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    • In this section we will try and address many of

    2019-04-22

    In this section we will try and address many of the frequently asked questions around preventive and prophylactic measures for patients either starting or already established on bone-targeted therapy (Figs. 2 and 3). In view of the difficulties in treating ONJ, preventive strategies would seem to make the most sense. The efficacy of preventive strategies was investigated in two studies. Authors tried to compare the incidence of ONJ between the investigational group and a control group. The investigational group underwent preventive measures including dental assessment prior to bisphosphonate initiation so that any invasive dental procedures could be completed prior to initiation of bisphosphonate therapy. Bisphosphonate treatment was delayed for 6–8 weeks until complete wound healing after surgical procedures. Whenever possible minor dental interventions with preservation of dental roots, and avoidance of dento-alveolar surgery were preferred over tooth extraction and prophylactic 3ʹ-deoxy-3′,4ʹ-didehydro-CTP were used with invasive procedures. The retrospective control group of patients had received bisphosphonates before implementation of preventive measures. Incidence of ONJ was reduced by two-three times in patients on preventive measures [44,45]. While this data is not from a randomized trial the authors did comment that given the effectiveness of ONJ preventive measures, performing a randomised study with a control group not receiving these measures would likely be considered unethical. According to these studies and numerous recommendations, patients should be consulted about risk of developing ONJ prior to initiation of bone-targeted treatments and informed about the importance of maintaining their oral hygiene. Patients should be advised to have a dental examination, treatment existing dental problem and extraction of teeth that cannot be restored, preferably by a dental surgeon familiar with the risks of ONJ, prior to starting bisphosphonate therapy. Patients should also avoid dento-alveolar surgical procedures involving the mandibular or maxillary bone while actively receiving intravenous bisphosphonates, or for several months after completion of the therapy [5]. For patients receiving on-going bone-targeted therapies they too should continue to have frequent dental examinations. This allows the identification and early treatment of any dental disease, and the establishment of a suitable recall and oral hygiene program. Maintenance of good oral hygiene is essential to the prevention of dental disease and is therefore particularly important for this group of patients. Patients need to be kept aware of the ongoing risks of ONJ and their association with surgical dental procedures [46]. A meta-analysis of seven published single centre, non-randomised studies with a prospective interventional cohort and retrospective control group investigating the efficacy of preventive measures was presented recently at cancer-induced bone disease symposium in Lyon. It showed efficacy of preventive measures with a relative reduction of 68% of ONJ risk (RR 0.32; 95% CI 0.20–0.50; p<0.001).(Prevention of Osteonecrosis of the Jaw (ONJ) in Cancer Patients Receiving Bisphosphonates: Empty Promise or Effective strategy? Tim Van den Wyngaert et al., Antwerp University Hospital, Edegem, Belgium, 12th International Conference on Cancer-Induced Bone Disease, 15–17 November, 2012, poster P31, www.nature.com/bonekey) Given that strategies to avoid ONJ are likely to be more effective than treating the condition once it occurs, it also seems sensible to reduce bisphosphonate exposure as much as possible. This can be accomplished by using less potent agents or less intensive infusion schedules, particularly in those patients who have been on bone-targeted agents for protracted periods of time. In multiple myeloma patients most guidelines recommend stopping bisphosphonates after two years. Recently emerging data in multiple myeloma patients suggests that the incidence of ONJ might be lowered by a reduced dosing schedule without affecting the incidence of skeletal-related events [47]. The risk of ONJ was eight-fold lower with the reduced schedule (monthly injection during the first year and every 3 months thereafter) than with the standard monthly schedule. However, this small retrospective study is not conclusive regarding the efficacy of less frequent dosing or its impact on the development of ONJ. However, a number of ongoing studies are investigating the efficacy of less intensive regimens of bisphosphonates in metastatic bone disease (NCT00320710, NCT00424983). The ZOOM trial, comparing a standard 4 weeks versus 12 weeks schedule of zoledronic acid for the prevention and delay of skeletal related events in metastatic breast cancer patients was presented at the ASCO meeting 2012 and showed equivalent results for these two regimens [48].