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Zheng H, Wang Q, Si M. Dapagliflozin combined with metformin improves blood glucose, bone metabolism and bone mineral density in elderly patients with type 2 diabetes mellitus complicated with osteoporosis. Kaohsiung J Med Sci 2025; 41:e12937. [PMID: 39810714 DOI: 10.1002/kjm2.12937] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/22/2024] [Revised: 11/29/2024] [Accepted: 12/25/2024] [Indexed: 01/16/2025] Open
Abstract
The incidence of type 2 diabetes mellitus (T2DM) complicated with osteoporosis (OP) (T2DM-OP) is growing. Dapagliflozin and metformin are commonly prescribed to manage glycemic levels in T2DM patients. We investigated the clinical efficacy of combining dapagliflozin with metformin in elderly patients with T2DM-OP. Totally 144 T2DM-OP patients were prospectively enrolled and allocated into two groups: the Metformin and Dapagliflozin + Metformin groups. Each group received treatment for 12 months. Fasting peripheral blood samples were collected before and after 12 months of treatment. Glycemic parameters and bone metabolic parameters were measured using oral glucose tolerance test, automatic biochemical analyzers, or liquid chromatography. Bone mineral density (BMD) changes at lumbar vertebrae (L1-4), femoral neck (FN) and total hip (TH) were assessed using dual-energy X-ray bone mineral densitometry. Pain severity was evaluated using the visual analog scale (VAS). The total effective rate, fracture incidence, and adverse reaction rate were also evaluated. After 12 months, both groups showed improvements in glycemic parameters, bone metabolic parameters, and BMD at L1-4, FN, and TH, and reductions in VAS scores. The Dapagliflozin + Metformin group exhibited more significant improvements. The overall effective rate was higher and fracture incidence, was lower in Dapagliflozin + Metformin group, with comparable rates of adverse reactions and safety profiles between the two groups. Taken together, treatment with a combination of dapagliflozin and metformin led to improvements in blood glucose levels, bone metabolism, and BMD in elderly patients with T2DM-OP, demonstrating superior efficacy and safety compared to metformin monotherapy.
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Affiliation(s)
- Haiyan Zheng
- Department of Endocrinology, Renmin Hospital, Hubei University of Medicine, Shiyan, Hubei, China
| | - Qian Wang
- Department of Endocrinology, Renmin Hospital, Hubei University of Medicine, Shiyan, Hubei, China
| | - Min Si
- Department of Endocrinology, Renmin Hospital, Hubei University of Medicine, Shiyan, Hubei, China
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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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Chen Y, Zhao W, Hu A, Lin S, Chen P, Yang B, Fan Z, Qi J, Zhang W, Gao H, Yu X, Chen H, Chen L, Wang H. Type 2 diabetic mellitus related osteoporosis: focusing on ferroptosis. J Transl Med 2024; 22:409. [PMID: 38693581 PMCID: PMC11064363 DOI: 10.1186/s12967-024-05191-x] [Citation(s) in RCA: 17] [Impact Index Per Article: 17.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/21/2024] [Accepted: 04/12/2024] [Indexed: 05/03/2024] Open
Abstract
With the aging global population, type 2 diabetes mellitus (T2DM) and osteoporosis(OP) are becoming increasingly prevalent. Diabetic osteoporosis (DOP) is a metabolic bone disorder characterized by abnormal bone tissue structure and reduced bone strength in patients with diabetes. Studies have revealed a close association among diabetes, increased fracture risk, and disturbances in iron metabolism. This review explores the concept of ferroptosis, a non-apoptotic cell death process dependent on intracellular iron, focusing on its role in DOP. Iron-dependent lipid peroxidation, particularly impacting pancreatic β-cells, osteoblasts (OBs) and osteoclasts (OCs), contributes to DOP. The intricate interplay between iron dysregulation, which comprises deficiency and overload, and DOP has been discussed, emphasizing how excessive iron accumulation triggers ferroptosis in DOP. This concise overview highlights the need to understand the complex relationship between T2DM and OP, particularly ferroptosis. This review aimed to elucidate the pathogenesis of ferroptosis in DOP and provide a prospective for future research targeting interventions in the field of ferroptosis.
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Affiliation(s)
- Yili Chen
- Guangdong Provincial Hospital of Traditional Chinese Medicine, Guangzhou University of Chinese Medicine, Guangzhou, 510006, China
| | - Wen Zhao
- Guangzhou University of Traditional Chinese Medicine, Guangzhou, 510006, China
| | - An Hu
- Guangzhou University of Traditional Chinese Medicine, Guangzhou, 510006, China
| | - Shi Lin
- Guangzhou University of Traditional Chinese Medicine, Guangzhou, 510006, China
| | - Ping Chen
- Guangdong Provincial Hospital of Traditional Chinese Medicine, Guangzhou University of Chinese Medicine, Guangzhou, 510006, China
| | - Bing Yang
- Guangdong Provincial Hospital of Traditional Chinese Medicine, Guangzhou University of Chinese Medicine, Guangzhou, 510006, China
| | - Zhirong Fan
- Guangdong Provincial Hospital of Traditional Chinese Medicine, Guangzhou University of Chinese Medicine, Guangzhou, 510006, China
| | - Ji Qi
- Guangdong Provincial Hospital of Traditional Chinese Medicine, Guangzhou University of Chinese Medicine, Guangzhou, 510006, China
| | - Wenhui Zhang
- Guangdong Provincial Hospital of Traditional Chinese Medicine, Guangzhou University of Chinese Medicine, Guangzhou, 510006, China
| | - Huanhuan Gao
- Guangdong Provincial Hospital of Traditional Chinese Medicine, Guangzhou University of Chinese Medicine, Guangzhou, 510006, China
| | - Xiubing Yu
- Guangdong Provincial Hospital of Traditional Chinese Medicine, Guangzhou University of Chinese Medicine, Guangzhou, 510006, China
| | - Haiyun Chen
- Guangdong Provincial Hospital of Traditional Chinese Medicine, Guangzhou University of Chinese Medicine, Guangzhou, 510006, China
| | - Luyuan Chen
- Stomatology Center, Shenzhen Hospital, Southern Medical University, Shenzhen, Guangdong, 510086, China.
| | - Haizhou Wang
- Guangdong Provincial Hospital of Traditional Chinese Medicine, Guangzhou University of Chinese Medicine, Guangzhou, 510006, China.
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He X, Liu M, Ding X, Bian N, Wang J, Wang G, Liu J. Parathyroid Hormone is Negatively Correlated with Glycated Hemoglobin in Newly Diagnosed Type 2 Diabetic Patients. Int J Endocrinol 2024; 2024:8414689. [PMID: 38590929 PMCID: PMC11001476 DOI: 10.1155/2024/8414689] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/31/2023] [Revised: 11/16/2023] [Accepted: 03/08/2024] [Indexed: 04/10/2024] Open
Abstract
Objective The growing evidence shows that parathyroid hormone (PTH) may affect glucose metabolism. However, the relationship between them is still controversial among diabetic patients. The current study aimed to investigate the relationship between PTH and glucose metabolism in the patients with newly diagnosed type 2 diabetes (T2D). Methods A total of 532 participants, including 387 patients with newly diagnosed T2D and 145 healthy controls, were recruited in the present study. PTH and metabolic parameters were measured in all participants. Results The PTH levels were significantly lower in the newly diagnosed T2D patients compared with the control group (35.10 (25.90, 47.20) vs. 47.15 (35.83, 58.65) pg/ml, P < 0.001). The T2D patients with a higher glycated hemoglobin (HbA1c) tertile had lower PTH levels than the patients with a lower HbA1c tertile (32.90 (24.85, 41.40) vs. 37.50 (26.10, 54.55) pg/ml, P < 0.001). Spearman correlation analysis showed that PTH was positively correlated with the body mass index (BMI), fasting insulin (FINS), homeostasis model assessment of β-cell function (HOMA-β), and homeostasis model assessment of insulin resistance (HOMA-IR) and negatively correlated with HbA1c, blood calcium (Ca), blood phosphorus (P), and 25-hydroxyvitamin D3 (25-OH-D3). Multiple linear regression analysis demonstrated that PTH was significantly associated with HbA1c (β = -1.475, P=0.003) and HOMA-β (β = 0.090, P=0.001) after adjusting for age, sex, BMI, season, 25-OH-D3, Ca, and P. Conclusion PTH was negatively correlated with HbA1c in the newly diagnosed T2D patients. Our results suggested that the PTH level within the reference range is related to islet β-cell function and hyperglycemia.
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Affiliation(s)
- Xueqing He
- Department of Endocrinology, Beijing Chao-Yang Hospital, Capital Medical University, Beijing 100020, China
| | - Man Liu
- Department of Endocrinology, Beijing Chao-Yang Hospital, Capital Medical University, Beijing 100020, China
| | - Xiaoyu Ding
- Department of Endocrinology, Beijing Chao-Yang Hospital, Capital Medical University, Beijing 100020, China
| | - Nannan Bian
- Department of Endocrinology, Beijing Chao-Yang Hospital, Capital Medical University, Beijing 100020, China
| | - Jiaxuan Wang
- Department of Endocrinology, Beijing Chao-Yang Hospital, Capital Medical University, Beijing 100020, China
| | - Guang Wang
- Department of Endocrinology, Beijing Chao-Yang Hospital, Capital Medical University, Beijing 100020, China
| | - Jia Liu
- Department of Endocrinology, Beijing Chao-Yang Hospital, Capital Medical University, Beijing 100020, China
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Huang DN, Zeng Y, Ding HR, Zhang ZK, Wang Y, Han DX, Zhang XZ, Song LG. Characteristics of bone metabolism in the male patients with diabetic neuropathy. J Chin Med Assoc 2024; 87:292-298. [PMID: 38289285 DOI: 10.1097/jcma.0000000000001062] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 03/06/2024] Open
Abstract
BACKGROUND This study aimed to evaluate the characteristics of bone metabolism and fracture risk in the type 2 diabetes mellitus (T2DM) patients with distal symmetric polyneuropathy (DSPN). METHODS A total of 198 T2DM individuals were recruited from January 2017 to December 2020. Patients with DSPN were evaluated by strict clinical and sensory thresholds. Biochemical parameters and bone mineral density (BMD) were measured. The BMD, bone turnover markers, and probability of fracture were compared between two groups, and the factors related to BMD and probability of hip fracture in 10 years were further explored. RESULTS Compared with type 2 diabetes mellitus without distal symmetric polyneuropathy (T2DN-) patients, type 2 diabetes mellitus with distal symmetric polyneuropathy (T2DN+) patients had lower level of cross-linked C-telopeptide (CTX) (0.32 ± 0.19 vs 0.38 ± 0.21 ng/mL, p = 0.038) and higher level of bone-specific alkaline phosphatase (BALP) (15.28 ± 5.56 vs 12.58 ± 4.41 μg/mL, p = 0.003). T2DN+ patients had higher BMD of lumbar L1-L4 (1.05 ± 0.19 vs 0.95 ± 0.37, p = 0.027) and higher probability of hip fracture (0.98 ± 0.88 vs 0.68 ± 0.63, p = 0.009) as compared to T2DN- individuals. Univariate correlation analysis showed that BALP level (coefficient (coef) = -0.054, p = 0.038), CTX level (coef = -2.28, p = 0.001), and hip fracture risk (coef = -1.02, p < 0.001) were negatively related to the BMD of L1-L4. As for the risk of hip fracture evaluated by WHO Fracture Risk Assessment Tool (FRAX), age (coef = 0.035, p < 0.001), use of insulin (coef = 0.31, p =0.015), and levels of BALP (coef = 0.031, p = 0.017) and CTX (coef = 0.7, p = 0.047) were positively related to the risk of hip fracture. Multivariate regression analysis showed that CTX level (coef = -1.41, p = 0.043) was still negatively related to BMD at the lumbar spine. CONCLUSION This study indicates that T2DM patients with DSPN have special bone metabolism represented by higher BALP level and lower CTX level which may increase BMD at the lumbar spine.
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Affiliation(s)
- Dong-Ni Huang
- Department of Endocrinology, Shanghai Tongji Hospital, School of Medicine, Tongji University, Shanghai, China
- Institute of Osteoporosis and Metabolic Bone Diseases, School of Medicine, Tongji University, Shanghai, China
| | - Yue Zeng
- Department of Endocrinology, Shanghai Tongji Hospital, School of Medicine, Tongji University, Shanghai, China
- Institute of Osteoporosis and Metabolic Bone Diseases, School of Medicine, Tongji University, Shanghai, China
| | - Hui-Ru Ding
- Department of Endocrinology, Shanghai Tongji Hospital, School of Medicine, Tongji University, Shanghai, China
- Institute of Osteoporosis and Metabolic Bone Diseases, School of Medicine, Tongji University, Shanghai, China
| | - Zi-Kai Zhang
- Division of Science and Research, Shanghai Tongji Hospital, School of Medicine, Tongji University, Shanghai, China
| | - Yu Wang
- Department of Endocrinology, Shanghai Tongji Hospital, School of Medicine, Tongji University, Shanghai, China
- Institute of Osteoporosis and Metabolic Bone Diseases, School of Medicine, Tongji University, Shanghai, China
| | - Dong-Xu Han
- Department of Endocrinology, Shanghai Tongji Hospital, School of Medicine, Tongji University, Shanghai, China
- Institute of Osteoporosis and Metabolic Bone Diseases, School of Medicine, Tongji University, Shanghai, China
| | - Xiu-Zhen Zhang
- Department of Endocrinology, Shanghai Tongji Hospital, School of Medicine, Tongji University, Shanghai, China
- Institute of Osteoporosis and Metabolic Bone Diseases, School of Medicine, Tongji University, Shanghai, China
| | - Li-Ge Song
- Department of Endocrinology, Shanghai Tongji Hospital, School of Medicine, Tongji University, Shanghai, China
- Institute of Osteoporosis and Metabolic Bone Diseases, School of Medicine, Tongji University, Shanghai, China
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Emanuelsson F, Afzal S, Jørgensen NR, Nordestgaard BG, Benn M. Hyperglycaemia, diabetes and risk of fragility fractures: observational and Mendelian randomisation studies. Diabetologia 2024; 67:301-311. [PMID: 38095658 PMCID: PMC10789835 DOI: 10.1007/s00125-023-06054-8] [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: 07/31/2023] [Accepted: 10/12/2023] [Indexed: 01/16/2024]
Abstract
AIMS/HYPOTHESIS Fragility fractures may be a complication of diabetes, partly caused by chronic hyperglycaemia. We hypothesised that: (1) individuals with hyperglycaemia and diabetes have increased risk of fragility fracture; (2) hyperglycaemia is causally associated with increased risk of fragility fracture; and (3) diabetes and fragility fracture jointly associate with the highest risk of all-cause mortality. METHODS In total, 117,054 individuals from the Copenhagen City Heart Study and the Copenhagen General Population Study (the Copenhagen studies) and 390,374 individuals from UK Biobank were included for observational and one-sample Mendelian randomisation (MR) analyses. Fragility fractures were defined as fractures at the hip, spine and arm (humerus/wrist), collected from national health registries. Summary data for fasting glucose and HbA1c concentrations from 196,743 individuals in the Meta-Analyses of Glucose and Insulin-related traits Consortium (MAGIC) were combined with data on fragility fractures from the Copenhagen studies in two-sample MR analyses. RESULTS Higher fasting and non-fasting glucose and HbA1c concentrations were associated with higher risk of any fragility fracture (p<0.001). Individuals with vs without diabetes had HRs for fragility fracture of 1.50 (95% CI 1.19, 1.88) in type 1 diabetes and 1.22 (1.13, 1.32) in type 2 diabetes. One-sample MR supported a causal association between high non-fasting glucose concentrations and increased risk of arm fracture in the Copenhagen studies and UK Biobank combined (RR 1.41 [1.11, 1.79], p=0.004), with similar results for fasting glucose and HbA1c in two-sample MR analyses (ORs 1.50 [1.03, 2.18], p=0.03; and 2.79 [1.12, 6.93], p=0.03, respectively). The corresponding MR estimates for any fragility fracture were 1.18 (1.00, 1.41), p=0.06; 1.36 (0.89, 2.09), p=0.15; and 2.47 (0.95, 6.43), p=0.06, respectively. At age 80 years, cumulative death was 27% in individuals with fragility fracture only, 54% in those with diabetes only, 67% in individuals with both conditions and 17% in those with neither. CONCLUSIONS/INTERPRETATION Hyperglycaemia and diabetes are risk factors for fragility fracture and one- and two-sample MR analyses supported a causal effect of hyperglycaemia on arm fractures. Diabetes and previous fragility fracture jointly conferred the highest risk of death in the general population.
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Affiliation(s)
- Frida Emanuelsson
- Department of Clinical Biochemistry, Copenhagen University Hospital Rigshospitalet, Centre of Diagnostic Investigation, Copenhagen, Denmark
- Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
| | - Shoaib Afzal
- Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
- Department of Clinical Biochemistry, Copenhagen University Hospital Herlev and Gentofte, Herlev, Denmark
- The Copenhagen General Population Study, Copenhagen University Hospital Herlev and Gentofte, Herlev, Denmark
| | - Niklas R Jørgensen
- Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
- Department of Clinical Biochemistry, Copenhagen University Hospital Rigshospitalet, Centre of Diagnostic Investigation, Glostrup, Denmark
| | - Børge G Nordestgaard
- Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
- Department of Clinical Biochemistry, Copenhagen University Hospital Herlev and Gentofte, Herlev, Denmark
- The Copenhagen General Population Study, Copenhagen University Hospital Herlev and Gentofte, Herlev, Denmark
| | - Marianne Benn
- Department of Clinical Biochemistry, Copenhagen University Hospital Rigshospitalet, Centre of Diagnostic Investigation, Copenhagen, Denmark.
- Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
- The Copenhagen General Population Study, Copenhagen University Hospital Herlev and Gentofte, Herlev, Denmark.
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Kang Y, Yao J, Gao X, Zhong H, Song Y, Di X, Feng Z, Xie L, Zhang J. Exercise ameliorates anxious behavior and promotes neuroprotection through osteocalcin in VCD-induced menopausal mice. CNS Neurosci Ther 2023; 29:3980-3994. [PMID: 37402694 PMCID: PMC10651954 DOI: 10.1111/cns.14324] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/10/2023] [Revised: 04/06/2023] [Accepted: 05/25/2023] [Indexed: 07/06/2023] Open
Abstract
AIMS As the ovaries age and women transition to menopause and postmenopause, reduced estradiol levels are associated with anxiety and depression. Exercise contributes to alleviate anxiety and depression and the bone-derived hormone osteocalcin has been reported to be necessary to prevent anxiety-like behaviors. The aim of this study was to investigate the effects of exercise on anxiety behaviors in climacteric mice and whether it was related to osteocalcin. METHODS Menopausal mouse model was induced by intraperitoneal injection of 4-vinylcyclohexene diepoxide (VCD). Open field, elevated plus maze, and light-dark tests were used to detect anxious behavior in mice. The content of serum osteocalcin was measured and its correlation with anxiety behavior was analyzed. BRDU and NEUN co-localization cells were detected with immunofluorescence. Western blot was applied to obtain apoptosis-related proteins. RESULTS The VCD mice showed obvious anxiety-like behaviors and 10 weeks of treadmill exercise significantly ameliorated the anxiety and increased circulating osteocalcin in VCD mice. Exercise increased the number of BRDU and NEUN co-localization cells in hippocampal dentate gyrus, reduced the number of impaired hippocampal neurons, inhibited the expression of BAX, cleaved Caspase3, and cleaved PARP, promoted the expression of BCL-2. Importantly, circulating osteocalcin levels were positively associated with the improvements of anxiety, the number of BRDU and NEUN co-localization cells in hippocampal dentate gyrus and negatively related to impaired hippocampal neurons. CONCLUSION Exercise ameliorates anxiety behavior, promotes hippocampal dentate gyrus neurogenesis, and inhibits hippocampal cell apoptosis in VCD-induced menopausal mice. They are related to circulating osteocalcin, which are increased by exercise.
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Affiliation(s)
- Yiting Kang
- Key Laboratory of Biomedical Information Engineering of Ministry of Education, Institute of Health and Rehabilitation Science, School of Life Science and TechnologyXi'an Jiaotong UniversityXi'anChina
| | - Jie Yao
- Key Laboratory of Biomedical Information Engineering of Ministry of Education, Institute of Health and Rehabilitation Science, School of Life Science and TechnologyXi'an Jiaotong UniversityXi'anChina
- School of NursingShaanxi University of Chinese MedicineXianyangChina
| | - Xiaohang Gao
- Key Laboratory of Biomedical Information Engineering of Ministry of Education, Institute of Health and Rehabilitation Science, School of Life Science and TechnologyXi'an Jiaotong UniversityXi'anChina
| | - Hao Zhong
- Key Laboratory of Biomedical Information Engineering of Ministry of Education, Institute of Health and Rehabilitation Science, School of Life Science and TechnologyXi'an Jiaotong UniversityXi'anChina
| | - Yifei Song
- Key Laboratory of Biomedical Information Engineering of Ministry of Education, Institute of Health and Rehabilitation Science, School of Life Science and TechnologyXi'an Jiaotong UniversityXi'anChina
| | - Xiaohui Di
- Key Laboratory of Biomedical Information Engineering of Ministry of Education, Institute of Health and Rehabilitation Science, School of Life Science and TechnologyXi'an Jiaotong UniversityXi'anChina
| | - Zeguo Feng
- Key Laboratory of Biomedical Information Engineering of Ministry of Education, Institute of Health and Rehabilitation Science, School of Life Science and TechnologyXi'an Jiaotong UniversityXi'anChina
| | - Lin Xie
- Key Laboratory of Biomedical Information Engineering of Ministry of Education, Institute of Health and Rehabilitation Science, School of Life Science and TechnologyXi'an Jiaotong UniversityXi'anChina
| | - Jianbao Zhang
- Key Laboratory of Biomedical Information Engineering of Ministry of Education, Institute of Health and Rehabilitation Science, School of Life Science and TechnologyXi'an Jiaotong UniversityXi'anChina
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Schini M, Vilaca T, Gossiel F, Salam S, Eastell R. Bone Turnover Markers: Basic Biology to Clinical Applications. Endocr Rev 2022; 44:417-473. [PMID: 36510335 PMCID: PMC10166271 DOI: 10.1210/endrev/bnac031] [Citation(s) in RCA: 132] [Impact Index Per Article: 44.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/26/2022] [Revised: 11/26/2022] [Accepted: 12/05/2022] [Indexed: 12/15/2022]
Abstract
Bone turnover markers (BTMs) are used widely, in both research and clinical practice. In the last 20 years, much experience has been gained in measurement and interpretation of these markers, which include commonly used bone formation markers bone alkaline phosphatase, osteocalcin, and procollagen I N-propeptide; and commonly used resorption markers serum C-telopeptides of type I collagen, urinary N-telopeptides of type I collagen and tartrate resistant acid phosphatase type 5b. BTMs are usually measured by enzyme-linked immunosorbent assay or automated immunoassay. Sources contributing to BTM variability include uncontrollable components (e.g., age, gender, ethnicity) and controllable components, particularly relating to collection conditions (e.g., fasting/feeding state, and timing relative to circadian rhythms, menstrual cycling, and exercise). Pregnancy, season, drugs, and recent fracture(s) can also affect BTMs. BTMs correlate with other methods of assessing bone turnover, such as bone biopsies and radiotracer kinetics; and can usefully contribute to diagnosis and management of several diseases such as osteoporosis, osteomalacia, Paget's disease, fibrous dysplasia, hypophosphatasia, primary hyperparathyroidism, and chronic kidney disease-mineral bone disorder.
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Affiliation(s)
- Marian Schini
- Department of Oncology and Metabolism, University of Sheffield, Sheffield, UK.,Sheffield Teaching Hospitals NHS Foundation Trust, Sheffield, UK
| | - Tatiane Vilaca
- Department of Oncology and Metabolism, University of Sheffield, Sheffield, UK
| | - Fatma Gossiel
- Department of Oncology and Metabolism, University of Sheffield, Sheffield, UK
| | - Syazrah Salam
- Department of Oncology and Metabolism, University of Sheffield, Sheffield, UK.,Sheffield Teaching Hospitals NHS Foundation Trust, Sheffield, UK
| | - Richard Eastell
- Department of Oncology and Metabolism, University of Sheffield, Sheffield, UK
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Fazullina ON, Korbut AI, Klimontov VV. Factors associated with trabecular bone score in postmenopausal women with type 2 diabetes and normal bone mineral density. World J Diabetes 2022; 13:553-565. [PMID: 36051426 PMCID: PMC9329840 DOI: 10.4239/wjd.v13.i7.553] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/15/2022] [Revised: 05/02/2022] [Accepted: 06/24/2022] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Osteoporosis and type 2 diabetes (T2D) have been recognized as a widespread comorbidity leading to excess mortality and an enormous healthcare burden. In T2D, bone mineral density (BMD) may underestimate the risk of low-energy fractures as bone quality is reduced. It was hypothesized that a decrease in the trabecular bone score (TBS), a parameter assessing bone microarchitecture, may be an early marker of impaired bone health in women with T2D. AIM To identify clinical and body composition parameters that affect TBS in postmenopausal women with T2D and normal BMD. METHODS A non-interventional cross-sectional comparative study was conducted. Potentially eligible subjects were screened at tertiary referral center. Postmenopausal women with T2D, aged 50-75 years, with no established risk factors for secondary osteoporosis, were included. BMD, TBS and body composition parameters were assessed by dual-energy X-ray absorptiometry. In women with normal BMD, a wide range of anthropometric, general and diabetes-related clinical and laboratory parameters were evaluated as risk factors for TBS decrease using univariate and multivariate regression analysis and analysis of receiver operating characteristic (ROC) curves. RESULTS Three hundred twelve women were initially screened, 176 of them met the inclusion criteria and underwent dual X-ray absorptiometry. Those with reduced BMD were subsequently excluded; 96 women with normal BMD were included in final analysis. Among them, 43 women (44.8%) showed decreased TBS values (≤ 1.31). Women with TBS ≤ 1.31 were taller and had a lower body mass index (BMI) when compared to those with normal TBS (Р = 0.008 and P = 0.007 respectively). No significant differences in HbA1c, renal function, calcium, phosphorus, alkaline phosphatase, PTH and 25(ОН)D levels were found. In a model of multivariate linear regression analysis, TBS was positively associated with gynoid fat mass, whereas the height and androgen fat mass were associated negatively (all P < 0.001). In a multiple logistic regression, TBS ≤ 1.31 was associated with lower gynoid fat mass (adjusted odd ratio [OR], 0.9, 95% confidence interval [CI], 0.85-0.94, P < 0.001), higher android fat mass (adjusted OR, 1.13, 95%CI, 1.03-1.24, P = 0.008) and height (adjusted OR, 1.13, 95%CI, 1.05-1.20, P < 0.001). In ROC-curve analysis, height ≥ 162.5 cm (P = 0.04), body mass index ≤ 33.85 kg/m2 (P = 0.002), gynoid fat mass ≤ 5.41 kg (P = 0.03) and android/gynoid fat mass ratio ≥ 1.145 (P < 0.001) were identified as the risk factors for TBS reduction. CONCLUSION In postmenopausal women with T2D and normal BMD, greater height and central adiposity are associated with impaired bone microarchitecture.
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Affiliation(s)
- Olga N Fazullina
- Laboratory of Endocrinology, Research Institute of Clinical and Experimental Lymphology - Branch of the Institute of Cytology and Genetics, Siberian Branch of Russian Academy of Sciences, Novosibirsk 630060, Russia
| | - Anton I Korbut
- Laboratory of Endocrinology, Research Institute of Clinical and Experimental Lymphology - Branch of the Institute of Cytology and Genetics, Siberian Branch of Russian Academy of Sciences, Novosibirsk 630060, Russia
| | - Vadim V Klimontov
- Laboratory of Endocrinology, Research Institute of Clinical and Experimental Lymphology - Branch of the Institute of Cytology and Genetics, Siberian Branch of Russian Academy of Sciences, Novosibirsk 630060, Russia
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Hofbauer LC, Busse B, Eastell R, Ferrari S, Frost M, Müller R, Burden AM, Rivadeneira F, Napoli N, Rauner M. Bone fragility in diabetes: novel concepts and clinical implications. Lancet Diabetes Endocrinol 2022; 10:207-220. [PMID: 35101185 DOI: 10.1016/s2213-8587(21)00347-8] [Citation(s) in RCA: 203] [Impact Index Per Article: 67.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/30/2021] [Revised: 12/09/2021] [Accepted: 12/09/2021] [Indexed: 12/12/2022]
Abstract
Increased fracture risk represents an emerging and severe complication of diabetes. The resulting prolonged immobility and hospitalisations can lead to substantial morbidity and mortality. In type 1 diabetes, bone mass and bone strength are reduced, resulting in up to a five-times greater risk of fractures throughout life. In type 2 diabetes, fracture risk is increased despite a normal bone mass. Conventional dual-energy x-ray absorptiometry might underestimate fracture risk, but can be improved by applying specific adjustments. Bone fragility in diabetes can result from cellular abnormalities, matrix interactions, immune and vascular changes, and musculoskeletal maladaptation to chronic hyperglycaemia. This Review summarises how the bone microenvironment responds to type 1 and type 2 diabetes, and the mechanisms underlying fragility fractures. We describe the value of novel imaging technologies and the clinical utility of biomarkers, and discuss current and future therapeutic approaches that protect bone health in people with diabetes.
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Affiliation(s)
- Lorenz C Hofbauer
- Division of Endocrinology, Diabetes and Bone Diseases, Department of Medicine III, and Center for Healthy Aging, University Medical Center, Technische Universität Dresden, Dresden, Germany.
| | - Björn Busse
- Department of Osteology and Biomechanics, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Richard Eastell
- Department of Oncology and Metabolism, Mellanby Centre for Musculoskeletal Research, University of Sheffield, Sheffield, UK
| | - Serge Ferrari
- Service and Laboratory of Bone Diseases, Geneva University Hospital and Faculty of Medicine, Geneva, Switzerland
| | - Morten Frost
- Molecular Endocrinology Laboratory and Steno Diabetes Centre Odense, Odense University Hospital, Odense, Denmark
| | - Ralph Müller
- Institute of Biomechanics, Department of Health Sciences and Technology, ETH Zurich, Zurich, Switzerland
| | - Andrea M Burden
- Institute of Pharmaceutical Sciences, Department of Chemistry and Applied Biosciences, ETH Zurich, Zurich, Switzerland
| | | | - Nicola Napoli
- RU of Endocrinology and Diabetes, Campus Bio-Medico University of Rome and Fondazione Policlinico Campus Bio-Medico, Rome, Italy; Division of Bone and Mineral Diseases, Washington University in St Louis, St Louis, MO, USA
| | - Martina Rauner
- Division of Endocrinology, Diabetes and Bone Diseases, Department of Medicine III, and Center for Healthy Aging, University Medical Center, Technische Universität Dresden, Dresden, Germany
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