Quality Resource Guide l Bisphosphonate and Other Medication-Related Jaw Necrosis Part Two 6th Edition 5 www.metdental.com In cases of advanced stage MRONJ where control of bone destruction or infection is not possible, or in cases of pathologic fracture, an alveolectomy, sequestrectomy or resection of affected bone and reconstruction may be necessary. Placement of a titanium reconstruction plate following resolution of the infection will permit re-establishment of normal contour and acceptable levels of function. Generally, conservative management strategies are advocated with minimal surgical entry into small areas of necrotic bone associated with the use of oral bisphosphonates, with the exception of reducing any minor areas of uneven or sharp bone edges impinging on oral soft tissues. Approximately 60% of patients with oral bisphosphonate-associated MRONJ will heal after 6 to 12 months following discontinuation of the bisphosphonate without significant surgical intervention. The remaining patients may require surgical debridement. 5 [See Table 4 for stage- specific management strategies] Recent studies concerning the use of alternatives to bisphosphonate agents, monoclonal antibodies (denosumab) that bind to mediators of osteoclast differentiation, activation and survival or calcium analogues (strontium ranelate) have shown efficacy, however, MRONJ has also been noted following the use of denosumab, which blocks the RANKL pathway and interferes with osteoclast activation and function. 19,20,21,22 An additional management strategy has been described that places platelet-derived growth factors into defects created following marginal resection of necrotic alveolar bone. Results of this technique, though only used in a small number of patients, demonstrated complete healing, with mucosal coverage at previous defect sites. 23 Other therapies include utilization of vitamin D in conjunction with pentoxifylline, teriparatide, a parathormone analog and hyperbaric oxygen. oxygen. 24 Clear is the fact that treatment remains controversial with absence of a so-called “gold standard” protocol, which is uniformly effective. That said, approaches range from non-invasive ones where medical intervention of laser surface application may be attempted as an initial approach, clinical factors permitting. Invasive/ surgical procedures range from conservative to Table 4 - Stage-specific management of established osteonecrosis of the jaws 1 Stage 0 • No treatment - observe Stage 1 • Chlorhexidine 0.125% rinses twice daily • Patient education; quarterly follow-up • Evaluate and adjust any ill-fitting prostheses • Re-evaluate indications for continued bisphosphonate treatment Stage 2 • Chlorhexidine rinses 0.12% twice daily • Oral antibiotics, e.g., penicillin VK, cephalexin, 1st generation fluoroquinolone* • Pain management • Superficial debridement if soft tissue irritation is present Stage 3 • Chlorhexidine rinses 0.12% twice daily • Antibiotic treatment * • Pain management* • Surgical debridement; Resection of infected bone for longer term palliation and pain control* * The specific duration of antibiotic and analgesic administration should be guided by the clinical response obtained. The American Dental Association recommends a 14-day time span of antibiotic administration for the dental patient being treated with oral bisphosphonates, having unexpected pain, purulence or active sequestration after a dental procedure. 21 Far more problematic is determination of antibiotic use following surgical debridement of established stage 3 MRONJ cases. Clinical judgment with regard to severity on the part of the treating clinician would seem to be most appropriate. Marx advocates the rare use of continuous long-term intravenous antibiotics with or without concomitant use of prednisone in MRONJ cases with refractory infection. 23 Caveats: When symptomatic teeth are present within segments of exposed and necrotic bone, their extraction may be a valid consideration, given that such treatment will not likely accelerate or exacerbate necrosis. Atraumatic removal of a mobile sequestrum without exposure of uninvolved bone should be considered. In cases of oral bisphosphonate-related osteonecrosis, consideration should be given to discontinuation of the drug, if clinical circumstances permit, in concert with the patient’s treating physician. In cases of MRONJ-related use of intravenous bisphosphonates, there is no evidence of short-term benefit following discontinuation of the drug; however, there may be stabilization of existing MRONJ sites and a reduction of local symptoms over time when the drug is discontinued. A discussion with the patient and their oncologist should precede this decision. aggressive withn the former involving debridement and sequestrectomy with the latter involving resection of the affected area and reconstruction. Finally, combined surgical and less aggressive / less invasive procedures may be considered as dictated by clinical circumstances. Treatment goals should be directed toward management of pain, control and elimination of infection and reducing the progression of necrosis. Achieving these goals will eliminate the negative impact on quality of life in these patients. 25