Risk factors associated with onset of medication-related osteonecrosis of the jaw in patients treated with denosumab

Abstract

Objectives While risk factors of bisphosphonate (BP) associated osteonecrosis of the jaw have been properly analyzed, studies focusing on risk factors associated with denosumab (DNO) are sparse. The purpose of this study was to identify risk factors influencing the onset of medication-related osteonecrosis of the jaw (MRONJ) in patients receiving antiresorptive treatment (ART) with DNO by comparing patients suffering from MRONJ and patients without MRONJ. Multiple variables were evaluated including the impact of a previous BP intake. Materials and methods A retrospective single-center cohort study with patients receiving DNO was conducted. One-hundred twenty-eight patients were included and divided into three groups: I (control, n = 40) receiving DNO with absence of MRONJ; group II (Test 1, n = 46), receiving DNO with presence of MRONJ; and group III (Test 2, n = 42) sequentially receiving BP and DNO with presence of MRONJ. Patients’ medical history, focusing on the identification of MRONJ risk factors, was collected and evaluated. Parameters were sex, age, smoking habit, alcohol consumption, underlying disease (cancer type, osteoporosis), internal diseases, additional chemo/hormonal therapy, oral inflammation, and trauma. Results The following risk factors were identified to increase MRONJ onset significantly in patients treated with DNO: chemo/hormonal therapy (p = 0.02), DNO dosage (p < 0.01), breast cancer (p = 0.03), intake of corticosteroids (p = 0.04), hypertension (p = 0.02), diabetes mellitus (p = 0.04), periodontal disease (p = 0.03), apical ostitis (p = 0.02), and denture use (p = 0.02). A medication switch did not affect MRONJ development (p = 0.86). Conclusions Malignant diseases, additional chemotherapy, DNO dosage, and oral inflammations as well as diabetes mellitus and hypertension influence MRONJ onset in patients treated with DNO significantly. Clinical relevance Patients receiving ART with DNO featuring aforementioned risk factors have a higher risk of MRONJ onset. These patients need a sound and regular prophylaxis in order to prevent the onset of MRONJ under DNO treatment.

Medication-Related Osteonecrosis of the Jaw: A Cross-Sectional Survey among Urologists in Switzerland, Germany, and Austria

“…Notably, only a small subset (8.5%) of the respondents singled out hypertension as a risk factor for MRONJ. This observation may be because hypertension has only recently been described as a risk factor for MRONJ [ 24 ]. Nevertheless, we considered the knowledge level sufficient, contrasting with the results of other studies among physicians in other countries.…”

“…Although some reports show that MRONJ can develop spontaneously without a clear initiating cause, many risk factors are associated with the development of MRONJ, such as intravenous (IV) administration of BPs, frequency of administration, higher dose per administration, and the duration of drug intake [ 20 , 21 ]. In addition, the use of corticosteroids and concomitant systemic diseases, such as diabetes mellitus, hypertension, renal failure, and immunosuppression, enhance the likelihood of developing MRONJ [ 22 , 23 , 24 ]. Furthermore, invasive dental measures (e.g., tooth extraction), preexisting periodontal inflammation, and prosthesis-related oral mucosal lesions represent significant risk factors for MRONJ, as has also been demonstrated in preclinical research using primarily rodent models [ 25 , 26 , 27 , 28 ].…”

Association between elevated plasma glucose levels and medication-related osteonecrosis of the jaw

“…Among the aforementioned factors, abnormal glucose levels is the most signi cant risk factor for the development of MRONJ. Moreover, dysglycemia, smoking, and alcohol consumption can be risk factors of necrosis [32][33][34][35][36]. Vascular anomaly and immune dysfunction due to hyperglycemia can be predisposing factor for the development of necrosis after tooth extraction.…”

Surgical and conservative treatment outcomes of medication-related osteonecrosis of the jaw in relation to tori: A retrospective study

“…Among local risk factors, tooth extraction is the single most frequently reported predisposing factor for the development of MRONJ (62-82%) [5,16,[26][27][28]. Pressure from ill-tting dentures and local trauma during intubation and mastication as well as the presence of tori and exostoses are all considered local risk factors [27,[29][30][31].…”