Summary Safety Review - Bisphosphonates - Assessing the Risk of Jaw Bone Loss (osteonecrosis of the jaw)
Review decision
A Summary Safety Review complements other safety related information to help Canadians make informed decisions about their use of health products. Each summary outlines what was assessed in Health Canada’s review, what was found and what action was taken by Health Canada, if any.
Issued: 2016-11-25
Product
Oral and injectable bisphosphonates (alendronate, clodronate, etidronate, pamidronate, risedronate and zoledronate)
Potential Safety Issue
Jaw bone loss (osteonecrosis of the jaw)
Overview
Use in Canada
- Bisphosphonates are used to strengthen bones in a variety of bone-related diseases such as:
- bones that become weak and brittle (osteoporosis);
- bones that grow too large and weak (Paget's disease of bone);
- the spread of cancer to bone (bone metastases);
- an increase in calcium levels in the blood due to cancer (hypercalcemia of malignancy); and
- blood cell (plasma cell) cancer (multiple myeloma).
- There are different kinds of bisphosphonate formulations currently marketed in Canada:
- used orally: alendronate (brand names Fosamax and Fosavance), risedronate (brand names Actonel, Actonel DR and Actonel Plus Calcium), etidronate (brand names Didronel and Didrocal);
- used intravenously (IV): all generics of pamidronate, zoledronate (brand name Zometa and Aclasta); and
- used either orally or intravenously: clodronate disodium (brand names Clasteon and Bonefos).
Safety Review Findings
- At the time of the review, Health Canada received 125 unique Canadian reports of jaw bone loss associated with the use of bisphosphonate products. Jaw bone loss was commonly reported in cancer patients.
- A review of recent publications and an analysis of the Canadian reports above showed a higher risk of jaw bone loss with the use of bisphosphonates, especially when IV formulations are used compared to oral formulations. Higher doses and strengths as well as longer treatment periods also contribute to the risk.
- This review also found other risk factors for jaw bone loss including dental conditions and procedures, radiation therapy, and medical conditions such as having fewer than normal red blood cells (anaemia) or bleeding disorders where blood clotting ability is impaired (coagulopathies).
- At the time of the review, the product information for all bisphosphonates already included a warning about the risk of jaw bone loss, but there were differences in the way the risk was described for the different drugs in this class.
Conclusions and actions
- Health Canada's safety review concluded that there is a higher risk of osteonecrosis of the jaw with the use of intravenous bisphosphonate products compared to the oral form, especially in cancer patients.
- Health Canada will be working with the manufacturers to update the Canadian product safety information for bisphosphonate products:
- Intravenous formulations will reflect the increased risk of jaw bone loss including stopping bisphosphonate use if jaw bone loss occurs while on treatment and delaying the start of bisphosphonate use in patients with unhealed open wounds in the mouth.
- All formulations will mention the additional factors that may play a role in jaw bone loss.
- Health Canada will also issue a notice in the Health Product InfoWatch when the product information is updated.
- Health Canada will continue to monitor side effect information for bisphosphonates, as it does for all health products on the Canadian market, to identify and assess possible harms. Health Canada will take appropriate and timely action, if and when any new health risks are identified.
Additional information
The analysis that contributed to this safety review included scientific and medical literature, Canadian and international adverse reaction reports and what is known about the use of these drugs both in Canada and internationally.
For additional information, contact the Marketed Health Products Directorate.