Bisphosphonates and Osteonecrosis

Notice type: 3rd Party Publications

Date: 31/08/2006


Product name or type:
Bisphosphonates and Osteonecrosis MIMS Advisor

MIMS Publication August 2006

Problem Or Issue:
The above currently authorised products belong to the class of medicines collectively known as bisphosphonates that are indicated for the treatment of osteoporosis and the prevention of skeletal related events in patients with advanced malignancies involving bone. 

Following identification of cases of maxillofacial osteonecrosis associated with the administration of bisphosphonates via spontaneous adverse reaction reports and documented in the scientific literature, a European-wide review and assessment of the available data was conducted. This review was recently completed and concluded as follows: 

• The occurrence of maxillofacial osteonecrosis is positively associated with the intravenous forms of administration. 

• Maxillofacial osteonecrosis is also strongly related to the potency of the bisphosphonate, and to the underlying malignancy. 

• To date, the majority of cases have been reported in association with the most potent bisphosphonate, zoledronic acid, however, many patients received more than one product. 

• The time to onset varies widely for the individual products, as well as between products. 

• The main characteristics of the reported cases include female gender, advanced age, the presence of underlying malignant disease and mandibular location. 

• A number of risk factors were identified e.g. malignant disease, malnutrition, chemotherapy, radiotherapy, concomitant treatment with corticosteroids, advanced age, vascular disorders and dental procedures. 

• Osteonecrosis of the jaw has also been reported in patients with osteoporosis receiving oral bisphosphonates. • The aetiology and underlying pathophysiological mechanism remain unknown. 

• A causal relationship between the use of bisphosphonates and osteonecrosis in general, or osteonecrosis of the jaw specifically, was not confirmed. 

The review recommended that the currently approved product information for bisphosphonates should be updated to reflect that osteonecrosis of the jaw, generally associated with tooth extraction and/or local infection (including osteomyelitis) has been reported in patients with cancer receiving treatment regimens including primarily intravenously administered bisphosphonates. 

A dental examination with appropriate preventive dentistry should be considered prior to treatment with bisphosphonates in patients with concomitant risk factors (e.g. cancer, chemotherapy, radiotherapy, corticosteroids, poor oral hygiene). 

While on treatment, patients should avoid invasive dental procedures if possible. For patients who develop osteonecrosis of the jaw while on bisphosphonate therapy, dental surgery may exacerbate the condition. For patients requiring dental procedures, there are no data available to suggest whether discontinuation of bisphosphonate treatment reduces the risk of osteonecrosis of the jaw. Clinical judgement of the treating healthcare professionals should guide the management plan for each patient, based on individual benefit/risk assessment. 

The IMB is currently working with companies marketing bisphosphonates in Ireland to ensure that the product information is appropriately updated to reflect this important safety information. Finally healthcare professionals are reminded that any suspected adverse reactions should be reported to the IMB in the usual way. A downloadable version of the ADR report form is available from the HPRA’s website ( Downloaded forms may be completed and sent by freepost to the HPRA. Envelopes should be marked “Freepost”, Pharmacovigilance Unit, Health Products Regulatory Authority, The Earlsfort Centre, Earlsfort Terrace, Dublin 2. Alternatively, completed forms may be submitted by fax (01- 6762517). Post-paid report cards are also available from the Pharmacovigilance Unit at the HPRA (01- 6764971).

Background Information Or Related Documents:
Bisphosphonates and Osteonecrosis Document

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