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Osteonecrosis of the jaws induced by anti-RANK ligand therapy

https://doi.org/10.1016/j.bjoms.2009.08.030Get rights and content

Abstract

Since the introduction of bisphosphonates to treat diseases that affect remodelling of bone, increasing numbers of patients with bisphosphonate-related osteonecrosis of the jaws have been reported; the number is currently unknown. Recently anti-RANKL agents (receptor activator of nuclear factor-κB ligand) such as denosumab (Prolia™, Amgen Inc., California, USA) that have a similar mode of action to bisphosphonates have been introduced to treat such diseases. We report a case of osteonecrosis that was induced by anti-RANKL therapy. To our knowledge this is the first case to have been induced by these agents.

Introduction

Bisphosphonates are used widely and effectively to treat diseases that affect the remodelling of bone such as postmenopausal osteoporosis, Paget disease, inflammatory arthritis, and metastatic bone diseases.1, 2, 3, 4 However, since their introduction increasing numbers of patients have been reported with bisphosphonate-related osteonecrosis of the jaws as a result of the treatment. Most cases arise after dental treatment or trauma, but spontaneous cases have also been described.5 The aetiology of bisphosphonate-related osteonecrosis of the jaws is not clear, but it is characterised by devitalised, hypocellular bone, and mucosal dehiscence.

The mechanism of action of bisphosphonates has not been fully elucidated, but it is known that they strongly inhibit osteoclast-mediated resorption, and reduce bone turnover.

A more recent therapeutic development for diseases that affect the remodelling of bone has been the blockade of receptor activator of nuclear factor-κB ligand (RANKL). One of these agents is denosumab (Prolia™) a highly specific fully human IgG2 monoclonal antibody to RANKL6. It targets RANKL and inhibits the interaction with receptor activator of nuclear factor-κB (RANK). RANK is a member of the tumour necrosis factor superfamily,7 and is an important molecule that controls differentiation and survival of osteoclasts that interfere with osteoclastogenesis.8

To date, denosumab has been well-tolerated in early clinical trials and its used has shown sustained reduction in bone turnover and an increase in bone mineral density, which may potentially offer superior results to bisphosphonates for the treatment of osteoporosis.6 Few patients have been treated with anti-RANKL agents, but investigations are currently being done into their use for the treatment of other diseases that affect remodelling of bone. To our knowledge, osteonecrosis resulting from treatment with these agents has not been reported previously.

Section snippets

Case report

A 60-year-old man with a lesion in the region of the left body of the mandible was referred to our department by his dentist. He complained of swelling and discharging pus from the left mandible of 2 months’ duration. On examination he had an ulcerated area of exposed bone roughly 3 cm long in this region that was discharging pus (Fig. 1, Fig. 2). He had a history of laryngeal carcinoma that had been treated with laser surgery (no radiotherapy), and metastatic prostatic adenocarcinoma. His

Discussion

The authors believe that our patient had osteonecrosis of the jaws induced by anti-RANKL treatment, and to our knowledge no other such case has been reported previously. As anti-RANKL agents are increasingly being used for the treatment of postmenopausal osteoporosis and are currently being investigated for the treatment of metastatic bone disease it is possible that the number of cases of osteonecrosis induced by anti-RANKL treatment will increase in future.

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