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Aleksova J, Ebeling P, Elder G. The effects of type 1 and type 2 diabetes mellitus on bone health in chronic kidney disease. Nat Rev Endocrinol 2025:10.1038/s41574-024-01083-8. [PMID: 39820573 DOI: 10.1038/s41574-024-01083-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 12/16/2024] [Indexed: 01/19/2025]
Abstract
Fracture is an under-recognized but common complication of diabetes mellitus, with an incidence approaching twofold in type 2 diabetes mellitus (T2DM) and up to sevenfold in type 1 diabetes mellitus (T1DM) compared with that in the general population. Both T1DM and T2DM induce chronic hyperglycaemia, leading to the accumulation of advanced glycosylation end products that affect osteoblast function, increased collagen crosslinking and a senescence phenotype promoting inflammation. Together with an increased incidence of microvascular disease and an increased risk of vitamin D deficiency, these factors reduce bone quality, thereby increasing bone fragility. In T1DM, reduced anabolic stimuli as well as the presence of autoimmune conditions might also contribute to reduced bone mass and increased fragility. Diabetes mellitus is the most common cause of kidney failure, and fracture risk is exacerbated when chronic kidney disease (CKD)-related mineral and bone disorders are superimposed on diabetic changes. Microvascular pathology, cortical thinning and trabecular deterioration are particularly prominent in patients with T1DM and CKD, who suffer more fragility fractures than do other patients with CKD. This Review explores the pathophysiology of bone fragility in patients with diabetes mellitus and CKD and discusses techniques to predict fracture and pharmacotherapy that might reduce fracture risk.
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Affiliation(s)
- Jasna Aleksova
- Department of Medicine, School of Clinical Sciences at Monash Health, Monash University, Clayton, Victoria, Australia.
- Hudson Institute for Medical Research, Clayton, Victoria, Australia.
- Department of Endocrinology, Monash Health, Clayton, Victoria, Australia.
| | - Peter Ebeling
- Department of Medicine, School of Clinical Sciences at Monash Health, Monash University, Clayton, Victoria, Australia
- Department of Endocrinology, Monash Health, Clayton, Victoria, Australia
| | - Grahame Elder
- Department of Renal Medicine, Westmead Hospital, Westmead, New South Wales, Australia
- Garvan Institute of Medical Research, Darlinghurst, New South Wales, Australia
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Durgia H, Palui R, Sahoo J, Kamalanathan S, Naik D. Role of Anabolic Anti-Osteoporosis Therapy in Diabetes Subjects. Indian J Endocrinol Metab 2025; 29:32-38. [PMID: 40181849 PMCID: PMC11964375 DOI: 10.4103/ijem.ijem_81_24] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/11/2024] [Revised: 11/26/2024] [Accepted: 11/29/2024] [Indexed: 04/05/2025] Open
Abstract
Diabetes mellitus (DM) is a metabolic disorder that leads to the destruction of various tissues including bones. The pathogenesis of osteoporosis (OP) varies in DM due to many specific factors. DM increases the risk of fracture as well as post-fracture mortality. It is because of this fact that OP treatment should not be neglected in patients with DM. OP therapy comprises anabolic as well as anti-resorptive agents. Primary OP as observed in post-menopausal women is associated with high bone turnover, whereas OP in DM is a disease of low bone turnover. Therefore, anabolic agents seem to be quite promising in cases of OP in DM. Although the anti-fracture efficacy of these drugs is proven beyond any doubt in the general population without DM, evidence in persons with DM is limited. Among the anabolic agents, teriparatide has the most evidence in favor of its efficacy and safety in persons with DM. Studies evaluating other anabolic agents such as abaloparatide and romosozumab in diabetic osteopathy are scarce in the literature. Future studies specifically in both type 1 and type 2 DM populations are needed to evaluate the effects of osteoanabolic agents.
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Affiliation(s)
- Harsh Durgia
- Dr. Harsh’s Endocrine and Diabetes Center, Rajkot, Gujarat, India
| | - Rajan Palui
- Department of Endocrinology, The Mission Hospital, Durgapur, West Bengal, India
| | - Jayaprakash Sahoo
- Department of Endocrinology, Jawaharlal Institute of Postgraduate Medical Education and Research (JIPMER), Puducherry, India
| | - Sadishkumar Kamalanathan
- Department of Endocrinology, Jawaharlal Institute of Postgraduate Medical Education and Research (JIPMER), Puducherry, India
| | - Dukhabandhu Naik
- Department of Endocrinology, Jawaharlal Institute of Postgraduate Medical Education and Research (JIPMER), Puducherry, India
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ElSayed NA, McCoy RG, Aleppo G, Bajaj M, Balapattabi K, Beverly EA, Briggs Early K, Bruemmer D, Cusi K, Echouffo-Tcheugui JB, Ekhlaspour L, Fleming TK, Garg R, Khunti K, Lal R, Levin SR, Lingvay I, Matfin G, Napoli N, Pandya N, Parish SJ, Pekas EJ, Pilla SJ, Pirih FQ, Polsky S, Segal AR, Jeffrie Seley J, Stanton RC, Verduzco-Gutierrez M, Younossi ZM, Bannuru RR. 4. Comprehensive Medical Evaluation and Assessment of Comorbidities: Standards of Care in Diabetes-2025. Diabetes Care 2025; 48:S59-S85. [PMID: 39651988 PMCID: PMC11635044 DOI: 10.2337/dc25-s004] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/14/2024]
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Leungsuwan DS, Chandran M. Bone Fragility in Diabetes and its Management: A Narrative Review. Drugs 2024; 84:1111-1134. [PMID: 39103693 DOI: 10.1007/s40265-024-02078-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 07/24/2024] [Indexed: 08/07/2024]
Abstract
Bone fragility is a serious yet under-recognised complication of diabetes mellitus (DM) that is associated with significant morbidity and mortality. Multiple complex pathophysiological mechanisms mediating bone fragility amongst DM patients have been proposed and identified. Fracture risk in both type 1 diabetes (T1D) and type 2 diabetes (T2D) continues to be understated and underestimated by conventional risk assessment tools, posing an additional challenge to the identification of at-risk patients who may benefit from earlier intervention or preventive strategies. Over the years, an increasing body of evidence has demonstrated the efficacy of osteo-pharmacological agents in managing skeletal fragility in DM. This review seeks to elaborate on the risk of bone fragility in DM, the underlying pathogenesis and skeletal alterations, the approach to fracture risk assessment in DM, management strategies and therapeutic options.
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Affiliation(s)
| | - Manju Chandran
- Osteoporosis and Bone Metabolism Unit, Department of Endocrinology, Singapore General Hospital, 20 College Road, ACADEMIA, Singapore, 169856, Singapore.
- DUKE NUS Medical School, Singapore, Singapore.
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Sheu A, White CP, Center JR. Bone metabolism in diabetes: a clinician's guide to understanding the bone-glucose interplay. Diabetologia 2024; 67:1493-1506. [PMID: 38761257 PMCID: PMC11343884 DOI: 10.1007/s00125-024-06172-x] [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: 02/06/2024] [Accepted: 04/10/2024] [Indexed: 05/20/2024]
Abstract
Skeletal fragility is an increasingly recognised, but poorly understood, complication of both type 1 and type 2 diabetes. Fracture risk varies according to skeletal site and diabetes-related characteristics. Post-fracture outcomes, including mortality risk, are worse in those with diabetes, placing these people at significant risk. Each fracture therefore represents a sentinel event that warrants targeted management. However, diabetes is a very heterogeneous condition with complex interactions between multiple co-existing, and highly correlated, factors that preclude a clear assessment of the independent clinical markers and pathophysiological drivers for diabetic osteopathy. Additionally, fracture risk calculators and routinely used clinical bone measurements generally underestimate fracture risk in people with diabetes. In the absence of dedicated prospective studies including detailed bone and metabolic characteristics, optimal management centres around selecting treatments that minimise skeletal and metabolic harm. This review summarises the clinical landscape of diabetic osteopathy and outlines the interplay between metabolic and skeletal health. The underlying pathophysiology of skeletal fragility in diabetes and a rationale for considering a diabetes-based paradigm in assessing and managing diabetic bone disease will be discussed.
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Affiliation(s)
- Angela Sheu
- Skeletal Diseases Program, Garvan Institute of Medical Research, Sydney, Australia.
- Clinical School, St Vincent's Hospital, Faculty of Medicine, University of New South Wales Sydney, Sydney, Australia.
- Department of Endocrinology and Diabetes, St Vincent's Hospital, Sydney, Australia.
| | - Christopher P White
- Clinical School, Prince of Wales Hospital, Faculty of Medicine, University of New South Wales Sydney, Sydney, Australia
- Department of Endocrinology and Metabolism, Prince of Wales Hospital, Sydney, Australia
| | - Jacqueline R Center
- Skeletal Diseases Program, Garvan Institute of Medical Research, Sydney, Australia
- Clinical School, St Vincent's Hospital, Faculty of Medicine, University of New South Wales Sydney, Sydney, Australia
- Department of Endocrinology and Diabetes, St Vincent's Hospital, Sydney, Australia
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Forner P, Sheu A. Bone Health in Patients With Type 2 Diabetes. J Endocr Soc 2024; 8:bvae112. [PMID: 38887632 PMCID: PMC11181004 DOI: 10.1210/jendso/bvae112] [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: 03/03/2024] [Indexed: 06/20/2024] Open
Abstract
The association between type 2 diabetes mellitus (T2DM) and skeletal fragility is complex, with effects on bone at the cellular, molecular, and biomechanical levels. As a result, people with T2DM, compared to those without, are at increased risk of fracture, despite often having preserved bone mineral density (BMD) on dual-energy x-ray absorptiometry (DXA). Maladaptive skeletal loading and changes in bone architecture (particularly cortical porosity and low cortical volumes, the hallmark of diabetic osteopathy) are not apparent on routine DXA. Alternative imaging modalities, including quantitative computed tomography and trabecular bone score, allow for noninvasive visualization of cortical and trabecular compartments and may be useful in identifying those at risk for fractures. Current fracture risk calculators underestimate fracture risk in T2DM, partly due to their reliance on BMD. As a result, individuals with T2DM, who are at high risk of fracture, may be overlooked for commencement of osteoporosis therapy. Rather, management of skeletal health in T2DM should include consideration of treatment initiation at lower BMD thresholds, the use of adjusted fracture risk calculators, and consideration of metabolic and nonskeletal risk factors. Antidiabetic medications have differing effects on the skeleton and treatment choice should consider the bone impacts in those at risk for fracture. T2DM poses a unique challenge when it comes to assessing bone health and fracture risk. This article discusses the clinical burden and presentation of skeletal disease in T2DM. Two clinical cases are presented to illustrate a clinical approach in assessing and managing fracture risk in these patients.
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Affiliation(s)
- Patrice Forner
- Clinical School, Faculty of Medicine, St Vincent's Hospital, University of New South Wales Sydney, Sydney, NSW 2010, Australia
- Department of Endocrinology and Diabetes, St Vincent's Hospital, Sydney, NSW 2010, Australia
| | - Angela Sheu
- Clinical School, Faculty of Medicine, St Vincent's Hospital, University of New South Wales Sydney, Sydney, NSW 2010, Australia
- Department of Endocrinology and Diabetes, St Vincent's Hospital, Sydney, NSW 2010, Australia
- Skeletal Diseases Program, Garvan Institute of Medical Research, Darlinghurst, NSW 2035, Australia
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Martiniakova M, Biro R, Penzes N, Sarocka A, Kovacova V, Mondockova V, Omelka R. Links among Obesity, Type 2 Diabetes Mellitus, and Osteoporosis: Bone as a Target. Int J Mol Sci 2024; 25:4827. [PMID: 38732046 PMCID: PMC11084398 DOI: 10.3390/ijms25094827] [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: 04/05/2024] [Revised: 04/25/2024] [Accepted: 04/27/2024] [Indexed: 05/13/2024] Open
Abstract
Obesity, type 2 diabetes mellitus (T2DM) and osteoporosis are serious diseases with an ever-increasing incidence that quite often coexist, especially in the elderly. Individuals with obesity and T2DM have impaired bone quality and an elevated risk of fragility fractures, despite higher and/or unchanged bone mineral density (BMD). The effect of obesity on fracture risk is site-specific, with reduced risk for several fractures (e.g., hip, pelvis, and wrist) and increased risk for others (e.g., humerus, ankle, upper leg, elbow, vertebrae, and rib). Patients with T2DM have a greater risk of hip, upper leg, foot, humerus, and total fractures. A chronic pro-inflammatory state, increased risk of falls, secondary complications, and pharmacotherapy can contribute to the pathophysiology of aforementioned fractures. Bisphosphonates and denosumab significantly reduced the risk of vertebral fractures in patients with both obesity and T2DM. Teriparatide significantly lowered non-vertebral fracture risk in T2DM subjects. It is important to recognize elevated fracture risk and osteoporosis in obese and T2DM patients, as they are currently considered low risk and tend to be underdiagnosed and undertreated. The implementation of better diagnostic tools, including trabecular bone score, lumbar spine BMD/body mass index (BMI) ratio, and microRNAs to predict bone fragility, could improve fracture prevention in this patient group.
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Affiliation(s)
- Monika Martiniakova
- Department of Zoology and Anthropology, Faculty of Natural Sciences and Informatics, Constantine the Philosopher University in Nitra, 949 01 Nitra, Slovakia; (R.B.); (V.K.)
| | - Roman Biro
- Department of Zoology and Anthropology, Faculty of Natural Sciences and Informatics, Constantine the Philosopher University in Nitra, 949 01 Nitra, Slovakia; (R.B.); (V.K.)
| | - Noemi Penzes
- Department of Botany and Genetics, Faculty of Natural Sciences and Informatics, Constantine the Philosopher University in Nitra, 949 01 Nitra, Slovakia; (N.P.); (A.S.); (V.M.); (R.O.)
| | - Anna Sarocka
- Department of Botany and Genetics, Faculty of Natural Sciences and Informatics, Constantine the Philosopher University in Nitra, 949 01 Nitra, Slovakia; (N.P.); (A.S.); (V.M.); (R.O.)
| | - Veronika Kovacova
- Department of Zoology and Anthropology, Faculty of Natural Sciences and Informatics, Constantine the Philosopher University in Nitra, 949 01 Nitra, Slovakia; (R.B.); (V.K.)
| | - Vladimira Mondockova
- Department of Botany and Genetics, Faculty of Natural Sciences and Informatics, Constantine the Philosopher University in Nitra, 949 01 Nitra, Slovakia; (N.P.); (A.S.); (V.M.); (R.O.)
| | - Radoslav Omelka
- Department of Botany and Genetics, Faculty of Natural Sciences and Informatics, Constantine the Philosopher University in Nitra, 949 01 Nitra, Slovakia; (N.P.); (A.S.); (V.M.); (R.O.)
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Chen SY, Liao J, Huang PX, Wu KF, Deng LM. Bibliometric and visualized analysis of type 2 diabetic osteoporosis from 2013 to 2022. Arch Osteoporos 2024; 19:30. [PMID: 38647606 DOI: 10.1007/s11657-024-01386-3] [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: 08/10/2023] [Accepted: 04/09/2024] [Indexed: 04/25/2024]
Abstract
Type 2 diabetic osteoporosis (T2DOP) has received increasing attention from researchers. In this study, a total of 453 publications related to T2DOP from 2013 to 2022 were analyzed using bibliometric and visual analysis to identify the research trends and research hotspots in the field of T2DOP. PURPOSE The objective of this study was to conduct a comprehensive bibliometric analysis of T2DOP-related publications from 2013 to 2022 to determine global research trends in T2DOP in terms of number of publications, countries/regions, institutions, authors, journals, funding agencies, and keywords. METHODS All data were collected from the Web of Science Core Collection (WoSCC). All original research publications regarding T2DOP from 2013 to 2022 were retrieved. VOSviewer and Microsoft Office Excel were used to conduct the bibliometric and visual analysis. RESULTS From 2013 to 2022, 515 relevant publications were published, with a peak in 2022 in the annual number of publications. The countries leading the research were USA and China. Sugimoto was the most influential authors. Capital Medical University and Nanjing Medical University were the most prolific institutions. Osteoporosis International was the most productive journal concerning T2DOP research. National Natural Science Foundation of China was the primary funding source for this research area. "Bone-mineral density", "fracture risk", and "postmenopausal women" were the most high-frequency keywords over the past 10 years. CONCLUSION This was the first bibliometric study of diabetes mellitus and osteoporosis to exclusively examine type 2 diabetes mellitus. Our findings would provide guidance to understand the research frontiers and hot directions in the near future.
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Affiliation(s)
- Si-Yu Chen
- Marine Biomedical Research Institution, Guangdong Medical University, Zhanjiang, 524023, People's Republic of China
- Marine Biomedical Research Institution of Guangdong Zhanjiang, Zhanjiang, 524023, People's Republic of China
| | - Jing Liao
- The Affiliated Hospital of Guangdong Medical University, Zhanjiang, 524023, People's Republic of China
| | - Pei-Xin Huang
- Marine Biomedical Research Institution, Guangdong Medical University, Zhanjiang, 524023, People's Republic of China
- Marine Biomedical Research Institution of Guangdong Zhanjiang, Zhanjiang, 524023, People's Republic of China
| | - Ke-Feng Wu
- Marine Biomedical Research Institution, Guangdong Medical University, Zhanjiang, 524023, People's Republic of China.
- Marine Biomedical Research Institution of Guangdong Zhanjiang, Zhanjiang, 524023, People's Republic of China.
- GuangDong Engineering Technology Research Center for the Development and Utilization of Mangrove Wetland Medicinal Resources, Guangdong Medical University, Zhanjiang, 524023, People's Republic of China.
| | - Lu-Ming Deng
- Marine Biomedical Research Institution, Guangdong Medical University, Zhanjiang, 524023, People's Republic of China.
- Marine Biomedical Research Institution of Guangdong Zhanjiang, Zhanjiang, 524023, People's Republic of China.
- GuangDong Engineering Technology Research Center for the Development and Utilization of Mangrove Wetland Medicinal Resources, Guangdong Medical University, Zhanjiang, 524023, People's Republic of China.
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Vilaca T, Eastell R. Efficacy of Osteoporosis Medications in Patients with Type 2 Diabetes. Curr Osteoporos Rep 2024; 22:1-10. [PMID: 38093031 PMCID: PMC10912145 DOI: 10.1007/s11914-023-00833-3] [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] [Accepted: 10/25/2023] [Indexed: 03/05/2024]
Abstract
PURPOSE OF THE REVIEW The purpose of the review is to summarise the current scientific evidence on the efficacy of osteoporosis medications in patients with type 2 diabetes. RECENT FINDINGS Type 2 diabetes (T2D) is a growing global epidemic. The highest prevalence is observed in the elderly, the same population affected by osteoporosis. Despite normal or even increased bone mineral density and low bone turnover, T2D is associated with an increased risk of fractures in most skeletal sites. These findings raised concerns over the efficacy of anti-osteoporosis drugs in this population. There is no randomised controlled trial designed specifically for people with T2D. However, observational studies and post-hoc analyses of randomised controlled trials have provided valuable insights into the effects of various anti-osteoporosis treatments in this population. Overall, most anti-osteoporosis drugs seem to have similar efficacy and safety profiles for people with and without type 2 diabetes. However, continued research and long-term safety data are needed to optimise treatment strategies and improve bone health outcomes in this population. The current evidence suggests that most anti-osteoporosis drugs exhibit comparable efficacy in people with and without T2D.
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Affiliation(s)
- Tatiane Vilaca
- Mellanby Centre for Musculoskeletal Research, Division of Clinical Medicine, University of Sheffield, Sheffield, UK.
- Metabolic Bone Centre - Northern General Hospital, Herries Road, Sheffield, S5 7AU, UK.
| | - Richard Eastell
- Mellanby Centre for Musculoskeletal Research, Division of Clinical Medicine, University of Sheffield, Sheffield, UK
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ElSayed NA, Aleppo G, Bannuru RR, Bruemmer D, Collins BS, Cusi K, Ekhlaspour L, Fleming TK, Hilliard ME, Johnson EL, Khunti K, Lingvay I, Matfin G, McCoy RG, Napoli N, Perry ML, Pilla SJ, Polsky S, Prahalad P, Pratley RE, Segal AR, Seley JJ, Stanton RC, Verduzco-Gutierrez M, Younossi ZM, Gabbay RA. 4. Comprehensive Medical Evaluation and Assessment of Comorbidities: Standards of Care in Diabetes-2024. Diabetes Care 2024; 47:S52-S76. [PMID: 38078591 PMCID: PMC10725809 DOI: 10.2337/dc24-s004] [Citation(s) in RCA: 45] [Impact Index Per Article: 45.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/18/2023]
Abstract
The American Diabetes Association (ADA) "Standards of Care in Diabetes" includes the ADA's current clinical practice recommendations and is intended to provide the components of diabetes care, general treatment goals and guidelines, and tools to evaluate quality of care. Members of the ADA Professional Practice Committee, an interprofessional expert committee, are responsible for updating the Standards of Care annually, or more frequently as warranted. For a detailed description of ADA standards, statements, and reports, as well as the evidence-grading system for ADA's clinical practice recommendations and a full list of Professional Practice Committee members, please refer to Introduction and Methodology. Readers who wish to comment on the Standards of Care are invited to do so at professional.diabetes.org/SOC.
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Prasad TN, Arjunan D, Pal R, Bhadada SK. Diabetes and Osteoporosis. Indian J Orthop 2023; 57:209-217. [PMID: 38107797 PMCID: PMC10721588 DOI: 10.1007/s43465-023-01049-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/20/2023] [Accepted: 11/07/2023] [Indexed: 12/19/2023]
Abstract
Bone fragility is an emerging complication of diabetes. People with diabetes are at a significantly higher risk of fractures compared to the general population. Bone fragility occurs in diabetes as a result of complex and poorly understood mechanisms occurring at the cellular level contributed by vascular, inflammatory and mechanical derangements. Bone mineral density (BMD) as assessed by DEXA is low in type 1 diabetes. Type 2 diabetes has a high risk of fracture despite a normal to raised BMD. DEXA thus underestimates the fracture risk in diabetes. Data are scare regarding the efficacy of the available therapies in this low bone turnover state.
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Affiliation(s)
- Trupti Nagendra Prasad
- Department of Endocrinology, Postgraduate Institute of Medical Education and Research (PGIMER), Chandigarh, India
| | - Durairaj Arjunan
- Department of Endocrinology, Postgraduate Institute of Medical Education and Research (PGIMER), Chandigarh, India
| | - Rimesh Pal
- Department of Endocrinology, Postgraduate Institute of Medical Education and Research (PGIMER), Chandigarh, India
| | - Sanjay Kumar Bhadada
- Department of Endocrinology, Postgraduate Institute of Medical Education and Research (PGIMER), Chandigarh, India
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Vilaca T, Eastell R. Antiresorptive Versus Anabolic Therapy in Managing Osteoporosis in People with Type 1 and Type 2 Diabetes. JBMR Plus 2023; 7:e10838. [PMID: 38025034 PMCID: PMC10652175 DOI: 10.1002/jbm4.10838] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/30/2023] [Revised: 09/21/2023] [Accepted: 10/10/2023] [Indexed: 12/01/2023] Open
Abstract
Diabetes is characterized by hyperglycemia, but the two main types, type 1 diabetes (T1D) and type 2 diabetes (T2D), have distinct pathophysiology and epidemiological profiles. Individuals with T1D and T2D have an increased risk of fractures, particularly of the hip, upper arm, ankle, and nonvertebral sites. The risk of fractures is higher in T1D compared to T2D. The diagnosis of osteoporosis in individuals with T1D and T2D follows similar criteria as in the general population, but treatment thresholds may differ. Antiresorptive therapies, the first-line treatment for osteoporosis, are effective in individuals with T2D. Observational studies and post hoc analyses of previous trials have indicated that antiresorptive drugs, such as bisphosphonates and selective estrogen receptor modulators, are equally effective in reducing fracture risk and increasing bone mineral density (BMD) in individuals with and without T2D. Denosumab has shown similar effects on vertebral fracture risk but increases the risk of nonvertebral fractures. Considering the low bone turnover observed in T1D and T2D, anabolic therapies, which promote bone formation and resorption, have emerged as a potential treatment option for bone fragility in this population. Data from observational studies and post hoc analyses of previous trials also showed similar results in increasing BMD and reducing the risk of fractures in people with or without T2D. However, no evidence suggests that anabolic therapy has greater efficacy than antiresorptive drugs. In conclusion, there is an increased risk of fractures in T1D and T2D. Reductions in BMD cannot solely explain the relationship between T1D and T2D and fractures. Bone microarchitecture and other factors play a role. Antiresorptive and anabolic therapies have shown efficacy in reducing fracture risk in individuals with T2D, but the evidence is more robust for antiresorptive drugs. Evidence in T1D is scant. Further research is needed to fully understand the underlying mechanisms and optimize management strategies for bone fragility in T1D and T2D. © 2023 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.
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Affiliation(s)
- Tatiane Vilaca
- Mellanby Centre for Musculoskeletal Research, Department of Oncology and MetabolismUniversity of SheffieldSheffieldUK
| | - Richard Eastell
- Mellanby Centre for Musculoskeletal Research, Department of Oncology and MetabolismUniversity of SheffieldSheffieldUK
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Prasad TN, Bhadada SK, Singla V, Aggarwal N, Ram S, Saini UC, Kumar A, Pal R. Efficacy of zoledronate, denosumab or teriparatide in postmenopausal women with type 2 diabetes mellitus at high risk of fragility fractures: protocol of an open, blinded endpoint randomized controlled pilot trial. Ther Adv Endocrinol Metab 2023; 14:20420188231207516. [PMID: 37873516 PMCID: PMC10590540 DOI: 10.1177/20420188231207516] [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: 04/18/2023] [Accepted: 09/26/2023] [Indexed: 10/25/2023] Open
Abstract
Background People with type 2 diabetes (T2D) are at high risk of fragility fractures; however, there are no randomized controlled trials evaluating the efficacy of anti-osteoporosis drugs as a primary pre-specified endpoint in T2D. Objectives To compare the efficacy of anti-osteoporotic drugs in postmenopausal women with T2D. Design Prospective, randomized, open, blinded endpoint clinical pilot trial. Methods Postmenopausal women (⩾50 years) with T2D (duration ⩾5 years), HbA1c 7-10%, eGFR ⩾45 mL/min/1.73 m2 and prior vertebral (clinical/morphometric), hip, radius, humeral fragility fracture or bone mineral density (BMD) T-score (adjusted for diabetes) at lumbar spine/femoral neck ⩽-2.5 and high FRAX score will be eligible for inclusion. Subjects with secondary causes of osteoporosis, prior exposure to bone-active therapies or history of use of glucocorticoids/pioglitazone/thiazides/canagliflozin will be excluded. Finally, eligible subjects will undergo estimation of serum calcium, phosphate, alkaline phosphatase, parathyroid hormone, 25-hydroxyvitamin D and bone turnover markers (BTMs) (total procollagen type I N-propeptide, β-CTX) along with trabecular bone score (TBS) and high-resolution peripheral quantitative computed tomography (HR-pQCT) of non-dominant hand and leg. After a 2-week run in phase, they will be randomized in a 1:1:1:1 ratio to receive yearly zoledronate, or biannually denosumab or daily teriparatide (in addition to standard of care, i.e., calcium 1000 mg/day and cholecalciferol 1000 IU/day) or only standard of care (control). The primary endpoints will be change in areal BMD and frequency of incident fractures at 18 months. The secondary endpoints will be change in HR-pQCT parameters, TBS and BTMs at 18 months. Adverse events will be recorded for all randomized participants. Ethics The study has been approved by the Institute Ethics Committee. Written informed consent will be obtained from each participant. Discussion The trial is expected to provide information regarding optimal anti-osteoporotic therapy in people with T2D and bone fragility. Registration Prospectively registered in Clinical Trial Registry of India (CTRI/2022/02/039978).
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Affiliation(s)
- Trupti Nagendra Prasad
- Department of Endocrinology, Postgraduate Institute of Medical Education and Research, Chandigarh, India
| | - Sanjay Kumar Bhadada
- Department of Endocrinology, Postgraduate Institute of Medical Education and Research, Chandigarh, India
| | - Veenu Singla
- Department of Radiodiagnosis and Imaging, Postgraduate Institute of Medical Education and Research, Chandigarh, India
| | - Neelam Aggarwal
- Department of Gynaecology and Obstetrics, Postgraduate Institute of Medical Education and Research, Chandigarh, India
| | - Sant Ram
- Department of Biochemistry, Postgraduate Institute of Medical Education and Research, Chandigarh, India
| | - Uttam Chand Saini
- Department of Orthopaedics, Postgraduate Institute of Medical Education and Research, Chandigarh, India
| | - Ashok Kumar
- National Institute of Nursing Education (NINE), Postgraduate Institute of Medical Education and Research, Chandigarh, India
| | - Rimesh Pal
- Department of Endocrinology, Postgraduate Institute of Medical Education and Research, Chandigarh 160012, India
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14
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Sun S, Tao S, Xi X, Jiang T, Zhu Q, Zhou Y, Li H. Analysis of the predictive value of the Geriatric Nutritional Risk Index for osteoporosis in elderly patients with T2DM: a single-center retrospective study. J Orthop Surg Res 2023; 18:760. [PMID: 37805606 PMCID: PMC10560427 DOI: 10.1186/s13018-023-04237-y] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/10/2023] [Accepted: 09/26/2023] [Indexed: 10/09/2023] Open
Abstract
BACKGROUND Malnutrition is recognized as a risk factor for osteoporosis and T2DM. Previous studies have demonstrated the relationship between nutritional assessment tools and BMD. However, few studies have compared the effects of three nutritional risk assessment tools (GNRI, CONUT, and PNI). This study aimed to investigate the correlation between three nutritional assessment tools and BMD and to compare their validity in predicting osteoporosis in type 2 diabetes mellitus in the elderly. METHODS This retrospective study collected clinical data from 525 elderly patients with type 2 diabetes mellitus and categorized the patients into osteoporotic and non-osteoporotic groups. The correlation between the three nutritional assessment tools and BMD was analyzed using Spearman partial correlation. Binary logistics regression was used to analyze the relationship between GNRI and osteoporosis. ROC curves were used to compare the validity of GNRI, PNI, and CONUT in predicting osteoporosis. RESULTS Spearman's partial correlation showed a positive correlation between femoral neck BMD and lumbar spine BMD, but no correlation was observed between total hip BMD and GNRI. Logistic regression analyses showed no association between PNI, CONUT scores, and the development of osteoporosis. After adjusting for age, sex, smoking, alcohol consumption, BMI, ALB, Cr, UA, FBG, TG, and HDL, the correlation between GNRI and osteoporosis remained. ROC curve analysis showed that GNRI in combination with age and albumin had better predictive ability for osteoporosis than PNI and CONUT. CONCLUSION GNRI was an independent protective factor against osteoporosis in elderly patients with T2DM, and the predictive ability of GNRI for osteoporosis in elderly patients with T2DM was better than that of PNI and CONUT scores.
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Affiliation(s)
- Silu Sun
- School of Nursing, Chengdu Medical College, Tianhui Road, Chengdu, 610083, China
| | - Simin Tao
- School of Nursing, Chengdu Medical College, Tianhui Road, Chengdu, 610083, China
| | - Xiaoyan Xi
- Department of Orthopedics, The First Affiliated Hospital of Chengdu Medical College, 278 Baoguang Avenue, Middle Section, Chengdu, 610599, China
| | - Tao Jiang
- Department of Orthopedics, The First Affiliated Hospital of Chengdu Medical College, 278 Baoguang Avenue, Middle Section, Chengdu, 610599, China
| | - Qian Zhu
- School of Nursing, Chengdu Medical College, Tianhui Road, Chengdu, 610083, China
| | - Yan Zhou
- School of Nursing, Chengdu Medical College, Tianhui Road, Chengdu, 610083, China
| | - Hui Li
- School of Nursing, Chengdu Medical College, Tianhui Road, Chengdu, 610083, China.
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15
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Merugu C, Sahoo J, Kamalanathan S, Ramkumar G, Reddy SVB, Kar SS, Naik D, Roy A, Narayanan N, Patel D, Suryadevara V. Effect of a single dose of zoledronic acid on bone mineral density and trabecular bone score in Indian postmenopausal osteoporotic women with and without type 2 diabetes mellitus - A prospective cohort pilot study. Endocrine 2023; 82:171-180. [PMID: 37368233 DOI: 10.1007/s12020-023-03432-5] [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: 03/19/2023] [Accepted: 06/15/2023] [Indexed: 06/28/2023]
Abstract
PURPOSE The objectives were to study the effect of a single dose of intravenous (IV) zoledronic acid (ZA) on changes in bone mineral density (BMD) (lumbar spine (LS), hip, & distal forearm), trabecular bone score (TBS) and bone turnover markers (BTMs) in postmenopausal osteoporotic women with and without diabetes over 12 months. METHODS Patients were divided into two groups: type 2 diabetes mellitus (T2DM) (n = 40) and non-DM (n = 40). Both groups received a single dose of 4 mg IV ZA at baseline. The BMD with TBS and BTMs (β-CTX, sclerostin, P1NP) were measured at baseline, six months, and 12 months. RESULTS At baseline, BMD in all three sites was similar in both groups. T2DM patients were older and had lower BTMs than non-DM patients. The mean increase in LS-BMD (gram/cm2) at 12 months in T2DM and the non-DM group was 3.6 ± 4.7% and 6.2 ± 4.7 %, respectively (P = 0.01). However, the age adjusted mean difference in LS BMD increment between two groups at one year was - 2.86 % (-5.02% to -0.69%), P = 0.01. There was a comparable change in BMD at other two sites, BTMs, and TBS in both the groups over one year follow-up. CONCLUSION The gain in the LS-BMD was significantly lower in T2DM group compared to non-DM subjects over 12 months after a single IV infusion of 4 mg ZA. The explanation for this could be low bone turnover in diabetes subjects at baseline.
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Affiliation(s)
| | | | | | | | | | | | | | - Ayan Roy
- Department of Endocrinology, AIIMS, Kalyani, West Bengal, India
| | | | - Deepika Patel
- Department of Endocrinology, JIPMER, Puducherry, India
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16
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Marino S, Akel N, Li S, Cregor M, Jones M, Perez B, Troncoso G, Meeks J, Stewart S, Sato AY, Nookaew I, Bellido T. Reversal of the diabetic bone signature with anabolic therapies in mice. Bone Res 2023; 11:19. [PMID: 37076478 PMCID: PMC10115794 DOI: 10.1038/s41413-023-00261-0] [Citation(s) in RCA: 10] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/10/2023] [Revised: 03/01/2023] [Accepted: 03/22/2023] [Indexed: 04/21/2023] Open
Abstract
The mechanisms underlying the bone disease induced by diabetes are complex and not fully understood; and antiresorptive agents, the current standard of care, do not restore the weakened bone architecture. Herein, we reveal the diabetic bone signature in mice at the tissue, cell, and transcriptome levels and demonstrate that three FDA-approved bone-anabolic agents correct it. Diabetes decreased bone mineral density (BMD) and bone formation, damaged microarchitecture, increased porosity of cortical bone, and compromised bone strength. Teriparatide (PTH), abaloparatide (ABL), and romosozumab/anti-sclerostin antibody (Scl-Ab) all restored BMD and corrected the deteriorated bone architecture. Mechanistically, PTH and more potently ABL induced similar responses at the tissue and gene signature levels, increasing both formation and resorption with positive balance towards bone gain. In contrast, Scl-Ab increased formation but decreased resorption. All agents restored bone architecture, corrected cortical porosity, and improved mechanical properties of diabetic bone; and ABL and Scl-Ab increased toughness, a fracture resistance index. Remarkably, all agents increased bone strength over the healthy controls even in the presence of severe hyperglycemia. These findings demonstrate the therapeutic value of bone anabolic agents to treat diabetes-induced bone disease and suggest the need for revisiting the approaches for the treatment of bone fragility in diabetes.
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Affiliation(s)
- Silvia Marino
- Department of Physiology and Cell Biology, University of Arkansas for Medical Sciences, Little Rock, AR, USA
- Central Arkansas Veterans Healthcare System, John L. McClellan Little Rock, Little Rock, AR, USA
| | - Nisreen Akel
- Department of Physiology and Cell Biology, University of Arkansas for Medical Sciences, Little Rock, AR, USA
- Central Arkansas Veterans Healthcare System, John L. McClellan Little Rock, Little Rock, AR, USA
| | - Shenyang Li
- Central Arkansas Veterans Healthcare System, John L. McClellan Little Rock, Little Rock, AR, USA
| | - Meloney Cregor
- Department of Physiology and Cell Biology, University of Arkansas for Medical Sciences, Little Rock, AR, USA
- Central Arkansas Veterans Healthcare System, John L. McClellan Little Rock, Little Rock, AR, USA
| | - Meghan Jones
- Department of Physiology and Cell Biology, University of Arkansas for Medical Sciences, Little Rock, AR, USA
| | - Betiana Perez
- Department of Physiology and Cell Biology, University of Arkansas for Medical Sciences, Little Rock, AR, USA
| | - Gaston Troncoso
- Department of Physiology and Cell Biology, University of Arkansas for Medical Sciences, Little Rock, AR, USA
| | - Jomeeka Meeks
- Department of Physiology and Cell Biology, University of Arkansas for Medical Sciences, Little Rock, AR, USA
| | - Scott Stewart
- Department of Biostatistics, University of Arkansas for Medical Sciences, Little Rock, AR, USA
| | - Amy Y Sato
- Department of Physiology and Cell Biology, University of Arkansas for Medical Sciences, Little Rock, AR, USA
- Central Arkansas Veterans Healthcare System, John L. McClellan Little Rock, Little Rock, AR, USA
| | - Intawat Nookaew
- Department of Biomedical Informatics, University of Arkansas for Medical Sciences, Little Rock, AR, USA
- Winthrop P. Rockefeller Cancer Institute, University of Arkansas for Medical Sciences, Little Rock, AR, USA
| | - Teresita Bellido
- Department of Physiology and Cell Biology, University of Arkansas for Medical Sciences, Little Rock, AR, USA.
- Central Arkansas Veterans Healthcare System, John L. McClellan Little Rock, Little Rock, AR, USA.
- Winthrop P. Rockefeller Cancer Institute, University of Arkansas for Medical Sciences, Little Rock, AR, USA.
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17
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Cianferotti L, Cipriani C, Corbetta S, Corona G, Defeudis G, Lania AG, Messina C, Napoli N, Mazziotti G. Bone quality in endocrine diseases: determinants and clinical relevance. J Endocrinol Invest 2023:10.1007/s40618-023-02056-w. [PMID: 36918505 DOI: 10.1007/s40618-023-02056-w] [Citation(s) in RCA: 34] [Impact Index Per Article: 17.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/31/2022] [Accepted: 03/01/2023] [Indexed: 03/15/2023]
Abstract
PURPOSE Bone is one of the main targets of hormones and endocrine diseases are frequent causes of secondary osteoporosis and fractures in real-world clinical practice. However, diagnosis of skeletal fragility and prediction of fractures in this setting could be a challenge, since the skeletal alterations induced by endocrine disorders are not generally captured by dual-energy X-ray absorptiometry (DXA) measurement of bone mineral density (BMD), that is the gold standard for diagnosis of osteoporosis in the general population. The aim of this paper is to review the existing evidence related to bone quality features in endocrine diseases, proposing assessment with new techniques in the future. METHODS A comprehensive search within electronic databases was performed to collect reports of bone quality in primary hyperparathyroidism, hypoparathyroidism, hyperthyroidism, hypercortisolism, growth hormone deficiency, acromegaly, male hypogonadism and diabetes mellitus. RESULTS Using invasive and non-invasive techniques, such as high-resolution peripheral quantitative computed tomography or DXA measurement of trabecular bone score (TBS), several studies consistently reported altered bone quality as predominant determinant of fragility fractures in subjects affected by chronic endocrine disorders. CONCLUSIONS Assessment of skeletal fragility in endocrine diseases might take advantage from the use of techniques to detect perturbation in bone architecture with the aim of best identifying patients at high risk of fractures.
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Affiliation(s)
- L Cianferotti
- Department of Experimental and Clinical Biomedical Sciences "Mario Serio", University of Florence, Viale GB Morgagni 50, 50134, Florence, Italy
| | - C Cipriani
- Department of Clinical, Internal, Anesthesiological and Cardiovascular Sciences, Sapienza University of Rome, Viale del Policlinico 155, 00161, Rome, Italy
| | - S Corbetta
- Department of Biomedical, Surgical and Dental Sciences, University of Milan, Milan, Italy
- Endocrinology and Diabetology Service, IRCCS Istituto Ortopedico Galeazzi, Milan, Italy
| | - G Corona
- Endocrinology Unit, Medical Department, Azienda Usl, Maggiore-Bellaria Hospital, Bologna, Italy
| | - G Defeudis
- Unit of Endocrinology and Diabetes, Department of Medicine, University Campus Bio-Medico di Roma, 00128, Rome, Italy
- Department of Movement, Human and Health Sciences, Health Sciences Section, University "Foro Italico", Rome, Italy
| | - A G Lania
- Department of Biomedical Sciences, Humanitas University, Via R. Levi Montalcini 4, 20090, Pieve Emanuele, MI, Italy
- Endocrinology, Diabetology and Andrology Unit, IRCCS Humanitas Research Hospital, Via A Manzoni 56, 20089, Rozzano, MI, Italy
| | - C Messina
- Radiology Unit, IRCCS Istituto Ortopedico Galeazzi, Milan, Italy
- University of Milan, Department of Biomedical Sciences for Health, Milan, Italy
| | - N Napoli
- Unit of Endocrinology and Diabetes, Department of Medicine, University Campus Bio-Medico di Roma, 00128, Rome, Italy
- Division of Bone and Mineral Diseases, Washington University in St Louis, St Louis, MO, USA
| | - G Mazziotti
- Department of Biomedical Sciences, Humanitas University, Via R. Levi Montalcini 4, 20090, Pieve Emanuele, MI, Italy.
- Endocrinology, Diabetology and Andrology Unit, IRCCS Humanitas Research Hospital, Via A Manzoni 56, 20089, Rozzano, MI, Italy.
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18
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Sheu A, Greenfield JR, White CP, Center JR. Contributors to impaired bone health in type 2 diabetes. Trends Endocrinol Metab 2023; 34:34-48. [PMID: 36435679 DOI: 10.1016/j.tem.2022.11.003] [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: 09/14/2022] [Revised: 10/30/2022] [Accepted: 11/04/2022] [Indexed: 11/27/2022]
Abstract
Type 2 diabetes (T2D) is associated with numerous complications, including increased risk of fragility fractures, despite seemingly protective factors [e.g., normal bone mineral density and increased body mass index(BMI)]. However, fracture risk in T2D is underestimated by current fracture risk calculators. Importantly, post-fracture mortality is worse in T2D following any fracture, highlighting the importance of identifying high-risk patients that may benefit from targeted management. Several diabetes-related factors are associated with increased fracture risk, including exogenous insulin therapy, vascular complications, and poor glycaemic control, although detailed comprehensive studies to identify the independent contributions of these factors are lacking. The underlying pathophysiological mechanisms are complex and multifactorial, with different factors contributing during the course of T2D disease. These include obesity, hyperinsulinaemia, hyperglycaemia, accumulation of advanced glycation end products, and vascular supply affecting bone-cell function and survival and bone-matrix composition. This review summarises the current understanding of the contributors to impaired bone health in T2D, and proposes an updated approach to managing these patients.
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Affiliation(s)
- Angela Sheu
- Bone Biology Division, Garvan Institute of Medical Research, Sydney, Australia; Clinical School, St Vincent's Hospital, Faculty of Medicine, University of New South Wales Sydney, Sydney, Australia; Department of Endocrinology and Diabetes, St Vincent's Hospital, Sydney, Australia.
| | - Jerry R Greenfield
- Clinical School, St Vincent's Hospital, Faculty of Medicine, University of New South Wales Sydney, Sydney, Australia; Department of Endocrinology and Diabetes, St Vincent's Hospital, Sydney, Australia; Diabetes and Metabolism, Garvan Institute of Medical Research, Sydney, Australia
| | - Christopher P White
- Clinical School, Prince of Wales Hospital, Faculty of Medicine, University of New South Wales Sydney, Sydney, Australia; Department of Endocrinology and Metabolism, Prince of Wales Hospital, Sydney, Australia
| | - Jacqueline R Center
- Bone Biology Division, Garvan Institute of Medical Research, Sydney, Australia; Clinical School, St Vincent's Hospital, Faculty of Medicine, University of New South Wales Sydney, Sydney, Australia; Department of Endocrinology and Diabetes, St Vincent's Hospital, Sydney, Australia
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19
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Wu B, Fu Z, Wang X, Zhou P, Yang Q, Jiang Y, Zhu D. A narrative review of diabetic bone disease: Characteristics, pathogenesis, and treatment. Front Endocrinol (Lausanne) 2022; 13:1052592. [PMID: 36589835 PMCID: PMC9794857 DOI: 10.3389/fendo.2022.1052592] [Citation(s) in RCA: 33] [Impact Index Per Article: 11.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/24/2022] [Accepted: 12/01/2022] [Indexed: 12/23/2022] Open
Abstract
Recently, the increasing prevalence of diabetes mellitus has made it a major chronic illness which poses a substantial threat to human health. The prevalence of osteoporosis among patients with diabetes mellitus has grown considerably. Diabetic bone disease is a secondary osteoporosis induced by diabetes mellitus. Patients with diabetic bone disease exhibit variable degrees of bone loss, low bone mineral density, bone microarchitecture degradation, and increased bone fragility with continued diabetes mellitus, increasing their risk of fracture and impairing their ability to heal after fractures. At present, there is extensive research interest in diabetic bone disease and many significant outcomes have been reported. However, there are no comprehensive review is reported. This review elaborates on diabetic bone disease in the aspects of characteristics, pathogenesis, and treatment.
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Affiliation(s)
| | | | | | | | | | | | - Dong Zhu
- Department of Orthopaedic Trauma, Center of Orthopaedics and Traumatology, The First Hospital of Jilin University, Changchun, China
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20
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Zawada A, Ratajczak AE, Rychter AM, Szymczak-Tomczak A, Dobrowolska A, Krela-Kaźmierczak I. Treatment of Diabetes and Osteoporosis—A Reciprocal Risk? Biomedicines 2022; 10:biomedicines10092191. [PMID: 36140292 PMCID: PMC9495959 DOI: 10.3390/biomedicines10092191] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/05/2022] [Revised: 08/29/2022] [Accepted: 08/30/2022] [Indexed: 11/30/2022] Open
Abstract
Diabetes mellitus is a metabolic and systematic disorder that requires individualized therapy. The disease leads to various consequences, resulting in the destruction of tissues and organs. The aforementioned outcomes also include bone mineral disorders, caused by medications as well as diet therapy and physical activity. Some drugs may have a beneficial effect on both bone mineral density and the risk of fractures. Nevertheless, the impact of other medications remains unknown. Focusing on pharmacotherapy in diabetes may prevent bone mineral disorders and influence both the treatment and quality of life in patients suffering from diabetes mellitus. On the other hand, anti-osteoporosis drugs, such as antiresorptive or anabolic drugs, as well as drugs with a mixed mechanism of action, may affect carbohydrate metabolism, particularly in patients with diabetes. Therefore, the treatment of diabetes as well as osteoporosis prevention are vital for this group of patients.
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Affiliation(s)
- Agnieszka Zawada
- Department of Gastroenterology, Dietetics and Internal Diseases, Poznan University of Medical Sciences, 61-701 Poznn, Poland
- Correspondence: (A.Z.); (A.E.R.); Tel.: +48-667-385-996 or +48-8691-343 (A.E.R.); Fax: +48-8691-686 (A.E.R.)
| | - Alicja Ewa Ratajczak
- Department of Gastroenterology, Dietetics and Internal Diseases, Poznan University of Medical Sciences, 61-701 Poznn, Poland
- Doctoral School, Poznan University of Medical Sciences, 61-701 Poznan, Poland
- Correspondence: (A.Z.); (A.E.R.); Tel.: +48-667-385-996 or +48-8691-343 (A.E.R.); Fax: +48-8691-686 (A.E.R.)
| | - Anna Maria Rychter
- Department of Gastroenterology, Dietetics and Internal Diseases, Poznan University of Medical Sciences, 61-701 Poznn, Poland
- Doctoral School, Poznan University of Medical Sciences, 61-701 Poznan, Poland
| | - Aleksandra Szymczak-Tomczak
- Department of Gastroenterology, Dietetics and Internal Diseases, Poznan University of Medical Sciences, 61-701 Poznn, Poland
| | - Agnieszka Dobrowolska
- Department of Gastroenterology, Dietetics and Internal Diseases, Poznan University of Medical Sciences, 61-701 Poznn, Poland
| | - Iwona Krela-Kaźmierczak
- Department of Gastroenterology, Dietetics and Internal Diseases, Poznan University of Medical Sciences, 61-701 Poznn, Poland
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21
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Sheu A, Greenfield JR, White CP, Center JR. Assessment and treatment of osteoporosis and fractures in type 2 diabetes. Trends Endocrinol Metab 2022; 33:333-344. [PMID: 35307247 DOI: 10.1016/j.tem.2022.02.006] [Citation(s) in RCA: 60] [Impact Index Per Article: 20.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/23/2021] [Revised: 02/01/2022] [Accepted: 02/22/2022] [Indexed: 01/10/2023]
Abstract
There is substantial, and growing, evidence that type 2 diabetes (T2D) is associated with skeletal fragility, despite often preserved bone mineral density. As post-fracture outcomes, including mortality, are worse in people with T2D, bone management should be carefully considered in this highly vulnerable group. However, current fracture risk calculators inadequately predict fracture risk in T2D, and dedicated randomised controlled trials identifying optimal management in patients with T2D are lacking, raising questions about the ideal assessment and treatment of bone health in these people. We synthesise the current literature on evaluating bone measurements in T2D and summarise the evidence for safety and efficacy of both T2D and anti-osteoporosis medications in relation to bone health in these patients.
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Affiliation(s)
- Angela Sheu
- Bone Biology Division, Garvan Institute of Medical Research, Sydney, Australia; Clinical School, St Vincent's Hospital, Faculty of Medicine, University of New South Wales Sydney, Sydney, Australia; Department of Endocrinology and Diabetes, St Vincent's Hospital, Sydney, Australia.
| | - Jerry R Greenfield
- Clinical School, St Vincent's Hospital, Faculty of Medicine, University of New South Wales Sydney, Sydney, Australia; Department of Endocrinology and Diabetes, St Vincent's Hospital, Sydney, Australia; Diabetes and Metabolism, Garvan Institute of Medical Research, Sydney, Australia
| | - Christopher P White
- Clinical School, Prince of Wales Hospital, Faculty of Medicine, University of New South Wales Sydney, Sydney, Australia; Department of Endocrinology and Metabolism, Prince of Wales Hospital, Sydney, Australia
| | - Jacqueline R Center
- Bone Biology Division, Garvan Institute of Medical Research, Sydney, Australia; Clinical School, St Vincent's Hospital, Faculty of Medicine, University of New South Wales Sydney, Sydney, Australia; Department of Endocrinology and Diabetes, St Vincent's Hospital, Sydney, Australia
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22
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Effects of Type 2 Diabetes Mellitus on Osteoclast Differentiation, Activity, and Cortical Bone Formation in POSTmenopausal MRONJ Patients. J Clin Med 2022; 11:jcm11092377. [PMID: 35566506 PMCID: PMC9102751 DOI: 10.3390/jcm11092377] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/30/2022] [Revised: 04/20/2022] [Accepted: 04/21/2022] [Indexed: 01/22/2023] Open
Abstract
Osteoporosis is a common metabolic bone disease in patients with diabetes, which can develop simultaneously with type 2 diabetes (T2D) in postmenopausal women. Bisphosphonate (BP) is administered to patients with both conditions and may cause medication-related osteonecrosis of the jaw (MRONJ). It affects the differentiation and function of osteoclasts as well as the thickness of the cortical bone through bone mineralization. Therefore, this study aimed to investigate the effects of T2D on osteoclast differentiation and activity as well as cortical bone formation in postmenopausal patients with MRONJ. Tissue samples were collected from 10 patients diagnosed with T2D and stage III MRONJ in the experimental group and from 10 patients without T2D in the control group. A histological examination was conducted, and the expression of dendritic cell-specific transmembrane protein (DC-STAMP) and tartrate-resistant acid phosphatase (TRAP) was assessed. Cortical bone formation was analyzed using CBCT images. The number of TRAP-positive osteoclasts and DC-STAMP-positive mononuclear cells was significantly less in the experimental group (p < 0.05). Furthermore, the thickness and ratio of cortical bone were significantly greater in the experimental group (p < 0.05). In conclusion, T2D decreased the differentiation and function of osteoclasts and increased cortical bone formation in postmenopausal patients with MRONJ.
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23
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Munekawa C, Hashimoto Y, Kitagawa N, Osaka T, Hamaguchi M, Fukui M. Effect of Teriparatide on Bone Mineral Density and Trabecular Bone Score in Type 2 Diabetic Patients with Osteoporosis: A Retrospective Cohort Study. Medicina (B Aires) 2022; 58:medicina58040481. [PMID: 35454320 PMCID: PMC9030978 DOI: 10.3390/medicina58040481] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/21/2022] [Revised: 03/23/2022] [Accepted: 03/24/2022] [Indexed: 11/16/2022] Open
Abstract
The BMDs of the lumbar spine, whole femur, and femoral neck and TBS were measured. Change in BMD or TBS was defined as the BMD or TBS at follow-up, performed 1 year after baseline, minus baseline BMD or TBS. Results: This retrospective cohort study included 93 patients, of whom 52 received no medication, 26 received bisphosphonates, and 15 received weekly teriparatide. BMD of the lumbar spine increased in all three groups. There was no change in BMD of the whole femur and femoral neck in the no medication and bisphosphonates groups, whereas the BMD of the whole femur (from 0.73 (0.15) to 0.74 (0.15) g/cm2, p = 0.011) and femoral neck (from 0.59 (0.16) to 0.60 (0.16) g/cm2, p = 0.011) in the teriparatide group increased. The change in BMD of the femoral neck (no medication; −0.002 (0.034) g/cm2, bisphosphonates; −0.0001 (0.024) g/cm2, and teriparatide; 0.017 (0.022) g/cm2, p = 0.091) or TBS (no medication; −0.007 (0.051), bisphosphonates; −0.058 (0.258), and teriparatide; 0.021 (0.044), p = 0.191) in the teriparatide group tended to be higher than that in the other groups, although there was no statistically significant difference. Conclusions: Teriparatide increased the BMD of the femoral neck and TBS in osteoporosis patients with type 2 diabetes mellitus, compared to bisphosphonates and no medication.
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Affiliation(s)
- Chihiro Munekawa
- Department of Endocrinology and Metabolism, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto 602-8566, Japan; (C.M.); (N.K.); (T.O.); (M.H.); (M.F.)
| | - Yoshitaka Hashimoto
- Department of Endocrinology and Metabolism, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto 602-8566, Japan; (C.M.); (N.K.); (T.O.); (M.H.); (M.F.)
- Correspondence: ; Tel.: +81-75-251-5505
| | - Noriyuki Kitagawa
- Department of Endocrinology and Metabolism, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto 602-8566, Japan; (C.M.); (N.K.); (T.O.); (M.H.); (M.F.)
- Department of Diabetology, Kameoka Municipal Hospital, Kameoka 621-8585, Japan
| | - Takafumi Osaka
- Department of Endocrinology and Metabolism, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto 602-8566, Japan; (C.M.); (N.K.); (T.O.); (M.H.); (M.F.)
- Department of Endocrinology and Diabetology, Ayabe City Hospital, Ayabe 623-0011, Japan
| | - Masahide Hamaguchi
- Department of Endocrinology and Metabolism, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto 602-8566, Japan; (C.M.); (N.K.); (T.O.); (M.H.); (M.F.)
| | - Michiaki Fukui
- Department of Endocrinology and Metabolism, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto 602-8566, Japan; (C.M.); (N.K.); (T.O.); (M.H.); (M.F.)
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24
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Ebeling PR, Nguyen HH, Aleksova J, Vincent AJ, Wong P, Milat F. Secondary Osteoporosis. Endocr Rev 2022; 43:240-313. [PMID: 34476488 DOI: 10.1210/endrev/bnab028] [Citation(s) in RCA: 139] [Impact Index Per Article: 46.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/02/2020] [Indexed: 02/07/2023]
Abstract
Osteoporosis is a global public health problem, with fractures contributing to significant morbidity and mortality. Although postmenopausal osteoporosis is most common, up to 30% of postmenopausal women, > 50% of premenopausal women, and between 50% and 80% of men have secondary osteoporosis. Exclusion of secondary causes is important, as treatment of such patients often commences by treating the underlying condition. These are varied but often neglected, ranging from endocrine to chronic inflammatory and genetic conditions. General screening is recommended for all patients with osteoporosis, with advanced investigations reserved for premenopausal women and men aged < 50 years, for older patients in whom classical risk factors for osteoporosis are absent, and for all patients with the lowest bone mass (Z-score ≤ -2). The response of secondary osteoporosis to conventional anti-osteoporosis therapy may be inadequate if the underlying condition is unrecognized and untreated. Bone densitometry, using dual-energy x-ray absorptiometry, may underestimate fracture risk in some chronic diseases, including glucocorticoid-induced osteoporosis, type 2 diabetes, and obesity, and may overestimate fracture risk in others (eg, Turner syndrome). FRAX and trabecular bone score may provide additional information regarding fracture risk in secondary osteoporosis, but their use is limited to adults aged ≥ 40 years and ≥ 50 years, respectively. In addition, FRAX requires adjustment in some chronic conditions, such as glucocorticoid use, type 2 diabetes, and HIV. In most conditions, evidence for antiresorptive or anabolic therapy is limited to increases in bone mass. Current osteoporosis management guidelines also neglect secondary osteoporosis and these existing evidence gaps are discussed.
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Affiliation(s)
- Peter R Ebeling
- Department of Medicine, School of Clinical Sciences, Monash University, Clayton, Victoria 3168, Australia.,Department of Endocrinology, Monash Health, Clayton, Victoria 3168, Australia
| | - Hanh H Nguyen
- Department of Medicine, School of Clinical Sciences, Monash University, Clayton, Victoria 3168, Australia.,Department of Endocrinology, Monash Health, Clayton, Victoria 3168, Australia.,Department of Endocrinology and Diabetes, Western Health, Victoria 3011, Australia
| | - Jasna Aleksova
- Department of Endocrinology, Monash Health, Clayton, Victoria 3168, Australia.,Hudson Institute of Medical Research, Clayton, Victoria 3168, Australia
| | - Amanda J Vincent
- Department of Endocrinology, Monash Health, Clayton, Victoria 3168, Australia.,Monash Centre for Health Research and Implementation, School of Public Health and Preventative Medicine, Monash University, Clayton, Victoria 3168, Australia
| | - Phillip Wong
- Department of Medicine, School of Clinical Sciences, Monash University, Clayton, Victoria 3168, Australia.,Department of Endocrinology, Monash Health, Clayton, Victoria 3168, Australia.,Hudson Institute of Medical Research, Clayton, Victoria 3168, Australia
| | - Frances Milat
- Department of Medicine, School of Clinical Sciences, Monash University, Clayton, Victoria 3168, Australia.,Department of Endocrinology, Monash Health, Clayton, Victoria 3168, Australia.,Hudson Institute of Medical Research, Clayton, Victoria 3168, Australia
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25
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Bidwell J, Tersey SA, Adaway M, Bone RN, Creecy A, Klunk A, Atkinson EG, Wek RC, Robling AG, Wallace JM, Evans-Molina C. Nmp4, a Regulator of Induced Osteoanabolism, Also Influences Insulin Secretion and Sensitivity. Calcif Tissue Int 2022; 110:244-259. [PMID: 34417862 PMCID: PMC8792173 DOI: 10.1007/s00223-021-00903-7] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/22/2021] [Accepted: 08/04/2021] [Indexed: 02/03/2023]
Abstract
A bidirectional and complex relationship exists between bone and glycemia. Persons with type 2 diabetes (T2D) are at risk for bone loss and fracture, however, heightened osteoanabolism may ameliorate T2D-induced deficits in glycemia as bone-forming osteoblasts contribute to energy metabolism via increased glucose uptake and cellular glycolysis. Mice globally lacking nuclear matrix protein 4 (Nmp4), a transcription factor expressed in all tissues and conserved between humans and rodents, are healthy and exhibit enhanced bone formation in response to anabolic osteoporosis therapies. To test whether loss of Nmp4 similarly impacted bone deficits caused by diet-induced obesity, male wild-type and Nmp4-/- mice (8 weeks) were fed either low-fat diet or high-fat diet (HFD) for 12 weeks. Endpoint parameters included bone architecture, structural and estimated tissue-level mechanical properties, body weight/composition, glucose-stimulated insulin secretion, glucose tolerance, insulin tolerance, and metabolic cage analysis. HFD diminished bone architecture and ultimate force and stiffness equally in both genotypes. Unexpectedly, the Nmp4-/- mice exhibited deficits in pancreatic β-cell function and were modestly glucose intolerant under normal diet conditions. Despite the β-cell deficits, the Nmp4-/- mice were less sensitive to HFD-induced weight gain, increases in % fat mass, and decreases in glucose tolerance and insulin sensitivity. We conclude that Nmp4 supports pancreatic β-cell function but suppresses peripheral glucose utilization, perhaps contributing to its suppression of induced skeletal anabolism. Selective disruption of Nmp4 in peripheral tissues may provide a strategy for improving both induced osteoanabolism and energy metabolism in comorbid patients.
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Affiliation(s)
- Joseph Bidwell
- Department of Anatomy, Cell Biology, & Physiology (ACBP), Indiana University School of Medicine (IUSM), Indianapolis, IN, 46202, USA.
- Indiana Center for Musculoskeletal Health, IUSM, Indianapolis, USA.
| | - Sarah A Tersey
- Department of Pediatrics, Indiana University School of Medicine (IUSM), Indianapolis, IN, 46202, USA
- Section of Endocrinology, Diabetes and Metabolism, Department of Medicine, The University of Chicago, Chicago, IL, 60637, USA
| | - Michele Adaway
- Department of Anatomy, Cell Biology, & Physiology (ACBP), Indiana University School of Medicine (IUSM), Indianapolis, IN, 46202, USA
| | - Robert N Bone
- Department of Pediatrics, Indiana University School of Medicine (IUSM), Indianapolis, IN, 46202, USA
- Center for Diabetes and Metabolic Disease and the Wells Center for Pediatric Research, IUSM, Indianapolis, IN, 46202, USA
| | - Amy Creecy
- Department of Biomedical Engineering, Indiana University-Purdue University at Indianapolis (IUPUI), Indianapolis, IN, 46202, USA
| | - Angela Klunk
- Department of Anatomy, Cell Biology, & Physiology (ACBP), Indiana University School of Medicine (IUSM), Indianapolis, IN, 46202, USA
| | - Emily G Atkinson
- Department of Anatomy, Cell Biology, & Physiology (ACBP), Indiana University School of Medicine (IUSM), Indianapolis, IN, 46202, USA
| | - Ronald C Wek
- Department of Biochemistry & Molecular Biology, IUSM, Indianapolis, USA
| | - Alexander G Robling
- Department of Anatomy, Cell Biology, & Physiology (ACBP), Indiana University School of Medicine (IUSM), Indianapolis, IN, 46202, USA
- Indiana Center for Musculoskeletal Health, IUSM, Indianapolis, USA
| | - Joseph M Wallace
- Indiana Center for Musculoskeletal Health, IUSM, Indianapolis, USA.
- Department of Biomedical Engineering, Indiana University-Purdue University at Indianapolis (IUPUI), Indianapolis, IN, 46202, USA.
| | - Carmella Evans-Molina
- Department of Pediatrics, Indiana University School of Medicine (IUSM), Indianapolis, IN, 46202, USA.
- Center for Diabetes and Metabolic Disease and the Wells Center for Pediatric Research, IUSM, Indianapolis, IN, 46202, USA.
- Richard L. Roudebush VA Medical Center, Indianapolis, USA.
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26
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Peng S, Gao Y, Shi S, Zhao D, Cao H, Fu T, Cai X, Xiao J. LncRNA-AK137033 inhibits the osteogenic potential of adipose-derived stem cells in diabetic osteoporosis by regulating Wnt signaling pathway via DNA methylation. Cell Prolif 2022; 55:e13174. [PMID: 34953002 PMCID: PMC8780896 DOI: 10.1111/cpr.13174] [Citation(s) in RCA: 16] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/11/2021] [Revised: 12/06/2021] [Accepted: 12/09/2021] [Indexed: 02/05/2023] Open
Abstract
OBJECTIVES Bone tissue engineering based on adipose-derived stem cells (ASCs) is expected to become a new treatment for diabetic osteoporosis (DOP) patients with bone defects. However, compared with control ASCs (CON-ASCs), osteogenic potential of DOP-ASCs is decreased, which increased the difficulty of bone reconstruction in DOP patients. Moreover, the cause of the poor osteogenesis of ASCs in a hyperglycemic microenvironment has not been elucidated. Therefore, this study explored the molecular mechanism of the decline in the osteogenic potential of DOP-ASCs from the perspective of epigenetics to provide a possible therapeutic target for bone repair in DOP patients with bone defects. MATERIALS AND METHODS An animal model of DOP was established in mice. CON-ASCs and DOP-ASCs were isolated from CON and DOP mice, respectively. AK137033 small interfering RNA (SiRNA) and an AK137033 overexpression plasmid were used to regulate the expression of AK137033 in CON-ASCs and DOP-ASCs in vitro. Lentiviruses that carried shRNA-AK137033 or AK137033 cDNA were used to knockdown or overexpress AK137033, respectively, in CON-ASCs and DOP-ASCs in vivo. Hematoxylin and eosin (H&E), Masson's, alizarin red, and alkaline phosphatase (ALP) staining, micro-computed tomography (Micro-CT), flow cytometry, qPCR, western blotting, immunofluorescence, and bisulfite-specific PCR (BSP) were used to analyze the functional changes of ASCs. RESULTS The DOP mouse model was established successfully. Compared with CON-ASCs, AK137033 expression, the DNA methylation level of the sFrp2 promoter region, Wnt signaling pathway markers, and the osteogenic differentiation potential were decreased in DOP-ASCs. In vitro experiments showed that AK137033 silencing inhibited the Wnt signaling pathway and osteogenic ability of CON-ASCs by reducing the DNA methylation level in the sFrp2 promoter region. Additionally, overexpression of AK137033 in DOP-ASCs rescued these changes caused by DOP. Moreover, the same results were obtained in vivo. CONCLUSIONS LncRNA-AK137033 inhibits the osteogenic potential of DOP-ASCs by regulating the Wnt signaling pathway via modulating the DNA methylation level in the sFrp2 promoter region. This study provides an important reference to find new targets for the treatment of bone defects in DOP patients.
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Affiliation(s)
- Shuanglin Peng
- Department of Oral ImplantologyThe Affiliated Stomatology Hospital of Southwest Medical UniversityLuzhouChina
- State Key Laboratory of Oral DiseasesWest China Hospital of StomatologySichuan UniversityChengduChina
- National Key Clinical SpecialtyThe Affiliated Hospital of Southwest Medical UniversityLuzhouChina
| | - Yujin Gao
- Department of Oral ImplantologyThe Affiliated Stomatology Hospital of Southwest Medical UniversityLuzhouChina
- Orofacial Reconstruction and Regeneration LaboratoryThe Affiliated Stomatology Hospital of Southwest Medical UniversityLuzhouChina
- Department of Oral and Maxillofacial SurgeryThe Affiliated Stomatology Hospital of Southwest Medical UniversityLuzhouChina
| | - Sirong Shi
- State Key Laboratory of Oral DiseasesWest China Hospital of StomatologySichuan UniversityChengduChina
| | - Dan Zhao
- State Key Laboratory of Oral DiseasesWest China Hospital of StomatologySichuan UniversityChengduChina
| | - Huayue Cao
- Department of Oral ImplantologyThe Affiliated Stomatology Hospital of Southwest Medical UniversityLuzhouChina
- National Key Clinical SpecialtyThe Affiliated Hospital of Southwest Medical UniversityLuzhouChina
- Department of Oral and Maxillofacial SurgeryThe Affiliated Stomatology Hospital of Southwest Medical UniversityLuzhouChina
| | - Ting Fu
- Department of Oral ImplantologyThe Affiliated Stomatology Hospital of Southwest Medical UniversityLuzhouChina
- National Key Clinical SpecialtyThe Affiliated Hospital of Southwest Medical UniversityLuzhouChina
- Department of Oral and Maxillofacial SurgeryThe Affiliated Stomatology Hospital of Southwest Medical UniversityLuzhouChina
| | - Xiaoxiao Cai
- State Key Laboratory of Oral DiseasesWest China Hospital of StomatologySichuan UniversityChengduChina
| | - Jingang Xiao
- Department of Oral ImplantologyThe Affiliated Stomatology Hospital of Southwest Medical UniversityLuzhouChina
- National Key Clinical SpecialtyThe Affiliated Hospital of Southwest Medical UniversityLuzhouChina
- Orofacial Reconstruction and Regeneration LaboratoryThe Affiliated Stomatology Hospital of Southwest Medical UniversityLuzhouChina
- Department of Oral and Maxillofacial SurgeryThe Affiliated Stomatology Hospital of Southwest Medical UniversityLuzhouChina
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27
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Vescini F, Chiodini I, Falchetti A, Palermo A, Salcuni AS, Bonadonna S, De Geronimo V, Cesareo R, Giovanelli L, Brigo M, Bertoldo F, Scillitani A, Gennari L. Management of Osteoporosis in Men: A Narrative Review. Int J Mol Sci 2021; 22:ijms222413640. [PMID: 34948434 PMCID: PMC8705761 DOI: 10.3390/ijms222413640] [Citation(s) in RCA: 33] [Impact Index Per Article: 8.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/20/2021] [Revised: 12/13/2021] [Accepted: 12/15/2021] [Indexed: 12/12/2022] Open
Abstract
Male osteoporosis is a still largely underdiagnosed pathological condition. As a consequence, bone fragility in men remains undertreated mainly due to the low screening frequency and to controversies in the bone mineral density (BMD) testing standards. Up to the 40% of overall osteoporotic fractures affect men, in spite of the fact that women have a significant higher prevalence of osteoporosis. In addition, in males, hip fractures are associated with increased morbidity and mortality as compared to women. Importantly, male fractures occur about 10 years later in life than women, and, therefore, due to the advanced age, men may have more comorbidities and, consequently, their mortality is about twice the rate in women. Gender differences, which begin during puberty, lead to wider bones in males as compared with females. In men, follicle-stimulating hormones, testosterone, estrogens, and sex hormone-binding levels, together with genetic factors, interact in determining the peak of bone mass, BMD maintenance, and lifetime decrease. As compared with women, men are more frequently affected by secondary osteoporosis. Therefore, in all osteoporotic men, a complete clinical history should be collected and a careful physical examination should be done, in order to find clues of a possible underlying diseases and, ultimately, to guide laboratory testing. Currently, the pharmacological therapy of male osteoporosis includes aminobisphosphonates, denosumab, and teriparatide. Hypogonadal patients may be treated with testosterone replacement therapy. Given that the fractures related to mortality are higher in men than in women, treating male subjects with osteoporosis is of the utmost importance in clinical practice, as it may impact on mortality even more than in women.
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Affiliation(s)
- Fabio Vescini
- Endocrinology and Metabolism Unit, University-Hospital S. Maria della Misericordia, 33100 Udine, Italy; (F.V.); (A.S.S.)
| | - Iacopo Chiodini
- Istituto Auxologico Italiano, IRCCS, 20149 Milan, Italy; (A.F.); (S.B.)
- Department of Medical Biotechnology and Translational Medicine, University of Milan, 20122 Milan, Italy;
- Correspondence:
| | - Alberto Falchetti
- Istituto Auxologico Italiano, IRCCS, 20149 Milan, Italy; (A.F.); (S.B.)
| | - Andrea Palermo
- Unit of Endocrinology and Diabetes, Campus Bio-Medico University, 00128 Rome, Italy;
| | - Antonio Stefano Salcuni
- Endocrinology and Metabolism Unit, University-Hospital S. Maria della Misericordia, 33100 Udine, Italy; (F.V.); (A.S.S.)
| | - Stefania Bonadonna
- Istituto Auxologico Italiano, IRCCS, 20149 Milan, Italy; (A.F.); (S.B.)
- Department of Medical Biotechnology and Translational Medicine, University of Milan, 20122 Milan, Italy;
| | | | - Roberto Cesareo
- Center of Metabolic Disease, S.M. Goretti Hospital, 04100 Latina, Italy;
| | - Luca Giovanelli
- Department of Medical Biotechnology and Translational Medicine, University of Milan, 20122 Milan, Italy;
| | - Martina Brigo
- Department of Medicine, University of Verona, 37129 Verona, Italy; (M.B.); (F.B.)
| | - Francesco Bertoldo
- Department of Medicine, University of Verona, 37129 Verona, Italy; (M.B.); (F.B.)
| | - Alfredo Scillitani
- Unit of Endocrinology, Ospedale “Casa Sollievo della Sofferenza”, IRCCS, San Giovanni Rotondo, 71013 Foggia, Italy;
| | - Luigi Gennari
- Department of Medicine, Surgery and Neurosciences, University of Siena, 53100 Siena, Italy;
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28
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Shah M, Appuswamy AV, Rao SD, Dhaliwal R. Treatment of bone fragility in patients with diabetes: antiresorptive versus anabolic? Curr Opin Endocrinol Diabetes Obes 2021; 28:377-382. [PMID: 34010225 PMCID: PMC8244995 DOI: 10.1097/med.0000000000000645] [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] [Indexed: 11/26/2022]
Abstract
PURPOSE OF REVIEW The pathogenesis of bone fragility in diabetes has not been fully characterized. The antifracture efficacy of available therapies remains unproven in patients with diabetes. We aim to collate current evidence of the treatment of diabetic bone fragility, and to provide a rationale for considering optimal therapeutic option in patients with diabetes. RECENT FINDINGS The antifracture efficacy of antiresorptive and anabolic therapies is well established in patients without diabetes. Studies in patients with osteoporosis have shown that anabolic therapies lead to faster and larger benefits to bone mineral density and offer greater protection against fracture than antiresorptive therapies. Available data suggest that antiresorptive and anabolic therapies have similar effect on bone density and fracture risk reduction in patients with and without diabetes. However, the evidence in diabetes is limited to observational studies and post hoc analyses of osteoporosis studies. SUMMARY There are no specific guidelines for the treatment of bone fragility in patients with diabetes. We offer a rationale for use of anabolic therapies in diabetes which is a low bone formation state, in contrast to postmenopausal osteoporosis that is characterized by increased bone turnover. Prospective studies evaluating the effect of available therapies on bone quality and fracture outcomes in patients with diabetes are needed.
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Affiliation(s)
- Meghna Shah
- Metabolic Bone Disease Center, State University of New York Upstate Medical University, NY
| | | | - Sudhaker D. Rao
- Bone and Mineral Research Laboratory, Henry Ford Hospital, Detroit, MI
| | - Ruban Dhaliwal
- Metabolic Bone Disease Center, State University of New York Upstate Medical University, NY
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29
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Chiodini I, Gaudio A, Palermo A, Napoli N, Vescini F, Falchetti A, Merlotti D, Eller-Vainicher C, Carnevale V, Scillitani A, Pugliese G, Rendina D, Salcuni A, Bertoldo F, Gonnelli S, Nuti R, Toscano V, Triggiani V, Cenci S, Gennari L. Management of bone fragility in type 2 diabetes: Perspective from an interdisciplinary expert panel. Nutr Metab Cardiovasc Dis 2021; 31:2210-2233. [PMID: 34059385 DOI: 10.1016/j.numecd.2021.04.014] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/28/2021] [Revised: 04/11/2021] [Accepted: 04/15/2021] [Indexed: 12/22/2022]
Abstract
AIM Bone fragility is increasingly recognized as a relevant complication of type 2 diabetes (T2D) and diabetic patients with fragility fractures have higher mortality rates than non diabetic individuals or diabetic patients without fractures. However, current diagnostic approaches for fracture risk stratification, such as bone mineral density measurement or the use of risk assessment algorithms, largely underestimate fracture risk in T2D patients. A multidisciplinary expert panel was established in order to in order to formulate clinical consensus recommendations on bone health assessment and management of fracture risk in patients with T2D. DATA SYNTHESIS The following key questions were addressed: a) which are the risk factors for bone fragility in T2D?, b) which diagnostic procedures can be currently used to stratify fracture risk in T2D patients?, c) which are the effects of antidiabetic treatments on bone?, and d) how to prevent and treat bone fragility in T2D patients? Based on the available data members of this panel suggest that the stratification of fracture risk in patients with diabetes should firstly rely on the presence of a previous fragility fracture and on the individual risk profile, with the inclusion of T2D-specific risk factors (namely T2D duration above 10 yrs, presence of chronic T2D complications, use of insulin or thiazolidinediones and persistent HbA1c levels above 8% for at least 1 year). Two independent diagnostic approaches were then suggested in the presence or the absence of a prevalent fragility fracture, respectively. CONCLUSIONS Clinical trials in T2D patients at risk for fragility fractures are needed to determine the efficacy and safety of available antiresorptive and anabolic agents in this specific setting.
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Affiliation(s)
- Iacopo Chiodini
- Unit for Bone Metabolism Diseases and Diabetes and Lab of Endocrine and Metabolic Research, IRCCS Istituto Auxologico Italiano, Milan, Italy; Department of Medical Science and Community Health, University of Milan, Milan, Italy
| | - Agostino Gaudio
- Department of Clinical and Experimental Medicine, University of Catania, University Hospital "G. Rodolico" Catania, Italy
| | - Andrea Palermo
- Department of Endocrinology and Diabetes, University Campus Bio-Medico, Rome, Italy
| | - Nicola Napoli
- Department of Endocrinology and Diabetes, University Campus Bio-Medico, Rome, Italy
| | - Fabio Vescini
- Endocrinology and Metabolism Unit, University-Hospital S. M. Misericordia of Udine, Italy
| | - Alberto Falchetti
- Unit for Bone Metabolism Diseases and Diabetes and Lab of Endocrine and Metabolic Research, IRCCS Istituto Auxologico Italiano, Milan, Italy; EndOsMet, Villa Donatello Private Hospital, Florence, Italy
| | - Daniela Merlotti
- Department of Medicine, Surgery and Neurosciences, University of Siena, Policlinico Le Scotte, Siena, Italy; Division of Genetics and Cell Biology, San Raffaele Scientific Institute, Milan, Italy
| | | | - Vincenzo Carnevale
- Unit of Internal Medicine, "Casa Sollievo della Sofferenza" Hospital, IRCCS, San Giovanni Rotondo, (FG), Italy
| | - Alfredo Scillitani
- Unit of Endocrinology, "Casa Sollievo della Sofferenza" Hospital, IRCCS, San Giovanni Rotondo, (FG), Italy
| | - Giuseppe Pugliese
- Department of Clinical and Molecular Medicine, "La Sapienza" University, and Diabetes Unit, Sant'Andrea University Hospital, Rome, Italy
| | - Domenico Rendina
- Department of Clinical Medicine and Surgery, "Federico II" University of Naples, Naples, Italy
| | - Antonio Salcuni
- Endocrinology Unit, Department of Medical Sciences and Public Health, University of Cagliari, Cagliari, Italy
| | - Francesco Bertoldo
- Department of Medicine, University of Verona, Policlinico GB Rossi, Verona, Italy
| | - Stefano Gonnelli
- Department of Medicine, Surgery and Neurosciences, University of Siena, Policlinico Le Scotte, Siena, Italy
| | - Ranuccio Nuti
- Department of Medicine, Surgery and Neurosciences, University of Siena, Policlinico Le Scotte, Siena, Italy
| | - Vincenzo Toscano
- Department of Clinical and Molecular Medicine, "La Sapienza" University, Rome, Italy
| | - Vincenzo Triggiani
- Interdisciplinary Department of Medicine, Section of Internal Medicine, Geriatrics, Endocrinology and Rare Diseases. University of Bari "Aldo Moro", Bari, Italy
| | - Simone Cenci
- Division of Genetics and Cell Biology, San Raffaele Scientific Institute, Milan, Italy
| | - Luigi Gennari
- Department of Medicine, Surgery and Neurosciences, University of Siena, Policlinico Le Scotte, Siena, Italy.
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30
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Palui R, Pramanik S, Mondal S, Ray S. Critical review of bone health, fracture risk and management of bone fragility in diabetes mellitus. World J Diabetes 2021; 12:706-729. [PMID: 34168723 PMCID: PMC8192255 DOI: 10.4239/wjd.v12.i6.706] [Citation(s) in RCA: 17] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/27/2021] [Revised: 04/08/2021] [Accepted: 04/29/2021] [Indexed: 02/06/2023] Open
Abstract
The risk of fracture is increased in both type 1 diabetes mellitus (T1DM) and type 2 diabetes mellitus (T2DM). However, in contrast to the former, patients with T2DM usually possess higher bone mineral density. Thus, there is a considerable difference in the pathophysiological basis of poor bone health between the two types of diabetes. Impaired bone strength due to poor bone microarchitecture and low bone turnover along with increased risk of fall are among the major factors behind elevated fracture risk. Moreover, some antidiabetic medications further enhance the fragility of the bone. On the other hand, antiosteoporosis medications can affect the glucose homeostasis in these patients. It is also difficult to predict the fracture risk in these patients because conventional tools such as bone mineral density and Fracture Risk Assessment Tool score assessment can underestimate the risk. Evidence-based recommendations for risk evaluation and management of poor bone health in diabetes are sparse in the literature. With the advancement in imaging technology, newer modalities are available to evaluate the bone quality and risk assessment in patients with diabetes. The purpose of this review is to explore the pathophysiology behind poor bone health in diabetic patients. Approach to the fracture risk evaluation in both T1DM and T2DM as well as the pragmatic use and efficacy of the available treatment options have been discussed in depth.
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Affiliation(s)
- Rajan Palui
- Department of Endocrinology, The Mission Hospital, Durgapur 713212, West Bengal, India
| | - Subhodip Pramanik
- Department of Endocrinology, Neotia Getwel Healthcare Centre, Siliguri 734010, West Bengal, India
| | - Sunetra Mondal
- Department of Endocrinology, Institute of Post Graduate Medical Education and Research (IPGMER), Kolkata 700020, West Bengal, India
| | - Sayantan Ray
- Department of Endocrinology, Medica Superspeciality Hospital and Medica Clinic, Kolkata 700099, West Bengal, India
- Department of Endocrinology, Jagannath Gupta Institute of Medical Sciences and Hospital, Kolkata 700137, West Bengal, India
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31
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Napoli N, Incalzi RA, De Gennaro G, Marcocci C, Marfella R, Papalia R, Purrello F, Ruggiero C, Tarantino U, Tramontana F, Conte C. Bone fragility in patients with diabetes mellitus: A consensus statement from the working group of the Italian Diabetes Society (SID), Italian Society of Endocrinology (SIE), Italian Society of Gerontology and Geriatrics (SIGG), Italian Society of Orthopaedics and Traumatology (SIOT). Nutr Metab Cardiovasc Dis 2021; 31:1375-1390. [PMID: 33812734 DOI: 10.1016/j.numecd.2021.01.019] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/18/2021] [Revised: 01/24/2021] [Accepted: 01/25/2021] [Indexed: 02/08/2023]
Abstract
Bone fragility is one of the possible complications of diabetes, either type 1 (T1D) or type 2 (T2D). Bone fragility can affect patients of different age and with different disease severity depending on type of diabetes, disease duration and the presence of other complications. Fracture risk assessment should be started at different stages in the natural history of the disease depending on the type of diabetes and other risk factors. The risk of fracture in T1D is higher than in T2D, imposing a much earlier screening and therapeutic intervention that should also take into account a patient's life expectancy, diabetes complications etc. The therapeutic armamentarium for T2D has been enriched with drugs that may influence bone metabolism, and clinicians should be aware of these effects. Considering the complexity of diabetes and osteoporosis and the range of variables that influence treatment choices in a given individual, the Working Group on bone fragility in patients with diabetes mellitus has identified and issued recommendations based on the variables that should guide screening of bone fragility and management of diabetes and bone fragility: (A)ge, (B)MD, (C)omplications, (D)uration of disease, & (F)ractures (ABCD&F). Consideration of these parameters may help clinicians identify the best time for screening, the appropriate glycaemic target and anti-osteoporosis drug for patients with diabetes at risk of or with bone fragility.
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Affiliation(s)
- Nicola Napoli
- Unit of Endocrinology and Diabetes, Departmental Faculty of Medicine and Surgery, Campus Bio-Medico University of Rome, Rome, Italy; Division of Bone and Mineral Diseases, Washington University in St. Louis, St. Louis, MO, USA.
| | - Raffaele A Incalzi
- Unit of Geriatrics, Departmental Faculty of Medicine and Surgery, Campus Bio-Medico University of Rome, Rome, Italy.
| | - Giovanni De Gennaro
- Diabetes Center, Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy
| | - Claudio Marcocci
- Endocrinology Unit, Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy
| | - Raffaele Marfella
- Department of Advanced Medical and Surgical Sciences, University of Campania "Luigi Vanvitelli", Naples, Italy
| | - Rocco Papalia
- Unit of Orthopedic and Trauma Surgery, Departmental Faculty of Medicine and Surgery, Campus Bio-Medico University of Rome, Rome, Italy
| | - Francesco Purrello
- Department of Clinical and Experimental Medicine, University of Catania, 95100 Catania, Italy; Department of Clinical and Experimental Medicine, Internal Medicine, Garibaldi-Nesima Hospital, University of Catania, Catania, Italy
| | - Carmelinda Ruggiero
- Institute of Gerontology and Geriatrics, Department of Medicine, University of Perugia, Perugia, Italy
| | - Umberto Tarantino
- Department of Clinical Sciences and Translational Medicine, Faculty of Medicine and Surgery, "Tor Vergata" University of Rome, Rome, Italy; Department of Orthopaedics and Traumatology, "Policlinico Tor Vergata" Foundation, Rome, Italy
| | - Flavia Tramontana
- Unit of Endocrinology and Diabetes, Departmental Faculty of Medicine and Surgery, Campus Bio-Medico University of Rome, Rome, Italy
| | - Caterina Conte
- Department of Human Sciences and Promotion of the Quality of Life, San Raffaele Roma Open University, Rome, Italy; Department of Endocrinology, Nutrition and Metabolic Diseases, IRCCS MultiMedica, Milan, Italy
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Anastasilakis AD, Tsourdi E, Tabacco G, Naciu AM, Napoli N, Vescini F, Palermo A. The Impact of Antiosteoporotic Drugs on Glucose Metabolism and Fracture Risk in Diabetes: Good or Bad News? J Clin Med 2021; 10:jcm10050996. [PMID: 33801212 PMCID: PMC7957889 DOI: 10.3390/jcm10050996] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/17/2021] [Revised: 02/18/2021] [Accepted: 02/22/2021] [Indexed: 12/20/2022] Open
Abstract
Osteoporosis and diabetes mellitus represent global health problems due to their high, and increasing with aging, prevalence in the general population. Osteoporosis can be successfully treated with both antiresorptive and anabolic drugs. While these drugs are clearly effective in reducing the risk of fracture in patients with postmenopausal and male osteoporosis, it is still unclear whether they may have the same efficacy in patients with diabetic osteopathy. Furthermore, as bone-derived cytokines (osteokines) are able to influence glucose metabolism, it is conceivable that antiosteoporotic drugs may have an effect on glycemic control through their modulation of bone turnover that affects the osteokines’ release. These aspects are addressed in this narrative review by means of an unrestricted computerized literature search in the PubMed database. Our findings indicate a balance between good and bad news. Active bone therapies and their modulation of bone turnover do not appear to play a clinically significant role in glucose metabolism in humans. Moreover, there are insufficient data to clarify whether there are any differences in the efficacy of antiosteoporotic drugs on fracture incidence between diabetic and nondiabetic patients with osteoporosis. Although more studies are required for stronger recommendations to be issued, bisphosphonates appear to be the first-line drug for treatment of osteoporosis in diabetic patients, while denosumab seems preferable for older patients, particularly for those with impaired renal function, and osteoanabolic agents should be reserved for patients with more severe forms of osteoporosis.
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Affiliation(s)
| | - Elena Tsourdi
- Department of Medicine (III) &Center for Healthy Aging, Technische Universität Dresden Medical Center, 01307 Dresden, Germany
- Correspondence: ; Tel.: +49-351-458-12933; Fax: +49-351-458-5801
| | - Gaia Tabacco
- Unit of Endocrinology and Diabetes, Campus Bio-Medico University, 00128 Rome, Italy; (G.T.); (A.M.N.); (N.N.); (A.P.)
| | - Anda Mihaela Naciu
- Unit of Endocrinology and Diabetes, Campus Bio-Medico University, 00128 Rome, Italy; (G.T.); (A.M.N.); (N.N.); (A.P.)
| | - Nicola Napoli
- Unit of Endocrinology and Diabetes, Campus Bio-Medico University, 00128 Rome, Italy; (G.T.); (A.M.N.); (N.N.); (A.P.)
| | - Fabio Vescini
- Department of Endocrinology and Diabetes, Santa Maria della Misericordia Hospital, 33100 Udine, Italy;
| | - Andrea Palermo
- Unit of Endocrinology and Diabetes, Campus Bio-Medico University, 00128 Rome, Italy; (G.T.); (A.M.N.); (N.N.); (A.P.)
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33
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Postmenopausal osteoporosis coexisting with other metabolic diseases: Treatment considerations. Maturitas 2021; 147:19-25. [PMID: 33832643 DOI: 10.1016/j.maturitas.2021.02.007] [Citation(s) in RCA: 18] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/13/2021] [Revised: 02/18/2021] [Accepted: 02/27/2021] [Indexed: 12/13/2022]
Abstract
In postmenopausal women, osteoporosis may coexist with other metabolic diseases, including, but not limited to, obesity, diabetes, nonalcoholic fatty liver disease (NAFLD), dyslipidemia and cardiovascular disease (CVD). This association may lie beyond simple coincidence owing to high prevalence of all these diseases, especially in the aging population, as common pathogenetic mechanisms between them and osteoporosis may exist. In this context, anti-osteoporotic medications may affect the pathogenesis of some of these metabolic diseases; this is an important consideration when selecting the most appropriate medication for osteoporotic patients with coexistent metabolic diseases. Conversely, some current or emerging medications for metabolic diseases adversely affect bone metabolism and, if possible, should be avoided in women with postmenopausal osteoporosis. The main aim of this review is to summarize the evidence on anti-osteoporotic treatment in postmenopausal women with concomitant metabolic diseases, i.e. obesity, diabetes, NAFLD, dyslipidemia and CVD. The secondary aim is to present data on the effect of current or emerging medication for metabolic diseases on bone metabolism of postmenopausal women. Deeper understanding of the underlying links between osteoporosis and metabolic diseases may have clinical implications. However, mechanistic studies are needed to elucidate the potential pathophysiological links, as well as clinical trials in women with postmenopausal osteoporosis coexisting with specific metabolic diseases; these may guide clinical practice in the future for the selection of the best anti-osteoporotic medication for each patient with specific metabolic diseases.
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Romero-Díaz C, Duarte-Montero D, Gutiérrez-Romero SA, Mendivil CO. Diabetes and Bone Fragility. Diabetes Ther 2021; 12:71-86. [PMID: 33185853 PMCID: PMC7843783 DOI: 10.1007/s13300-020-00964-1] [Citation(s) in RCA: 32] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/06/2020] [Accepted: 10/29/2020] [Indexed: 02/08/2023] Open
Abstract
Diabetes is a highly prevalent disease with complications that impact most bodily systems. However, the impact of diabetes on bone health is frequently ignored or underestimated. Both type 1 (T1D) and type 2 diabetes (T2D) are associated with a higher risk of fractures, albeit through different mechanisms. T1D is characterized by near total insulinopenia, which affects the anabolic tone of bone and results in reduced bone mineral density (BMD). Meanwhile, patients with T2D have normal or high BMD, but carry an increased risk of fractures due to alterations of bone microarchitecture and a local humoral environment that stimulates osteoclast activity. Chronic hyperglycemia induces non-enzymatic glycation of collagen in both types of diabetes. Epidemiological evidence confirms a largely increased fracture risk in T1D and T2D, but also that it can be substantially reduced by opportune monitoring of fracture risk and appropriate treatment of both diabetes itself and osteopenia or osteoporosis if they are present. In this review, we summarize the mechanistic, epidemiological, and clinical evidence that links diabetes and bone fragility, and describe the impact of available diabetes treatments on bone health.
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Affiliation(s)
| | | | | | - Carlos O Mendivil
- School of Medicine, Universidad de los Andes, Bogotá, Colombia.
- Department of Internal Medicine, Endocrinology Section, Fundación Santa Fe de Bogotá, Bogotá, Colombia.
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Kanazawa I, Inaba M, Inoue D, Uenishi K, Saito M, Shiraki M, Suzuki A, Takeuchi Y, Hagino H, Fujiwara S, Sugimoto T. Executive summary of clinical practice guide on fracture risk in lifestyle diseases. J Bone Miner Metab 2020; 38:746-758. [PMID: 32892240 DOI: 10.1007/s00774-020-01149-3] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/02/2020] [Accepted: 08/23/2020] [Indexed: 12/16/2022]
Abstract
Accumulating evidence has shown that patients with lifestyle diseases such as type 2 diabetes mellitus, chronic kidney disease, and chronic obstructive pulmonary disease are at increased risk of osteoporotic fracture. Fractures deteriorate quality of life, activities of daily living, and mortality as well as a lifestyle disease. Therefore, preventing fracture is an important issue for those patients. Although the mechanism of the lifestyle diseases-induced bone fragility is still unclear, not only bone mineral density (BMD) reduction but also bone quality deterioration are involved in it. Because fracture predictive ability of BMD and FRAX® is limited, especially for patients with lifestyle diseases, the optimal management strategy should be established. Thus, when the intervention of the lifestyle diseases-induced bone fragility is initiated, the deterioration of bone quality should be taken into account. We here review the association between lifestyle diseases and fracture risk and proposed an algorism of starting anti-osteoporosis drugs for patients with lifestyle diseases.
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Affiliation(s)
- Ippei Kanazawa
- Kanazawa Diabetes and Osteoporosis Clinic, 990-2-1 Enya-cho, Izumo, Shimane, 693-0021, Japan.
| | - Masaaki Inaba
- Department of Metabolism, Endocrinology, and Molecular Medicine, Osaka City University Graduate School of Medicine, Osaka, Japan
| | - Daisuke Inoue
- Third Department of Medicine, Teikyo University Chiba Medical Center, Chiba, Japan
| | - Kazuhiro Uenishi
- Division of Nutritional Physiology, Kagawa Nutrition University, Saitama, Japan
| | - Mitsuru Saito
- Department of Orthopaedic Surgery, Jikei University School of Medicine, Tokyo, Japan
| | - Masataka Shiraki
- Research Institute and Practice for Involutional Diseases, Nagano, Japan
| | - Atsushi Suzuki
- Department of Endocrinology and Metabolism, Fujita Health University, Aichi, Japan
| | - Yasuhiro Takeuchi
- Endocrine Center, Toranomon Hospital and Okinaka Memorial Institute for Medical Research, Tokyo, Japan
| | - Hiroshi Hagino
- School of Health Science Faculty of Medicine, Tottori University, Tottori, Japan
| | - Saeko Fujiwara
- Department of Pharmacy, Yasuda Women's University, Hiroshima, Japan
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Ferrari S, Eastell R, Napoli N, Schwartz A, Hofbauer LC, Chines A, Wang A, Pannacciulli N, Cummings SR. Denosumab in postmenopausal women with osteoporosis and diabetes: Subgroup analysis of FREEDOM and FREEDOM extension. Bone 2020; 134:115268. [PMID: 32058020 DOI: 10.1016/j.bone.2020.115268] [Citation(s) in RCA: 39] [Impact Index Per Article: 7.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/17/2019] [Revised: 01/22/2020] [Accepted: 02/09/2020] [Indexed: 01/06/2023]
Abstract
PURPOSE Diabetes and osteoporosis occur frequently in older adults and are both associated with increased fracture risk. Denosumab treatment reduced new vertebral, nonvertebral, and hip fractures over 3 years, with continued low fracture incidence for up to 10 years in postmenopausal women with osteoporosis. However, its effects in diabetic subjects with osteoporosis have not yet been investigated. METHODS Post hoc analysis of the 3-year, placebo-controlled FREEDOM study and 7-year Extension included postmenopausal women with osteoporosis and diabetes. Effects on BMD, vertebral, and nonvertebral fracture incidence were evaluated. RESULTS Of 7808 subjects in FREEDOM, 508 with diabetes received denosumab (n = 266) or placebo (n = 242). Among those, BMD increased significantly with denosumab versus placebo in FREEDOM, and continued to increase during the Extension in long-term (continuing denosumab) and crossover (placebo to denosumab) denosumab subjects. In FREEDOM, denosumab-treated subjects with diabetes had significantly lower new vertebral fracture rates (1.6%) versus placebo (8.0%) (RR: 0.20 [95% CI 0.07-0.61]; p = .001). Nonvertebral fracture incidence was higher with denosumab (11.7%) versus placebo (5.9%) (HR: 1.94 [95% CI 1.00-3.77]; p = .046), although there were fewer hip fractures with denosumab (World Health Organization, 2017 [1]) than placebo (4; nonsignificant). During the first 3 years in FREEDOM Extension, new vertebral and nonvertebral fracture incidences were low in long-term and crossover denosumab diabetic groups (≤6%), consistent with the overall Extension population; yearly nonvertebral fracture incidence was comparable to the FREEDOM placebo group. CONCLUSION Denosumab significantly increased BMD and decreased vertebral fracture risk in subjects with osteoporosis and diabetes. No reduction in nonvertebral fractures was observed.
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Affiliation(s)
- Serge Ferrari
- Division of Bone Diseases, Geneva University Hospitals, Geneva, Switzerland.
| | - Richard Eastell
- Academic unit of Bone Metabolism, University of Sheffield, Sheffield, UK
| | - Nicola Napoli
- John T. Milliken Department of Medicine, Campus Bio-Medico, University of Rome, Rome, Italy; Ospedale Galeazzi IRCCS, Milan, Italy
| | - Ann Schwartz
- School of Medicine, University of California San Francisco, San Francisco, CA, USA
| | - Lorenz C Hofbauer
- Center for Healthy Aging and Division of Endocrinology, Diabetes, and Bone Diseases, Technische Universität Dresden, Dresden, Germany
| | - Arkadi Chines
- Global Development, Amgen Inc., Thousand Oaks, CA, USA
| | - Andrea Wang
- Global Biostatistical Science, Amgen Inc., Thousand Oaks, CA, USA
| | | | - Steven R Cummings
- School of Medicine, University of California San Francisco, San Francisco, CA, USA
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Dhaliwal R, Hans D, Hattersley G, Mitlak B, Fitzpatrick LA, Wang Y, Schwartz AV, Miller PD, Josse RG. Abaloparatide in Postmenopausal Women With Osteoporosis and Type 2 Diabetes: A Post Hoc Analysis of the ACTIVE Study. JBMR Plus 2020; 4:e10346. [PMID: 32258965 PMCID: PMC7117849 DOI: 10.1002/jbm4.10346] [Citation(s) in RCA: 33] [Impact Index Per Article: 6.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/19/2019] [Revised: 01/15/2020] [Accepted: 01/26/2020] [Indexed: 01/06/2023] Open
Abstract
Type 2 diabetes mellitus (T2DM) increases fracture risk despite normal or increased BMD. Abaloparatide reduces fracture risk in patients with postmenopausal osteoporosis (PMO); however, its efficacy in women with T2DM is unknown. This post hoc analysis evaluated the efficacy and safety of abaloparatide in patients with T2DM. The analysis included patients with T2DM from the Abaloparatide Comparator Trial In Vertebral Endpoints (ACTIVE), a phase 3, double‐blind, randomized, placebo‐ and active‐controlled trial. In ACTIVE, participants were randomized 1:1:1 to daily s.c. injections of placebo, abaloparatide (80 μg), or open‐label teriparatide (20 μg) for 18 months. A total of 198 women with PMO and T2DM from 21 centers in 10 countries were identified from ACTIVE through review of their medical records. The main outcomes measured included effect of abaloparatide versus placebo on BMD and trabecular bone score (TBS), with secondary outcomes of fracture risk and safety, in patients from ACTIVE with T2DM. Significant (p < 0.001) improvements in BMD at total hip (mean change 3.0% versus −0.4%), femoral neck (2.6% versus −0.2%), and lumbar spine (8.9% versus 1.3%) and TBS at lumbar spine (3.72% versus −0.56%) were observed with abaloparatide versus placebo at 18 months. Fracture events were fewer with abaloparatide treatment in patients with T2DM, and differences were not significant between groups except nonvertebral fractures in the abaloparatide versus placebo groups (p = 0.04). Safety was consistent with the ACTIVE population. In conclusion, in women with PMO and T2DM, abaloparatide treatment resulted in significant improvements in BMD and TBS versus placebo, consistent with the overall ACTIVE population © 2020 The Authors. JBMR Plus published by Wiley Periodicals, Inc. on behalf of American Society for Bone and Mineral Research.
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Affiliation(s)
- Ruban Dhaliwal
- Metabolic Bone Disease Center State University of New York Upstate Medical University Syracuse NY USA
| | - Didier Hans
- Center of Bone Disease, Bones & Joints Department Lausanne University Hospital Lausanne Switzerland
| | | | - Bruce Mitlak
- Clinical Development, Radius Health, Inc. Waltham MA USA
| | | | - Yamei Wang
- Biostatistics, Radius Health, Inc. Waltham MA USA
| | - Ann V Schwartz
- Department of Epidemiology and Biostatistics UCSF School of Medicine San Francisco CA USA
| | - Paul D Miller
- Research, Colorado Center for Bone Research Lakewood CO USA
| | - Robert G Josse
- Research, St. Michael's Hospital University of Toronto Toronto Canada
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38
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Liu JM, Zhu DL, Mu YM, Xia WB. Management of fracture risk in patients with diabetes-Chinese Expert Consensus. J Diabetes 2019; 11:906-919. [PMID: 31219236 DOI: 10.1111/1753-0407.12962] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/05/2019] [Revised: 05/20/2019] [Accepted: 06/17/2019] [Indexed: 02/06/2023] Open
Affiliation(s)
- Jian-Min Liu
- Department of Endocrine and Metabolic Diseases, Rui-jin Hospital, Shanghai Jiao-tong University School of Medicine, Shanghai, China
| | - Da-Long Zhu
- Department of Endocrinology, Nanjing Drum Tower Hospital Affiliated to Nanjing University Medical School, Nanjing, China
| | - Yi-Ming Mu
- Department of Endocrinology, The General Hospital of the Chinese People's Liberation Army, Beijing, China
| | - Wei-Bo Xia
- Department of Endocrinology, Peking Union Medical College Hospital, Chinese Academy of Medical Science, Beijing, China
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39
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Costantini S, Conte C. Bone health in diabetes and prediabetes. World J Diabetes 2019; 10:421-445. [PMID: 31523379 PMCID: PMC6715571 DOI: 10.4239/wjd.v10.i8.421] [Citation(s) in RCA: 53] [Impact Index Per Article: 8.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/06/2019] [Revised: 06/03/2019] [Accepted: 07/20/2019] [Indexed: 02/05/2023] Open
Abstract
Bone fragility has been recognized as a complication of diabetes, both type 1 diabetes (T1D) and type 2 diabetes (T2D), whereas the relationship between prediabetes and fracture risk is less clear. Fractures can deeply impact a diabetic patient's quality of life. However, the mechanisms underlying bone fragility in diabetes are complex and have not been fully elucidated. Patients with T1D generally exhibit low bone mineral density (BMD), although the relatively small reduction in BMD does not entirely explain the increase in fracture risk. On the contrary, patients with T2D or prediabetes have normal or even higher BMD as compared with healthy subjects. These observations suggest that factors other than bone mass may influence fracture risk. Some of these factors have been identified, including disease duration, poor glycemic control, presence of diabetes complications, and certain antidiabetic drugs. Nevertheless, currently available tools for the prediction of risk inadequately capture diabetic patients at increased risk of fracture. Aim of this review is to provide a comprehensive overview of bone health and the mechanisms responsible for increased susceptibility to fracture across the spectrum of glycemic status, spanning from insulin resistance to overt forms of diabetes. The management of bone fragility in diabetic patient is also discussed.
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Affiliation(s)
- Silvia Costantini
- Department of Immunology, Transplantation and Infectious Diseases, Vita-Salute San Raffaele University, Milan 20123, Italy
- Epatocentro Ticino, Lugano 6900, Switzerland
| | - Caterina Conte
- Department of Immunology, Transplantation and Infectious Diseases, Vita-Salute San Raffaele University, Milan 20123, Italy
- IRCCS Ospedale San Raffaele, Internal Medicine and Transplantation, Milan 20123, Italy
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40
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Hygum K, Starup-Linde J, Langdahl BL. Diabetes and bone. Osteoporos Sarcopenia 2019; 5:29-37. [PMID: 31346556 PMCID: PMC6630041 DOI: 10.1016/j.afos.2019.05.001] [Citation(s) in RCA: 26] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/14/2019] [Revised: 04/11/2019] [Accepted: 05/03/2019] [Indexed: 12/16/2022] Open
Abstract
Bone disease is a serious complication to diabetes. Patients with type 1 diabetes (T1D) and type 2 diabetes (T2D) suffer from an increased risk of fracture, most notably at the hip, compared with patients without diabetes. Confounders such as patient sex, age, body mass index, blood glucose status, fall risk, and diabetes medications may influence the fracture risk. Different underlying mechanisms contribute to bone disease in patients with diabetes. Bone quality is affected by low bone turnover in T1D and T2D, and furthermore, incorporation of advanced glycation end-products, changes in the incretin hormone response, and microvascular complications contribute to impaired bone quality and increased fracture risk. Diagnosis of bone disease in patients with diabetes is a challenge as current methods for fracture prediction such as bone mineral density T-score and fracture risk assessment tools underestimate fracture risk for patients with T1D and T2D. This review focuses on bone disease and fracture risk in patients with diabetes regarding epidemiology, underlying disease mechanisms, and diagnostic methods, and we also provide considerations regarding the management of diabetes patients with bone disease in terms of an intervention threshold and different treatments.
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Affiliation(s)
| | | | - Bente L. Langdahl
- Department of Endocrinology and Internal Medicine, Aarhus University Hospital, Aarhus, Denmark
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41
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Bone disorders associated with diabetes mellitus and its treatments. Joint Bone Spine 2019; 86:315-320. [DOI: 10.1016/j.jbspin.2018.08.002] [Citation(s) in RCA: 25] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 06/20/2018] [Indexed: 01/02/2023]
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Picke AK, Campbell G, Napoli N, Hofbauer LC, Rauner M. Update on the impact of type 2 diabetes mellitus on bone metabolism and material properties. Endocr Connect 2019; 8:R55-R70. [PMID: 30772871 PMCID: PMC6391903 DOI: 10.1530/ec-18-0456] [Citation(s) in RCA: 84] [Impact Index Per Article: 14.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/21/2019] [Accepted: 01/24/2019] [Indexed: 11/23/2022]
Abstract
The prevalence of type 2 diabetes mellitus (T2DM) is increasing worldwide, especially as a result of our aging society, high caloric intake and sedentary lifestyle. Besides the well-known complications of T2DM on the cardiovascular system, the eyes, kidneys and nerves, bone strength is also impaired in diabetic patients. Patients with T2DM have a 40-70% increased risk for fractures, despite having a normal to increased bone mineral density, suggesting that other factors besides bone quantity must account for increased bone fragility. This review summarizes the current knowledge on the complex effects of T2DM on bone including effects on bone cells, bone material properties and other endocrine systems that subsequently affect bone, discusses the effects of T2DM medications on bone and concludes with a model identifying factors that may contribute to poor bone quality and increased bone fragility in T2DM.
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Affiliation(s)
- Ann-Kristin Picke
- Institute of Comparative Molecular Endocrinology, Ulm University, Ulm, Germany
| | - Graeme Campbell
- Institute of Biomechanics, TUHH Hamburg University of Technology, Hamburg, Germany
| | - Nicola Napoli
- Diabetes and Bone Network, Department Endocrinology and Diabetes, University Campus Bio-Medico of Rome, Rome, Italy
- Division of Bone and Mineral Diseases, Washington University in St Louis, St Louis, Missouri, USA
| | - Lorenz C Hofbauer
- Department of Medicine III & Center for Healthy Aging, Technische Universität Dresden, Dresden, Germany
| | - Martina Rauner
- Department of Medicine III & Center for Healthy Aging, Technische Universität Dresden, Dresden, Germany
- Correspondence should be addressed to M Rauner:
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Silverman S, Langdahl BL, Fujiwara S, Saag K, Napoli N, Soen S, Enomoto H, Melby TE, Disch DP, Marin F, Krege JH. Reduction of Hip and Other Fractures in Patients Receiving Teriparatide in Real-World Clinical Practice: Integrated Analysis of Four Prospective Observational Studies. Calcif Tissue Int 2019; 104:193-200. [PMID: 30343436 DOI: 10.1007/s00223-018-0485-2] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/08/2018] [Accepted: 10/12/2018] [Indexed: 12/27/2022]
Abstract
The phase 3 teriparatide Fracture Prevention Trial showed significant reductions in vertebral (VF) and nonvertebral (NVF) fractures; however, patient exposure was insufficient for full analysis of low-incidence fractures, including hip. We assessed fracture results in pooled data from four prospective, observational teriparatide studies. Ambulatory women and men with osteoporosis received subcutaneous teriparatide 20 µg/day for up to 24 months per routine clinical practice. Fracture rates were compared between 6-month periods, using 0 to 6 months of treatment as the reference period. Analyses used a piecewise exponential model for first fracture. Hip, NVF, clinical VF (CVF), any clinical, and wrist fractures were assessed. For 8828 patients analyzed, mean age was 71 years; mean (SD) treatment duration was 17.4 (8.6) months. The rate of hip fracture decreased significantly for the > 12 to 18-month (- 47.7%) and > 18-month periods (-85.2%) versus the first 6 months of therapy, and for the > 18 versus the > 6 to 12-month period. NVF, CVF, and all clinical fractures were all significantly decreased in each post-reference period, with maximum decreases (> 18-month period) of 52.7%, 69.4%, and 61.2%, respectively, versus 0 to 6 months. No significant reduction was seen for rates of wrist fracture. Teriparatide treatment was associated with statistically significant decreases in hip fracture rate, particularly for > 18 months of treatment, and in NVF, CVF, and all clinical fracture rate in real-world patients. These results should be interpreted in the context of the non-controlled design of the source studies.
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Affiliation(s)
- Stuart Silverman
- Cedars-Sinai Medical Center, David Geffen School of Medicine, UCLA, and OMC Clinical Research Center, 8641 Wilshire Blvd, Suite 301, Beverly Hills, CA, 90211, USA.
| | | | - Saeko Fujiwara
- Department of Pharmacy, Yasuda Women's University, Hiroshima, Japan
| | - Ken Saag
- University of Alabama at Birmingham, Birmingham, AL, USA
| | - Nicola Napoli
- University Campus Bio-Medico, Rome, Italy
- Istituto Ortopedico Galeazzi, Milan, Italy
| | - Satoshi Soen
- Department of Orthopaedic Surgery and Rheumatology, Kindai University Nara Hospital, Ikoma, Japan
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Ferrari SL, Abrahamsen B, Napoli N, Akesson K, Chandran M, Eastell R, El-Hajj Fuleihan G, Josse R, Kendler DL, Kraenzlin M, Suzuki A, Pierroz DD, Schwartz AV, Leslie WD. Diagnosis and management of bone fragility in diabetes: an emerging challenge. Osteoporos Int 2018; 29:2585-2596. [PMID: 30066131 PMCID: PMC6267152 DOI: 10.1007/s00198-018-4650-2] [Citation(s) in RCA: 227] [Impact Index Per Article: 32.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/07/2018] [Accepted: 07/19/2018] [Indexed: 12/11/2022]
Abstract
Fragility fractures are increasingly recognized as a complication of both type 1 and type 2 diabetes, with fracture risk that increases with disease duration and poor glycemic control. Yet the identification and management of fracture risk in these patients remains challenging. This review explores the clinical characteristics of bone fragility in adults with diabetes and highlights recent studies that have evaluated bone mineral density (BMD), bone microstructure and material properties, biochemical markers, and fracture prediction algorithms (i.e., FRAX) in these patients. It further reviews the impact of diabetes drugs on bone as well as the efficacy of osteoporosis treatments in this population. We finally propose an algorithm for the identification and management of diabetic patients at increased fracture risk.
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Affiliation(s)
- S L Ferrari
- Division of Bone Diseases, Department of Internal Medicine Specialties, Geneva University Hospital & Faculty of Medicine, 1205, Geneva, Switzerland.
| | - B Abrahamsen
- Department of Medicine, Holbaek Hospital, Holbaek, Denmark
- OPEN, Institute of Clinical Research, University of Southern Denmark, Odense, Denmark
| | - N Napoli
- Unit of Endocrinology and Diabetes, Department of Medicine, Università Campus Bio-Medico di Roma, Rome, Italy
- Division of Bone and Mineral Diseases, Washington University in St Louis, St Louis, MO, USA
| | - K Akesson
- Department of Clinical Sciences, Clinical and Molecular Osteoporosis Unit, Lund University, Malmö, Sweden
| | - M Chandran
- Osteoporosis and Bone Metabolism Unit, Department of Endocrinology, Singapore General Hospital, Singapore, Singapore
| | - R Eastell
- Academic Unit of Bone Metabolism, Mellanby Centre for Bone Research, University of Sheffield, Sheffield, UK
| | - G 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, Lebanon
| | - R Josse
- Department of Medicine and Department of Nutritional Sciences, University of Toronto, Toronto, ON, Canada
- Division of Endocrinology and Metabolism, St. Michael's Hospital, Toronto, ON, Canada
| | - D L Kendler
- Department of Medicine, Division of Endocrinology, University of British Columbia, Vancouver, BC, Canada
| | - M Kraenzlin
- Endonet, Endocrine Clinic and Laboratory, Basel, Switzerland
| | - A Suzuki
- Division of Endocrinology and Metabolism, Fujita Health University, Toyoake, Aichi, Japan
| | - D D Pierroz
- International Osteoporosis Foundation, Nyon, Switzerland
| | - A V Schwartz
- Department of Epidemiology and Biostatistics, University of California, San Francisco, CA, USA
| | - W D Leslie
- Department of Internal Medicine, University of Manitoba, Winnipeg, Manitoba, Canada
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Langdahl BL, Silverman S, Fujiwara S, Saag K, Napoli N, Soen S, Enomoto H, Melby TE, Disch DP, Marin F, Krege JH. Real-world effectiveness of teriparatide on fracture reduction in patients with osteoporosis and comorbidities or risk factors for fractures: Integrated analysis of 4 prospective observational studies. Bone 2018; 116:58-66. [PMID: 30021126 DOI: 10.1016/j.bone.2018.07.013] [Citation(s) in RCA: 63] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/01/2018] [Revised: 07/09/2018] [Accepted: 07/13/2018] [Indexed: 02/07/2023]
Abstract
INTRODUCTION Teriparatide significantly reduces fracture rates in clinical trials; however, those study populations were relatively restricted and included too few patients to analyze fracture outcomes within clinically important patient subgroups. We assessed fracture outcomes in subgroups of osteoporosis patients from 4 real-world teriparatide observational studies. METHODS Patients received teriparatide 20 μg/day for up to 24 months. Fracture rates were compared between 0 to 6 months versus >6 months using a piecewise exponential model for first fracture. Analyses included incident clinical vertebral fractures (CVF) and nonvertebral fractures (NVF), and clinical fractures (CVF and NVF) by subgroups of gender, age <75 or ≥75 years, diabetes, prior bisphosphonates use, rheumatoid arthritis (RA), glucocorticoid use, prior hip, and prior vertebral fracture. RESULTS The population included 8828 patients (8117 women, 92%) with mean (SD) age 71 (10.6) years and teriparatide treatment duration 17.4 (8.6) months. Overall, CVF, NVF, clinical fracture, and hip fracture rates decreased by 62%, 43%, 50%, and 56%, respectively (all p < .005) for >6 months versus 0 to 6 months. Subgroup analyses all showed significantly decreased rates after >6 months except for NVF reduction in males (n = 710, fracture rate low during months 0 to 6) and in patients using glucocorticoids, and CVF in patients with prior hip fracture. The effects of teriparatide on CVF, NVF, and clinical fractures over time were statistically consistent in all subgroups except age for CVF (p = .074, patients <75 years of age responded better), and diabetes for clinical fractures (p = .046, patients with diabetes responded better), although all of these subgroups experienced significant reductions over time. Glucocorticoids, prior bisphosphonate, and prior vertebral fracture were associated with increased CVF, NVF, and clinical fracture rates; RA, prior hip fracture and female gender were associated with higher NVF and clinical fracture rates; increased age was associated with higher CVF and clinical fracture rates. CONCLUSIONS Data from 4 real-world observational studies showed statistically significant reductions during teriparatide treatment in rates of CVF, NVF, and clinical fractures in clinically relevant patient subgroups. These results should be interpreted in the context of the non-controlled design of the source studies.
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Affiliation(s)
- Bente L Langdahl
- Department of Endocrinology and Internal Medicine, Aarhus University Hospital, Aarhus, Denmark.
| | - Stuart Silverman
- Cedars-Sinai/UCLA Medical Center and OMC Clinical Research Center, Beverly Hills, CA, USA.
| | - Saeko Fujiwara
- Health Management and Promotion Center, Hiroshima Atomic Bomb Casualty Council, Hiroshima, Japan
| | - Ken Saag
- Division of Clinical Immunology and Rheumatology, Center for Education and Research on Therapeutics University of Alabama at Birmingham, Birmingham, AL, USA.
| | - Nicola Napoli
- Division of Endocrinology and Diabetes, Campus Bio-Medico University of Rome, Rome, Italy; IRCCS Istituto Ortopedico Galeazzi, Milan, Italy
| | - Satoshi Soen
- Department of Orthopaedic Surgery and Rheumatology, Kindai University Nara Hospital, Ikoma, Japan.
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Fuglsang-Nielsen R, Starup-Linde J, Gregersen S, Vestergaard P. The effect of meals on bone turnover - a systematic review with focus on diabetic bone disease. Expert Rev Endocrinol Metab 2018; 13:233-249. [PMID: 30234398 DOI: 10.1080/17446651.2018.1518131] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
INTRODUCTION Type 2 diabetes is associated with an increased risk of bone fractures. Bone mineral density (BMD) is increased and bone turnover is low in type 2 diabetes and the increased BMD does not explain the increased fracture risk. However, the low bone turnover may lead to insufficient bone renewal with unrepaired micro-cracks and thus increase fracture risk. Ingestion of food acutely decreases bone resorption markers and the macronutrient composition of meals and meal frequency may influence bone metabolism adversely in subjects with unhealthy eating patterns, e.g., patients with type 2 diabetes. AREAS COVERED The treatment strategy of bone disease in type 2 diabetics is covered in this review. The current management of diabetic bone disease consists of anti-osteoporotic treatment. However, anti-resorptives may further reduce an already low bone turnover with uncertain effects. Furthermore, the acute and long-term effects of meal ingestion, weight loss alone and in combination with exercise as well as the possible underlying mechanisms are covered in this systematic review. EXPERT COMMENTARY Current management of diabetic bone disease is based on principles of anti-osteoporotic treatment in non-diabetic subjects. However, studies are urged to investigate whether anti-resorptives are equally beneficial in type 2 diabetes as in non-diabetic individuals.
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Affiliation(s)
| | - Jakob Starup-Linde
- b Steno Diabetes Center North Jutland , Aalborg University Hospital , Denmark
| | - Søren Gregersen
- a Department of Endocrinology and Internal Medicine , Aarhus University Hospital , Denmark
| | - Peter Vestergaard
- b Steno Diabetes Center North Jutland , Aalborg University Hospital , Denmark
- c Department of Endocrinology , Aalborg University Hospital , Denmark
- d Department of Clinical Medicine , Aalborg University , Denmark
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Starup-Linde J, Hygum K, Langdahl BL. Skeletal Fragility in Type 2 Diabetes Mellitus. Endocrinol Metab (Seoul) 2018; 33:339-351. [PMID: 30229573 PMCID: PMC6145952 DOI: 10.3803/enm.2018.33.3.339] [Citation(s) in RCA: 23] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/17/2018] [Revised: 08/22/2018] [Accepted: 08/29/2018] [Indexed: 12/16/2022] Open
Abstract
Type 2 diabetes (T2D) is associated with an increased risk of fracture, which has been reported in several epidemiological studies. However, bone mineral density in T2D is increased and underestimates the fracture risk. Common risk factors for fracture do not fully explain the increased fracture risk observed in patients with T2D. We propose that the pathogenesis of increased fracture risk in T2D is due to low bone turnover caused by osteocyte dysfunction resulting in bone microcracks and fractures. Increased levels of sclerostin may mediate the low bone turnover and may be a novel marker of increased fracture risk, although further research is needed. An impaired incretin response in T2D may also affect bone turnover. Accumulation of advanced glycosylation endproducts may also impair bone strength. Concerning antidiabetic medication, the glitazones are detrimental to bone health and associated with increased fracture risk, and the sulphonylureas may increase fracture risk by causing hypoglycemia. So far, the results on the effect of other antidiabetics are ambiguous. No specific guideline for the management of bone disease in T2D is available and current evidence on the effects of antiosteoporotic medication in T2D is sparse. The aim of this review is to collate current evidence of the pathogenesis, detection and treatment of diabetic bone disease.
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Affiliation(s)
- Jakob Starup-Linde
- Department of Endocrinology and Internal Medicine, Aarhus University Hospital, Aarhus, Denmark
- Steno Diabetes Center North Jutland, Aalborg University Hospital, Aalborg, Denmark
| | - Katrine Hygum
- Department of Endocrinology and Internal Medicine, Aarhus University Hospital, Aarhus, Denmark
| | - Bente Lomholt Langdahl
- Department of Endocrinology and Internal Medicine, Aarhus University Hospital, Aarhus, Denmark.
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Anagnostis P, Paschou SA, Gkekas NN, Artzouchaltzi AM, Christou K, Stogiannou D, Vryonidou A, Potoupnis M, Goulis DG. Efficacy of anti-osteoporotic medications in patients with type 1 and 2 diabetes mellitus: a systematic review. Endocrine 2018; 60:373-383. [PMID: 29411304 DOI: 10.1007/s12020-018-1548-x] [Citation(s) in RCA: 40] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/06/2017] [Accepted: 01/25/2018] [Indexed: 01/11/2023]
Abstract
PURPOSE Both type 1 (T1DM) and type 2 diabetes mellitus (T2DM) have been associated with bone fragility and increased fracture risk. However, little is known regarding the effect of anti-osteoporotic treatment on bone mineral density (BMD) and/or fracture risk in these patients. We aimed to systematically investigate the efficacy of anti-osteoporotic medications in patients with diabetes in comparison with non-diabetic subjects. METHODS MEDLINE and Scopus databases were searched (up to 31st October 2017). RESULTS Nine studies fulfilled the pre-defined inclusion criteria [patients with T2DM (n = 8) or either T1DM or T2DM (n = 1)]. Regarding fracture risk, five studies were identified. Alendronate demonstrated comparable vertebral anti-fracture efficacy in patients with and without diabetes (n = 2), whereas non-vertebral fracture risk was either the same (n = 1) or higher in diabetic patients (n = 1). Raloxifene also demonstrated comparable vertebral anti-fracture efficacy in both groups (n = 2), without any effect on non-vertebral fractures in either group. In one study, diabetic patients exposed to raloxifene demonstrated the same vertebral and non-vertebral fracture risk with non-diabetic patients. Teriparatide (n = 1) demonstrated the same non-vertebral fracture rates in both patients with and without T2DM. Regarding BMD, equal increases in spine BMD were observed with alendronate (n = 4), risedronate (n = 1), and teriparatide (n = 1). With respect to hip BMD, similar increases were observed with teriparatide (n = 1), whereas data regarding alendronate were controversial (n = 3). No eligible study was found for zoledronic acid, ibandronate, strontium ranelate, denosumab, or bazedoxifene. CONCLUSIONS The presence of diabetes does not alter anti-osteoporotic treatment response, regarding BMD increase and vertebral fracture risk reduction.
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Affiliation(s)
- Panagiotis Anagnostis
- Unit of Reproductive Endocrinology, First Department of Obstetrics and Gynecology, Medical School, Aristotle University of Thessaloniki, Thessaloniki, Greece.
- Police Medical Center of Thessaloniki, Thessaloniki, Greece.
| | - Stavroula A Paschou
- Division of Endocrinology and Diabetes, "Aghia Sophia" Hospital, Medical School, National and Kapodistrian University of Athens, Athens, Greece
| | - Nifon N Gkekas
- Police Medical Center of Thessaloniki, Thessaloniki, Greece
| | | | | | | | - Andromachi Vryonidou
- Department of Endocrinology and Diabetes, Hellenic Red Cross Hospital, Athens, Greece
| | - Michael Potoupnis
- Academic Orthopaedic Unit, General Hospital Papageorgiou, Aristotle University Medical School, Thessaloniki, Greece
| | - Dimitrios G Goulis
- Unit of Reproductive Endocrinology, First Department of Obstetrics and Gynecology, Medical School, Aristotle University of Thessaloniki, Thessaloniki, Greece
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Abstract
Type 2 diabetes (T2DM) is a rapidly growing public health problem. It is associated with an increased risk of fracture, particularly of the hip, despite normal or high bone mineral density. Longer duration of disease and poor glycaemic control are both associated with higher fracture risk. The factors underlying increased fracture risk have not been clearly established, but increased falls risk, obesity, sarcopenia and co-morbidities are likely to contribute. The basis for reduced bone strength despite higher bone mineral density remains to be fully elucidated. Bone turnover is reduced in individuals with T2DM, with evidence of impaired bone formation. Most studies indicate normal or superior trabecular bone structure although reduced lumbar spine trabecular bone score (TBS) has been reported. Deficits in cortical bone structure have been demonstrated in some, but not all, studies whilst reduced bone material strength index (BMSi), as assessed by microindentation, has been a consistent finding. Accumulation of advanced glycation end products in bone may also contribute to reduced bone strength. The use of FRAX in individuals with T2DM underestimates fracture probability. Clinical management should focus on falls prevention strategies, avoidance of known risk factors, maintenance of good glycaemic control and bone protective intervention in individuals at high risk of fracture. Dietary and surgical strategies to reduce weight have beneficial effects on diabetes but may have adverse effects on skeletal health. Future research priorities include better definition of the mechanisms underlying increased fracture risk in T2DM and optimal strategies for identifying and treating those at high risk.
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Affiliation(s)
- J Compston
- Department of Medicine, Cambridge Biomedical Campus, Cambridge, UK
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50
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Gennari L, Bilezikian JP. New and developing pharmacotherapy for osteoporosis in men. Expert Opin Pharmacother 2018; 19:253-264. [DOI: 10.1080/14656566.2018.1428559] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Affiliation(s)
- Luigi Gennari
- Department Medicine, Surgery and Neurosciences, University of Siena, Siena, Italy
| | - John P. Bilezikian
- Medicine and Pharmacology, International Education and Research, Division of Endocrinology, Emeritus, Metabolic Bone Diseases Unit, Department of Medicine, College of Physicians and Surgeons, Columbia University, New York, NY, USA
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