Published: June 2012

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Osteonecrosis: A Pain in the Jaw

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Prescriber Update 33(2): 13-14
June 2012

Osteonecrosis of the Jaw (ONJ) has been associated with a number of medicines and is a potentially debilitating condition that is difficult to treat. Prescribers are advised to recommend oral hygiene measures and closely monitor patients who are at risk of experiencing ONJ.

ONJ is characterised by the presence of necrotic, exposed bone in the jaw. The jaws are particularly sensitive to osteonecrosis due to high bone turnover resulting from daily activity and the presence of teeth¹.

Patients usually experience pain, possible secondary swelling, painful lesions, tooth mobility, ulceration and various dysaesthesias. However, patients can also be asymptomatic.

Medicines associated with the development of osteonecrosis include:

• bisphosphonates (both oral and intravenous)
• corticosteroids
• angiogenesis inhibitors such as bevacizumab (Avastin) and sunitinib (Sutent)
• denosumab (Prolia), a new medicine for osteoporosis.

Patients may be considered to have bisphosphonaterelated ONJ if they have current or previous treatment with a bisphosphonate and have exposed or necrotic bone in the maxillofacial region that has persisted for more than eight weeks with no history of radiation therapy to the jaws².

Additional factors that may have an additive impact on the risk of ONJ are invasive dental procedures, radiotherapy, renal insufficiency, alcohol use, smoking, obesity, increasing age, anaemia, diabetes, rheumatoid arthritis and vitamin D deficiency³.

To date, the Centre for Adverse Reactions Monitoring (CARM) has received a total of 28 reports of ONJ that they considered to be related to the medicine. Alendronic acid was suspected in 13 cases, pamidronic acid in 11 cases and zoledronic acid in seven cases (some cases involved more than one suspect medicine).

Bisphosphonate-induced ONJ is estimated at 0.1% for patients with cancer being treated for associated bone problems that have not had invasive dental procedures⁴. The incidence of ONJ associated with oral bisphosphonate treatment is much lower, possibly in the region of one in 60 thousand⁵.

In a literature review of case reports, the minimum onset time was 10 months with zoledronic acid, 18 months with pamidronic acid and three years with oral bisphosphonate treatment⁶. The average cumulative minimum dose prior to diagnosis was 49mg for zoledronic acid, 2,217mg for pamidronic acid and 13,870mg for oral bisphosphonates⁶.

Despite the association of these medicines with ONJ, the benefits of bisphosphonate treatment are still considered to outweigh the risks of experiencing this condition.

References

1. Shannon J, Modelevsky S, Grippo AA. 2011. Bisphosphonates and osteonecrosis of the jaw. Journal of the American Geriatrics Society 59: 2350-5.
2. Ruggiero SL. 2011. Bisphosphonate-related osteonecrosis of the jaw: an overview. Annals of the New York Academy of Sciences 1218: 38-46.
3. Hoff AO, Toth B, Hu M, et al. 2011. Epidemiology and risk factors for osteonecrosis of the jaw in cancer patients. Annals of the New York Academy of Sciences 1218: 47-54.
4. Hellstein JW, Adler RA, Edwards B, et al. 2011. Managing the care of patients receiving antiresorptive therapy for prevention and treatment of osteoporosis: executive summary of recommendations from the American Dental Association Council on Scientific Affairs. Journal of the American Dental Association 142: 1243-51.
5. Bolland M, Hay D, Grey A, et al. 2006. Osteonecrosis of the jaw and bisphosphonates-putting the risk in perspective. New Zealand Medical Journal 119: U2339.
6. Palaska PK, Cartsos V, Zavras AI. 2009. Bisphosphonates and time to osteonecrosis development. Oncologist 14: 1154-66.
7. Borromeo GL, Tsao CE, Darby IB, et al. 2011. A review of the clinical implications of bisphosphonates in dentistry. Australian Dental Journal 56: 2-9.