UPFRONT

seems to have been understood. With regard to rotation of Cryer elevator within the cavity these two cases one patient had bilateral the ‘mixing’ point, the BMJ has taken a similar the tooth eventually ‘popped out’ distally. maxillary MRONJ ( two approach for many years and indeed a ‘tongue This enabled the extraction in an atraumatic years, leflunomide six years) following in cheek’ paper in its 2017 Christmas issue manner with no removal or tooth . In addition to this case was even picked up and enjoyed by the main sectioning required. a further two cases of methotrexate related national media. While we are not seeking to J. Liew, A. Beech, Gloucester are also being managed. copy the BMJ we feel that some dental levity is Methotrexate jaw necrosis is very rare and 1. Mamoun J. Use of elevator instruments when luxating just as appropriate and were delighted that in and extracting teeth in dentistry: clinical techniques. often preceded by lymphoproliferative our issue, the second of its kind, we published J Korean Assoc Oral Maxillofac Surg 2017; 43: 204–211. disorder, however, in both our cases this was contributions from readers who had been 2. Kaminishi R M, Davis W H, Nelson N E. Surgical removal absent but both on long-term leflunomide.2 of impacted mandibular third molars. Dent Clin North inspired by previous issues. To put this is in Am 1979; 23: 413–425. Of these two cases, one failed to heal post another context, the BDJ publishes something DOI: 10.1038/sj.bdj.2018.131 extraction while the other case had sponta- of the order of 1,000 pages of editorial content neous necrosis in a dentate region. a year; the ‘spoof’ matter takes up less than Pharmacology Leflunomide is not a new drug and in 0.01%. I am pleased to be able to reassure the absence of literature reported cases of MRONJ risk factor Dr Lawrence that we will not be marking the osteonecrosis of the jaw directly related to Summer Solstice or any other seasonal celebra- Sir, medication-related osteonecrosis of the jaw it as well as evidence of its impact on bone, tions in a similar manner so he may read the (MRONJ) is a well-documented complication it remains reasonable to consider it as a rest of the 2018 issues with unguarded belief. associated with bone modulating therapy from risk factor for MRONJ along with the other DOI: 10.1038/sj.bdj.2018.130 various and . In already recognised immunosuppressant additional anti-angiogenic medication (tyrosine when taken concomitantly with those drugs Oral surgery kinase inhibitors and new biologics including that have been implicated in jaw necrosis. monoclonal antibodies) have also been D. Patel, V. Patel, by email A helpful wisdom tooth implicated and hence the list of drugs continues 1. Urushibara M, Takayanagi H, Koga T et al. The antirheu- Sir, we would like to share a rather amusing to grow. Once patients are ‘at risk’ of MRONJ, matic drug leflunomide inhibits osteoclastogenesis by case involving an extraction technique on well established risk factors for development interfering with receptor activator of NF-κB ligand– a tooth with its own point of application. of the complication include dental extractions, stimulated induction of nuclear factor of activated T cells c1. Arthritis Rheum 2004; 50: 794–804. A patient was admitted for removal of 38 smoking, trauma, poor dental health and 2. Henien M, Carey B, Hullah E, Sproat C, Patel V. Meth- under local anaesthetic in our outpatient those who are immunocompromised and otrexate-associated osteonecrosis of the jaw: A report of two cases. Oral Surg Oral Med Oral Pathol Oral Radiol department. The tooth was partly erupted immunosuppressed. In this latter group certain 2017; 124: e283–287. but in a fairly vertical position. When a medications such as , azathio- DOI: 10.1038/sj.bdj.2018.132 mucoperiosteal flap was raised we noticed a prine, mycophenolate mofetil and methotrexate No studies carious cavity buccally which was not visible have been particularly identified. on the radiograph. Therefore, without the Leflunomide (Arava) is a disease Sir, I wish to congratulate Patel and need of bone removal, a Cryer elevator modifying anti-rheumatic drug (DMARD) colleagues for their article1 in which they was applied to the cavity as a point of that has been used in the treatment of evaluated medication-related osteone- application and the tooth was elevated in a rheumatoid and psoriatic arthritis for many crosis of the jaw (MRONJ) in early stage straightforward manner. years and can be given in combination with breast .1 The authors stated that oral In the available literature the drilling of a bisphosphonates and methotrexate. In vitro clodronate and i.v. appear cavity into a tooth to create an application studies indicate that leflunomide selectively to be equally effective in reducing breast point during elevation has been described.1,2 inhibits RANK-L-induced differentiation cancer recurrence and mortality in the In our case this tooth already had an of , which in turn directly affects adjuvant setting. However, to date, there appropriately sized buccal cavity created by bone remodelling as well as inhibiting are no studies comparing efficacy of oral caries subgingivally and hence no drilling several tyrosine kinases.1 These actions bisphosphonates with i.v. zoledronic acid was required (Fig. 1). The figure reveals a are exactly those targeted by the various in terms of reducing clinical outcome when slight distally curved root and the tooth implicated MRONJ drugs mentioned earlier. they are used in breast cancer at adjuvant morphology favoured the path of withdrawal Leflunomide has not been reported setting. Furthermore, it is expected that of this tooth in a distal direction. With slight as a MRONJ drug. However, we wish to intravenous bisphosphonates could be more highlight this drug as a possible candidate effective than oral due to their potentially to be added to the other immunosuppres- more anti-tumoral activity.2 sants that have already been recognised to K. Altundag, Ankara, Turkey increase the risk of MRONJ when taken 1. Patel V, Mansi J, Ghosh S et al. MRONJ risk of adjuvant in conjunction with bone modulating and bisphosphonates in early stage breast cancer. Br Dent J anti-angiogenic therapy. In our dedicated 2017; 224: 74–79. jaw necrosis clinic, 102 patients have been 2. Tonyali O, Arslan C, Altundag K. The role of zoledronic acid in the adjuvant treatment of breast cancer: current perspec- Fig. 1 The ‘helpful’ tooth which was straightforward registered with MRONJ of which only two tives. Expert Opin Pharmacother 2010; 11: 2715–2725. to extract cases are from oral bisphosphonates. In DOI: 10.1038/sj.bdj.2018.133

198 BRITISH DENTAL JOURNAL | VOLUME 224 NO. 4 | FEBRUARY 23 2018 Official j ournal of the British Dental Associati on.