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      Diabetes Mellitus-induced Bone Fragility

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          Abstract

          Accumulating evidence has shown that the risk of osteoporotic fractures is increased in patients with diabetes mellitus (DM). Thus, DM-induced bone fragility has been recently recognized as a diabetic complication. Because the fracture risk is independent of the reduction in bone mineral density, deterioration of the bone quality may be the main cause of bone fragility. Although its mechanism remains poorly understood, accumulated collagen cross-links of advanced glycation end-products (AGEs) and dysfunctions of osteoblast and osteocyte may be involved. Previous studies have suggested that various diabetes-related factors, such as chronic hyperglycemia, insulin, insulin-like growth factor-I, AGEs, and homocysteine, are associated with the risk of bone fragility caused by impaired bone formation and bone remodeling. Furthermore, several anti-diabetic drugs are known to affect bone metabolism and fracture risk. We herein review the association between DM and fracture risk as well as the mechanism of DM-induced bone fragility based on recent evidence.

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          Systematic review of type 1 and type 2 diabetes mellitus and risk of fracture.

          Mohsen Janghorbani, Rob Van Dam, Walter C. Willett … (2007)
          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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            Assessment of fracture risk and its application to screening for postmenopausal osteoporosis: synopsis of a WHO report. WHO Study Group.

            J Kanis (1994)
            The criteria required for an effective screening strategy for osteoporosis are largely met in Caucasian women. The disease is common and readily diagnosed by the measurement of bone mineral with single- or dual-energy absorptiometry. Such measurements have high specificity but lower sensitivity, so that the value of the technique is greater for those identified as being at higher risk. Against this background there is little evidence that osteoporosis can usefully be tackled by a public health policy to influence risk factors such as smoking, exercise and nutrition. This suggests that it is appropriate to consider targetting of treatment with agents affecting bone metabolism to susceptible individuals. Since the main benefits of the use of hormone replacement therapy (HRT) are probably on cardiovascular morbidity, the major role for selective screening is to direct non-HRT interventions. An appropriate time to consider screening and intervention is at the menopause, but screening at later ages is also worthy of consideration. Since the cost of screening is low and that of bone-active drugs is high, the selective use of screening techniques will improve the cost-benefit ratio of intervention.
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              Association of BMD and FRAX score with risk of fracture in older adults with type 2 diabetes.

              Ann Schwartz, Eric Vittinghoff, Douglas Bauer … (2011)
              Type 2 diabetes mellitus (DM) is associated with higher bone mineral density (BMD) and paradoxically with increased fracture risk. It is not known if low BMD, central to fracture prediction in older adults, identifies fracture risk in patients with DM. To determine if femoral neck BMD T score and the World Health Organization Fracture Risk Algorithm (FRAX) score are associated with hip and nonspine fracture risk in older adults with type 2 DM. Data from 3 prospective observational studies with adjudicated fracture outcomes (Study of Osteoporotic Fractures [December 1998-July 2008]; Osteoporotic Fractures in Men Study [March 2000-March 2009]; and Health, Aging, and Body Composition study [April 1997-June 2007]) were analyzed in older community-dwelling adults (9449 women and 7436 men) in the United States. Self-reported incident fractures, which were verified by radiology reports. Of 770 women with DM, 84 experienced a hip fracture and 262 a nonspine fracture during a mean (SD) follow-up of 12.6 (5.3) years. Of 1199 men with DM, 32 experienced a hip fracture and 133 a nonspine fracture during a mean (SD) follow-up of 7.5 (2.0) years. Age-adjusted hazard ratios (HRs) for 1-unit decrease in femoral neck BMD T score in women with DM were 1.88 (95% confidence interval [CI], 1.43-2.48) for hip fracture and 1.52 (95% CI, 1.31-1.75) for nonspine fracture, and in men with DM were 5.71 (95% CI, 3.42-9.53) for hip fracture and 2.17 (95% CI, 1.75-2.69) for nonspine fracture. The FRAX score was also associated with fracture risk in participants with DM (HRs for 1-unit increase in FRAX hip fracture score, 1.05; 95% CI, 1.03-1.07, for women with DM and 1.16; 95% CI, 1.07-1.27, for men with DM; HRs for 1-unit increase in FRAX osteoporotic fracture score, 1.04; 95% CI, 1.02-1.05, for women with DM and 1.09; 95% CI, 1.04-1.14, for men with DM). However, for a given T score and age or for a given FRAX score, participants with DM had a higher fracture risk than those without DM. For a similar fracture risk, participants with DM had a higher T score than participants without DM. For hip fracture, the estimated mean difference in T score for women was 0.59 (95% CI, 0.31-0.87) and for men was 0.38 (95% CI, 0.09-0.66). Among older adults with type 2 DM, femoral neck BMD T score and FRAX score were associated with hip and nonspine fracture risk; however, in these patients compared with participants without DM, the fracture risk was higher for a given T score and age or for a given FRAX score.
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                Author and article information

                Journal
                Journal ID (nlm-ta): Intern Med
                Journal ID (iso-abbrev): Intern. Med
                Title: Internal Medicine
                Publisher: The Japanese Society of Internal Medicine
                ISSN (Print): 0918-2918
                ISSN (Electronic): 1349-7235
                Publication date (Electronic): 18 May 2018
                Publication date (Print): 1 October 2018
                Volume: 57
                Issue: 19
                Pages: 2773-2785
                Affiliations
                [1 ]Internal Medicine 1, Shimane University Faculty of Medicine, Japan
                Author notes

                Correspondence to Dr.　Ippei Kanazawa, ippei.k@ 123456med.shimane-u.ac.jp

                Article
                DOI: 10.2169/internalmedicine.0905-18
                PMC ID: 6207820
                PubMed ID: 29780142
                SO-VID: 6ca231e1-9131-4e61-8793-8b2ae4a295df
                Copyright © Copyright © 2018 by The Japanese Society of Internal Medicine
                License:

                The Internal Medicine is an Open Access article distributed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License. To view the details of this license, please visit ( https://creativecommons.org/licenses/by-nc-nd/4.0/).

                History
                Date received : 26 January 2018
                Date accepted : 28 February 2018
                Categories
                Subject: Review Article

                Keywords: diabetes mellitus,bone fragility,osteoporosis,advanced glycation end products,osteoblast,osteocyte
                Data availability:
                Keywords: diabetes mellitus, bone fragility, osteoporosis, advanced glycation end products, osteoblast, osteocyte

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