis of the jaw (ONJ) update

A decade has now passed since publication of the first reports of osteonecrosis of the jaw (ONJ) in bisphosphonate (BP) users. Since that time, an association between BP therapy and ONJ has been clearly shown with route of administration (for example, intravenous administration results in greater risk than does oral route), dose (potency) and duration- dependent effects.

Bart L. Clarke, M.D., of the Division of Endocrinology, Diabetes, Metabolism, & Nutrition at Mayo Clinic in Rochester, Minn., says: "Typically patients being treated with BPs in adjuvant fashion to prevent skeletal-related events secondary to cancer or chemotherapy are most at risk of developing ONJ. However, not all patients receiving BP therapy for either cancer or osteoporosis suffer from ONJ, and specific comorbidities have been identified with dentoalveolar surgery, like a dental extraction, local dental suppuration (associated with a dental infection), periodontal disease, radiation therapy to the affected jaw site and systemic steroid therapy being the principal agents."

James M. Van Ess, D.D.S., M.D., of the Division of Oral Diagnosis and Oral and Maxillofacial Surgery, at Mayo Clinic in Rochester, Minn., says: "The reported cumulative incidence of bisphosphonate-related ONJ ranges from 0.8 to 12 percent; whereas, the cumulative incidence due to orally administered bisphosphonates is much lower at 0.01 to 0.06 percent. Evidence is accumulating that oral BP use for longer than three years may be associated with increased risk of ONJ. These data indicate that ONJ in oral BP users is a relatively rare occurrence and, therefore, comforting to many patients. Nevertheless, ONJ when it occurs is difficult to resolve and can create significant clinical management challenges."

Sreenivas Koka, D.D.S., M.S., Ph.D., M.B.A., previously at Mayo Clinic in Rochester, Minn., says: "Clinically, ONJ lesions present as white-yellowish areas of exposed bone, sometimes accompanied by pain and erythema of the mucosa or gingival tissue surrounding the lesion. In some patients, the lesions can go unnoticed, especially when the lesions are located on the mylohyoid ridge or in the retromolar region of the mandible. This area is relatively easily traumatized, and the bony protuberance of the mylohyoid ridge and thin-covering mucosa are contributing factors. Otherwise, sites of recent dental extraction or exostosis with thin-covering mucosa (tori) are also common locations for ONJ to develop.

"In general, suppressed bone turnover in BP users renders these sites unable to mount the necessary osseous healing response to trauma or extraction and ONJ ensues. In the case of dental extractions, molar teeth provide the greatest wound-healing challenge due to the large size of the extraction site and hence are the most common sites of ONJ, which is far less commonly seen with extractions of anterior teeth."

Dr. Van Ess adds: "Patients undergoing dentoalveolar surgery such as extractions, and who are receiving IV bisphosphonates, are five to 10 times more likely to develop ONJ than are patients who are not having any surgery. As the highest reported incidence of ONJ is in this specific patient population, our patients needing extractions are reassured that the risk of developing ONJ is low, especially when taken in the oral form. Dental implant therapy in osteoporosis-directed oral BP users is as safe a treatment option as in non-BP users, with ONJ being very rare and dental implant survival rates statistically similar in the two groups."

Management protocols

Clinical management of patients with ONJ lesions is best undertaken using the American Association of Oral and Maxillofacial Surgeons or American Dental Association staging systems. Depending upon the size of the lesion and associated findings, management protocols range from use of topical analgesics and antibacterial mouthwashes in minor cases to systemic antibiotic therapy for larger lesions. In advanced cases, surgical therapy provided by an experienced oral surgeon may be considered.

The clinical utility of serum carboxy-terminal collagen crosslinks (CTX) testing to identify patients at risk of developing ONJ has received considerable attention. Dr. Clarke comments: "Current evidence indicates that, by itself, serum CTX testing has little support either as an ONJ risk management tool or as an ONJ predictor tool. Therefore, patients and clinicians should avoid the expense and effort in obtaining this test until the time when CTX testing has been proven to have clinical relevance. At present, CTX testing is not recommended, as it provides meaningless information that is of low patient-centric value."