How cancer patients can lower the risk of bisphosphonate-related osteonecrosis of the jaw (BRONJ)

How cancer patients can lower the risk of bisphosphonate-related osteonecrosis of the jaw (BRONJ)

What we know

Bisphosphonate (BP) treatment is typically the first medicine used for patients with osteoporosis to slow the breakdown of bone and reduce the chance of fractures. Anti-resorptive agents, especially the BP zoledronic acid (or Zometa®) and the non-BP denosumab (or XGEVA®, Prolia®) are used to prevent the spread of cancers to the bone and elevated calcium levels that can accompany cancer in the bones, which occurs commonly in patients with late-stage cancers, including prostate cancer, breast cancer and myeloma. Anti-resorptive agent-treated cancer patients often report a reduction in pain. The clinical trials show a reduction of fractures by 36% [1].

However, cancer patients who are given high doses of potent anti-resorptive treatment, such as Zometa and XGEVA have an increased risk of developing a rare, but severe complication, osteonecrosis of the jaw (BRONJ)[2] BRONJ is identified when the bone in the jaw does not heal as a result of dental surgery[3], like a tooth extraction. BRONJ is likely to occur from a combination of the immuno-suppression of the cancer medicine, the trauma of a dental extraction, and the bacteria present in the mouth, but can be worsened by potently suppressing bone turnover. BRONJ affects the life quality of cancer patients, causing pain and swelling in the gum and poor healing of the jaw bone after dental surgery [4].

What can a cancer patient do to reduce the risk of BRONJ?

Maintain a healthy lifestyle

Studies show that people with diabetes have nearly three times the risk of developing BRONJ [14,15]. Smoking also increases the risk of BRONJ. Therefore, keeping a healthy diet and lifestyle can improve bone health and reduce the risk of infections in the jaw [15].

Prior to potent anti-resorptive therapy

See the dentist before starting potent anti-resorptive treatment

Tooth extraction is one of the key factors causing BRONJ in cancer patients taking BP or denosumab treatments [5]. Before starting such treatment, see your dentist and schedule all dental operations, such as tooth extraction, periodontal and endodontic treatments.

Consider taking antibiotics before dental surgery

More than 90% of the patients with BRONJ get a bacterial infection called Actinomycosis [6,12] in their jaw. A case-control study on myeloma patients receiving high doses of BP treatment for >20 months [3] found that a course of antibiotics markedly reduced the risk of BRONJ. Talk with your doctor about taking an antibiotic, such as penicillin, before any major dental procedures, if you are on Zometa or XGEVA for cancer.

During BP treatment

See your doctor before any dental procedures

If you have been taking BPs for more than 3 years, ask your doctor if you need to stop taking them for 3-6 months before any dental surgery.

Regular dental care

Work closely with your dentist and oncologist to keep your teeth and gums healthy. Plan to visit the dentist at least 4 times a year while you are on treatment [13].

Control and monitor any infections

Continuous infections can stimulate the progression of BRONJ [5]. If you have a high risk of BRONJ, use antibacterial mouthwash to prevent the risk of infection. If you develop infection or inflammation, speak with your doctor about starting an antibiotic and medicines to relieve pain.

References

[1] Saad, Fred, et al. “Long-term efficacy of zoledronic acid for the prevention of skeletal complications in patients with metastatic hormone-refractory prostate cancer.” Journal of the National Cancer Institute 96.11 (2004): 879-882.

[2] Reid, Ian R., and Jillian Cornish. “Epidemiology and pathogenesis of osteonecrosis of the jaw.” Nature Reviews Rheumatology 8.2 (2012): 90.

[3] Montefusco, Vittorio, et al. “Antibiotic prophylaxis before dental procedures may reduce the incidence of osteonecrosis of the jaw in patients with multiple myeloma treated with bisphosphonates.” Leukemia & lymphoma 49.11 (2008): 2156-2162.

[4] Gadiwalla, Yusuf, and Vinod Patel. “Osteonecrosis of the jaw unrelated to medication or radiotherapy.” Oral Surgery, Oral Medicine, Oral Pathology and Oral Radiology (2017).

[5] Eleutherakis‐Papaiakovou, Evangelos, and Aristotelis Bamias. “Antiresorptive treatment‐associated ONJ.” European journal of cancer care 26.6 (2017).

[6] Hansen, Torsten, et al. “Osteonecrosis of the jaws in patients treated with bisphosphonates–histomorphologic analysis in comparison with infected osteoradionecrosis.” Journal of oral pathology & medicine 35.3 (2006): 155-160.

[7] Hansen, Torsten, et al. “Actinomycosis of the jaws—histopathological study of 45 patients shows significant involvement in bisphosphonate-associated osteonecrosis and infected osteoradionecrosis.” Virchows Archiv 451.6 (2007): 1009-1017.

[8] Lugassy, Gilles, et al. “Severe osteomyelitis of the jaw in long-term survivors of multiple myeloma: a new clinical entity.” The American journal of medicine 117.6 (2004): 440-441.

[9] Biasotto, Matteo, et al. “Clinical aspects and management of bisphosphonates-associated osteonecrosis of the jaws.” Acta Odontologica Scandinavica 64.6 (2006): 348-354.

[10] Bisdas, S., et al. “Biphosphonate-induced osteonecrosis of the jaws: CT and MRI spectrum of findings in 32 patients.” Clinical radiology 63.1 (2008): 71-77.

[11] Lazarovici, Towy Sorel, et al. “Bisphosphonate-related osteonecrosis of the jaws: a single-center study of 101 patients.” Journal of Oral and Maxillofacial Surgery 67.4 (2009): 850-855.

[12] Naik, Nimesh H., and Thomas A. Russo. “Bisphosphonate-related osteonecrosis of the jaw: the role of actinomyces.” Clinical Infectious Diseases 49.11 (2009): 1729-1732.

[13] Mücke, Thomas, et al. “Prevention of bisphosphonate-related osteonecrosis of the jaws in patients with prostate cancer treated with zoledronic acid–A prospective study over 6 years.” Journal of Cranio-Maxillo-Facial Surgery 44.10 (2016): 1689-1693.

[14] Molcho, Shira, et al. “Diabetes microvascular disease and the risk for bisphosphonate-related osteonecrosis of the jaw: a single center study.” The Journal of Clinical Endocrinology & Metabolism 98.11 (2013): E1807-E1812.

[15] Nisi, M., et al. “Risk factors influencing BRONJ staging in patients receiving intravenous bisphosphonates: a multivariate analysis.” International journal of oral and maxillofacial surgery44.5 (2015): 586-591.

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