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      Cells Derived from Human Long Bone Appear More Differentiated and More Actively Stimulate Osteoclastogenesis Compared to Alveolar Bone-Derived Cells

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          Abstract

          Osteoblasts derived from mouse skulls have increased osteoclastogenic potential compared to long bone osteoblasts when stimulated with 1,25(OH) 2 vitamin D 3 (vitD 3). This indicates that bone cells from specific sites can react differently to biochemical signals, e.g., during inflammation or as emitted by bioactive bone tissue-engineering constructs. Given the high turn-over of alveolar bone, we hypothesized that human alveolar bone-derived osteoblasts have an increased osteogenic and osteoclastogenic potential compared to the osteoblasts derived from long bone. The osteogenic and osteoclastogenic capacity of alveolar bone cells and long bone cells were assessed in the presence and absence of osteotropic agent vitD 3. Both cell types were studied in osteogenesis experiments, using an osteogenic medium, and in osteoclastogenesis experiments by co-culturing osteoblasts with peripheral blood mononuclear cells (PBMCs). Both osteogenic and osteoclastic markers were measured. At day 0, long bones seem to have a more late-osteoblastic/preosteocyte-like phenotype compared to the alveolar bone cells as shown by slower proliferation, the higher expression of the matrix molecule Osteopontin ( OPN) and the osteocyte-enriched cytoskeletal component Actin alpha 1 ( ACTA1). This phenotype was maintained during the osteogenesis assays, where long bone-derived cells still expressed more OPN and ACTA1. Under co-culture conditions with PBMCs, long bone cells also had a higher Tumor necrose factor-alfa ( TNF-α) expression and induced the formation of osteoclasts more than alveolar bone cells. Correspondingly, the expression of osteoclast genes dendritic cell specific transmembrane protein ( DC-STAMP) and Receptor activator of nuclear factor kappa-Β ligand (RankL) was higher in long bone co-cultures. Together, our results indicate that long bone-derived osteoblasts are more active in bone-remodeling processes, especially in osteoclastogenesis, than alveolar bone-derived cells. This indicates that tissue-engineering solutions need to be specifically designed for the site of application, such as defects in long bones vs. the regeneration of alveolar bone after severe periodontitis.

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          Bisphosphonate use and atypical fractures of the femoral shaft.

          Studies show conflicting results regarding the possible excess risk of atypical fractures of the femoral shaft associated with bisphosphonate use. In Sweden, 12,777 women 55 years of age or older sustained a fracture of the femur in 2008. We reviewed radiographs of 1234 of the 1271 women who had a subtrochanteric or shaft fracture and identified 59 patients with atypical fractures. Data on medications and coexisting conditions were obtained from national registries. The relative and absolute risk of atypical fractures associated with bisphosphonate use was estimated by means of a nationwide cohort analysis. The 59 case patients were also compared with 263 control patients who had ordinary subtrochanteric or shaft fractures. The age-adjusted relative risk of atypical fracture was 47.3 (95% confidence interval [CI], 25.6 to 87.3) in the cohort analysis. The increase in absolute risk was 5 cases per 10,000 patient-years (95% CI, 4 to 7). A total of 78% of the case patients and 10% of the controls had received bisphosphonates, corresponding to a multivariable-adjusted odds ratio of 33.3 (95% CI, 14.3 to 77.8). The risk was independent of coexisting conditions and of concurrent use of other drugs with known effects on bone. The duration of use influenced the risk (odds ratio per 100 daily doses, 1.3; 95% CI, 1.1 to 1.6). After drug withdrawal, the risk diminished by 70% per year since the last use (odds ratio, 0.28; 95% CI, 0.21 to 0.38). These population-based nationwide analyses may be reassuring for patients who receive bisphosphonates. Although there was a high prevalence of current bisphosphonate use among patients with atypical fractures, the absolute risk was small. (Funded by the Swedish Research Council.).
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            Bone remodelling at a glance.

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              Osteonecrosis of the jaws associated with the use of bisphosphonates: a review of 63 cases

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                Author and article information

                Journal
                Int J Mol Sci
                Int J Mol Sci
                ijms
                International Journal of Molecular Sciences
                MDPI
                1422-0067
                17 July 2020
                July 2020
                : 21
                : 14
                : 5072
                Affiliations
                [1 ]Department of Oral Implantology and Prosthodontics, Academic Centre For Dentistry Amsterdam (ACTA), University of Amsterdam and Vrije Universiteit Amsterdam, Gustav Mahlerlaan 3004, 1081 LA Amsterdam, The Netherlands
                [2 ]Department of Oral Cell Biology, Academic Centre For Dentistry Amsterdam (ACTA), University of Amsterdam and Vrije Universiteit Amsterdam, Amsterdam Movement Sciences, Gustav Mahlerlaan 3004, 1081 LA Amsterdam, The Netherlands; a.bakker@ 123456acta.nl
                [3 ]Department of Dental Material Sciences, Academic Centre For Dentistry Amsterdam (ACTA), University of Amsterdam and Vrije Universiteit Amsterdam, Gustav Mahlerlaan 3004, 1081 LA Amsterdam, The Netherlands; c.kleverlaan@ 123456acta.nl
                [4 ]Department of Oral and Maxillofacial Surgery and Oral Pathology, Amsterdam UMC, Location VUmc, Vrije Universiteit, and ACTA, University of Amsterdam and Vrije Universiteit, Gustav Mahlerlaan 3004, 1081 LA Amsterdam, The Netherlands; m.gilijamse@ 123456amsterdamumc.nl or
                [5 ]Department of Oral and Maxillofacial Surgery, OLVG, 1081 LA Amsterdam, The Netherlands
                [6 ]Department of Periodontology, Academic Centre For Dentistry Amsterdam (ACTA), University of Amsterdam and Vrije Universiteit Amsterdam, Amsterdam Movement Sciences, Gustav Mahlerlaan 3004, 1081 LA Amsterdam, The Netherlands
                Author notes
                Author information
                https://orcid.org/0000-0001-6464-5172
                Article
                ijms-21-05072
                10.3390/ijms21145072
                7404058
                32709153
                8790f3e9-a8ab-4d42-ba4d-04f4a1346d0f
                © 2020 by the authors.

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

                History
                : 17 June 2020
                : 16 July 2020
                Categories
                Article

                Molecular biology
                jaw bone,vitamin d3,calcitriol,cell differentiation,osteoblasts,osteoclasts
                Molecular biology
                jaw bone, vitamin d3, calcitriol, cell differentiation, osteoblasts, osteoclasts

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