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      Deproteinized bovine bone and freeze‐dried bone allograft in sinus floor augmentation: A randomized controlled trial

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          Abstract

          Purpose

          The aim of this study was to investigate the effects of deproteinized bovine bone (DBB, Bio‐Oss®) and freeze‐dried bone allograft (FDBA, SureOss®) on bone healing during maxillary sinus floor augmentation (MSFA) using histology, immunohistochemistry, and gene expressions of the marker genes including Runx2, Opn, Ocn, Col1a1, Rankl, and Tnf‐α.

          Materials and Methods

          Fourteen participants who required two‐stage maxillary sinus augmentation were randomly assigned to DBB and FDBA bone grafting groups. Six months after the sinus augmentation procedure, bone samples were collected before implant placement with a trephine bur. Gene expression of Runx2, Opn, Ocn, Col1a1, Rankl, and Tnf‐α of the bone samples was assessed by real‐time polymerase chain reaction as a primary outcome. Histological analysis of H&E‐stained sections, immunohistochemistry for OPN quantification, and CBCT‐based bone tissue examination were performed to investigate the bone healing effects of DBB and FDBA substitutes.

          Results

          The FDBA treated group showed higher gene expression when compared with the DBB treated group in Opn (2.83 ± 1.23 vs. 1.40 ± 0.69; p = 0.04), Runx2 (1.49 ± 0.44 vs. 0.67 ± 0.14; p = 0.01), and Rankl (2.34 ± 0.85 vs. 0.69 ± 0.39; p = 0.03). In the DBB treated group a downregulated expression was found of Ocn relative to maxillary edentulous bone (1.18 ± 0.40 vs. 2.51 ± 0.78; p = 0.02).

          Conclusion

          Two‐stage maxillary sinus augmentation with FDBA upregulated specific bone remodeling genes when compared to DBB. The outcome of gene expression matched with the ones for OPN immunoreactivity, being higher in the FDBA group. FDBA had an expression pattern similar to native bone and showed stronger expression of bone forming related‐genes suggesting it may be clinically preferable over DBB.

          This clinical trial was not registered prior to participant recruitment and randomization (clinical registration number TCTR20221217002).

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          Most cited references28

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          The biology of fracture healing.

          The biology of fracture healing is a complex biological process that follows specific regenerative patterns and involves changes in the expression of several thousand genes. Although there is still much to be learned to fully comprehend the pathways of bone regeneration, the over-all pathways of both the anatomical and biochemical events have been thoroughly investigated. These efforts have provided a general understanding of how fracture healing occurs. Following the initial trauma, bone heals by either direct intramembranous or indirect fracture healing, which consists of both intramembranous and endochondral bone formation. The most common pathway is indirect healing, since direct bone healing requires an anatomical reduction and rigidly stable conditions, commonly only obtained by open reduction and internal fixation. However, when such conditions are achieved, the direct healing cascade allows the bone structure to immediately regenerate anatomical lamellar bone and the Haversian systems without any remodelling steps necessary. In all other non-stable conditions, bone healing follows a specific biological pathway. It involves an acute inflammatory response including the production and release of several important molecules, and the recruitment of mesenchymal stem cells in order to generate a primary cartilaginous callus. This primary callus later undergoes revascularisation and calcification, and is finally remodelled to fully restore a normal bone structure. In this article we summarise the basic biology of fracture healing. Copyright © 2011 Elsevier Ltd. All rights reserved.
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            Functions of RANKL/RANK/OPG in bone modeling and remodeling.

            The discovery of the RANKL/RANK/OPG system in the mid 1990s for the regulation of bone resorption has led to major advances in our understanding of how bone modeling and remodeling are regulated. It had been known for many years before this discovery that osteoblastic stromal cells regulated osteoclast formation, but it had not been anticipated that they would do this through expression of members of the TNF superfamily: receptor activator of NF-kappaB ligand (RANKL) and osteoprotegerin (OPG), or that these cytokines and signaling through receptor activator of NF-kappaB (RANK) would have extensive functions beyond regulation of bone remodeling. RANKL/RANK signaling regulates osteoclast formation, activation and survival in normal bone modeling and remodeling and in a variety of pathologic conditions characterized by increased bone turnover. OPG protects bone from excessive resorption by binding to RANKL and preventing it from binding to RANK. Thus, the relative concentration of RANKL and OPG in bone is a major determinant of bone mass and strength. Here, we review our current understanding of the role of the RANKL/RANK/OPG system in bone modeling and remodeling.
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              Is Open Access

              Bone grafts and biomaterials substitutes for bone defect repair: A review

              Bone grafts have been predominated used to treat bone defects, delayed union or non-union, and spinal fusion in orthopaedic clinically for a period of time, despite the emergency of synthetic bone graft substitutes. Nevertheless, the integration of allogeneic grafts and synthetic substitutes with host bone was found jeopardized in long-term follow-up studies. Hence, the enhancement of osteointegration of these grafts and substitutes with host bone is considerably important. To address this problem, addition of various growth factors, such as bone morphogenetic proteins (BMPs), parathyroid hormone (PTH) and platelet rich plasma (PRP), into structural allografts and synthetic substitutes have been considered. Although clinical applications of these factors have exhibited good bone formation, their further application was limited due to high cost and potential adverse side effects. Alternatively, bioinorganic ions such as magnesium, strontium and zinc are considered as alternative of osteogenic biological factors. Hence, this paper aims to review the currently available bone grafts and bone substitutes as well as the biological and bio-inorganic factors for the treatments of bone defect.
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                Author and article information

                Contributors
                (View ORCID Profile)
                Journal
                Clinical Implant Dentistry and Related Research
                Clin Implant Dent Rel Res
                Wiley
                1523-0899
                1708-8208
                April 2023
                January 11 2023
                April 2023
                : 25
                : 2
                : 343-351
                Affiliations
                [1 ] Faculty of Dentistry Chulalongkorn University Bangkok Thailand
                [2 ] Department of Oral and Maxillofacial Surgery, Faculty of Dentistry Chulalongkorn University Bangkok Thailand
                [3 ] Department of Prosthodontics, Faculty of Dentistry Chulalongkorn University Bangkok Thailand
                [4 ] Center of Excellence in Genomics and Precision Dentistry Faculty of Dentistry, Chulalongkorn University Bangkok Thailand
                Article
                10.1111/cid.13179
                36628938
                322619d1-a8de-4fe5-874d-38034cce07d0
                © 2023

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