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Zhu MC, Xu MZ, Li CX, Wang JH, Li C, Gong YQ, Jin J, Lu K, Hao YM. A cross-sectional study on the correlation between fasting blood glucose and bone turnover markers in Chinese patients with osteoporotic fractures. Front Med (Lausanne) 2025; 12:1564957. [PMID: 40276745 PMCID: PMC12018312 DOI: 10.3389/fmed.2025.1564957] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/22/2025] [Accepted: 03/24/2025] [Indexed: 04/26/2025] Open
Abstract
Background Recent studies suggest that metabolic factors, such as fasting blood glucose (FBG), may significantly affect bone health, influencing the risk and severity of osteoporotic fractures (OPFs). This study examined the association between FBG levels and bone turnover markers (BTMs) in patients hospitalized for OPFs requiring surgical intervention. Methods A retrospective cross-sectional analysis was conducted on 888 patients treated for OPFs at Kunshan Hospital affiliated with Jiangsu University from November 2018 to August 2023. Serum levels of FBG, procollagen type 1 N-terminal propeptide (P1NP), and β-C-terminal telopeptide of type I collagen (β-CTX) were measured, with FBG serving as an independent variable, and P1NP and β-CTX as outcome variables. Patients were stratified into tertiles based on FBG levels, and multiple regression models were adjusted for confounding variables, including age, gender, BMI, and clinical parameters. Non-linear relationships and threshold effects were analyzed. Results Adjusted regression models identified a negative association between FBG and BTMs. For each 1 mmol/L increase in FBG, β-CTX levels decreased by 0.02 ng/mL (95% CI: -0.04 to -0.01; p < 0.01), and P1NP levels decreased by 2.91 ng/mL (95% CI: -4.38 to -1.45; p < 0.01). Non-linear relationships were observed, with an inflection point at 7.93 mmol/L for both markers. Below this threshold, higher FBG levels were associated with a steeper decline in BTMs. Conclusion FBG levels exhibit a negative non-linear association with P1NP and β-CTX in patients with OPFs. Elevated FBG levels may adversely affect BTMs, potentially contributing to the progression of osteoporosis (OP). These findings underscore the importance of glycemic control in managing bone health among patients with OPFs.
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Affiliation(s)
- Meng-cheng Zhu
- Department of Orthopedics, Affiliated Kunshan Hospital of Jiangsu University, Suzhou, Jiangsu, China
- Kunshan Biomedical Big Data Innovation Application Laboratory, Suzhou, Jiangsu, China
| | - Min-zhe Xu
- Department of Orthopedics, Affiliated Kunshan Hospital of Jiangsu University, Suzhou, Jiangsu, China
- Kunshan Biomedical Big Data Innovation Application Laboratory, Suzhou, Jiangsu, China
| | - Chang-xuan Li
- Kunshan Biomedical Big Data Innovation Application Laboratory, Suzhou, Jiangsu, China
- Department of Orthopedics, The First People's Hospital of Kunshan, Gusu School, Nanjing Medical University, Suzhou, Jiangsu, China
| | - Jia-hao Wang
- Kunshan Biomedical Big Data Innovation Application Laboratory, Suzhou, Jiangsu, China
- Department of Orthopedics, The First People's Hospital of Kunshan, Gusu School, Nanjing Medical University, Suzhou, Jiangsu, China
| | - Chong Li
- Department of Orthopedics, Affiliated Kunshan Hospital of Jiangsu University, Suzhou, Jiangsu, China
- Kunshan Biomedical Big Data Innovation Application Laboratory, Suzhou, Jiangsu, China
| | - Ya-qin Gong
- Kunshan Biomedical Big Data Innovation Application Laboratory, Suzhou, Jiangsu, China
- Information Department, Affiliated Kunshan Hospital of Jiangsu University, Suzhou, Jiangsu, China
| | - Jian Jin
- Kunshan Municipal Health and Family Planning Information Center, Suzhou, Jiangsu, China
| | - Ke Lu
- Department of Orthopedics, Affiliated Kunshan Hospital of Jiangsu University, Suzhou, Jiangsu, China
- Kunshan Biomedical Big Data Innovation Application Laboratory, Suzhou, Jiangsu, China
| | - Yan-ming Hao
- Department of Orthopedics, Affiliated Kunshan Hospital of Jiangsu University, Suzhou, Jiangsu, China
- Kunshan Biomedical Big Data Innovation Application Laboratory, Suzhou, Jiangsu, China
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Wang X, Cao Y. A Narrative Review: Relationship Between Glycemic Variability and Emerging Complications of Diabetes Mellitus. Biomolecules 2025; 15:188. [PMID: 40001491 PMCID: PMC11853042 DOI: 10.3390/biom15020188] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/28/2024] [Revised: 01/24/2025] [Accepted: 01/26/2025] [Indexed: 02/27/2025] Open
Abstract
A growing body of evidence emphasizes the role of glycemic variability (GV) in the development of conventional diabetes-related complications. Furthermore, advancements in diabetes management and increased life expectancy have led to the emergence of new complications, such as cancer, liver disease, fractures, infections, and cognitive dysfunction. GV is considered to exacerbate oxidative stress and inflammation, acting as a major mechanism underlying these complications. However, few reviews have synthesized the association between GV and these emerging complications or examined their underlying mechanisms. Hence, this narrative review provides a comprehensive discussion of the burden, risks, and mechanisms of GV in these complications, offering further evidence supporting GV as a potential therapeutic target for diabetes management.
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Affiliation(s)
| | - Yanli Cao
- Department of Endocrinology and Metabolism, Institute of Endocrinology, NHC Key Laboratory of Diagnosis and Treatment of Thyroid Diseases, The First Affiliated Hospital of China Medical University, Shenyang 110001, China;
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Chen F, Wang P, Dai F, Zhang Q, Ying R, Ai L, Chen Y. Correlation Between Blood Glucose Fluctuations and Osteoporosis in Type 2 Diabetes Mellitus. Int J Endocrinol 2025; 2025:8889420. [PMID: 39949568 PMCID: PMC11824305 DOI: 10.1155/ije/8889420] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/04/2024] [Accepted: 01/08/2025] [Indexed: 02/16/2025] Open
Abstract
The purpose of this review is to investigate the impacts of blood glucose fluctuations on diabetic osteoporosis, a complication of Type 2 diabetes mellitus (T2DM) that remains poorly understood. We reviewed the current evidence of the relationship between blood glucose fluctuations and diabetic osteoporosis in patients with T2DM. The findings indicate that blood glucose fluctuations may contribute to inhibiting the processes of bone formation and resorption, promoting diabetic osteoporosis and fractures in T2DM. Mechanistic studies, both in vitro and in vivo, reveal that these effects are largely mediated by oxidative stress, advanced glycation end products, inflammatory mediators, and multiple pathways inducing cell apoptosis or autophagy. Thus, maintaining the long-term stability of blood glucose levels emerges as a target to be pursued in clinical practice in order to safely reduce mean blood glucose and for its direct effects on osteoporosis and fractures in T2DM.
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Affiliation(s)
- Fuhua Chen
- Department of Endocrinology, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui, China
| | - Ping Wang
- Department of Endocrinology, The 2nd People's Hospital of Anhui, Hefei, Anhui, China
| | - Fang Dai
- Department of Endocrinology, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui, China
| | - Qiu Zhang
- Department of Endocrinology, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui, China
| | - Ruixue Ying
- Department of Endocrinology, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui, China
| | - Liya Ai
- Department of Endocrinology, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui, China
| | - Yiqing Chen
- Department of Endocrinology, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui, China
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Van Hulten V, Driessen JHM, Andersen S, Kvist A, Viggers R, Bliuc D, Center JR, Brouwers MCJG, Vestergaard P, van den Bergh JP. Fracture risk revisited: Bone mineral density T-score and fracture risk in type 2 diabetes. Diabetes Obes Metab 2024; 26:5325-5335. [PMID: 39228286 DOI: 10.1111/dom.15890] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/19/2024] [Revised: 08/01/2024] [Accepted: 08/04/2024] [Indexed: 09/05/2024]
Abstract
AIM To study the association between femoral neck (FN) bone mineral density (BMD) T-score and fracture risk in individuals with and without type 2 diabetes (T2D). MATERIALS AND METHODS We performed a single-centre retrospective cohort study using the Danish National Health Service. BMD of the FN was measured by dual-energy X-ray absorptiometry. Cox proportional hazards regression models were used to study the association between FN BMD T-score and fractures in individuals with and without T2D separately, adjusted for age, comorbidities and comedication. The results from this analysis were used to estimate the 10-year absolute fracture risk. RESULTS In total, there were 35,129 women (2362 with T2D) and 7069 men (758 with T2D). The FN BMD T-score was significantly associated with risk of any, hip and major osteoporotic fracture in men and women with [adjusted hazard risk ratios (aHR) women, hip: 1.57; 95% confidence interval (CI) 1.24-2.00, incidence rate (IR) 8.7; aHR men, hip: 1.55; 95% CI 1.01-2.36, IR 4.6] and without T2D (aHR women, hip: 1.75; 95% CI 1.64-1.87, IR 7.0; aHR men, hip: 1.97, 95% CI 1.73-2.25, IR 6.3), and its ability to predict fracture risk was similar. Fracture IRs were not significantly different for individuals with or without T2D, nor was the estimated cumulative 10-year fracture risk. CONCLUSIONS The FN BMD T-score was significantly associated with hip, non-spine and major osteoporotic fracture risk in men and women with and without T2D. Fracture risk for a given T-score and age was equal in individuals with and without T2D, as was the ability of the FN BMD T-score to predict fracture risk.
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Affiliation(s)
- V Van Hulten
- Department of Clinical Pharmacy and Toxicology, Maastricht University Medical Centre+ (MUMC+), Maastricht, The Netherlands
- School of Nutrition and Translational Research in Metabolism (NUTRIM), Maastricht University, Maastricht, The Netherlands
- Department of Clinical Pharmacy, Cardiovascular Research Institute Maastricht (CARIM), Maastricht University, Maastricht, The Netherlands
| | - J H M Driessen
- Department of Clinical Pharmacy and Toxicology, Maastricht University Medical Centre+ (MUMC+), Maastricht, The Netherlands
- Department of Clinical Pharmacy, Cardiovascular Research Institute Maastricht (CARIM), Maastricht University, Maastricht, The Netherlands
| | - S Andersen
- Steno Diabetes Center North Denmark, Aalborg, Denmark
| | - A Kvist
- Steno Diabetes Center North Denmark, Aalborg, Denmark
- Department of Endocrinology and Metabolism, Molecular Endocrinology & Stem Cell Research Unit (KMEB), Odense University Hospital, Odense, Denmark
| | - R Viggers
- Steno Diabetes Center North Denmark, Aalborg, Denmark
- Department of Endocrinology, Aalborg University Hospital, Aalborg, Denmark
| | - D Bliuc
- Bone Biology Division, Garvan Institute of Medical Research, Sydney, New South Wales, Australia
- School of population Health, Faculty of Medicine and Health, University of New South Wales Sydney, Sydney, New South Wales, Australia
| | - J R Center
- Bone Biology Division, Garvan Institute of Medical Research, Sydney, New South Wales, Australia
- Clinical School, St Vincent's Hospital, Faculty of Medicine, University of New South Wales Sydney, Sydney, New South Wales, Australia
- Department of Endocrinology and Diabetes, St Vincent's Hospital, Sydney, New South Wales, Australia
| | - M C J G Brouwers
- Department of Internal Medicine, Maastricht University Medical Centre+ (MUMC+), Maastricht, Netherlands
- Cardiovascular Research Institute Maastricht (CARIM), Maastricht University, Maastricht, Netherlands
- Care and Public Health Research Institute (CAPHRI), Maastricht University, Maastricht, Netherlands
| | - P Vestergaard
- Steno Diabetes Center North Denmark, Aalborg, Denmark
- Department of Endocrinology, Aalborg University Hospital, Aalborg, Denmark
| | - J P van den Bergh
- School of Nutrition and Translational Research in Metabolism (NUTRIM), Maastricht University, Maastricht, The Netherlands
- Department of Internal Medicine, Division of Rheumatology, Maastricht University Medical Centre+ (MUMC+), Maastricht, The Netherlands
- Department of Internal Medicine, Subdivision of Endocrinology, VieCuri Medical Center, Venlo, The Netherlands
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Yang J, Zhang Y, Liu X, Chen B, Lei L. Effect of type 2 diabetes on biochemical markers of bone metabolism: a meta-analysis. Front Physiol 2024; 15:1330171. [PMID: 39100278 PMCID: PMC11294215 DOI: 10.3389/fphys.2024.1330171] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/30/2023] [Accepted: 06/26/2024] [Indexed: 08/06/2024] Open
Abstract
Objective This meta-analysis aims to examine differences in biochemical markers of bone metabolism between individuals with type 2 diabetes (T2DM) and non-T2DM control groups. Materials and methods Two independent evaluators searched five databases: PubMed, EMBASE, EBSCOhost, Web of Science, and the Cochrane Library. We aimed to identify observational studies investigating the impact of T2DM on biochemical markers of bone metabolism. Literature retrieval covered the period from the establishment of the databases up to November 2022. Studies were included if they assessed differences in biochemical markers of bone metabolism between T2DM patients and non-T2DM control groups using cross-sectional, cohort, or case-control study designs. Results Fourteen studies were included in the analysis, comprising 12 cross-sectional studies and 2 cohort studies. Compared to the non-T2DM control group, T2DM patients showed reduced levels of Osteocalcin and P1NP, which are markers of bone formation. Conversely, levels of Alkaline phosphatase and Bone-specific alkaline phosphatase, other bone formation markers, increased. The bone resorption marker CTX showed decreased levels, while TRACP showed no significant difference. Conclusion In individuals with T2DM, most bone turnover markers indicated a reduced rate of bone turnover. This reduction can lead to increased bone fragility despite higher bone mineral density, potentially increasing the risk of osteoporosis. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/display_record.php? identifier CRD42022366430.
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Affiliation(s)
- Jie Yang
- School of Athletic Performance, Shanghai University of Sport, Shanghai, China
| | - Yuan Zhang
- School of Athletic Performance, Shanghai University of Sport, Shanghai, China
| | - Xiaohua Liu
- Department of Rehabilitation Medicine, Shanghai Shangti Orthopaedic Hospital, Shanghai University of Sport, Shanghai, China
| | - Binglin Chen
- The Second School of Clinical Medical College, Xuzhou Medical University, Xuzhou, Jiangsu, China
| | - Le Lei
- Department of Rehabilitation Medicine, Shanghai Shangti Orthopaedic Hospital, Shanghai University of Sport, Shanghai, China
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Mostafa SM, Elebrashy I, Haddad HE, Shaker O, Razek NA, Fayed A. Association between bone turnover markers, bone mineral density, and serum osteoglycine in middle-aged men with Type 2 Diabetes mellitus. Diabetol Metab Syndr 2024; 16:155. [PMID: 38982537 PMCID: PMC11232153 DOI: 10.1186/s13098-024-01388-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/24/2024] [Accepted: 06/24/2024] [Indexed: 07/11/2024] Open
Abstract
BACKGROUND Patients with Type 2 diabetes mellitus (T2DM) have decreased bone health. We aimed to investigate serum levels of bone turnover markers (BTMs) (markers of bone formation and bone resorption) and bone mineral density (BMD) at three sites (lumber, neck femur, and total femur) in middle-aged men with type 2 diabetes and to analyze the relationship between them. Also to evaluate serum osteoglycin as a novel marker and its relation to BTMs, BMD, and diabetic status. METHODS We recruited seventy-eight patients with T2DM and thirteen non-diabetic, male volunteers as a control group. BMD was measured using a DEXA scan. BTMs (carboxy-terminal crosslinking telopeptide of type 1 collagen [CTX] and procollagen type 1 N propeptide [P1NP]), osteoglycin, PTH, and vitamin D were estimated. Data was compared among subjects and statistical analysis was performed. RESULTS Most of the patients were having normal BMD with no significant difference between patients and the controls. BTMs and osteoglycin were significantly higher and vitamin D was significantly lower in the diabetic patients. Serum osteoglycin was positively correlated with DEXA Neck Femur (r = 0.233; p-value < 0.05). CONCLUSION Body mass index and Serum osteoglycin have a significant positive effect on BMD. Both markers of bone formation and bone resorption were increased indicating a state of increased bone turnover in T2DM.
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Affiliation(s)
- Salma Mohamed Mostafa
- Endocrinology Unit, Internal Medicine Department, Kasr Alainy School of Medicine, Cairo University, Giza, Egypt
| | - Ibrahim Elebrashy
- Endocrinology Unit, Internal Medicine Department, Kasr Alainy School of Medicine, Cairo University, Giza, Egypt
| | - Hemmat El Haddad
- Endocrinology Unit, Internal Medicine Department, Kasr Alainy School of Medicine, Cairo University, Giza, Egypt
| | - Olfat Shaker
- Medical Biochemistry and Molecular Biology Department, Kasr Alainy School of Medicine, Cairo University, Giza, Egypt
| | - Naglaa Abdel Razek
- Diagnostic and Interventional Radiology Department, Kasr Alainy School of Medicine, Cairo University, Giza, Egypt
| | - Ahmed Fayed
- Nephrology Unit, Internal Medicine Department, Kasr Alainy School of Medicine, Cairo University, Giza, Egypt.
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Snow T, Woolley W, Acevedo C, Kingstedt OT. Effect of in vitro ribosylation on the dynamic fracture behavior of mature bovine cortical bone. J Mech Behav Biomed Mater 2023; 148:106171. [PMID: 37890344 DOI: 10.1016/j.jmbbm.2023.106171] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/01/2022] [Revised: 05/01/2023] [Accepted: 10/09/2023] [Indexed: 10/29/2023]
Abstract
In this study, the fracture behavior of ribosylated bovine cortical bone is investigated under loading conditions simulating a fall event. Single edge notched specimens, separated into a control group (n = 11) and a ribosylated group (n = 8), were extracted from the mid-diaphysis of a single bovine femur harvested from a mature cow. A seven-day ribosylation process results in the accumulation of Advanced-Glycation End Products (AGEs) cross-links and AGE adducts. Specimens were subjected to symmetric three point bending (opening mode) and an impact velocity of 1.6 m/s using a drop tower. Near-crack displacement fields up to fracture initiation are determined from high-speed images post-processed using digital image correlation. A constrained over-deterministic least squares regression and orthotropic material linear elastic fracture mechanics theory are used to extract the in-plane critical stress intensity factors at fracture initiation (i.e., fracture initiation toughness values). Statistically significant differences were not observed when comparing the in-plane fracture initiation toughness values (p≥0.96) or energy release rate (p=0.90) between the control and seven-day ribosylated groups. The intrinsic variability of bone may require high sample numbers in order to achieve an adequately powered experiment when assessing dynamic fracture behavior. While there are no detectable differences due to the ribosylation treatment investigated, this is likely due to the limited sample sizes utilized.
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Affiliation(s)
- Tanner Snow
- Department of Mechanical Engineering, University of Utah, Salt Lake City, UT, 84112, USA
| | - William Woolley
- Department of Mechanical Engineering, University of Utah, Salt Lake City, UT, 84112, USA; Department of Mechanical and Aerospace Engineering, University of California San Diego, San Diego, CA, 92093, USA
| | - Claire Acevedo
- Department of Mechanical Engineering, University of Utah, Salt Lake City, UT, 84112, USA; Department of Biomedical Engineering, University of Utah, Salt Lake City, UT, 84112, USA; Department of Mechanical and Aerospace Engineering, University of California San Diego, San Diego, CA, 92093, USA.
| | - Owen T Kingstedt
- Department of Mechanical Engineering, University of Utah, Salt Lake City, UT, 84112, USA.
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Zhang X, Krishnamoorthy S, Tang CTL, Hsu WWQ, Li GHY, Sing CW, Tan KCB, Cheung BMY, Wong ICK, Kung AWC, Cheung CL. Association of Bone Mineral Density and Bone Turnover Markers with the Risk of Diabetes: Hong Kong Osteoporosis Study and Mendelian Randomization. J Bone Miner Res 2023; 38:1782-1790. [PMID: 37850799 DOI: 10.1002/jbmr.4924] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/18/2023] [Revised: 10/08/2023] [Accepted: 10/13/2023] [Indexed: 10/19/2023]
Abstract
Preclinical studies demonstrated that bone plays a central role in energy metabolism. However, how bone metabolism is related to the risk of diabetes in humans is unknown. We investigated the association of bone health (bone mineral density [BMD] and bone turnover markers) with incident type-2 diabetes mellitus (T2DM) based on the Hong Kong Osteoporosis Study (HKOS). A total of 993 and 7160 participants from the HKOS were studied for the cross-sectional and prospective analyses, respectively. The cross-sectional study evaluated the association of BMD and bone biomarkers with fasting glucose and glycated hemoglobin (HbA1c ) levels, whereas the prospective study examined the associations between BMD at study sites and the risk of T2DM by following subjects a median of 16.8 years. Body mass index (BMI) was adjusted in all full models. Mendelian randomization (MR) was conducted for causal inference. In the cross-sectional analysis, lower levels of circulating bone turnover markers and higher BMD were significantly associated with increased fasting glucose and HbA1c levels. In the prospective analysis, higher BMD (0.1 g/cm2 ) at the femoral neck and total hip was associated with increased risk of T2DM with hazard ratios (HRs) of 1.10 (95% confidence interval [CI], 1.03 to 1.18) and 1.14 (95% CI, 1.08 to 1.21), respectively. The presence of osteoporosis was associated with a 30% reduction in risk of T2DM compared to those with normal BMD (HR = 0.70; 95% CI, 0.55 to 0.90). The MR results indicate a robust genetic causal association of estimated BMD (eBMD) with 2-h glucose level after an oral glucose challenge test (estimate = 0.043; 95% CI, 0.007 to 0.079) and T2DM (odds ratio = 1.064; 95% CI, 1.036 to 1.093). Higher BMD and lower levels of circulating bone biomarkers were cross-sectionally associated with poor glycemic control. Moreover, higher BMD was associated with a higher risk of incident T2DM and the association is probably causal. © 2023 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).
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Affiliation(s)
- Xiaowen Zhang
- Department of Pharmacology and Pharmacy, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China
| | - Suhas Krishnamoorthy
- Department of Pharmacology and Pharmacy, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China
| | - Casey Tze-Lam Tang
- Department of Pharmacology and Pharmacy, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China
| | - Warrington Wen-Qiang Hsu
- Department of Pharmacology and Pharmacy, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China
| | - Gloria Hoi-Yee Li
- Department of Health Technology and Informatics, Faculty of Health and Social Sciences, The Hong Kong Polytechnic University, Hong Kong, China
| | - Chor-Wing Sing
- Department of Pharmacology and Pharmacy, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China
| | - Kathryn Choon-Beng Tan
- Department of Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China
| | - Bernard Man-Yung Cheung
- Department of Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China
| | - Ian Chi-Kei Wong
- Department of Pharmacology and Pharmacy, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China
- Research Department of Practice and Policy, School of Pharmacy, University College London, London, UK
- Laboratory of Data Discovery for Health (D24H), Hong Kong Science Park, Pak Shek Kok, Hong Kong, China
| | - Annie Wai-Chee Kung
- Department of Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China
| | - Ching-Lung Cheung
- Department of Pharmacology and Pharmacy, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China
- Laboratory of Data Discovery for Health (D24H), Hong Kong Science Park, Pak Shek Kok, Hong Kong, China
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9
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Trandafir AI, Sima OC, Gheorghe AM, Ciuche A, Cucu AP, Nistor C, Carsote M. Trabecular Bone Score (TBS) in Individuals with Type 2 Diabetes Mellitus: An Updated Review. J Clin Med 2023; 12:7399. [PMID: 38068450 PMCID: PMC10707110 DOI: 10.3390/jcm12237399] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/06/2023] [Revised: 11/15/2023] [Accepted: 11/27/2023] [Indexed: 01/03/2025] Open
Abstract
Bone fragility is a complication of type 2 diabetes mellitus (T2DM) that has been identified in recent decades. Trabecular bone score (TBS) appears to be more accurate than bone mineral density (BMD) in diabetic bone disease, particularly in menopausal women with T2DM, to independently capture the fracture risk. Our purpose was to provide the most recent overview on TBS-associated clinical data in T2DM. The core of this narrative review is based on original studies (PubMed-indexed journals, full-length, English articles). The sample-based analysis (n = 11, N = 4653) confirmed the use of TBS in T2DM particularly in females (females/males ratio of 1.9), with ages varying between 35 and 91 (mean 65.34) years. With concern to the study design, apart from the transversal studies, two others were prospective, while another two were case-control. These early-post-pandemic data included studies of various sample sizes, such as: males and females (N of 245, 361, 511, and 2294), only women (N of 80, 96, 104, 243, 493, and 887), and only men (N = 169). Overall, this 21-month study on published data confirmed the prior profile of BMD-TBS in T2DM, while the issue of whether checking the fracture risk is mandatory in adults with uncontrolled T2DM remains to be proven or whether, on the other hand, a reduced TBS might function as a surrogate marker of complicated/uncontrolled T2DM. The interventional approach with bisphosphonates for treating T2DM-associated osteoporosis remains a standard one (n = 2). One control study on 4 mg zoledronic acid showed after 1 year a statistically significant increase of lumbar BMD in both diabetic and non-diabetic groups (+3.6%, p = 0.01 and +6.2%, p = 0.01, respectively). Further studies will pinpoint additive benefits on glucose status of anti-osteoporotic drugs or will confirm if certain glucose-lowering regimes are supplementarily beneficial for fracture risk reduction. The novelty of this literature research: these insights showed once again that the patients with T2DM often have a lower TBS than those without diabetes or with normal glucose levels. Therefore, the decline in TBS may reflect an early stage of bone health impairment in T2DM. The novelty of the TBS as a handy, non-invasive method that proved to be an index of bone microarchitecture confirms its practicality as an easily applicable tool for assessing bone fragility in T2DM.
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Affiliation(s)
- Alexandra-Ioana Trandafir
- PhD Doctoral School, Carol Davila University of Medicine and Pharmacy, 050474 Bucharest, Romania; (A.-I.T.); (O.-C.S.); (A.-M.G.); (A.-P.C.)
| | - Oana-Claudia Sima
- PhD Doctoral School, Carol Davila University of Medicine and Pharmacy, 050474 Bucharest, Romania; (A.-I.T.); (O.-C.S.); (A.-M.G.); (A.-P.C.)
| | - Ana-Maria Gheorghe
- PhD Doctoral School, Carol Davila University of Medicine and Pharmacy, 050474 Bucharest, Romania; (A.-I.T.); (O.-C.S.); (A.-M.G.); (A.-P.C.)
| | - Adrian Ciuche
- Department 4—Cardio-Thoracic Pathology, Thoracic Surgery II Discipline, Carol Davila University of Medicine and Pharmacy, 050474 Bucharest, Romania;
- Thoracic Surgery Department, Dr. Carol Davila Central Military Emergency University Hospital, 010242 Bucharest, Romania
| | - Anca-Pati Cucu
- PhD Doctoral School, Carol Davila University of Medicine and Pharmacy, 050474 Bucharest, Romania; (A.-I.T.); (O.-C.S.); (A.-M.G.); (A.-P.C.)
- Thoracic Surgery Department, Dr. Carol Davila Central Military Emergency University Hospital, 010242 Bucharest, Romania
| | - Claudiu Nistor
- Department 4—Cardio-Thoracic Pathology, Thoracic Surgery II Discipline, Carol Davila University of Medicine and Pharmacy, 050474 Bucharest, Romania;
- Thoracic Surgery Department, Dr. Carol Davila Central Military Emergency University Hospital, 010242 Bucharest, Romania
| | - Mara Carsote
- Department of Endocrinology, Carol Davila University of Medicine and Pharmacy, 050474 Bucharest, Romania;
- Department of Clinical Endocrinology V, C.I. Parhon National Institute of Endocrinology, 020021 Bucharest, Romania
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10
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Pini SF, Pariente E, Olmos JM, Martín-Millán M, Pascua R, Martínez-Taboada VM, Hernández JL. Diffuse idiopathic skeletal hyperostosis (DISH) and trabecular bone score (TBS) in postmenopausal women: The Camargo cohort. Semin Arthritis Rheum 2023; 61:152217. [PMID: 37186972 DOI: 10.1016/j.semarthrit.2023.152217] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/31/2023] [Revised: 04/21/2023] [Accepted: 05/02/2023] [Indexed: 05/17/2023]
Abstract
OBJECTIVES The potential relationship between diffuse idiopathic skeletal hyperostosis (DISH) and bone microstructure has not been studied in women. We aimed to assess the association between the trabecular bone score (TBS) and DISH in postmenopausal women, as well as the role of other parameters related to bone metabolism, such as bone mineral density (BMD), calciotropic hormones, and bone remodeling markers. METHODS Cross-sectional study, nested in a prospective population-based cohort (Camargo cohort). Clinical covariates, DISH, TBS, vitamin D, parathormone, BMD and serum bone turnover markers, were analyzed. RESULTS We have included 1545 postmenopausal women (mean age, 62±9 years). Those with DISH (n = 152; 8.2%) were older and had a significantly higher prevalence of obesity, metabolic syndrome, hypertension, and type 2 diabetes mellitus (p<0.05). Moreover, they had lower TBS values (p = 0.0001) despite having a higher lumbar spine BMD (p<0.0001) and a higher prevalence of vertebral fractures than women without DISH (28.6% vs. 15.1%; p = 0.002). When analyzing DISH through Schlapbach grades, women without DISH had a median TBS value consistent with a normal trabecular structure while the values for women with DISH from grades 1 to 3 were consistent with a partially degraded trabecular structure. Women with vertebral fractures and DISH had a mean TBS corresponding to a degraded trabecular structure (1.219±0.1). After adjusting for confounders, the estimated TBS means were 1.272 (1.253-1.290) in the DISH group, and 1.334 (1.328-1.339) in the NDISH group (p<0.0001). CONCLUSION An association between DISH and TBS has been shown in postmenopausal women, in which hyperostosis has been significantly and consistently related to trabecular degradation and, therefore, to deterioration in bone quality after adjusting for confounding variables.
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Affiliation(s)
- Stefanie F Pini
- Hospital at Home Department, Hospital Universitario Marqués de Valdecilla, Instituto de Investigación Valdecilla (IDIVAL), Santander, Cantabria, Spain
| | - Emilio Pariente
- Camargo Interior Primary Care Center, Servicio Cántabro de Salud, Depto. de Medicina y Psiquiatría, Universidad de Cantabria, Instituto de Investigación Valdecilla (IDIVAL), Santander, Cantabria, Spain.
| | - José M Olmos
- Internal Medicine Department. Bone Metabolism Unit, Hospital Universitario Marqués de Valdecilla, Depto. de Medicina y Psiquiatría, Universidad de Cantabria, Instituto de Investigación Valdecilla (IDIVAL), Santander, Cantabria, Spain
| | - Marta Martín-Millán
- Internal Medicine Department. Bone Metabolism Unit, Hospital Universitario Marqués de Valdecilla, Depto. de Medicina y Psiquiatría, Universidad de Cantabria, Instituto de Investigación Valdecilla (IDIVAL), Santander, Cantabria, Spain
| | - Raquel Pascua
- Instituto de Investigación Valdecilla (IDIVAL), Santander, Cantabria, Spain
| | - Victor M Martínez-Taboada
- Rheumatology Division, Hospital Universitario Marqués de Valdecilla, Depto. de Medicina y Psiquiatría, Universidad de Cantabria, Instituto de Investigación Valdecilla (IDIVAL), Santander, Cantabria, Spain
| | - José L Hernández
- Internal Medicine Department. Bone Metabolism Unit, Hospital Universitario Marqués de Valdecilla, Depto. de Medicina y Psiquiatría, Universidad de Cantabria, Instituto de Investigación Valdecilla (IDIVAL), Santander, Cantabria, Spain
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11
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Xing W, Liang L, Dong N, Chen L, Liu Z. Abnormal changes of bone metabolism markers with age in children with cerebral palsy. Front Pediatr 2023; 11:1214608. [PMID: 37593441 PMCID: PMC10427878 DOI: 10.3389/fped.2023.1214608] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/30/2023] [Accepted: 07/17/2023] [Indexed: 08/19/2023] Open
Abstract
Cerebral palsy (CP) is a broad range of diseases with permanent and nonprogressive motor impairments, carrying a high cost for both the individual and the society. The characteristics of low bone mineral density and high risk of fractures suggest that bone metabolism disorders are present in CP. This study aims to investigate the association between indicators of bone metabolism and children with CP. A total of 139 children (75 children with CP and 64 healthy controls) were included in this cross-sectional study. Participants were divided into three age groups (0-2 years, 2.1-4 years, and 4.1-7 years). All children with CP were diagnosed according to clinical criteria and furtherly divided into clinical subtypes. The levels of total procollagen type I N-terminal propeptide (TPINP), N-MID osteocalcin (OC), beta-crosslaps (β-CTX), 25-hydroxyvitamin D (25-OHD) and parathyroid hormone (PTH) in the serum were measured with corresponding detection kits according to the manufacturer's instructions. Serum levels of TPINP and 25-OHD were lower with older age, whereas β-CTX and PTH were higher with older age. In the CP group, TPINP (age 0-2 years and 2.1-4 years) and OC (age 2.1-4 years) levels were higher, while β-CTX (age 2.1-4 years and 4.1-7 years) and PTH (age 2.1-4 years) values were lower than the control group. In addition, there were no statistically significant differences in the levels of these indicators among the CP subgroups with different clinical characteristics. Our study shows that bone turnover markers, indicators of bone metabolism, in children with CP differ significantly from healthy controls. The indicators we studied changed with age, and they did not correlate with disease severity.
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Affiliation(s)
| | | | | | | | - Zhizhong Liu
- Department of Clinical Laboratory, Beijing Bo'ai Hospital, China Rehabilitation Research Center, Beijing, China
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12
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Meier C, Eastell R, Pierroz DD, Lane NE, Al-Daghri N, Suzuki A, Napoli N, Mithal A, Chakhtoura M, Fuleihan GEH, Ferrari S. Biochemical Markers of Bone Fragility in Patients with Diabetes. A Narrative Review by the IOF and the ECTS. J Clin Endocrinol Metab 2023; 108:dgad255. [PMID: 37155585 PMCID: PMC10505554 DOI: 10.1210/clinem/dgad255] [Citation(s) in RCA: 20] [Impact Index Per Article: 10.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/22/2022] [Revised: 04/24/2023] [Accepted: 05/03/2023] [Indexed: 05/10/2023]
Abstract
CONTEXT The risk of fragility fractures is increased in both type 1 and type 2 diabetes. Numerous biochemical markers reflecting bone and/or glucose metabolism have been evaluated in this context. This review summarizes current data on biochemical markers in relation to bone fragility and fracture risk in diabetes. METHODS Literature review by a group of experts from the International Osteoporosis Foundation (IOF) and European Calcified Tissue Society (ECTS) focusing on biochemical markers, diabetes, diabetes treatments and bone in adults. RESULTS Although bone resorption and bone formation markers are low and poorly predictive of fracture risk in diabetes, osteoporosis drugs seem to change bone turnover markers in diabetics similarly to non-diabetics, with similar reductions in fracture risk. Several other biochemical markers related to bone and glucose metabolism have been correlated with BMD and/or fracture risk in diabetes, including osteocyte-related markers such as sclerostin, HbA1c and advanced glycation end products (AGEs), inflammatory markers and adipokines, as well as IGF-1 and calciotropic hormones. CONCLUSION Several biochemical markers and hormonal levels related to bone and/or glucose metabolism have been associated with skeletal parameters in diabetes. Currently, only HbA1c levels seem to provide a reliable estimate of fracture risk, while bone turnover markers could be used to monitor the effects of anti-osteoporosis therapy.
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Affiliation(s)
- Christian Meier
- Department of Endocrinology, Diabetology and Metabolism, University Hospital Basel, 4031 Basel, Switzerland
| | - Richard Eastell
- Academic Unit of Bone Metabolism, Mellanby Centre for Bone Research, University of Sheffield, S57AU Sheffield, UK
| | | | - Nancy E Lane
- Department of Medicine and Rheumatology, Davis School of Medicine, University of California, Sacramento, CA 95817, USA
| | - Nasser Al-Daghri
- Department of Biochemistry, College of Science, King Saud University, Riyadh 11451, Saudi Arabia
| | - Atsushi Suzuki
- Department of Endocrinology, Diabetes and Metabolism, Fujita Health University, Toyoake, Aichi 470-1192, Japan
| | - Nicola Napoli
- Unit of Endocrinology and Diabetes, Department of Medicine, Università Campus Bio-Medico di Roma, 00128 Rome, Italy
| | - Ambrish Mithal
- Institute of Diabetes and Endocrinology, Max Healthcare, Saket, New Delhi 110017, India
| | - Marlene Chakhtoura
- Department of Internal Medicine, Division of Endocrinology, Calcium Metabolism and Osteoporosis Program, WHO Collaborating Center for Metabolic Bone Disorders, American University of Beirut Medical Center, Riad El Solh, Beirut 6044, Lebanon
| | - Ghada El-Hajj Fuleihan
- Department of Internal Medicine, Division of Endocrinology, Calcium Metabolism and Osteoporosis Program, WHO Collaborating Center for Metabolic Bone Disorders, American University of Beirut Medical Center, Riad El Solh, Beirut 6044, Lebanon
| | - Serge Ferrari
- Service and Laboratory of Bone Diseases, Geneva University Hospital and Faculty of Medicine, 1205 Geneva, Switzerland
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13
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Maagensen H, Helsted MM, Gasbjerg LS, Vilsbøll T, Knop FK. The Gut-Bone Axis in Diabetes. Curr Osteoporos Rep 2023; 21:21-31. [PMID: 36441432 DOI: 10.1007/s11914-022-00767-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 11/03/2022] [Indexed: 11/29/2022]
Abstract
PURPOSE OF REVIEW To describe recent advances in the understanding of how gut-derived hormones regulate bone homeostasis in humans with emphasis on pathophysiological and therapeutic perspectives in diabetes. RECENT FINDINGS The gut-derived incretin hormone glucose-dependent insulinotropic polypeptide (GIP) is important for postprandial suppression of bone resorption. The other incretin hormone, glucagon-like peptide 1 (GLP-1), as well as the intestinotrophic glucagon-like peptide 2 (GLP-2) has been shown to suppress bone resorption in pharmacological concentrations, but the role of the endogenous hormones in bone homeostasis is uncertain. For ambiguous reasons, both patients with type 1 and type 2 diabetes have increased fracture risk. In diabetes, the suppressive effect of endogenous GIP on bone resorption seems preserved, while the effect of GLP-2 remains unexplored both pharmacologically and physiologically. GLP-1 receptor agonists, used for the treatment of type 2 diabetes and obesity, may reduce bone loss, but results are inconsistent. GIP is an important physiological suppressor of postprandial bone resorption, while GLP-1 and GLP-2 may also exert bone-preserving effects when used pharmacologically. A better understanding of the actions of these gut hormones on bone homeostasis in patients with diabetes may lead to new strategies for the prevention and treatment of skeletal frailty related to diabetes.
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Affiliation(s)
- Henrik Maagensen
- Clinical Research, Copenhagen University Hospital-Steno Diabetes Center Copenhagen, Herlev, Denmark
- Center for Clinical Metabolic Research, Copenhagen University Hospital-Herlev and Gentofte, Gentofte Hospitalsvej 7, 3rd floor, DK-2900, Hellerup, Denmark
| | - Mads M Helsted
- Center for Clinical Metabolic Research, Copenhagen University Hospital-Herlev and Gentofte, Gentofte Hospitalsvej 7, 3rd floor, DK-2900, Hellerup, Denmark
| | - Lærke S Gasbjerg
- Center for Clinical Metabolic Research, Copenhagen University Hospital-Herlev and Gentofte, Gentofte Hospitalsvej 7, 3rd floor, DK-2900, Hellerup, Denmark
- Department of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
| | - Tina Vilsbøll
- Clinical Research, Copenhagen University Hospital-Steno Diabetes Center Copenhagen, Herlev, Denmark
- Center for Clinical Metabolic Research, Copenhagen University Hospital-Herlev and Gentofte, Gentofte Hospitalsvej 7, 3rd floor, DK-2900, Hellerup, Denmark
- Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
| | - Filip K Knop
- Clinical Research, Copenhagen University Hospital-Steno Diabetes Center Copenhagen, Herlev, Denmark.
- Center for Clinical Metabolic Research, Copenhagen University Hospital-Herlev and Gentofte, Gentofte Hospitalsvej 7, 3rd floor, DK-2900, Hellerup, Denmark.
- Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
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14
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Dincel AS, Jørgensen NR. New Emerging Biomarkers for Bone Disease: Sclerostin and Dickkopf-1 (DKK1). Calcif Tissue Int 2023; 112:243-257. [PMID: 36165920 DOI: 10.1007/s00223-022-01020-9] [Citation(s) in RCA: 23] [Impact Index Per Article: 11.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/18/2022] [Accepted: 08/26/2022] [Indexed: 01/25/2023]
Abstract
A healthy skeleton depends on a continuous renewal and maintenance of the bone tissue. The process of bone remodeling is highly controlled and consists of a fine-tuned balance between bone formation and bone resorption. Biochemical markers of bone turnover are already in use for monitoring diseases and treatment involving the skeletal system, but novel biomarkers reflecting specific biological processes in bone and interacting tissues may prove useful for diagnostic, prognostic, and monitoring purposes. The Wnt-signaling pathway is one of the most important pathways controlling bone metabolism and consequently the action of inhibitors of the pathway such as sclerostin and Dickkopf-related protein 1 (DKK1) have crucial roles in controlling bone formation and resorption. Thus, they might be potential markers for clinical use as they reflect a number of physiological and pathophysiological events in bone and in the cross-talk with other tissues in the human body. This review focuses on the clinical utility of measurements of circulating sclerostin and DKK1 levels based on preanalytical and analytical considerations and on evidence obtained from published clinical studies. While accumulating evidence points to clear associations with a number of disease states for the two markers, and thus, the potential for especially sclerostin as a biochemical marker that may be used clinically, the lack of standardization or harmonization of the assays still hampers the clinical utility of the markers.
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Affiliation(s)
- Aylin Sepinci Dincel
- Department of Medical Biochemistry, Faculty of Medicine, Gazi University, Ankara, Turkey
- Department of Clinical Biochemistry, Rigshospitalet, Valdemar Hansens Vej 13 Glostrup, 2600, Copenhagen, Denmark
- Institute of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
| | - Niklas Rye Jørgensen
- Department of Medical Biochemistry, Faculty of Medicine, Gazi University, Ankara, Turkey.
- Department of Clinical Biochemistry, Rigshospitalet, Valdemar Hansens Vej 13 Glostrup, 2600, Copenhagen, Denmark.
- Institute of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
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15
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Yang J, Zheng C, Wang Y, Yang L, Liu L. Correlation Between Mean Amplitude of Glycemic Excursion and Bone Turnover Markers in Patients with Type 2 Diabetes: A Cross-Sectional Study. Diabetes Metab Syndr Obes 2023; 16:397-407. [PMID: 36798908 PMCID: PMC9926982 DOI: 10.2147/dmso.s388919] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/09/2022] [Accepted: 01/13/2023] [Indexed: 02/12/2023] Open
Abstract
OBJECTIVE The present study explores the relationship between glycemic excursion and bone turnover markers. METHODS A total of 250 patients with type 2 diabetes mellitus (T2DM) (142 female and 108 male patients) were enrolled in this study. All participants underwent 72 hours of continuous glycemic monitoring to evaluate the mean amplitude of glycemic excursions (MAGE) of each person. Bone turnover markers and other biochemical data were measured for each patient. Linear regression was performed to explore the relationship between bone turnover markers and glycemic excursion. A value of P < 0.05 was considered statistically significant. RESULTS MAGE was negatively correlated to N-terminal propeptide of type 1 collagen (P1NP) female: [odds ratios (95% confidence interval) (OR (95% CI)), -2.516 (-5.389, 0.356)]; male: [-2.895, (-6.521, -0.731)] and C-terminal telopeptide fragments of type-I collagen (β-CTX) female [-0.025, (-0.036, 0.005)]; male [-0.043, (-0.082, 0.003)]. MAGE was still negatively correlated with β-CTX female [-0.036, (-0.198, -0.030)]; male [-0.048, (-0.089, -0.007)] after adjusting for clinical data and biochemical indices. CONCLUSION An independent negative relationship between glycemic excursion and bone turnover markers in patients with T2DM was identified in this study.
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Affiliation(s)
- Jiamiao Yang
- Department of Endocrinology, Shanghai Punan Hospital of Pudong New District, Shanghai, People’s Republic of China
| | - Chao Zheng
- Department of Endocrinology, Shanghai Punan Hospital of Pudong New District, Shanghai, People’s Republic of China
| | - Yan Wang
- Department of Endocrinology, Shanghai Punan Hospital of Pudong New District, Shanghai, People’s Republic of China
| | - Ling Yang
- Department of Endocrinology, Shanghai Punan Hospital of Pudong New District, Shanghai, People’s Republic of China
| | - Lianyong Liu
- Department of Endocrinology, Shanghai Punan Hospital of Pudong New District, Shanghai, People’s Republic of China
- Correspondence: Lianyong Liu; Ling Yang, Department of Endocrinology, Shanghai Punan Hospital of Pudong New District, No. 279, Linyi Road, Pudong New District, Shanghai, 200125, People’s Republic of China, Tel +86-18930502267; Tel +86-18930502267, Email ;
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16
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Faienza MF, Pontrelli P, Brunetti G. Type 2 diabetes and bone fragility in children and adults. World J Diabetes 2022; 13:900-911. [PMID: 36437868 PMCID: PMC9693736 DOI: 10.4239/wjd.v13.i11.900] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/30/2022] [Revised: 08/17/2022] [Accepted: 10/11/2022] [Indexed: 11/11/2022] Open
Abstract
Type 2 diabetes (T2D) is a global epidemic disease. The prevalence of T2D in adolescents and young adults is increasing alarmingly. The mechanisms leading to T2D in young people are similar to those in older patients. However, the severity of onset, reduced insulin sensitivity and defective insulin secretion can be different in subjects who develop the disease at a younger age. T2D is associated with different complications, including bone fragility with consequent susceptibility to fractures. The purpose of this systematic review was to describe T2D bone fragility together with all the possible involved pathways. Numerous studies have reported that patients with T2D show preserved, or even increased, bone mineral density compared with controls. This apparent paradox can be explained by the altered bone quality with increased cortical bone porosity and compr-omised mechanical properties. Furthermore, reduced bone turnover has been described in T2D with reduced markers of bone formation and resorption. These findings prompted different researchers to highlight the mechanisms leading to bone fragility, and numerous critical altered pathways have been identified and studied. In detail, we focused our attention on the role of microvascular disease, advanced glycation end products, the senescence pathway, the Wnt/β-catenin pathway, the osteoprotegerin/receptor-activator of nuclear factor kappa B ligand, osteonectin and fibroblast growth factor 23. The understanding of type 2 myeloid bone fragility is an important issue as it could suggest possible interventions for the prevention of poor bone quality in T2D and/or how to target these pathways when bone disease is clearly evident.
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Affiliation(s)
- Maria Felicia Faienza
- Department of Biomedical Sciences and Human Oncology, Pediatric Unit, University of Bari Aldo Moro, Bari 70124, Italy
| | - Paola Pontrelli
- Division of Nephrology, Department of Emergency and Organ Transplantation, University of Bari Aldo Moro, Bari 70124, Italy
| | - Giacomina Brunetti
- Department of Biosciences, Biotechnologies and Biopharmaceutics, University of Bari Aldo Moro, Bari 70125, Italy
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17
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Willett TL, Voziyan P, Nyman JS. Causative or associative: A critical review of the role of advanced glycation end-products in bone fragility. Bone 2022; 163:116485. [PMID: 35798196 PMCID: PMC10062699 DOI: 10.1016/j.bone.2022.116485] [Citation(s) in RCA: 16] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/04/2022] [Revised: 06/27/2022] [Accepted: 06/29/2022] [Indexed: 11/02/2022]
Abstract
The accumulation of advanced glycation end-products (AGEs) in the organic matrix of bone with aging and chronic disease such as diabetes is thought to increase fracture risk independently of bone mass. However, to date, there has not been a clinical trial to determine whether inhibiting the accumulation of AGEs is effective in preventing low-energy, fragility fractures. Moreover, unlike with cardiovascular or kidney disease, there are also no pre-clinical studies demonstrating that AGE inhibitors or breakers can prevent the age- or diabetes-related decrease in the ability of bone to resist fracture. In this review, we critically examine the case for a long-standing hypothesis that AGE accumulation in bone tissue degrades the toughening mechanisms by which bone resists fracture. Prior research into the role of AGEs in bone has primarily measured pentosidine, an AGE crosslink, or bulk fluorescence of hydrolysates of bone. While significant correlations exist between these measurements and mechanical properties of bone, multiple AGEs are both non-fluorescent and non-crosslinking. Since clinical studies are equivocal on whether circulating pentosidine is an indicator of elevated fracture risk, there needs to be a more complete understanding of the different types of AGEs including non-crosslinking adducts and multiple non-enzymatic crosslinks in bone extracellular matrix and their specific contributions to hindering fracture resistance (biophysical and biological). By doing so, effective strategies to target AGE accumulation in bone with minimal side effects could be investigated in pre-clinical and clinical studies that aim to prevent fragility fractures in conditions that bone mass is not the underlying culprit.
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Affiliation(s)
- Thomas L Willett
- Biomedical Engineering Program, Systems Design Engineering, University of Waterloo, Waterloo, Ontario, Canada.
| | - Paul Voziyan
- Department of Orthopaedic Surgery, Vanderbilt University Medical Center, Nashville, TN 37232, USA
| | - Jeffry S Nyman
- Department of Orthopaedic Surgery, Vanderbilt University Medical Center, Nashville, TN 37232, USA; Department of Veterans Affairs, Tennessee Valley Healthcare System, Nashville, TN 37212, USA.
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18
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Zemanova N, Omelka R, Mondockova V, Kovacova V, Martiniakova M. Roles of Gut Microbiome in Bone Homeostasis and Its Relationship with Bone-Related Diseases. BIOLOGY 2022; 11:1402. [PMID: 36290306 PMCID: PMC9598716 DOI: 10.3390/biology11101402] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 08/12/2022] [Revised: 09/14/2022] [Accepted: 09/19/2022] [Indexed: 11/16/2022]
Abstract
The extended microbial genome-the gut microbiome (GM)-plays a significant role in host health and disease. It is able to influence a number of physiological functions. During dysbiosis, GM is associated with the development of various chronic diseases with impaired bone quality. In general, GM is important for bone homeostasis and can affect it via several mechanisms. This review describes the roles of GM in bone homeostasis through influencing the immune and endocrine functions, short-chain fatty acids production, calcium absorption and the gut-brain axis. The relationship between GM composition and several bone-related diseases, specifically osteoporosis, osteoarthritis, rheumatoid arthritis, diabetes mellitus, obesity and bone cancer, is also highlighted and summarized. GM manipulation may become a future adjuvant therapy in the prevention of many chronic diseases. Therefore, the beneficial effects of probiotic therapy to improve the health status of individuals with aforementioned diseases are provided, but further studies are needed to clearly confirm its effectiveness. Recent evidence suggests that GM is responsible for direct and indirect effects on drug efficacy. Accordingly, various GM alterations and interactions related to the treatment of bone-related diseases are mentioned as well.
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Affiliation(s)
- Nina Zemanova
- Department of Botany and Genetics, Faculty of Natural Sciences and Informatics, Constantine the Philosopher University in Nitra, 949 74 Nitra, Slovakia
| | - Radoslav Omelka
- Department of Botany and Genetics, Faculty of Natural Sciences and Informatics, Constantine the Philosopher University in Nitra, 949 74 Nitra, Slovakia
| | - Vladimira Mondockova
- Department of Botany and Genetics, Faculty of Natural Sciences and Informatics, Constantine the Philosopher University in Nitra, 949 74 Nitra, Slovakia
| | - Veronika Kovacova
- Department of Zoology and Anthropology, Faculty of Natural Sciences and Informatics, Constantine the Philosopher University in Nitra, 949 74 Nitra, Slovakia
| | - Monika Martiniakova
- Department of Zoology and Anthropology, Faculty of Natural Sciences and Informatics, Constantine the Philosopher University in Nitra, 949 74 Nitra, Slovakia
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19
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Liu J, Wei Y, Zang P, Wang W, Feng Z, Yuan Y, Zhou H, Zhang Z, Lei H, Yang X, Liu J, Lu B, Shao J. Circulating osteocalcin is associated with time in range and other metrics assessed by continuous glucose monitoring in type 2 diabetes. Diabetol Metab Syndr 2022; 14:109. [PMID: 35927761 PMCID: PMC9351112 DOI: 10.1186/s13098-022-00863-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/20/2022] [Accepted: 06/13/2022] [Indexed: 11/10/2022] Open
Abstract
BACKGROUND Osteocalcin, a protein secreted mainly by mature osteoblasts, has been shown to be involved in glucose metabolism through various pathways. However, few studies has explored the association between osteocalcin and Time in range (TIR). Continuous glucose monitoring (CGM) -derived metrics, such as TIR and other indexes have been gradually and widely used in clinical practice to assess glucose fluctuations. The main purpose of this study was to investigate the correlation between osteocalcin and indexes from CGM in patients with type 2 diabetes mellitus (T2DM). METHOD The total number of 376 patients with T2D were enrolled, all of them performed three consecutive days of monitoring. They were divided into four groups on account of the quartile of osteocalcin. Time in range, Time below range (TBR), Time above range(TAR) and measures of glycemic variability (GV) were assessed for analysing. After a 100 g standard steamed bread meal, blood glucose (Glu0h Glu0.5 h, Glu1h, Glu2h, GLu3h), C-peptide (Cp0h, Cp0.5 h, Cp1h, Cp2h, Cp3h), serum insulin (INS0h, INS0.5 h, INS1h, INS2h, INS3h) concentrations at different time points were obtained. HOMA-IS, HOMA-βwas calculated to evaluate insulin sensitivity and insulin secreting of the participants. RESULTS Patients with higher osteocalcin level had higher TIR (P < 0.05). Spearman correlation analysis showed that osteocalcin was positively correlated with TBR (although the P value for TBR was greater than 0.05) (r = 0.227, P < 0.001 r = 0.068, P = 0.189) and negatively correlated with TAR (- 0.229, P < 0.001). Similarly, there was a negative correlation between osteocalcin and glycemic variability (GV) indicators, including SD, MBG, MODD, ADDR, and MAGE (P value of MAGE > 0.05). Multiple stepwise regression showed that osteocalcin was an independent contributor to TIR, TAR and HOMA-IS. CONCLUSION Circulating osteocalcin is positively correlated with TIR and negatively correlated with MODD, ADDR, and MAGE. Osteocalcin may have a beneficial impact on glucose homeostasis in T2DM patients.
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Affiliation(s)
- Jun Liu
- Department of Endocrinology, Jinling Hospital, Southern Medical University, Nanjing, China
| | - Yinghua Wei
- Department of Endocrinology, School of Medicine, Jinling Hospital, Nanjing University, Nanjing, China
| | - Pu Zang
- Department of Endocrinology, School of Medicine, Jinling Hospital, Nanjing University, Nanjing, China
| | - Wei Wang
- Department of Endocrinology, School of Medicine, Jinling Hospital, Nanjing University, Nanjing, China
| | - Zhouqin Feng
- Department of Endocrinology, Jinling Hospital, Southern Medical University, Nanjing, China
| | - Yanyu Yuan
- Department of Endocrinology, Jinling Hospital, Nanjing Medical University, Nanjing, China
| | - Hui Zhou
- Department of Endocrinology, Jinling Hospital, Southern Medical University, Nanjing, China
| | - Zhen Zhang
- Department of Endocrinology, Jinling Hospital, Southern Medical University, Nanjing, China
| | - Haiyan Lei
- Department of Endocrinology, Jinling Hospital, Southern Medical University, Nanjing, China
| | - Xinyi Yang
- Department of Endocrinology, School of Medicine, Jinling Hospital, Nanjing University, Nanjing, China
| | - Jun Liu
- Department of Endocrinology, Jinling Hospital, Nanjing Medical University, Nanjing, China
| | - Bin Lu
- Department of Endocrinology, School of Medicine, Jinling Hospital, Nanjing University, Nanjing, China.
| | - Jiaqing Shao
- Department of Endocrinology, Jinling Hospital, Southern Medical University, Nanjing, China.
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20
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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; 11:2206. [PMID: 35456299 PMCID: PMC9024806 DOI: 10.3390/jcm11082206] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/02/2022] [Revised: 03/30/2022] [Accepted: 04/13/2022] [Indexed: 01/25/2023] Open
Abstract
Bone fragility is a common complication in subjects with type 2 diabetes mellitus (T2DM). However, traditional techniques for the evaluation of bone fragility, such as dual-energy X-ray absorptiometry (DXA), do not perform well in this population. Moreover, the Fracture Risk Assessment Tool (FRAX) usually underestimates fracture risk in T2DM. Importantly, novel technologies for the assessment of one microarchitecture in patients with T2DM, such as the trabecular bone score (TBS), high-resolution peripheral quantitative computed tomography (HR-pQCT), and microindentation, are emerging. Furthermore, different serum and urine bone biomarkers may also be useful for the evaluation of bone quality in T2DM. Hence, in this article, we summarize the limitations of conventional tools for the evaluation of bone fragility and review the current evidence on novel approaches for the assessment of quality and bone microstructure alterations in patients with T2DM.
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Affiliation(s)
- José Ignacio Martínez-Montoro
- Department of Endocrinology and Nutrition, Virgen de la Victoria University Hospital, Instituto de Investigación Biomédica de Málaga (IBIMA), Faculty of Medicine, University of Malaga, 29010 Malaga, Spain;
| | - Beatriz García-Fontana
- Bone Metabolic Unit, Endocrinology and Nutrition Division, University Hospital Clínico San Cecilio, 18016 Granada, Spain
- Instituto de Investigación Biosanitaria de Granada (Ibs. GRANADA), 18012 Granada, Spain
- Centro de Investigación Biomédica en Red Fragilidad y Envejecimiento Saludable (CIBERFES), Instituto de Salud Carlos III, 28029 Madrid, Spain
| | - Cristina García-Fontana
- Bone Metabolic Unit, Endocrinology and Nutrition Division, University Hospital Clínico San Cecilio, 18016 Granada, Spain
- Instituto de Investigación Biosanitaria de Granada (Ibs. GRANADA), 18012 Granada, Spain
- Centro de Investigación Biomédica en Red Fragilidad y Envejecimiento Saludable (CIBERFES), Instituto de Salud Carlos III, 28029 Madrid, Spain
| | - Manuel Muñoz-Torres
- Bone Metabolic Unit, Endocrinology and Nutrition Division, University Hospital Clínico San Cecilio, 18016 Granada, Spain
- Instituto de Investigación Biosanitaria de Granada (Ibs. GRANADA), 18012 Granada, Spain
- Centro de Investigación Biomédica en Red Fragilidad y Envejecimiento Saludable (CIBERFES), Instituto de Salud Carlos III, 28029 Madrid, Spain
- Department of Medicine, University of Granada, 18016 Granada, Spain
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21
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Starup-Linde J, Ornstrup MJ, Kjær TN, Lykkeboe S, Handberg A, Gregersen S, Harsløf T, Pedersen SB, Vestergaard P, Langdahl BL. Bone Density and Structure in Overweight Men With and Without Diabetes. Front Endocrinol (Lausanne) 2022; 13:837084. [PMID: 35360074 PMCID: PMC8960162 DOI: 10.3389/fendo.2022.837084] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/16/2021] [Accepted: 02/10/2022] [Indexed: 12/04/2022] Open
Abstract
OBJECTIVE Metabolic syndrome (MetS), type 1 diabetes (T1D), and type 2 diabetes, are associated with an increased risk of fractures; however, the impact of obesity on bone deficits in diabetes is unknown. We aimed to compare markers of bone structure, bone density, and bone turnover in non-diabetic overweight men with MetS and overweight men with T1D or T2D. METHODS AND RESEARCH DESIGN In this cross-sectional study we included participants from two previously described study cohorts consisting of participants with diabetes and participants with MetS. Participants underwent dual-energy X-ray absorptiometry measuring areal bone mineral density (aBMD) at the hip and lumbar spine, High Resolution peripheral Quantitative (HRpQCT) scan of the tibia and radius and measurement of circulating bone turnover markers. We compared groups with unpaired t test and performed multiple linear regression with adjustment for age, body mass index, and smoking. RESULTS We included 33 participants with T1D, 25 participants with T2D, and 34 participants with MetS. Bone turnover markers levels were comparable between T1D and MetS. aBMD at the hip was lower in T1D compared to MetS, also after adjustment. P1NP and Osteocalcin levels were lower among individuals with T2D compared to MetS, whereas aBMD were similar between the groups after multiple adjustments. We observed no difference in volumetric BMD at the tibia or radius between MetS and T1D and T2D, respectively. Participants with T2D had a higher trabecular number and lower trabecular separation compared to individuals with MetS at the tibia, which remained signficant after multiple adjustments. CONCLUSION In conclusion, we observed no clinically important differences in bone density or structure between men with T2D, T1D, or MetS. However, men with T2D displayed lower bone turnover compared to MetS highlighting that T2D per se and not obesity, is associated with low bone turnover.
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Affiliation(s)
- Jakob Starup-Linde
- Department of Endocrinology and Internal Medicine, Aarhus University Hospital, Aarhus, Denmark
- Steno Diabetes Center Aarhus, Aarhus University Hospital, Aarhus, Denmark
- Steno Diabetes Center North Jutland, Aalborg University Hospital, Aalborg, Denmark
- *Correspondence: Jakob Starup-Linde,
| | - Marie Juul Ornstrup
- Department of Endocrinology and Internal Medicine, Aarhus University Hospital, Aarhus, Denmark
| | - Thomas Nordstrøm Kjær
- Department of Endocrinology and Internal Medicine, Aarhus University Hospital, Aarhus, Denmark
| | - Simon Lykkeboe
- Department of Clinical Biochemistry, Aalborg University Hospital, Aalborg, Denmark
| | - Aase Handberg
- Department of Clinical Biochemistry, Aalborg University Hospital, Aalborg, Denmark
- Department of Clinical Medicine, The Faculty of Medicine, Aalborg University, Aalborg, Denmark
| | - Søren Gregersen
- Department of Endocrinology and Internal Medicine, Aarhus University Hospital, Aarhus, Denmark
- Steno Diabetes Center Aarhus, Aarhus University Hospital, Aarhus, Denmark
| | - Torben Harsløf
- Department of Endocrinology and Internal Medicine, Aarhus University Hospital, Aarhus, Denmark
| | - Steen Bønløkke Pedersen
- Department of Endocrinology and Internal Medicine, Aarhus University Hospital, Aarhus, Denmark
- Steno Diabetes Center Aarhus, Aarhus University Hospital, Aarhus, Denmark
| | - Peter Vestergaard
- Steno Diabetes Center North Jutland, Aalborg University Hospital, Aalborg, Denmark
- Department of Clinical Medicine, The Faculty of Medicine, Aalborg University, Aalborg, Denmark
- Department of Endocrinology, Aalborg University Hospital, Aalborg, Denmark
| | - Bente Lomholt Langdahl
- Department of Endocrinology and Internal Medicine, Aarhus University Hospital, Aarhus, Denmark
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22
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Ballato E, Deepika F, Prado M, Russo V, Fuenmayor V, Bathina S, Villareal DT, Qualls C, Armamento-Villareal R. Circulating osteogenic progenitors and osteoclast precursors are associated with long-term glycemic control, sex steroids, and visceral adipose tissue in men with type 2 diabetes mellitus. Front Endocrinol (Lausanne) 2022; 13:936159. [PMID: 36171900 PMCID: PMC9511027 DOI: 10.3389/fendo.2022.936159] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/04/2022] [Accepted: 08/10/2022] [Indexed: 11/23/2022] Open
Abstract
INTRODUCTION Type 2 diabetes mellitus (T2DM) is well-known to be associated with normal bone density but, concurrently, low bone turnover and increased risk for fracture. One of the proposed mechanisms is possible derangement in bone precursor cells, which could be represented by deficiencies in circulating osteogenic progenitor (COP) cells and osteoclast precursors (OCP). The objective of our study is to understand whether extent of glycemic control has an impact on these cells, and to identify other factors that may as well. METHODS This was a secondary analysis of baseline data from 51 male participants, aged 37-65 in an ongoing clinical trial at Michael E. DeBakey VA Medical Center, Houston, Texas, USA. At study entry serum Hemoglobin A1c was measured by high-performance liquid chromatography osteocalcin (OCN) and C-terminal telopeptide of type 1 collagen (CTx) were measured by ELISA, and testosterone and estradiol by liquid-chromatography/mass-spectrometry. Areal bone mineral density (BMD), trabecular bone score and body composition were measured by dual energy x-ray absorptiometry, while COP and OCP were measured by flow cytometry. RESULTS When adjusted for serum testosterone, parathyroid hormone, and 25-hydroxyvitamin D, those with poor long-term glycemic control had significantly higher percentage of COP (p = 0.04). COP correlated positively with visceral adipose tissue (VAT) volume (r = 0.37, p = 0.01) and negatively with free testosterone (r = -0.28, p = 0.05) and OCN (r = -0.28, p = 0.07), although only borderline for the latter. OCP correlated positively with age, FSH, lumbar spine BMD, and COP levels, and negatively with glucose, triglycerides, and free estradiol. Multivariable regression analyses revealed that, in addition to being predictors for each other, another independent predictor for COP was VAT volume while age, glucose, and vitamin D for OCP. CONCLUSION Our results suggest that high COP could be a marker of poor metabolic control. However, given the complex nature and the multitude of factors influencing osteoblastogenesis/adipogenesis, it is possible that the increase in COP is a physiologic response of the bone marrow to increased osteoblast apoptosis from poor glycemic control. Alternatively, it is also likely that a metabolically unhealthy profile may retard the development of osteogenic precursors to fully mature osteoblastic cells.
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Affiliation(s)
- Elliot Ballato
- Division of Endocrinology, Diabetes and Metabolism, Department of Medicine, Baylor College of Medicine, Houston, TX, United States
- Center for Translational Research on Inflammatory Disease, Michael E DeBakey Veterans Affairs (VA) Medical Center, Houston, TX, United States
| | - Fnu Deepika
- Division of Endocrinology, Diabetes and Metabolism, Department of Medicine, Baylor College of Medicine, Houston, TX, United States
- Center for Translational Research on Inflammatory Disease, Michael E DeBakey Veterans Affairs (VA) Medical Center, Houston, TX, United States
| | - Mia Prado
- Division of Endocrinology, Diabetes and Metabolism, Department of Medicine, Baylor College of Medicine, Houston, TX, United States
- Center for Translational Research on Inflammatory Disease, Michael E DeBakey Veterans Affairs (VA) Medical Center, Houston, TX, United States
| | - Vittoria Russo
- Center for Translational Research on Inflammatory Disease, Michael E DeBakey Veterans Affairs (VA) Medical Center, Houston, TX, United States
| | - Virginia Fuenmayor
- Division of Endocrinology, Diabetes and Metabolism, Department of Medicine, Baylor College of Medicine, Houston, TX, United States
- Center for Translational Research on Inflammatory Disease, Michael E DeBakey Veterans Affairs (VA) Medical Center, Houston, TX, United States
| | - Siresha Bathina
- Division of Endocrinology, Diabetes and Metabolism, Department of Medicine, Baylor College of Medicine, Houston, TX, United States
- Center for Translational Research on Inflammatory Disease, Michael E DeBakey Veterans Affairs (VA) Medical Center, Houston, TX, United States
| | - Dennis T. Villareal
- Division of Endocrinology, Diabetes and Metabolism, Department of Medicine, Baylor College of Medicine, Houston, TX, United States
- Center for Translational Research on Inflammatory Disease, Michael E DeBakey Veterans Affairs (VA) Medical Center, Houston, TX, United States
| | - Clifford Qualls
- Biomedical Research Institute of New Mexico, Albuquerque, NM, United States
- Research Service Line, New Mexico Veterans Affairs Health Care System, Albuquerque, NM, United States
| | - Reina Armamento-Villareal
- Division of Endocrinology, Diabetes and Metabolism, Department of Medicine, Baylor College of Medicine, Houston, TX, United States
- Center for Translational Research on Inflammatory Disease, Michael E DeBakey Veterans Affairs (VA) Medical Center, Houston, TX, United States
- *Correspondence: Reina Armamento-Villareal,
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