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      Association of type 2 diabetes and an inflammatory marker with incident bone fracture among a Japanese cohort

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          Abstract

          Aims/Introduction

          There are various causes of incident bone fracture. Not only aging, low bone mineral density and history of previous fracture, but also diabetes mellitus and inflammation are regarded as risk factors for fracture. The purpose of the present study was to verify the association of glycemic control or one inflammatory marker with incident fracture in a large‐scale Japanese cohort.

          Materials and Methods

          The present study was carried out at the Hiroshima Atomic Bomb Casualty Council and included 6,556 participants (2,785 men and 3,771 women, aged 55–87 years) who underwent annual health examinations and were followed for 7.4 years. Information about incident fractures was collected at interviews. Participants were classified into three groups: normal, borderline and diabetes mellitus according to glycohemoglobin levels (treated diabetes patients were included in the diabetes mellitus group). Furthermore, participants were classified into four additional groups by glycemic control (diabetes mellitus or non‐diabetes mellitus) and C‐reactive protein ( CRP) levels (low or high). Hazard ratios ( HRs) of diabetes mellitus, CRP and their combined risk of incident fracture were evaluated.

          Results

          After adjusting for age, bone mineral density and previous fracture, CRP was associated with increased fracture risk (in men HR 1.04, 95% confidence interval [ CI]: 1.003–1.06; in women HR 1.07, 95% CI: 1.03–1.13), and diabetes mellitus predicted fracture risk in men ( HR 1.31, 95% CI: 1.02–1.51). Fracture risk was significantly higher among the diabetes mellitus with high CRP group compared with the non‐diabetes mellitus with low CRP group (in men HR 1.47, 95% CI: 1.02–1.98; in women HR 1.41, 95% CI: 1.04–1.92).

          Conclusions

          Among a Japanese cohort, CRP measurements were helpful to detect high fracture risk in patients with type 2 diabetes mellitus.

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          Most cited references22

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          Osteoporosis prevention, diagnosis, and therapy.

          (2001)
          To clarify the factors associated with prevention, diagnosis, and treatment of osteoporosis, and to present the most recent information available in these areas. From March 27-29, 2000, a nonfederal, nonadvocate, 13-member panel was convened, representing the fields of internal medicine, family and community medicine, endocrinology, epidemiology, orthopedic surgery, gerontology, rheumatology, obstetrics and gynecology, preventive medicine, and cell biology. Thirty-two experts from these fields presented data to the panel and an audience of 699. Primary sponsors were the National Institute of Arthritis and Musculoskeletal and Skin Diseases and the National Institutes of Health Office of Medical Applications of Research. MEDLINE was searched for January 1995 through December 1999, and a bibliography of 2449 references provided to the panel. Experts prepared abstracts for presentations with relevant literature citations. Scientific evidence was given precedence over anecdotal experience. The panel, answering predefined questions, developed conclusions based on evidence presented in open forum and the literature. The panel composed a draft statement, which was read and circulated to the experts and the audience for public discussion. The panel resolved conflicts and released a revised statement at the end of the conference. The draft statement was posted on the Web on March 30, 2000, and updated with the panel's final revisions within a few weeks. Though prevalent in white postmenopausal women, osteoporosis occurs in all populations and at all ages and has significant physical, psychosocial, and financial consequences. Risks for osteoporosis (reflected by low bone mineral density [BMD]) and for fracture overlap but are not identical. More attention should be paid to skeletal health in persons with conditions associated with secondary osteoporosis. Clinical risk factors have an important but poorly validated role in determining who should have BMD measurement, in assessing fracture risk, and in determining who should be treated. Adequate calcium and vitamin D intake is crucial to develop optimal peak bone mass and to preserve bone mass throughout life. Supplementation with these 2 nutrients may be necessary in persons not achieving recommended dietary intake. Gonadal steroids are important determinants of peak and lifetime bone mass in men, women, and children. Regular exercise, especially resistance and high-impact activities, contributes to development of high peak bone mass and may reduce risk of falls in older persons. Assessment of bone mass, identification of fracture risk, and determination of who should be treated are the optimal goals when evaluating patients for osteoporosis. Fracture prevention is the primary treatment goal for patients with osteoporosis. Several treatments have been shown to reduce the risk of osteoporotic fractures, including those that enhance bone mass and reduce the risk or consequences of falls. Adults with vertebral, rib, hip, or distal forearm fractures should be evaluated for osteoporosis and given appropriate therapy.
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            Systematic review of type 1 and type 2 diabetes mellitus and risk of fracture.

            The authors conducted a systematic review of published data on the association between diabetes mellitus and fracture. The authors searched MEDLINE through June 2006 and examined the reference lists of pertinent articles (limited to studies in humans). Summary relative risks and 95% confidence intervals were calculated with a random-effects model. The 16 eligible studies (two case-control studies and 14 cohort studies) included 836,941 participants and 139,531 incident cases of fracture. Type 2 diabetes was associated with an increased risk of hip fracture in both men (summary relative risk (RR) = 2.8, 95% confidence interval (CI): 1.2, 6.6) and women (summary RR = 2.1, 95% CI: 1.6, 2.7). Results were consistent between studies of men and women and between studies conducted in the United States and Europe. The association between type of diabetes and hip fracture incidence was stronger for type 1 diabetes (summary RR = 6.3, 95% CI: 2.6, 15.1) than for type 2 diabetes (summary RR = 1.7, 95% CI: 1.3, 2.2). Type 2 diabetes was weakly associated with fractures at other sites, and most effect estimates were not statistically significant. These findings strongly support an association between both type 1 and type 2 diabetes and increased risk of hip fracture in men and women.
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              Patients with prior fractures have an increased risk of future fractures: a summary of the literature and statistical synthesis.

              Numerous studies have reported increased risks of hip, spine, and other fractures among people who had previous clinically diagnosed fractures, or who have radiographic evidence of vertebral fractures. However, there is some variability in the magnitudes of associations among studies. We summarized the literature and performed a statistical synthesis of the risk of future fracture, given a history of prior fracture. The strongest associations were observed between prior and subsequent vertebral fractures; women with preexisting vertebral fractures (identified at baseline by vertebral morphometry) had approximately 4 times greater risk of subsequent vertebral fractures than those without prior fractures. This risk increases with the number of prior vertebral fractures. Most studies reported relative risks of approximately 2 for other combinations of prior and future fracture sites (hip, spine, wrist, or any site). The confidence profile method was used to derive a single pooled estimate from the studies that provided sufficient data for other combinations of prior and subsequent fracture sites. Studies of peri- and postmenopausal women with prior fractures had 2.0 (95 % CI = 1.8, 2.1) times the risk of subsequent fracture compared with women without prior fractures. For other studies (including men and women of all ages), the risk was increased by 2.2 (1.9, 2.6) times. We conclude that history of prior fracture at any site is an important risk factor for future fractures. Patients with a history of prior fracture, therefore, should receive further evaluation for osteoporosis and fracture risk.
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                Author and article information

                Contributors
                s-fujiwara@gentaikyo.or.jp
                Journal
                J Diabetes Investig
                J Diabetes Investig
                10.1111/(ISSN)2040-1124
                JDI
                Journal of Diabetes Investigation
                John Wiley and Sons Inc. (Hoboken )
                2040-1116
                2040-1124
                13 March 2017
                September 2017
                : 8
                : 5 ( doiID: 10.1111/jdi.2017.8.issue-5 )
                : 709-715
                Affiliations
                [ 1 ] Department of Molecular and Internal Medicine Graduate School of Biomedical & Health Sciences Hiroshima University Hiroshima Japan
                [ 2 ] Health Management & Promotion Center Hiroshima Atomic Bomb Casualty Council Hiroshima Japan
                Author notes
                [*] [* ] Correspondence

                Saeko Fujiwara

                Tel.: +81‐82‐243‐2451

                Fax: +81‐82‐241‐0414

                E‐mail address: s-fujiwara@ 123456gentaikyo.or.jp

                Article
                JDI12632
                10.1111/jdi.12632
                5583964
                28122172
                6522a389-4cbb-43e9-a7e9-c387de3d78f6
                © 2017 The Authors. Journal of Diabetes Investigation published by Asian Association for the Study of Diabetes (AASD) and John Wiley & Sons Australia, Ltd

                This is an open access article under the terms of the Creative Commons Attribution‐NonCommercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.

                History
                : 15 August 2016
                : 14 December 2016
                : 22 January 2017
                Page count
                Figures: 1, Tables: 3, Pages: 7, Words: 5267
                Funding
                Funded by: Health examination at the Health Management & Promotion Center
                Funded by: Hiroshima Atomic Bomb Casualty Council
                Categories
                Original Article
                Articles
                Clinical Science and Care
                Custom metadata
                2.0
                jdi12632
                September 2017
                Converter:WILEY_ML3GV2_TO_NLMPMC version:5.1.9 mode:remove_FC converted:05.09.2017

                c‐reactive protein,diabetes mellitus,incident bone fracture

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