Up to a quarter of patients with osteonecrosis of the jaw associated with antiresorptive agents remain undiagnosed

Abstract

Recent data suggest that the traditional definition of bisphosphonate-associated osteonecrosis of the jaw (ONJ) may exclude patients who present with the non-exposed variant of the condition. To test the hypothesis that a proportion of patients with ONJ remain undiagnosed because their symptoms do not conform to the traditional case definition, we did a secondary analysis of data from MISSION (Multicentre study on phenotype, definition and classification of osteonecrosis of the jaws associated with bisphosphonates), a cross-sectional study of a large population of patients with bisphosphonate-associated ONJ who were recruited in 13 European centres. Patients with exposed and non-exposed ONJ were included. The main aim was to quantify the proportion of those who, according to the traditional case definition, would not be diagnosed with ONJ because they had no exposed necrotic bone. Data analysis included descriptive statistics, median regression, and Fisher's exact test. A total of 886 consecutive patients were recruited and 799 were studied after data cleaning (removal or correction of inaccurate data). Of these, 607 (76%) were diagnosed according to the traditional definition. Diagnosis in the remaining 192 (24%) could not be adjudicated, as they had several abnormal features relating to the jaws but no visible necrotic bone. The groups were similar for most of the phenotypic variables tested. To our knowledge this is the first study in a large population that shows that use of the traditional definition may result in one quarter of patients remaining undiagnosed. Those not considered to have ONJ had the non-exposed variant. These findings show the importance of adding this description to the traditional case definition.

Osteonecrosis of jaw beyond antiresorptive (bone-targeted) agents: new horizons in oncology

“…As 20-30% of ONJ cases escape the classical definition (requiring 8-week lasting bone exposure), [24,35,36] great attention should be paid to imaging studies (particularly by CT or bone scan scintigraphy) in order to avoid underestimation of MRONJ.…”

“…Furthermore, the purely clinical-based definition of ONJ is questioned by the emergent role of imaging studies. [35,36] 3. ONJ related to drugs other than antiresorptives Between 2003 and 2008, the medical literature registered an explosion of Reports and Papers regarding ONJ related to BPs, the so-called BRONJ.…”

Bisphosphonate-related osteonecrosis of the jaw: from the sine qua non condition of bone exposure to a non-exposed BRONJ entity

“…Non-exposed BRONJ has been associated with oral bisphosphonates, 16,23 osteoporosis, odontogenic infections, 23 tooth extraction and prosthetic appliances 16 ( Table 2). Schiodt et al 20 reported tooth extraction prior to BRONJ in 79% of patients with non-exposed lesions.…”

“…[12][13][14][15][16][17][18][19][20] Since then, two updates have been performed by the AAOMS 21,22 and several authors have discussed the possibility of BRONJ occurrence despite the absence of bone exposure. 16,18,20,23,24 According to them, this condition should be called nonexposed BRONJ. 18,20,24 BRONJ is a relatively recent entity and many doubts regarding its aetiopathogenesis and approach still persist.…”

“…In a retrospective multicentre study that still used the 2009 AAOMS criteria, 21 Fedele et al 23 reported that BRONJ diagnosis was missed in a quarter of patients. According to the authors, in some patients, symptoms seemed to fit Stage 0, but a BRONJ diagnosis was not established because, at that time, the definition of the disease still required bone exposure.…”