Anti-resorptive drugs

Anti-resorptive drugs inhibit osteoclast differentiation and function, leading to decreased bone resorption and remodelling.

There are two main types of anti-resorptive drugs that have been associated with osteonecrosis of the jaw, the bisphosphonates and denosumab.

These are used in the management of osteoporosis and other non-malignant and malignant conditions.

Anti-resorptive drugs can have a significantly positive effect on the quality of life of patients by reducing or delaying onset of disease or treatment complications, such as bone fractures and bone pain.

Bisphosphonates are used to reduce the symptoms and complications of metastatic bone disease. The drugs are usually delivered as regular high dose intravenous infusions in this patient group.

Bisphosphonates are also indicated for:

  • treatment of osteoporosis
  • treatment of Paget's disease
  • treatment of osteogenesis imperfecta
  • treatment of fibrous dysplasia
  • prophylaxis to counteract the osteoporotic effects of glucocorticoids
  • prevention of bone-related/skeletal complications in patients with primary hyperparathyroidism and cystic fibrosis

Patients in these groups can take the drugs orally (usually once a week) or the drugs can be given as quarterly or yearly infusions.

The bisphosphonates have a high affinity for hydroxyapatite and persist in the skeletal tissue for a significant period of time, with alendronate having a half-life in bone of around 10 years. However, it is unclear how this influences the risk of MRONJ once a patient has stopped taking the drugs.

Denosumab is a fully human monoclonal antibody which inhibits osteoclast function and associated bone resorption by binding to the receptor activator nuclear factor kappa B ligand (RANKL).

Like the bisphosphonates, denosumab is indicated for the prophylaxis and treatment of osteoporosis and to reduce skeletal-related events related to metastasis.

Denosumab is administered subcutaneously every six months in osteoporosis patients, with a higher dose given monthly in patients with metastatic disease.

Denosumab does not bind to bone and its effects on bone turnover diminish within nine months of treatment completion.