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Just a decade ago, the outlook appeared limitless for the use of bisphosphonates for the treatment of a large number of metabolic bone diseases ranging from osteoporosis to cancer-related bone alterations to oral bone loss. Soon thereafter, however, osteonecrosis of the jaw (ONJ) emerged as a rare but significant condition associated with bisphosphonate treatment. Although many questions remain concerning ONJ, some significant knowledge has been gained over the past decade. Ideas have emerged regarding how to stage and treat the condition, and a number of preclinical models have been developed that will soon begin to speed progress toward understanding the pathophysiology of this condition. Researchers have also discovered that ONJ is not specific to bisphosphonates, as other potent antiremodeling agents have now been associated with the condition. While antiremodeling agents remain essential tools in medicine, ONJ has somewhat slowed the momentum for this drug class, especially as it relates to new and emerging applications. Until more effective prevention or treatment regimens for ONJ are developed, this side effect of remodeling suppression will continue--for better or worse--to have a significant impact on the field. One potential treatment option may be in the form of osteoanabolics. Exciting new data have emerged demonstrating the efficacy of teriparatide (parathyroid hormone) in reversing oral cavity bone loss and even as a potential therapy for ONJ. [ABSTRACT FROM AUTHOR]

We describe the management of BRONJ triggered by dental implants in a patient on oral bisphosphonates. The sequestrum in the body of the mandible was large and involved the inferior alveolar nerve, causing a painful neuropathy. A successful outcome was obtained by combining conservative and surgical interventions. [ABSTRACT FROM AUTHOR]

The aim of the present study was to investigate the potential of bone mesenchymal stem cells (BMSCs) treated with a combination of vascular endothelial growth factor (VEGF) and bone morphogenetic protein-6 (BMP-6) genes for the treatment of avascular necrosis of the femoral head (ANFH). Rat BMSCs were isolated and purified using a density gradient centrifugation method. The purity and characteristics of the BMSCs were detected by cell surface antigens identification using flow cytometry. The experimental groups were administered with one of the following adeno-associated virus (AAV) vector constructs: AAV-green fluorescent protein (AAV-GFP), AAV-BMP-6, AAV-VEGF or AAV-VEGF-BMP-6. The expression of VEGF and BMP-6 was detected by reverse transcription-quantitative polymerase chain reaction, western blotting and ELISA assays. The effects of VEGF and BMP-6 on BMSCs were evaluated by angiogenic and osteogenic assays. The transfected BMSCs were combined with a biomimetic synthetic scaffold poly lactide-co-glycolide (PLAGA) and they were then subcutaneously implanted into nude mice. After four weeks, the implants were analyzed with histology and subsequent immunostaining to evaluate the effects of BMSCs on blood vessel and bone formation in vivo. In the AAV-VEGF-BMP-6 group, the expression levels of VEGF and BMP-6 were significantly increased and human umbilical vein endothelial cells tube formation was significantly enhanced compared with other groups. Capillaries and bone formation in the AAV-VEGF-BMP-6 group was significantly higher compared with the other groups. The results of the present study suggest that BMSCs expressing both VEGF and BMP-6 induce an increase in blood vessels and bone formation, which provides theoretical support for ANFH gene therapy. [ABSTRACT FROM AUTHOR]

Recurrent bacterial infections in cases of bisphosphonate-related osteonecrosis of jaw (BRONJ) frequently occur. Therefore, BRONJ are usually treated by radical saucerization followed by intensive antibiotic medications without bisphosphonate therapy. The postoperative exudate (POE) from BRONJ lesions may directly indicate the inflammatory status of osteomyelitis in patients, but so far, the POE has rarely been examined for its expression of various cytokines and wound healing proteins. A total of 27 cases of BRONJ, which involved the mandible, were selected and their individual POE collected 6 h, 1 day, and 2 days after surgical intervention was analyzed by immunoprecipitation high performance liquid chromatography (IP-HPLC). The different protein expressions in the BRONJ POE were compared with findings from ten cases of chronic mandibular osteomyelitis (CMO) exudate as the control group. For the protein expressions for inflammation, osteogenesis, and angiogenesis, in the 6 h POE sample, the BRONJ exudate exhibited more expression of IL-10, IL-28, OPG, and osteocalcin, but less expression of TNFα and LL-37 than the control. In the 1 day POE sample, the BRONJ exudate showed more expression of TNFα, IL-6, 8, 12, 28, α1-antitrypsin, VEGF-A, and VEGF-C, but less expression of CD68, lysozyme, bFGF, RANKL, bFGF, and ALP than the control. In the 2 day POE sample, the BRONJ exudate consistently showed more expression of LL-37, β-defensin-1, and VEGF-A than the control. The present BRONJ POE revealed the rapid progress of bony wound healing through increased molecular signaling for inflammation, angiogenesis, and osteogenesis compared to the control. Therefore, it was suggested that the POE obtained from the postoperative bony lesions should be collected and analyzed by the IP-HPLC method to predict the prognosis of seriously complicated inflammatory bony diseases such as BRONJ. [ABSTRACT FROM AUTHOR]

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Background: Avascular necrosis of the lunate has been the topic of debate for the last century. A relatively new treatment for a symptomatic patient with a Lichtman stage IIIB or stage IV is lunate pyrocarbon implant arthroplasty. The purpose of this study is to document the clinical outcomes and evaluate the results of this new modality. Methods: A retrospective cohort study of patients with a symptomatic Kienböck's disease stage IIIB treated by lunate pyrocarbon implant arthroplasty stabilized with a tendon graft. Presurgical and postsurgical assessment was performed including a questionnaire, X-ray, goniometric measurements, and grip strength. Results: Between 2010 and 2013, 16 patients with a mean follow-up of 24 months were treated. Average VAS score improved from 5 to 2.6 and average PRHWE score from 58 to 24. The average flexion extension arc and wrist deviation arc were decreased 26 and 14 degrees. The average grip strength increased from 23 to 29. Most patients were very satisfied about the operation; 14 out of 16 would undergo the same procedure again, given the same circumstances. Conclusions: Both the subjective and objective results are comparable to previous reported data of conventional treatments, and it may therefore be a suitable alternative to proximal row carpectomy (PRC). The implant lifespan is not known, but it could postpone the need for salvage procedures in young patients. Further research is needed to provide long-term outcomes and help guide future treatment of patients with Kienböck's disease. Level of evidence: Level IV, therapeutic study. [ABSTRACT FROM AUTHOR]

Background Free vascularized fibular flaps (FVFFs) are accepted surgical options to treat osteonecrosis of the femoral head and neck (ONFHN) to prevent conversion to total hip replacement (THR), yet many studies are single institution cohorts, with little generalizability. Purpose The purpose of this study was to perform a systematic review examining the comparative effectiveness of FVFF to treat ONFHN, particularly preventing conversion to a THR and improving hip function/symptoms. Methods We searched PubMed and EMBASE databases using femoral head, free fibula, and femoral neck keywords. Articles were excluded if not translated into English, n < 10 hips, article was a compilation/review, outcomes were not relevant, or prior to 1994. If from the same institution, we included the largest cohort and excluded others within the same timeline. Two investigators independently reviewed articles and reported number of patients/hips, average age/follow-up time/graft survival before THR, Harris hip score, THR rate, complications, and radiographic progression rates. Results We identified 128 and 157 articles from PubMed and EMBASE. After screening/duplicate removal, 21 studies were included from 14 institutions in 9 countries. Overall, 71% were level IV evidence. The average patient number was 129, number of hips was 166, age at surgery was 34 years, and follow-up time was 92 months. HHS improved on average 21.7 points, with the number of patients requiring THR being 19.4%. Graft survival before THR was 5.2 years, and 47.7% of hips had radiographic progression. Conclusions There is a significant amount of level IV evidence describing the favorable role of FVFF to treat ONFHN. Although efficacious, there is a need for higher level evidence. The level of evidence is 3. [ABSTRACT FROM AUTHOR]

Purpose Details regarding risk factors, onset, and outcomes for denosumab-related osteonecrosis (DRONJ) are sparse. This study examines the clinical characteristics and operative and non-operative therapeutic outcomes in patients with DRONJ not previously exposed to other antiresorptives. Methods A retrospective medical record review was conducted, and data were collected, including clinical findings, management, healing outcomes, and radiologic, histologic, and micro-computed tomography (CT) analyses. Results Seventeen patients were treated with denosumab, with 14.1 ± 8.3 doses before DRONJ onset. The majority of lesions were observed at sites of dental prostheses (41%) and dental extractions (35%). Sixteen patients were managed non-operatively (10/16) or operatively (6/16) with either major (5/6) or minor surgery (1/6) and included in the follow-up analysis. Complete healing was significant in patients treated with major surgery (80%) compared to the non-operative group (20%; p < 0.035). Denosumab was discontinued in 60% of non-operative patients and major surgery patients with no effect on healing. Histologic findings of 4 patients analyzed exhibited a decreased number of osteocyte lacunae, and micro-CT of 3 patients scanned revealed trabecular thickening. Conclusion DRONJ lesions occurred mostly at sites of prostheses sores after a mean of 14 doses of denosumab. Major surgery demonstrated more complete healing than non-operative management, and denosumab cessation did not improve healing outcomes. [ABSTRACT FROM AUTHOR]

We report a case of a 66-year-old severely osteoporotic woman with bisphosphonate-related osteonecrosis of the jaw (BRONJ) around her dental implants, who was treated successfully with teriparatide and sequestrectomy of the mandible. After 5 months of teriparatide therapy, the sequestrum separation had progressed and a sequestrectomy was performed under general anesthesia. Five months after the operation, new bone formation was observed around the bone defect in the region of the sequestrectomy. A repeat computed tomographic image revealed improvement in the bone defect in the mandible. These results suggest that teriparatide provides beneficial effects in the treatment of advanced BRONJ around dental implants. [ABSTRACT FROM AUTHOR]

Bone drilling is performed around the world in surgical operations to repair the fractured parts of bones. Significant amount of heat is generated during the bone drilling process which may be one of the causes of thermal necrosis and osteonecrosis. In the present research work drilling experiments were performed on the porcine bone. Efforts were made to reduce the cutting temperature while drilling with the diamond coated hollow tool and the results were compared with the temperature obtained when drilling performed using twist drill bit. Temperature during the bone drilling was measured by embedded thermocouples method which were placed at a location of 1.0, 1.5 and 2.0 mm from the drilled site. Results showed that hollow tool generated lower temperature with respect to the drill bit and temperature continuously decreased with the increase in radial distance from the periphery of drill hole. It was also observed that lower spindle speed, feed rate and drill diameter generated lower temperature for both the drill bits. [ABSTRACT FROM AUTHOR]

No studies have examined the transplantation of a bone marrow aspirate (BMA) containing mesenchymal stem cells (MSCs) combined with human parathyroid hormone 1-34 (hPTH1-34) administration. Therefore, we evaluated the feasibility and efficacy of autologous BMA transplantation combined with hPHT1-34 administration in a bone necrosis model. The metatarsal bones of rabbits were necrotized using liquid nitrogen, and the rabbits received a BMA transplantation or saline injection followed by hPTH1-34 (30 μg/kg) or saline administration three times per week (n = 3-4 per group). The rabbits were euthanized at 12 weeks after the initiation of treatment. No systemic adverse effects or local neoplastic lesions were observed. Importantly, the rabbits in the BMA transplantation plus hPTH1-34 group showed the highest bone volumes and histological scores of new bone. These data confirmed the feasibility of BMA transplantation combined with hPTH1-34, at least during the experimental period. The observed efficacy may be explained by a synergistic effect from the stimulation of MSC differentiation to osteoblasts with hPTH1-34-mediated suppression of apoptosis in osteoblasts. These results indicate the promising potential for BMA transplantation combined with hPTH1-34 administration in bone necrosis treatment. Longer term experiments are needed to confirm the safety of this therapeutic strategy. [ABSTRACT FROM AUTHOR]

Osteonecrosis of the jaw may be caused by radiation, medication, or infection. Optimal therapy requires a multimodal approach that combines surgery with adjuvant treatments. This review focuses on the use of adjunctive hyperbaric oxygen therapy for this condition. In addition to evidence regarding the basic and clinical science behind hyperbaric oxygen therapy, controversies in the field and economic implications are discussed. [ABSTRACT FROM AUTHOR]

Purpose: There is no consensus on how to successfully treat medication-related osteonecrosis of the jaws (MRONJ). We report here on the application of piezoelectric bone surgery to treat MRONJ in combination with antibiotherapy and on its possible benefit. Materiel and methods: A cohort of 18 consecutive patients has been treated for MRONJ; they involved 20 sites, 15 in the mandible, and five in the maxilla. Surgical removal of the necrotic areas and debridement was performed with a powerful piezoelectric surgery device (max 90 W) in combination with antibiotherapy. Results: All patients healed and obtained a complete soft tissue closure within 1 month. No recurrence of the symptoms was observed during the present follow-up (10-54 months). Conclusion: We hypothesize that healing of all treated sites might have resulted from the synergic effect of bone ablation, biofilm alteration, and antibiotic administration. Biofilm alteration might have permitted a better access of antibiotics to the involved germs. These encouraging results warrant further studies on the use of ultrasonic surgery to treat MRONJ patients in order to confirm or refute the hypothesized effect. [ABSTRACT FROM AUTHOR]

Many congenital and acquired defects occur in the maxillofacial area. The buccal fat pad flap (BFP) is a simple and reliable flap for the treatment of many of these defects because of its rich blood supply and location, which is close to the location of various intraoral defects. In this article, we have reviewed BFP and the associated anatomical background, surgical techniques, and clinical applications. The surgical procedure is simple and has shown a high success rate in various clinical applications (approximately 90%), including the closure of oroantral fistula, correction of congenital defect, treatment of jaw bone necrosis, and reconstruction of tumor defects. The control of etiologic factors, size of defect, anatomical location of defect, and general condition of patient could influence the prognosis after grafting. In conclusion, BFP is a reliable flap that can be applied to various clinical situations. [ABSTRACT FROM AUTHOR]

The treatment of adult osteonecrosis of the femoral head ( ONFH), with 8.12 million patients in China, remains a challenge to surgeons. To standardize and improve the efficacy of the treatment of ONFH, Chinese specialists updated the experts' suggestions in March 2015, and an experts' consensus was given to provide a current basis for the diagnosis, treatment and evaluation of ONFH. The current guideline provides recommendations for ONFH with respect to epidemiology, etiology, diagnostic criteria, differential diagnosis, staging, treatment, as well as rehabilitation. Risk factors of non-traumatic ONFH include corticosteroid use, alcohol abuse, dysbarism, sickle cell disease and autoimmune disease and others, but the etiology remains unclear. The Association Research Circulation Osseous ( ARCO) staging system, including plain radiograph, magnetic resonance imaging, radionuclide examination, and histological findings, is frequently used in staging ONFH. A staging and classification system was proposed by Chinese scholars in recent years. The major differential diagnoses include mid−late term osteoarthritis, transient osteoporosis, and subchondral insufficiency fracture. Management alternatives for ONFH consist of non-operative treatment and operative treatment. Core decompression is currently the most common procedure used in the early stages of ONFH. Vascularized bone grafting is the recommended treatment for ARCO early stage III ONFH. This guideline gives a brief account of principles for selection of treatment for ONFH, and stage, classification, volume of necrosis, joint function, age of the patient, patient occupation, and other factors should be taken into consideration. [ABSTRACT FROM AUTHOR]

Background: The objective of this study was to investigate the protective effects of molecular hydrogen, a novel and selective antioxidant, on steroid-induced osteonecrosis (ON) in a rabbit model.Methods: Sixty rabbits were randomly divided into two groups (model group and hydrogen group). Osteonecrosis was induced according to an established protocol of steroid-induced ON. Rabbits in the hydrogen group were treated with intraperitoneal injections of molecular hydrogen at 10 ml/kg body weight for seven consecutive days. Plasma levels of total cholesterol, triglycerides, soluble thrombomodulin(sTM), glutathione(GSH) and malondialdehyde(MDA) were measured before and after steroid administration. The presence or absence of ON was examined histopathologically. Oxidative injury and vascular injury were assessed in vivo by immunohistochemical staining of 8-hydoxy-2-deoxyguanosine(8-OHdG) and MDA, and ink artery infusion angiography. The terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) assays were performed to measure apoptosis.Results: The incidence of steroid-induced ON was significantly lower in hydrogen group (28.6%) than that in model group (68.0%). No statistically differences were observed on the levels of total cholesterol and triglycerides. Oxidative injury, vascular injury and apoptosis were attenuated in the hydrogen group compared with those in the model group in vivo.Conclusions: These results suggested that molecular hydrogen prevents steroid-induced osteonecrosis in rabbits by suppressing oxidative injury, vascular injury and apoptosis. [ABSTRACT FROM AUTHOR]

Objective Dentoalveolar procedures in patients receiving bisphosphonates and other antiresorptive agents are associated with an increased risk of medication-related osteonecrosis of the jaw (MRONJ). The aim of present study was to evaluate the effects of perioperative teriparatide (TPD) therapy in prevention of MRONJ. Subjects and methods Two protocols of TPD therapy were studied. For protocol A, 25 TPD-treated (AT) and 25 control (AC) rats received 5 weekly injection of 0.06 mg/kg zoledronate. At the end of week 5, extraction of bilateral mandibular first molars was performed for all rats, and 4-week TPD (20 μg/kg/day) and saline therapy was started for AT and AC rats, respectively. For protocol B, 25 TPD-treated (BT) and 25 control (BC) rats received 5 weekly injection of 0.06 mg/kg zoledronate. One week later, 4-week TPD and saline therapy was started for BT and BC rats, respectively. Both groups underwent tooth extraction at the end of week 7 of the experiment. All rats were sacrificed 8 weeks after tooth extraction and assessed clinically for bone exposure/fistula, and histologically for density of osteocytes in newly formed bone and empty osteocyte lacunae in alveolar bone. Results Incidence of bone exposure/fistula and mean numbers of osteocytes and empty lacunae per 25 mm 2 (at 400× magnification) were 20%, 15.36, and 2.63 in AT group; 78%, 5.78, and 6.81 in AC group; 14%, 16.94, and 2.08 in BT group; and 78%, 7.54, and 5.95 in BC group; respectively. The differences between AT and AC and between BT and BC were statistically significant ( P < 0.001). However, no statistically significant difference between AT and BT and between AC and BC was found. Conclusion Four weeks of TPD therapy, beginning at the same day or 2 weeks before tooth extraction, had a potential role in prevention of ONJ. [ABSTRACT FROM AUTHOR]

Background: Mueller-Weiss disease is a rarely diagnosed deformity where the navicular bone undergoes spontaneous osteonecrosis in adults. Until now, there is no widely accepted operative treatment for this unusual disease. We aimed to compare clinical and radiological outcomes between the open triple fusion and talonavicular-cuneiform arthrodesis for Mueller-Weiss disease of stage 4. Methods: During the period from February 2012 to June 2016, 10 patients (11 feet) suffering from Mueller-Weiss disease of stage 4 were treated by the same senior surgeon. Among them, 5 patients (5 feet) were treated with open triple fusion and 5 patients (6 feet) were treated with talonavicular-cuneiform arthrodesis. Clinical outcomes were evaluated by American Orthopaedic Foot and Ankle Society (AOFAS) ankle-hindfoot score. Radiological results were assessed based on the X-ray and CT. Postoperative complications were also recorded. Results: There were no significant differences in AOFAS score between the two groups (p = 0.1 > 0.05). For the open triple fusion, the average AOFAS ankle-hindfoot score improved from 30.2 ± 3.27 preoperatively to 79 ± 3.81 at the last follow-up (p = 0.008). And for the talonavicular-cuneiform (TNC) arthrodesis, the average AOFAS ankle-hindfoot score improved from 33.2 ± 5.63 preoperatively to 86.2 ± 3.49 at the last follow-up (p = 0.007). Conclusions: Both triple fusion and TNC arthrodesis are reasonable methods for the treatment of Mueller-Weiss disease if properly used. It is crucial to use radiological assessment to evaluate the involved joints preoperatively and then chose the appropriate method to treat different patients. [ABSTRACT FROM AUTHOR]

Background: Collapse of the femoral head associated with nontraumatic osteonecrosis (NOFH) is one of the most common causes of disability in young adult patients. Excessive bone resorption by osteoclast coincident with the suppression of osteogenesis are believed to be responsible for collapse progression. Alendronate that inhibits bone resorption by inducing osteoclast apoptosis has been traditionally used for treating NOFH; however, several reports documented serious complications by the use of this drug. On the other hand, teriparatide activates osteoblasts leading to an overall increase in bone volume, and is expected to reduce the progression of femoral head collapse in NOFH. Therefore, the present study was undertaken to examine pharmacological effects of teriparatide on collapse progression of NOFH and to compare these effects with alendronate.Methods: We conducted a retrospective study in our facility for comparing the pharmacological effects of teriparatide and alendronate on 32 NOFH patients diagnosed with osteoporosis. Between 2007 and 2013, patients were treated with daily administration of 20 μg teriparatide (15 patients: 18 hips), or with 35 mg of alendronate once a week (17 patients: 22 hips). The mean period of follow-up was 18.7 months. The progression of collapse was evaluated prior to the administration and later every three months by anteroposterior radiographs. Collapse progression with > 1 mm was defined as advanced collapse, while with < 1 mm was defined as stable radiologic disease. Student's t-test and the chi-square test was used to do compare the pharmacological effects of the two groups.Results: Treatment with terparatide had a tendency to reduce the rate of advanced collapse as compared to that with alendronate (p = 0.105). Kaplan-Meier curves related to stable radiologic disease showed that teriparatide-treated patients had better stable states than these treated with alendronate (p = 0.08, log-rank test). Moreover, treatment with teriparatide resulted in a significant reduction in collapse progression as compared to that with alendronate, noted at the end of follow-up period (p = 0.049).Conclusion: The present study suggests that teriparatide has greater pharmacological effects than alendronate for treating NOFH and preventing the collapse of femoral head.Trial Registration: The registration number in UMIN Clinical Trial Registry is UMIN000017582 . The date of registration is May 5, 2015. [ABSTRACT FROM AUTHOR]

Osteonecrosis of the femoral head (ONFH) can cause femoral head depression and cortical discontinuity. Treatment for ONFH remains challenging. We performed botulinum toxin type A injection to psoas major muscle in five patients with radiological femoral head collapse (Association Research Circulation Osseus classification stage III) who were non-responsive after two years of conservative treatment (tramadol 200 mg/day, mefenamic acid 1,000 mg/day). At two weeks after the procedure, their mean hip pain was decreased from 88 ± 0.4/100 mm to 22 ± 0.4/100 mm based on visual analogue scale (VAS). The pain was maintained at a minimum of 20/100 mm and a maximum of 30/100 mm in VAS for at least six weeks after the procedure. These values were mean ± SD. These patients were followed-up for 6 months. There was no exacerbation of pain from repeated (three times) botulinum toxin type A injection to the psoas major muscle. [ABSTRACT FROM AUTHOR]

The authors examined a 55-year-old female who had received eight intravenous infusions of a potent bisphosphonate (BP) for metastatic bone disease. A mandibular extraction was subsequently performed. At presentation, infection with suppuration and sequestrum formation were observed in the area of extraction. Both the oncologist and dental practitioner must be made aware that when BPs are going to be administered, dental care should be performed in a timely fashion. Prophylactic measures must be taken by the dentist if dental surgery is required for a patient who has received BP. [ABSTRACT FROM AUTHOR]

Objective Although over a decade has passed since first introduction of BRONJ, the exact pathophysiology of this disease is still unclear. The present experimental study aimed to determine whether the oral mucosa or alveolar bone serves as the starting point for BRONJ development. Subjects and methods Sixty male Wistar rats were randomly assigned into study and control groups (each, n = 30), and received intraperitoneal injection of 0.06 mg/kg zoledronate and saline, respectively, once a week for 12 weeks. At the end of the week 4 of the experiment, all 60 rats underwent unilateral mandibular first molar extraction. A 4 mm defect was made in the contralateral canine alveolar mucosa. At the end of the experiment, rats were sacrificed, and the three areas of interest including extraction, soft tissue defect, and the non-intervention (canine area on the same side of extraction) sites were assessed clinically for presence of bone exposure/fistula, and histologically for status of bone remodeling (only at extraction site) and osteonecrosis. Results In the study group, the frequency of bone exposure/fistula was 80%, 0%, and 0%; and the rate of histological bone necrosis was 83.3%, 20%, and 0%; at the extraction, soft tissue defect, and non-intervention sites, respectively. No clinical and histological sign of bone necrosis was found in the control group. Normal bone remodeling was observed in 0% and 100% of the extraction sockets in the study and control groups, respectively. Conclusion Injury to alveolar bone was a stronger trigger for BRONJ development compared to oral mucosal damages. [ABSTRACT FROM AUTHOR]

Medication-related osteonecrosis of the jaws (MR-ONJ) is one of the most relevant side effects of bisphosphonate therapy; it is clinically defined as a non-healing wound in combination with an avascular and necrotic jaw within ongoing bisphosphonate therapy or after completed bisphosphonate therapy. Different theories concerning the development of MR-ONJ have been reported, while the exact pathophysiology is still unknown. Recent studies have increasingly focused on angiogenesis and revascularization concerning MR-ONJ pathophysiology, which seems to be a relevant factor in the development of MR-ONJ and a possible and promising point of action for MR-ONJ prevention and therapy. Therefore, and with respect to the different aspects and specific forms of angiogenesis, the enclosed review summarizes the possible role of angiogenesis and revascularization in the pathophysiology of MR-ONJ. Special focus is given to the strong negative influence of bisphosphonates on progenitor and mature endothelial cells in vitro as well as on microvessel sprouting in vitro and in vivo, which might result in overall reduced wound healing of oral soft and hard tissues, and therefore in an exposed and avascular jaw from a clinical viewpoint. Further, it will be summarized whether and in what way the aspect of angiogenesis might be used for possible MR-ONJ prevention and therapy. [ABSTRACT FROM AUTHOR]

Maxillofacial tuberculosis (TB) is rare. The cases of 19 patients showing extreme bony destruction in the mandible, collected over a 3-month period in West Africa, are presented. Clinical, radiographic, and histological evidence indicated Mycobacterium tuberculosis as a possible cause. Further studies are in progress. [ABSTRACT FROM AUTHOR]

Introduction: Transient osteoporosis of the hip (TOH) is a self-limiting disorder characterized by bone marrow edema at the femoral head and neck. Patients report pain as moderate or severe at onset; pain gradually subsides at about six months (range four to 12 months). Differential diagnosis of the early stages of osteonecrosis of the femoral head (ONFH) is sometimes difficult. Because hyperbaric oxygen (HBO2) therapy is effective for reduction of edema in soft tissue injury and early stages of ONFH, we hypothesized that HBO2 could be effective in TOH for accelerated recovery. Methods: Five cases of TOH treated with HBO2 were clinically evaluated. HBO2 was started from three to eight weeks after onset and performed four or five times a week, averaging a total of 27.8 ± 4.7 treatments (range 20-32). Clinical features were evaluated repeatedly with clinical examination, subjective evaluation of pain, and imaging methods that included magnetic resonance imaging (MRI) and bone scans. Results: The average time to return-to-normal hip range of motion was 15.4 ± 7.8 weeks after onset, and relief of subjective pain was 16.6 ± 4.0 weeks. The average time to return-to-normal signal level in MRI was 22.0 ± 2.5 weeks, which was one to two months after relief of subjective pain. Conclusions: Multiple HBO2 treatments have the possibility of contributing to recovery acceleration in patients with TOH. However, in this study, we found that HBO2 treatment did not significantly accelerate the recovery of these five patients with TOH. The use of HBO2 should therefore be limited to patients in whom the differential diagnosis between TOH and early stage ONFH cannot be established. [ABSTRACT FROM AUTHOR]

Background: Osteoradionecrosis is the most dreadful complication after head and neck irradiation. Orocutaneous fistula makes patients difficult to eat food. Fibular free flap is the choice of the flap for mandibular reconstruction. Osteocutaneous flap can reconstruct both hard and soft tissues simultaneously. This study was to investigate the success rate and results of the free fibular flap for osteoradionecrosis of the mandible and which side of the flap should be harvested for better reconstruction. Methods: A total of eight consecutive patients who underwent fibula reconstruction due to jaw necrosis from March 2008 to December 2015 were included in this study. Patients were classified according to stages, primary sites, radiation dose, survival, and quality of life. Results: Five male and three female patients underwent operation. The mean age of the patients was 60.1 years old. Two male patients died of recurred disease of oral squamous cell carcinoma. The mean dose of radiation was 70.5 Gy. All fibular free flaps were survived. Five patients could eat normal diet after operation; however, three patients could eat only soft diet due to loss of teeth. Five patients reported no change of speech after operation, two reported worse speech ability, and one patient reported improved speech after operation. The ipsilateral side of the fibular flap was used when intraoral soft tissue defect with proximal side of the vascular pedicle is required. The contralateral side of the fibular flap was used when extraoral skin defect with proximal side of the vascular pedicle is required. Conclusions: Osteonecrosis of the jaw is hard to treat because of poor healing process and lack of vascularity. Free fibular flap is the choice of the surgery for jaw bone reconstruction and soft tissue fistula repair. The design and selection of the right or left fibular is dependent on the available vascular pedicle and soft tissue defect sites. [ABSTRACT FROM AUTHOR]

Zoledronate has been reported to exhibit pro-apoptotic and anti-angiogenic effects in endothelial cells, which partially contributes to bisphosphonate-associated osteonecrosis of the jaw (BP-ONJ). Zoledronate can also induce autophagic cell death. The present study hypothesized that Zoledronate may activate autophagy to exert pro-apoptotic effects in endothelial cells and aimed to investigate the effect of Zoledronate on human umbilical vein endothelial cells (HUVECs) and explore the underlying mechanisms. The current study demonstrated that Zoledronate induced autophagy in HUVECs in a dose-dependent manner, as demonstrated by increased levels of microtubule-associated proteins 1A/1B light chain 3B-II (LC3B-II) and Beclin-1, and decreased levels of sequestome 1 (SQSTM1). In addition, treatment with chloroquine further increased LC3B-II and increased SQSTM1 levels, indicating that Zoledronate induces autophagy by increasing autophagic activity. Flow cytometry and Hoechst 33258 staining revealed that inhibition of autophagy with 3-methyladenine markedly attenuated Zoledronate-induced apoptosis. Furthermore, genetic knockdown of Beclin-1 significantly inhibited autophagy and apoptosis induced by Zoledronate. The present study therefore demonstrated that Zoledronate may promote Beclin-1-mediated autophagy to induce endothelial cell apoptosis, and suggests that blocking autophagy may represent a novel approach for the prevention of BP-ONJ in patients receiving Zoledronate. [ABSTRACT FROM AUTHOR]

This is a retrospective analysis of the clinical effects of transplant of mesenchymal stem cells (MSCs) derived from human umbilical cord-derived MSCs (hUC-MSCs) for the treatment of osteonecrosis of the femoral head (ONFH). The biological characteristics of hUC-MSCs were assessed using flow cytometry. Nine eligible patients were enrolled in the study as they adhered to the Association Research Circulation Osseous (ARCO) classification of stage II-IIIa, and hUC-MSCs were grafted by intra-arterial infusion. Organize effective perfusion was assessed using the oxygen delivery index (ODI). The results showed that the ODI was increased at three days post-operation. The MRI results revealed that at 12 and 24 months after treatment, the necrotic volume of the femoral heads was significantly reduced. No obvious abnormalities were observed. Taken together, these data indicate that intra-arterially infused hUC-MSCs migrate into the necrotic field of femoral heads and differentiate into osteoblasts, thus improving the necrosis of femoral heads. This finding suggested that intra-arterial infusion of hUC-MSCs MSCs is a feasible and relatively safe method for the treatment of femoral head necrosis. [ABSTRACT FROM AUTHOR]

Background: Avascular necrosis of the femoral head (AVN) is the most serious complication after unstable slipped capital femoral epiphysis (SCFE), and is often unsalvageable. We report a minimum 10 years of clinical results for transtrochanteric rotational osteotomy of the femoral head (TRO) for AVN.Methods: This study included 7 patients (7 hips) with a mean age at surgery of 13.3 years, and the follow-up period was 15.8 years. All patients had prior treatment via closed reduction and pinning of the unstable SCFE, and showed severely collapsed femoral heads. The direction of rotation was anterior in 3 hips and posterior in 4. The Merle d'Aubigné-Postel score (MDPS) was used for clinical assessment, and joint degeneration was assessed with the Kellgren and Lawrence classification (KL-grade).Results: The spherical intact area of the femoral head was moved to the weight-bearing portion, and subluxation was corrected via rotation combined with intentional varus positioning. The mean MDPS improved from 10.3 points to 15.6 points at 5 years, and it was maintained at 15.0 points by 10 years; 3 hips were excellent, 1 was good, 2 were fair, and 1 showed poor outcomes. No patient experienced re-collapse after TRO or required conversion to hip replacement or arthrodesis. After 10 years, degenerative changes became evident over time, and 2 hips progressed to KL-4 with a decreased MDPS.Conclusions: Although some joint degeneration is inevitable in the long-term, TRO is an effective salvage procedure for treating AVN after unstable SCFE. [ABSTRACT FROM AUTHOR]

We evaluated retrospectively the efficacy of local resection for patients who presented with bisphosphonate-related osteonecrosis of the jaw (BRONJ). We studied 120 subjects with who required local resection of 129 BRONJ lesions that had not responded to medical treatment. The primary outcomes were improvement of the clinical stage of BRONJ and resolution of disease, and the secondary outcome was the influence of the surgeon's experience on the healing of the lesions. Age, sex, underlying diseases, smoking, and coexisting conditions were recorded. Logistic regression analysis was used to isolate factors that could potentially affect the outcome. Most of the lesions (n = 107, 84%) improved postoperatively, 20 showed no change, and one got worse. One patient died. Stratification indicated complete healing and total resolution of disease for all 26 stage I lesions, improvement for 67 of the 77 stage II lesions, and for 14 of the 25 stage III lesions. The disease resolved in 67 of the 69 stage II lesions, and 14 of the stage III cases. Logistic regression indicated that smoking and the stage of disease could affect the outcome. Analysis of the surgeons’ learning curve showed that performance improved significantly over time. Complete healing after local resection increased from 40% to 80% over a period of eight years (p < 0.001). We conclude that local resection may be the treatment of choice in BRONJ stages I and II. Stage III might be better treated with either resection or clinical monitoring according to the condition of the patient. [ABSTRACT FROM AUTHOR]

The pathogenesis of bisphosphonate-related osteonecrosis of the jaw (BRONJ) remains unknown, and the development of a reliable experimental model would help to improve our understanding of it. We used 12 domestic pigs of which 6 made up the experimental group and were treated with zoledronate 4 mg intravenously weekly for 5 weeks, while the control group (n = 6) were given no drugs. On day 60 the right second maxillary and mandibular third molars were extracted. Thirty days later 3 animals in each group were killed; the rest were killed 90 days later. Histopathological specimens from the extraction sites were analysed for bone density, collagen architecture, density of osteons, and the amount of non-mineralised bone. Bone density, amount of non-mineralised bone, and density of osteons differed significantly between the 2 groups (p < 0.001 in each case), but the chromatic pattern dictated by the collagen architecture did not. Our results correspond to the observations that have been made in patients with BRONJ, which means that the histomorphometric conditions seen in patients can be reproduced in this experimental setting. [ABSTRACT FROM AUTHOR]

The objective of this study was to evaluate the outcome of the surgical treatment of osteonecrosis of the jaw (ONJ) with the additional use of autologous membranes of platelet-rich fibrin (PRF). The study population consisted of 15 patients with ONJ lesions in the maxilla ( n = 3), mandible ( n = 11), or both ( n = 1). Eight patients had malignant disease and were treated with high-dose anti-resorptive medication; seven were treated with low-dose anti-resorptive drugs for osteoporosis. Thirteen patients had grade 2 ONJ lesions and two had grade 3 lesions. The following standardized surgical technique was applied: resection of necrotic bone, mobilization of mucoperiosteal flaps, and multiple layer coverage of bone with PRF membranes. At follow-up 7–20 months after surgery, complete mucosal healing and an absence of symptoms were found in 14 of the 15 patients (93%). The patient with persistent bone exposure had a grade 3 ONJ lesion before surgery. This study suggests that the use of PRF membranes in the surgical treatment of grade 2 ONJ may be a contributing factor to a successful outcome. [ABSTRACT FROM AUTHOR]

Background: Arsenic oxide compounds were traditionally used as devitalizing agents. Due to its toxicity, leakage of such compounds into the periodontium can cause gingival and osteo-necrosis. Their use is forbidden in Europe and the USA for decades, however, some dentists seem to still use it. Case report: We report the case of a 14-year-old girl referred to the paediatric dentistry department of Toulouse University hospital, France, presenting a bone necrosis following the use of an arsenic trioxide product to accelerate pulp necrosis. Treatment: The treatment included surgical removal of necrosis bone sequestrum, complete pulpectomy and an intermediate restoration of the tooth 27. Follow-up: After 1 week, the clinical conditions greatly improved. A restoration using a ceramic crown was performed after 2 months, and complete healing was observed after 1 year follow-up. Conclusion: Although arsenic trioxide is neither appropriate nor permitted for use in modern dentistry, especially in paediatric dentistry, some rare cases of arsenic-induced osteo-necrosis can still be encountered. A clearer message must be given to all dental practitioners against the use of arsenic trioxide in modern endodontic treatment. [ABSTRACT FROM AUTHOR]

The present work aimed to review the literature focusing on the diagnostic criteria for bisphosphonate-related osteonecrosis of the jaw (BRONJ) and its implications regarding the management of the disease. Since the report of the first cases, BRONJ concepts, diagnostic criteria and guidelines have been changed. The presence of bone exposure in the oral cavity was at first a sine qua non condition for diagnosis. However, it seems that the great concern now is the possibility of occurrence of BRONJ without this feature. Some authors warn that the bone exposure criterion leads to late diagnosis and poor response to treatment. Meanwhile, some radiographic features, such as bone sclerosis, have been postulated as early signs of the disease. Criticisms have also been raised about the clinical staging system of BRONJ. While there is no consensus on the subject, common sense recommends treating symptomatic patients taking bisphosphonate as having BRONJ despite the absence of bone exposure; and asymptomatic patients must be kept under dental follow-up, since all of them are at risk for BRONJ. [ABSTRACT FROM AUTHOR]

Osteonecrosis of the jaw (ONJ), a rare side effect of bisphosphonate therapy, is a debilitating disorder with a poorly understood etiology. FDA’s Adverse Event Reporting System (FAERS) provides the opportunity to investigate this disease. Our goals were to analyze FAERS data to discover possible relationships between ONJ and specific conditions and drugs and then to consult the scientific literature to deduce biological explanations. Our methodology revealed a very strong association between gastroesophageal reflux and bisphosphonate-induced ONJ, suggesting acidosis as a key factor. Overgrowth of acidophilic species, particularly Streptococcus mutans, in the oral microbiome in the context of insufficient acid buffering due to impaired salivary glands maintains the low pH that sustains damage to the mucosa. Significant associations between ONJ and adrenal insufficiency, vitamin C deficiency, and Sjögren’s syndrome were found. Glucose 6 phosphate dehydrogenase (G6PD) deficiency can explain much of the pathology. An inability to maintain vitamin C and other antioxidants in the reduced form leads to vascular oxidative damage and impaired adrenal function. Thus, pathogen-induced acidosis, hypoxia, and insufficient antioxidant defenses together induce ONJ. G6PD deficiency and adrenal insufficiency are underlying factors. Impaired supply of adrenal-derived sulfated sterols such as DHEA sulfate may drive the disease process. [ABSTRACT FROM AUTHOR]

This case report describes the first patient with avascular necrosis of the femoral head of Association Research Circulation Osseous stage IV, treated with radial extracorporeal shockwave therapy. By contrast, previous studies demonstrated the efficacy of a single treatment of focused extracorporeal shock wave therapy in improving pain and Harris Hip Scale in patients with avascular necrosis of the femoral head of Association Research Circulation Osseous stage I to III. The affected hip was treated with 6000 impulses of radial extracorporeal shock wave therapy at 10 Hz and an intensity ranging from 2.5 to 4.0 bar at 7-day intervals for 24 mos. The Harris Hip Scale values were 33, 43, 56, 77, 81, 88, and 92 at baseline and 1, 3, 6, 12, 18, and 24 mos, respectively. The radiographs showed that the subluxation of the right hip was slightly aggravated. Joint effusion was reduced, bone marrow edema disappeared, the density became more uniform, and the gluteal muscles were more developed based on magnetic resonance imaging. Increased tracer uptake was evident along the joint margin and superolateral aspect of the head both before and after radial extracorporeal shock wave therapy. This case report demonstrates the feasibility of long-term radial extracorporeal shock wave therapy in Association Research Circulation Osseous stage IV patients. [ABSTRACT FROM AUTHOR]

Osteonecrosis of the jaws (ONJ) is a complication of antiresorptive medications, such as denosumab or bisphosphonates, prescribed to patients with bone malignancy or osteoporosis. The most common instigating local factor in ONJ pathogenesis is tooth extraction. However, in adults the great majority of teeth are extracted due to dental disease. Here, we have investigated alveolar bone healing after extraction of healthy teeth or teeth with naturally occurring periradicular disease in mice treated with high dose zoledronic acid (ZA), a potent bisphosphonate, or OPG-Fc, a RANKL inhibitor. C57BL/6 mice were treated for eight weeks and in vivo micro-CT was performed to identify spontaneously occurring periradicular lesions around the roots of maxillary molars. Then, extractions of molars with and without dental disease were performed in all groups. Four weeks later, animals were euthanized and maxillae were dissected and analyzed. Clinically, all vehicle animals with extraction of healthy or diseased teeth, and most OPG-Fc or ZA animals with extraction of healthy teeth showed normal mucosal healing. On the contrary, most animals with OPG-Fc or ZA treatment and extraction of diseased teeth demonstrated impaired healing with visible mucosal defects. Radiographically, bone socket healing was significantly compromised in OPG-Fc and ZA-treated mice with periradicular disease in comparison to other groups. Histologically, all vehicle animals showed normal mucosal healing and socket remodeling. OPG-Fc and ZA animals with extraction of healthy teeth showed normal mucosal healing, woven bone formation in the socket, and decreased remodeling of the original socket confines. OPG-Fc and ZA animals with extraction of diseased teeth showed mucosal defects, persistent prominent inflammatory infiltrate, bone exposure and areas of osteonecrosis. These findings support that dental disease is critical in the pathogenesis of ONJ, not only as the instigating cause for tooth extraction, but also as a compounding factor in ONJ development and pathophysiology. [ABSTRACT FROM AUTHOR]

Core decompression is the most common procedure for treatment of the early stages of osteonecrosis of the femoral head. The purpose of this study was to compare the biomechanical performance of four different bone graft substitutes combined with core decompression. Subject-specific finite element models generated from computed tomography (CT) scan data were used for a comprehensive analysis. Two different contact conditions were simulated representing states of osseointegration at the interface. Our results showed that the use of a low-stiffness bone substitute did not increase the risk of femoral fracture in the early postoperative phase, but resulted in less micromotion and interfacial stresses than high-stiffness bone substitutes. [ABSTRACT FROM AUTHOR]

Recent reports suggest that uncemented total hip replacement arthroplasty (THR) results in favorable short- to mid-term clinical results. In the present study, we assessed the mid-term clinical results of VerSys Hip System uncemented THR at our hospital. Materials and Methods: We studied patients who received THR using VerSys Hip System and who could be followed-up more than 3 years. Clinical records were used to retrospectively identify patient characteristics, which included age, gender, disease requiring THR, preoperative and postoperative pain score of the Japan Orthopaedic Association scoring system, range of motion in flexion and abduction, operating time, intraoperative complication, and additional operation or revision surgery. Additionally, we investigated the loosening and alignment of implants from X-ray films. Results: Ninety-one patients and 108 hip joints were investigated. Subjects were 11 males and 97 females (mean age, 64.6 years). Mean follow-up period was 6.9 years. Reasons for requiring THR were as follows: secondary osteoarthritis, 87 joints; idiopathic osteonecrosis of the femoral head, 16 joints; rapidly destructive coxarthrosis, 4 joints; and idiopathic ossification of the labrum, 1 joint. Mean operating time was 166 minutes. A total of 11 intraoperative fractures occurred, and wiring was performed in 3 of those cases. Adverse events pertaining to the surgery were limited; however, another adverse event was that 1 case resulted in intraoperative perforation of femoral cortex, for which a revision surgery was performed. There was no dislocation. Pain score using the Japan Orthopaedic Association scoring system and range of motion tests showed statistically significant improvement following THR. At the final follow-up, although no loosening of femoral implants was observed, the loosening of acetabular component was seen in 1 case. Varus insertion of femoral implant was recognized in 40 joints. Moreover, the average inclination angle of acetabular implants was 52.2 degrees. Conclusion: These data suggest that patients receiving VerSys Hip System uncemented THR demonstrate favorable results pertaining pain score and range of motion. However, high rate of intraoperative fracture and malalignment of implants, which may be at a risk of dislocation and/or polyethylene wear in future, suggests that this implant technique requires improvement. [ABSTRACT FROM AUTHOR]

Background: Mesenchymal stem cells (MSCs) have been isolated from a variety of tissues, including bone marrow, adipose, and mucosa. MSCs have the capacity for self-renewal and differentiation. Reports have been published on the systemic administration of MSCs leading to functional improvements by engraftment and differentiation, thus providing a new strategy to regenerate damaged tissues. Recently, it has become clear that MSCs possess immunomodulatory properties and can therefore be used to treat diseases. However, the therapeutic effect mechanisms of MSCs are yet to be determined. Here, we investigated these mechanisms using a medicationrelated osteonecrosis of the jaw (MRONJ)-like mouse model. Methods: To generate MRONJ-like characteristics, mice received intravenous zoledronate and dexamethasone two times a week. At 1 week after intravenous injection, maxillary first molars were extracted, and at 1 week after tooth extraction, MSCs were isolated from the bone marrow of the mice femurs and tibias. To compare "diseased MSCs" from MRONJ-like mice (d-MSCs) with "control MSCs" from untreated mice (c-MSCs), the isolated MSCs were analyzed by differentiation and colony-forming unit-fibroblast (CFU-F) assays and systemic transplantation of either d-MSCs or c-MSCs into MRONJ-like mice. Furthermore, we observed the exchange of cell contents among d-MSCs and c-MSCs during coculture with all combinations of each MSC type. Results: d-MSCs were inferior to c-MSCs in differentiation and CFU-F assays. Moreover, the d-MSC-treated group did not show earlier healing in MRONJ-like mice. In cocultures with any combination, MSC pairs formed cell-cell contacts and exchanged cell contents. Interestingly, the exchange among c-MSCs and d-MSCs was more frequently observed than other pairs, and d-MSCs were distinguishable from c-MSCs. Conclusions: The interaction of c-MSCs and d-MSCs, including exchange of cell contents, contributes to the treatment potential of d-MSCs. This cellular behavior might be one therapeutic mechanism used by MSCs for MRONJ. [ABSTRACT FROM AUTHOR]

Background: Multiple small drilling for core decompression is widely used to preserve the femoral head in patients with avascular necrosis of the femoral head (ANFH). Nevertheless, the clinical outcome remains controversial. Simvastatin has been demonstrated to promote bone formation and reduce bone adsorption. The purpose of this study was to determine whether simvastatin enhanced the effect of multiple decompressions in preventing progression of ANFH and to identify independent risk factors associated with poor results.Methods: We retrospectively analyzed 58 hips in 36 patients, with a follow-up of 36 months. 20 patients (32 hips) underwent multiple drilling combined with simvastatin treatment (SIM group); 16 patients (26 hips) underwent multiple drilling alone (MD group). We defined clinical failure as a requirement for subsequent hip surgery or Harris Hip Score < 75. New occurrence of collapse or increased collapse > 2 mm on plain radiographs was defined as radiological failure.Results: Successful clinical results were achieved in 27 of 32 hips (84 %) in the SIM group compared with 15 of 26 hips (58 %) in the MD group (OR = 0.2, CI (0.1, 0.6.), P = 0.032). Successful radiological results were achieved in 27 of 32 hips (84 %) in the SIM group and in 16 of 26 hips (61.5 %) in the MD group (P = 0.048). Body mass index, disease stage and location of lesion were independent prognostic factors for overall survival.Conclusions: We believe that simvastatin could enhance the effects of multiple decompressions in preventing progression of ANFH and reducing the risk of femoral head collapse. [ABSTRACT FROM AUTHOR]

Bisphosphonate-related osteonecrosis of the jaw is a well-known potential side effect of long-term bisphosphonate therapy; the primary objective of the treatment should be to improve patient quality of life through pain and infection management, to prevent the development of new lesions, and to slow disease progression. In recent years, the use of laser for bisphosphonate-related osteonecrosis of the jaw has become more widespread, due to its use of administration and widely reported beneficial effects on tissue healing. The present systematic review of the literature sought to elucidate whether low-level laser therapy has positive effects on the treatment of bisphosphonate-related osteonecrosis of the jaw. We conducted a systematic search of the PubMed, EMBASE, and Cochrane Library electronic databases, with no restrictions on language or year of publication. Search strategies were formulated using keywords and Boolean operators. The electronic search strategy retrieved 55 records. From 55 articles, 16 were selected for full-text review, and of these, 10 were ultimately included for data analysis in this review. Our findings show that treatment modalities including laser were associated with superior outcomes in terms of cure or improvement of bisphosphonate-related osteonecrosis of the jaw lesions as compared with conventional surgical and/or conservative drug therapy. It can be concluded that combined treatment with antibiotics, minimally invasive surgery (including Er:YAG laser surgery), and low-level laser therapy in the early stages of the disease should be the gold standard for bisphosphonate-related osteonecrosis of the jaw management. [ABSTRACT FROM AUTHOR]

Avascular necrosis (AVN) of femoral head is a recognised complication of fracture dislocation of the hip joint but is not studied frequently in relation to acetabulum fractures. The aim was to establish the relationship between obturator externus and piriformis muscle morphology in acetabulum fractures and potenital development of AVN of the femoral head. Twenty-five fractures were included in this prospective study and were subjected to radiological assessment and computed tomography of the pelvis. Magnetic resonance imaging (MRI) of the hip was performed to assess the morphology of obturator externus and piriformis, and findings were compared intraoperatively (in 15 cases). Serial radiographs were taken at monthly intervals to assess the development of avascular necrosis. The patients with no evidence of AVN on radiographs at 6 months had additional MRI scans to look for such changes. Three patients developed AVN of femoral head and two had complete tears of piriformis and/or obturator externus muscles on the pre-operative MRI with the findings confirmed intraoperatively ( p = 0.013). None of the patients without changes of AVN at 6-month follow-up had complete tears of either or both muscles. Of these patients, there was one case each of T-type fracture, isolated posterior wall fracture with hip dislocation, and posterior wall with transverse fracture of the acetabulum. Complete tears of obturator externus and/or piriformis muscles are a strong predictor of future development of AVN of the femoral head. [ABSTRACT FROM AUTHOR]

The purpose is to describe the technique and report the results and complications of percutaneous femoral rotational osteotomy, secured with a trochanteric-entry, locked intramedullary rod, in adolescents with femoral anteversion. Our series comprised an IRB approved, retrospective, consecutive series of 85 osteotomies (57 patients), followed to implant removal. The average age at surgery was 13.3 years (range 8.8-18.3) with a female-to-male ratio of 2.8:1. The minimum follow-up was 2 years. Eighty-three osteotomies healed primarily. Two patients, subsequently found to have vitamin D deficiency, broke screws and developed nonunions; both healed after repeat reaming and rod exchange and vitamin supplementation. Preoperative symptoms, including in-toeing gait, tripping and anterior knee pain or patellar instability, were resolved consistently. We did not observe significant growth disturbance or osteonecrosis. We noted a 12.5 % incidence of broken interlocking screws; this did not affect the correction or outcome except for the two patients mentioned above. This prompted a switch from a standard screw (core diameter = 3 mm) to a threaded bolt (core diameter = 3.7 mm). These results have led this technique to replace the use of plates or blade plates for rotational osteotomies. [ABSTRACT FROM AUTHOR]

Introduction The delineation of the necrotic bone is a crucial step in the surgical treatment of medication-related osteonecrosis of the jaw (MRONJ). Several different approaches have been described including the innovative technique of fluorescence-guided surgery. However, until now there is a lack of data regarding the outcome. Therefore, the aim of the present study is to investigate the long-term success rates of fluorescence-guided surgery in the treatment of MRONJ. Patients and methods 54 Patients were prospectively assigned for surgical treatment of medication-related osteonecrosis of the jaw using fluorescence-guided surgery. Patients received doxycycline 100 mg twice a day for at least seven days preoperatively. Surgical treatment of MRONJ included complete removal of necrotic bone, which was monitored using the visual enhanced lesion scope (Velscope), followed by smoothening sharp bony edges and meticulous wound closure. Procedure success was assessed as postoperative maintenance of full mucosal coverage without pain, infection or bone exposure during regular follow-up. Results The study included a total of 54 patients (32 female and 22 male, mean age 71.4 ± 9.2 years). In the last follow-up an intact mucosa and absence of exposed bone, pain or signs of infection was identified in 47 of 54 patients (87%) and 56 of 65 lesions (86.2%) after first surgery using fluorescence-guidance. In 4 patients with 6 lesions a second fluorescence-guided surgery was necessary to achieve complete mucosal closure. Respectively, including the case with second surgical attempt 51 of 54 patients (94.4%) and 62 of 65 lesions (95.4%) showed complete mucosal healing. Conclusion The study shows that fluorescence-guided surgery is a safe and successful treatment option which can be considered for all stages of MRONJ. The technique seems also promising for MRONJ cases under denosumab. [ABSTRACT FROM AUTHOR]

Background: Avascular Necrosis (AVN) of hip is a devastating condition seen in younger individuals. It is the ischemic death of the constituents of the bone cartilage of the hip. The femoral head (FH) is the most common site for AVN. It results from interruption of the normal blood flow to the FH that fits into the hip socket. Earlier studies using autologous bone marrow stem cell concentrate injections have shown encouraging results with average success rates. The current study was designed to improve significantly the cartilage regeneration and clinical outcome. Methods: Total of 48 patients underwent autologous bone marrow stem cell and activated platelet-rich plasma derived growth factor concentrate (PRP-GFC) therapy for early and advanced stages AVN of femoral head in a single multi-specialty center. The total treatment was divided into three phases. In the phase I, all the clinical diagnostic measurements such as magnetic resonance imaging (MRI), computed tomography (CT) etc. with respect to the AVN patients and bone marrow aspiration from posterior iliac spine from the patients were carried out. In the phase II, isolation of stem cells and preparation from the patients were performed. Subsequently, in phase III, the stem cells and PRP- GFCs were transplanted in the enrolled patients. Results: Ninety three percent of the enrolled AVN patients showed marked enhancement in the hip bone joint space (more than 3mm) after combined stem cells and PRP-GFC treatment as evidenced by comparison of the pre- and posttreatment MRI data thus indicative of regeneration of cartilage. The treated patients showed significant improvement in their motor function, cartilage regrowth (3 to 10mm), and high satisfaction in the two-year follow-up. Conclusion: Combination of stem cell and PRP-GFC therapy has shown promising cartilage regeneration in 45 out of 48 patients of AVN. This study clearly demonstrates the safety and efficacy of this treatment. Larger numbers of patients need to be evaluated to better understand the efficacy of the combined stem cell and PRP-GFC therapy on AVN patients. [ABSTRACT FROM AUTHOR]

Objectives: The purpose of this case-control study was to find a correlation between certain imaging findings in dental panoramic radiographs and the risk for developing a medicationrelated osteonecrosis of the jaw (MRONJ) in patients taking antiresorptive therapy (AT). Methods: Randomized and blinded dental panoramic radiographs of 60 patients undergoing antiresorptive drug treatment (36 patients with MRONJ, 24 patients without MRONJ) and of 60 patients without AT were analyzed by 3 experts for the following signs: sequestrum, osteosclerosis, difference in sclerosing of alveolar process and body of mandible, visible alveolar socket, enhancement and loss of lamina dura, enhancement of the oblique ridge, enhancement of the mandibular canal, proliferative periostitis and osteolytic processes at the cortex. Results: Signs were seen significantly more often in patients undergoing AT than in the control group (CG) (osteosclerosis p-value = 0.019, visible alveolar socket p-value = 0.001, enhancement of lamina dura p-value < 0.001, enhancement of the mandibular canal p-value = 0.025, proliferative periostitis p-value = 0.05 and osteolytic processes at the cortex />-value < 0.001). While there is no significant difference between the CG and the group of patients with AT without manifest MRONJ for any sign, the significance increases when taking the group of patients under AT with manifest MRONJ into consideration. In addition, if medication was administered for malignant reasons, the signs visible alveolar socket, enhancement of the lamina dura and the enhancement of the mandibular canal were seen significantly more often. Conclusions: The radiographic findings mentioned above are not indicators for the development of MRONJ, as they are seen only in patients with manifest osteonecrosis. However, these findings could be important to assess the dimension and potency of a MRONJ. [ABSTRACT FROM AUTHOR]