From Volume 43, Issue 10, December 2016 | Pages 939-942
Osteonecrosis of the jaw associated with bisphosphonates and other medications is a growing problem facing dentists. It can have a significant and debilitating impact upon patients. Various treatment options ranging from surgical intervention to management with antibiotics and analgesics have been proposed. This article presents one method of conservative treatment and prosthetic rehabilitation in a patient with ongoing BRONJ of the maxilla unsuitable for surgical management.
First reported by Marx in 2003,1 bisphosphonate-related osteonecrosis of the jaw (BRONJ) continues to be an increasing problem facing the dental and medical profession.
The anti-resorptive and anti-angiogenic properties of bisphosphonates (BPs) give them a role in the management of various skeletal conditions, such as osteoporosis, osteopenia and Paget's disease, as well as in the treatment of multiple myeloma, prostate, lung and breast cancer.2
The side-effects of BPs on the alveolar bone is well documented, however, the aetiology is not fully understood. Other bones are seemingly unaffected – this may be explained by higher bone turnover rate of the jaws compared with other bones and bacterial ingress from the teeth and periodontium.3,4 Various theories have been proposed to explain the pathophysiology of BRONJ. These are discussed in more detail in other publications,2,3,4,5 however, two proposed theories are broadly as follows:
However, several studies now dispute reduced bone turnover as a factor.5,6 Conversely, the ‘outside in theory’ suggests bacteria from the oral cavity colonize the exposed bone following a traumatic event, such as tooth extraction or denture trauma, which leads to necrosis of the underlying bone. A variety of bacterium species have been isolated but actinomyces has been a common finding in osteonecrosis of the jaw (ONJ).5,7 However, BRONJ is more likely to be a multifactorial condition relying on the presence of multiple host factors before it occurs.2 There are numerous risk factors that increase the potential for BRONJ and these must be considered when planning treatment (Table 1).
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Bisphosphonates are not the only drugs to cause ONJ and, therefore, it has been proposed that medication-related osteonecrosis of the jaws (MRONJ) would be a more appropriate term.3 Denosumab (Prolia®, Amgen, Thousand Oaks, CA, USA), a RANK ligand inhibitor used in the treatment of osteoporosis, can result in the same oral presentation.3,15 ONJ has also been reported in patients taking the following medications: tyrosine kinase inhibitors, eg Sunitinib (Sutent®, Pfizer, New York City, NY, USA); monoclonal antibodies targeting vascular endothelial growth factor, eg Rituximab (Rituxan®, Biogen Idec Inc, Weston, MA, United States) and Bevacizumab (Avastin®, Genetech, San Francisco, CA, United States), used to treat various cancers.3,16,17,18,19 Dentists must be aware of these additional medications and screen patients appropriately prior to extractions and other similar surgical procedures.
A range of treatment options, from major surgical intervention to more conservative management with antibiotics and analgesics, have been proposed. However, there is as yet no consensus on what the gold standard treatment should be. The American Association of Oral and Maxillofacial Surgeons (AAOMS) staging criteria and treatment for MRONJ gives a useful guide as to the severity of the condition and how it might be managed (Table 2).
| Stage | Signs/Symptoms | Treatment |
|---|---|---|
| At Risk | No exposed bone but taking BPT | Patient education |
| Stage 0 | No exposed bone but nonspecific signs/symptoms | Analgesics/antibiotics |
| Stage 1 | Asymptomatic exposed bone | Antiseptic mouthwash Monitor 3/12 |
| Stage 2 | Symptomatic exposed bone, associated infection | Antibiotics |
| Stage 3 | Symptomatic exposed bone and infection. Pathologic fracture/extra-oral fistula/osteolysis to inferior border of mandible | Antiseptic mouthwash. Antibiotics, analgesia. |
In the current literature there is increased support for surgical intervention to remove bone sequestra, facilitate debridement and promote healing, particularly in symptomatic patients.3,20,21 A recent systematic review found that extensive surgical intervention or laser surgery resulted in the highest healing rates (80–100%).22 However, for some patients surgical treatment is not an option owing to other medical issues and MRONJ may become a chronic longstanding problem with limited resolution. Despite this, patients may seek prosthetic rehabilitation for aesthetic and functional reasons. This case report highlights one method of conservative prosthetic rehabilitation in a patient unsuitable for surgical intervention.
An 85-year-old female edentulous patient was referred by her GDP with exposed bone in the anterior region of the maxilla. She was treated jointly by the Oral Surgery and Restorative Dentistry departments. The patient experienced no pain but complained of a foul smelling/tasting discharge. On examination, two areas of exposed necrotic bone were noted bilaterally in the anterior maxilla; the areas were separated by a thin area of keratinized mucosa and a retained UR1 root (Figure 1). There was suppuration present but no loose bone fragments.
The patient was a wheelchair-user and had a complex medical history including: osteoporosis, under active thyroid, atrial fibrillation, asthma, hypertension, acid reflux and her current medication included bisoprolol, co-codamol, furosemide, hypromellose, levothyroxine, mometasone furoate, omeprazole, pregabalin, quinine sulphate, salbutamol and warfarin. The oral bisphosphonate, ibandronate sodium, was prescribed for more than 10 years for the management of the patient's osteoporosis. This was discontinued in December 2013.
Prior to referral, the patient had had a new set of complete dentures made. It was suspected that the upper denture had caused soft tissue trauma resulting in the exposed bone. In light of the patient's existing medical problems, invasive surgical treatment was deemed unsuitable. Instead, a conservative medical approach was employed. This involved chlorhexidine mouthrinses and prescription of long-term doxycycline and removal of loose bone fragments. This resolved the infection and discharge but initially no reduction in the surface area of exposed bone was observed. Despite this limited improvement, having been edentulous for over a year, the patient requested to have a further set of dentures made to improve aesthetics and function.
New acrylic dentures were constructed in a conventional manner. Primary alginate stock tray impressions were followed by medium-bodied silicone impressions in closely adapted special trays. Particular attention was paid to border-moulding with thermoplastic reline material (GC ISO Functional Sticks®). Registration was carried out using wax rims on heat-cured acrylic bases; this allowed the rims to be more stable and also provided insight as to the retention of the dentures at an early stage. For the try-in stage, a partial permanent soft reline material (Molloplast®) was placed around the areas of MRONJ to provide cushioning in these areas. However, this was taken a step further and a full, permanent, soft lining placed for the fit appointment (Figure 2). This not only improved retention further but, by providing a full soft lining, this limited any trauma to the whole of the denture-bearing area of the palate.
Given the amount of tissue necrosis, it was unclear what level of retention would be achievable with a denture; however, the result proved to be excellent. The patient and her family were very pleased with the result (Figure 3).
When the patient was reviewed 3 months later, she had lost approximately a 2 cm2 section of necrotic bone from the right maxilla and also the retained root. As a result, the upper denture had now become unstable. The denture was relined with further permanent soft lining in the laboratory. Again, this provided the patient with good retention and stability of the prosthesis. At a further 3 months follow-up appointment, the right maxillary region where the bone loss had occurred was noted to have healed significantly and there was now mucosal coverage in this area (Figure 4).
Given the progressive nature of this patient's MRONJ, it was reiterated that the denture may only be suitable for social use rather than daily function. Should the MRONJ progress, the prosthesis will have to be adapted further. However, for the time being the MRONJ has significantly improved following the loss of bone sequestrum in the area and so conservative treatment in this instance appears to have been effective.
Although complete resolution of the patient's condition has not yet been achieved, this case serves to highlight a method of conservatively rehabilitating patients with MRONJ who are unsuitable for surgical intervention. Surgical intervention in a medically fitter patient may provide improved healing in areas of MRONJ but this should be assessed on a case-by-case basis. As has been demonstrated with this case, patients must be kept under close review to ease any traumatic areas of the denture and modify the denture base appropriately.
The link between dentures and the development of MRONJ is considered to be significant, with the mandibular molar region most frequently affected.20,23 It has been shown that denture wearers have a shorter duration to the onset of MRONJ compared to non-denture wearers.20 However, conversely, it is reported that, with good oral hygiene, dentures may in fact reduce recurrence of MRONJ post-treatment,20,24 possibly as, once the prosthesis is relieved or relined, it then protects the mucosa from external trauma.
Further long-term research is required to ascertain the gold standard management of medication-related osteonecrosis of the jaw. Until this can be established, each patient must be assessed on an individual basis and kept under close review. This paper has demonstrated one method of managing a case of MRONJ, however, this would clearly not be suitable for every patient. This may be a useful treatment for short-term rehabilitation while healing of a site of exposed bone is still ongoing.
Dentists must remain vigilant for signs of osteonecrosis, in not only patients prescribed bisphosphonates, but also RANK ligand inhibitors, tyrosine kinase inhibitors and monoclonal antibodies. Patients must be well informed so that they understand their role in maintaining good oral hygiene and seeking help from the dentist should they develop any signs or symptoms or their prosthesis causes trauma.
