Comparison of mucosal and mucoperiosteal wound cover for the treatment of medication-related osteonecrosis of the jaw lesions: a retrospective cohort study.

OBJECTIVES: Actually, there is no detailed guidance on how to deal with wound closure after surgical removal of medication-related osteonecrosis of the jaw (MRONJ) lesions. This study attempts to compare the difference in outcome between the mucosal and the mucoperiosteal flap closure after surgery. PATIENTS AND METHODS: In this retrospective monocentric cohort study, patients (n = 61; 35 female/26 male) suffering from MRONJ and requiring surgical therapy at the University of Aachen between 2013 and 2015 were included. Due to intra-institutional variances, one group was treated with the mucosal, the other group with the mucoperiosteal technique. The success rate, i.e., mucosal closure and no relapse at the point of follow-up, was evaluated and compared. All patients were clinically investigated for the postoperative follow-up during a special consultation appointment. RESULTS: The success rates between the different techniques after 2 years follow-up were very similar. In the group of mucosal wound closure, 22 of 29 (75.86%) patients revealed mucosal integrity without signs of MRONJ. The rate in the mucoperiosteal wound closure group was almost identical (24 of 32 (75%)). CONCLUSION: No differences in the success rates between the two different techniques could be evaluated. CLINICAL RELEVANCE: The results of this study suggest that the complete removal of the necrotic bone might have a higher impact on the success rates than the technique of the wound closure. Due to the fact that the mucoperiosteal wound closure technique offers a better overview of the extent of the MRONJ lesion, the authors advise to use this technique.

Comparison of auto-fluorescence and tetracycline fluorescence for guided bone surgery of medication-related osteonecrosis of the jaw: a randomized controlled feasibility study.

Recent studies have indicated that bone shows auto-fluorescence under an appropriate fluorescence lamp. The aim of this preliminary study was to compare the success rates of the established tetracycline fluorescence-guided bone surgery with auto-fluorescence-guided bone surgery in the treatment of medication-related osteonecrosis of the jaw (MRONJ). Forty patients suffering from MRONJ were referred for surgical treatment and were divided randomly into two groups: auto-fluorescence (n=20) or tetracycline fluorescence (n=20) guided bone surgery. The primary endpoint was treatment success, defined as the absence of exposed bone at 8 weeks after surgery. Secondary outcomes assessed were mucosal integrity, signs of infection, pain, and loss of sensitivity; these were evaluated descriptively at 10 days, 8 weeks, 6 months, and 1 year after surgery. At 8 weeks postoperative, 18/20 patients (90%) in the auto-fluorescence group and 17/20 patients (85%) in the tetracycline fluorescence group showed mucosal integrity (P>0.05). At the last follow-up, 94% in the auto-fluorescence group and 89% in the tetracycline fluorescence group presented complete mucosal coverage with no exposed bone, infection, or pain (P>0.05). There was no significant difference between the two techniques for any of the secondary outcomes (P>0.05). The results of this preliminary study show that auto-fluorescence-guided bone surgery has comparable success rates to the established tetracycline fluorescence-guided bone surgery.

Can the inferior alveolar nerve be used as a marker in frozen section for free margin control after segmental mandibulectomy in tumour ablation?

This study critically assessed the possibility of tumour spread along the inferior alveolar nerve (IAN) and its sensitivity as an intraoperative marker for clear bony margin control in frozen section during segmental mandibulectomy. Fifteen patients with oral squamous cell carcinoma (OSCC) involving the mandible and requiring a segmental mandibulectomy were included in this prospective trial. The ends of the IAN were analyzed using quick section analysis and the results compared with those of the definite pathological report. Nerve tissue could be identified in 25 of the 27 specimens collected. No specimen revealed tumour invasion. All histological diagnoses were finally confirmed. Three positive bony margins with microscopic carcinoma infiltrates were found, whereas corresponding nerve tissue did not confirm tumour invasion. This study supports the assumption that the pattern of tumour invasion is rarely primarily along the IAN in OSCC involving the mandible. Quick section analysis of the nerve tissue alone is therefore not a valid marker for intraoperative bony margin control. However, it can be used as an additional intraoperative diagnostic tool combined with other methods in rare cases of primary tumour spread along the IAN. A review of current knowledge regarding bony margin control published in the literature is provided.

Auto-fluorescence of the bone and its use for delineation of bone necrosis.

Bisphosphonate-related osteonecrosis of the jaw (BRONJ) is a challenging complication of long-term bisphosphonate treatment. Currently, the drawback in the surgical management of BRONJ is the difficulty distinguishing between viable and necrotic bone. Intraoperative bone fluorescence induced by tetracyclines has been shown to be a valuable aid to overcome this problem. In this technical note we report the finding that viable bone is auto-fluorescent using the VELscope Vx fluorescence lamp. Necrotic bone shows an altered fluorescence pattern (pale or no fluorescence). Thus it is suggested that auto-fluorescence of bone might be of similar use during the surgical therapy of BRONJ.

[Biphosphonate-induced femoral stress fractures : A new problem and knowledge so far - case report]. / Bisphosphonatinduzierte Stressfrakturen am Femur : Ein neues Problem und bisherige Erkenntnisse - Fallbericht.

During the last several years the treatment of osteoporosis with bisphosphonates has become accepted as a safe and effective procedure. However, recently there have been increasing numbers of reports of rare complications in the literature. Particularly the occurrence of atypical fractures of the femur has become a focus of interest but the problem is insufficiently known and only rarely addressed in the scientific discussion. The case illustrated here and a survey of the important facts in the recent literature highlight essential aspects of long-term bisphosphonate therapy.

Future of local bone regeneration - Protein versus gene therapy.

The most promising attempts to achieve bone regeneration artificially are based on the application of mediators such as bone morphogenetic proteins (BMPs) directly to the deficient tissue site. BMPs, as promoters of the regenerative process, have the ability to induce de novo bone formation in various tissues, and many animal models have demonstrated their high potential for ectopic and orthotopic bone formation. However, the biological activity of the soluble factors that promote bone formation in vivo is limited by diffusion and degradation, leading to a short half-life. Local delivery remains a problem in clinical applications. Several materials, including hydroxyapatite, tricalcium phosphate, demineralised bone matrices, poly-lactic acid homo- and heterodimers, and collagen have been tested as carriers and delivery systems for these factors in a sustained and appropriate manner. Unfortunately these delivery vehicles often have limitations in terms of biodegradability, inflammatory and immunological rejection, disease transmission, and most importantly, an inability to provide a sustained, continuous release of these factors at the region of interest. In coping with these problems, new approaches have been established: genes encoding these growth factor proteins can be delivered to the target cells. In this way the transfected cells serve as local "bioreactors", as they express the exogenous genes and secrete the synthesised proteins into their vicinity. The purpose of this review is to present the different methods of gene versus growth factor delivery in tissue engineering. Our review focuses on these promising and innovative methods that are defined as regional gene therapy and provide an alternative to the direct application of growth factors. Various advantages and disadvantages of non-viral and viral vectors are discussed. This review identifies potential candidate genes and target cells, and in vivo as well as ex vivo approaches for cell transduction and transfection. In explaining the biological basis, this paper also refers to current experimental and clinical applications.

Dose-dependent new bone formation by extracorporeal shock wave application on the intact femur of rabbits.

BACKGROUND: Whereas various molecular working mechanisms of shock waves have been demonstrated, no study has assessed in detail the influence of varying energy flux densities (EFD) on new bone formation in vivo. METHODS: Thirty Chinchilla bastard rabbits were randomly assigned to 5 groups (EFD 0.0, 0.35, 0.5, 0.9 and 1.2 mJ/mm2) and treated with extracorporeal shock waves at the distal femoral region (1,500 pulses; 1 Hz frequency). To investigate new bone formation, animals were injected with oxytetracycline at days 5-9 after shock wave application and sacrificed on day 10. Histological sections of all animals were examined using broad-band epifluorescent illumination, contact microradiography and Giemsa-Eosin staining. RESULTS: Application of shock waves induced new bone formation beginning with 0.5 mJ/mm2 EFD and increasing with 0.9 mJ/mm2 and 1.2 mJ/mm2. The latter EFD resulted in new bone formation also on the dorsal cortical bone; cortical fractures and periosteal detachment also occurred. CONCLUSION: Here, for the first time, a threshold level is presented for new bone formation after applying shock waves to intact bone in vivo. The findings of this study are of considerable significance for preventing unwanted side effects in new approaches in the clinical application of shock waves.

Synthetic, pure-phase beta-tricalcium phosphate ceramic granules (Cerasorb) for bone regeneration in the reconstructive surgery of the jaws.

The aim of this study was to investigate the long-term effect of the ceramic beta-tricalcium phosphate (beta-TCP) at different sites of alveolar reconstruction and to evaluate its properties. From 1997 to 2002, beta-TCP was implanted as bone substitute in 152 patients using a standardized study protocol. Main indications were the filling of large mandibular cysts (n=52), secondary and tertiary alveolar cleft grafting (n=38), periodontal defects (n=24) and maxillary sinus floor augmentation (n=16). For defects exceeding 2cm in diameter, beta-TCP was combined with autologous bone taken from the retromolar area, the maxillary tuberosity or the chin region. A radiological, clinical and ultrasonographical examination was carried out 4, 12 and 52 weeks postoperative. In 16 cases, biopsies were taken after 12 months indicating complete bony regeneration. While wound-healing disturbances occurred in 9.2% of cases, partial loss of the bone substitute material was found in 5.9%, while total loss occurred in only 2%. Complete radiological replacement of beta-TCP by autologous bone was found after approximately 12 months, indicating its osteoconductive properties. Because of its versatility, low complication rate and good long-term results, synthetic, pure-phase beta-TCP is a suitable material for the filling of bone defects in the alveolar region.

[3D-Culturing of human osteoblastic cells with vessel like nutrient supply]. / 3D-Kultivierung humaner osteoblastärer Zellen unter gefässähnlicher Nährstoffversorgung.

AIM: The treatment of large, critical-size bone defects is a major therapeutic problem in orthopaedic and reconstructive surgery. The engineering of bone tissue could be used to replace lost bone mass. However, scaffolds seeded with vital cells and cultured in vitro suffer from poor oxygen and nutrient supply centrally, when the constructs exceed a critical volume. Therefore, we have established an osteoblastic cell culture in a new 3D-culture chamber with an artificial, vessel-like central membrane, allowing continuous nutrient supply. METHOD: Human osteoblasts were cultured in a 3D-like manner using a perfusion chamber for one week. In this system, the nutrient supply is guaranteed by a vessel-like, semipermeable polysulfone membrane with a continuous flow of medium. After fixation and cryosectioning, histological and immunohistological staining and scanning electron microscopy was carried out. RESULTS: Examinations reveal 3D cell growth around the central vessel. Formation of an extracellular matrix, rich in collagen type I and fibronectin, was detected immunohistochemically. Furthermore, we demonstrated cell adherence to the membrane and examined the surface morphology by scanning electron microscopy. CONCLUSION: The innovative approach for 3D-culturing of human osteoblasts in a system with a central nutrient supply opens up new possibilities for the in vitro cultivation for tissue engineering.