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      Evidence of impaired bone quality in men with type 1 diabetes: a cross-sectional study

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          Abstract

          Objective

          Type 1 diabetes (T1D) is associated with substantial fracture risk. Bone mineral density (BMD) is, however, only modestly reduced, suggesting impaired bone microarchitecture and/or bone material properties. Yet, the skeletal abnormalities have not been uncovered. Men with T1D seem to experience a more pronounced bone loss than their female counterparts. Hence, we aimed to examine different aspects of bone quality in men with T1D.

          Design and Methods

          In this cross-sectional study, men with T1D and healthy male controls were enrolled. BMD (femoral neck, total hip, lumbar spine, whole body) and spine trabecular bone score (TBS) were measured by dual x-ray absorptiometry, and bone material strength index (BMSi) was measured by in vivo impact microindentation. HbA 1c and bone turnover markers were analyzed.

          Results

          Altogether, 33 men with T1D (43 ± 12 years) and 28 healthy male controls (42 ± 12 years) were included. Subjects with T1D exhibited lower whole-body BMD than controls ( P = 0.04). TBS and BMSi were attenuated in men with T1D vs controls ( P = 0.016 and P = 0.004, respectively), and T1D subjects also had a lower bone turnover. The bone parameters did not differ between subjects with or without diabetic complications. Duration of disease correlated negatively with femoral neck BMD but not with TBS or BMSi.

          Conclusions

          This study revealed compromised bone material strength and microarchitecture in men with T1D. Moreover, our data confirm previous studies which found a modest decrease in BMD and low bone turnover in subjects with T1D. Accordingly, bone should be recognized as a target of diabetic complications.

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          Most cited references47

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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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            A critical evaluation of simple methods for the estimation of free testosterone in serum.

            The free and nonspecifically bound plasma hormone levels generally reflect the clinical situation more accurately than total plasma hormone levels. Hence, it is important to have reliable indexes of these fractions. The apparent free testosterone (T) concentration obtained by equilibrium dialysis (AFTC) as well as the fraction of serum T not precipitated by 50% ammonium sulfate concentration (non-SHBG-T; SHBG, sex hormone-binding globulin), often referred to as bioavailable T, appear to represent reliable indexes of biologically readily available T, but are not well suited for clinical routine, being too time consuming. Several other parameters have been used without complete validation, however: direct immunoassay of free T with a labeled T analog (aFT), calculation of free T (FT) from total T and immunoassayed SHBG concentrations (iSHBG), and the free androgen index (FAI = the ratio 100T/iSHBG). In the view of substantial discrepancies in the literature concerning the free or bioavailable T levels, we compared AFTC, FT, aFT, FAI, and non-SHBG-T levels in a large number of sera with SHBG capacities varying from low, as in hirsute women, to extremely high as in hyperthyroidism. All these indexes of bioavailable T correlated significantly with the AFTC concentration; AFTC and FT values were almost identical under all conditions studied, except during pregnancy. Values for aFT, however, were only a fraction of either AFTC or FT, the fraction varying as a function of SHBG levels. Also, the FAI/AFTC ratio varied as a function of the SHBG levels, and hence, neither aFT nor FAI is a reliable index of bioavailable T. The FT value, obtained by calculation from T and SHBG as determined by immunoassay, appears to be a rapid, simple, and reliable index ofbioavailable T, comparable to AFTC and suitable for clinical routine, except in pregnancy. During pregnancy, estradiol occupies a substantial part of SHBG-binding sites, so that SHBG as determined by immunoassay overestimates the actual binding capacity, which in pregnancy sera results in calculated FT values that are lower than AFTC. The nonspecifically bound T, calculated from FT, correlated highly significantly with and was almost identical to the values of non-SHBG-T obtained by ammonium sulfate precipitation, testifying to the clinical value of FT calculated from iSHBG.
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              Mechanisms of diabetes mellitus-induced bone fragility

              Diabetes mellitus is associated with an increased risk of fragility fractures. Here, Napoli and colleagues discuss the complex interactions between glucose homeostasis and bone fragility, the epidemiology of fractures in patients with diabetes mellitus and the effects of antidiabetic drugs on bone health.

                Author and article information

                Journal
                Endocr Connect
                Endocr Connect
                EC
                Endocrine Connections
                Bioscientifica Ltd (Bristol )
                2049-3614
                21 July 2021
                01 August 2021
                : 10
                : 8
                : 955-964
                Affiliations
                [1 ]Department of Clinical and Molecular Medicine , Faculty of Medicine and Health Sciences, Norwegian University of Science and Technology (NTNU), Trondheim, Norway
                [2 ]Department of Endocrinology , Trondheim University Hospital (St Olavs Hospital), Trondheim, Norway
                [3 ]Medical Clinic , Trondheim University Hospital (St Olavs Hospital), Trondheim, Norway
                [4 ]Department of Gastroenterology , Trondheim University Hospital (St Olavs Hospital), Trondheim, Norway
                [5 ]Department of Orthopedics , Trondheim University Hospital (St Olavs Hospital), Trondheim, Norway
                [6 ]Department of Biomaterials , University of Oslo, Oslo, Norway
                [7 ]Hormone Laboratory , Department of Medical Biochemistry, Oslo University Hospital, Aker, Oslo, Norway
                [8 ]K.G. Jebsen Center for Genetic Epidemiology , Department of Public Health and Nursing, NTNU, Trondheim, Norway
                Author notes
                Correspondence should be addressed to U Syversen: unni.syversen@ 123456ntnu.no
                Article
                EC-21-0193
                10.1530/EC-21-0193
                8428087
                34289447
                ac9138d0-7d21-42b0-9003-b8a3f827e380
                © The authors

                This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.

                History
                : 28 June 2021
                : 21 July 2021
                Categories
                Research

                type 1 diabetes,men,trabecular bone score,bone material strength index,microindentation

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