Medication-related osteonecrosis of the jaw in a breast cancer patient receiving denosumab for bone metastases: a case report

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Kosin Med J. 2025;40(4):322-326

Publication date (electronic) : 2025 December 26

doi : https://doi.org/10.7180/kmj.25.133

Min-Kyeong Kim

Department of Dentistry, Kosin University Gospel Hospital, Kosin University College of Medicine, Busan, Korea

Corresponding Author: Min-Kyeong Kim, DDS Department of Dentistry, Kosin University Gospel Hospital, Kosin University College of Medicine, 262 Gamcheon-ro, Seo-gu, Busan 49267, Korea Tel: +82-51-990-5150 Fax: +82-51-990-3005 E-mail: ks220618@kosinmed.or.kr

Received 2025 October 21; Accepted 2025 November 4.

Abstract

Introduction

The skeleton is a common site of metastatic involvement in many cancers, with bone lesions most often observed in multiple myeloma, breast cancer, and prostate cancer [1]. Among these malignancies, breast cancer demonstrates a particularly high incidence of bone metastasis, reported in up to 73% of patients with advanced disease, depending on clinical presentation [1].

Bone-modifying agents (BMAs), including bisphosphonates and denosumab, are widely used to inhibit bone resorption and manage skeletal diseases, as well as skeletal-related complications. They play an important role in managing malignancy-associated hypercalcemia and metastatic bone disease and also reduce the incidence of skeletal-related events (SREs) [2]. Despite these benefits, however, BMAs are associated with an increased risk of medication-related osteonecrosis of the jaw (MRONJ).

Initially defined in 2007 by the American Association of Oral and Maxillofacial Surgeons (AAOMS) as bisphosphonate-related osteonecrosis of the jaw, the terminology was revised in 2014 to MRONJ to reflect evidence that other antiresorptive and antiangiogenic agents, such as denosumab, may also induce this condition [3,4]. MRONJ is characterized by exposed bone in the oral or maxillofacial region that persists for more than 8 weeks in patients with a history of antiresorptive or antiangiogenic drug use, without prior radiation therapy or metastatic involvement of the jaws [5]. This condition can cause severe pain and significantly impair quality of life. Accordingly, a thorough dental examination prior to initiating BMA therapy is strongly recommended to identify and extract teeth with a poor prognosis [6,7].

Nevertheless, dental extractions or interventions involving alveolar bone may become unavoidable during cancer therapy with BMAs. The management strategies for MRONJ can be broadly classified into two categories [8]: (1) conservative treatment—antimicrobial mouth rinses (e.g., chlorhexidine), systemic antibiotics, and removal of detached sequestra; (2) surgical treatment—procedures ranging from conservative debridement of necrotic bone to more extensive interventions, including marginal or segmental resection of the jaw.

In patients receiving bisphosphonates or denosumab for the management of osteoporosis, dental procedures may be performed without discontinuation of the medication or modification of the prescribed dosing schedule [5]. In contrast, cancer patients typically receive high-dose BMAs, administered either intravenously or subcutaneously at shorter intervals. This makes it virtually impossible to establish an adequate drug holiday, and whether discontinuation would be beneficial for the patient’s overall health also remains unclear. Furthermore, there is a risk of MRONJ recurrence after resuming therapy. Herein, we present a case of MRONJ in a patient with breast cancer and bone metastasis who received denosumab therapy and was successfully managed with conservative treatment.

Case

A 55-year-old female patient with diabetes and stage IV breast cancer was referred to the Department of Dentistry during hospitalization for chemotherapy, presenting with discomfort in the left maxillary gingiva.

She was initially diagnosed with breast cancer in 2013 and underwent neoadjuvant chemotherapy (cyclophosphamide, methotrexate, and fluorouracil), followed by left breast-conserving surgery with axillary lymph node dissection and concomitant chemoradiotherapy. The patient was subsequently maintained on tamoxifen until spinal metastasis was detected in 2016, after which she received 10 sessions of radiotherapy to the T9 spine (total dose, 3,000 cGy) and continued on palliative therapy.

The patient had been receiving subcutaneous denosumab (Xgeva [Amgen], 120 mg every 4 weeks) for multiple bone metastases since July 2019, which was discontinued in September 2023 following the onset of dental symptoms. She has also been undergoing systemic intravenous chemotherapy with Verzenio (Eli Lilly) and fulvestrant since March 2022.

At her initial dental visit in October 2023, palatal bone exposure was observed in the region of the left maxillary second premolar, the first and second molars, all of which had been restored with gold crowns. Early buccal bone exposure was also observed (Fig. 1). Based on these clinical findings, a diagnosis of MRONJ was established. The patient presented with acute inflammation, swelling, purulent discharge, and pain. Consequently, conservative management was initiated, consisting of systemic antibiotics (amoxicillin-clavulanate 625 mg and metronidazole 250 mg, three times daily) and a 0.12% chlorhexidine mouth rinse twice daily.

Fig. 1.

Preoperative findings of the maxillary left molars. (A) Panoramic radiograph. Clinical photographs showing the buccal view (B) and the palatal view (C).

Surgical removal of the necrotic bone was considered high risk due to its proximity to the maxillary sinus floor, which posed a significant risk of sinus perforation, in addition to the patient’s compromised systemic condition. Accordingly, after initial control of acute inflammation, the left maxillary first and second molars, which were already separated from the necrotic bone and severely mobile, were extracted. One month later, the second premolar spontaneously exfoliated (Fig. 2). The patient was followed up monthly and managed with regular smoothing of the sharp bony edges, disinfection of the exposed necrotic bone, selective antibiotic therapy as required for recurrent inflammation, and reinforced oral hygiene education. During this period, the patient reported minimal discomfort in daily activities and demonstrated good adherence to treatment recommendations.

Fig. 2.

Approximately 5 months after extraction of the maxillary left second premolar, first molar, and second molar. (A) Panoramic radiograph showing an unhealed socket without sclerotic changes in the left maxilla. (B) Clinical photograph showing the occlusal view.

In August 2024, clinical examination revealed a sequestrum separating from the surrounding tissues. Two months later, the large necrotic bone fragments became mobile and were clinically removed. The overlying mucosa remained intact, and panoramic radiography confirmed the preservation of the maxillary sinus floor (Fig. 3). Subsequently, the left maxillary first premolar, which demonstrated marked mobility resulting from advanced distal alveolar bone resorption, was lost spontaneously. At approximately 1 year after the onset of MRONJ, complete mucosal healing was observed; however, considerable alveolar bone resorption was noted relative to the initial presentation (Fig. 1A, 3A). Prosthetic rehabilitation with a removable partial denture is planned once the patient transitions into the maintenance phase of cancer therapy.

Fig. 3.

Six months after removal of the bony sequestrum in the left maxilla. (A) Panoramic radiograph. (B) Clinical photograph showing the occlusal view.

Discussion

Compared with the doses used for osteoporosis, high-dose short-interval administration of BMAs in cancer therapy is associated with an increased incidence of MRONJ [5]. BMAs are administered to prevent SREs, including pathological fractures, spinal cord compression, hypercalcemia, and bone pain, in patients with bone metastases from breast cancer [9].

Once tumor cells metastasize to bone, they secrete parathyroid hormone-related peptides that stimulate osteoclast activity and promote abnormal osteoblast proliferation, ultimately resulting in pathological bone remodeling and subsequent SREs [2]. Among the widely used BMAs, zoledronic acid (a bisphosphonate) acts directly on osteoclasts to inhibit bone resorption and induce apoptosis, whereas denosumab, a monoclonal antibody, binds to the receptor activator of nuclear factor-κB ligand, thereby preventing osteoclast activation [10,11].

A previous study demonstrated that pretreatment dental evaluation significantly reduced the incidence of MRONJ, particularly in patients aged >65 years receiving BMAs for bone metastases [8]. Although denosumab has been associated with a higher incidence of MRONJ than zoledronic acid, the same study reported that the healing duration tended to be shorter with denosumab [8].

Tooth extraction is an established risk factor for MRONJ, particularly in patients with cancer receiving high-dose BMAs [4]. Although the AAOMS recommends avoiding invasive alveolar procedures in this clinical setting [4], retaining severely inflamed teeth may also increase the risk of MRONJ [12]. Some studies have suggested that preexisting periodontal disease may constitute an even greater risk factor than the extraction itself [13]. In this case, MRONJ developed adjacent to the teeth without prior surgical intervention, suggesting that chronic inflammation may have contributed to the disease onset.

In the present case, upon confirmation of MRONJ, denosumab therapy was discontinued in consultation with the oncology team. The 2009 AAOMS position paper recommended that the continuation of BMAs be determined following referral to the oncologist, with the decision subsequently made jointly by the oncologist and patient [14]. However, recent evidence indicates that discontinuation of BMAs has minimal impact on prognosis, and the 2022 AAOMS guidelines note that the potential of drug holidays to improve surgical outcomes has not yet been established [5]. Therefore, in patients receiving BMAs for bone metastases, careful consideration is required to determine whether the discontinuation would ultimately be more beneficial for the patient’s overall health.

Recent treatment strategies for MRONJ include teriparatide, which promotes mucosal coverage by stimulating osteoblasts to reduce exposed bone [15], and pentoxifylline/tocopherol, which has demonstrated the potential to facilitate bone regeneration and reduce pain [16,17]. Photobiomodulation therapy using low-level lasers has recently been reported to provide beneficial effects as an adjunct to surgical and antibiotic treatment [18]. Nevertheless, further clinical validation is required before these approaches can be integrated into routine clinical practice.

The primary therapeutic goal in the management of MRONJ is to achieve mucosal coverage, thereby optimizing the patient’s quality of life. According to Yarom et al. [19], MRONJ outcomes are classified into four categories: resolution (absence of clinical symptoms and complete mucosal coverage of previously exposed bone), improvement (reduction of clinical symptoms and decreased extent of exposed bone), stabilization (no progression of disease but without significant improvement), and progression (worsening of symptoms or expansion of exposed bone). Given the complete mucosal coverage and spontaneous sequestrum elimination observed following conservative therapy, the present case may be classified as a resolution.

Our institution frequently manages patients with cancer who develop complications related to MRONJ. Although many patients exhibit stabilization or gradual improvement, recurrence may occur even after apparent resolution.

This case demonstrates that conservative therapy, including antimicrobial rinses and systemic antibiotics, can result in complete resolution of MRONJ in a patient with breast cancer receiving denosumab, with healing achieved over the course of 1 year. These findings suggest that conservative management may represent a viable treatment option in selected patients, although careful long-term follow-up remains necessary.

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