Osteoporosis prevention, diagnosis and management in postmenopausal women and men over 50 years of age

Recommendations

Medication-related osteonecrosis of the jaw

Medication-related osteonecrosis of the jaw (MRONJ) is defined as an area of exposed bone in the maxillofacial region that has persisted for more than eight weeks, in a patient receiving bisphosphonates, denosumab or antiangiogenic therapy for cancer, and where there is no history of radiation therapy to the jaws or obvious metastatic disease to the jaws.1

A recently described condition with few prevalence studies published, MRONJ appears to occur more rarely in patients undergoing osteoporosis therapy than in patients with cancer being treated with anti-resorptives to prevent skeletal-related adverse events. The reported prevalence is between <1 and 10 cases per 10,000 in patients receiving oral bisphosphonate therapy for osteoporosis, marginally higher than the incidence in the general population.2,3 Duration of oral bisphosphonate therapy for osteoporosis is a risk factor for MRONJ, with one study reporting 21 cases per 10,000 after four years of therapy.2 This time frame may be shortened if the patient is also being treated with long-term glucocorticoids or anti-angiogenic drugs.1 A prevalence of 1.7 cases per 10,000 has been reported for patients undergoing annual intravenous zoledronic therapy for three years, with no change after six years therapy.4,5 For denosumab, the risk of MRONJ is reported to be four cases per 10,000.6 Compared with patients receiving higher doses of anti-resorptives (eg zoledronic acid or denosumab) for cancer treatment, the risk of MRONJ for patients with osteoporosis exposed to anti-resorptive medications is approximately 100 times smaller.1

The aetiology of MRONJ is uncertain, but appears to be multifactorial and related to the dose and duration of exposure to the anti-resorptive agent, pre-existing oral disease profile, dentoalveolar oral surgery and genetic polymorphisms.7

Recent consensus recommendations from the American Association of Oral and Maxillofacial Surgeons (AAOMS)1 and the International Task Force on Osteonecrosis of the Jaw7 state that elective dentoalveolar oral surgery does not appear to be contraindicated in patients undergoing anti-resorptive therapy for osteoporosis. However, identification and treatment of dental disease prior to the initiation of anti-resorptive therapy, if possible, is recommended.7 Patients should be adequately informed of the very small risk of MRONJ.

The AAOMS recommends that if systemic conditions permit, discontinuation of oral bisphosphonates for two months before and three months after elective invasive dental surgery may be considered in order to lower the risk of MRONJ.1 This guidance contrasts with that of the American Dental Association (ADA), as well as the International Task Force on Osteonecrosis of the Jaw, both of which state that there is insufficient evidence to recommend a break from anti-resorptive drug therapy, or a waiting period before performing minor oral surgical treatment.7,9 However, the International Task Force on Osteonecrosis of the Jaw recommends that in those at high risk for the development of MRONJ, pausing anti-resorptive therapy following extensive oral surgery should be considered until the surgical site heals with mature mucosal coverage.7 Patients with established MRONJ should avoid elective dentoalveolar oral surgery, as this may result in additional areas of exposed necrotic bone.1 Research also suggests an improved outcome of MRONJ if anti-resorptive therapy is ceased.8

Optimising oral hygiene prior to initiating anti-resorptive therapy may reduce the incidence of MRONJ.7 Good dental hygiene and care is therefore recommended for all patients undergoing anti-resorptive therapy for osteoporosis, particularly in those using long-term oral bisphosphonates. There is a strong association between periodontitis and MRONJ, due to the increased likelihood of extractions, the direct effects of bacterial infection and delayed healing due to inflammation.10 Improved dental awareness and prophylactic intervention have been shown to significantly reduce the incidence of MRONJ in patients receiving anti-resorptive therapy for cancer.11

More research to understand the pathophysiology of MRONJ is required, and future recommendations may change to reflect improved knowledge of this condition. However, it is important to be aware of the proven benefits of anti-resorptive therapy in terms of reducing fracture risk, in comparison with the very small risk of serious adverse events such as MRONJ.

  1. Ruggiero SL, Dodson TB, Fantasia J, et al. American Association of Oral and Maxillofacial Surgeons position paper on medicationrelated osteonecrosis of the jaw—2014 update. J Oral Maxillofac Surg 2014;72(10):1938–56.
  2. Lo JC, O’Ryan FS, Gordon NP, et al. Prevalence of osteonecrosis of the jaw in patients with oral bisphosphonate exposure. J Oral Maxillofac Surg 2010;68(2):243–53.
  3. Malden N, Lopes V. An epidemiological study of alendronate-related osteonecrosis of the jaws. A case series from the south-east of Scotland with attention given to case definition and prevalence. J Bone Miner Metab 2012;30(2):171–82.
  4. Grbic JT, Black DM, Lyles KW, et al. The incidence of osteonecrosis of the jaw in patients receiving 5 milligrams of zoledronic acid: Data from the health outcomes and reduced incidence with zoledronic acid once yearly clinical trials program. J Am Dent Assoc 2010;141(11):1365–70.
  5. Black DM, Reid IR, Boonen S, et al. The effect of 3 versus 6 years of zoledronic acid treatment of osteoporosis: A randomized extension to the HORIZON-Pivotal Fracture Trial (PFT). J Bone Miner Res 2012;27(2):243–54.
  6. Papapoulos S, Chapurlat R, Libanati C, et al. Five years of denosumab exposure in women with postmenopausal osteoporosis: Results from the first two years of the FREEDOM extension. J Bone Miner Res 2012;27(3):694–701.
  7. Khan AA, Morrison A, Hanley DA, et al, on behalf of the International Task Force on Osteonecrosis of the Jaw. Diagnosis and management of osteonecrosis of the jaw: A systematic review and international consensus. J Bone Miner Res 2015;30(1):3–23.
  8. Damm DD, Jones DM. Bisphosphonate-related osteonecrosis of the jaws: A potential alternative to drug holidays. Gen Dent 2013;61(5):33–38.
  9. Hellstein JW, Adler RA, Edwards B, et al, American Dental Association Council on Scientific Affairs Expert Panel on Antiresorptive Agents. 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. J Am Dent Assoc 2011;142(11):1243–51.
  10. Tsao C, Darby I, Ebeling PR, et al. Oral health risk factors for bisphosphonate-associated jaw osteonecrosis. J Oral Maxillofac Surg 2013;71(8):1360–66.
  11. Sim leW, Sanders KM, Borromeo GL, Seymour JF, Ebeling PR. Declining incidence of medication-related osteonecrosis of the jaw in patients with cancer. J Clin Endocrinol Metab 2015;100(10):3887–93.

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