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      Musculoskeletal ambulation disability symptom complex as a risk factor of incident bone fragility fracture

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          Abstract

          Objectives

          Influence of presenting musculoskeletal ambulation disability symptom complex (MADS) on occurrence of bone fragility fracture (BFF) is investigated with retrospective cohort study.

          Methods

          A total of 931 subjects joined in the study. Subjects were selected as bone fragility risk positive in the fracture assessment tool questionnaire. Their assumed risk factors were harvested from the medical records and X-ray pictures. They were followed up at least 8 years consecutively, and occurrence of incident BFF was set as primary endpoint. Each assumed risk factor including MADS was evaluated using Cox regression analysis. Subjects were divided into 2 groups according to presence of MADS (G-MADS and G-noMADS). Adjusted hazard ratios between the 2 groups was evaluated using Cox regression analysis. The statistical procedures were performed before and after propensity score matching (PSM) procedures in order to make parallel with assumed risk factors.

          Results

          Statistically significant risk factors within 5% were prevalent vertebral body fracture, disuse, MADS, cognitive disorder, hypertension, contracture, Parkinsonism, being female sex, hyperlipidemia, insomnia, T-score in the femoral neck ≤ −2.3, chronic kidney disease ≥ stage 2, chronic obstructive pulmonary diseases, glucocorticoid steroid administrated, and osteoarthritis in order of the adjusted hazard ratios (from highest to lowest). Adjusted hazard ratios between G-MADS and G-noMADS were 2.70 and 1.83 for before and after PSM, respectively.

          Conclusions

          MADS demonstrated as a significant risk factor of BFF occurrence. In treating osteoporosis, fall risk should be aware of as well as bone fragility risk.

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          Most cited references31

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          Regulation of bone mass by Wnt signaling.

          Wnt proteins are a family of secreted proteins that regulate many aspects of cell growth, differentiation, function, and death. Considerable progress has been made in our understanding of the molecular links between Wnt signaling and bone development and remodeling since initial reports that mutations in the Wnt coreceptor low-density lipoprotein receptor-related protein 5 (LRP5) are causally linked to alterations in human bone mass. Of the pathways activated by Wnts, it is signaling through the canonical (i.e., Wnt/beta-catenin) pathway that increases bone mass through a number of mechanisms including renewal of stem cells, stimulation of preosteoblast replication, induction of osteoblastogenesis, and inhibition of osteoblast and osteocyte apoptosis. This pathway is an enticing target for developing drugs to battle skeletal diseases as Wnt/beta-catenin signaling is composed of a series of molecular interactions that offer potential places for pharmacological intervention. In considering opportunities for anabolic drug discovery in this area, one must consider multiple factors, including (a) the roles of Wnt signaling for development, remodeling, and pathology of bone; (b) how pharmacological interventions that target this pathway may specifically treat osteoporosis and other aspects of skeletal health; and (c) whether the targets within this pathway are amenable to drug intervention. In this Review we discuss the current understanding of this pathway in terms of bone biology and assess whether targeting this pathway might yield novel therapeutics to treat typical bone disorders.
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              Estrogen deficiency and bone loss: an inflammatory tale.

              Estrogen plays a fundamental role in skeletal growth and bone homeostasis in both men and women. Although remarkable progress has been made in our understanding of how estrogen deficiency causes bone loss, the mechanisms involved have proven to be complex and multifaceted. Although estrogen is established to have direct effects on bone cells, recent animal studies have identified additional unexpected regulatory effects of estrogen centered at the level of the adaptive immune response. Furthermore, a potential role for reactive oxygen species has now been identified in both humans and animals. One major challenge is the integration of a multitude of redundant pathways and cytokines, each apparently capable of playing a relevant role, into a comprehensive model of postmenopausal osteoporosis. This Review presents our current understanding of the process of estrogen deficiency-mediated bone destruction and explores some recent findings and hypotheses to explain estrogen action in bone. Due to the inherent difficulties associated with human investigation, many of the lessons learned have been in animal models. Consequently, many of these principles await further validation in humans.
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                Author and article information

                Contributors
                Journal
                Osteoporos Sarcopenia
                Osteoporos Sarcopenia
                Osteoporosis and Sarcopenia
                Korean Society of Osteoporosis
                2405-5255
                2405-5263
                17 September 2021
                September 2021
                17 September 2021
                : 7
                : 3
                : 115-120
                Affiliations
                [a ]Department of Rheumatology and Musculoskeletal Medicine, Yoshii Hospital, Shimanto City, 787-0033, Kochi Prefecture, Japan
                [b ]Department of Rheumatology, Kochi Memorial Hospital, Kochi, 780-0824, Kochi Prefecture, Japan
                [c ]Department of Rheumatology, Dohgo Onsen Hospital, Matsuyama, 790-0858, Ehime Prefecture, Japan
                [d ]Department of Internal Medicine, Yoshii Hospital, Shimanto City, 787-0033, Kochi Prefecture, Japan
                Author notes
                []Corresponding author. 6-7-5 Nakamura-Ohashidori, Shimanto City, 787-0033, Kochi Prefecture, Japan. ichiroyoshii@ 123456gmail.com ichiroyo@ 123456giga.ocn.ne.jp
                Article
                S2405-5255(21)00063-7
                10.1016/j.afos.2021.09.004
                8486644
                34632115
                4edbf2f8-66c3-46d9-be7c-17bf84e58f18
                © 2021 The Korean Society of Osteoporosis. Publishing services by Elsevier B.V.

                This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

                History
                : 1 August 2021
                : 3 September 2021
                : 11 September 2021
                Categories
                Original Article

                bone fragility,fracture,risk factor,musculoskeletal ambulation disability symptom complex,fall risk

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