Oral fibroblasts rescue osteogenic differentiation of mesenchymal stem cells after exposure to Zoledronic acid in a paracrine effect.

Background: Medication-related osteonecrosis of the jaw is a serious complication that develops in oncologic patients treated with Zoledronic acid. Although used for over 30 years, the influence of Zoledronic acid on bone has been thoroughly investigated, mainly on osteoclasts. While decreasing osteoclast differentiation and function, for many years it was thought that Zoledronic acid increased osteoblast differentiation, thus increasing bone volume. Moreover, despite the influence of soft tissue on the bone healing process, the impact of zoledronic acid on the interaction between soft tissue and bone was not investigated. Aim: Our goal was to investigate the influence of Zoledronic Acid and soft tissue cells on osteogenic differentiation of mesenchymal stem cells (MSCs). Materials and methods: Osteogenic differentiation of MSCs was examined after exposure to Zoledronic Acid. To determine the influence of soft tissue cells on MSCs' osteogenic differentiation, conditioned media from keratinocytes and oral fibroblasts were added to osteogenic medium supplemented with Zoledronic Acid. Proteomic composition of keratinocytes' and fibroblasts' conditioned media were analyzed. Results: Zoledronic Acid decreased osteogenic differentiation of MSCs by seven-fold. The osteogenic differentiation of MSCs was restored by the supplementation of fibroblasts' conditioned medium to osteogenic medium, despite Zoledronic acid treatment. Five osteogenic proteins involved in the TGFß pathway were exclusively identified in fibroblasts' conditioned medium, suggesting their role in the rescue effect. Conclusion: Oral fibroblasts secrete proteins that enable osteogenic differentiation of MSCs in the presence of Zoledronic Acid.

Endoscopically Assisted Open Reduction and Internal Fixation of Sub-Condylar Fractures: Debunking Some of the Myths.

Endoscopically assisted open reduction and internal fixation has cumulate advantages over both open and closed techniques. Even though, this approach had not become popular. The study intended to summarize the outcomes and complications from the first 12 consecutive cases of sub condylar fractures that treated by endoscope and trans-buccal trocar. All patients experienced improvement in mouth opening. No postoperative malocclusion was noticed. The learning curve was assessed subjectively regarding the use of the endoscope and objectively by operating time reduction. The significant decrease in operating time and the ease of handling the endoscope were already noticed after the 5th operation. The mean time for endoscopically assisted open reduction and internal fixation in our study was 180 minutes, which was the same as for external approaches open reduction and internal fixation for sub-condylar fracture cases. No special designed instruments except an endoscope and a trans-buccal trocar were used. We can conclude that the learning curve for this technique is not as steep as it was thought to be, and it can be mastered after a relatively small number of operations. There is no difference in mean operation time comparing to external approaches. No need for special designed instruments.

A novel treatment of temporomandibular joint arthritis as a complication in familial Mediterranean fever-literature review and a case report.

OBJECTIVES: Articular involvement in familial Mediterranean fever (FMF) ranges between 40 and 70% of the patients. Involvement of temporomandibular joint (TMJ) in FMF is very rare, and only a few cases have been reported in the literature. There are no specific guidelines for treatment. We hereby present a new treatment for TMJ inflammation in FMF. MATERIALS AND METHODS: A literature search was performed using PubMed according to the following criteria: key terms included in the search were FMF arthritis, TMJ involvement in FMF patients, and arthroscopy in FMF patients. All keywords were included both as medical subject headings (MeSH) terms and text words. Selections were limited to the English language. RESULTS: Literature search yielded four reported cases of TMJ involvement in FMF patients. The four cases were treated differently, with no clear guidelines for management of TMJ involvement. Our patient suffered from painful swelling and redness over the involved TMJ area and severe trismus. She was treated by arthroscopic lysis and lavage of her TMJ followed by aggressive physiotherapy resulting to improvement of her mouth opening. CONCLUSIONS: The adverse effect of TMJ arthritis in FMF patients can be avascular necrosis and destruction of the mandibular condylar head. TMJ arthroscopy allows lysis and lavage of the joint with minimal operative and postoperative complication, resulting with satisfactory results. Thus, in case of TMJ arthritis in FMF, we recommend TMJ arthroscopy as soon as possible, following aggressive physiotherapy in order to gain normal mouth opening. CLINICAL RELEVANCE: FMF rates have been described among the Mediterranean and Middle Eastern population ranging from 1:5 to 1:3; thus, TMJ involvement due to the disease is not so rare in this region, and a clear treatment protocol is needed.

Diabetes microvascular disease and the risk for bisphosphonate-related osteonecrosis of the jaw: a single center study.

CONTEXT: Bisphosphonate-related osteonecrosis of the jaws (BRONJ) is a severe bone disease for which the exact pathogenesis mechanisms are not fully understood. OBJECTIVE: The objective of the study is to investigate a possible contribution of diabetes and microvascular disease to the pathophysiology of BRONJ. DESIGN: We identified 46 patients treated with bisphosphonates who were diagnosed with BRONJ based on their medical history during 2009 to 2012 and invited them for a dental assessment to confirm the diagnosis. Diabetes diagnosis was based on the American Diabetes Association criteria. The study group was compared to a control group of 38 patients treated with bisphosphonates without evidence of BRONJ. SETTING: The study was conducted at Rambam Health Care Campus, a referral center, Haifa, Israel. RESULTS: The results of our study showed that of the 46 patients with BRONJ, 31 (67.4%) had diabetes or impaired fasting glucose. The proportion with diabetes (37%) was higher than in the control group (26.3%; P = .009). The presence of diabetes or impaired fasting glucose increased the association with BRONJ by 2.78-fold (confidence interval = 1.27-6.07, P = .009). The prevalence of microvascular disease (neuropathy, retinopathy, nephropathy) was significantly higher in the BRONJ than in the control group (P = .01). The presence of diabetic nephropathy increased the association with BRONJ by 3.9-fold (confidence interval = 1.12-13.52, P = .02). CONCLUSIONS: This retrospective study suggests an association between diabetes, perhaps mediated through microvascular complications, and the development of BRONJ.

Oral cutaneous sinus tract, vertical root fracture, and bisphosphonate-related osteonecrosis: a case report.

INTRODUCTION: Oral cutaneous sinus tracts (OCSTs) of dental origin are often initially misdiagnosed and inappropriately treated. Accurate diagnosis is especially important in cases of bisphosphonate (BP) therapy because extraction may lead to a risk of osteonecrosis. A case report of misdiagnosis related to a tooth with a vertical root fracture in an oncologic patient treated with BPs is reported here. METHODS: In 2011, a 75-year-old woman was examined at the oral medicine clinic because of pain and swelling of the left submandibular area. The patient's medical history included oral and intravenous BP therapy because she was diagnosed with metastatic breast cancer and left maxillary stage 1 antiresorptive agent-induced osteonecrosis of the jaw. The lower left odontogenic region showed no signs or symptoms, and no apical pathosis was observed on imaging. Although antibiotics were applied, clinical symptoms worsened and an OCST appeared. Intravenous antibiotic treatment was pursued. Biopsy and direct smear from fistula were not conclusive. A diagnosis of a nonexposed variant of stage 3 antiresorptive agent-induced osteonecrosis of the jaw was established. RESULTS: Symptoms resolved after 2 weeks of antibiotic treatment and reappeared a month later. Endodontic examination revealed that the origin of the OCST was tooth no. 18 caused by a vertical root fracture, and the tooth was extracted. The patient was scheduled for routine checkups because of the fact that osteonecrosis may occur in intravenous BP-treated patients. CONCLUSIONS: Early correct diagnosis can prevent unnecessary and ineffective antibiotic therapy and surgical intervention, which is not recommended in intravenous BP cases.