Necrotic Bone Research Articles

Management of Rib Avascular Necrosis Complicated by Osteomyelitis in a Patient With Sickle Cell Anemia

Abstract Introduction Avascular necrosis of the rib is a rare presentation of sickle cell anemia's vaso-occlusive crisis. This report describes the case of a 45-year-old man known to have sickle cell anemia presenting with rib avascular necrosis complicated by osteomyelitis. The patient came to the outpatient department with left lateral chest wall pain. Antibiotics produced no improvement. A computed tomography scan of the chest revealed a left sixth rib fracture with a thick fluid collection consistent with pus. The patient was taken to surgery and underwent necrotic bone debridement and pus drainage. The patient showed improvement and became afebrile after the surgery. Conclusion The lack of distinct clinical indicators and low occurrence of rib avascular necrosis can lead to misdiagnosis and mismanagement of the disease.

Significance of medication discontinuation on bisphosphonate-related jaw osteonecrosis in a rat model

Bisphosphonate (BP) discontinuation has been advised as a measure to prevent the incidence of bisphosphonate-related osteonecrosis of the jaw (BRONJ), however, its efficacy remains controversial. This study aimed to analyze the efficacy of BP discontinuation in reducing BRONJ severity following tooth extraction in a rat model. Thirty-four male Sprague–Dawley rats were divided into two BRONJ model categories: oral administration (PO) of alendronate (1 mg/kg) for 3 and 8 weeks and intraperitoneal (IP) injection of pamidronate (3 mg/kg) and dexamethasone (1 mg/kg) for 20 days. The PO model was divided into five groups (a control group without BPs and four experimental groups with 1-week discontinuation). The IP model was divided into two groups consisting of group I (without discontinuation) and group II (1-week discontinuation). One molar from both sides of the mandible was extracted. After extraction, the PO models were sacrificed at 3 and 5 weeks, and the IP models were sacrificed either immediately or at 2, 4, 6, and 8 weeks. Micro-CT showed non-significant differences among PO groups but significant differences were observed between IP groups. Most bone remodeling parameters within group I of the IP model differed significantly (p-value < 0.05). Histologically, group I showed a significantly higher percentage of necrotic bone than group II (51.93 ± 12.75%, p < 0.05) and a higher number of detached osteoclasts in TRAP staining. With discontinuation of medication for at least 1 week in rats, the effects of BPs on alveolar bone are suppressed and bone turnover and osteoclast functions are restored.

Reconstruction of mandibular defects in osteoradionecrosis and medication-related osteonecrosis of the jaw using fibula free flap and management of postoperative wound infections.

Complications from osteoradionecrosis (ORN) and medication-related osteonecrosis of the jaw (MRONJ) include oro-cutaneous fistulas, necrotic bone exposure, soft-tissue defects, and pathologic fractures. The fibula free flap (FFF) is a common free flap method used to reconstruct the mandible in severe cases. Recently, we have used the FFF successfully for the reconstruction of ORN and MRONJ mandibular defects. We report this method as a recommended technique for the treatment of ORN and MRONJ and the management method of postoperative infections. Four patients who were diagnosed with ORN of the mandible and 3 patients who were diagnosed with MRONJ of the mandible were included in the study. Among the 7 patients, 3 patients also had pathologic fractures. Partial mandibulectomy and FFF reconstruction were performed at the Department of Oral and Maxillofacial Surgery, Samsung Medical Center from April 2019 to March 2021. All 7 patients recovered following the reconstruction of the defect by FFF. Four patients experienced infections after surgery and pus cultures were performed. All were well healed without flap damage after changing the antibiotics by consultation with infectious medicine experts. FFF is a widely used method and can provide an extensive flap to reconstruct the mandible, especially those affected by ORN or MRONJ. If an infection occurs after surgery, appropriate antibiotic changes should be made through cooperation with the infectious medicine department. Therefore, FFF is a well-established and recommended method even in cases of challenging reconstruction.

Actinomycotic Osteomyelitis and Myiasis in Oroantral Communication: Clinicopathological and Tomographic Findings

Actinomycotic osteomyelitis of the maxilla presenting with oroantral communication is very rare, herein we report the first case of this condition in association with myiasis. A 50-year-old man reported chronic sinusopathy and a non-healing maxillary lesion, with 30 years of evolution, presenting occasional nasal and intraoral purulent discharge, with foul smell, and recurrent episodes of larvae presence. Cone beam computed tomography showed a large hyperdense image inside the left maxillary sinus, with focal areas with soft tissue density, and extensive discontinuity of the maxillary sinus floor, confirming the oroantral fistula. The necrotic tissue curetted during surgery presented hard consistency, and dark greenish color, and was submitted for histopathological analysis. Microscopically, necrotic bone, masses of filamentous bacteria colonie s, compatible with actinomycosis, and large rhomboidal structures surrounded by eosinophilic capsule - suggestive of larvae, were observed. The diagnosis of actinomycotic osteomyelitis with presence of structures compatible with larvae was established.

Bisphosphonates: how to proceed in orthodontics

Bisphosphonates are mainly used in the treatment of osteoporosis and in oncology. They bind to bone and inhibit the action of osteoclasts, leading to a decrease in bone remodeling and thus hindering tooth movement. The main objective was to present, through a review of the literature, the indications and therapeutic modalities for orthodontic treatment of patients who are or have been treated with bisphosphonates. The second objective was to propose a decisional organization chart for medical care. The search was done by keywords on PubMed. 189articles were found, mostly case reports. 1)Intravenous treatment is a contraindication to ODF treatment. 2)Per os treatment is possible with precautions: to be in accordance with the prescribing practitioner, avoid major travels, avoid surgical procedures (extractions...) which must be as atraumatic as possible. A delay in healing is to be expected. The benefit-risk ratio must be taken into account. The risks – the patient must be informed of them– are slowed movement and osteonecrosis. Clinical and radiological follow-up is necessary and may warrant re-evaluation of treatment at any time: excessive tooth mobility, molar furcation damage, unusually persistent periodontal pain and symptoms, fistulas, exposed areas of necrotic bone. The articles are of low grade. Most of the articles are studies made on animals. Research is ongoing to evaluate the value of bisphosphonates as anchorage reinforcement.

172. Scottish experience of pentoxifylline and tocopherol for the management of patients with osteoradionecrosis (ORN) of the jaws: A mini case series

Osteoradionecrosis (ORN) is a condition that occurs secondary to radiotherapy treatment for head and neck cancer, causing a reduction in the blood supply to the jaw, resulting in devitalised necrotic bone. Management usually includes antibiotics and corticosteroids, but in some cases surgery is carried out combat symptoms.

A Case of Multiple Radiation-related Complications during Long-term Follow-up after Sacral Ulcer Surgery

We report the clinical course of a patient who developed a sacral radiation ulcer 19 years after treatment for cervical cancer. The patient's postoperative course after a free latissimus dorsi muscle flap transfer was favorable, but various late radiation complications, including rectal perforation, a rectal fistula, sacral necrosis, a rectointestinal fistula, and sacroiliac joint osteomyelitis, occurred within 11 years. Plastic surgeons who treat such ulcers need to know that patients may develop other serious radiation-related complications. Being aware of these complications will allow appropriate measures to be taken and aid decisions regarding future surgical strategies. More careful assessment of sacral necrosis and bone resection may have ameliorated some of the complications. When encountering similar patients, we believe that careful magnetic resonance imagery (MRI) and intraoperative evaluation are warranted, as sacral necrosis may be detectable in some patients.

Bone Concentration of Ampicillin/Sulbactam: A Pilot Study in Patients with Osteonecrosis of the Jaw.

Osteonecrosis of the jaw (ONJ) occurs typically after irradiation of the head and neck area or after the intake of antiresorptive agents. Both interventions can lead to compromised bone perfusion and can ultimately result in infection and necrosis. Treatment usually consists of surgical necrosectomy and prolonged antibiotic therapy, usually through beta-lactams such as ampicillin/sulbactam. The poor blood supply in particular raises the question as to whether this form of antibiosis can achieve sufficient concentrations in the bone. Therefore, we investigated the antibiotic concentration in plasma and bone samples in a prospective study. Bone samples were collected from the necrosis core and in the vital surrounding bone. The measured concentrations in plasma for ampicillin and sulbactam were 126.3 ± 77.6 and 60.2 ± 35.0 µg/mL, respectively. In vital bone and necrotic bone samples, the ampicillin/sulbactam concentrations were 6.3 ± 7.8/1.8 ± 2.0 µg/g and 4.9 ± 7.0/1.7 ± 1.7 µg/g, respectively. These concentrations are substantially lower than described in the literature. However, the concentration seems sufficient to kill most bacteria, such as Streptococci and Staphylococci, which are mostly present in the biofilm of ONJ. We, therefore, conclude that intravenous administration of ampicillin/sulbactam remains a valuable treatment in the therapy of ONJ. Nevertheless, increasing resistance of Escherichia coli towards beta-lactam antibiotics have been reported and should be considered.

Multimodal and Multiscale Characterization of the Bone-Bacteria Interface in a Case of Medication-Related Osteonecrosis of the Jaw.

Medication-related osteonecrosis of the jaw (MRONJ) is a known side effect of bisphosphonates (BPs). Although bacterial infection is usually present, the etiology of MRONJ remains unknown. Here we apply a multimodal and multiscale (micro-to-nano) characterization approach to investigate the interface between necrotic bone and bacteria in MRONJ. A non-necrotic bone sample was used as control. Both necrotic and non-necrotic bone samples were collected from the jaw of a female individual affected by MRONJ after using BPs for 23 years. For the first time, resin cast etching was used to expose bacteria at the necrotic site. The bone-bacteria interface was also resolved at the nanoscale by scanning transmission electron microscopy (STEM). Nanosized particulates, likely corresponding to degraded bone mineral, were often noted in close proximity to or enclosed by the bacteria. STEM also revealed that the bone-bacteria interface is composed of a hypermineralized front fading into a highly disordered region, with decreasing content of calcium and phosphorus, as assessed by electron energy loss spectroscopy (EELS). This, combined with the variation in calcium, phosphorus, and carbon across the necrotic bone-bacteria interface evaluated by scanning electron microscopy (SEM)-energy dispersive X-ray spectroscopy (EDX) and the lower mineral-to-matrix ratio measured by micro-Raman spectroscopy in necrotic bone, indicates the absence of a mineralization front in MRONJ. It appears that the bone-bacteria interface originates not only from uncontrolled mineralization but also from the direct action of bacteria degrading the bone matrix. © 2022 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.

Outcomes of Open Fronto-Facial Resection for Fungal Osteomyelitis of Frontal Bone.

The second wave of coronavirus disease 2019 (COVID-19) led to the resurgence of opportunistic infections due to the injudicious use of steroids. Sinonasal mucormycosis was declared an epidemic in India during the pandemic. Mucormycosis was managed effectively by surgical debridement along with systemic amphotericin B. Currently, a resurgence of mucormycosis following initial treatment, in the form of fungal osteomyelitis of the frontal bone, is being seen in India. This prospective study included 10 patients with fungal osteomyelitis of the frontal bone due to mucormycosis. All patients underwent surgical debridement of the sequestrum and involucrum, with systemic antifungal pharmacotherapy. The average duration of time until mucormycosis recurrence was 22 days following initial treatment (range 10-33 days). Patients presented with extracranial bossing following outer frontal cortex erosion (n=3), bicortical erosion (n=3), bifrontal involvement (n=2), dural involvement (n=3), and involvement of the brain parenchyma and prefrontal cortex (n=2). All cases underwent debridement of the entire sequestrous bone and involucrum until normal bone could be identified. The mean admission duration was 4 weeks (range 3-6 weeks). All treated patients are currently alive and without disease, confirmed by contrast-enhanced computed tomography. Based on our experience, the successful treatment of fungal osteomyelitis due to mucormycosis requires a four-pronged approach: early detection, multidisciplinary management of comorbidities, surgical debridement of necrotic bone, and adequate systemic antifungal therapy.

Functional Endoscopic Sinus Surgery and Recurrence of Post-COVID Mucormycosis.

PurposeTo evaluate the value and limitation of functional endoscopic sinus surgery alone for the management of post-COVID mucormycosis and need for adjunctive invasive procedure.Materials and MethodsThis is a clinical observational study that included a total of 17 patients who underwent FESS for post-COVID mucormycosis from April 2021 to May 2021. These patients reported to our institute with no improvement in their symptoms post-FESS from June 2021 to July 2021. Aggressive Surgical debridement of the involved sinuses, removal of surrounding necrotic bone and orbital exenteration (wherever necessary) was done in these patients. A regular follow-up till six months was done for every patient. Sixteen out of 17 patients did not report with any fresh complaint or recurrence.ResultsThe study included male and female in ratio of 12:5, with a mean age of 62.5 ± 7.7 years (range: 50–75 years). These patients underwent functional endoscopic sinus surgery, one to two months before reporting to our institute. Post-FESS, there was no improvement in the symptoms. All these patients were given systemic antifungal treatment post-operatively. The specimen was sent for histopathological as well as microbiological examination. All the FESS operated patients required a secondary more aggressive surgical intervention.ConclusionPost-COVID mucormycosis is an aggressive fungal infection, for which FESS proves inadequate. It requires an aggressive surgical debridement of the necrotic bone along with the debridement of the sinuses.

37-Year-Old Man With Headache and Nasal Congestion

37-Year-Old Man With Headache and Nasal Congestion

The Therapeutic Effectiveness Using Fluorescence-Guided Surgery for MRONJ.

Background Long-term application of antiresorptive and/or antiangiogenic agents may cause oral disorders, including medication-related osteonecrosis of the jaw (MRONJ), which remains an incurable disease. Surgical treatment can help alleviate infection of the jaw and block the progress of the disease, but postoperative recurrence is often caused by incomplete resection of necrotic bone during surgery. The traditional method for determining the boundary of necrotic bone resection is primarily based on the color, geology, and microcirculation-based bleeding state according to the bone tissue, which is easily affected by the surgeon's clinical experience and can cause insufficient resection of osteonecrosis bone. Recent studies have proposed using fluorescence technology-assisted necrotic bone resection. Objective Systematic literature review was conducted to evaluate the therapeutic effectiveness of fluorescence-guided MRONJ surgery. Design PubMed/MedLine, Scopus, and Web of Science databases were searched from inception to February 7, 2022. Randomized controlled trial (RCT) studies were evaluated according to the Cochrane risk of bias tool ROB 2, and non-RCT (N-RCT) studies were evaluated according to the ROBINS-I tool. Results A total of 6 articles were included in the systematic review, including 4 N-RCT studies (1 retrospective study and 3 prospective studies) and 2 RCT studies, with 240 patients and 280 MRONJ lesions. The vast majority of studies were with moderate risk of bias, and the quality of the evidence was moderate. Conclusion Evidence of moderate strength suggests that fluorescence-assisted techniques effectively determine the bone resection boundaries in MRONJ surgery. However, whether the prognosis of patients treated with fluorescence-guided surgery is significantly better than that of traditional surgery must be proved by randomized controlled studies with larger sample sizes and higher quality.

Correlation Analysis between Chronic Osteomyelitis and Bacterial Biofilm.

Objective To study the role of bacterial biofilm (BBF) in the formation of chronic osteomyelitis and its prevention and treatment. Methods In this paper, a large amount of relevant literature was searched for analysis and summary, and the key words “chronic osteomyelitis,” “bacterial biofilm,” “infection,” and “debridement” were searched in databases, mainly CNKI, Wanfang, and Wipu. The search was conducted until December 2020. The role of bacterial biofilm formation in chronic osteomyelitis and its prevention were analyzed. Results Chronic osteomyelitis is formed mainly due to poor blood supply and drug-resistant bacteria, of which cellular biofilm is the most important cause. BBF forms on the surface of necrotic soft tissue and bone tissue, which has a protective effect on bacteria and greatly enhances their resistance to antibiotics, leading to difficulties in complete bacterial clearance and recurrent infections in osteomyelitis. Conclusion Through an in-depth study of the molecular biology and signal transduction of osteomyelitis biofilm, antibiotic biofilm treatment strategies and surgical debridement remain the focus of clinical translation of chronic osteomyelitis.

Is Upfront Surgical Resection of Stage II MRONJ More Cost Effective than Nonsurgical Therapy?

The 2022 AAOMS update on medication-related osteonecrosis of the jaws (MRONJ) acknowledged the benefit of surgical intervention in its algorithm for the treatment of early stage disease.1 Surgical intervention, when appropriate, has been shown in the literature to have predictably high success rates, close to 95%.2,3 By comparison, nonsurgical treatment has significantly lower success rates when defined as mucosal closure. Medical treatment also risks disease progression, and prolongation of exposed, infected and necrotic bone can significantly affect a patient’s quality of life.

Medication-related osteonecrosis of the jaw: A literature review and update.

Since the initial description of medication-related osteonecrosis of the jaw (MRONJ) almost two decades ago, the potential pathophysiology and risk factors have been elaborated on in many investigations and guidelines. However, the definitive pathophysiology based on scientific evidence remains lacking. Consequently, the optimal clinical treatment and prevention strategies for MRONJ have not been established. Despite their different mechanisms of action, many drugs, including bisphosphonates, denosumab, angiogenesis inhibitors, and other medications, have been reported to be associated with MRONJ lesions in cancer and osteoporosis patients. Importantly, MRONJ occurs predominantly in the jawbones and other craniofacial regions, but not in the appendicular skeleton. In this up-to-date review, the currently available information and theories regarding MRONJ are presented from both clinical and basic science perspectives. The definition and epidemiology of MRONJ, triggering medication, and histopathology are comprehensively summarized. The immunopathology and the potential pathophysiology based on immune cells such as neutrophils, T and B cells, macrophages, dendritic cells, and natural killer cells are also discussed. In addition, antiangiogenesis, soft tissue toxicity, necrotic bone, osteocyte death, and single-nucleotide polymorphisms are examined. Moreover, other possible mechanisms of MRONJ development are considered based on the unique embryological characteristics, different cell behaviors between jawbones and appendicular skeleton, unique anatomical structures, and sustained bacterial exposure in the oral cavity as a basis for MRONJ site specificity. Based on the literature review, it was concluded that multiple factors may contribute to the development of MRONJ, although which one is the key player triggering MRONJ in the craniofacial region remains unknown.

Simultaneous reconstruction of septic composite defects in lower extremities: Combination of fasciocutaneous perforator flap and Masquelet technique.

BackgroundManagement of composite defects with deep infection is a challenge to reconstructive surgeons. This study aimed to demonstrate the versatility, safety, and complications of simultaneous reconstruction of infectious composite defects with fasciocutaneous perforator flap combined with the Masquelet technique.MethodsThis study presents 10 patients in whom a fasciocutaneous perforator flap combined with the Masquelet technique was used to restore soft tissue and bone defects of the lower extremity, and were admitted in two level 1 trauma centers in Shanghai. The first stage included debridement of necrotic bone and infected tissues, implantation of a polymethylmethacrylate cement spacer to cover the void; bridging fixation of the osseous defect using external or internal fixators, and soft-tissue reconstruction with a fasciocutaneous perforator flap. The second stage included cement spacer removal with membrane preservation, refreshing bone edges, and grafting the cavity with bone morphogenetic proteins and autologous iliac bone graft.ResultsThe mean follow-up duration after autologous bone graft was 17.5 months. The average bony defects and average flap dimensions were 7.1 cm and 44.9 cm2, respectively. All flaps survived uneventfully. No recurrence of infection was detected in either the second stage of surgery or follow-up period. The mean duration of bone consolidation was 31.9 weeks. One patient had a 2 cm leg length discrepancy, and one patient had mild foot drop. No residual deformity requiring a secondary procedure occurred.ConclusionFasciocutaneous perforator flap combined with Masquelet technique provides a reliable and versatile alternative for patients with composite defects resulting from lower extremity infection.

Therapeutic Effect of Benidipine on Medication-Related Osteonecrosis of the Jaw.

Medication-related osteonecrosis of the jaw (MRONJ) is an intractable disease that is typically observed in patients with osteoporosis or tumors that have been treated with either bisphosphonate (BP) or antiangiogenic medicine. The mechanism of MRONJ pathogenesis remains unclear, and no effective definitive treatment modalities have been reported to date. Previous reports have indicated that a single injection of benidipine, an antihypertensive calcium channel blocker, in the vicinity of a tooth extraction socket promotes wound healing in healthy rats. The present study was conducted to elucidate the possibility of using benidipine to promote the healing of MRONJ-like lesions. In this study, benidipine was administered near the site of MRONJ symptom onset in a model rat, which was then sacrificed two weeks after benidipine injection, and analyzed using histological sections and CT images. The analysis showed that in the benidipine groups, necrotic bone was reduced, and soft tissue continuity was recovered. Furthermore, the distance between epithelial edges, length of necrotic bone exposed in the oral cavity, necrotic bone area, and necrotic bone ratio were significantly smaller in the benidipine group. These results suggest that a single injection of benidipine in the vicinity of MRONJ-like lesions can promote osteonecrotic extraction socket healing.

A Multidisciplinary Pathway for the Diagnosis and Prosthodontic Management of a Patient with Medication-Related Osteonecrosis of the Jaw (MRONJ)

Background: Medication-Related Osteonecrosis of the Jaw (MRONJ) can occur as an adverse reaction to several antiresorptive medications such as bisphosphonate. It presents clinically as a necrotic exposed bone. Several factors including tooth extraction and ill-fitting dentures increase the risk of osteonecrosis development. Case Report: A 72-year-old female who had an ill-fitting partial denture that caused an exposed necrotic bone and traumatic ulcer on the left posterior mandible. Bony sequestrums were removed and submitted for histological examination, which confirmed the diagnosis of MRONJ. Conclusions: This case illustrates the importance of identifying all risk factors associated with MRONJ by dentists to reduce its development in patients receiving antiresorptive medications. Moreover, patients at risk of MRONJ development should be screened carefully on a regular basis and all dental risk factors should be adjusted or removed.

CRYOTHERAPY WITH LIQUID NITROGEN FOR ORAL LEUKOPLAKIA TREATMENT: CASE REPORT

Cryotherapy is the use of cryogenic substances aiming for local tissue destruction. Although considered an alternative therapy for oral leukoplakia (OL), postoperative complications may occur, reinforcing the challenge of treat these lesions. A 68-year-old Black female patient was diagnosed with a 5-cm OL with mild epithelial dysplasia in the right gingival mucosa. Cryotherapy with liquid nitrogen at −196°C was proposed. The lesion was mapped for better control of temperature and dispersion of liquid nitrogen occurred every 1.5 cm. Two application cycles were carried out, each with 20 seconds of freezing and 1 minute of thawing. On day 21 of postoperative follow-up (D7-14-21), incomplete re-epithelialization and 4-mm bone exposure were noted. Local cleaning with chlorhexidine digluconate 0.12% for 1 week was performed. Because there was no improvement, necrotic bone was debrided and application on the adjacent areas was interrupted. After 6 months, OL regression was observed in the applied area and intact mucosa.