Medication-Related Osteonecrosis of the Jaw (MRONJ) Mistaken for Acute Apical Abscess

Medication-related osteonecrosis of the jaw (MRONJ) is a rare and complex condition characterized by non-healing exposed bone, or a fistula that probes to bone, present for at least 8 weeks, in patients with a history of antiresorptive or antiangiogenic therapy and without prior radiation to the head and neck.¹ Antiresorptive therapy alters bony metabolism by reducing osteoclastic activity, whereas antiangiogenic therapy is used to reduce the growth of new blood vessels needed by tumors to grow and metastasize. MRONJ can present with odontalgia without an identifiable odontogenic cause, dull radiating jaw pain, sinus pain, loosening of teeth, and swelling. Radiographically, MRONJ is associated with diverse nonspecific radiographic findings not otherwise attributable to other diseases, including alveolar bone loss or resorption, osteosclerosis, lack of new bone in extraction sockets, trabecular changes, periapical radiolucency, and periodontal ligament thickening.^1,2

Factors influencing the development of MRONJ include the duration of medication therapy, route of medication administration, dentoalveolar trauma, pre-existing inflammatory dental disease, and local inflammatory lesions.¹ Patients receiving antiresorptive or antiangiogenic therapy for metastatic bone disease have a greater risk of developing MRONJ (under 5%) when compared to patients being treated for osteoporosis (under 0.05%).¹ A large systematic review found tooth extractions and periodontal disease as the most common reported dental risk factors for MRONJ, while chemotherapy, corticosteroid use, and smoking represented the most common medical risk factors. Roughly 10% of cases developed spontaneously without an identifiable inciting dental trigger.³

Preventative measures include the elimination of risk factors by maintaining good oral hygiene, completing surgical procedures prior to initiation of antiresorptive therapy, using pre- and postoperative antibiotics, and continuing routine dental visits aimed at surveillance.⁴ Treatment of MRONJ depends on the disease severity and progression as well as other patient-specific factors and includes nonoperative and operative therapies, ranging from antiseptic rinses to surgical resection of affected bone.^1,5 Outcomes in the setting of conservative treatment vary widely^6,7; however, surgical treatment has generally yielded favorable outcomes.^8-10 The objective of the present case study, therefore, is to report a case of MRONJ that was initially diagnosed and treated as periapical disease due to overlapping clinical features.

A 68-year-old female patient was referred for persistent pain in the mandibular left quadrant that remained unresolved following endodontic treatment on tooth No. 19. One month before her endodontic consultation, the patient developed dull pain in the mandibular left jaw that was diagnosed as a dental abscess on tooth No. 19. She underwent nonsurgical root canal therapy on this tooth, after which her symptoms progressively worsened. She completed two 10-day courses of clindamycin 300 mg three times daily with no change in symptoms. Mild improvement in pain was experienced with ibuprofen.

At the time of endodontic consultation, the patient reported severe, constant pain localized to the left jaw and temporomandibular joint (TMJ) with the sensation of significant pressure on her lower teeth. Records from the referring dentist did not include an endodontic diagnosis but mentioned the use of only percussion testing prior to root canal treatment and visualization of vital tissue during treatment. The patient's medical history was notable for metastatic breast cancer for which she was prescribed ibandronic acid (Boniva^®) and zoledronic acid (Reclast^®), with the last infusion of the latter drug occurring 9 months before the development of dental pain. Both medications are antiresorptive bisphosphonate drugs, with Boniva typically being used to manage osteoporosis in postmenopausal women, whereas Reclast is frequently utilized in the treatment of metastatic cancer to bony tissues.

Clinically, slight buccal swelling was noted extraorally, and there was tenderness and tightness in the left masseter and left TMJ, as well as left submandibular lymphadenopathy. The intraoral examination revealed a 7-mm diameter area of exposed bone on the mandibular left lingual torus surrounded by erythematous soft tissue, with two sinus tracts along the mesial and distal aspects of the bony exposure (Figure 1). Teeth Nos. 18 and 19 were restored with porcelain-fused-to-metal crowns. The periodontal examination revealed normal probing depths and grade II mobility of teeth Nos. 19 and 20. Teeth Nos. 19 and 20 tested positive to percussion and palpation, with No. 19 being more sensitive to testing. Tooth No. 18 was non-tender to percussion and palpation.

Radiographically, a cone-beam computed tomography (CBCT) scan of the area revealed the presence of root canal filling material in three canal spaces of tooth No. 19 without evidence of untreated anatomy and normal periodontal ligament (PDL) spaces surrounding roots (Figure 2). Tooth No. 20 was also shown to be adequately endodontically treated with the presence of a post and normal PDL spaces surrounding the tooth. The CBCT demonstrated interruptions in the cortex on the lingual torus and bony sequestra.

The differential diagnosis consisted of MRONJ, TMJ trauma from prior dental work, and osteomyelitis. The patient was prescribed another course of clindamycin 300 mg four times daily for 7 days and referred to an oral and maxillofacial surgeon (OMFS) for further evaluation. She was evaluated by the OMFS 4 days later and the diagnosis of MRONJ was confirmed. Conservative management was initiated. The patient was prescribed oral levofloxacin and chlorhexidine rinses. At the 2-month follow-up visit, given lack of symptomatic improvement, surgical debridement was performed and primary closure was obtained. Oral levofloxacin was continued for 2 weeks postoperatively. At 2 weeks postoperatively, the patient's symptoms had fully resolved and levofloxacin was discontinued.

The case presented highlights how the misdiagnosis of MRONJ can lead to unnecessary treatment and possible disease progression, and underscores how crucial comprehensive diagnostics are when considering endodontic treatment. Review of outside records revealed that pulp sensitivity testing was not performed to determine whether this patient's symptoms were odontogenic in origin. The American Association of Endodontists Guide to Clinical Endodontics states that providers must evaluate both pulpal and periapical status prior to initiating nonsurgical root canal therapy.¹¹ Achievement of these diagnoses requires deliberate testing. Pulp sensitivity testing, most typically via cold, will elucidate the pulpal diagnosis, whereas periapical testing by way of percussion and palpation will aid in making the periapical diagnosis. A percussion-sensitive tooth may indicate inflammation of the PDL or periapical involvement of a necrotic tooth but is not diagnostic of pulpal inflammation or necrosis, as it can instead represent several non-odontogenic disorders such as referred myofascial pain, neuropathic orofacial pain, and, as in this case, MRONJ.¹²

Given the non-specific characteristics of MRONJ in its early non-exposed stage, diagnosis largely involves exclusion of other possible etiologies. MRONJ symptoms can mimic those present in endodontic disease, and it is essential for clinicians to differentiate odontogenic pain from non-odontogenic pain. The proper etiology and correct pulpal and periapical diagnosis must be made prior to initiating endodontic treatment. In the present case, the referring provider relied solely on percussion testing, resulting in misdiagnosis and the provision of unnecessary endodontic treatment. Such unneeded treatment may have been avoided with a thorough diagnostic approach that included pulp sensitivity testing and a review of the patient's relevant medical history.

The American Association of Oral and Maxillofacial Sur­geons (AAOMS) has a classification system that characterizes the different clinical and radiographic presentations of MRONJ. This classification includes an "at risk" designation (asymp­tomatic patients with a history of intravenous or oral antiresorptive therapy) followed by staging according to symptom severity and extension of bony necrosis (Table 1). The AAOMS considers stage 0 as a potential precursor to MRONJ rather than a discrete disease state, defined by clinical findings and symptoms such as undifferentiated jaw pain and odontalgia, oral swelling, and tooth mobility, as well as radiographic findings that include bone loss that is not associated with periodontal disease, changes in trabecular pattern, osteosclerosis, and thickening of the PDL.¹ Epidemiologic evidence, however, demonstrates a significant underdiagnosis of MRONJ in the earlier disease stages. One study suggests that up to one-fourth of patients with MRONJ remain undiagnosed due to the absence of any characteristic bone exposure on examination.¹³

While some studies suggest that MRONJ is underdiagnosed because of reliance on the disease criteria of exposed bone and the under-utilization of radiographic imaging,^13,14 the AAOMS states concern that overemphasizing radiographic features commonly attributed to MRONJ may actually lead to an overestimation of the true disease frequency.¹ Stage 0 MRONJ can present a diagnostic challenge for clinicians. Limited awareness of the presenting features of MRONJ can lead to it being excluded from a provider's differential diagnosis. Some studies have highlighted limitations in provider education surrounding MRONJ. A questionnaire-based study of providers in Canada exploring competence in diagnosis and management of MRONJ showed that less than a quarter of providers followed the AAOMS guidelines, and that when presented with a sample case scenario, around half of responding dentists would choose an incorrect treatment strategy.¹⁵ A similar study by Al-Eid and colleagues showed that more than 50% of participants were unable to correctly identify MRONJ-predisposing medications.¹⁶

In the present case, records included no mention of bone exposure when the patient initially presented to her general dentist with symptoms of pain. Nonetheless, keeping MRONJ in the differential diagnosis when there is a history of antiresorptive therapy and an unclear odontogenic etiology of symptoms and performing a complete diagnostic examination may prevent unnecessary endodontic treatment and allow for timely referral to OMFS.

The diagnosis of orofacial pain requires the careful consideration of both clinical and radiographic data. Moreover, pulp sensitivity testing is foundational to the diagnosis of endodontic pathology. Although MRONJ is a rarely occurring condition, it can be debilitating for patients. Dental providers need to approach their diagnostic plan with due consideration for the patient's medical history and be able to distinguish endodontic disease from other possible etiologies, such as MRONJ, by employing the appropriate examination and testing.

The authors declare no conflicts of interest.

Mona Meshkin, DMD
Clinical Fellow, Harvard School of Dental Medicine, Boston, Massachusetts; Department of Dentistry, Massachusetts General Hospital, Boston, Massachusetts

Christian McDermott, BS
Dental Assistant, Upper Valley Endodontics, White River Junction, Vermont

Rebekah Lucier Pryles, DMD, Certificate in Endodontics
Assistant Clinical Professor, Department of Endodontics, Tufts University School of Dental Medicine, Boston, Massachusetts; Clinical Instructor, Department of Restorative Dentistry and Biomaterials Science, Harvard School of Dental Medicine, Boston, Massachusetts; Co-founder, Pulp Nonfiction Endodontics; Private Practice limited to Endodontics, White River Junction, Vermont

Brooke Blicher, DMD, Certificate in Endodontics
Assistant Clinical Professor, Department of Endodontics, Tufts University School of Dental Medicine, Boston, Massachusetts; Clinical Instructor, Department of Restorative Dentistry and Biomaterials Science, Harvard School of Dental Medicine, Boston, Massachusetts; Co-founder, Pulp Nonfiction Endodontics; Private Practice limited to Endodontics, White River Junction, Vermont