Inadequate Dental Imaging Delays Diagnosis of Pathologic Le Fort I Fracture Secondary to Bisphosphonate Use

Setareh Lavasani, DDS, MS; Ho-Hyun (Brian) Sun, DMD, MS; and Jeffrey A. Elo, DDS, MS

AUTHORS

Setareh Lavasani, DDS, MS, is an associate professor and the chief oral and maxillofacial radiologist at the division of oral radiology and advanced imaging at the Western University, College of Dental Medicine in Pomona, California. Conflict of Interest Disclosure: None reported.

Ho-Hyun (Brian) Sun, DMD, MS, is a clinical assistant professor in the division of oral and maxillofacial radiology at the Western University of Health Sciences, College of Dental Medicine and a clinical instructor in the department of oral and maxillofacial surgery at the University of the Pacific Arthur A. Dugoni School of Dentistry. He practices in an oral surgery private practice in San Jose, California. Conflict of Interest Disclosure: None reported.

Jeffrey A. Elo, DDS, MS, is a professor in the division of oral and maxillofacial surgery at the Western University of Health Sciences, College of Dental Medicine. He is a fellow of the American College of Surgeons. Conflict of Interest Disclosure: None reported.

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ABSTRACT

Background: Medication-related osteonecrosis of the jaws (MRONJ) is a progressive necrosis of the jaw that occurs in the aftermath of dental treatments including extractions, periodontal surgery or implant placement.

Case description: While the risk of incurring MRONJ is low even after invasive treatments, its manifestations can be severe with large-scale necrosis, infection and neuropathy. The exact mechanism behind MRONJ is not yet fully understood. Prevailing theories stipulate that it is associated with a defect in periodontal bone remodeling, likely as a result of downregulation of osteoclastic action and/ or angiogenesis. MRONJ is categorized into stages ranging from 0 to 3 depending on the severity of presentation. Treatment strategies also vary accordingly. Each stage is defined by specific clinical and radiographic findings during or after the occurrences of a suspected MRONJ trigger. Antiresorptives like bisphosphonates linger within bone for extended periods of up to 10 years.

Conclusions: Our experiences at a regional university-based dental center indicate that increasing numbers of supposedly “low-risk” patients are presenting with profound disease whose extent was notable only via detailed radiographic examination.

Practical implications: This case demonstrates that clinicians must employ proper diagnostic methodologies to help detect and prevent future cases.

Keywords: Medication-related osteonecrosis of the jaw, MRONJ, Le Fort I fracture, pathologic fracture, pathologic Le Fort I fracture

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Medication-related osteonecrosis of the jaw (MRONJ) is a progressive necrosis of the jaw that occurs in the aftermath of dental treatments including dental extractions, periodontal surgery or implant placement. 1 While the risk of incurring MRONJ is quite low even after invasive treatments, its manifestations can be severe with largescale necrosis, infection and neuropathy.

The exact mechanism behind MRONJ is not yet fully understood. Prevailing theories stipulate that it is associated with a defect in periodontal bone remodeling, likely as a result of downregulation of osteoclastic action and/or angiogenesis. A proper diagnosis requires fulfillment of criteria that include:

■ An area of appreciably exposed jawbone persisting for more than eight weeks.

■ A lack of radiation therapy to the head and neck region.

■ A history of antiresorptive and/or antiangiogenic medication use.

MRONJ is categorized into stages ranging from 0 to 3 depending on the severity of presentation. The treatment strategies also vary accordingly, with surveillance recommended primarily for the milder stages (stages 0 and 1) to antibiosis and surgical debridement for the increasingly advanced stages (stages 2 and 3). Each stage is defined by specific clinical and radiographic findings during or after the occurrence of a suspected MRONJ trigger:

■ Stage 0: Nonspecific symptoms such as dull pain, diffuse radiopacity or periodontal ligament (PDL) widening.

■ Stage 1: Necrotic bone that is appreciable visually or via probing.

■ Stage 2: Necrotic bone with infection or pain that is appreciable visually or via probing.

■ Stage 3: Necrotic bone with infection, erosion or fracture that extends beyond the alveoli.

Antiresorptives like bisphosphonates linger within bone for extended periods of up to 10 years. 5 In general, individuals are thought to be at a higher risk of developing MRONJ if the following criteria are met:

■ Antiresorptive treatment duration of greater than four years.

■ An intravenous route of antiresorptive treatment.

■ Application of antiresorptive medications as a part of cancer management.

■ Concurrent use of corticosteroids.

■ Underlying immunosuppressive diseases including diabetes mellitus.

■ Antiangiogenic lifestyle factors including tobacco use.

Nonetheless, our experiences at a regional university-based dental center indicate that increasing numbers of supposedly “low-risk” patients are presenting with profound disease whose extent was notable only via detailed radiographic examination. This case demonstrates that clinicians must employ proper diagnostic methodologies to help detect and prevent future cases.

Clinical Presentation

An 86-year-old Asian woman presented for evaluation of pain and swelling of the right palate. The patient endorsed a one-year history of pain in the right upper quadrant and rated 4 out of 10 on the Wong-Baker Faces Pain Rating Scale. Her medications included furosemide, amlodipine and nebivolol for hypertension; solifenacin for urinary incontinence; and memantine for mild Alzheimer’s disease. The patient also reported previously taking an “unknown” oral medication and dose “a short time for the joints.” She stated that she stopped taking this medication about a year prior to presentation in our clinic because of gastrointestinal upset. She denied any history of surgeries or past use of tobacco, alcohol or illicit substances. She also denied any history of trauma, radiation or immunosuppression.

Examination of the patient revealed a normocephalic patient with no external signs of edema, trauma or pathology. Intraorally, she was missing most of the posterior dentition in the upper arch, and a 30 mm x 10 mm segment of the posterior right maxillary alveolar bone was exposed with a medially adjacent 25 mm x 15 mm area of edematous mucosa (FIGURE 1). Applying digital pressure upon the swollen palatal soft tissue did not elicit blanching or suppuration. All remaining maxillary teeth and several areas of maxillary alveolar bone demonstrated gross mobility.

Discussion with the referring general dentist revealed that a routine, atraumatic extraction of a nonrestorable right maxillary first premolar (tooth No. 5) had been conducted in the area approximately one year prior without signs of postoperative infection or swelling. A recent set of full-mouth radiographs was provided by her dentist that showed an empty tooth No. 5 socket with a welldefined outline and without observable signs of erosions, fractures or sequestra (FIGURE 2).

Diagnosis and Management

Given that the provided set of full-mouth radiographs was poor in quality and lacked an appropriate field of view, they were deemed insufficient to properly establish an accurate diagnosis. As such, a cone beam computed tomography (CBCT) scan was taken and interpreted by a board-certified oral and maxillofacial radiologist. The images showed interruptions in the integrity of her bilateral maxillary sinus walls with complete opacification of the sinuses and the ostia resembling a Le Fort I-pattern maxillary fracture. It also showed thickening of the bilateral palatal soft tissues (FIGURE 3). Additionally, alveolar bone trabeculation was notably sparse with moth-eaten and permeativeappearing bone changes as well as irregular periodontal ligament widening (FIGURE 4). There were multiple areas of sequestered bone, the most notable of which was at the right posterior alveolar ridge (FIGURE 5). A presumed unhealed tooth socket without signs of trauma including overt widening or alveolar fracture was radiographically evident in the right maxillary alveolus (FIGURE 6). Severe thinning and interruption of buccal and palatal cortical plates with sparse and irregular trabecular bone pattern were also noted in the anterior maxilla (FIGURE 6).

The patient underwent biopsy of the right posterior maxillary exposed bone and adjacent palatal soft tissue. Hematoxylin and eosin-stained sections of the decalcified specimen revealed segments of nonvital lamellar bone demonstrating enlarged empty lacunae. Also noted were irregular external surfaces and medullary spaces coated with abundant adherent granular basophilic/ amphophilic bacterial colonies (biofilm), purulent exudate and subacutely inflamed granulation tissue. In short, the sample was indicative of a nonvital osseous sequestrum consistent with osteochemonecrosis along with inflamed palatal granulation tissue and fibrosis.

Upon consultation with the patient’s medical team, her extended medical records showed that she had undergone oral bisphosphonate therapy with 75 mg weekly alendronate for approximately three months about a year prior to help manage her osteoporosis. Her alendronate use did overlap with the timing of the extraction of tooth No. 5. She stopped taking the alendronate after only three months and was started on vitamin D and calcium supplementation instead. Considering the patient’s biopsy results, her clinical and radiographic findings and her past medical history, she was diagnosed with stage 3 MRONJ with a pathologic Le Fort I-pattern fracture.

Conclusion

MRONJ is defined as necrosis and exposure of the jaw bones lasting longer than eight weeks during or in the aftermath of antiresorptive therapy (often with bisphosphonates) but without a history of radiotherapy or malignant metastases to the maxillomandibular region. Though MRONJ is typically precipitated by surgical trauma, simple or atraumatic tooth extractions purportedly pose minimal risks and many dental procedures are undertaken without overt measures.

The literature also shows that the likelihood of MRONJ increases with several risk factors including the types and modes of antiresorptive administration as well as preexisting systemic factors. The significance of this case remains in its extraordinary extent despite the shortness and relative remoteness of oral bisphosphonate therapy, a patient with minimal systemic comorbidities, bisphosphonate use for osteoporosis as well as the atraumatic nature of the dental extraction conducted.

Our cases demonstrate that a standardized set of interview questions should be utilized for all patients who are likely candidates for antiresorptive medications, such as female postmenopausal patients or those with known metabolic diseases. The inquiries should include:

■ Have you ever been diagnosed with osteoporosis or cancer?

■ Have you ever been prescribed oral or injection medications for the purpose of strengthening bone or joints?

■ Have you ever been prescribed oral or injection medications for the purpose of preventing the spread of cancer into bone?

Dentists should consider requesting medical consultations and clarifications for patients who answer affirmatively. In the past year, these three questions have led to the identification of dozens of patients in our clinics who otherwise did not know or remembered to disclose their history of antiresorptive therapy.

It is also important to note that the patient underwent a “full-mouth” radiographic exam at the referring dentist’s office, which did not show appreciable osseous pathology save for the seemingly empty tooth No. 5 socket. An appropriate radiographic examination is critical when MRONJ is suspected or when persistently exposed bone is noted. An imaging modality that encompasses all the osseous structures of the jaws — such as a CBCT or panoramic radiograph — should be utilized. For this patient, reliance on bitewing and periapical radiographs may have allowed the disease to progress further into the bilateral maxillary sinuses as well as the pterygoid processes, leading to its current Le Fort-I fracture pattern and mobility of the entire palate.

Patients with profound necrosis are faced with a limited number of management options. Surgical resection and microvascular reconstruction may be considered in healthier, younger eligible patient populations. In others, management may require long-term systemic and local antibiosis to reduce the risks of infection and bacteremia. Recent investigations indicate that twice-daily therapy with 400 mg pentoxifylline and 400 IU of vitamin E supplementation can encourage mucosal healing over the necrotic bone to induce partial resolution of symptoms, 9 though their efficacy is often contested.

This patient was referred to a tertiary surgical center for evaluation and management. She was, however, deemed a poor surgical candidate considering her advanced age, Alzheimer’s disease and the amount of maxillary necrosis. Instead, she was started on a conservative medical therapy including long-term oral antibiotics, chlorhexidine oral rinses and a soft diet. She also began treatment with pentoxifylline and vitamin E. Despite such involvement of her maxilla, with conservative therapy she was able to retain adequate oral function with little to no pain. She was followed for a little over a year and a half, but then relocated.

This case unfortunately represents one of an increasingly large number of MRONJ cases diagnosed at our institutions arising in individuals treated with short courses of antiresorptives and subjected to relatively atraumatic procedures. While agents like bisphosphonates remain effective at maintaining bone density, clinicians must remain cognizant of the risks even in those patients at “low risk” of developing MRONJ. Dentists should carefully consider the rare but potentially catastrophic risk especially in populations who are likely to require extensive dental treatments in the near future.