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      Study on the association of the microstructure and bone metabolism in the osteoporotic femoral head

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          Abstract

          Background

          We compared the bone microstructure and metabolism of the femoral heads in patients with osteoporosis (OP) and non-OP patients to investigate the pathologic mechanism of OP and guide clinical treatment.

          Methods and results

          From January 2020 to June 2021, we obtained femoral head samples from 30 patients undergoing hip replacement due to femoral neck fracture. All patients were women aged approximately 67 to 80 years (mean age, 74 years). According to the dual-energy X-ray results, the femoral head samples were divided into the OP (T< − 2.5) and non-OP (T > − 1.5) groups. Microcomputed tomography scanning, bone metrology analysis, hematoxylin and eosin staining, and Masson’s trichrome staining were used to compare the local bone trabecular microstructure changes. Quantitative reverse transcription PCR was performed to identify changes in the osteogenesis-related genes and the osteoclast-related genes in specific regions to reflect osteogenic and osteoclastic activities. Femoral heads with OP showed significant changes in the local bone microstructure. Bone density, bone volume fraction, and the number and thickness of the bone trabeculae decreased. Local bone metabolism was imbalanced in the areas with microstructural changes in femoral heads with OP, with increased osteoclast activity and decreased osteoblast activity.

          Conclusions

          Deterioration of bone microstructure is closely related to abnormal bone metabolism associated with the activity of osteoblasts and osteoclasts in osteoporotic femoral heads. Promoting bone formation by improving local bone metabolism, enhancing osteogenic activity and inhibiting osteoclast activity may be a promising way of preventing local OP and osteoporotic fractures.

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          Most cited references25

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          Osteoclast differentiation and activation.

          Osteoclasts are specialized cells derived from the monocyte/macrophage haematopoietic lineage that develop and adhere to bone matrix, then secrete acid and lytic enzymes that degrade it in a specialized, extracellular compartment. Discovery of the RANK signalling pathway in the osteoclast has provided insight into the mechanisms of osteoclastogenesis and activation of bone resorption, and how hormonal signals impact bone structure and mass. Further study of this pathway is providing the molecular basis for developing therapeutics to treat osteoporosis and other diseases of bone loss.
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            Osteoporosis

            Fractures resulting from osteoporosis become increasingly common in women after age 55 years and men after age 65 years, resulting in substantial bone-associated morbidities, and increased mortality and health-care costs. Research advances have led to a more accurate assessment of fracture risk and have increased the range of therapeutic options available to prevent fractures. Fracture risk algorithms that combine clinical risk factors and bone mineral density are now widely used in clinical practice to target high-risk individuals for treatment. The discovery of key pathways regulating bone resorption and formation has identified new approaches to treatment with distinctive mechanisms of action. Osteoporosis is a chronic condition and long-term, sometimes lifelong, management is required. In individuals at high risk of fracture, the benefit versus risk profile is likely to be favourable for up to 10 years of treatment with bisphosphonates or denosumab. In people at a very high or imminent risk of fracture, therapy with teriparatide or abaloparatide should be considered; however, since treatment duration with these drugs is restricted to 18-24 months, treatment should be continued with an antiresorptive drug. Individuals at high risk of fractures do not receive adequate treatment and strategies to address this treatment gap-eg, widespread implementation of Fracture Liaison Services and improvement of adherence to therapy-are important challenges for the future.
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              Bone resorption by osteoclasts.

              Osteoporosis, a disease endemic in Western society, typically reflects an imbalance in skeletal turnover so that bone resorption exceeds bone formation. Bone resorption is the unique function of the osteoclast, and anti-osteoporosis therapy to date has targeted this cell. The osteoclast is a specialized macrophage polykaryon whose differentiation is principally regulated by macrophage colony-stimulating factor, RANK ligand, and osteoprotegerin. Reflecting integrin-mediated signals, the osteoclast develops a specialized cytoskeleton that permits it to establish an isolated microenvironment between itself and bone, wherein matrix degradation occurs by a process involving proton transport. Osteopetrotic mutants have provided a wealth of information about the genes that regulate the differentiation of osteoclasts and their capacity to resorb bone.
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                Author and article information

                Contributors
                wangchengbjmu@bjmu.edu.cn
                pengwang0106@163.com
                lfmed@sina.com
                liyangdr@bjmu.edu.cn
                zmw@bjmu.edu.cn
                fenghuizsu@163.com
                menghaoye@126.com
                lijunyang@ouc.edu.cn
                pengshi@cityu.edu.hk
                pengjiang301@126.com
                tianhua@bjmu.edu.cn
                Journal
                Mol Biol Rep
                Mol Biol Rep
                Molecular Biology Reports
                Springer Netherlands (Dordrecht )
                0301-4851
                1573-4978
                21 July 2023
                21 July 2023
                2023
                : 50
                : 9
                : 7437-7444
                Affiliations
                [1 ]GRID grid.411642.4, ISNI 0000 0004 0605 3760, Department of Orthopaedics/Engineering Research Center of Bone and Joint Precision Medicine, Ministry of Education /Beijing Key Laboratory of Spinal Disease Research, , Peking University Third Hospital, ; 49 North Garden Road, Haidian District, Beijing, 100191 China
                [2 ]GRID grid.414252.4, ISNI 0000 0004 1761 8894, Institute of Orthopaedics, Beijing Key Laboratory of Regenerative Medicine in Orthopedics/Key Laboratory of Musculoskeletal Trauma & War Injuries PLA/The Fourth Medical Center of the General Hospital of People’s Liberation Army, ; Beijing, 100853 China
                [3 ]GRID grid.4422.0, ISNI 0000 0001 2152 3263, Department of Electronic Engineering, , Ocean University of China, ; Qingdao, China
                [4 ]GRID grid.35030.35, ISNI 0000 0004 1792 6846, Centre for Robotics and Automation, , Shenzhen Research Institute of City University of Hong Kong, ; Shenzhen, China
                Author information
                http://orcid.org/0000-0001-7139-3372
                Article
                8505
                10.1007/s11033-023-08505-2
                10460722
                37479877
                c1420e49-3077-440d-8b64-a0c0cd9d2365
                © The Author(s) 2023

                Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.

                History
                : 13 February 2023
                : 4 May 2023
                Funding
                Funded by: FundRef http://dx.doi.org/10.13039/501100001809, National Natural Science Foundation of China;
                Award ID: 82001481
                Award ID: U20A20194
                Award Recipient :
                Funded by: FundRef http://dx.doi.org/10.13039/501100012326, International Science and Technology Cooperation Programme;
                Award ID: No.BYSYZD2019037
                Award Recipient :
                Funded by: FundRef http://dx.doi.org/10.13039/100016966, Bethune Charitable Foundation;
                Award ID: G-X-2019-1107-8
                Award Recipient :
                Categories
                Original Article
                Custom metadata
                © Springer Nature B.V. 2023

                Molecular biology
                osteoporosis,femoral head,bone metabolism,bone microstructure
                Molecular biology
                osteoporosis, femoral head, bone metabolism, bone microstructure

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