Pit Jacob Voss

Surgical treatment of bisphosphonate-associated osteonecrosis of the jaw: Technical report and follow up of 21 patients

INTRODUCTION Bisphosphonates are used to reduce skeletal related events in patients with bone consuming diseases such as osteoporosis and bone metastases. However recently there has been an increased awareness of bisphosphonate-associated necrosis of the jaws (BP-ONJ). Many authors propose conservative management in these cases but invariably the problem is not treated successfully allowing the bone defect to worsen. Recently there has been a move to treat this problem surgically. The aim of this retrospective study was to provide a surgical solution for patients suffering from BP-ONJ. MATERIALS AND METHODS All patients presenting with BP-ONJ were treated with bone debridement of the affected area and multilayer wound closure. The considered variables were: gender, age, underlying diagnosis, type of bisphosphonate (BP) used, duration of bisphosphonate use, route of administration, location of the osteonecrosis, clinical symptoms, association with dental treatment and surgical outcome. RESULTS Nineteen cases of a total of 21 demonstrated no recurrence of osteonecrosis during follow up (Mean 16 months - Range 12-24 months). One patient with a bilateral defect showed a dehiscence on one side and a small fistula on the contralateral side 6 weeks post-operatively and required revision surgery. Another patient developed a fistula after 4 weeks that was treated successfully with antibiotics and curettage. No patients had evidence of exposed bone, bland mucosa nor pain at the surgical site. CONCLUSION The technique described can be recommended for patients with BP-ONJ if a conservative treatment fails.

Comparison of virtual and titanium clip marking of tumour resection margins for improved radiation planning in head and neck cancer surgery.

Communication between the surgeon and the radiation oncologist is improved with the use of virtual models of the final tumour resection, combining three-dimensional imaging and conventional clip marking with computer-aided navigation. This investigation was designed to determine the deviation of virtual marking procedures compared to conventional marking by titanium ligature clips in oral cancer with different localizations. Seventeen patients with surgically placed clips and virtual landmarks on the resection margin after complete tumour ablation were evaluated. To determine whether the virtual landmarks remain predictive of the resection margin, the deviation of the virtual points from their corresponding clips was analyzed by measuring the distance between their centres of gravity. In total, 189 clips were evaluated. Metric analyses of the deviation between the virtual points and clips showed a deviation of 2.3 ± 0.6mm for tumours with a maxilla localization, 7.2 ± 2.5mm for tumours with a mandible localization, and 12.6 ± 3.8mm for tumours with a tongue localization. A significant statistical relationship was demonstrated in the virtual point-clip deviation as a function of tumour localization. Virtual marking of maxillary tumour resection margins allows accurate definition of the former tumour bed and could lead to novel adjuvant treatment strategies.

Gorham-Stout syndrome of the facial bones: a review of pathogenesis and treatment modalities and report of a case with a rare cutaneous manifestations

Gorham disease is a very rare condition associated with spontaneous destruction and resorption of 1 or more bones anywhere in the body. Many authors have suggested and/or implicated trauma as the initiating factor in the majority of the reported cases. It can affect almost all bones, and a combination of bones has been reported. In the maxillofacial skeleton, the first facial case was reported by Romer in 1928. Until now, only a few cases of Gorham disease affecting the maxillofacial bones, including this case report, have been reported. We present a brief review of the pathogenesis and treatment modalities of the disease and report a very rare clinical picture of the disease affecting a young and otherwise healthy patient with massive osteolysis of the mandibular bone and extensive involvement of the mouth floor and skin of the chin, which to our knowledge, is the only case report with skin manifestation affecting the maxillofacial region. Such skin manifestations play an important role for the diagnosis and add a clue for management of such condition.

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.

The validity of surgical clips as radiographic markers for the tumour resection cavity in head and neck cancer treatment.

BACKGROUND A prerequisite of irradiation after advanced head and neck tumour resection is the accurate localization of the tumour resection margin. The purpose of the following study is to evaluate the use of surgical clips placed in the tumour resection margins for use as radiographic markers to facilitate focussed adjuvant radiation therapy. MATERIALS To evaluate whether the clips remain predictive for the resection margin, we analysed the deviation of each clip in two postoperative CT scans on different days. Bone registration points were used to fuse the two CT scans in the region of the primary tumour and the distances between corresponding clips were measured. RESULTS The tumour resection margins were labelled with an average of 18 titanium clips. In total 282 clips were evaluated. Metric analysis of clip deviation between the two postoperative CT scans found a mean distance of 4.5 mm ± 2.5 mm with a range of 0.5-11.8 mm. No significant statistical relationship of the clip differences as a function of time, the method of reconstruction or administered radiotherapy could be demonstrated. CONCLUSION Placement of surgical clips in the cavity walls after complete tumour resection provides an easy and inexpensive approach for defining resection margins and allows for increased accuracy of adjuvant treatment. Clinical trial number DRKS00007534.

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.

The lower trapezius island myocutaneous flap in tunnelled technique to cover complicated tissue defects located between the craniocervical and cervicothoracic junction following spinal surgery

PURPOSE Stable coverage of complicated defects located between the craniocervical and cervicothoracic junction following wound healing disturbance after spinal surgery can be challenging. Especially in cases where devices are exposed, well-vascularized coverage is required to achieve stable wound conditions. Therefore, the aim of the present study was to evaluate the clinical outcome of the lower trapezius island myocutaneous flap (LTIMF) as a possible treatment option. MATERIALS AND METHODS Four patients with a mean age of 68.8 years (ranging from 50 to 93 years) with wound healing disturbance following spinal surgery leading to defects of the dorsal neck/upper back refractory to conservative treatment and surgical debridement were included. All defects were reconstructed with a LTIMF based on the transverse cervical artery. RESULTS Mean follow-up was 16.5 months (ranging from 5 to 30 months). No major flap failure occurred; minor complications in three patients including lateral superficial skin necrosis were easily handled. In all patients, excellent functional and aesthetic results were achieved. CONCLUSION The lower trapezius island myocutaneous flap represents a reliable treatment option to cover complicated defects located between the craniocervical and cervicothoracic junction following wound disturbance after spinal surgery.