ONJ Position Paper

Position Statement of the Irish Osteoporosis Society on Bisphosphonate-associated Osteonecrosis of the Jaw (ONJ)

ONJ is a very rare but potentially serious adverse effect of bisphosphonate therapy. The majority (85%) of cases have occurred where the drug has been used in cancer patients who then have dental procedures. Other cases have been associated with oral infection or with direct trauma. This Position Statement is a considered assessment of the current evidence on this topic. Any decision about medical, dental or other treatment must be taken by doctor and patient together. We will continue to review the literature and the advice emerging from international clinical, research and drug safety bodies.

The risk of developing ONJ compared with the risk of fracture

Each year, fewer than one per 100,000 people on a bisphosphonate for osteoporosis will develop ONJ

The true incidence of ONJ is unclear, estimated at 0.001 to 3% across all uses of the drug. In osteoporosis, data has been obtained from case reports and from obligatory responses from pharmaceutical companies to drug safety agencies.

These figures indicate a risk of 0.7 per 100 000 patient years among osteoporosis patients. A patient-year is a way of gaining an average figure between people taking the drug for many years and those who have started the drug more recently. Each year, fewer than one per 100,000 people will develop ONJ. Compared with a risk of 3% in cancer-related treatment, this means a 3000-times lower risk in osteoporosis patients taking these drugs.

Most cases of ONJ have occurred with higher doses of intravenous zoledronic acid in cancer. In studies of this drug in osteoporosis patients (given once a year), two cases of ONJ occurred among 9892 patients – one in a patient receiving zoledronic acid, and one in the group receiving the inactive (placebo) treatment, a reminder that not all cases of ONJ are caused by bisphosphonate.

The decision to recommend a bisphosphonate.

Over 2,000 people will avoid a fracture for every one potential case of ONJ

Osteoporosis is a disorder of bone resulting in increased bone fragility and an increased risk of fracture. The risk of fracture is best determined by a combined assessment of clinical risk factors and a measurement of bone mineral density by DXA. A recommendation for treatment should take account of the probability of fracture, and should not be based exclusively on the T-score obtained from a DXA scan.

On average, across a range of studies, one fracture is prevented for every 30-50 patients prescribed a bisphosphonate (the figure for preventing spine fractures is typically smaller). Therefore over 2,000 people will avoid a fracture for every one potential case of ONJ.

The otherclasses of treatment for prevention of fracture (HRT, calcitriol, SERMs, calcitonin, Strontium, Ranelate and PTH analogues) have not been associated with ONJ. The risks and effectiveness of these as alternatives to bisphosphonates should be discussed by each individual with the doctor prescribing for them. 

Factors which increase the risk of ONJ and of fracture

Patient and doctor should appropriately weigh the very small risk of ONJ against the significant chance of another fracture

 

The risk of fracture is significantly increased in women, in advancing age and by continued use of corticosteroids. These same factors have been associated with an increased risk of ONJ in observations of those developing ONJ to date. As the vast majority of these cases received high doses of bisphosphonate during cancer treatment, it is unclear that these same issues pose a greater risk of ONJ among those with osteoporosis. However, it is certain that these factors do increase the risk of fracture. In the prevention of steroid-related osteoporosis, only the bisphosphonate class of drugs are currently licensed for use. Patient and doctor should appropriately weigh the very small risk of ONJ against the significant chance of (another) fracture. 

Dental care and bisphosphonate use

Complete any recommended dental treatment but do not delay starting bisphosphonate more than three months
You do not need to stop your bisphosphonate if a dental procedure is needed while you are on treatment

 

Almost all cases of ONJ, whether associated with cancer treatment or otherwise, have occurred following dental procedures. The Irish Osteoporosis Society respects the opinion of dental professional bodies in their recommendations. However, dental guidelines do not take account of the high incidence of fracture in osteoporosis, the effects of fracture on health and mortality, and the importance of bisphosphonates  in preventing fractures in those at risk.

The IOS supports the principal of preventative dental care. Where a dentist has recommended dental treatment, we advise patients to complete such treatment before commencing a bisphosphonate where this does not cause delay.

In those who suffer a fragility fracture, there is a two-fold increased risk of another fracture within a year without treatment. It is likely that bisphosphonates take six months to achieve a significant reduction in fracture risk, so delayed treatment may result in a fracture that could have been prevented.

The IOS does not advise stopping bisphosphonate when a dental procedure is required in a person already on this drug. Bisphosphonates adhere to the mineral in bone, and are only released slowly. Thus, it is unlikely that a brief (3 month) interruption of therapy would have any effect on bone metabolism or on the risk of ONJ. To date, there are no studies to indicate that the risk of ONJ is reduced by interrupting bisphosphonate therapy. In contrast, there is a significant risk that patients who cease treatment will have an increased fracture risk.