The objective of this study was to evaluate the outcome of the surgical treatment of osteonecrosis of the jaw (ONJ) with the additional use of autologous membranes of platelet-rich fibrin (PRF). The study population consisted of 15 patients with ONJ lesions in the maxilla ( n = 3), mandible ( n = 11), or both ( n = 1). Eight patients had malignant disease and were treated with high-dose anti-resorptive medication; seven were treated with low-dose anti-resorptive drugs for osteoporosis. Thirteen patients had grade 2 ONJ lesions and two had grade 3 lesions. The following standardized surgical technique was applied: resection of necrotic bone, mobilization of mucoperiosteal flaps, and multiple layer coverage of bone with PRF membranes. At follow-up 7–20 months after surgery, complete mucosal healing and an absence of symptoms were found in 14 of the 15 patients (93%). The patient with persistent bone exposure had a grade 3 ONJ lesion before surgery. This study suggests that the use of PRF membranes in the surgical treatment of grade 2 ONJ may be a contributing factor to a successful outcome.
Osteonecrosis of the jaw (ONJ) is a complication of treatment with anti-resorptive medications and has been recognized since 2003. The condition appears in patients with malignant diseases on high-dose anti-resorptive drug treatment and in patients with osteoporosis treated with low-dose anti-resorptive drugs. The necrotic bone itself is typically asymptomatic, but the frequent occurrence of infection causes pain and discomfort, leading to impaired quality of life and oral health profile. Furthermore, the exposed bone is often associated with daily discomfort from sharp edges, food retention, and odour, and extra hygiene measures have to be taken.
According to international recommendations, the first choice of treatment is a conservative approach including local debridement and disinfection with antimicrobial solutions (e.g. chlorhexidine) or systemic antibiotic treatment (American Association of Oral and Maxillofacial Surgeons (AAOMS) position paper 2014, International Consensus 2015 ). This can result in cure or improvement in many patients, however a number of patients will continue to experience symptoms from the lesions and recurrent infections, which tend to increase the extent of the osteonecrosis. When these factors are present, a surgical intervention to eliminate the bone is attractive to the patient.
Successful surgical treatment depends on a number of factors, including sufficient removal of the necrotic bone, infection control, tension-free wound closure, and the prevention of wound dehiscence. A number of techniques to ensure predictable healing have been described, with high success rates reported.
Platelet concentrates add growth factors to the surgical site and have been used in a number of studies to accelerate bone and soft tissue healing. The present study used leucocyte-rich and platelet-rich fibrin (L-PRF), which is prepared without the addition of chemicals. It can be prepared in the form of membranes with physical properties that allow it to be handled and layered to cover the bone.
Surgical interventions in patients with ONJ treated with anti-resorptive drugs should be as predictable and non-invasive as possible. Therefore, knowledge is needed on the various measures that could improve the outcome using as gentle a surgical technique as possible.
The aim of this study was to evaluate the outcome of surgical treatment of ONJ with the use of L-PRF.
Materials and methods
Consecutive patients diagnosed with ONJ in the department of oral and maxillofacial surgery of a university hospital in Denmark between January 2014 and June 2015 were included in the study.
Patients were considered candidates for surgery if they fulfilled the criteria for stage 2 or 3 ONJ according to the definition of the AAOMS and if conservative treatment had not resulted in a sufficient improvement. Information on treatment options and the possible risk of treatment failure was given to all patients and consent was obtained.
The diagnosis of ONJ and planning of treatment were based on a systematic review of the patient’s history and physical and oral examinations, as well as the necessary radiological examination (panoramic radiograph or cone beam computed tomography (CBCT) scan). Detailed information was obtained on the patients’ medical history including anti-resorptive drug treatment and any concomitant medications.
Oral antibiotic treatment was initiated the day before surgery for patients treated as outpatients under local anaesthesia. Intravenous antibiotics were given during surgery for patients undergoing general anaesthesia. The standard antibiotic regime was 2 MIU penicillin and 1 g metronidazole preoperatively, followed by 1 MIU penicillin four times a day for 4 weeks and 0.5 g metronidazole twice a day for 5 days. Clindamycin 600 mg three times a day was used in the case of an allergy to penicillin. Treatment was performed under either local anaesthesia ( n = 7) or general anaesthesia ( n = 8) depending on the extent of surgery and the patient’s general condition.
The L-PRF was prepared from blood samples collected before surgery from the cubital vein in 10-ml tubes with no anticoagulants ( n = 4–8 samples). The samples were centrifuged at 1300 rpm for 14 min using the L-PRF centrifuge (PROCESS for PRF, Nice, France), in accordance with a previously described method. To ensure separation of the components of the blood samples it is important to initiate the centrifugation immediately after drawing the blood, thus avoiding the natural coagulation process. Blood sampling was performed by a trained nurse; when using eight tubes, centrifugation was started once the first four tubes had been filled and was restarted after the last four tubes had been obtained. After centrifugation, the tubes were placed vertically in a rack to allowing the blood to clot for 10–15 min. Lastly, the fibrin clots in the middle of the tubes were transferred to the surgical table to be put under gentle pressure for a few minutes, after which they were ready for use as membranes with a size of approximately 10 mm × 20 mm × 2 mm.
The surgical procedure included elevation of a mucoperiosteal flap mobilized to facilitate tension-free closure. Necrotic bone was removed with a piezoelectric device or with rotating burs and the bone surface was smoothened to remove any sharp edges. The extent of the resection was based on the preoperative radiological findings and perioperative appearance of the bone at the resected surface. No additional measures were used to determine the extent of the bony lesion. Multiple layers of the PRF membranes were subsequently used to cover the bony surfaces. A buccal fat pad was mobilized to help cover the bony defect in five patients. The mucoperiosteal flap was adapted and a tension-free closure with 5–0 resorbable sutures was performed. Figure 1 shows the radiology and individual surgical steps for one of the patients.
Postoperatively, the use of any dentures was not allowed for the first 2 weeks; dentures were subsequently allowed only if they did not expose the wound to pressure. A soft diet was prescribed for 2 weeks and mouth rinse with 0.12% chlorhexidine was used for 2 weeks. The patients were followed up for at least 6 months postoperatively, and a successful outcome was defined as complete mucosal healing and no symptoms from the jaw.
Fifteen patients were treated surgically with resection of the necrotic bone of the jaw. Details of the individual patients are given in Table 1 . Eleven of the patients were female and four were male. Their mean age was 68.5 years (range 54–83 years). Follow-up of these patients ranged from 7 to 20 months. The ONJ lesions were located in the maxilla in three patients, in the mandible in 11 patients, and in both jaws in one patient. The development of ONJ was initiated by a dental extraction in 11 patients, pressure from a prosthesis in three patients, and was spontaneous in one patient. A buccal fat pad was mobilized to add a layer in the coverage of the bony lesion in five patients; three of these lesions were in the maxilla and two in the posterior mandible.
|Patient number||Age, years||Sex||Diagnosis||Anti-resorptive drug treatment||Duration of anti-resorptive drugs, months||Location of ONJ||Stage of ONJ||Anti-resorptive drugs stopped||Outcome||Follow-up, months|
|2||66||F||Breast cancer||Denosumab (H)||72||23, 45||3||Yes||Cured||17|
|3||68||F||Osteoporosis||Alendronate (L)||84||36, 37||2||No||Cured||17|
|4||83||F||Breast cancer||Ibandronate (H)||17||43||2||Yes||Cured||16|
|5||82||F||Myeloma||Pamidronate (H)||24||43, 44||2||Yes||Cured||14|
|6||59||F||Osteoporosis||Denosumab (L)||72||26, 27||2||No||Cured||13|
|7||73||M||Renal cancer||Zoledronate (H)||15||47||2||Yes||Cured||12|
|8||75||F||Osteoporosis||Denosumab (L)||170||35, 36||2||No||Cured||12|
|9||54||F||Breast cancer||Zoledronate (H)||18||36||2||Yes||Cured||11|
|11||70||F||Osteoporosis||Alendronate (L)||180||43, 44||2||No||Cured||10|
|12||68||F||Breast cancer||Zoledronate (H)||73||15, 16||2||Yes||Cured||8|
|13||69||M||Prostate cancer||Denosumab (H)||20||45, 46||2||Yes||Cured||7|
|14||61||F||Renal cancer||Zoledronate (H)||31||35, 46||3||Yes||Exposed||7|