title: Denosumab: Prevention and management of hypocalcemia, osteonecrosis of the jaw and atypical fractures.
abstract: Denosumab, a bone-modifying agent, reduces the risk of skeletal-related events in patients with bone metastases from solid tumors and is generally well tolerated. However, hypocalcemia, osteonecrosis of the jaw (ONJ) and atypical fracture are potential and important toxicities of denosumab therapy that require attention. In pivotal phase III trials in patients with bone metastases from solid tumors, the incidence of hypocalcemia was 9.6% in denosumab-treated patients, with most events being asymptomatic, grade 2 and resolving by week 4. Established hypocalcaemia requires additional short-term calcium and vitamin D supplementation and, if severe, administration of intravenous calcium. ONJ was reported in 1.8% of patients receiving denosumab over 3 years in these trials. Involvement of an experienced oro-maxillary surgeon is important if ONJ is suspected. Atypical fractures were rare in a large study of denosumab using the dose and scheduling approved for the treatment of osteoporosis. To prevent toxicities, patients should maintain calcium and vitamin D supplementation, good oral hygiene and regular dental reviews throughout treatment. This article presents case studies from our clinical practice and discusses the pathophysiology of these toxicities along with guidance on prevention, diagnosis and management.
authors.affiliation: The Queen Elizabeth Hospital, South Australia, Australia.
authors.forename: Kenneth
authors.initials: K
authors.lastname: Pittman
authors.affiliation: Cabrini Institute, Cabrini Health, and Department of Oncology, Frankston Hospital, Victoria, Australia.
authors.forename: Yoland C
authors.initials: YC
authors.lastname: Antill
authors.affiliation: Department of Haematology and Oncology, Amgen Australia, Australia.
authors.forename: Amanda
authors.initials: A
authors.lastname: Goldrick
authors.affiliation: Royal Brisbane & Women's Hospital, Queensland, Australia.
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Goh
authors.affiliation: Royal Melbourne and Epworth Hospitals, Victoria, Australia.
authors.forename: Richard H
authors.initials: RH
authors.lastname: de Boer
mesh_terms: D001859:Bone Neoplasms / Q000188:drug therapy* / Q000517:prevention & control*; D000069448:Denosumab / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D006996:Hypocalcemia / Q000188:drug therapy* / Q000517:prevention & control*; D007571:Jaw Diseases / Q000188:drug therapy* / Q000517:prevention & control*; D008297:Male; D010020:Osteonecrosis / Q000188:drug therapy* / Q000517:prevention & control*
chemical_list: D000069448:Denosumab
keywords: atypical fracture; case studies; denosumab (Xgeva); hypocalcemia; osteonecrosis of the jaw