Osteonecrosis of the jaw after long-term oral bisphosphonates, followed by short-term denosumab treatment for osteoporosis: a case report

Bisphosphonates and denosumab are antiresoptive agents and are mainly used for management of metastatic bone cancer, osteoporosis and other diseases. Bisphosphonates (BP) can reduce skeletal related events (SRE) by 30–50%1; denosumab (D) has been found even more effective than BP2. BP and D have been both associated to osteonecrosis of the jaw (ONJ). We report a case of an osteoporotic woman (62 yrs), complaining maxillary intense pain after a recent tooth molar extraction, observed in July 2013 at our centre. She mentioned previous treatments with monthly ibandronate (Bonviva ® 150 mg) per os (from January 2003 to April 2010), risedronate (35 mg weekly, from May 2010 to May 2012) and two administrations (in August 2012 and in January 2013) of denosumab (Prolia ®, 60 mg sc every 6 months). Of note, she also reported a previous incisor extraction that was performed in July 2012 (before denosumab) without ONJ onset. No further systemic or local risk factors were referred. Intraorally, bone exposure of right emimaxilla was present; osteolysis area was observed in in CT scans. According to Bedogni et al.3, the ONJ case was classified as stage II B. Medical therapy (ampicillin/sulbactam im 2 times/die, metronidazole per os 3 times/die, chlorhexidine 0.2% mouth rinses) was administered. One week later, the patient was asymptomatic but within the same stage (IIA); she was referred to Oral and Maxillofacial surgery for surgical management

L-PRF application in extraction sockets of bisphosphonate-treated patients: preliminary results

Bisphosphonate-related osteonecrosis of the jaw (BRONJ) is a severe adverse event related to bisphosphonates (BPs) therapy; tooth extraction has been described as the main trigger. Autologous platelet concentrates, such Leukocyte-Platelet Rich Fibrin (L-PRF, Intraspin !) are designed to release platelet growth factors, improving the tissue healing in oral surgery. The aim of this study was to evaluate the efficacy and safety of our dental extraction protocol applied in BPs patients

Unexpected high frequency of genital involvement in women with clinical and hostological features of oral lichen planus

The main aims of this cross-sectional study were: (i) to assess the frequency of genital (vulval) lichen planus (VLP) and vulval lichen sclerosus (VLS) in women affected with oral lichen planus (OLP), regardless of the genital symptoms reported; and (ii) to verify whether any demographic, clinical, or histological features of OLP are associated with a higher risk of vulvo-vaginal involvement. Fifty-five women, presenting OLP, consecutively underwent gynaecological examination and, if they demonstrated positive clinical signs of VLP, underwent biopsy. After a drop-out of 14 subjects, 31/41 (75.6%) were found to have signs of genital involvement, of which 13/31 (44.0%) were asymptomatic. Following genital biopsy, 27/31 (87.1%) had histologically confirmed VLP or VLS. Following both univariate and multivariate statistical analyses, no significant association was found between gynaecological concomitance and demographic, clinical, histological features of OLP. This unpredictably common genital involvement in females with OLP emphasizes the importance of routinely performing both oral and gynaecological examinations, to facilitate an early and correct therapeutic approach. © 2006 Acta Dermato-Venereologica

Prevalence of vulval lichen planus in a cohort of women with oral lichen planus:an interdisciplinary study

BACKGROUND: Lichen planus (LP) is a mucocutaneous inflammatory dermatosis that frequently involves the oral and genital mucosae. Patients with LP affecting these sites are often seen by oral medicine specialists or gynaecologists who work in isolation and depend heavily on histopathologists to help them in confirming the diagnosis. There are few studies in the literature combining the experiences of these specialists who share the care of patients with both oral and genital LP. OBJECTIVES: To estimate the prevalence of vulval LP (VLP) in a cohort of patients with histologically confirmed oral LP (OLP). METHODS: The study group consisted of 42 women histologically diagnosed with OLP. The mean age was 60.5 years (range 27-81). They underwent genital examination, colposcopy and vulvoscopy. For the histological confirmation of clinical VLP biopsies were performed whenever a clinical lesion was found. Oral and genital biopsy specimens were processed through histological and immunohistochemical staining. Histological diagnoses of LP were made according to the modified World Health Organization histopathological criteria proposed by van der Meij and van der Waal for the diagnosis of OLP, and extended to VLP. Patients with clinical evidence, but without the histological confirmation of OLP and VLP, were excluded from the study group. RESULTS: Thirty-two vulval and one vaginal biopsy specimens were obtained. Histological diagnoses were confirmed in 24 of 32 (75%) patients who underwent a vulval biopsy: these represent 57% (24 of 42) of the study group. Of the 12 patients free of symptoms such as itching, burning and dyspareunia, but with clinical vulval lesions, 11 (92%) had histological confirmation of VLP. Vulval lichen sclerosus was ascertained in five of 32 (16%) cases. CONCLUSIONS: This study showed a 57% prevalence of VLP in selected patients with OLP. The high prevalence of VLP of 92% in the women who were free of vulval symptoms confirmed the usefulness of this careful integrated approach

Assessment of numerical methods for fully resolved simulations of particle-laden turbulent flows

This work was granted access to the HPC resources of CALMIP and the National Center for Atmospheric Researchs (NCAR) supercomputing centers. P. Costa acknowledges the funding from the Portuguese Foundation for Science and Technology under grant no. SFRH/BD/85501/2012. L.-P. Wang acknowledges the funding from the U.S. National Science Foundation (NSF) under grants CBET-1706130.Peer reviewedPostprin

Osteonecrosis of the jaws in patients assuming oral bisphosphonates for osteoporosis: A retrospective multi-hospital-based study of 87 Italian cases

BACKGROUND: Bisphosphonates (BPs) are currently the chief drugs for the prevention/treatment of osteoporosis; one of their adverse effects is the osteonecrosis of the jaw (BRONJ). The primary endpoints of this multi-center cross-sectional study are: i) an observation of the clinical features of BRONJ in 87 osteoporotic, non-cancer patients; and ii) an evaluation of their demographic variables and comorbidities. METHODS: 87 BRONJ patients in therapy for osteoporosis with BPs from 8 participating clinical Italian centers were consecutively identified and studied. After BRONJ diagnosis and staging, comorbidities and data relating to local and drug-related risk factors for BRONJ were collected. RESULTS: 77/87 (88.5%) patients in our sample used alendronate as a BP type; the duration of bisphosphonate therapy ranged from 2 to 200 months, and 51.7% of patients were in treatment for ≤ 38 months (median value). No comorbidities or local risk factors were observed in 17 (19.5%) patients, indicating the absence of cases belonging to BRONJ forms triggered by surgery. BRONJ localization was significantly associated with age: an increased risk of mandible localization (p=0.002; OR=6.36, 95%CI=[1.89; 21.54]) was observed for those over 72 yrs. At multivariate analysis, the increased risk of BRONJ in the mandible for people over 72 yrs (OR'=6.87, 95%CI=[2.13; 2.21]) was confirmed for a BP administration >56 months (OR'=4.82, 95%CI=[2.13; 22.21]). CONCLUSION: Our study confirms the fundamental necessity of applying protocols of prevention in order to reduce the incidence of BRONJ in osteoporotic, non-cancer patients in the presence of comorbidities and/or local risk factor as well as, less frequently, in their absence

The treatment of medication-related osteonecrosis of the jaw (Mronj): A systematic review with a pooled analysis of only surgery versus combined protocols

Medication-related osteonecrosis of the jaw (MRONJ) is a serious adverse reaction of antiresorptive and antiangiogenic agents, and it is also a potentially painful and debilitating condition. To date, no specific studies have prospectively evaluated the efficacy of its treatment and no robust standard of care has been established. Therefore, a systematic review (2007–2020) with a pooled analysis was performed in order to compare MRONJ surgical techniques (conservative or aggressive) versus combined surgical procedures (surgery plus a non-invasive procedure), where 1137 patients were included in the pooled analysis. A statistically significant difference in the 6-month improvement rate, comparing combined conservative surgery versus only aggressive (91% versus 72%, p = 0.05), was observed. No significant difference regarding any group with respect to the 6-month total resolution rate (82% versus 72%) was demonstrated. Of note, conservative surgery combined with various, adjuvant, non-invasive procedures (ozone, LLLT or blood component + Nd:YAG) was found to achieve partial or full healing in all stages, with improved results and the amelioration of many variables. In conclusion, specific adjuvant treatments associated with minimally conservative surgery can be considered effective and safe in the treatment of MRONJ, although well-controlled studies are a requisite in arriving at definitive statements