Risk Reduction of Medication-Related Osteonecrosis of the Jaw

© Springer-Verlag Berlin Heidelberg 2015

Sven Otto (ed.)Medication-Related Osteonecrosis of the Jaws10.1007/978-3-662-43733-9_14

14. Risk Reduction of Medication-Related Osteonecrosis of the Jaw

Noam Yarom  and Stefano Fedele1

Oral Medicine Unit, UCL Eastman Dental Institute, University College London, 256 Gray’s Inn Road, London, WC1X 8LD, UK
Noam Yarom
Management of Medication-Related Osteonecrosis of the Jaw is challenging and outcomes of treatment are unpredictable. There is wide consensus that risk of ONJ can be, at least in part, reduced through control of a number of factors associated with increased likelihood of ONJ development. Robust evidence however remains limited. The aim of this chapter is to provide a comprehensive summary of available evidence upon risk-reduction measures for patients at risk of ONJ.


Medication-Related Osteonecrosis of the Jaw (ONJ) is a potentially severe adverse side effect associated with the use of several medications, most notably bisphosphonates and denosumab [1]. Treatment of ONJ remains challenging and there remains no definitive curative with the possible exception of surgical resection in selected cases. Considering that the vast majority of patients are also affected by metastatic incurable cancer, therapy of ONJ is often aimed at controlling painful symptoms and infection [2].
Several studies have reported a number of risk factors that increase the likelihood of patients to develop ONJ (see chapter 3, page 27); accordingly, it has been suggested that control of these factors could translate into a reduced risk of ONJ. During the last decade, a number of risk-reduction strategies have been suggested and introduced [35]. However, relevant recommendations have been mostly based on expert opinion with little, if any, solid supporting clinical evidence. There remains virtually no well-designed randomised controlled trial and very few small prospective observational studies that have investigated the efficacy of risk-reduction strategies in individuals exposed to anti-resorptive agents. The aim of this chapter is to provide a comprehensive summary of available evidence regarding risk-reduction measures for patients at risk of ONJ. The relevance of genetics and bone turnover markers for the prediction of ONJ will be discussed as well. Considering the different risk profiles of cancer patients with respect to individuals with osteoporosis [6], risk-reduction strategies will be discussed separately for these two populations.

Risk-Reduction Strategies in Patients with Cancer

Before Commencement of Anti-resorptive Therapy

There is robust evidence that a significant number of ONJ cases in cancer patients are associated with a history of surgical procedures to the jaw bones (e.g. dental extraction and placement of osteointegrated implants) [7]. Although the exact portion of ONJ cases associated with surgical procedures vs those who develop ONJ “spontaneously” remains unclear, recent studies suggest that at least 50–60 % of all ONJ cases can present jawbone surgery as likely trigger [7]. As consequence, avoidance of surgical procedures during and after anti-resorptive therapy has been suggested to represent a potentially effective risk-reduction strategy. Most recommendations suggest that cancer patients who are due to start anti-resorptive therapy should be examined by an oral health practitioner with the aim of restoring diseased dentition and removing non-restorable teeth before treatment initiation. The ultimate goal is to prevent the clinical scenario where patients may require surgical intervention to manage dental infection during or after anti-resorptive therapy.
It is also important to highlight that available literature has suggested an association between ONJ development and active dental infection. Therefore, resolution of dental infection via restorative therapy is also believed to represent a risk-reduction strategy to be performed before commencement of anti-resorptive therapy, where possible.
It is suggested that oncologists refer patients to oral health practitioner as early as possible in order to allow mucosal and possibly bone healing (about 3–6 weeks) in individuals who receive extraction of non-restorable teeth before initiation of anti-resorptive therapy. It is also important that patients are instructed regarding regular oral hygiene procedures, as well as receive meticulous professional dental plaque and calculus removal 2–4 times per year and have caries and periodontal disease treated as soon as they are diagnosed. This is believed to increase the chances of preventing acute dental infection and the need of surgical extraction during anti-resorptive therapy.
Unfortunately, the real efficacy of the above risk-reduction strategies was only evaluated in a few observational uncontrolled studies. A reduction in the occurrence of ONJ among solid cancer patients was observed after the implementation of a prophylactic dental programme compared with historical controls [3, 4]. Similar findings were found among multiple myeloma patients treated with zoledronic acid [5]. In conclusion, although the above measures are routinely applied in many centres worldwide, robust scientific evidence is lacking as relevant studies are burdened by a number of significant limitations.

After Commencement of Anti-resorptive Therapy

Risk-reduction strategies in individuals who have commenced anti-resorptive therapy are aimed at avoiding acute dental infection and surgery to the jawbones [2, 8]. This includes elective surgical procedures, such as placement of osteointegrated implants, which should not be performed in these patients.
There is general agreement that individuals who are using anti-resorptive agents should be instructed to keep meticulous oral hygiene habits and receive regular professional dental plaque and calculus removal [2, 8]. Dental caries and periodontal infections that develop during anti-resorptive therapy should be promptly managed with restorative and nonsurgical procedures as soon as the medical status of the patient allows.
Most recommendations suggest that non-restorable or fractured teeth should not be extracted [8]. Root canal treatment should be the treatment of choice for all infected teeth, including those that are non-restorable whose roots can be left in situ. Similarly, periodontally diseased teeth should be managed conservatively with regular scaling and root planning so as to minimise the risk of acute infection.
Management of existing dental implants should follow similar recommendations, as it has been documented that ONJ may develop around dental implants [9].
Notwithstanding the recommendation that surgical procedures should be avoided, there are instances where dental extraction represents the only reliable treatment. Examples include severe periodontitis causing tooth mobility, root fractures, as well as recurrent infections not responding to conservative procedures. In these cases conventional dental extractions would significantly increase the likelihood of ONJ development. A number of potential strategies have been suggested to minimise the risk of ONJ in these individuals, including antibiotic cover [10], “atraumatic extraction” [11], primary closure of surgical site [12], orthodontic extrusion [13], use of plasma rich in growth factors (PRGF) [14], Nd:YAG low-level laser [15], etc. Unfortunately, there remains very little evidence to support any of these strategies due to the lack of well-designed case-control randomised clinical trials.
Patients’ prognosis should be taken into account while planning dental treatment. Patients with grave prognosis should be approached differently from patients with life expectancy of a few years.
Dentists should always keep in mind that those patients are usually on ongoing anti-neoplastic treatment such as chemotherapy and radiotherapy. Therefore, a thorough medical status update should be performed before each dental treatment session.

Patients with Previous History of Exposure to Anti-resorptive Therapy

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Nov 4, 2015 | Posted by in General Dentistry | Comments Off on Risk Reduction of Medication-Related Osteonecrosis of the Jaw
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