A Medicolegal Perspective on Medication-Related Osteonecrosis of the Jaw
Medication-related osteonecrosis of the jaw (MRONJ) is a rare but serious adverse reaction seen in patients administered one of several drugs used to treat skeletal conditions (1-3). It is most commonly associated with bisphosphonate (BP), which is frequently used to treat multiple myeloma and bone metastases from solid tumours (2, 4) and osteoporosis (4, 5), but can also follow the use of various other anti-angiogenic and anti-resorptive drugs (3, 4, 6). The condition is characterised by the occurrence of exposed bone in the maxillofacial region, which persists for more than 8 weeks, in a patient currently or previously treated with BP, or similar drugs, and with no history of radiation therapy to the jaw (1-6). Reports of the frequency of MRONJ vary considerably, and range from 0.6% to 11% for BP-treated patients with breast cancer or multiple myeloma (2-6). The incidence in patients with osteoporosis is up to 100 times lower (3-6). The condition can have a substantial impact on the patient’s quality of life, with many reporting significant pain levels, difficulty in eating and drinking and associated psychological symptoms (5).
MRONJ may occur spontaneously, but it is more often triggered by an invasive dental procedure, such as an extraction (1-6). As most patients who go on to develop MRONJ will receive care from both a doctor and a dentist, attributing causation and potential or actual liability can be very complicated. While dentists are often more closely related to the occurrence of MRONJ from a chronological viewpoint, physicians prescribing the medications that potentially give rise to MRONJ also have a duty to ascertain patient risk factors before treatment and to re-evaluate the patient during and after treatment (1). Therefore, the attribution of liability may depend on a number of issues.
All practitioners have a duty to regularly update their knowledge by reading relevant scientific publications and attending continuing education courses, as reliance on outdated diagnostic criteria and treatment options could be construed as negligence (1). MRONJ has only been recognised as an adverse reaction in recent years. Although most healthcare professionals are aware of the condition (1, 7), many do not mention the risk to patients when prescribing associated medications, and only one-third would consult a dentist before commencing such treatment. There is also a lack of awareness of the clinical presentation of MRONJ and of guidelines for the condition (7), and many do not emphasise the need for high standards of oral health (3). Many dentists do not know how to treat MRONJ once established and cannot distinguish between the different types of bisphosphonates and their relationship with MRONJ. This distinction is important, as it may influence the diagnostic procedures and preventive measures used, such as antibiotic administration (1). Furthermore, nearly two-thirds of dentists do not feel confident in performing an extraction on a patient receiving BP (3).
Clearly, inadequate knowledge such as this could leave a practitioner open to litigation. Furthermore, it could lead to incorrect information being given to the patient, which could also lead to a claim of negligence (1, 3). Although most patients know why they are receiving BP or similar medications, far fewer are clear about the likely duration of their treatment, and a high number do not recall being told about possible side effects (1, 3, 5). However, it is unclear whether this is due to failings on the part of the healthcare provider or the patient’s inability to recall the information given (1). Even so, informed consent can only be given once the patient understands the benefits and side effects of treatment, as well as alternative treatment options and the risk of no treatment (1, 4-6). It is also important to stress that although there is a risk of developing MRONJ, that risk is very small, so that the patient is not discouraged from either taking their medication or seeking dental treatment (4, 5, 8). Effective communication between doctors and dentists is vital so that the patient is fully aware of all aspects of the proposed treatment and therefore can give valid consent (1).
The precise mechanism by which MRONJ arises is not yet fully understood (1, 5, 6), although the unique nature of the blood supply and anatomical structure and function of the jaw bones are thought to be important (4, 5). Although it is not currently possible to define the risk of developing MRONJ in an individual patient (1), there are several recognised risk factors, including the duration of BP treatment, alcohol and tobacco usage, anaemia, uncontrolled diabetes and concomitant corticosteroid administration (2, 4-6, 8), which may place a patient into a higher or lower risk category (8). Preventive measures should focus around controlling these risk factors wherever possible (1). While this is chiefly the responsibility of the prescribing physician, dental practitioners also have a duty to enquire about a patient’s medical history and current prescriptions (1, 8), even though this can sometimes be challenging due to time constraints and the willingness of GPs to provide the relevant information (3). For patients who have ever received treatment with BP or other MRONJ-associated drugs, appropriate prevention strategies, such as the suspension of medication, or antibiotic administration, may need to be implemented if surgical dental procedures are required (1, 2). However, these measures may themselves place the patient at risk of other complications (1).
It is also important that all patients for whom BP treatment is being considered undergo a thorough dental examination before treatment commences (2, 4-6, 8). This will allow any necessary remedial procedures to be carried out far enough in advance that healing is complete before BP administration begins (2, 4), although the optimal interval between dental interventions and the initiation of BP treatment is currently unknown. An interval of at least 4 weeks has been suggested, but in patients who require urgent BP treatment, due to the number and aggressiveness of metastases, this may be difficult to achieve (2). Any tooth with a poor prognosis should be removed, and poorly fitting dentures adjusted or replaced, so that future mucosal trauma is avoided (2, 3, 5, 8). Healing after invasive procedures should be carefully monitored, and if it is not complete after 8 weeks and there is any suspicion of MRONJ, referral to a specialist should be considered (8).
One important aspect of prevention is the role played by the patient. In order to avoid invasive dental procedures, it is vital that he or she adheres to a good oral hygiene programme, including the use of a chlorhexidine rinse; maintains a healthy diet; avoids sugary foods; and reduces alcohol intake and stops smoking, if applicable (1, 2, 4-6, 8). The patient is also responsible for attending follow-up appointments (5, 6). Barriers to this include a reluctance to seek dental advice due to fear or financial restraints, and the need to travel considerable distances for treatment (5). Despite this, a patient who has received all of the relevant information, but is non-compliant, may subsequently be considered negligent and this may limit, or even exclude, the healthcare providers liability should MRONJ be diagnosed (1).
Although bone exposure is a characteristic sign of MRONJ, it is not always present, particularly in the early stages of the disease, the signs of which are still disputed (1). This may lead to diagnosis being delayed or even missed altogether. Common misdiagnoses include alveolar osteitis, sinusitis, dental problems, atypical neuralgia, sarcoma and temporomandibular joint disorders (4, 6). Therefore, healthcare providers need to maintain a high index of suspicion in patients who present with any of the signs or symptoms of the condition, including the unexposed forms (1). In order to make a timely diagnosis, patients should be monitored regularly for early signs and symptoms of MRONJ, both by the prescribing physician and their dentist (1, 2, 4). In addition, prescribers need to re-evaluate BP therapy in the context of the underlying condition, and monitor the control of established risk factors for MRONJ and the patient’s compliance with any oral health maintenance programme (1).
Once MRONJ has been diagnosed, effective treatment can be difficult (1, 5) and early diagnosis leads to a higher success rate (2, 6). Conservative treatment includes pain relief, local disinfection with mouth rinses, antibiotic administration and superficial removal of necrotic bone. Where this fails, surgical intervention, consisting of the complete resection of necrotic bone, may be necessary (1, 6), although some physicians prefer to use surgical techniques as a first-line therapy. One major challenge of surgery is identifying viable from necrotic bone, so that the minimum amount is removed, and this is often dependent upon the surgeon’s skill (6). Comparison of the results of these two approaches shows no major difference in success rates (1, 4). While current guidance suggests a conservative approach should be used in the early stages of the disease (4, 6), given the scant evidence regarding treatment strategies, it is difficult to determine whether the result would have been better had a different treatment strategy been used, and it is unlikely that healthcare providers will be held liable for the choice of treatment given (1).
Although MRONJ is rare, it results in high morbidity and a significant impact on the patient’s quality of life. Treatment is complex and may not always be successful; prevention strategies also have limited effectiveness. Although attributing liability may not always be straightforward, negligence claims arising from the management of patients at risk of MRONJ have risen in recent years and legal cases have been launched in several continents (1). As the population ages, prescribing rates for MRONJ-associated drugs has risen and is likely to increase further (3). Improved cancer survival rates, necessitating longer exposures to BPs or similar drugs, also suggest that future rates of MRONJ will be higher (6). A collaborative approach between physicians and dentists in promoting prevention strategies, particularly the importance of oral health, and sharing patient medical records could reduce the risk of a patient developing MRONJ (2-4, 6).
1. Lo Russo L, Ciavarella D, Buccelli C, Di Fede O, Campisi G, Lo Muzio L, et al. Legal liability in bisphosphonate-related osteonecrosis of the jaw. Br Dent J. 2014;217(6):273-8.
2. Vandone AM, Donadio M, Mozzati M, Ardine M, Polimeni MA, Beatrice S, et al. Impact of dental care in the prevention of bisphosphonate-associated osteonecrosis of the jaw: a single-center clinical experience. Ann Oncol. 2012;23(1):193-200.
3. Sturrock A, Preshaw PM, Hayes C, Wilkes S. General dental practitioners’ perceptions of, and attitudes towards, improving patient safety through a multidisciplinary approach to the prevention of medication-related osteonecrosis of the jaw (MRONJ): a qualitative study in the North East of England. BMJ Open. 2019;9(6):e029951.
4. Ruggiero SL, Dodson TB, Fantasia J, Goodday R, Aghaloo T, Mehrotra B, et al. American Association of Oral and Maxillofacial Surgeons position paper on medication-related osteonecrosis of the jaw–2014 update. J Oral Maxillofac Surg. 2014;72(10):1938-56.
5. Sturrock A, Preshaw PM, Hayes C, Wilkes S. Perceptions and attitudes of patients towards medication-related osteonecrosis of the jaw (MRONJ): a qualitative study in England. BMJ Open. 2019;9(3):e024376.
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7. Rahman Z, Nayani S, Anstey H, Murphy MJ. A survey evaluating the awareness of MRONJ within the Birmingham GMP community. Oral Surgery. 2019;12(1):22-9.
8. Scottish Dental Clinical Effectiveness Programme. Oral Health Management of Patients at Risk of Medication-related Osteonecrosis of the Jaw: Guidance in Brief 2017 [Available from: https://www.sdcep.org.uk/media/tsklutfj/sdcep-oral-health-management-of-patients-at-risk-of-mronj-guidance-in-brief.pdf.