J.P. Richard van Merkesteyn

Treating low- and medium-potency bisphosphonate-related osteonecrosis of the jaws with a protocol for the treatment of chronic suppurative osteomyelitis: report of 7 cases.

OBJECTIVE Treatment of bisphosphonate-related osteonecrosis of the jaws has been reported to be very difficult. In this article a small series of 7 patients, treated with a relatively simple protocol, similar to the treatment of chronic suppurative osteomyelitis, consisting of surgery and antimicrobial treatment, is reported. STUDY DESIGN A retrospective review of patients who were treated for bisphosphonate-related osteonecrosis of the jaws in the department of Oral and Maxillofacial Surgery during the period of 2002-2006 was performed. Seven patients, all treated with the low- and medium-potency bisphosphonates clodronate or pamidronate, were selected as having an established bisphosphonate-related osteonecrosis of the jaws. Treatment consisted of sequestrectomy with curettage of the defect in combination with intravenous antimicrobial therapy. RESULTS In 6 patients, signs and symptoms disappeared during follow-up which varied from 5 to 52 months. One patient had fewer complaints and developed a stable area of denuded bone. CONCLUSION From these data it is concluded that a protocol consisting of thorough surgical debridement of the infected and necrotic tissue, rounding off of the affected bone, and primary closure leaving no dead space, supported by intravenous antimicrobial therapy for 1 week, followed by oral administration for 3 weeks, might lead to predictable good results in cases of low- and medium-potency bisphosphonate-related osteonecrosis of the jaws.

Initial results of the treatment of diffuse sclerosing osteomyelitis of the mandible with bisphosphonates

OBJECTIVE Diffuse sclerosing osteomyelitis (DSO) of the mandible is characterised by recurrent pain, swelling of the cheek and trismus. Treatment is difficult and symptoms often recur. Recently case reports and small series have reported good results after treatment with bisphosphonates. STUDY DESIGN Seven patients suffering from treatment resistant DSO were treated with intravenous bisphosphonates. Diagnosis was based on clinical, radiological and histopathological examination. Symptoms had been present for between 20 and 167 months (mean 78). Patients were admitted, laboratory tests and Technetium-scans were performed. Pamidronate was administered intravenously up to four times a year. Follow-up varied from 18 to 46 months (mean 30). RESULTS In all patients, symptoms and the need for analgesic drugs diminished considerably. One patient remained free of symptoms after one treatment. In two patients a switch in bisphosphonate was made based on a decreased response. All patients showed a decrease in uptake in the DSO-area on the Tc-scans when comparing pre- and post-treatment. One patient was lost to follow-up. CONCLUSION In therapy-resistant DSO bisphosphonate treatment may be a good option.

Denosumab osteonecrosis of the mandible: A new entity?A case report

In the treatment of osteoporosis, M. Kahler and bone metastases from prostate and breast cancer bisphosphonates play a major role. Not all patients respond well to bisphosphonate treatment. Since a few years adverse effects of these drugs have been reported. A new drug, denosumab, a fully human monoclonal antibody to RANKL, has recently been developed. This case reports a 74-year-old male patient with a medical history of diabetes mellitus, angina pectoris, coronary bypasses, hypertension, and prostate cancer with multiple metastases to lymph nodes, bone and lungs. The prostate cancer was treated according to the protocol. But he was never treated with bisphosphonates. Instead he was included in a phase III randomized double blind multicenter trial, testing the efficacy of denosumab compared to zoledronic acid in the treatment of bone metastases of hormone resistant prostate cancer. Only 7 months after start of denosumab infectious symptoms developed, followed by infestation of the mandible. Despite surgical treatment fistula and exposed bone remained. This case illustrates that use of denosumab can lead to a type of osteonecrosis resembling bisphosphonate related osteonecrosis of the jaws.

Bad split during bilateral sagittal split osteotomy of the mandible with separators: a retrospective study of 427 patients

An unfavourable fracture, known as a bad split, is a common operative complication in bilateral sagittal split osteotomy (BSSO). The reported incidence ranges from 0.5 to 5.5%/site. Since 1994 we have used sagittal splitters and separators instead of chisels for BSSO in our clinic in an attempt to prevent postoperative hypoaesthesia. Theoretically an increased percentage of bad splits could be expected with this technique. In this retrospective study we aimed to find out the incidence of bad splits associated with BSSO done with splitters and separators. We also assessed the risk factors for bad splits. The study group comprised 427 consecutive patients among whom the incidence of bad splits was 2.0%/site, which is well within the reported range. The only predictive factor for a bad split was the removal of third molars at the same time as BSSO. There was no significant association between bad splits and age, sex, class of occlusion, or the experience of the surgeon. We think that doing a BSSO with splitters and separators instead of chisels does not increase the risk of a bad split, and is therefore safe with predictable results.

Bisphosphonate related osteonecrosis of the jaws: spontaneous or dental origin?

OBJECTIVE(S) Bisphosphonates are frequently used worldwide mostly in osteoporosis and skeletal bone metastases. However, a serious side-effect is bisphosphonate related osteonecrosis of the jaws (BRONJ). The mechanism behind BRONJ remains unclear. In literature several origins are suggested. Presence of the teeth in the jaws may play an important role. Therefore in this study 45 patients were analyzed retrospectively. STUDY DESIGN Files of 45 patients with a diagnosis of BRONJ were analyzed, meaning clinical features, bisphosphonate use, dental history including luxating moment and (previous) treatment. RESULTS In 97.5% (n = 44) a certain or presumable dental focus, such as extractions, a previous dental treatment or prosthesis complaints were found as initiating factor of BRONJ. CONCLUSION In contrast to findings in literature, in our group of patients a dental focus was found in 44 of 45 cases. This implies a dentoalveolar start of BRONJ with subsequent spreading into the jaws in nearly all cases.

Presence of mandibular third molars during bilateral sagittal split osteotomy increases the possibility of bad split but not the risk of other post-operative complications

Timing of third molar removal in relation to bilateral sagittal split osteotomy (BSSO) is controversial, especially with regard to post-operative complications. We investigated the influence of mandibular third molar presence on complications after BSSO with sagittal splitters and separators, by a retrospective record review of 251 patients (502 surgical sites). Mandibular third molars were present during surgery at 169 sites and removed at least 6 months preoperatively in 333 sites. Bad splits occurred at 3.0 % (5/169) and 1.5% (5/333) of the respective sites. Presence of mandibular third molars significantly increased the risk of bad splits (OR 1.08, CI 1.02-1.13, p < 0.01). The mean incidences of permanent neurosensory disturbances, post-operative infection, and symptomatic removal of the osteosynthesis material were 5.4% (OR, 0.89; 95% CI, 0.79-1.00; p = 0.06), 8.2% (OR, 1.09; 95% CI, 0.99-1.20; p = 0.63), and 3.4% (OR, 0.97; 95% CI, .92-1.03; p = 0.35) per site, respectively, without a significant influence of mandibular third molar status. In conclusion, the presence of mandibular third molars during surgery increases the possibility of bad split but does not affect the risk of other complications. Therefore, third molars can be removed concomitantly with BSSO using sagittal splitters and separators.

Unusual case of a conservatively treated pathological fracture after sequestrectomy in a patient with long-term oral bisphosphonate use

Bisphosphonates are used in the management of metastatic bone disease, Pagets disease of bone and osteoporosis. A long-term complication of these drugs is bisphosphonate-related osteonecrosis of the jaws (BRONJ). Treatment of BRONJ can be quite challenging, and remains a topic of debate. We report the case of a 74-year-old woman who had used Fosamax(®) (alendronate sodium) orally for four years. After 3½ years she developed pain, swelling, and a fistula in the left mandible. After exploration and sequestrectomy in combination with antibiotic treatment, osteolysis with a pathological fracture developed. Given the extent of the disorder and a decrease in complaints after the surgery, a non-surgical approach was chosen with continuation of the antibiotic treatment for 10 weeks, a soft diet and not wearing of dentures. During follow-up complaints subsided, the intra-oral fistula disappeared and the fracture healed. This is the first report of healing of a BRONJ patient stage III with pathological fracture. It illustrates the remaining healing potential of the bisphosphonate-treated bone.

Bisphosphonate-related osteonecrosis of the jaws: Cohort study of surgical treatment results in seventy-four stage II/III patients

INTRODUCTION Bisphosphonates are used in the treatment of osteoporosis and bone metastases. They inhibit osteoclast function, thereby decreasing bone resorption. A side effect of these drugs is bisphosphonate-related osteonecrosis of the jaw (BRONJ), which can be difficult to treat. The purpose of this study was to evaluate the surgical treatment protocol used in our hospital for BRONJ patients. The patients were retrospectively analyzed and followed-up at the Leiden University Medical Center. METHODS All patients who were referred to our hospital with therapy-resistant BRONJ between 2003 and 2014 were seen. At first presentation, the clinical features, medical and dental history, bisphosphonate use, and the use of other medications were recorded. Patients underwent surgical intervention, performed by senior surgeons, following the principles of our previously published protocol. RESULTS Seventy-four patients were followed-up for 6-96 months. Curation was successful with this surgical approach in 93.2% of the patients. DISCUSSION All the patients were cured with our surgical protocol, for up to 5 years after surgery. We conclude that this treatment protocol has a high success rate in treating all stages of BRONJ.

Angled Osteotomy Design Aimed to Influence the Lingual Fracture Line in Bilateral Sagittal Split Osteotomy: A Human Cadaveric Study

PURPOSE The traditional osteotomy design in the bilateral sagittal split osteotomy includes a horizontal lingual bone cut, a connecting sagittal bone cut, and a vertical buccal bone cut perpendicular to the inferior mandibular cortex. The buccal bone cut extends as an inferior border cut into the lingual cortex. This study investigated a modified osteotomy design including an angled oblique buccal bone cut that extended as a posteriorly aimed inferior border cut near the masseteric tuberosity. MATERIALS AND METHODS The authors implemented a randomized controlled study. The study sample was comprised of 28 cadaveric dentulous mandibles. The primary outcome variable was the pattern of lingual fracture induced using the conventional (n = 14) and modified (n = 14) osteotomy designs. The secondary outcome variables included the incidence of bad splits and the status of the inferior alveolar nerve (IAN). Descriptive and bivariate statistics were computed. RESULTS The angled osteotomy design resulted in a significantly larger number of the lingual fractures originating from the inferior border cut (odds ratio [OR] = 1.54; 95% confidence interval [CI], 1.27-1.86; P < .01), with a significantly more posterior relation of the fracture line to the mandibular canal (OR = 2.11; 95% CI, 1.22-3.63; P < .01) and foramen (OR = 1.99; 95% CI, 1.28-3.08; P < .01). No bad splits occurred with the angled design, whereas 3 bad splits occurred with the conventional design, although this difference was not statistically significant (OR = 1.11; 95% CI, 0.99-1.25; P = .07). IAN status was comparable between designs, although the nerve more frequently required manipulation from the proximal mandibular segment when the conventional design was used (OR = 1.21; 95% CI, 0.99-1.47; P = .06). CONCLUSION The results suggest that the angled osteotomy design promotes a more posterior lingual fracture originating from the inferior border cut and a trend was apparent that this also might decrease the incidence of bad splits and IAN entrapment. These results must be carefully extrapolated to the clinical setting, with future studies clarifying these findings.

Removal of bicortical screws and other osteosynthesis material that caused symptoms after bilateral sagittal split osteotomy: a retrospective study of 251 patients, and review of published papers

Rigid fixation with either bicortical screws or miniplates is the current standard way to stabilise the mandibular segments after bilateral sagittal split osteotomy (BSSO). Both techniques are widely used and the superiority of one or other method is still debatable. One complication of rigid fixation is the need to remove the osteosynthesis material because of associated complaints. The main aim of this retrospective study was to analyse how often we needed to remove bicortical screws because they caused symptoms after BSSO in our clinic. Review of other published papers also enabled us to investigate the reported rates of removal of screws and miniplates at other centres. The mean (SD) duration of follow-up of 251 patients (502 sites) was 432 (172) days, and the number of bicortical screws removed in our clinic was 14/486 sites (3%). Other methods of fixation were used at 16 sites. We found no significant association between removal of bicortical screws and age, sex, presence of third molars, or bad splits. Published rates of removal of bicortical screws and miniplates are 3.1%-7.2% and 6.6%-22.2% per site, respectively. These findings show that fixation with bicortical screws after BSSO is associated with a low rate of removal of osteosynthesis material. Reported incidences imply a lower rate of removal for screws than for miniplates.