Multiple idiopathic external cervical root resorption in patient treated continuously with denosumab: a case report

Abstract

Background External root resorption is an irreversible loss of dental hard tissue as a result of odontoclastic action. Multiple external cervical root resorptions in permanent teeth are rare. The exact cause of external cervical root resorption is unclear. It is currently well established that RANK/RANKL signaling is essential for osteoclastogenesis and osteoclast-mediated bone resorption. Denosumab is an anti-RANKL antibody used for the treatment of postmenopausal osteoporosis. RANK/RANKL pathway suppression by denosumab is expected to suppress the activity of clastic cells responsible for hard tissue resorption involving both osteoclasts and odontoclasts. Case presentation This case report demonstrates aggressive and generalized idiopathic external cervical root resorption that started and advanced during ongoing antiresorptive therapy with the human monoclonal RANKL-blocking antibody denosumab without discontinuation of therapy in a 74-year-old female patient treated for postmenopausal osteoporosis. The extent of resorptive defects was too large and progressively led to fractures of the teeth. The number of teeth involved and the extend of destruction excluded conservative treatment. The affected teeth had to be extracted for functional prosthetic reconstruction. Conclusions This finding suggests that treatment with denosumab may be associated with severe and aggressive odontoclastic resorption of multiple dental roots despite an adequate inhibitory effect on osteoclasts in the treatment of osteoporosis. The RANKL-independent pathways of clastic cell formation are likely to be involved in this pathological process.

Multiple idiopathic cervical root resorption: A systematic review

“…An osteoporosis patient developed MICRR after denosumab discontinuation, and the author believed that this may be a potential cause of MICRR (Deeb et al, 2019). Meanwhile, in two recent case reports, patients developed MICRR despite continued denosumab treatment for osteoporosis or de novo metabolic breast cancer metastasized to bone (Beaumont et al, 2022; Mikušková et al, 2022). Only one study reported a family cluster of MICRR cases and reported that three of the four affected family members had missense mutations in the IRF8 gene heterozygous c.1219 G>A. Functional studies have suggested that this mutation may inhibit IRF8 expression and weaken IRF8 protein function to promote osteoclasts generation at the transcription level and increase the risk for root resorption (Thumbigere‐Math et al, 2019).…”

“…Deeb et al (2019) reported that one patient developed MICRR after denosumab discontinuation and proposed the "rebound effect hypothesis." Meanwhile, subsequent studies reported two MICRR patients during denosumab use, which overturned this hypothesis (Beaumont et al, 2022;Mikušková et al, 2022). Denosumab, a human monoclonal RANKL-directed antibody, prevents RANK receptor binding, thereby decreasing osteoclast-induced bone resorption (Miller, 2009).…”

“…The pathogenesis of MICRR is still unclear. MICRR was reported in a pertussis patient, indicating that it may be due to the neurogene spreading of pertussis virus (Kjaer et al, 2012) (Beaumont et al, 2022;Mikušková et al, 2022).…”

Introducing a new auto edge detection technique capable of revealing cervical root resorption in CBCT scans with pronounced metallic artifacts

“…ECR is mainly asymptomatic and would incidentally be detected through radiographic examinations unless it involves the pulp or periodontal tissues. Since effective treatments for ECR are needed to be timely, precise identification of their location and magnitude is crucial 4 , 8 – 10 .…”

Repair of an Extensive External Cervical Resorption Lesion Using Intentional Replantation with Crown Rotation

“…Although classification using 2D methods can be problematic, particularly for molars, they still play an important role in the preliminary treatment planning for ECR. Recently, cases of ECR with different aetiologies, including medications have been reported [ 4 , 5 ]. In addition, histopathological, cone-beam computed tomography (CBCT), micro-CT, nano-CT, and scanning electron microscopy have revealed different pathogenesis mechanisms [ 6 – 8 ].…”