31 research outputs found
Anticipated effects of burosumab treatment on long-term clinical sequelae in XLH: expert perspectives
X-linked hypophosphatemia (XLH) is a rare, progressive, genetic disease with multisystem impact that typically begins to manifest in early childhood. Two treatment options exist: oral phosphate in combination with active vitamin D (âconventional therapyâ) and a fully human monoclonal anti-FGF23 antibody, burosumab. The clinical benefit of conventional therapy in adults is limited, and poor tolerance and complications are common. Burosumab was first approved as a treatment for XLH in 2018 and its disease-modifying benefits in clinical trials in children suggest burosumab treatment could also alter the disease course in adults. Without long-term clinical data on multiple XLH-related sequelae available, the results of an elicitation exercise are reported, in which eight global experts in XLH posited how long-term treatment with burosumab is anticipated to impact the life course of clinical sequelae in adults with XLH. Based on their clinical experiences, the available evidence and their disease understanding, the experts agreed that some long-term benefits of using burosumab are likely in adults with XLH even if they have a misaligned skeleton from childhood. Burosumab treatment is anticipated to reduce the incidence of fractures and halt the progression of clinical sequelae associated with conventional therapy. While the trajectories for established dental abscesses are not expected to improve with burosumab treatment, dental abscess development may be prevented. Starting treatment with burosumab in childhood to increase the likelihood of an aligned skeleton and continuation into and throughout adulthood to maintain euphosphatemia may optimize patient outcomes, although future real-world investigation is required to support this hypothesis
International Lower Limb Collaborative (INTELLECT) study: a multicentre, international retrospective audit of lower extremity open fractures
Réponses immunitaires pathogéniques (des traits communs entre maladies parodontales et polyarthrite rhumatoïde?)
MONTROUGE-BUFR Odontol.PARIS5 (920492101) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF
An Fgfr3-activating mutation in immature osteoblasts affects the appendicular and craniofacial skeleton
International audienceAchondroplasia (ACH), the most common form of dwarfism is caused by a missense mutation in the gene coding for fibroblast growth factor receptor 3 (FGFR3). The resulting increase in FGFR3 signaling perturbs the proliferation and differentiation of chondrocytes (CCs), alters the process of endochondral ossification and thus reduces bone elongation. Increased FGFR3 signaling in osteoblasts (OBs) might also contribute to bone anomalies in ACH. In the present study of a mouse model of ACH, we sought to determine whether or not FGFR3 overactivation in OBs leads to bone modifications. The model carries an Fgfr3 activating mutation (Fgfr3 Y367C/+) that accurately mimics ACH; we targeted the mutation to either immature OBs and hypertrophic CCs or to mature OBs by using the Osx-cre and collagen 1α1 (2.3kb-Col1α1)-cre mouse strains, respectively. We observed that Fgfr3 activation in immature OBs and hypertrophic CCs (Osx-Fgfr3) not only perturbed the hypertrophic cells of the growth plate (thus affecting long bone growth) but also led to osteopenia and low cortical thickness in long bones in adult (3-month-old) mice but not in growing (3-week-old) mice. Importantly, craniofacial membranous bone defects were present in the adult mice. In contrast, activation of Fgfr3 in mature OBs (Col1-Fgfr3) had very limited effects on skeletal shape, size and micro-architecture. In vitro, we observed that Fgfr3 activation in immature OBs was associated with low mineralization activity. In conclusion, immature OBs appears to be affected by Fgfr3 overactivation, which might contribute to the bone modifications observed in ACH independently of CCs
Prevalence and risk indicators of first-wave COVID-19 among oral health-care workers: A French epidemiological survey.
BackgroundPrevious studies have highlighted the increased risk of contracting the COVID-19 for health-care workers and suggest that oral health-care workers may carry the greatest risk. Considering the transmission route of the SARS-CoV-2 infection, a similar increased risk can be hypothesized for other respiratory infections. However, no study has specifically assessed the risk of contracting COVID-19 within the dental profession.MethodsAn online survey was conducted within a population of French dental professionals between April 1 and April 29, 2020. Univariable and multivariable logistic regression analyses were performed to explore risk indicators associated with laboratory-confirmed COVID-19 and COVID-19-related clinical phenotypes (i.e. phenotypes present in 15% or more of SARS-CoV-2-positive cases).Results4172 dentists and 1868 dental assistants responded to the survey, representing approximately 10% of French oral health-care workers. The prevalence of laboratory-confirmed COVID-19 was 1.9% for dentists and 0.8% for dental assistants. Higher prevalence was found for COVID-19-related clinical phenotypes both in dentists (15.0%) and dental assistants (11.8%). Chronic kidney disease and obesity were associated with increased odds of laboratory-confirmed COVID-19, whereas working in a practice limited to endodontics was associated with decreased odds. Chronic obstructive pulmonary disease, use of public transportation and having a practice limited to periodontology were associated with increased odds of presenting a COVID-19-related clinical phenotype. Moreover, changes in work rhythm or clinical practice were associated with decreased odds of both outcomes.ConclusionsAlthough oral health-care professionals were surprisingly not at higher risk of COVID-19 than the general population, specific risk indicators could exist, notably among high aerosol-generating dental subspecialties such as periodontology. Considering the similarities between COVID-19-related clinical phenotypes other viral respiratory infections, lessons can be learned from the COVID-19 pandemic regarding the usefulness of equipping and protecting oral health-care workers, notably during seasonal viral outbreaks, to limit infection spread.ImpactResults from this study may provide important insights for relevant health authorities regarding the overall infection status of oral health-care workers in the current pandemic and draw attention to particular at-risk groups, as illustrated in the present study. Protecting oral health-care workers could be an interesting public health strategy to prevent the resurgence of COVID-19 and/or the emergence of new pandemics
Coordination of early cellular reactions during activation of bone resorption in the rat mandible periosteum: An immunohistochemical study
The activation step of bone remodeling remains poorly characterized. Activation comprises determination of the site to be remodeled, osteoclast precursor recruitment, their migration to the site of remodeling, and differentiation. These actions involve different compartments and cell types. The aim of this study was to investigate events and cell types involved during activation. We used a bone remodeling model in rats where extractions of the upper jaw molars initiate remodeling of the antagonist lower jaw (mandible) cortex along the periosteum. In this model osteoclastic resorption peaks 4 days after extractions. We previously reported that mast cell activation in the periosteum fibrous compartment is an early event of activation, associated with recruitment of circulating monocyte osteoclast precursors. By using immunohistochemistry, we observed 9 hours after induction a spatially oriented expression of InterCellular Adhesion Molecule-1 in the vessels that was inhibited by antagonists of histamine receptors 1 and 2. It was followed at 12 hours by the recruitment of ED1+ monocytes. In parallel, at 9 hours, Vascular Cellular Adhesion Molecule-1+ fibroblast-like cells scattered in the fibrous compartment of the periosteum between the vessels and the osteogenic compartment increased; these cells may be implicated in osteoclast precursor migration. Receptor Activator of NF KappaB Ligand+ cells increased at 12 hours in the osteogenic compartment and reached a peak at 18 hours. At 24 hours the numbers of osteogenic cells and subjacent osteocytes expressing semaphorin 3a, a repulsive for osteoclast precursors, decreased before returning to baseline at 48 hours. These data show that during activation the two periosteum compartments and several cell types are coordinated to recruit and guide osteoclast precursors towards the bone surface
Burosumab and Dental Abscesses in Children With XâLinked Hypophosphatemia
International audienc
Dental impact of anti-fibroblast growth factor 23 therapy in X-linked hypophosphatemia
Abstract Elevated fibroblast growth factor 23 (FGF23) in X-linked hypophosphatemia (XLH) results in rickets and phosphate wasting, manifesting by severe bone and dental abnormalities. Burosumab, a FGF23-neutralizing antibody, an alternative to conventional treatment (phosphorus and active vitamin D analogs), showed significant improvement in the long bone phenotype. Here, we examined whether FGF23 antibody (FGF23-mAb) also improved the dentoalveolar features associated with XLH. Four-week-old male Hyp mice were injected weekly with 4 or 16âmg·kgâ1 of FGF23-mAb for 2 months and compared to wild-type (WT) and vehicle (PBS) treated Hyp mice (nâ=â3â7 mice). Micro-CT analyses showed that both doses of FGF23-mAb restored dentin/cementum volume and corrected the enlarged pulp volume in Hyp mice, the higher concentration resulting in a rescue similar to WT levels. FGF23-mAb treatment also improved alveolar bone volume fraction and mineral density compared to vehicle-treated ones. Histology revealed improved mineralization of the dentoalveolar tissues, with a decreased amount of osteoid, predentin and cementoid. Better periodontal ligament attachment was also observed, evidenced by restoration of the acellular cementum. These preclinical data were consistent with the retrospective analysis of two patients with XLH showing that burosumab treatment improved oral features. Taken together, our data show that the dentoalveolar tissues are greatly improved by FGF23-mAb treatment, heralding its benefit in clinics for dental abnormalities
FGFR3 mutation causes abnormal membranous ossification in achondroplasia
International audienc
Prevalence of Enthesopathies in Adults With X-linked Hypophosphatemia: Analysis of Risk Factors
International audienceAbstract Context Enthesopathies are the determinant of a poor quality of life in adults with X-linked hypophosphatemia (XLH). Objective To describe the prevalence of patients with enthesopathies and to identify the risk factors of having enthesopathies. Methods Retrospective study in the French Reference Center for Rare Diseases of the Calcium and Phosphate Metabolism between June 2011 and December 2020. Adult XLH patients with full body X-rays performed using the EOSŸ low-dose radiation system and clinical data collected from medical records. The main outcome measures were demographics, PHEX mutation, conventional treatment, and dental disease with the presence of enthesopathies. Results Of the 114 patients included (68% women, mean age 42.2 ± 14.3 years), PHEX mutation was found in 105 patients (94.6%), 86 (77.5%) had been treated during childhood. Enthesopathies (spine and/or pelvis) were present in 67% of the patients (n = 76). Patients with enthesopathies were significantly older (P = .001) and more frequently reported dental disease collected from medical records (P = .03). There was no correlation between the PHEX mutations and the presence of enthesopathies. Sixty-two patients had a radiographic dental examination in a reference center. Severe dental disease (number of missing teeth, number of teeth endodontically treated, alveolar bone loss, and proportion of patients with 5 abscesses or more) was significantly higher in patients with enthesopathies. Conclusion Adult XLH patients have a high prevalence of enthesopathies in symptomatic adults patients with XLH seen in a reference center. Age and severe dental disease were significantly associated with the presence of enthesopathies