OBJECTIVE: Nonsurgical treatment of mandibular fractures secondary to medication-related osteonecrosis of the jaw (MRONJ) or osteoradionecrosis (ORN) mostly results in nonunion, whereas nonsurgical fracture treatment of atrophic fractures can achieve favorable results in selected cases. The aim of this study was to compare callus formation in pathological mandibular fractures due to MRONJ, ORN, or extreme mandibular atrophy. METHODS: A retrospective cohort study reviewing the medical records of all MRONJ-, ORN-, or atrophy-related fractures treated at the departments of maxillofacial surgery in the Leuven or Lille university hospitals between 2010 and 2019 was undertaken. The primary predictor variable in this study was disease state (MRONJ, ORN, or extreme mandibular atrophy). The primary outcome variable was callus formation after 1 month of follow-up (present, absent). Additional study variables measured included patient age and gender. T-tests, Fisher exact tests, and multiple logistic regression were used for statistical analysis. The significance level was set at P < .05. RESULTS: Seventy patients were analyzed (12 MRONJ cases, 54 ORN fractures, 4 atrophic fractures). The callus formation prevalence in nonsurgically approached fractures secondary to ORN and MRONJ after 1 month of follow-up was 3.03% (2/66 cases). In contrast, callus was detected in all patients in the mandibular atrophy-related fracture group. Osteonecrosis was statistically correlated with impaired callus formation (P = .0121). CONCLUSIONS: Whereas one would expect indirect fracture healing and thus callus formation to occur in all non-surgically treated fractures, our data demonstrate its absence in the majority of MRONJ- and ORN-related fractures. Multiple plausible explanations for this phenomenon were identified: periosteal damage with loss of callus-forming cells, compromised vasculature, and bacterial colonization.