Keywords

Osteonecrosis of the Jaw; Oral Surgery; Tooth Extraction; Bisphosphonates.

Introduction

Bisphosphonates (BP) are broadly used for metabolic bone disorders and bone metastasis treatment [1-4]. Medication related osteonecrosis of the jaw (MRONJ) is a known side effect of bisphosphonates use and other antiresorptive or antiangiogenic agents [5, 6]. Osteonecrosis of the jaw developed for BP represents an estimate prevalence of 0.10% related to oral antiresorptive agents [7]. MRONJ is especially linked to high dose, long-term treatments and intravenous administration of BP for myeloma multiple, breast and prostate cancer [1, 8-10] particularly the use of highly potent nitrogen-bisphosphonate as zolendronate and pamidronate in the case of BP [10-12].

The MRONJ is also known as avascular necrosis of bone or osteodhondritis dissecans. The clinical hallmark is exposed bone in the maxillofacial region for at list 8 weeks without history of head and neck radiation therapy [5], but with previous treatment of antiresorptive or antiangiogenic agents [6]. Some cases are associated to pain, local swelling, signs of infection after any invasive dental procedure or dental prosthesis trauma [5].

MRONJ pathogenesis is still understood, BP inhibits osteoclasts and leads with limit bone-remodeling process additionally the angiogenesis capacity is inhibited, affecting the ability of soft and bone tissue healing [13]. It is believed that MRONJ just appears in the maxillofacial region because of the high turnover of alveolar bone in addition to the outside environment exposition throughout the teeth and periodontal ligament. Any kind of trauma over the alveolar region exposes bone to bacterial flora leading to MRONJ [13].

Patients with need for oral surgery including tooth extraction represents the higher risk factor for MRONJ development among bisphosphonates users [10], this is thought because the risk of bacterial invasion through the open wound after tooth extraction, fact that could be precipitated with periodontal disease. Mandible is the most affected region, especially the molar region [9].

Image findings of MRONJ are not precise and are similar to osteomyelitis,osteoradionecrosis, Paget`s disease and bone metastasis. Images involve osteosclerosis, osteolysis, dense woven bone, thick lamina dura, failure of bone remodeling after surgical procedures those findings have to be correlated to patient medical history and clinical sings and symptoms of MRONJ [14].

Ideal treatments modalities for MRONJ have not been proposed. Conservative treatments could be performed in those patients without sing of infection [15], surgical procedures could be an option to reduce infection and complications, and nevertheless the total resolution of BONJ is low to succeed [11].

The aim of this paper is to described a case of MRONJ and relapse after molar tooth extraction in a 54 years old man diagnosed with myeloma multiple, treated with zolendronate for three years.

Case Report

A 54 old white male was referred to the oral clinical surgery of Aracatuba Dental School, UNESP - Univ. Estadual Paulista in March 2010 with the main complains of pain and purulent discharge at the right mandibular area. The patient medical history revealed myeloma multiple diagnosed on 2003. He received chemotherapy, bone marrow transplant and zoledronic acid intake for three years (2003-2006). The patient denied other illness, smoking or abuse of alcohol. Her dental history consisted of extraction of the first right inferior molar on August 2009 due to periodontitis, since then, the area did not heal.

Clinical examination showed bone exposure, purulent discharge and soft tissue swelling at the extraction area (Figure 1). Diagnostic image showed lack of dental alveolar bone healing and bony sequestrum (Figure 2).

×

Figure 1:

Close

Figure 1. Clinical aspect of bone exposure after seven month of dental extraction.

×

Figure 2:

Close

Figure 2. An Orthopantomograph showing a lack of healing after seven month of dental extraction in the mandibular area and bony sequestrum.

Treatment Protocol

Under general anesthesia, a crestal incision, extended along the gingival sulcus of the teeth next of the defect was carried out, then a vertical incision was made at this level, next a mucoperiosteal flap was raised to remove the necrotic and infected bone with surgical burs (Figure 3). Followed by smoothing of sharp edges. Bone margins were determined until bleeding bone was seen, the adjacent posterior tooth was also removed, because was next to the margin of the sequestrum (Figure 4). Wound closure with complete gingival closure was achieved without tension. Antibiotic therapy with clindamycin and metronidazole were prescribed in addition to 30 sessions of hyperbaric oxygen. Even though wound closure was achieved during the surgical procedure, after the healing period a complete gingival coverage was not maintained. At the sixth month postoperative the patient complains of pulsatile pain, exposed bone as shown in Figure 5, purulent exudate at the treated area and facial edema. Antibiotic therapy with clindamycin and metronidazole were prescribed. Surgical debridement until bleeding bone was carried out under local anesthesia. Clinical signs and symptoms of infection were not present but recurrence occurred. Complete gingival coverage was achieved until the second year postoperative, at this time just mouth rinses were advised.

×

Figure 3:

Close

Figure 3. Clinical aspect of the surgical procedure.

×

Figure 4:

Close

Figure 4. Bony sequestrum and the extracted teeth.

×

Figure 5:

Close

Figure 5. Recurrent bone exposure after 6 months of sequestrectomy.

Discussion

Treatment protocol to deal with total resolution of MRONJ in BP users is an ideal that has not being elucidated. On this paper was discussed a clinical case with recurrence after different treatments modalities in a patient who was treated with bisphosphonates for tree years and develop MRONJ after a dental extraction carried out after three years of having finished the treatment.

There are recommendations, protocols, and guidelines for MRONJ treatment without clear evidence to support them [6-13, 16-18]. Conservative treatment with the use of mouth rinses and analgesic intake are recommended in AAOMS stage I, which is characterized by necrotic bone exposure without sings of infection [5].

Conservative treatments

The use of analgesic and antibiotic and mouth rinses are recommended without any surgical management in patients with necrotic bone exposure, pain and signs of infection that is the clinical picture of AAOMS stage II. The isolated microbes have been sensitive to antibiotic therapy with penicillin. Clindamycin, metronidazole, quinolones, doxycycline and erythromycin in are advised in whom are allergic to penicillin [5, 6].

Minimal invasive debridement seems suitable in some cases, to reduce the volume of exposed necrotic bone and the biofilm formation around it; this procedure can benefit the antibiotic therapy [6]. Primary mucosal closure with reduce periosteal stripping, when possible offers reliable results, since bone is necrotic and avascular, the overlying mucosa is vascular in patients with AAOMS stage III [5, 7, 19].

Surgical approach

Surgical procedures to remove bone sequestrum, decortication, or segmental resection are advised in advance stages of MRONJ (stage III), necrotic bone is debrided until bleeding surgical margins are achieved [16, 18, 20]. Segmental resection contributes to mucosa closure without large manipulation of soft tissue [19]. Even though, sequestrectomy until bleeding margins was carried out and primary mucosal closure without periosteal stripping was achieved during the first surgical procedure, it was not expected to have a MRONJ recurrence after six months on this case.

Adjunctive Therapies

Adjunctive treatments including laser, growth factors, ozone and hyperbaric oxygen therapy have been proposed, due to the benefits of the reactive oxygen involved in bone turnover during osteoradionecrosis treatment [17, 21, 22]. There is still scarce evidence about the real benefits of the in this case, nonetheless recurrence occur.

BP holyday treatment in BONJ diagnosis is still controversial; there are no prospective clinical trials to support this treatment modality, it is known the long lasting effects of bisphosphonates in the skeleton, oscillating among one to ten years, however bone metabolism caused by bisphosphonates will not possible decline and provoke clinical changes on MRONJ after holyday treatment for short periods [1, 7]. The oncologist or patient physician should measure the risk and benefits of bisphosphonates therapy discontinuation [5]. It is important to highlight that in this case zoledronic acid intake was three years previous dental invasive treatment.

ONJ pathophysiology is still understood, we believe, this fact is the key of treatments failure. BPs suppress bone turnover [23], which provoke accumulative bone microdamage and avoid them to repair due to the BPs antiresorptive effect, provoking microdamage accumulation, [24, 25] this effect follow for disruption of mucosa integrity that lead microorganism invasion, and subsequently local infection development [23, 25, 26] in which macrophages that are cells uncharged of defense are affected by BP use. Macrophages are derived from the same line of monocytes as osteoclasts, we relate this fact with the incapacity of macrophages to react facing the infection [27]. BP has an effect on bone marrow monocytes the macrophages, osteoclast precursors. Macrophages act during inflammatory response [23, 28], but in the case of MRONJ they are unable to react facing the local infection, we believe that this last issue is more related to the challenge on MRNJ treatment and the difficult of successful outcomes.

Conclusion

Management of MRONJ remains a challenge, a complete resolution of MRONJ was not achieved with all treatment modalities proposed and performed on this case, at the first instance; antibiotic, surgical debridement, hyperbaric oxygen were not effective for achieving the desire result.