Osteonecrosis of the jaw complicating bisphosphonate treatment for bone disease in multiple myeloma: an overview with recommendations for prevention and treatment

Abstract

Osteonecrosis of the Jaw (ONJ) is a recently recognised and potentially highly morbid complication of bisphosphonate therapy in the setting of metastatic malignancy, including myeloma. Members of the Medical and Scientific Advisory Group of the Myeloma Foundation of Australia formulated guidelines for the management of bisphosphonates around the issue of ONJ, based on the best available evidence in June 2008. Prior to commencement of therapy, patients should have an oral health assessment and be educated about the risks of ONJ. Dental assessment should occur 6 monthly during therapy. If tooth extraction is required, sufficient time should be allowed for complete healing to occur prior to commencement of bisphosphonate. As the risk of ONJ increases with duration of bisphosphonate therapy, we recommend annual assessment of dose with modification to 3 monthly i.v. therapy or to oral therapy with clodronate for those with all but the highest risk of skeletal-related event. Established ONJ should be managed conservatively; a bisphosphonate "drug holiday" is usually indicated and invasive surgery should generally be avoided. These recommendations will assist with clinical decision making for myeloma patients who are at risk of bisphosphonate-associated ONJ.

Bevacizumab and osteonecrosis of the jaw: incidence and association with bisphosphonate therapy in three large prospective trials in advanced breast cancer

“…Recent guidelines recommend that invasive dental procedures are completed before initiation of high-dose bisphosphonate therapy [36,37]. Non-urgent procedures should be delayed for 3-6 months following interruption of bisphosphonate therapy.…”

A review of the clinical implications of bisphosphonates in dentistry

“…[56][57][58][60][61][62][63][64][65] However, the AmDA also promotes oral evaluation as beneficial either before or early on in oral bisphosphonate therapy, 58 the AAOMS recommend oral evaluation if oral bisphosphonates have been received in the last three months, 63 and the Canadian Consensus Practice Guidelines (CCPG) recommend oral evaluation prior to oral bisphosphonate therapy when appropriate dental care and good oral hygiene are not present. 60 The Australian Therapeutic Guidelines favour a firm preventive approach, advising a comprehensive oral evaluation and establishment of oral health prior to commencement of all bisphosphonates, including oral.…”

“…Under these circumstances patients must be warned of the possible risk of ONJ, and written informed consent considered. The guidelines are not consistent for advising cessation of bisphosphonates prior to invasive dental procedures 56,57,60,62,64 (Table 2). Nonetheless, IV bisphosphonates are best ceased at least one month prior to invasive dental procedures, and not recommenced until healing is achieved (systemic condition permitting).…”

“…Extractions should always be performed as atraumatically as possible with direct closure of the socket by suturing and antibiotic prophylaxis considered, especially in immunocompromised patients. 64,65 Two guidelines also recommend prophylactic chlorhexidine mouthwashes. 58,64 It should be noted that root planing is a low risk invasive procedure, 15 and whilst caution is advised, cessation of bisphosphonates may not be warranted.…”

“…68 Given that the risk of ONJ in cancer correlates with duration of administration of IV bisphosphonates, and zoledronic acid in particular, a number of international and Australian guidelines have been established to reduce the cumulative dose of IV bisphosphonates received in multiple myeloma. 61,62,64 In general, monthly IV NBPs are advised for disease with active osseous involvement, but after this initial treatment phase reassessment occurs (12-24 months), and alternatives such as complete NBP cessation, oral bisphosphonates or three-monthly IV NBPs are to be considered.…”