Philipp Poxleitner

The Prevention of Medication-related Osteonecrosis of the Jaw.

BACKGROUND Medication-related osteonecrosis of the jaw (MRONJ) is a preventable complication of antiresorptive treatment. It arises in 1-20% of patients with bone metastases of solid tumors and hematologic malignancies and in 0.1-2% of patients being treated for osteoporosis with bisphosphonates. Depending on the underlying disease and medication dosage, the risk of MRONJ can be elevated even in the first year of antiresorptive treatment. The treatment of MRONJ is difficult and often involves surgery of the jaw. METHODS We systematically reviewed publications retrieved by a selective search for literature on the prevention of MRONJ in the PubMed and Cochrane Library databases and with the aid of the Google Scholar search engine. RESULTS 15 of 559 retrieved publications were included in the analysis. The quality of the evidence in the studies was generally moderate to low, with most of them being case series. In one case series of over 1200 patients with multiple myeloma, the incidence of MRONJ was lowered from 4.6% to 0.8% through regular dental checkups and improved oral hygiene. Tooth extraction, in particular, is associated with a high risk of MRONJ. In a retrospective study, 57% of patients who underwent tooth extraction without antibiotic prophylaxis developed MRONJ, compared to 0% with antibiotic prophylaxis. CONCLUSION Before antiresorptive medication is begun, oral hygiene should be improved. Moreover, it seems that perioperative antibiotic prophylaxis and adequate plastic wound closure can often prevent MRONJ. In view of the fact that bisphosphonates can persist in bone for more than 15 years, patients should be thoroughly informed of the risk that antiresorptive treatment can cause MRONJ, and the measures discussed should be initiated.

Microvascular transplants in head and neck reconstruction: 3D evaluation of volume loss.

BACKGROUND Despite oversized latissimus dorsi free flap reconstruction in the head and neck area, esthetic and functional problems continue to exist due to the well-known occurrence of transplant shrinkage. The purpose of this study was to acquire an estimation of the volume and time of the shrinkage process. MATERIALS AND METHODS The assessment of volume loss was performed using a 3D evaluation of two postoperative CT scans. A retrospective review was conducted on all latissimus dorsi free flap reconstructions performed between 2004 and 2013. Inclusion criteria for the assessment were: resection of an oral carcinoma and microsurgical defect coverage with latissimus dorsi free flap; a first postoperative CT (CT1) performed between 3 weeks and a maximum of 3 months after reconstruction surgery; and an additional CT scan (CT2) performed at least one year postoperatively. The exclusion criterion was surgical intervention in the local area between the acquisition of CT1 and CT2. The effect of adjuvant radiation therapy was considered. Volume determination of the transplant was carried out in CT1 and CT2 by manual segmentation of the graft. RESULTS Fifteen patients were recruited. 3D evaluation showed an average volume loss of 34.4%. In the consideration of postoperative radiotherapy the volume reduction was 39.2% in patients with radiotherapy and 31.3% in patients without radiotherapy. CONCLUSION The reconstruction flap volume required for overcorrection of the surgical defect was investigated. This study indicates that a volume loss of more than 30% could be expected one or more years after latissimus dorsi free flap reconstruction. Clinical trial number DRKS00007534.

Zoledronate induces osteonecrosis of the jaw in sheep

INTRODUCTION The treatment of bisphosphonate-related osteonecrosis of the jaw has become routine in maxillofacial hospitals. However, the etiopathology has not yet been fully understood. The aim of this study was to develop a large animal model for medication-related osteonecrosis of the jaw (MRONJ). MATERIAL AND METHODS Eight Swiss mountain sheep were randomly assigned into two groups. Group I received 0.075 mg/kg zoledronate (ZOL) intravenously every third week for 16 weeks. After 16 weeks, extraction of the first and second lower left premolar was performed. Group II underwent surgery and no ZOL was administered. After surgery, Group I continued to receive ZOL infusions; after 16 weeks, all animals were euthanized. The jaw bones were investigated macroscopically, radiographically (computed tomography) and histologically. RESULTS Osteonecrosis of the jaw was observed at all extraction sites in all the animals receiving ZOL, and at none of the sites in animals without ZOL. All ZOL-treated animals spontaneously developed exposed bone lesions in the oral cavity at sites where no surgical intervention was performed. CT imaging shows persistent alveolar extraction sockets 16 weeks after surgery in all animals of the ZOL-group, and healed alveolar extraction sockets in non-ZOL-treated animals. CONCLUSION Sheep treated with ZOL reproducibly demonstrated osteonecrosis of the jaw after tooth extraction, and spontaneous development of exposed bone in the oral cavity at sites where no manipulation was performed. This animal model can be used for further research in the fields of BP-ONJ etiopathology, oral implantology, bone and fracture healing and periodontology.

Update MRONJ and perspectives of its treatment

Antiresorptive agents are widely used in catabolic bone diseases. Not only bisphosphonates but also new drugs like Denosumab may induce osteonecrosis of the jaw as a side effect. The present review describes the current effect mechanisms of commonly used antiresorptives, pathogenetic theories for the development of antiresorptive-related osteonecrosis of the jaw (ARONJ), and potential risk factors. Furthermore, diagnostic modalities and treatment options as well as new and innovative strategies are discussed. The major key factor to avoid the occurrence of ARONJ still remains the implementation of throughout preventive measures.

Evaluation of BP-ONJ in osteopenic and healthy sheep: comparing ZTE-MRI with µCT

OBJECTIVES Bisphosphonate-associated osteonecrosis of the jaw (BP-ONJ) is a side effect of antiresorptive treatment that is increasingly prescribed for patients with osteoporosis or malignant diseases with bone metastases. Surgical treatment of BP-ONJ requires adequate pre-operative imaging. To date, CT is the imaging standard in clinical routine; however, defining the extent of the pathological area is difficult and soft tissues are poorly displayed. MRI with zero echo time (ZTE-MRI) to display hard tissues enables a precise display of calcified structures and soft tissues for the delineation of bone necrosis and soft-tissue reactions. METHODS BP-ONJ was induced in eight sheep by extraction of two premolars in the left mandible and zoledronate (ZOL) administration. Eight sheep without ZOL administration served as the control group. Four sheep of each main group underwent osteopenia induction via ovariectomy, glucocorticoid administration and a calcium-free diet. After sacrifice, the area of tooth extraction was harvested and scanned with micro-CT (µCT) and ZTE-MRI. Two trained dentists analyzed digital imaging and communications in medicine data sets using three-dimensional imaging software. The periosteal reaction and the remaining extraction sockets were measured. RESULTS BP-ONJ was evident, and the remaining extraction sockets were observed in all animals treated with ZOL. Periosteal reactions were more pronounced in animals treated with ZOL, and they appeared broader in ZTE-MRI. CONCLUSIONS BP-ONJ lesions in the sheep mandible can be detected using µCT and ZTE-MRI. Although illustration of sequester was more consistent using the µCT, ZTE-MRI was advantageous in evaluation of periosteal reaction.

Necrotizing fasciitis as a complication of osteonecrosis of the jaw related to oral bisphosphonate application in a patient with osteoporosis: a case report

BackgroundNecrotizing fasciitis has been reported as a complication secondary to bisphosphonate-related osteonecrosis of the jaw (BRONJ) in a low number of patients. The only report of such a case in an osteoporosis patient found in current literature was related to short-term bisphosphonate but long time corticosteroid and methotrexate treatment.Case presentationIn this article, we report a case of necrotizing fasciitis secondary to osteonecrosis of the jaw related to long-term oral bisphosphonate treatment in an osteoporosis patient additionally suffering from poorly controlled type 2 diabetes. Diabetes mellitus not only has been reported to be a systemic risk factor regarding BRONJ but also to be the most common comorbidity in patients presenting with necrotizing fasciitis and to increase mortality of this condition. Necrotizing fasciitis and BRONJ in the patient could eventually be resolved by a surgical approach and intravenous antibiotic therapy.ConclusionsThe case presented suggests diabetes mellitus potentially having been an important factor in the particularly unfavorable course of therapy. It emphasizes the importance of an adequate therapy and surveillance of modifiable systemic risk factors like diabetes mellitus in patients being at risk for development of BRONJ. If necrotizing fasciitis is suspected, early diagnosis and aggressive surgical and medical management are essential to minimize morbidity and mortality.

Osteonecrosis of the jaw in patients transitioning from bisphosphonates to denosumab treatment for osteoporosis

Antiresorptive-related osteonecrosis of the jaw (ARONJ) is a rare but severe side effect of antiresorptive treatment with bisphosphonates or RANKL-antibody denosumab in patients with malignant diseases or osteoporosis. Whilst osteonecrosis of the jaw (ONJ) related to the administration of bisphosphonates (BPs) has been investigated for more than 1 decade now, only few data are available on denosumab-related ONJ, especially in patients with osteoporosis. From 2008 to 2016, 52 osteoporosis patients were treated with ARONJ in the Department of Oral and Maxillofacial Surgery, University Medical Center Freiburg, Germany. In all patients, a surgical regimen consisting of complete removal of necrotic bone, primary wound closure and perioperative i.v. antibiotic therapy was applied. Of the 52 patients, 38 developed ARONJ after BP monotherapy; in 11 patients, antiresorptive therapy had been transitioned from BPs to denosumab and 3 patients had received denosumab monotherapy. From July 2013, when the first patient with ONJ and transitioning therapy from BPs to denosumab presented to our department, to October 2016, we found recurrences in 17.6% of the patients with BP monotherapy and in 45.5% of the patients with transitioning therapy from BPs to denosumab. Transitioning antiresorptive therapy from BPs to denosumab may be an additional risk factor for developing ARONJ. In these patients, treatment of ARONJ-lesions seems to provoke more complications. An additional dental screening before transitioning should be initiated. Further studies are needed to evaluate if a first-line treatment with denosumab decreases the incidence of ARONJ in patients with osteoporosis and simplifies its treatment.