Building bone in the jaw with denosumab in adult Langerhans cell histiocytosis.

Abstract

A patient with multisystem Langerhans cell histiocytosis and extensive jaw osteolysis experienced remarkable mandibular bone regeneration following short-term denosumab therapy. This unique observation challenges current concepts of denosumab action in the jaw and provides novel in vivo evidence of structural repair through RANKL inhibition.

Background: Denosumab is an established inhibitor of receptor activator of nuclear factor-κB ligand (RANKL) that effectively suppresses osteoclastic bone resorption but has also been associated with medication-related osteonecrosis of the jaw (MRONJ).

Case presentation: We report a 41-year-old man with multisystem Langerhans cell histiocytosis (LCH) presenting with extensive osteolytic destruction of the maxilla and mandible following multiple dental extractions, clinically resembling MRONJ. Molecular analysis identified a MAP2K1 mutation, and staging confirmed multisystem disease involving the jaw, clavicle, and lungs. The patient received denosumab (120 mg every 2 months for 6 months), resulting in rapid pain relief, marked suppression of serum C-terminal telopeptide of type I collagen and procollagen type I N-terminal propeptide, and substantial reduction in metabolic activity on FDG-PET/CT. Most remarkably, serial imaging demonstrated extensive new bone formation with restoration of mandibular cortical integrity and alveolar architecture despite profound suppression of bone turnover. This striking regenerative response contrasts with the established association between denosumab and MRONJ and suggests that inhibition of disease-driven RANKL signaling in LCH may permit reversal of severe jaw destruction.

Conclusion: These observations provide novel in vivo evidence that denosumab may promote structural repair of LCH-associated jaw lesions and raise important mechanistic questions regarding the role of RANKL in pathological jaw bone remodeling.