exposure to antiresorptive therapy with bisphosphonates does not induce histological changes in human alveolar jawbone

Aim: The identification of specific alterations in the alveolar jawbone of patients treated with nitrogen-containing bisphosphonates (NBP) but without bisphosphonate-related osteonecrosis of the jaw (BRONJ) may help to identify the early steps of BRONJ and to select patients at risk for it. Materials and Methods: We performed a case-control study. Cases were 60 individuals treated with NBP without clinical and radiological signs of BRONJ and requiring surgical tooth extraction. Controls were 60 individuals never treated with NBP and requiring tooth extraction. Cases and controls were matched by sex (same) and age (within 5 years). 18 categorical (basophile reversal lines, osteoblasts, osteoblastic lines, osteocytes, empty osteocytic lacunae, osteoclasts, Howship's lacunae, vessel dilatation, vascular congestion, arteriolar thickening, intravascular fat globules, calcific fat necrosis, fatty bone marrow, ruptured adipocytes, granular cytoplasm of adipocytes, oil cysts, perivascular fibrosis, diffuse fibrous metaplasia) and 2 ordinal histopathological variables (inflammation and bone maturation) were investigated. Exact univariable and multivariable (correction for gender and age) logistic regression was used to test the association between NBP use and the histopathological variables. Because of multiple comparisons, the critical p-value was set to 0.0025 (0.05/20). Results: Cases and controls did not differ for any study variable except for vascular congestion that was significantly associated with NBP use (multivariable OR = 0.24, exact 95% CI 0.10 to 0.57 for cases vs. controls, p = 0.0006). Conclusions: Use of NBP does not produce specific histological alveolar bone alterations in the absence of overt BRONJ disease

TRATTAMENTO DELLA OSTEONECROSI DELLE OSSA MASCELLARI FARMACO-RELATA (ONJ)

Il trattamento di ONJ \ue8, dalla sua comparsa in letteratura, argomen- to molto dibattuto, prima, come osteonecrosi delle ossa mascellari (BRONJ) associata a bisfosfonati (BP), recentemente un\u2019ulteriore complessit\ue0 si \ue8 aggiunta con l\u2019identificazione di numerose molecole di nuova generazione, diverse dai BP, in grado di favorire lo sviluppo di ONJ (definite nel presente testo \u201cnon-BRONJ\u201d); queste molecole, nei pazienti oncologici per lesioni scheletriche, sono prescritte pi\uf9 o meno in associazione o in sequenza con i BP stessi (e.g. denosu- mab, inibitori delle tirosin-kinasi, anticorpi monoclonali anti-VEGF, inibitori di mTOR)1\u20133

Staging of osteonecrosis of the jaw requires computed tomography for accurate definition of the extent of bony disease

Management of osteonecrosis of the jaw associated with antiresorptive agents is challenging, and outcomes are unpredictable. The severity of disease is the main guide to management, and can help to predict prognosis. Most available staging systems for osteonecrosis, including the widely-used American Association of Oral and Maxillofacial Surgeons (AAOMS) system, classify severity on the basis of clinical and radiographic findings. However, clinical inspection and radiography are limited in their ability to identify the extent of necrotic bone disease compared with computed tomography (CT). We have organised a large multicentre retrospective study (known as MISSION) to investigate the agreement between the AAOMS staging system and the extent of osteonecrosis of the jaw (focal compared with diffuse involvement of bone) as detected on CT. We studied 799 patients with detailed clinical phenotyping who had CT images taken. Features of diffuse bone disease were identified on CT within all AAOMS stages (20%, 8%, 48%, and 24% of patients in stages 0, 1, 2, and 3, respectively). Of the patients classified as stage 0, 110/192 (57%) had diffuse disease on CT, and about 1 in 3 with CT evidence of diffuse bone disease was misclassified by the AAOMS system as having stages 0 and 1 osteonecrosis. In addition, more than a third of patients with AAOMS stage 2 (142/405, 35%) had focal bone disease on CT. We conclude that the AAOMS staging system does not correctly identify the extent of bony disease in patients with osteonecrosis of the jaw

Temporary Denosumab discontinuation promotes bone healing of Osteonecrosis of the jaw and minimizes the invasiveness of surgery: a case presentation

Denosumab has proved effective at low doses in increasing bone mineral density in osteoporosis patients. In contrast to high-doses antiresorptive therapy, denosumab has a transient effect on the inhibition of bone remodeling process, suggesting that denosumab-related osteonecrosis is a self-limiting disease, with high curative potential of surgery when performed after a proper time of RANKL-inhibitor suspension. We report the long-term clinical and radiological (CT scan) data of a patient affected by secondary osteoporosis (CTIBL for metastatic breast cancer) who under-went surgical treatment for stage II denosumab-related osteonecrosis of the upper maxilla 7-month after denosumab suspension. A minimally invasive approach was performed whit ex-traction of the first right upper molar and debridement of the surrounding alveolar bone. After surgery, patient was followed-up at three-month intervals up to 1 year and clinical and radiologi-cal data (CT scan) were recorded at each follow-up for early detection of signs of recurrent disease. Mucosal healing maintained stable in the long-term with radiological signs of bone remodeling in the post-operative site since the 6-month follow-up. The case presented strengthens the hypothesis that denosumab induces temporary alterations of bone turnover with predictable curative effect of minimal surgical procedures in cases of denosumab-related osteonecrosis of the jaw

A novel nasal endoscopic approach for removing displaced dental implants from the maxillary sinus.

Introduction: Over the last 30 years, dental implants have become widespread all over the world. Though the implantation procedure is standardized and safe, the displacement of implants into the maxillary sinus can occur. The aim of the study has been to describe a novel combined nasal endoscopic approach through the middle and lower meatus for managing dental implants displaced into the maxillary sinus. Methods/Results: A 40-year-old man was examined for a titanium osteo-integrated implant displaced within the alveolar recess of the left maxillary sinus. The indications and procedure are reported in detail. The pros and cons of this approach are compared with those of other standard surgical methods. Conclusions: The main strength of the technique described here lies in the ample view and ideal control of the displaced dental implant achieved by fashioning a second window at the lower meatus that enables enlargement of the natural ostium to be minimized, thereby ensuring an anatomically and functionally better result

Replacement of fractured reconstruction plate with customised mandible implant: A novel technique

In the case presented the authors faced up to the urgent necessity of lateral mandibular reconstruction in a patient affected by multiple myeloma who had already experienced two consecutives ruptures of conventional load-bearing plate. Given the insufficient remaining bone surface for stable plate fixation, especially at the proximal condylar segment, further plate substitution with standard method was not practicable. Moreover, patient\u2019s progressive declining in health, highly contraindicated mandibular reconstruction with vascularized bone graft. Therefore, it was decided to virtually plan and fabricate a customized mandible-like titanium prototyped plate, which was pre-shaped according to the individual anatomical bone conditions. The solution proposed may represent a valid option for the substitution of fractured/displaced mandibular reconstruction plates under complex anatomical conditions

Intraoral endoscopic enucleation of a solitary bone cyst of the mandibular condyle.

Solitary bone cysts are benign osteolytic lesions rarely involving the mandibular condyle. They are considered pseudocysts due to the absence of epithelium and their pathogenesis is unknown. These lesions are also known with a variety of synonyms, such as traumatic bone cysts, simple bone cysts, haemorrhagic bone cysts and unicameral cysts. The authors report a case of a solitary cyst of the condylar head treated by enucleation and curettage via an intraoral endoscopic-assisted surgical approach, which avoids the risk of facial nerve injury, reduces the patient's hospitalization and speeds up functional recovery

Worsening of osteonecrosis of the jaw during treatment with sunitinib in a patient with metastatic renal cell carcinoma.

We report on the potential association of suspected bisphosphonate-associated osteonecrosis of the jaw (BRONJ) recurrence with the use of the novel antiangiogenic drug sunitinib. A 59 year-old patient affected by metastatic renal cell carcinoma (RCC) and established BRONJ experienced consecutive episodes of painful jaw infection with cutaneous fistula and bone sequestration which occurred during active treatment with sunitinib, improved after discontinuation and antibiotic therapy, then rapidly worsened with resumption of sunitinib. We hypothesize that the potent antiangiogenic activity of sunitinib may amplify the inhibition of bone remodeling exerted by aminobisphosphonates entrapped within the osteonecrotic mineral matrix, antagonize mucosal healing and expose to infections during treatment. This supports the emerging role of soft-tissue damage in the pathogenesis of osteonecrosis of the jaw