IRIS H MEDICINE S BOA RD

BISPHOSPHONATES AND OSTEONECROSIS OF THE JAW: UPDATE ON RISK MINIMISATION INCLUDING NEW RECOMMENDATIONS ON PREVENTATIVE DENTAL MEASURES Bisphosphonates are a class of medicines together with current guidelines produced by approved for various indications related to their learned societies. The review also incorporated inhibitory effect on bone resorption in certain advice from a group of experts representing all malignant and benign diseases, including areas of medicine where bisphosphonates are prophylaxis and treatment of osteoporosis; used, dentistry and bone surgery, and treatment of Paget’s disease; and as part of some representatives of patients’ organisations.Whilst it cancer regimens, particularly for metastatic bone is recognised that risk factors for ONJ are multiple cancer and multiple myeloma. Detailed information and currently not fully elucidated, the most on the approved indications for use, warnings and significant risk factors for the development of ONJ precautions etc. is described in the product in association with bisphosphonates are information for the individual products concerned considered to be bisphosphonate potency, route of (alendronic acid, clodronic acid, etidronic acid, administration and cumulative dose of ibandronic acid, neridronic acid, pamidronic acid, bisphosphonate exposure. A history of dental risedronic acid, tiludronic acid, zoledronic acid). disease, including invasive dental procedures, The risk of osteonecrosis of the jaw (ONJ) in dental trauma, periodontal disease, and poorly association with the use of bisphosphonates has fitting dentures is associated with an increased risk been closely monitored and reviewed at EU level of ONJ. Further research is needed to increase on several occasions, with a number of risk knowledge about the underlying mechanisms and minimisation measures taken, including updates risk factors for ONJ, and about how best to minimise to the product information and communication to these risks. The EU regulatory authorities will healthcare professionals. The most recent review explore strategies to promote this research and the of information on the risk of bisphosphonate European Medicines Agency (EMA) has adopted a associated ONJ included assessment of the definition of ONJ related to bisphosphonates to currently available published literature and data facilitate future case reporting and research. provided by the Marketing Authorisation Holders However, healthcare professionals should consider (including data from experimental and preclinical these risk factors when evaluating an individual’s studies, clinical trials, and post-marketing reports), risk of developing ONJ . iv This information is supplied by the IMB for use in the Irish Medicines Formulary. However, the IMB is independent and impartial to any other information contained in this formulary. Advice for Healthcare Professionals maintaining good oral hygiene in preventing • The risk of developing ONJ in association with dental disease. oral bisphosphonates seems to be low. The risk of ONJ is substantially greater for patients • There is a need to ensure oral and dental follow- receiving intravenous bisphosphonates for up performed by a dentist. cancer indications than for patients receiving oral bisphosphonates for osteoporosis or Paget’s • Dental examination is recommended as soon as disease. the patient develops oral symptoms, such as pain or swelling. • There is clear evidence to suggest bisphosphonate-specific and indication-specific • Dental interventions should be as conservative risk factors for the development of ONJ, such as and preservative as possible (preservation of potency (highest for zoledronic acid), route of tooth). The dentist should refer the patient to administration (e.g. intravenous ibandronic acid, specialist centres if extractions or invasive pamidronic acid and zoledronic acid); and procedures are contemplated. cumulative dose. The evidence base is less robust for other proposed risk factors (e.g. For patients receiving bisphosphonates for NON- duration and type of malignant disease, CANCER indications, the recommendations are concomitant treatment, smoking, and comorbid as follows: conditions). However, healthcare professionals should consider these risk factors when Before starting treatment with bisphosphonates: evaluating an individual’s risk of developing ONJ. • A dental examination should be performed if the dental status of the patient is poor. Since the • A history of dental disease – including invasive start of bisphosphonate treatment may not be dental procedures, dental trauma, periodontal urgent in this setting, oral and dental assessment disease, and poorly fitting dentures is associated may be followed by dental care if necessary. with an increased risk of ONJ. During treatment with bisphosphonates: Risk Minimisation – Recommendations for • Patients should be advised of the importance of preventative dental measures (baseline maintaining good oral hygiene to prevent dental assessment and ongoing monitoring) disease.

For patients receiving bisphosphonates for • Routine dental checkups by a regular dentist are CANCER indications; the recommendations are recommended. Dental examination is as follows: recommended as soon as the patient develops dental problems whilst on treatment. Dental Before starting treatment with bisphosphonates: interventions should be as conservative and • An oral and dental assessment should be preservative as possible. performed by a dentist or oral surgeon to optimise dental health. If dental treatment is required, this Key message: All patients with cancer should have should take place as quickly as possible before a dental check-up before bisphosphonate start of bisphosphonate treatment. If urgent treatment. All other patients who start treatment with a bisphosphonate is necessary, bisphosphonates should have a dental this treatment should not be delayed and the examination if they have poor dental status. patient should be referred in an expedited During bisphosphonate treatment, patients manner for a dental examination. should be advised to maintain good oral hygiene, receive routine dental check-ups, and report any During treatment with bisphosphonates: oral symptoms such as dental mobility, pain or • Patients should be advised of the importance of swelling.

This information is supplied by the IMB for use in the Irish Medicines Formulary. However, the v IMB is independent and impartial to any other information contained in this formulary.