Age-related trends and annual rates of change in trabecular bone scores and bone mineral density in Chinese men with Type 2 diabetes mellitus: a cross-sectional and longitudinal study

Age-related trends and annual rates of change in trabecular bone scores and bone mineral density in Chinese men with Type 2 diabetes mellitus: a cross-sectional and longitudinal study | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Age-related trends and annual rates of change in trabecular bone scores and bone mineral density in Chinese men with Type 2 diabetes mellitus: a cross-sectional and longitudinal study Yunyun Lin, Juanjuan Tang, Cheng Xue, Wenjuan Di, Peng Cheng This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-3974658/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Purpose Patients with Type 2 diabetes mellitus(T2DM) typically have an average or higher bone mineral density (BMD) but are at a significantly higher risk of fracture than patients without diabetes. Trabecular bone score (TBS), a textural index that evaluates pixel gray-level variations in the projected lumbar spine DXA image, has been introduced as an indirect measure of bone quality. Methods This study aimed to discuss the trends and annual rates of change in BMD and TBS with age in Chinese men with T2DM and men without diabetes mellitus. Results Lumbar spine(LS) TBS was found to be significantly lower in males with T2DM compared to normal males (1.279 ± 0.117 vs. 1.301 ± 0.090, P = 0.005). However, TBS in men with T2DM peaked around age 60, which was later and lower than in normal men at age 50 (1.294 ± 0.126 vs. 1.328 ± 0.088). Femoral neck, total hip, and lumbar spine BMD in men with T2DM were not significantly different from those in ordinary men. The results of the 3-year follow-up showed that men, both men with or without T2DM, exhibited the lowest annual rates of change at 66–75 years of age, with values of -1.05%(P < 0.001) and − 0.90%(P < 0.001), respectively. Patients with great glycemic control demonstrated higher TBS and BMD. Conclusion Men with T2DM have later and lower peak TBS and faster bone loss, which may reflect the effects of diabetes on bone microarchitecture and bone mineral. type 2 diabetes bone mineral density trabecular bone score men average annual rate of change Figures Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 Introduction Osteoporosis is a systemic skeletal disease characterized by diminished bone mass or defects in bone microarchitecture, which leads to decreased bone strength and an increased risk of fractures.[ 1 ] The results of the China Osteoporosis Epidemiology Survey, released by the National Health Commission of China in 2018, indicated that the prevalence of osteoporosis among individuals aged 50 years or older was 19.2%, with the prevalence among those aged 65 years or older reaching 32.0%. With the demographic aging trend, the prevalence continues to rise annually. Type 2 diabetes, another prevalent chronic ailment, poses a substantial global public health burden associated with aging. The worldwide prevalence of diabetes among adults (aged 20–79 years) is projected to be 7.7%, affecting 439 million adults in 2030. [ 2 , 3 ] Increased bone fragility is acknowledged as a frequent and severe complication in diabetic patients. The fracture risk is notably higher in individuals with diabetes in comparison to those without the condition. Moreover, a substantial number of individuals at risk of osteoporosis may also have diabetes, impacting their quality of life and potentially leading to severe health consequences such as paralysis. Prolonged immobilization and hospitalization, as a result, can contribute to significant morbidity and mortality. Consequently, there is a critical need for early identification of diabetic patients at high risk of fractures, a comprehensive understanding of the connection between these two conditions, and the development of effective assessment and management strategies to mitigate their impact on patients' health. Bone mineral density (BMD) measured by dual-energy X-ray absorptiometry (DXA) is the gold standard for assessing osteoporosis. Nevertheless, prevailing research indicates that individuals with T2DM often exhibit average or higher BMD levels compared to their non-diabetic counterparts. In addition, T2DM patients have a higher rate of obesity, which is also associated with elevated BMD. [ 4 – 7 ] A meta-analysis demonstrated an elevated risk of hip and non-spine fractures among individuals with T2DM. [ 8 ] Interestingly, there tends to be an underestimation of the fracture risk in diabetic individuals. The Trabecular Bone Score (TBS) is a non-invasive tool, utilizing DXA pixel gray level analysis to indirectly assess bone microstructure by analyzing trabecular bone texture sparseness. Particularly for patients with similar BMD levels, TBS reveals distinctions in bone microstructure and quality, offering information independent of BMD. The combined use of TBS and BMD significantly enhances fracture risk prediction. [ 9 ] Specifically, lumbar spine(LS) TBS emerges as a predictor of osteoporotic fractures in individuals with diabetes, capturing a more significant portion of the diabetes-associated fracture risk compared to BMD. [ 10 – 13 ] While the majority of TBS studies in T2DM populations have focused on women, limited research has explored the impact of TBS in Asian men with type 2 diabetes. This paper aims to investigate the differences in TBS and BMD between Chinese men with T2DM and non-T2DM men and the correlation with age through cross-sectional and longitudinal studies. Material and Methods Study population All subjects were recruited from Nanjing (China) and its surrounding areas, and all underwent a detailed medical history and physical examination. The men diagnosed with T2DM were patients hospitalized in the geriatric endocrinology department of our hospital, while non-T2DM men had regular physical examinations in our hospital between 2013 and 2023. As most of the patients attending endocrinology hospitalization and physical examination in our hospital were older, and to ensure an adequate sample size, individuals younger than 36 years and older than 96 years were excluded. Ultimately, our study included 446 male patients with T2DM and 322 normal adult males. Age, height, weight, BMI, BMD by site, TBS, and HbA1c of T2DM patients were recorded for each subject. The exclusion criteria comprised BMI > 35kg/m2, BMI < 15kg/m2, as well as common chronic diseases affecting bone metabolism, including various endocrine disorders (hypogonadism, hyperthyroidism), rheumatic immune disorders, gastrointestinal disorders, hematologic disorders, neuromuscular disorders, neurological disorders, chronic hepatic, renal, and cardiopulmonary disorders. Additionally, individuals on medications influencing bone metabolism, such as glucocorticoids, proton pump inhibitors, antiepileptic drugs, aromatase inhibitors, gonadotropin-releasing hormone analogs, antivirals, thiazolidinediones, and excess thyroid hormones, were excluded. Patients with type 1 diabetes mellitus were also excluded based on a review of their medical history. Bone mineral density and trabecular bone score Bone density DXA scans and TBS analyses were conducted at the Department of Geriatric Endocrinology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China. All patients underwent scans using the same machine. The TBS was derived by uploading the raw DXA images of the lumbar spine to the TBS iNsight software (version 2.0.0.1, Med-Imaps, Bordeaux, France) and subsequently calculating the LS TBS within the same region as the LS BMD. We utilize a proprietary algorithm to calculate the LS TBS within the identical measurement area as the LS BMD and to calibrate the equipment used in this study accurately. The TBS index measures bone microstructure texture, calculated from anterior and posterior dual-energy X-ray absorptiometry (DXA) lumbar spine scans. [ 14 ]TBS can be retrospectively applied to previously acquired DXA images without additional X-ray exposure, time, or economic cost. It is widely accessible without new equipment, provided it is correctly calibrated. The TBS estimate is usually robust and helpful in collecting empirical data. TBS is associated with diabetes, primary hyperthyroidism, rheumatoid arthritis, adrenal gland disease, and other conditions such as adrenal incidentalomas, chronic kidney disease, and fractures in individuals on long-term glucocorticoid therapy. [ 15 , 16 ] Diabetes and other parameters Standardized methods were employed to collect basic information, including age, gender, and medical history. Participants were instructed to wear lightweight clothing during height, weight, and DXA measurements. BMI was calculated as weight divided by the square of height (kg/m2). The diagnosis of diabetes mellitus was based on a fasting plasma glucose (FPG) level of ≥ 7.0 mmol/L, a 2-hour oral glucose tolerance test (OGTT) result of ≥ 11.1 mmol/L, or an glycated hemoglobin (HbA1c) level of ≥ 6.5% (mmol/mol), or a random blood glucose level of ≥ 11.1 mmol/L in patients exhibiting typical symptoms of hyperglycemia or hyperglycemic crisis.[ 17 ] The HbA1c was measured by chromatography. Statistical analysis The study organized participants into age groups, with each age subgroup spanning a decade. Following the assessment of normal distribution, data were presented as mean ± standard deviation (SD). One-way analysis of variance (ANOVA) and independent samples t-tests were employed to evaluate differences in BMD and TBS among the various age groups and the two populations. A linear trend test was employed to examine the trend of TBS and BMD in different age subgroups of males with T2DM and males without T2DM. We utilized Pearson's correlation analysis to establish the correlation between TBS and biochemical parameters. The average annual change rate represented the longitudinal changes in TBS and BMD. SPSS V27.0 statistical software was utilized in this study, and a significance level of P < 0.05 was considered statistically significant. Results Table 1 summarizes the baseline characteristics of men with T2DM, including height, weight, BMI, and HbA1c. A total of 446 male diabetic patients aged 36 to 95 were enrolled. A visual comparison of T2DM males with normal male controls is presented in Fig. 1 . TBS was found to be significantly lower in males with T2DM compared to normal males (1.279 ± 0.117 vs. 1.301 ± 0.090, P = 0.005). The relationship between TBS levels and age subgroups is depicted in Fig. 3 . TBS in all age groups of males with T2DM exhibited an increasing trend until the age of 60, followed by a decreasing trend after 60 years of age, reaching a peak of 1.294 at the age range of 56–65 years. TBS was negatively correlated with age (r=-0.102, P = 0.031), and the difference was significant when analyzed by linear trend test (P = 0.031). Lumbar spine TBS in non-diabetic men displayed significant variation with age, as analyzed by a linear trend test (P < 0.001). In contrast to diabetic men, LS TBS reached its highest value at 46–55 years of age, 1.328, followed by a decreasing trend. LS TBS in T2DM men peaked later than in normal males and exhibited a significantly lower peak than in normal males. Table 1 Baseline Characteristics of Study Subjects Age groups Height, cm Weight, kg BMI, kg/m 2 HbA1c, % (mmol/mol) Years Number Mean SD Mean SD Mean SD Mean SD 36–45 31 173.7 5.6 78.6 12.3 26.1 3.8 7.7 1.8 46–55 111 171.1 4.7 77.2 9.6 26.4 2.8 7.1 1.5 56–65 134 171.3 6.2 75.1 9.9 25.5 2.4 7.1 1.7 66–75 75 169.2 6.2 69.2 8.5 24.2 2.5 7.3 1.3 76–85 49 167.0 7.8 66.3 8.5 23.8 2.7 7.4 1.5 86–95 46 166.3 5.8 63.8 10.1 23.0 3.5 7.9 2.0 Total 446 170.1 6.3 72.7 10.8 25.1 3.0 7.3 1.6 Notes: Data are presented as mean+ SD or number(percentage) The relationship between BMD and age subgroups in men with T2DM is depicted in Fig. 4 . Through an independent samples t-test, no differences in BMD were observed by site between non-T2DM men and men with T2DM, as illustrated in Fig. 2 . Specifically, LS BMD (1.041 ± 0.169 g/cm2vs.1.033 ± 0.162, P = 0.500), FN BMD (0.790 ± 0.121 g/ cm2vs.0.783 ± 0.121, P = 0.418), and TH BMD (0.941 ± 0.125 g/cm2vs.0.939 ± 0.127, P = 0.810) showed no significant differences. In T2DM patients, FN BMD and TH BMD exhibited a decrease after 40 years (P = 0.002 and P = 0.004, respectively), while LS BMD demonstrated a progressive increase (P = 0.003). LS BMD was positively correlated with age (r = 0.147, P = 0.002) in T2DM men. The relationship between the respective LS BMD and TBS in the two populations is shown in Fig. 5 and Fig. 6 , and both were positively correlated, T2DM (r = 0.302, P<0.001) and non-T2DM (r = 0.449, P < 0.001). In this study, a cohort of 165 T2DM patients and 310 non-diabetic men underwent at least two TBS and BMD examinations at our institution, with a mean follow-up of 3.6 and 3.0 years, respectively. Upon data analysis, the mean annual rate of change was calculated for LSTBS, LSBMD, FNBMD, and THBMD. A negative mean yearly speed of change indicates bone loss during the follow-up period, while a positive rate indicates bone gain. Table 2 shows the annual rates of change in T2DM men and ordinary men in different age subgroups. The mean annual rates of change in LS, FN, and TH BMD in T2DM men were 0.33%, 0.06%, and 0.15%, respectively, while the mean annual rate of change in LS TBS was − 0.10%. In contrast, the mean annual rate of change in LS TBS in non-diabetic men was − 0.19%. Both men with and without T2DM exhibited the lowest annual rates of change at 66–75 years of age, with values of -1.05% and − 0.90%, respectively. Table 2 Average Annual Change Rate (%/Year) of BMD at Each Site and LS TBS in 10-Year Age Subgroups Age groups(years) LS TBS(%/years) LS BMD(%/years) FN BMD(%/years) TH BMD(%/years) a b a b a b a b 36–45 0.01 ± 2.41 1.22 ± 5.56 0.19 ± 2.29 0.38 ± 3.72 -0.05 ± 2.27 -0.41 ± 1.10 0.24 ± 1.71 -0.48 ± 0.37 46–55 -0.31 ± 2.70 0.46 ± 4.30 0.63 ± 1.66 0.04 ± 1.72 -0.04 ± 2.81 0.07 ± 2.41 -0.04 ± 2.18 0.28 ± 1.80 56–65 -0.02 ± 2.30 0.10 ± 6.57 0.64 ± 1.68 0.29 ± 2.18 -0.32 ± 1.79 -0.49 ± 2.50 0.08 ± 2.20 0.38 ± 1.98 66–75 -0.90 ± 2.48 -1.05 ± 4.41 0.98 ± 1.74 0.27 ± 2.34 0.04 ± 1.91 0.44 ± 4.45 0.25 ± 1.62 -1.09 ± 3.16 76–85 0.24 ± 1.69 -0.81 ± 6.09 1.08 ± 1.72 1.06 ± 1.99 -0.22 ± 2.24 -0.11 ± 2.84 0.19 ± 1.48 1.07 ± 2.19 86–95 0.24 ± 2.95 -0.27 ± 4.99 0.20 ± 2.26 0.54 ± 1.89 0.81 ± 2.13 1.27 ± 4.42 0.38 ± 1.82 0.65 ± 3.18 Total -0.19 ± 2.46 -0.10 ± 5.39 0.66 ± 1.83 0.33 ± 2.12 -0.08 ± 2.21 0.06 ± 3.18 0.13 ± 1.94 0.15 ± 2.40 Notes: Variables are expressed as mean± SD. a, men without T2DM; b, men with T2DM. The glycated hemoglobin (HbA1c) level, reflecting the average ambient fasting and postprandial glycemia over a 2–3-month period, plays a critical role in clinically managing hyperglycemia. In our study, HbA1c was also recorded in men with T2DM, and patients' glycemic control was assessed based on the HbA1c levels. HbA1c 6% (mmol/mol) suggests poor control. We investigated the difference between glycemic control and TBS and BMD. We found that in patients with HbA1c 6% (mmol/mol), the mean TBS was 1.287, the mean LS BMD was 1.017 g/cm2, the mean TH BMD was 0.775 g/cm2, and the mean FN BMD was 0.932g/cm2. Patients with great glycemic control demonstrated higher TBS and BMD. Discussion Numerous studies have shown that diabetic patients have lower TBS than non-diabetic patients. [ 18 ], [ 19 ] In a study on diabetes and TBS in Vietnam, it was shown that diabetic TBS was lower in women. In contrast, in men, the difference between diabetic status and TBS was not statistically significant. [ 20 ]In another cross-sectional observational study based on a Spanish population, LS BMD was significantly higher in patients with T2DM, but TBS was substantially lower. [ 21 ] The study from the FRISBEE cohort also indicated that BMD was higher in T2DM than in controls, and TBS was significantly lower in the T2DM group compared to controls. [ 22 ] Although there was no significant difference between non-T2DM and T2DM men's BMD values at each site in our study, TBS was significantly lower (1.279 ± 0.117 vs. 1.301 ± 0.090, P = 0.005). Furthermore, the peak TBS of men with T2DM occurred at a later age, possibly indicating the impact of diabetes on bone microstructure. The pathophysiological mechanisms of bone fragility in patients with T2DM are complex and multifactorial. Increasing evidence suggests it may be associated with hyperglycemia or insulin resistance. [ 23 ] Chronic hyperglycemia and accumulation of advanced glycation endproducts (AGE), insulin resistance, bone marrow fatty changes, inflammatory factors, adipokines from visceral fat, and oxidative stress are primary mechanisms by which T2DM induces bone fragility. [ 24 , 25 ] Chronic hyperglycemic stimulation and insulin resistance may disrupt the normal calcium and phosphorus metabolism in bone tissue. [ 9 ] In diabetic patients, AGE levels are elevated and accumulate due to hyperglycemia and increased levels of oxidative stress. Activating the receptor for AGEs (RAGE) expressed in human bone-derived cells enhances the production of inflammatory cytokines and reactive oxygen species (ROS), activating osteoblastic bone formation and inhibiting osteoclast differentiation, resulting in impaired bone material properties. [ 15 , 26 – 30 ] In addition, it has been hypothesized that diabetic bone loss may be a microvascular complication of diabetes mellitus. Microangiopathy is suggested to accelerate age-related bone loss, resulting in decreased bone mass, deterioration of bone microarchitecture, and increased skeletal fragility. These interconnected and overlapping mechanisms ultimately lead to insufficient peak bone mass accumulation in patients with T2DM. [ 28 , 31 ] A cross-sectional study conducted in Korea suggested a negative correlation between lumbar spine TBS and insulin resistance. [ 3 ] Hyperinsulinemia is probably responsible for the preserved, or improved, trabecular bone microarchitectural parameters observed in patients with T2DM, as insulin is osteoanabolic. It is hypothesized that elevated insulin levels resulting from insulin resistance may initially protect the skeleton. The higher BMI in patients with T2DM may be associated with increased bone mass, indicating a protective mechanism leading to reduced bone turnover. This may result in a delayed peak TBS in patients with T2DM. [ 32 , 33 ] A previous study on longitudinal changes in BMD and TBS in Korean adults found a mean annual rate of change of 0.3% for LS BMD and − 0.27% for LS TBS in men. [ 34 ] A recent study in a Chinese population of healthy men showed a mean annual rate of change in TBS of -0.17%. [ 35 ] However, few previous studies have evaluated the average annual rate of change in TBS and BMD in male patients with T2DM. The 3-year follow-up revealed that the lowest annual rate of change in TBS was observed in the 66–75 age group for both men with T2DM and men without T2DM, at -1.05% and − 0.90%, respectively. Research has shown that bone loss in adult males begins to accelerate significantly after the age of 65. Higher rates of cortical and trabecular bone loss have been linked to lower levels of bioactive steroids and elevated levels of follicle-stimulating hormone and bone turnover markers.[ 36 ] The significant decline in TBS suggests that men in this age group experience rapid bone loss and are at a greater risk of fracture. Therefore, it is especially important to prevent bone loss and decrease the risk of fractures in men over 65 years of age. A meta-analysis revealed that BMD was significantly higher in the femoral neck, total hip, and lumbar spine in patients with T2DM. [ 37 ] In our study population, there was no significant difference in BMD at each site between men without non-T2DM and patients with T2DM. As a result, conventional diagnostic tools that incorporate BMD into fracture risk assessment often underestimate fracture risk in patients with T2DM. In patients with T2DM, the use of a combined assessment of TBS and BMD in short-term follow-up more accurately reflects changes in bone strength and predicts osteoporotic fractures. [ 38 – 40 ] In our study, TBS and BMD were higher in patients with good glycemic control. This is similar to numerous previous studies. For example, a study in Rotterdam reported that patients with T2DM and HbA1c ≥ 7.5% (mmol/mol) had a 62% higher fracture risk than patients with HbA1c ≤ 7.5% (mmol/mol). [ 26 ]Another cross-sectional analysis of 493 women aged 65 years and older concluded that longer duration of T2DM and higher HbA1c levels were associated with higher hip BMD and lower TBS. [ 41 ]In addition, several extensive population-based cohort studies have confirmed that poor glycemic control is strongly associated with fracture risk; the fracture risk is similar between nondiabetic subjects and adequately controlled T2DM patients.[ 42 – 44 ] Before interpreting our results, we acknowledge specific strengths and limitations. The strengths of our study include analyzing men with T2DM from both cross-sectional and longitudinal perspectives compared to non-T2DM men. This allowed us to capture the variations in BMD and TBS at different sites. Additionally, all participants were scanned using the same DXA equipment, minimizing inter-machine errors. Both populations were also followed up, and data have been collected from participants over the past ten years. In our study, we conducted a comparative analysis of glycemic control status. However, we did not consider the duration of T2DM and its complications. T2DM may often remain undiagnosed for many years, which is a limitation of our study. Ideally, individuals under 36 should have been included in the analysis to determine the age at which our population reached peak BMD and TBS. Regrettably, the analysis of trends across the entire age range was not feasible due to the limited number of individuals under 35 in the population studied at our hospital. Finally, osteoporosis management's primary focus should be reducing the risk of fractures. However, this study's limited number of fractures made it impossible to establish the relationship between TBS and fracture risk. Conclusions TBS is lower and peaks later in diabetic patients. As in normal men, TBS declines most rapidly, around the age of 70 years. TBS can be used as an indicator for recognizing bone deterioration in diabetic patients with high BMD and is critical for the early recognition and prevention of osteoporosis and for the timely administration of medications to slow bone loss. Abbreviations BMI, body mass index; T2DM, type 2 diabetes mellitus; DXA, dual-energy X-ray absorptiometry; BMD, bone mineral density; TBS, trabecular bone score; FN, femoral neck; TH, total hip; LS, lumbar spine. trabecular bone score; HbA1c, glycated hemoglobin. Declarations Data Sharing Statement The datasets generated during and/or analysed during the current study are available from the corresponding author on reasonable request. Acknowledgments The authors would like to gratefully acknowledge all participants for their significant contributions to this work. Conflict of Interest The authors declare that they have no conflict of interest. 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Low Bone Turnover Markers in Young and Middle-Aged Male Patients with Type 2 Diabetes Mellitus. J Diabetes Res (2020) 2020: p. 6191468. doi:10.1155/2020/6191468. Murray CE, Coleman CM. Impact of Diabetes Mellitus on Bone Health. Int J Mol Sci (2019) 20(19):4873. doi:10.3390/ijms20194873. Park SY, Choi KH, Jun JE, Chung HY. Effects of Advanced Glycation End Products on Differentiation and Function of Osteoblasts and Osteoclasts. J Korean Med Sci (2021)36(37): p. e239. doi:10.3346/jkms.2021.36.e239. Eller-Vainicher C, Cairoli E, Grassi G, Grassi F, Catalano A, MerlottiD, et al. Pathophysiology and Management of Type 2 Diabetes Mellitus Bone Fragility. J Diabetes Res (2020) 2020: p. 7608964. doi:10.1155/2020/7608964. Khosla S, Samakkarnthai P, Monroe DG, Farr JN. Update on the pathogenesis and treatment of skeletal fragility in type 2 diabetes mellitus. Nat Rev Endocrinol (2021) 17(11):685-697. doi:10.1038/s41574-021-00555-5. Carnevale V, Romagnoli E, D'Erasmo L, D'Erasmo E. Bone damage in type 2 diabetes mellitus. Nutr Metab Cardiovasc Dis (2014) 24(11):1151-1157. doi:10.1016/j.numecd.2014.06.013. Lecka-Czernik B. Diabetes, bone and glucose-lowering agents: basic biology. Diabetologia (2017) 60(7):1163-1169. doi:10.1007/s00125-017-4269-4. Park SY, Kim JH, Choi HJ, Ku EJ, Hong AR, Lee JH, et al. Longitudinal changes in bone mineral density and trabecular bone score in Korean adults: a community-based prospective study. Arch Osteoporos (2020) 15(1): p. 100. doi:10.1007/s11657-020-00731-6. Tang H, Di W, Qi H, Liu J, Yu J, Cai J, et al. Age-Related Changes in Trabecular Bone Score and Bone Mineral Density in Chinese Men: A Cross-Sectional and Longitudinal Study. Clin Interv Aging (2022) 17: p. 429-437. doi:10.2147/CIA.S358951. Riggs BL, Melton LJ, Robb RA, Camp JJ, Atkinson EJ, McdDaniel L, et al. A population-based assessment of rates of bone loss at multiple skeletal sites: evidence for substantial trabecular bone loss in young adult women and men. J Bone Miner Res (2008) 23(2):205-214. doi:10.1359/jbmr.071020. Martínez-Montoro JI, García-Fontana B, García-Fontana C, Muñoz-Torres M. Evaluation of Quality and Bone Microstructure Alterations in Patients with Type 2 Diabetes: A Narrative Review. J Clin Med (2022) 11(8). doi:10.3390/jcm11082206. McCloskey EV, Odén A, Harvey NC, Leslie WD, Hans D, Johansson H, et al. A Meta-Analysis of Trabecular Bone Score in Fracture Risk Prediction and Its Relationship to FRAX. J Bone Miner Res (2016) 31(5):940-948. doi:10.1002/jbmr.2734. Hans D, Goertzen AL, Krieg MA, Leslie WD. Bone microarchitecture assessed by TBS predicts osteoporotic fractures independent of bone density: the Manitoba study. J Bone Miner Res (2011) 26(11):2762-2769. doi:10.1002/jbmr.499. Leslie WD, Aubry-Rozier B, Lix LM, Morin SN, Majumdar SR, Hans D. Spine bone texture assessed by trabecular bone score (TBS) predicts osteoporotic fractures in men: the Manitoba Bone Density Program. Bone (2014) 67:10-14. doi:10.1016/j.bone.2014.06.034. Palomo T, Dreyer P, Muszkat P, Weiler FG, Bonansea TC, Domingues FC, et al. Effect of soft tissue noise on trabecular bone score in postmenopausal women with diabetes: A cross sectional study. Bone (2022) 157:116339. doi:10.1016/j.bone.2022.116339. Dufour AB, Kiel DP, Williams SA, Weiss RJ, Samelson EJ. Risk Factors for Incident Fracture in Older Adults With Type 2 Diabetes: The Framingham Heart Study. Diabetes Care (2021) 44(7):1547-1555. doi:10.2337/dc20-3150. Li CI, Liu CS, Lin WY, Meng NH, Chen CC, Yang SY, et al. Glycated Hemoglobin Level and Risk of Hip Fracture in Older People with Type 2 Diabetes: A Competing Risk Analysis of Taiwan Diabetes Cohort Study. J Bone Miner Res (2015) 30(7):1338-1346. doi:10.1002/jbmr.2462. Oei L, Zillikens MC, Dehghan A, Buitendijk GHS, Castaño-Betancourt MC, Estrada K, et al. High bone mineral density and fracture risk in type 2 diabetes as skeletal complications of inadequate glucose control: the Rotterdam Study. Diabetes Care (2013) 36(6):1619-1628. doi:10.2337/dc12-1188. Additional Declarations No competing interests reported. Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-3974658","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":274075433,"identity":"31200406-bbe5-439d-b798-6dd4f834b576","order_by":0,"name":"Yunyun Lin","email":"","orcid":"","institution":"The First Affiliated Hospital of Nanjing Medical University","correspondingAuthor":false,"prefix":"","firstName":"Yunyun","middleName":"","lastName":"Lin","suffix":""},{"id":274075434,"identity":"472792e1-5861-4bd2-b9c6-a0a2c3ae5a0e","order_by":1,"name":"Juanjuan Tang","email":"","orcid":"","institution":"The First Affiliated Hospital of Nanjing Medical University","correspondingAuthor":false,"prefix":"","firstName":"Juanjuan","middleName":"","lastName":"Tang","suffix":""},{"id":274075435,"identity":"381244a8-2170-47a8-8b85-bcc806851e3e","order_by":2,"name":"Cheng Xue","email":"","orcid":"","institution":"The First Affiliated Hospital of Nanjing Medical University","correspondingAuthor":false,"prefix":"","firstName":"Cheng","middleName":"","lastName":"Xue","suffix":""},{"id":274075436,"identity":"312a73c0-b11c-4419-9ba5-fc3183fa30bc","order_by":3,"name":"Wenjuan Di","email":"","orcid":"","institution":"The First Affiliated Hospital of Nanjing Medical University","correspondingAuthor":false,"prefix":"","firstName":"Wenjuan","middleName":"","lastName":"Di","suffix":""},{"id":274075437,"identity":"bc0ec6ca-c3b0-4eda-a327-b2f750c53238","order_by":4,"name":"Peng Cheng","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAAkklEQVRIiWNgGAWjYFACHjaGDwwMCaRpYZxBshZmHpK08M/uPfbY5o9NnsEB5oePbhCjReLOuXTj3La0YoMDbMbGOcRoMZDIMZPObTicuOEAD5s08Vos/pCshYGNFC0Sd86YSfa2pSXOPEysX/hn95hJ/Phjk9h3vPnhY6K0MEjAGMxEKUfRMgpGwSgYBaMAFwAAzw4uWWmHp9EAAAAASUVORK5CYII=","orcid":"","institution":"The First Affiliated Hospital of Nanjing Medical University","correspondingAuthor":true,"prefix":"","firstName":"Peng","middleName":"","lastName":"Cheng","suffix":""}],"badges":[],"createdAt":"2024-02-21 05:44:16","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-3974658/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-3974658/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":51562438,"identity":"39a13399-4f43-4b64-a28d-5e588f9dc5a6","added_by":"auto","created_at":"2024-02-23 18:31:15","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":49446,"visible":true,"origin":"","legend":"\u003cp\u003eComparison of TBS between men with T2DM and controls\u003c/p\u003e","description":"","filename":"Fig.1.png","url":"https://assets-eu.researchsquare.com/files/rs-3974658/v1/b38af8d3c8621bea3322c900.png"},{"id":51562439,"identity":"849b9e0b-7072-4091-ba55-75289b465d09","added_by":"auto","created_at":"2024-02-23 18:31:15","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":50233,"visible":true,"origin":"","legend":"\u003cp\u003eComparison of BMD between men with T2DM and controls\u003c/p\u003e","description":"","filename":"Fig.2.png","url":"https://assets-eu.researchsquare.com/files/rs-3974658/v1/d3e06fbbe52c5ea10a8bcc65.png"},{"id":51562444,"identity":"16a27091-e481-467e-a88c-c16d7706f842","added_by":"auto","created_at":"2024-02-23 18:31:16","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":78728,"visible":true,"origin":"","legend":"\u003cp\u003eAverage TBS for 10-year age subgroups in men with T2DM and controls. P for trend according to the 10-year age subgroups using linear trend test.\u003c/p\u003e","description":"","filename":"Fig.3.png","url":"https://assets-eu.researchsquare.com/files/rs-3974658/v1/401e3337934cb51351bd4c40.png"},{"id":51562440,"identity":"75eff1d4-295b-4f7d-8f73-181ed2dd700f","added_by":"auto","created_at":"2024-02-23 18:31:15","extension":"png","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":160025,"visible":true,"origin":"","legend":"\u003cp\u003eAverage BMD at the total hip, femoral neck, and lumbar spine for 10-year age subgroups in men with T2DM and controls. P for trend according to the 10-year age subgroups using linear trend test.\u003c/p\u003e","description":"","filename":"Fig.4.png","url":"https://assets-eu.researchsquare.com/files/rs-3974658/v1/5324660b18ee449ad83ca950.png"},{"id":51562443,"identity":"9e773748-6cd6-415a-aa9d-52b87dcf1d0c","added_by":"auto","created_at":"2024-02-23 18:31:15","extension":"png","order_by":5,"title":"Figure 5","display":"","copyAsset":false,"role":"figure","size":184748,"visible":true,"origin":"","legend":"\u003cp\u003eScatter plots between TBS and BMD in men with T2DM.\u003c/p\u003e","description":"","filename":"Fig.5.png","url":"https://assets-eu.researchsquare.com/files/rs-3974658/v1/d3d100bc7c24e737364da917.png"},{"id":51562441,"identity":"5a50c0bd-9b60-4576-a154-ddcf1ff4e8f1","added_by":"auto","created_at":"2024-02-23 18:31:15","extension":"png","order_by":6,"title":"Figure 6","display":"","copyAsset":false,"role":"figure","size":154103,"visible":true,"origin":"","legend":"\u003cp\u003eScatter plots between TBS and BMD in men without T2DM.\u003c/p\u003e","description":"","filename":"Fig.6.png","url":"https://assets-eu.researchsquare.com/files/rs-3974658/v1/551a09be8680f9fe659d8313.png"},{"id":53399939,"identity":"7aa90791-4e50-4304-b998-22b2e6e4040b","added_by":"auto","created_at":"2024-03-25 14:21:13","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1011227,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-3974658/v1/274e5561-e674-4b73-a8e5-8db15290d268.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Age-related trends and annual rates of change in trabecular bone scores and bone mineral density in Chinese men with Type 2 diabetes mellitus: a cross-sectional and longitudinal study","fulltext":[{"header":"Introduction","content":"\u003cp\u003eOsteoporosis is a systemic skeletal disease characterized by diminished bone mass or defects in bone microarchitecture, which leads to decreased bone strength and an increased risk of fractures.[\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e] The results of the China Osteoporosis Epidemiology Survey, released by the National Health Commission of China in 2018, indicated that the prevalence of osteoporosis among individuals aged 50 years or older was 19.2%, with the prevalence among those aged 65 years or older reaching 32.0%. With the demographic aging trend, the prevalence continues to rise annually. Type 2 diabetes, another prevalent chronic ailment, poses a substantial global public health burden associated with aging. The worldwide prevalence of diabetes among adults (aged 20\u0026ndash;79 years) is projected to be 7.7%, affecting 439\u0026nbsp;million adults in 2030. [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e, \u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e] Increased bone fragility is acknowledged as a frequent and severe complication in diabetic patients. The fracture risk is notably higher in individuals with diabetes in comparison to those without the condition. Moreover, a substantial number of individuals at risk of osteoporosis may also have diabetes, impacting their quality of life and potentially leading to severe health consequences such as paralysis. Prolonged immobilization and hospitalization, as a result, can contribute to significant morbidity and mortality. Consequently, there is a critical need for early identification of diabetic patients at high risk of fractures, a comprehensive understanding of the connection between these two conditions, and the development of effective assessment and management strategies to mitigate their impact on patients' health.\u003c/p\u003e \u003cp\u003eBone mineral density (BMD) measured by dual-energy X-ray absorptiometry (DXA) is the gold standard for assessing osteoporosis. Nevertheless, prevailing research indicates that individuals with T2DM often exhibit average or higher BMD levels compared to their non-diabetic counterparts. In addition, T2DM patients have a higher rate of obesity, which is also associated with elevated BMD. [\u003cspan additionalcitationids=\"CR5 CR6\" citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e] A meta-analysis demonstrated an elevated risk of hip and non-spine fractures among individuals with T2DM. [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e] Interestingly, there tends to be an underestimation of the fracture risk in diabetic individuals. The Trabecular Bone Score (TBS) is a non-invasive tool, utilizing DXA pixel gray level analysis to indirectly assess bone microstructure by analyzing trabecular bone texture sparseness. Particularly for patients with similar BMD levels, TBS reveals distinctions in bone microstructure and quality, offering information independent of BMD. The combined use of TBS and BMD significantly enhances fracture risk prediction. [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e] Specifically, lumbar spine(LS) TBS emerges as a predictor of osteoporotic fractures in individuals with diabetes, capturing a more significant portion of the diabetes-associated fracture risk compared to BMD. [\u003cspan additionalcitationids=\"CR11 CR12\" citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e] While the majority of TBS studies in T2DM populations have focused on women, limited research has explored the impact of TBS in Asian men with type 2 diabetes.\u003c/p\u003e \u003cp\u003eThis paper aims to investigate the differences in TBS and BMD between Chinese men with T2DM and non-T2DM men and the correlation with age through cross-sectional and longitudinal studies.\u003c/p\u003e"},{"header":"Material and Methods","content":"\n\u003cp\u003eStudy population\u003c/p\u003e\n\n\u003cp\u003eAll subjects were recruited from Nanjing (China) and its surrounding areas, and all underwent a detailed medical history and physical examination. The men diagnosed with T2DM were patients hospitalized in the geriatric endocrinology department of our hospital, while non-T2DM men had regular physical examinations in our hospital between 2013 and 2023. As most of the patients attending endocrinology hospitalization and physical examination in our hospital were older, and to ensure an adequate sample size, individuals younger than 36 years and older than 96 years were excluded. Ultimately, our study included 446 male patients with T2DM and 322 normal adult males. Age, height, weight, BMI, BMD by site, TBS, and HbA1c of T2DM patients were recorded for each subject. The exclusion criteria comprised BMI\u0026thinsp;\u0026gt;\u0026thinsp;35kg/m2, BMI\u0026thinsp;\u0026lt;\u0026thinsp;15kg/m2, as well as common chronic diseases affecting bone metabolism, including various endocrine disorders (hypogonadism, hyperthyroidism), rheumatic immune disorders, gastrointestinal disorders, hematologic disorders, neuromuscular disorders, neurological disorders, chronic hepatic, renal, and cardiopulmonary disorders. Additionally, individuals on medications influencing bone metabolism, such as glucocorticoids, proton pump inhibitors, antiepileptic drugs, aromatase inhibitors, gonadotropin-releasing hormone analogs, antivirals, thiazolidinediones, and excess thyroid hormones, were excluded. Patients with type 1 diabetes mellitus were also excluded based on a review of their medical history.\u003c/p\u003e\n\n\u003cp\u003eBone mineral density and trabecular bone score\u003c/p\u003e\n\n\u003cp\u003eBone density DXA scans and TBS analyses were conducted at the Department of Geriatric Endocrinology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China. All patients underwent scans using the same machine. The TBS was derived by uploading the raw DXA images of the lumbar spine to the TBS iNsight software (version 2.0.0.1, Med-Imaps, Bordeaux, France) and subsequently calculating the LS TBS within the same region as the LS BMD. We utilize a proprietary algorithm to calculate the LS TBS within the identical measurement area as the LS BMD and to calibrate the equipment used in this study accurately. The TBS index measures bone microstructure texture, calculated from anterior and posterior dual-energy X-ray absorptiometry (DXA) lumbar spine scans. [\u003cspan class=\"CitationRef\"\u003e14\u003c/span\u003e]TBS can be retrospectively applied to previously acquired DXA images without additional X-ray exposure, time, or economic cost. It is widely accessible without new equipment, provided it is correctly calibrated. The TBS estimate is usually robust and helpful in collecting empirical data. TBS is associated with diabetes, primary hyperthyroidism, rheumatoid arthritis, adrenal gland disease, and other conditions such as adrenal incidentalomas, chronic kidney disease, and fractures in individuals on long-term glucocorticoid therapy. [\u003cspan class=\"CitationRef\"\u003e15\u003c/span\u003e, \u003cspan class=\"CitationRef\"\u003e16\u003c/span\u003e]\u003c/p\u003e\n\n\u003cp\u003eDiabetes and other parameters\u003c/p\u003e\n\n\u003cp\u003eStandardized methods were employed to collect basic information, including age, gender, and medical history. Participants were instructed to wear lightweight clothing during height, weight, and DXA measurements. BMI was calculated as weight divided by the square of height (kg/m2). The diagnosis of diabetes mellitus was based on a fasting plasma glucose (FPG) level of \u0026ge;\u0026thinsp;7.0 mmol/L, a 2-hour oral glucose tolerance test (OGTT) result of \u0026ge;\u0026thinsp;11.1 mmol/L, or an glycated hemoglobin (HbA1c) level of \u0026ge;\u0026thinsp;6.5% (mmol/mol), or a random blood glucose level of \u0026ge;\u0026thinsp;11.1 mmol/L in patients exhibiting typical symptoms of hyperglycemia or hyperglycemic crisis.[\u003cspan class=\"CitationRef\"\u003e17\u003c/span\u003e] The HbA1c was measured by chromatography.\u003c/p\u003e\n\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e\n \u003ch2\u003eStatistical analysis\u003c/h2\u003e\n \u003cp\u003eThe study organized participants into age groups, with each age subgroup spanning a decade. Following the assessment of normal distribution, data were presented as mean\u0026thinsp;\u0026plusmn;\u0026thinsp;standard deviation (SD). One-way analysis of variance (ANOVA) and independent samples t-tests were employed to evaluate differences in BMD and TBS among the various age groups and the two populations. A linear trend test was employed to examine the trend of TBS and BMD in different age subgroups of males with T2DM and males without T2DM. We utilized Pearson\u0026apos;s correlation analysis to establish the correlation between TBS and biochemical parameters. The average annual change rate represented the longitudinal changes in TBS and BMD. SPSS V27.0 statistical software was utilized in this study, and a significance level of P\u0026thinsp;\u0026lt;\u0026thinsp;0.05 was considered statistically significant.\u003c/p\u003e\n\u003c/div\u003e\n"},{"header":"Results","content":"\u003cp\u003eTable\u0026nbsp;\u003cspan\u003e1\u003c/span\u003e summarizes the baseline characteristics of men with T2DM, including height, weight, BMI, and HbA1c. A total of 446 male diabetic patients aged 36 to 95 were enrolled. A visual comparison of T2DM males with normal male controls is presented in Fig.\u0026nbsp;\u003cspan\u003e1\u003c/span\u003e. TBS was found to be significantly lower in males with T2DM compared to normal males (1.279\u0026thinsp;\u0026plusmn;\u0026thinsp;0.117 vs. 1.301\u0026thinsp;\u0026plusmn;\u0026thinsp;0.090, P\u0026thinsp;=\u0026thinsp;0.005). The relationship between TBS levels and age subgroups is depicted in Fig.\u0026nbsp;\u003cspan\u003e3\u003c/span\u003e. TBS in all age groups of males with T2DM exhibited an increasing trend until the age of 60, followed by a decreasing trend after 60 years of age, reaching a peak of 1.294 at the age range of 56\u0026ndash;65 years. TBS was negatively correlated with age (r=-0.102, P\u0026thinsp;=\u0026thinsp;0.031), and the difference was significant when analyzed by linear trend test (P\u0026thinsp;=\u0026thinsp;0.031). Lumbar spine TBS in non-diabetic men displayed significant variation with age, as analyzed by a linear trend test (P\u0026thinsp;\u0026lt;\u0026thinsp;0.001). In contrast to diabetic men, LS TBS reached its highest value at 46\u0026ndash;55 years of age, 1.328, followed by a decreasing trend. LS TBS in T2DM men peaked later than in normal males and exhibited a significantly lower peak than in normal males.\u003c/p\u003e\n\u003cdiv\u003e\n \u003ctable id=\"Tab1\" border=\"1\"\u003e\n \u003ccaption language=\"En\"\u003e\n \u003cdiv\u003eTable 1\u003c/div\u003e\n \u003cdiv\u003e\n \u003cp\u003eBaseline Characteristics of Study Subjects\u003c/p\u003e\n \u003c/div\u003e\n \u003c/caption\u003e\n \u003ccolgroup cols=\"10\"\u003e\u003c/colgroup\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003cth align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003eAge groups\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003eHeight, cm\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003eWeight, kg\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003eBMI, kg/m\u003csup\u003e2\u003c/sup\u003e\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003eHbA1c, % (mmol/mol)\u003c/p\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eYears\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eNumber\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eMean\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eSD\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eMean\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eSD\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eMean\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eSD\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eMean\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eSD\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e36\u0026ndash;45\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e31\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e173.7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e5.6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e78.6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e12.3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e26.1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3.8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e7.7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.8\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e46\u0026ndash;55\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e111\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e171.1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e4.7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e77.2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e9.6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e26.4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2.8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e7.1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.5\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e56\u0026ndash;65\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e134\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e171.3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e6.2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e75.1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e9.9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e25.5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2.4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e7.1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.7\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e66\u0026ndash;75\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e75\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e169.2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e6.2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e69.2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e8.5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e24.2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2.5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e7.3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.3\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e76\u0026ndash;85\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e49\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e167.0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e7.8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e66.3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e8.5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e23.8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2.7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e7.4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.5\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e86\u0026ndash;95\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e46\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e166.3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e5.8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e63.8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e10.1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e23.0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3.5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e7.9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2.0\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eTotal\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e446\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e170.1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e6.3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e72.7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e10.8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e25.1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3.0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e7.3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.6\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003c/table\u003e\n\u003c/div\u003e\n\u003cp\u003e\u003cstrong\u003eNotes:\u003c/strong\u003e Data are presented as mean+\u0026nbsp;SD or number(percentage)\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe relationship between BMD and age subgroups in men with T2DM is depicted in Fig.\u0026nbsp;\u003cspan\u003e4\u003c/span\u003e. Through an independent samples t-test, no differences in BMD were observed by site between non-T2DM men and men with T2DM, as illustrated in Fig.\u0026nbsp;\u003cspan\u003e2\u003c/span\u003e. Specifically, LS BMD (1.041\u0026thinsp;\u0026plusmn;\u0026thinsp;0.169 g/cm2vs.1.033\u0026thinsp;\u0026plusmn;\u0026thinsp;0.162, P\u0026thinsp;=\u0026thinsp;0.500), FN BMD (0.790\u0026thinsp;\u0026plusmn;\u0026thinsp;0.121 g/ cm2vs.0.783\u0026thinsp;\u0026plusmn;\u0026thinsp;0.121, P\u0026thinsp;=\u0026thinsp;0.418), and TH BMD (0.941\u0026thinsp;\u0026plusmn;\u0026thinsp;0.125 g/cm2vs.0.939\u0026thinsp;\u0026plusmn;\u0026thinsp;0.127, P\u0026thinsp;=\u0026thinsp;0.810) showed no significant differences. In T2DM patients, FN BMD and TH BMD exhibited a decrease after 40 years (P\u0026thinsp;=\u0026thinsp;0.002 and P\u0026thinsp;=\u0026thinsp;0.004, respectively), while LS BMD demonstrated a progressive increase (P\u0026thinsp;=\u0026thinsp;0.003). LS BMD was positively correlated with age (r\u0026thinsp;=\u0026thinsp;0.147, P\u0026thinsp;=\u0026thinsp;0.002) in T2DM men. The relationship between the respective LS BMD and TBS in the two populations is shown in Fig.\u0026nbsp;\u003cspan\u003e5\u003c/span\u003e and Fig.\u0026nbsp;\u003cspan\u003e6\u003c/span\u003e, and both were positively correlated, T2DM (r\u0026thinsp;=\u0026thinsp;0.302, P\u0026lt;0.001) and non-T2DM (r\u0026thinsp;=\u0026thinsp;0.449, P\u0026thinsp;\u0026lt;\u0026thinsp;0.001).\u003c/p\u003e\n\u003cp\u003eIn this study, a cohort of 165 T2DM patients and 310 non-diabetic men underwent at least two TBS and BMD examinations at our institution, with a mean follow-up of 3.6 and 3.0 years, respectively. Upon data analysis, the mean annual rate of change was calculated for LSTBS, LSBMD, FNBMD, and THBMD. A negative mean yearly speed of change indicates bone loss during the follow-up period, while a positive rate indicates bone gain. Table\u0026nbsp;\u003cspan\u003e2\u003c/span\u003e shows the annual rates of change in T2DM men and ordinary men in different age subgroups. The mean annual rates of change in LS, FN, and TH BMD in T2DM men were 0.33%, 0.06%, and 0.15%, respectively, while the mean annual rate of change in LS TBS was \u0026minus;\u0026thinsp;0.10%. In contrast, the mean annual rate of change in LS TBS in non-diabetic men was \u0026minus;\u0026thinsp;0.19%. Both men with and without T2DM exhibited the lowest annual rates of change at 66\u0026ndash;75 years of age, with values of -1.05% and \u0026minus;\u0026thinsp;0.90%, respectively.\u003c/p\u003e\n\u003cdiv\u003e\n \u003ctable id=\"Tab2\" border=\"1\"\u003e\n \u003ccaption language=\"En\"\u003e\n \u003cdiv\u003eTable 2\u003c/div\u003e\n \u003cdiv\u003e\n \u003cp\u003eAverage Annual Change Rate (%/Year) of BMD at Each Site and LS TBS in 10-Year Age Subgroups\u003c/p\u003e\n \u003c/div\u003e\n \u003c/caption\u003e\n \u003ccolgroup cols=\"9\"\u003e\u003c/colgroup\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003cth align=\"left\" rowspan=\"2\"\u003e\n \u003cp\u003eAge groups(years)\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003eLS TBS(%/years)\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003eLS BMD(%/years)\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003eFN BMD(%/years)\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003eTH BMD(%/years)\u003c/p\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003ea\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eb\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003ea\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eb\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003ea\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eb\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003ea\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eb\u003c/p\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e36\u0026ndash;45\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.01\u0026thinsp;\u0026plusmn;\u0026thinsp;2.41\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e1.22\u0026thinsp;\u0026plusmn;\u0026thinsp;5.56\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.19\u0026thinsp;\u0026plusmn;\u0026thinsp;2.29\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.38\u0026thinsp;\u0026plusmn;\u0026thinsp;3.72\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e-0.05\u0026thinsp;\u0026plusmn;\u0026thinsp;2.27\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e-0.41\u0026thinsp;\u0026plusmn;\u0026thinsp;1.10\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.24\u0026thinsp;\u0026plusmn;\u0026thinsp;1.71\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e-0.48\u0026thinsp;\u0026plusmn;\u0026thinsp;0.37\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e46\u0026ndash;55\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e-0.31\u0026thinsp;\u0026plusmn;\u0026thinsp;2.70\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.46\u0026thinsp;\u0026plusmn;\u0026thinsp;4.30\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.63\u0026thinsp;\u0026plusmn;\u0026thinsp;1.66\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.04\u0026thinsp;\u0026plusmn;\u0026thinsp;1.72\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e-0.04\u0026thinsp;\u0026plusmn;\u0026thinsp;2.81\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.07\u0026thinsp;\u0026plusmn;\u0026thinsp;2.41\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e-0.04\u0026thinsp;\u0026plusmn;\u0026thinsp;2.18\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.28\u0026thinsp;\u0026plusmn;\u0026thinsp;1.80\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e56\u0026ndash;65\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e-0.02\u0026thinsp;\u0026plusmn;\u0026thinsp;2.30\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.10\u0026thinsp;\u0026plusmn;\u0026thinsp;6.57\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.64\u0026thinsp;\u0026plusmn;\u0026thinsp;1.68\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.29\u0026thinsp;\u0026plusmn;\u0026thinsp;2.18\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e-0.32\u0026thinsp;\u0026plusmn;\u0026thinsp;1.79\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e-0.49\u0026thinsp;\u0026plusmn;\u0026thinsp;2.50\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.08\u0026thinsp;\u0026plusmn;\u0026thinsp;2.20\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.38\u0026thinsp;\u0026plusmn;\u0026thinsp;1.98\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e66\u0026ndash;75\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e-0.90\u0026thinsp;\u0026plusmn;\u0026thinsp;2.48\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e-1.05\u0026thinsp;\u0026plusmn;\u0026thinsp;4.41\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.98\u0026thinsp;\u0026plusmn;\u0026thinsp;1.74\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.27\u0026thinsp;\u0026plusmn;\u0026thinsp;2.34\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.04\u0026thinsp;\u0026plusmn;\u0026thinsp;1.91\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.44\u0026thinsp;\u0026plusmn;\u0026thinsp;4.45\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.25\u0026thinsp;\u0026plusmn;\u0026thinsp;1.62\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e-1.09\u0026thinsp;\u0026plusmn;\u0026thinsp;3.16\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e76\u0026ndash;85\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.24\u0026thinsp;\u0026plusmn;\u0026thinsp;1.69\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e-0.81\u0026thinsp;\u0026plusmn;\u0026thinsp;6.09\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e1.08\u0026thinsp;\u0026plusmn;\u0026thinsp;1.72\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e1.06\u0026thinsp;\u0026plusmn;\u0026thinsp;1.99\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e-0.22\u0026thinsp;\u0026plusmn;\u0026thinsp;2.24\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e-0.11\u0026thinsp;\u0026plusmn;\u0026thinsp;2.84\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.19\u0026thinsp;\u0026plusmn;\u0026thinsp;1.48\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e1.07\u0026thinsp;\u0026plusmn;\u0026thinsp;2.19\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e86\u0026ndash;95\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.24\u0026thinsp;\u0026plusmn;\u0026thinsp;2.95\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e-0.27\u0026thinsp;\u0026plusmn;\u0026thinsp;4.99\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.20\u0026thinsp;\u0026plusmn;\u0026thinsp;2.26\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.54\u0026thinsp;\u0026plusmn;\u0026thinsp;1.89\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.81\u0026thinsp;\u0026plusmn;\u0026thinsp;2.13\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e1.27\u0026thinsp;\u0026plusmn;\u0026thinsp;4.42\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.38\u0026thinsp;\u0026plusmn;\u0026thinsp;1.82\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.65\u0026thinsp;\u0026plusmn;\u0026thinsp;3.18\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eTotal\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e-0.19\u0026thinsp;\u0026plusmn;\u0026thinsp;2.46\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e-0.10\u0026thinsp;\u0026plusmn;\u0026thinsp;5.39\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.66\u0026thinsp;\u0026plusmn;\u0026thinsp;1.83\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.33\u0026thinsp;\u0026plusmn;\u0026thinsp;2.12\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e-0.08\u0026thinsp;\u0026plusmn;\u0026thinsp;2.21\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.06\u0026thinsp;\u0026plusmn;\u0026thinsp;3.18\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.13\u0026thinsp;\u0026plusmn;\u0026thinsp;1.94\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.15\u0026thinsp;\u0026plusmn;\u0026thinsp;2.40\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003c/table\u003e\n\u003c/div\u003e\n\u003cp\u003e\u003cstrong\u003eNotes:\u0026nbsp;\u003c/strong\u003eVariables are expressed as mean\u0026plusmn; SD. a, men without T2DM; b, men with T2DM.\u003c/p\u003e\n\u003cp\u003eThe glycated hemoglobin (HbA1c) level, reflecting the average ambient fasting and postprandial glycemia over a 2\u0026ndash;3-month period, plays a critical role in clinically managing hyperglycemia. In our study, HbA1c was also recorded in men with T2DM, and patients\u0026apos; glycemic control was assessed based on the HbA1c levels. HbA1c\u0026thinsp;\u0026lt;\u0026thinsp;6% (mmol/mol) indicates excellent glycemic control, and HbA1c\u0026thinsp;\u0026gt;\u0026thinsp;6% (mmol/mol) suggests poor control. We investigated the difference between glycemic control and TBS and BMD. We found that in patients with HbA1c\u0026thinsp;\u0026lt;\u0026thinsp;6% (mmol/mol), the mean TBS was 1.307, the mean LS BMD was 1.045 g/cm2, the mean TH BMD was 0.799 g/cm2, and the mean FN BMD was 0.944 g/cm2; in patients with HbA1c\u0026thinsp;\u0026gt;\u0026thinsp;6% (mmol/mol), the mean TBS was 1.287, the mean LS BMD was 1.017 g/cm2, the mean TH BMD was 0.775 g/cm2, and the mean FN BMD was 0.932g/cm2. Patients with great glycemic control demonstrated higher TBS and BMD.\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eNumerous studies have shown that diabetic patients have lower TBS than non-diabetic patients. [\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e], [\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e] In a study on diabetes and TBS in Vietnam, it was shown that diabetic TBS was lower in women. In contrast, in men, the difference between diabetic status and TBS was not statistically significant. [\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e]In another cross-sectional observational study based on a Spanish population, LS BMD was significantly higher in patients with T2DM, but TBS was substantially lower. [\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e] The study from the FRISBEE cohort also indicated that BMD was higher in T2DM than in controls, and TBS was significantly lower in the T2DM group compared to controls. [\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e] Although there was no significant difference between non-T2DM and T2DM men's BMD values at each site in our study, TBS was significantly lower (1.279\u0026thinsp;\u0026plusmn;\u0026thinsp;0.117 vs. 1.301\u0026thinsp;\u0026plusmn;\u0026thinsp;0.090, P\u0026thinsp;=\u0026thinsp;0.005). Furthermore, the peak TBS of men with T2DM occurred at a later age, possibly indicating the impact of diabetes on bone microstructure. The pathophysiological mechanisms of bone fragility in patients with T2DM are complex and multifactorial. Increasing evidence suggests it may be associated with hyperglycemia or insulin resistance. [\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e]\u003c/p\u003e \u003cp\u003eChronic hyperglycemia and accumulation of advanced glycation endproducts (AGE), insulin resistance, bone marrow fatty changes, inflammatory factors, adipokines from visceral fat, and oxidative stress are primary mechanisms by which T2DM induces bone fragility. [\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e, \u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e] Chronic hyperglycemic stimulation and insulin resistance may disrupt the normal calcium and phosphorus metabolism in bone tissue. [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e] In diabetic patients, AGE levels are elevated and accumulate due to hyperglycemia and increased levels of oxidative stress. Activating the receptor for AGEs (RAGE) expressed in human bone-derived cells enhances the production of inflammatory cytokines and reactive oxygen species (ROS), activating osteoblastic bone formation and inhibiting osteoclast differentiation, resulting in impaired bone material properties. [\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e, \u003cspan additionalcitationids=\"CR27 CR28 CR29\" citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e] In addition, it has been hypothesized that diabetic bone loss may be a microvascular complication of diabetes mellitus. Microangiopathy is suggested to accelerate age-related bone loss, resulting in decreased bone mass, deterioration of bone microarchitecture, and increased skeletal fragility. These interconnected and overlapping mechanisms ultimately lead to insufficient peak bone mass accumulation in patients with T2DM. [\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e, \u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e] A cross-sectional study conducted in Korea suggested a negative correlation between lumbar spine TBS and insulin resistance. [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e] Hyperinsulinemia is probably responsible for the preserved, or improved, trabecular bone microarchitectural parameters observed in patients with T2DM, as insulin is osteoanabolic. It is hypothesized that elevated insulin levels resulting from insulin resistance may initially protect the skeleton. The higher BMI in patients with T2DM may be associated with increased bone mass, indicating a protective mechanism leading to reduced bone turnover. This may result in a delayed peak TBS in patients with T2DM. [\u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e, \u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e]\u003c/p\u003e \u003cp\u003eA previous study on longitudinal changes in BMD and TBS in Korean adults found a mean annual rate of change of 0.3% for LS BMD and \u0026minus;\u0026thinsp;0.27% for LS TBS in men. [\u003cspan citationid=\"CR34\" class=\"CitationRef\"\u003e34\u003c/span\u003e] A recent study in a Chinese population of healthy men showed a mean annual rate of change in TBS of -0.17%. [\u003cspan citationid=\"CR35\" class=\"CitationRef\"\u003e35\u003c/span\u003e] However, few previous studies have evaluated the average annual rate of change in TBS and BMD in male patients with T2DM. The 3-year follow-up revealed that the lowest annual rate of change in TBS was observed in the 66\u0026ndash;75 age group for both men with T2DM and men without T2DM, at -1.05% and \u0026minus;\u0026thinsp;0.90%, respectively. Research has shown that bone loss in adult males begins to accelerate significantly after the age of 65. Higher rates of cortical and trabecular bone loss have been linked to lower levels of bioactive steroids and elevated levels of follicle-stimulating hormone and bone turnover markers.[\u003cspan citationid=\"CR36\" class=\"CitationRef\"\u003e36\u003c/span\u003e] The significant decline in TBS suggests that men in this age group experience rapid bone loss and are at a greater risk of fracture. Therefore, it is especially important to prevent bone loss and decrease the risk of fractures in men over 65 years of age. A meta-analysis revealed that BMD was significantly higher in the femoral neck, total hip, and lumbar spine in patients with T2DM. [\u003cspan citationid=\"CR37\" class=\"CitationRef\"\u003e37\u003c/span\u003e] In our study population, there was no significant difference in BMD at each site between men without non-T2DM and patients with T2DM. As a result, conventional diagnostic tools that incorporate BMD into fracture risk assessment often underestimate fracture risk in patients with T2DM. In patients with T2DM, the use of a combined assessment of TBS and BMD in short-term follow-up more accurately reflects changes in bone strength and predicts osteoporotic fractures. [\u003cspan additionalcitationids=\"CR39\" citationid=\"CR38\" class=\"CitationRef\"\u003e38\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR40\" class=\"CitationRef\"\u003e40\u003c/span\u003e]\u003c/p\u003e \u003cp\u003eIn our study, TBS and BMD were higher in patients with good glycemic control. This is similar to numerous previous studies. For example, a study in Rotterdam reported that patients with T2DM and HbA1c\u0026thinsp;\u0026ge;\u0026thinsp;7.5% (mmol/mol) had a 62% higher fracture risk than patients with HbA1c\u0026thinsp;\u0026le;\u0026thinsp;7.5% (mmol/mol). [\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e]Another cross-sectional analysis of 493 women aged 65 years and older concluded that longer duration of T2DM and higher HbA1c levels were associated with higher hip BMD and lower TBS. [\u003cspan citationid=\"CR41\" class=\"CitationRef\"\u003e41\u003c/span\u003e]In addition, several extensive population-based cohort studies have confirmed that poor glycemic control is strongly associated with fracture risk; the fracture risk is similar between nondiabetic subjects and adequately controlled T2DM patients.[\u003cspan additionalcitationids=\"CR43\" citationid=\"CR42\" class=\"CitationRef\"\u003e42\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR44\" class=\"CitationRef\"\u003e44\u003c/span\u003e]\u003c/p\u003e \u003cp\u003eBefore interpreting our results, we acknowledge specific strengths and limitations. The strengths of our study include analyzing men with T2DM from both cross-sectional and longitudinal perspectives compared to non-T2DM men. This allowed us to capture the variations in BMD and TBS at different sites. Additionally, all participants were scanned using the same DXA equipment, minimizing inter-machine errors. Both populations were also followed up, and data have been collected from participants over the past ten years. In our study, we conducted a comparative analysis of glycemic control status. However, we did not consider the duration of T2DM and its complications. T2DM may often remain undiagnosed for many years, which is a limitation of our study. Ideally, individuals under 36 should have been included in the analysis to determine the age at which our population reached peak BMD and TBS. Regrettably, the analysis of trends across the entire age range was not feasible due to the limited number of individuals under 35 in the population studied at our hospital. Finally, osteoporosis management's primary focus should be reducing the risk of fractures. However, this study's limited number of fractures made it impossible to establish the relationship between TBS and fracture risk.\u003c/p\u003e"},{"header":"Conclusions","content":"\u003cp\u003eTBS is lower and peaks later in diabetic patients. As in normal men, TBS declines most rapidly, around the age of 70 years. TBS can be used as an indicator for recognizing bone deterioration in diabetic patients with high BMD and is critical for the early recognition and prevention of osteoporosis and for the timely administration of medications to slow bone loss.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cp\u003eBMI, body mass index; T2DM, type 2 diabetes mellitus; DXA, dual-energy X-ray absorptiometry; BMD, bone mineral density; TBS, trabecular bone score; FN, femoral neck; TH, total hip; LS, lumbar spine. trabecular bone score; HbA1c, glycated hemoglobin.\u003c/p\u003e\n"},{"header":"Declarations","content":"\u003cp\u003eData Sharing Statement\u003c/p\u003e\n\u003cp\u003eThe datasets generated during and/or analysed during the current study are available from the corresponding author on reasonable request.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgments\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors would like to gratefully acknowledge all participants for their significant contributions to this work.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eConflict of Interest\u003c/p\u003e\n\u003cp\u003eThe authors declare that they have no conflict of interest.\u003c/p\u003e\n\u003cp\u003eFunding\u003c/p\u003e\n\u003cp\u003eThis work was supported by the National Natural Science Foundation of China (grant numbers 82170898).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eAuthor Contributions\u003c/p\u003e\n\u003cp\u003eYL and WD conceived and designed the experiments. YL and CX collected data, performed the data analysis, and wrote the manuscript. PC and JT provided supervision. All authors contributed to the article and approved the submitted version.\u003c/p\u003e\n\u003cp\u003eEthics approval\u003c/p\u003e\n\u003cp\u003eThe study was approved by the Ethics Committee of the First Affiliated Hospital with Nanjing Medical University and conformed to the provisions of the Declaration of Helsinki (revised in Brazil in 2013). The patients\u0026apos; identities were anonymized.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eMohsin S, Kaimala S, Sunny JJ, Adeghate E, Brown EM. Type 2 Diabetes Mellitus Increases the Risk to Hip Fracture in Postmenopausal Osteoporosis by Deteriorating the Trabecular Bone Microarchitecture and Bone Mass.J Diabetes Res (2019) 2019:3876957. Published 2019 Nov 7. doi:10.1155/2019/3876957.\u003c/li\u003e\n\u003cli\u003eShaw JE, Sicree RA, Zimmet PZ. 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Diabetes Care (2013) 36(6):1619-1628. doi:10.2337/dc12-1188.\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"type 2 diabetes, bone mineral density, trabecular bone score, men, average annual rate of change","lastPublishedDoi":"10.21203/rs.3.rs-3974658/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-3974658/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003ePurpose\u003c/h2\u003e \u003cp\u003ePatients with Type 2 diabetes mellitus(T2DM) typically have an average or higher bone mineral density (BMD) but are at a significantly higher risk of fracture than patients without diabetes. Trabecular bone score (TBS), a textural index that evaluates pixel gray-level variations in the projected lumbar spine DXA image, has been introduced as an indirect measure of bone quality.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e \u003cp\u003eThis study aimed to discuss the trends and annual rates of change in BMD and TBS with age in Chinese men with T2DM and men without diabetes mellitus.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e \u003cp\u003eLumbar spine(LS) TBS was found to be significantly lower in males with T2DM compared to normal males (1.279\u0026thinsp;\u0026plusmn;\u0026thinsp;0.117 vs. 1.301\u0026thinsp;\u0026plusmn;\u0026thinsp;0.090, P\u0026thinsp;=\u0026thinsp;0.005). However, TBS in men with T2DM peaked around age 60, which was later and lower than in normal men at age 50 (1.294\u0026thinsp;\u0026plusmn;\u0026thinsp;0.126 vs. 1.328\u0026thinsp;\u0026plusmn;\u0026thinsp;0.088). Femoral neck, total hip, and lumbar spine BMD in men with T2DM were not significantly different from those in ordinary men. The results of the 3-year follow-up showed that men, both men with or without T2DM, exhibited the lowest annual rates of change at 66\u0026ndash;75 years of age, with values of -1.05%(P\u0026thinsp;\u0026lt;\u0026thinsp;0.001) and \u0026minus;\u0026thinsp;0.90%(P\u0026thinsp;\u0026lt;\u0026thinsp;0.001), respectively. Patients with great glycemic control demonstrated higher TBS and BMD.\u003c/p\u003e\u003ch2\u003eConclusion\u003c/h2\u003e \u003cp\u003eMen with T2DM have later and lower peak TBS and faster bone loss, which may reflect the effects of diabetes on bone microarchitecture and bone mineral.\u003c/p\u003e","manuscriptTitle":"Age-related trends and annual rates of change in trabecular bone scores and bone mineral density in Chinese men with Type 2 diabetes mellitus: a cross-sectional and longitudinal study","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-02-23 18:31:10","doi":"10.21203/rs.3.rs-3974658/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"9d62adbc-88a6-478d-ab83-aa2342f0065f","owner":[],"postedDate":"February 23rd, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2024-04-12T12:59:31+00:00","versionOfRecord":[],"versionCreatedAt":"2024-02-23 18:31:10","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-3974658","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-3974658","identity":"rs-3974658","version":["v1"]},"buildId":"qtupq5eGEP_6zYnWcrvyt","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}