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1
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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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2
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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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3
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Zhang SC, Makebeh T, Mesinovic J, Djopseu K, Martin C, Lui LY, Cawthon PM, Schneider ALC, Zmuda JM, Strotmeyer ES, Schafer A, Ebeling PR, Zebaze RM. Epidemiology of fractures in adults of African ancestry with diabetes mellitus: A systematic review and meta-analysis. Bone 2024; 185:117133. [PMID: 38789095 DOI: 10.1016/j.bone.2024.117133] [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: 01/29/2024] [Revised: 04/16/2024] [Accepted: 05/21/2024] [Indexed: 05/26/2024]
Abstract
Diabetes mellitus (DM) is associated with increased fracture risk in White adults. However, the impact of DM on fractures in Black adults is unknown. This systematic review and meta-analysis investigated the association between DM and fractures in adults of African ancestry. MEDLINE, Scopus, CINAHL and Embase databases were searched from their inception up to November 2023 for all studies in the English language investigating the epidemiology of fractures (prevalence, incidence, or risk) in Black men and women (age ≥ 18 years) with type 1 or type 2 DM. Effect sizes for prevalence of previous fractures (%) and incident fracture risk (hazard ratio [HR]) were calculated using a random-effects model on Stata (version 18.0). There were 13 eligible studies, of which 12 were conducted in Black adults from the United States, while one was conducted in adults of West African ancestry from Trinidad and Tobago. We found no fracture data in Black adults with DM living in Africa. Five studies were included in a meta-analysis of incident fracture risk, reporting data from 2926 Black and 6531 White adults with DM. There was increased risk of fractures in Black adults with DM compared to non-DM (HR = 1.65; 95 % confidence interval [CI]: 1.14, 2.39). The risk of fractures was also higher in White adults with DM compared to non-DM (HR = 1.31; 95 % CI: 1.06, 1.61) among these studies. Five studies were included in a meta-analysis of fracture prevalence, of which three also reported fracture prevalence in White adults. There were 175 previous fractures among 993 Black adults with DM and 384 previous fractures among 1467 White adults with DM, with a pooled prevalence of 17.5 % (95 % CI: 15.4, 19.6) and 25.8 % (95 % CI: 4.8, 46.8), respectively. Our results indicate a high burden of fractures in Black adults with DM.
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Affiliation(s)
- Simon C Zhang
- Department of Medicine, School of Clinical Sciences, Monash University, Clayton, Victoria, Australia
| | | | - Jakub Mesinovic
- Department of Medicine, School of Clinical Sciences, Monash University, Clayton, Victoria, Australia; Institute for Physical Activity and Nutrition, School of Exercise and Nutrition Sciences, Deakin University, Burwood, Australia
| | | | - Catherine Martin
- School of Public Health and Preventive Medicine, Monash University, Clayton, Victoria, Australia
| | - Li-Yung Lui
- Research Institute, California Pacific Medical Center, San Francisco, CA, USA
| | - Peggy M Cawthon
- Research Institute, California Pacific Medical Center, San Francisco, CA, USA; Department of Epidemiology and Biostatistics, University of California, San Francisco, CA, USA
| | - Andrea L C Schneider
- Department of Neurology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA; Department of Biostatistics, Epidemiology, and Informatics, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA
| | - Joseph M Zmuda
- Department of Epidemiology, School of Public Health, University of Pittsburgh, Pittsburgh, PA, USA
| | - Elsa S Strotmeyer
- Department of Epidemiology, School of Public Health, University of Pittsburgh, Pittsburgh, PA, USA
| | - Anne Schafer
- Department of Epidemiology and Biostatistics, University of California, San Francisco, CA, USA; Endocrine Research Unit, San Francisco Veterans Affairs Health Care System, San Francisco, USA.; Department of Medicine, University of California, San Francisco, CA, USA
| | - Peter R Ebeling
- Department of Medicine, School of Clinical Sciences, Monash University, Clayton, Victoria, Australia; Department of Endocrinology, Monash Health, Clayton, Victoria, Australia
| | - Roger M Zebaze
- Department of Medicine, School of Clinical Sciences, Monash University, Clayton, Victoria, Australia; Department of Endocrinology, Monash Health, Clayton, Victoria, Australia.
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Dresner-Pollak R. Skeletal Fragility in Adult People Living With Type 1 Diabetes. Endocr Pract 2024; 30:592-597. [PMID: 38556079 DOI: 10.1016/j.eprac.2024.03.392] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/16/2024] [Revised: 03/23/2024] [Accepted: 03/27/2024] [Indexed: 04/02/2024]
Abstract
Advances in the management of people with type 1 diabetes (T1D) led to longer life expectancy, but with it an aging population with age-associated conditions. While macrovascular and microvascular complications are widely recognized, bone fragility has received considerably less attention, although fractures lead to high morbidity and mortality. Hip fracture risk is up to sixfold higher in T1D than in nondiabetic controls and significantly higher than in type 2 diabetes. Hip fractures occur at a younger age, and the consequences are worse. The risk of nonvertebral fractures is also significantly increased. Altered bone quality is a major underlying mechanism. Areal BMD measured by DXA underestimates fracture risk. BMD testing is recommended in T1D patients with poor glycemic control and/or microvascular complications. Trabecular bone score is mildly reduced, and its ability to predict fractures in T1D is unknown. Bone turnover markers, particularly procollagen type 1 N-terminal propeptide, are suppressed and do not predict fracture risk in T1D. T1D-related risk factors for fractures include disease onset at age <20 years, longer disease duration, HbA1c ≥8%, hypoglycemic episodes and microvascular complications. Data regarding the efficacy of therapeutic interventions to prevent or treat skeletal fragility in T1D is scant. Adequate calcium and vitamin D intake and fall prevention are recommended. Antiosteoporosis therapies are recommended in T1D patients with previous hip or vertebral fragility fracture, more than 1 other fragility fracture, BMD T-score < -2.5 at the femoral neck or spine, and increased FRAX score. Fracture risk assessment needs to be part of the management of people with T1D.
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Affiliation(s)
- Rivka Dresner-Pollak
- Department of Endocrinology and Metabolism, Division of Medicine, Hadassah Medical Organization, Faculty of Medicine, Hebrew University of Jerusalem, Jerusalem, Israel.
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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, Kovacova V, Babikova M, Zemanova N, Mondockova V, Omelka R. Current knowledge of bone-derived factor osteocalcin: its role in the management and treatment of diabetes mellitus, osteoporosis, osteopetrosis and inflammatory joint diseases. J Mol Med (Berl) 2024; 102:435-452. [PMID: 38363329 PMCID: PMC10963459 DOI: 10.1007/s00109-024-02418-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/30/2023] [Revised: 12/21/2023] [Accepted: 01/10/2024] [Indexed: 02/17/2024]
Abstract
Osteocalcin (OC) is the most abundant non-collagenous and osteoblast-secreted protein in bone. It consists of two forms such as carboxylated OC (cOC) and undercarboxylated OC (ucOC). While cOC promotes bone mineralization and increases bone strength, ucOC is regarded an endocrinologically active form that may have several functions in multiple end organs and tissues. Total OC (tOC) includes both of these forms (cOC and ucOC) and is considered a marker of bone turnover in clinical settings. Most of the data on OC is limited to preclinical studies and therefore may not accurately reflect the situation in clinical conditions. For the stated reason, the aim of this review was not only to summarize current knowledge of all forms of OC and characterize its role in diabetes mellitus, osteoporosis, osteopetrosis, inflammatory joint diseases, but also to provide new interpretations of its involvement in the management and treatment of aforementioned diseases. In this context, special emphasis was placed on available clinical trials. Significantly lower levels of tOC and ucOC could be associated with the risk of type 2 diabetes mellitus. On the contrary, tOC level does not seem to be a good indicator of high bone turnover status in postmenopausal osteoporosis, osteoarthritis and rheumatoid arthritis. The associations between several pharmacological drugs used to treat all disorders mentioned above and OC levels have also been provided. From this perspective, OC may serve as a medium through which certain medications can influence glucose metabolism, body weight, adiponectin secretion, and synovial inflammation.
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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, Tr. A. Hlinku 1, 949 01, Nitra, Slovakia
| | - Roman Biro
- Department of Zoology and Anthropology, Faculty of Natural Sciences and Informatics, Constantine the Philosopher University in Nitra, Tr. A. Hlinku 1, 949 01, Nitra, Slovakia
| | - Veronika Kovacova
- Department of Zoology and Anthropology, Faculty of Natural Sciences and Informatics, Constantine the Philosopher University in Nitra, Tr. A. Hlinku 1, 949 01, Nitra, Slovakia
| | - Martina Babikova
- Department of Botany and Genetics, Faculty of Natural Sciences and Informatics, Constantine the Philosopher University in Nitra, Tr. A. Hlinku 1, 949 01, Nitra, Slovakia
| | - Nina Zemanova
- Department of Botany and Genetics, Faculty of Natural Sciences and Informatics, Constantine the Philosopher University in Nitra, Tr. A. Hlinku 1, 949 01, Nitra, Slovakia
| | - Vladimira Mondockova
- Department of Botany and Genetics, Faculty of Natural Sciences and Informatics, Constantine the Philosopher University in Nitra, Tr. A. Hlinku 1, 949 01, Nitra, Slovakia
| | - Radoslav Omelka
- Department of Botany and Genetics, Faculty of Natural Sciences and Informatics, Constantine the Philosopher University in Nitra, Tr. A. Hlinku 1, 949 01, Nitra, Slovakia.
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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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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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10
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Meier C, Eastell R, Pierroz DD, Lane NE, Al-Daghri N, Suzuki A, Napoli N, Mithal A, Chakhtoura M, Fuleihan GEH, Ferrari S. Biochemical Markers of Bone Fragility in Patients with Diabetes. A Narrative Review by the IOF and the ECTS. J Clin Endocrinol Metab 2023; 108:dgad255. [PMID: 37155585 PMCID: PMC10505554 DOI: 10.1210/clinem/dgad255] [Citation(s) in RCA: 20] [Impact Index Per Article: 10.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/22/2022] [Revised: 04/24/2023] [Accepted: 05/03/2023] [Indexed: 05/10/2023]
Abstract
CONTEXT The risk of fragility fractures is increased in both type 1 and type 2 diabetes. Numerous biochemical markers reflecting bone and/or glucose metabolism have been evaluated in this context. This review summarizes current data on biochemical markers in relation to bone fragility and fracture risk in diabetes. METHODS Literature review by a group of experts from the International Osteoporosis Foundation (IOF) and European Calcified Tissue Society (ECTS) focusing on biochemical markers, diabetes, diabetes treatments and bone in adults. RESULTS Although bone resorption and bone formation markers are low and poorly predictive of fracture risk in diabetes, osteoporosis drugs seem to change bone turnover markers in diabetics similarly to non-diabetics, with similar reductions in fracture risk. Several other biochemical markers related to bone and glucose metabolism have been correlated with BMD and/or fracture risk in diabetes, including osteocyte-related markers such as sclerostin, HbA1c and advanced glycation end products (AGEs), inflammatory markers and adipokines, as well as IGF-1 and calciotropic hormones. CONCLUSION Several biochemical markers and hormonal levels related to bone and/or glucose metabolism have been associated with skeletal parameters in diabetes. Currently, only HbA1c levels seem to provide a reliable estimate of fracture risk, while bone turnover markers could be used to monitor the effects of anti-osteoporosis therapy.
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Affiliation(s)
- Christian Meier
- Department of Endocrinology, Diabetology and Metabolism, University Hospital Basel, 4031 Basel, Switzerland
| | - Richard Eastell
- Academic Unit of Bone Metabolism, Mellanby Centre for Bone Research, University of Sheffield, S57AU Sheffield, UK
| | | | - Nancy E Lane
- Department of Medicine and Rheumatology, Davis School of Medicine, University of California, Sacramento, CA 95817, USA
| | - Nasser Al-Daghri
- Department of Biochemistry, College of Science, King Saud University, Riyadh 11451, Saudi Arabia
| | - Atsushi Suzuki
- Department of Endocrinology, Diabetes and Metabolism, Fujita Health University, Toyoake, Aichi 470-1192, Japan
| | - Nicola Napoli
- Unit of Endocrinology and Diabetes, Department of Medicine, Università Campus Bio-Medico di Roma, 00128 Rome, Italy
| | - Ambrish Mithal
- Institute of Diabetes and Endocrinology, Max Healthcare, Saket, New Delhi 110017, India
| | - Marlene Chakhtoura
- Department of Internal Medicine, Division of Endocrinology, Calcium Metabolism and Osteoporosis Program, WHO Collaborating Center for Metabolic Bone Disorders, American University of Beirut Medical Center, Riad El Solh, Beirut 6044, Lebanon
| | - Ghada El-Hajj Fuleihan
- Department of Internal Medicine, Division of Endocrinology, Calcium Metabolism and Osteoporosis Program, WHO Collaborating Center for Metabolic Bone Disorders, American University of Beirut Medical Center, Riad El Solh, Beirut 6044, Lebanon
| | - Serge Ferrari
- Service and Laboratory of Bone Diseases, Geneva University Hospital and Faculty of Medicine, 1205 Geneva, Switzerland
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11
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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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Vandenput L, Johansson H, McCloskey EV, Liu E, Åkesson KE, Anderson FA, Azagra R, Bager CL, Beaudart C, Bischoff-Ferrari HA, Biver E, Bruyère O, Cauley JA, Center JR, Chapurlat R, Christiansen C, Cooper C, Crandall CJ, Cummings SR, da Silva JAP, Dawson-Hughes B, Diez-Perez A, Dufour AB, Eisman JA, Elders PJM, Ferrari S, Fujita Y, Fujiwara S, Glüer CC, Goldshtein I, Goltzman D, Gudnason V, Hall J, Hans D, Hoff M, Hollick RJ, Huisman M, Iki M, Ish-Shalom S, Jones G, Karlsson MK, Khosla S, Kiel DP, Koh WP, Koromani F, Kotowicz MA, Kröger H, Kwok T, Lamy O, Langhammer A, Larijani B, Lippuner K, Mellström D, Merlijn T, Nordström A, Nordström P, O'Neill TW, Obermayer-Pietsch B, Ohlsson C, Orwoll ES, Pasco JA, Rivadeneira F, Schei B, Schott AM, Shiroma EJ, Siggeirsdottir K, Simonsick EM, Sornay-Rendu E, Sund R, Swart KMA, Szulc P, Tamaki J, Torgerson DJ, van Schoor NM, van Staa TP, Vila J, Wareham NJ, Wright NC, Yoshimura N, Zillikens MC, Zwart M, Harvey NC, Lorentzon M, Leslie WD, Kanis JA. Update of the fracture risk prediction tool FRAX: a systematic review of potential cohorts and analysis plan. Osteoporos Int 2022; 33:2103-2136. [PMID: 35639106 DOI: 10.1007/s00198-022-06435-6] [Citation(s) in RCA: 60] [Impact Index Per Article: 20.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/10/2022] [Accepted: 05/18/2022] [Indexed: 12/15/2022]
Abstract
We describe the collection of cohorts together with the analysis plan for an update of the fracture risk prediction tool FRAX with respect to current and novel risk factors. The resource comprises 2,138,428 participants with a follow-up of approximately 20 million person-years and 116,117 documented incident major osteoporotic fractures. INTRODUCTION The availability of the fracture risk assessment tool FRAX® has substantially enhanced the targeting of treatment to those at high risk of fracture with FRAX now incorporated into more than 100 clinical osteoporosis guidelines worldwide. The aim of this study is to determine whether the current algorithms can be further optimised with respect to current and novel risk factors. METHODS A computerised literature search was performed in PubMed from inception until May 17, 2019, to identify eligible cohorts for updating the FRAX coefficients. Additionally, we searched the abstracts of conference proceedings of the American Society for Bone and Mineral Research, European Calcified Tissue Society and World Congress of Osteoporosis. Prospective cohort studies with data on baseline clinical risk factors and incident fractures were eligible. RESULTS Of the 836 records retrieved, 53 were selected for full-text assessment after screening on title and abstract. Twelve cohorts were deemed eligible and of these, 4 novel cohorts were identified. These cohorts, together with 60 previously identified cohorts, will provide the resource for constructing an updated version of FRAX comprising 2,138,428 participants with a follow-up of approximately 20 million person-years and 116,117 documented incident major osteoporotic fractures. For each known and candidate risk factor, multivariate hazard functions for hip fracture, major osteoporotic fracture and death will be tested using extended Poisson regression. Sex- and/or ethnicity-specific differences in the weights of the risk factors will be investigated. After meta-analyses of the cohort-specific beta coefficients for each risk factor, models comprising 10-year probability of hip and major osteoporotic fracture, with or without femoral neck bone mineral density, will be computed. CONCLUSIONS These assembled cohorts and described models will provide the framework for an updated FRAX tool enabling enhanced assessment of fracture risk (PROSPERO (CRD42021227266)).
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Affiliation(s)
- L Vandenput
- Mary McKillop Institute for Health Research, Australian Catholic University, Melbourne, Australia
- Sahlgrenska Osteoporosis Centre, Department of Internal Medicine and Clinical Nutrition, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
| | - H Johansson
- Mary McKillop Institute for Health Research, Australian Catholic University, Melbourne, Australia
- Centre for Metabolic Bone Diseases, University of Sheffield, Sheffield, UK
| | - E V McCloskey
- Centre for Metabolic Bone Diseases, University of Sheffield, Sheffield, UK
- MRC Versus Arthritis Centre for Integrated Research in Musculoskeletal Ageing, Mellanby Centre for Musculoskeletal Research, University of Sheffield, Sheffield, UK
| | - E Liu
- Mary McKillop Institute for Health Research, Australian Catholic University, Melbourne, Australia
| | - K E Åkesson
- Clinical and Molecular Osteoporosis Research Unit, Department of Clinical Sciences, Lund University, Lund, Sweden
- Department of Orthopedics, Skåne University Hospital, Malmö, Sweden
| | - F A Anderson
- GLOW Coordinating Center, Center for Outcomes Research, University of Massachusetts Medical School, Worcester, MA, USA
| | - R Azagra
- Department of Medicine, Autonomous University of Barcelona, Barcelona, Spain
- Health Center Badia del Valles, Catalan Institute of Health, Barcelona, Spain
- GROIMAP (Research Group), Unitat de Suport a La Recerca Metropolitana Nord, Institut Universitari d'Investigació en Atenció Primària Jordi Gol, Santa Coloma de Gramenet, Barcelona, Spain
| | - C L Bager
- Nordic Bioscience A/S, Herlev, Denmark
| | - C Beaudart
- WHO Collaborating Centre for Public Health Aspects of Musculoskeletal Health and Aging, Division of Public Health, Epidemiology and Health Economics, University of Liège, Liège, Belgium
| | - H A Bischoff-Ferrari
- Department of Aging Medicine and Aging Research, University Hospital, Zurich, and University of Zurich, Zurich, Switzerland
- Centre On Aging and Mobility, University of Zurich and City Hospital, Zurich, Switzerland
| | - E Biver
- Division of Bone Diseases, Department of Medicine, Geneva University Hospitals and Faculty of Medicine, University of Geneva, Geneva, Switzerland
| | - O Bruyère
- WHO Collaborating Centre for Public Health Aspects of Musculoskeletal Health and Aging, Division of Public Health, Epidemiology and Health Economics, University of Liège, Liège, Belgium
| | - J A Cauley
- Department of Epidemiology, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, Philadelphia, USA
| | - J R Center
- Bone Biology, Healthy Ageing Theme, Garvan Institute of Medical Research, Sydney, NSW, Australia
- St Vincent's Clinical School, Faculty of Medicine, University of New South Wales Sydney, Sydney, NSW, Australia
- School of Medicine Sydney, University of Notre Dame Australia, Sydney, NSW, Australia
| | - R Chapurlat
- INSERM UMR 1033, University of Lyon, Hôpital Edouard Herriot, Lyon, France
| | | | - C Cooper
- MRC Lifecourse Epidemiology Unit, University of Southampton, Southampton, UK
- National Institute for Health Research Southampton Biomedical Research Centre, University of Southampton and University Hospitals Southampton NHS Foundation Trust, Southampton, UK
- National Institute for Health Research Oxford Biomedical Research Unit, , University of Oxford, Oxford, UK
| | - C J Crandall
- Division of General Internal Medicine and Health Services Research, David Geffen School of Medicine, University of California, Los Angeles, CA, USA
| | - S R Cummings
- San Francisco Coordinating Center, California Pacific Medical Center Research Institute, San Francisco, CA, USA
| | - J A P da Silva
- Coimbra Institute for Clinical and Biomedical Research, Faculty of Medicine, University of Coimbra, Coimbra, Portugal
- Rheumatology Department, University Hospital and University of Coimbra, Coimbra, Portugal
| | - B Dawson-Hughes
- Bone Metabolism Laboratory, Jean Mayer US Department of Agriculture Human Nutrition Research Center On Aging, Tufts University, Boston, MA, USA
| | - A Diez-Perez
- Department of Internal Medicine, Hospital del Mar and CIBERFES, Autonomous University of Barcelona, Barcelona, Spain
| | - A B Dufour
- Marcus Institute for Aging Research, Hebrew SeniorLife, Boston, MA, USA
- Department of Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA, USA
| | - J A Eisman
- St Vincent's Clinical School, Faculty of Medicine, University of New South Wales Sydney, Sydney, NSW, Australia
- School of Medicine Sydney, University of Notre Dame Australia, Sydney, NSW, Australia
- Osteoporosis and Bone Biology Division, Garvan Institute of Medical Research, Sydney, NSW, Australia
| | - P J M Elders
- Department of General Practice, Amsterdam UMC, Location VUmc, Amsterdam Public Health Research Institute, Amsterdam, The Netherlands
| | - S Ferrari
- Division of Bone Diseases, Department of Medicine, Geneva University Hospitals and Faculty of Medicine, University of Geneva, Geneva, Switzerland
| | - Y Fujita
- Department of Public Health, Faculty of Medicine, Kindai University, Osaka, Japan
| | - S Fujiwara
- Department of Pharmacy, Yasuda Women's University, Hiroshima, Japan
| | - C-C Glüer
- Section Biomedical Imaging, Molecular Imaging North Competence Center, Department of Radiology and Neuroradiology, University Medical Center Schleswig-Holstein Kiel, Kiel University, Kiel, Germany
| | - I Goldshtein
- Maccabitech Institute of Research and Innovation, Maccabi Healthcare Services, Tel Aviv, Israel
- Department of Epidemiology and Preventive Medicine, School of Public Health, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
| | - D Goltzman
- Department of Medicine, McGill University and McGill University Health Centre, Montreal, Canada
| | - V Gudnason
- Icelandic Heart Association, Kopavogur, Iceland
- University of Iceland, Reykjavik, Iceland
| | - J Hall
- MRC Centre for Reproductive Health, University of Edinburgh, Edinburgh, UK
| | - D Hans
- Centre of Bone Diseases, Bone and Joint Department, Lausanne University Hospital, Lausanne, Switzerland
| | - M Hoff
- Department of Neuromedicine and Movement Science, Norwegian University of Science and Technology, Trondheim, Norway
- Department of Rheumatology, St Olavs Hospital, Trondheim, Norway
| | - R J Hollick
- Aberdeen Centre for Arthritis and Musculoskeletal Health, Epidemiology Group, University of Aberdeen, Aberdeen, UK
| | - M Huisman
- Department of Epidemiology and Data Science, Amsterdam Public Health Research Institute, VU University Medical Center, Amsterdam, The Netherlands
- Department of Sociology, VU University, Amsterdam, The Netherlands
| | - M Iki
- Department of Public Health, Faculty of Medicine, Kindai University, Osaka, Japan
| | - S Ish-Shalom
- Endocrine Clinic, Elisha Hospital, Haifa, Israel
| | - G Jones
- Menzies Institute for Medical Research, University of Tasmania, Hobart, Australia
| | - M K Karlsson
- Clinical and Molecular Osteoporosis Research Unit, Department of Clinical Sciences, Lund University, Lund, Sweden
- Department of Orthopaedics, Skåne University Hospital, Malmö, Sweden
| | - S Khosla
- Robert and Arlene Kogod Center On Aging and Division of Endocrinology, Mayo Clinic College of Medicine, Mayo Clinic, Rochester, MN, USA
| | - D P Kiel
- Marcus Institute for Aging Research, Hebrew SeniorLife, Boston, MA, USA
- Department of Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA, USA
| | - W-P Koh
- Healthy Longevity Translational Research Programme, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
- Singapore Institute for Clinical Sciences, Agency for Science Technology and Research (A*STAR), Singapore, Singapore
| | - F Koromani
- Department of Internal Medicine, Erasmus University Medical Center, Rotterdam, The Netherlands
- Department of Radiology and Nuclear Medicine, Erasmus University Medical Center, Rotterdam, The Netherlands
| | - M A Kotowicz
- IMPACT (Institute for Mental and Physical Health and Clinical Translation), Deakin University, Geelong, VIC, Australia
- Barwon Health, Geelong, VIC, Australia
- Department of Medicine - Western Health, The University of Melbourne, St Albans, Victoria, Australia
| | - H Kröger
- Department of Orthopedics and Traumatology, Kuopio University Hospital, Kuopio, Finland
- Kuopio Musculoskeletal Research Unit, University of Eastern Finland, Kuopio, Finland
| | - T Kwok
- Department of Medicine and Therapeutics, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, Hong Kong
- Jockey Club Centre for Osteoporosis Care and Control, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, Hong Kong
| | - O Lamy
- Centre of Bone Diseases, Lausanne University Hospital, Lausanne, Switzerland
- Service of Internal Medicine, Lausanne University Hospital, Lausanne, Switzerland
| | - A Langhammer
- Department of Public Health and Nursing, Faculty of Medicine and Health Sciences, HUNT Research Centre, Norwegian University of Science and Technology, Trondheim, Norway
| | - B Larijani
- Endocrinology and Metabolism Research Center, Endocrinology and Metabolism Clinical Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran
| | - K Lippuner
- Department of Osteoporosis, Bern University Hospital, University of Bern, Bern, Switzerland
| | - D Mellström
- Geriatric Medicine, Department of Internal Medicine and Clinical Nutrition, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
- Geriatric Medicine, Sahlgrenska University Hospital Mölndal, Mölndal, Sweden
| | - T Merlijn
- Department of General Practice, Amsterdam UMC, Location VUmc, Amsterdam Public Health Research Institute, Amsterdam, The Netherlands
| | - A Nordström
- Division of Sustainable Health, Department of Public Health and Clinical Medicine, Umeå University, Umeå, Sweden
- School of Sport Sciences, Arctic University of Norway, Tromsø, Norway
| | - P Nordström
- Unit of Geriatric Medicine, Department of Community Medicine and Rehabilitation, Umeå University, Umeå, Sweden
| | - T W O'Neill
- National Institute for Health Research Manchester Biomedical Research Centre, Manchester University NHS Foundation Trust, Manchester Academic Health Science Centre, Manchester, UK
- Centre for Epidemiology Versus Arthritis, University of Manchester, Manchester, UK
| | - B Obermayer-Pietsch
- Department of Internal Medicine, Division of Endocrinology and Diabetology, Medical University Graz, Graz, Austria
- Center for Biomarker Research in Medicine, Graz, Austria
| | - C Ohlsson
- Sahlgrenska Osteoporosis Centre, Department of Internal Medicine and Clinical Nutrition, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
- Department of Drug Treatment, Sahlgrenska University Hospital, Region Västra Götaland, Gothenburg, Sweden
| | - E S Orwoll
- Department of Medicine, Oregon Health and Science University, Portland, OR, USA
| | - J A Pasco
- Institute for Physical and Mental Health and Clinical Translation (IMPACT), Deakin University, Geelong, Australia
- Department of Medicine-Western Health, The University of Melbourne, St Albans, Australia
- Barwon Health, Geelong, Australia
- Department of Epidemiology and Preventive Medicine, Monash University, Melbourne, Australia
| | - F Rivadeneira
- Department of Internal Medicine, Erasmus University Medical Center, Rotterdam, The Netherlands
| | - B Schei
- Department of Public Health and Nursing, Norwegian University of Science and Technology, Trondheim, Norway
- Department of Gynecology, St Olavs Hospital, Trondheim, Norway
| | - A-M Schott
- Université Claude Bernard Lyon 1, U INSERM 1290 RESHAPE, Lyon, France
| | - E J Shiroma
- Laboratory of Epidemiology and Population Sciences, National Institute On Aging, Baltimore, MD, USA
| | - K Siggeirsdottir
- Icelandic Heart Association, Kopavogur, Iceland
- Janus Rehabilitation, Reykjavik, Iceland
| | - E M Simonsick
- Translational Gerontology Branch, National Institute On Aging Intramural Research Program, Baltimore, MD, USA
| | | | - R Sund
- Kuopio Musculoskeletal Research Unit, University of Eastern Finland, Kuopio, Finland
| | - K M A Swart
- Department of General Practice, Amsterdam UMC, Location VUmc, Amsterdam Public Health Research Institute, Amsterdam, The Netherlands
| | - P Szulc
- INSERM UMR 1033, University of Lyon, Hôpital Edouard Herriot, Lyon, France
| | - J Tamaki
- Department of Hygiene and Public Health, Faculty of Medicine, Educational Foundation of Osaka Medical and Pharmaceutical University, Osaka, Japan
| | - D J Torgerson
- York Trials Unit, Department of Health Sciences, University of York, York, UK
| | - N M van Schoor
- Department of Epidemiology and Data Science, Amsterdam Public Health Research Institute, VU University Medical Center, Amsterdam, The Netherlands
| | - T P van Staa
- Centre for Health Informatics, Faculty of Biology, Medicine and Health, School of Health Sciences, University of Manchester, Manchester, UK
| | - J Vila
- Statistics Support Unit, Hospital del Mar Medical Research Institute, CIBER Epidemiology and Public Health (CIBERESP), Barcelona, Spain
| | - N J Wareham
- MRC Epidemiology Unit, University of Cambridge, Cambridge, UK
| | - N C Wright
- Department of Epidemiology, University of Alabama at Birmingham, Birmingham, AL, USA
| | - N Yoshimura
- Department of Preventive Medicine for Locomotive Organ Disorders, The University of Tokyo Hospital, Tokyo, Japan
| | - M C Zillikens
- Department of Internal Medicine, Erasmus University Medical Center, Rotterdam, The Netherlands
| | - M Zwart
- Health Center Can Gibert del Plà, Catalan Institute of Health, Girona, Spain
- Department of Medical Sciences, University of Girona, Girona, Spain
- GROIMAP (Research Group), Institut Universitari d'Investigació en Atenció Primària Jordi Gol, Barcelona, Spain
| | - N C Harvey
- MRC Lifecourse Epidemiology Centre, University of Southampton, Southampton, UK
- NIHR Southampton Biomedical Research Centre, University of Southampton and University Hospital Southampton NHS Foundation Trust, Southampton, UK
| | - M Lorentzon
- Mary McKillop Institute for Health Research, Australian Catholic University, Melbourne, Australia
- Sahlgrenska Osteoporosis Centre, Institute of Medicine, University of Gothenburg, Gothenburg, Sweden
- Geriatric Medicine, Region Västra Götaland, Sahlgrenska University Hospital, Mölndal, Sweden
| | - W D Leslie
- Department of Medicine, University of Manitoba, Winnipeg, MB, Canada
| | - J A Kanis
- Mary McKillop Institute for Health Research, Australian Catholic University, Melbourne, Australia.
- Centre for Metabolic Bone Diseases, University of Sheffield, Sheffield, UK.
- Centre for Metabolic Bone Diseases, University of Sheffield Medical School, Sheffield, UK.
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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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Rasmussen NH, Vestergaard P. Diabetes and osteoporosis - Treating two entities: A challenge or cause for concern? Best Pract Res Clin Rheumatol 2022; 36:101779. [PMID: 36154803 DOI: 10.1016/j.berh.2022.101779] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
People with T1D and T2D have an increased risk of fractures than the general population, posing several significant pathophysiologic, diagnostic, and therapeutic challenges. The pathophysiology is still not fully elucidated, but it is considered a combination of increased skeletal fragility and falls. Diagnostics issues exist, as regular and even newer scan methods underestimate the true incidence of osteoporosis and thus the fracture risk. Therefore, co-managing diabetes and osteoporosis by using top-line strategies is essential to preserve bone health and minimize the risk of falls. The therapeutic focus should start with lifestyle implementation and physical exercise interventions to reduce diabetic complications, strengthen bones, and improve postural control strategies. In addition, osteoporosis should be treated according to current guidelines by including bisphosphonates and antidiabetic drugs that support bone health. Finally, potentially modifiable risk factors for falls should be managed.
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Affiliation(s)
| | - Peter Vestergaard
- Steno Diabetes Center North Denmark, Aalborg University Hospital, Denmark
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Huang X, Li S, Lu W, Xiong L. Metformin activates Wnt/β-catenin for the treatment of diabetic osteoporosis. BMC Endocr Disord 2022; 22:189. [PMID: 35869471 PMCID: PMC9306077 DOI: 10.1186/s12902-022-01103-6] [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] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/19/2022] [Accepted: 07/15/2022] [Indexed: 11/10/2022] Open
Abstract
BACKGROUND With the deepening of social aging, the incidence rate of osteoporosis and diabetes continues to rise. More and more clinical studies show that diabetes is highly correlated with osteoporosis. Diabetes osteoporosis is considered as a metabolic bone disease of diabetes patients. This study aims to explore the role and mechanism of metformin (Met) in diabetic osteoporosis. METHODS Mouse MC3T3-E1 cells were treated with Met (0.5 mM) and exposed to high glucose (HG, 35 mM). The cells were cultured in an osteogenic medium for osteogenic differentiation, and the cell proliferation ability was determined using Cell Counting Kit-8; Alkaline phosphatase (ALP) activity detection and alizarin red staining were utilized to evaluate the effect of Met on MC3T3-E1 osteogenic differentiation. Western blot was used to detect the expressions of osteogenesis-related proteins (Runx2 and OCN) as well as Wnt/β-catenin signaling pathway-related proteins in MC3T3-E1 cells. RESULTS HG inhibited proliferation and calcification of MC3T3-E1 cells, down-regulated ALP activity, and the expression of Runx2 and OCN in MC3T3-E1 cells. Meanwhile, the activity of the Wnt/β-catenin signaling pathway was inhibited. Met treatment was found to significantly stimulate the proliferation and calcification of MC3T3-E1 cells under HG conditions, as well as increase the ALP activity and the protein expression level of Runx2 and OCN in the cells. As a result, osteogenic differentiation was promoted and osteoporosis was alleviated. Apart from this, Met also increased the protein expression level of Wnt1, β-catenin, and C-myc to activate the Wnt/β-catenin signaling pathway. CONCLUSION Met can stimulate the proliferation and osteogenic differentiation of MC3T3-E1 cells under HG conditions. Met may also treat diabetic osteoporosis through Wnt/β-catenin activation.
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Affiliation(s)
- Xiaopeng Huang
- Department of Orthopedics, Jiangxi Province Hospital of Integrated Chinese & Western Medicine, Nanchang, 330003, China
| | - Siyun Li
- Department of Orthopedics, Jiangxi Province Hospital of Integrated Chinese & Western Medicine, Nanchang, 330003, China
| | - Wenjie Lu
- Department of Orthopedics, Jiangxi Province Hospital of Integrated Chinese & Western Medicine, Nanchang, 330003, China
| | - Longjiang Xiong
- Department of Orthopedics, Jiangxi Province Hospital of Integrated Chinese & Western Medicine, Nanchang, 330003, China.
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16
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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: 62] [Impact Index Per Article: 20.7] [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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17
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Wang B, Wang Z, Poundarik AA, Zaki MJ, Bockman RS, Glicksberg BS, Nadkarni GN, Vashishth D. Unmasking Fracture Risk in Type 2 Diabetes: The Association of Longitudinal Glycemic Hemoglobin Level and Medications. J Clin Endocrinol Metab 2022; 107:e1390-e1401. [PMID: 34888676 PMCID: PMC8947783 DOI: 10.1210/clinem/dgab882] [Citation(s) in RCA: 21] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/13/2021] [Indexed: 11/19/2022]
Abstract
CONTEXT Fracture risk is underestimated in people with type 2 diabetes (T2D). OBJECTIVE To investigate the longitudinal relationship of glycated hemoglobin (HbA1c) and common medications on fracture risk in people with T2D. METHODS This retrospective population-based cohort study was conducted using de-identified claims and electronic health record data obtained from the OptumLabs Data Warehouse for the period January 1, 2007, to September 30, 2015. For each individual, the study was conducted within a 2-year HbA1c observation period and a 2-year fracture follow-up period. A cohort of 157 439 individuals with T2D [age ≥ 55 years with mean HbA1c value ≥ 6%] were selected from 4 018 250 US Medicare Advantage/Commercial enrollees with a T2D diagnosis. All fractures and fragility fractures were measured. RESULTS With covariates adjusted, poor glycemic control in T2D individuals was associated with an 29% increase of all fracture risk, compared with T2D individuals who had adequate glycemic control (HR: 1.29; 95% CI, 1.22-1.36). Treatment with metformin (HR: 0.88; 95% CI, 0.85-0.92) and DPP4 inhibitors (HR: 0.93; 95% CI, 0.88-0.98) was associated with a reduced all fracture risk, while insulin (HR: 1.26; 95% CI, 1.21-1.32), thiazolidinediones (HR: 1.23; 95% CI, 1.18-1.29), and meglitinides (HR: 1.12; 95% CI, 1.00-1.26) were associated with an increased all fracture risk (All P value < 0.05). Bisphosphonates were associated similarly with increased fracture risk in the T2D and nondiabetic groups. CONCLUSION Longitudinal 2-year HbA1c is independently associated with elevated all fracture risk in T2D individuals during a 2-year follow-up period. Metformin and DPP4 inhibitors can be used for management of T2D fracture risk.
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Affiliation(s)
- Bowen Wang
- Center for Biotechnology and Interdisciplinary Studies, Department of Biomedical Engineering, Rensselaer Polytechnic Institute, Troy, NY 12180, USA
- OptumLabs Visiting Fellow, Eden Prairie, MN 55344, USA
| | - Zehai Wang
- Center for Biotechnology and Interdisciplinary Studies, Department of Biomedical Engineering, Rensselaer Polytechnic Institute, Troy, NY 12180, USA
| | - Atharva A Poundarik
- Center for Biotechnology and Interdisciplinary Studies, Department of Biomedical Engineering, Rensselaer Polytechnic Institute, Troy, NY 12180, USA
| | - Mohammed J Zaki
- Department of Computer Science, Rensselaer Polytechnic Institute, Troy, NY 12180, USA
| | - Richard S Bockman
- Division of Endocrinology and Metabolic Bone Disease, Hospital for Special Surgery, New York, NY 10021, USA
| | - Benjamin S Glicksberg
- Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA
- Hasso Plattner Institute for Digital Health at Mount Sinai, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA
| | - Girish N Nadkarni
- Division of Nephrology, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA
- Hasso Plattner Institute for Digital Health at Mount Sinai, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA
| | - Deepak Vashishth
- Center for Biotechnology and Interdisciplinary Studies, Department of Biomedical Engineering, Rensselaer Polytechnic Institute, Troy, NY 12180, USA
- OptumLabs Visiting Fellow, Eden Prairie, MN 55344, USA
- Correspondence: Deepak Vashishth, PhD, Center for Biotechnology & Interdisciplinary Studies, Professor of Biomedical Engineering, 110 8th Street, BT 2213, Troy NY, USA 12180-3590.
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18
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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: 150] [Impact Index Per Article: 50.0] [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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19
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Viggers R, Al-Mashhadi Z, Starup-Linde J, Vestergaard P. The Efficacy of Alendronate Versus Denosumab on Major Osteoporotic Fracture Risk in Elderly Patients With Diabetes Mellitus: A Danish Retrospective Cohort Study. Front Endocrinol (Lausanne) 2022; 12:826997. [PMID: 35154013 PMCID: PMC8825412 DOI: 10.3389/fendo.2021.826997] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/01/2021] [Accepted: 12/24/2021] [Indexed: 12/25/2022] Open
Abstract
Objective Patients with diabetes mellitus have an increased risk of fractures; however, the underlying mechanism is largely unknown. We aimed to investigate whether the risk of major osteoporotic fractures in diabetes patients differs between subjects initiated with alendronate and denosumab, respectively. Methods and Research Design We conducted a retrospective nationwide cohort study through access to all discharge diagnoses (ICD-10 system) from the National Danish Patient Registry along with all redeemed drug prescriptions (ATC classification system) from the Health Service Prescription Registry. We identified all subjects with a diabetes diagnosis between 2000 and 2018 and collected data on the first new prescription of anti-osteoporotic treatment between 2011 and 2018. Exposure was defined as either alendronate or denosumab treatment initiated after diabetes diagnosis. Outcome information was collected by identification of all major osteoporotic fracture (MOF) diagnoses, i.e., hip, spine, forearm, and humerus, from exposure until 2018 or censoring by emigration or death. The risk of fracture was calculated as hazard ratios (HR) using multiply adjusted Cox proportional models with death as a competing risk. Results We included 8,745 subjects initiated with either alendronate (n = 8,255) or denosumab (n = 490). The cohort consisted of subjects with a mean age of 73.62 (SD ± 9.27) years, primarily females (69%) and suffering mainly from type 2 diabetes (98.22%) with a median diabetes duration at baseline of 5.45 years (IQR 2.41-9.19). Those in the denosumab group were older (mean 75.60 [SD ± 9.72] versus 73.51 [SD ± 9.23] years), had a higher proportion of women (81% versus 68%, RR 1.18 [95% CI 1.13-1.24], and were more comorbid (mean CCI 2.68 [95% CI 2.47-2.88] versus 1.98 [95% CI 1.93-2.02]) compared to alendronate initiators. In addition, denosumab users had a higher prevalence of previous fractures (64% versus 46%, RR 1.38 [95% CI 1.28-1.48]). The adjusted HR for any MOF after treatment initiation with denosumab was 0.89 (95% CI 0.78-1.02) compared to initiation with alendronate. Conclusion The risk of incident MOF among subjects with diabetes was similar between those initially treated with alendronate and denosumab. These findings indicate that the two treatment strategies are equally effective in preventing osteoporotic fractures in subjects with diabetes.
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Affiliation(s)
- Rikke Viggers
- Steno Diabetes Center North Jutland, Department of Endocrinology, Aalborg University Hospital, Aalborg, Denmark
- Department of Clinical Medicine, Aalborg University, Aalborg, Denmark
| | - Zheer Al-Mashhadi
- Steno Diabetes Center Aarhus, Aarhus University Hospital, Aarhus, Denmark
- Department of Clinical Medicine, Aarhus University, Aarhus, Denmark
| | - Jakob Starup-Linde
- Steno Diabetes Center Aarhus, Aarhus University Hospital, Aarhus, Denmark
- Department of Endocrinology and Internal Medicine, Aarhus University Hospital, Aarhus, Denmark
| | - Peter Vestergaard
- Steno Diabetes Center North Jutland, Department of Endocrinology, Aalborg University Hospital, Aalborg, Denmark
- Department of Clinical Medicine, Aalborg University, Aalborg, Denmark
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20
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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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21
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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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22
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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: 15] [Impact Index Per Article: 3.8] [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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23
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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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24
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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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25
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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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Huang JF, Wu QN, Zheng XQ, Sun XL, Wu CY, Wang XB, Wu CW, Wang B, Wang XY, Bergman M, Wu AM. The Characteristics and Mortality of Osteoporosis, Osteomyelitis, or Rheumatoid Arthritis in the Diabetes Population: A Retrospective Study. Int J Endocrinol 2020; 2020:8821978. [PMID: 33224196 PMCID: PMC7669351 DOI: 10.1155/2020/8821978] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/01/2020] [Revised: 09/05/2020] [Accepted: 10/22/2020] [Indexed: 02/08/2023] Open
Abstract
BACKGROUND Patients with diabetes mellitus are prone to develop osteoporosis, osteomyelitis, or rheumatoid arthritis (RA). Furthermore, the presence of these complications in those with diabetes may lead to higher mortality. The aim of our study was to assess characteristics and mortality of osteoporosis, osteomyelitis, or rheumatoid arthritis in individuals with diabetes. METHODS We analyzed osteoporosis, osteomyelitis, and RA deaths associated with diabetes from 1999-2017 using the CDC WONDER system (CDC WONDER; https://wonder.cdc.gov). We used ICD-10 codes to categorize the underlying and contributing causes of death. Crude mortality rates (CMR) and age-adjusted mortality rates (AAMR) per 1,000,000 person-years were calculated. RESULTS The AAMR for osteoporosis in the population with diabetes was significantly higher in females (AAMR: 4.17, 95% CI: 4.10-4.24) than in males (AAMR: 1.12, 95% CI: 1.07-1.16). Deaths due to osteoporosis increased gradually from 1999, peaked in 2003 (AAMR: 3.78, 95% CI: 3.55-4.00), and reached a nadir in 2016 (AAMR: 2.32, 95% CI: 2.15-2.48). The AAMR for RA associated with diabetes was slightly higher in females (AAMR: 4.04, 95% CI: 3.98-4.11) than in males (AAMR: 2.45, 95% CI: 2.39-2.51). The mortality rate due to RA increased slightly from 1999 (AAMR: 3.18, 95% CI: 2.97-3.39) to 2017 (AAMR: 3.20, 95% CI: 3.02-3.38). The AAMR for osteomyelitis associated with diabetes was higher in males (AAMR: 4.36, 95% CI: 4.28-4.44) than in females (AAMR: 2.31, 95% CI: 2.26-2.36). From 1999 to 2017, the AAMR from osteomyelitis in this population was 2.63 (95% CI: 2.44-2.82) per 1,000,000 person-years in 1999 and 4.25 (95% CI: 4.05-4.46) per 1,000,000 person-years in 2017. CONCLUSIONS We found an increase in the age-adjusted mortality rates of RA and osteomyelitis and a decrease of osteoporosis associated with diabetes from 1999 to 2017. We suggest that increased attention should therefore be given to these diseases in the population with diabetes, especially in efforts to develop preventative and treatment strategies.
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Affiliation(s)
- Jin-Feng Huang
- Department of Orthopaedics, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325027, China
- The Second School of Medicine, Wenzhou Medical University, Wenzhou, Zhejiang 325027, China
| | - Qi-Nan Wu
- Endocrinology and Nephrology Department, Chongqing University Cancer Hospital and Chongqing Cancer Institute and Chongqing Cancer Hospital, Chongqing, China
| | - Xuan-Qi Zheng
- Department of Orthopaedics, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325027, China
- The Second School of Medicine, Wenzhou Medical University, Wenzhou, Zhejiang 325027, China
| | - Xiao-Lei Sun
- Department of Orthopaedics, Tianjin Hospital, Tianjin 300210, China
| | - Chen-Yu Wu
- Department of Orthopaedics, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325027, China
- The Second School of Medicine, Wenzhou Medical University, Wenzhou, Zhejiang 325027, China
| | - Xiao-Bing Wang
- Department of Rheumatology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China
| | - Chen-Wei Wu
- Diabetes Center and Department of Endocrinology, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, China
| | - Bin Wang
- Department of Sports Medicine and Adult Reconstruction Surgery, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing 210009, China
| | - Xiang-Yang Wang
- Department of Orthopaedics, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325027, China
- The Second School of Medicine, Wenzhou Medical University, Wenzhou, Zhejiang 325027, China
| | - Michael Bergman
- NYU Grossman School of Medicine, NYU Langone Diabetes Prevention Program, New York, NY 10016, USA
| | - Ai-Min Wu
- Department of Orthopaedics, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325027, China
- The Second School of Medicine, Wenzhou Medical University, Wenzhou, Zhejiang 325027, China
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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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Chen YJ, Kung PT, Chou WY, Tsai WC. Alendronate medication possession ratio and the risk of second hip fracture: an 11-year population-based cohort study in Taiwan. Osteoporos Int 2020; 31:1555-1563. [PMID: 32221674 DOI: 10.1007/s00198-020-05399-9] [Citation(s) in RCA: 5] [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: 10/16/2019] [Accepted: 03/20/2020] [Indexed: 01/22/2023]
Abstract
UNLABELLED Alendronate is effective in preventing second hip fracture in osteoporotic patients. However, no consensus exists on the duration that is effective in preventing a second hip fracture. Our study demonstrated that risk can be reduced when the prescription is ≥ 6 months for the year following the index hip fracture. INTRODUCTION Alendronate is effective in preventing second hip fracture in osteoporotic patients. However, no consensus exists on the accurate medication possession ratio (MPR) that is effective in preventing a second hip fracture. Our objective was to compare the risk of second hip fracture in patients treated with different MPR of alendronate. METHODS In this population-based cohort study, data from National Health Insurance Research Database of Taiwan were analyzed. Patients 50 years and older who had an index hip fracture and were not receiving any osteoporotic medications before their fracture during 2000-2010 were included. The cohort consisted of 88,320 patients who were new alendronate users (n = 9278) and non-users (n = 79,042). Those without alendronate were matched 4:1 as the control group. Patients were subdivided into those with no medication, MPR < 25%, MPR 25-50%, MPR 50-75%, and MPR 75-100%. Cox proportional hazard models were used to calculate the adjusted hazard ratios for different MPRs of alendronate. RESULTS After matching, 38,675 patients were included in this study; 20,363 (52.7%) were women, and 30,940 (80%) patients were without medication of alendronate. During follow-up on December 31, 2012, 2392 patients had a second hip fracture, for an incidence of 1449/100,000 person-years. Patients with alendronate MPR 50-75% had a lower risk of a second hip fracture compared to non-users (hazard ratio 0.66). When the MPR increased to 75-100%, the hazard ratio decreased to 0.61. CONCLUSIONS In this population-based cohort study, risk of a second hip fracture can be reduced when the alendronate MPR is ≥ 50% for the year following the index hip fracture. As the MPR increases, the risk of a second hip fracture decreases.
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Affiliation(s)
- Y J Chen
- Department of Health Services Administration, China Medical University, Taiwan, No.91, Hsueh-Shih Road, Taichung, Taiwan, 40402, Republic of China
- Department of Orthopedic Surgery, China Medical University Hospital, Taiwan, No. 2, Yuh-Der Road, Taichung, Taiwan, 40402, Republic of China
- School of Medicine, China Medical University, No.91, Hsueh-Shih Road, Taichung, Taiwan, 40402, Republic of China
| | - P T Kung
- Department of Health Administration, Asia University, Taiwan, No. 500, Liufeng Road., Wufeng, Taichung, Taiwan, 41354, Republic of China
- Department of Medical Research, China Medical University Hospital, China Medical University, No.91, Hsueh-Shih Road, Taichung, Taiwan, Republic of China
| | - W Y Chou
- Department of Health Services Administration, China Medical University, Taiwan, No.91, Hsueh-Shih Road, Taichung, Taiwan, 40402, Republic of China
| | - W C Tsai
- Department of Health Services Administration, China Medical University, Taiwan, No.91, Hsueh-Shih Road, Taichung, Taiwan, 40402, Republic of China.
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Vilaca T, Schini M, Harnan S, Sutton A, Poku E, Allen IE, Cummings SR, Eastell R. The risk of hip and non-vertebral fractures in type 1 and type 2 diabetes: A systematic review and meta-analysis update. Bone 2020; 137:115457. [PMID: 32480023 DOI: 10.1016/j.bone.2020.115457] [Citation(s) in RCA: 144] [Impact Index Per Article: 28.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/24/2020] [Revised: 05/22/2020] [Accepted: 05/25/2020] [Indexed: 02/06/2023]
Abstract
BACKGROUND Diabetes is associated with increased fracture risk but we do not know what affects this risk. We investigated the risk of hip and non-vertebral fractures in diabetes and whether this risk was affected by age, gender, body mass index, diabetes type and duration, insulin use and diabetic complications. METHODS We selected a previously published review to be updated. MEDLINE, Embase and Cochrane databases were searched up to March 2020. We included observational studies with age and gender-adjusted risk of fractures in adults with diabetes compared to adults without diabetes. We extracted data from published reports that we summarised using random effects model. FINDINGS From the 3140 records identified, 49 were included, 42 in the hip fracture analysis, reporting data from 17,571,738 participants with 319,652 fractures and 17 in the non-vertebral fracture review, reporting data from 2,978,487 participants with 181,228 fractures. We found an increase in the risk of fracture in diabetes both for hip (RR 4.93, 3.06-7.95, in type 1 diabetes and RR1.33, 1.19-1.49, in type 2 diabetes) and for non-vertebral fractures (RR 1.92, 0.92-3.99, in type 1 and RR 1.19, 1,11-1.28 in type 2). At the hip, the risk was higher in the younger population in both type 1 and type 2 diabetes. In those with type 2 diabetes, longer diabetes duration and insulin use was associated with an increased risk. We did not investigate the effect of bone density, falls, anti-diabetic drugs and hypoglycemia. CONCLUSION Diabetes is associated with an increase in both hip and non-vertebral fracture risk.
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Affiliation(s)
- Tatiane Vilaca
- Academic Unit of Bone Metabolism, The Mellanby Centre for Bone Research, University of Sheffield, UK.
| | - Marian Schini
- Academic Unit of Bone Metabolism, The Mellanby Centre for Bone Research, University of Sheffield, UK.
| | - Susan Harnan
- School of Health and Related Research (ScHARR), University of Sheffield, UK.
| | - Anthea Sutton
- School of Health and Related Research (ScHARR), University of Sheffield, UK.
| | - Edith Poku
- School of Health and Related Research (ScHARR), University of Sheffield, UK.
| | | | - Steven R Cummings
- San Francisco Coordinating Center, Sutter Health, University of California, San Francisco, USA.
| | - Richard Eastell
- Academic Unit of Bone Metabolism, The Mellanby Centre for Bone Research, University of Sheffield, UK.
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Rasmussen NH, Dal J, de Vries F, van den Bergh JP, Jensen MH, Vestergaard P. Diabetes and fractures: new evidence of atypical femoral fractures? Osteoporos Int 2020; 31:447-455. [PMID: 31838553 DOI: 10.1007/s00198-019-05224-y] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/20/2019] [Accepted: 11/05/2019] [Indexed: 12/12/2022]
Abstract
UNLABELLED Patients with diabetes have an increased risk of fractures. In this study, subtrochanteric and femoral shaft fractures were increased in patients with type 1 diabetes compared with the general population. In the light of this, more evidence points towards an association between diabetes and atypical femoral fractures. INTRODUCTION Patients with diabetes have an increased risk of femoral fractures, but little is known about the risk of atypical femoral fractures (AFFs). The aim of this study was to identify the risk of subtrochanteric and femoral shaft (ST/FS) fractures and estimate the risk of AFFs in patients with type 1 (T1D) and type 2 diabetes (T2D). METHODS From the nationwide Danish National Patient Register, we identified patients with T1D (n = 19,896), T2D (n = 312,188), and sex- and aged-matched controls without diabetes (n = 996,252) from the general population and all ST/FS fractures (n = 7509). Data were analyzed using a Cox proportional-hazards model and the incidence rate and rate ratio of ST/FS fractures were estimated. RESULTS The incidence rate of ST/FS fractures in T1D was 52.14 events per 100,000 person years and 73.21 per 100,000 person years in T2D. T1D was associated with an increased risk of ST/FS (HR 2.07 (95% CI 1.68-2.56)), whereas T2D was not (HR 0.99 (95% CI 0.94-1.10)). Previous ST/FS fractures were associated with an increased risk of subsequent ST/FS fractures (HR 6.95 (95% CI 6.00-8.05)) and the use of bisphosphonates with an increased risk of ST/FS fractures (HR 1.72 (95% CI 1.54-1.91)). CONCLUSION Patients with T1D have a higher risk of ST/FS fractures compared with sex- and age-matched controls. Since a proportion of ST/FS fractures are classified as AFFs, this could point towards the fact that AFFs also are increased in patients with T1D, but not T2D.
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Affiliation(s)
- N H Rasmussen
- Steno Diabetes Center North, Aalborg University Hospital, Aalborg, Denmark.
| | - J Dal
- Department of Endocrinology, Aalborg University Hospital, Aalborg, Denmark
| | - F de Vries
- Department of Clinical Pharmacy & Toxicology, Maastricht UMC+, Maastricht, The Netherlands
- Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Utrecht, The Netherlands
| | - J P van den Bergh
- Department of Internal Medicine, VieCuri Medical Center, Venlo, The Netherlands
- Department of Internal Medicine, Maastricht UMC+, Maastricht, The Netherlands
- Faculty of Medicine and Life Sciences, University Hasselt, Hasselt, Belgium
| | - M H Jensen
- Steno Diabetes Center North, Aalborg University Hospital, Aalborg, Denmark
| | - P Vestergaard
- Steno Diabetes Center North, Aalborg University Hospital, Aalborg, Denmark
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Tebé C, Martínez-Laguna D, Carbonell-Abella C, Reyes C, Moreno V, Diez-Perez A, Collins GS, Prieto-Alhambra D. The association between type 2 diabetes mellitus, hip fracture, and post-hip fracture mortality: a multi-state cohort analysis. Osteoporos Int 2019; 30:2407-2415. [PMID: 31444526 DOI: 10.1007/s00198-019-05122-3] [Citation(s) in RCA: 37] [Impact Index Per Article: 6.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/10/2019] [Accepted: 07/31/2019] [Indexed: 12/20/2022]
Abstract
UNLABELLED Type 2 diabetes mellitus (T2DM) is associated with an excess risk of fractures and overall mortality. This study compared hip fracture and post-hip fracture mortality in T2DM and non-diabetic subjects. The salient findings are that subjects in T2DM are at higher risk of dying after suffering a hip fracture. INTRODUCTION Previous research suggests that individuals with T2DM are at an excess risk of both fractures and overall mortality, but their combined effect is unknown. Using multi-state cohort analyses, we estimate the association between T2DM and the transition to hip fracture, post-hip fracture mortality, and hip fracture-free all-cause death. METHODS Population-based cohort from Catalonia, Spain, including all individuals aged 65 to 80 years with a recorded diagnosis of T2DM on 1 January 2006; and non-T2DM matched (up to 2:1) by year of birth, gender, and primary care practice. RESULTS A total of 44,802 T2DM and 81,233 matched controls (53% women, mean age 72 years old) were followed for a median of 8 years: 23,818 died without fracturing and 3317 broke a hip, of whom 838 subsequently died. Adjusted HRs for hip fracture-free mortality were 1.32 (95% CI 1.28 to 1.37) for men and 1.72 (95% CI 1.65 to 1.79) for women. HRs for hip fracture were 1.24 (95% CI 1.08 to 1.43) and 1.48 (95% CI 1.36 to 1.60), whilst HRs for post-hip fracture mortality were 1.28 (95% CI 1.02 to 1.60) and 1.57 (95% CI 1.31 to 1.88) in men and women, respectively. CONCLUSION T2DM individuals are at increased risk of hip fracture, post-hip fracture mortality, and hip fracture-free death. After adjustment, T2DM men were at a 28% higher risk of dying after suffering a hip fracture and women had 57% excess risk of post-hip fracture mortality.
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Affiliation(s)
- C Tebé
- Biostatistics Unit at Bellvitge Biomedical Research Institute (IDIBELL), L'Hospitalet, Spain
- Universitat de Barcelona, Barcelona, Spain
- Universitat Rovira i Virgili, Reus, Spain
| | - D Martínez-Laguna
- Atenció Primària Barcelona Ciutat, Institut Català de la Salut, Barcelona, Spain
- Grupo de Investigación GREMPAL, IDIAP Jordi Gol and CIBERFes, Universitat Autònoma de Barcelona and Instituto de Salud Carlos III, Barcelona, Spain
| | - C Carbonell-Abella
- Atenció Primària Barcelona Ciutat, Institut Català de la Salut, Barcelona, Spain
- Grupo de Investigación GREMPAL, IDIAP Jordi Gol and CIBERFes, Universitat Autònoma de Barcelona and Instituto de Salud Carlos III, Barcelona, Spain
| | - C Reyes
- Grupo de Investigación GREMPAL, IDIAP Jordi Gol and CIBERFes, Universitat Autònoma de Barcelona and Instituto de Salud Carlos III, Barcelona, Spain
| | - V Moreno
- Biostatistics Unit at Bellvitge Biomedical Research Institute (IDIBELL), L'Hospitalet, Spain
- Universitat de Barcelona, Barcelona, Spain
- Cancer Prevention and Control Program, Catalan Institute of Oncology-IDIBELL, 08908, L'Hospitalet de Llobregat, Spain
- CIBER Epidemiología y Salud Pública (CIBERESP), Madrid, Spain
| | - A Diez-Perez
- Musculoskeletal Research Unit, IMIM-Hospital del Mar and CIBERFes, Universitat Autònoma de Barcelona and Instituto de Salud Carlos III, 08003, Barcelona, Spain
| | - G S Collins
- Centre for Statistics in Medicine, Nuffield Department of Orthopaedics, Rheumatology, and Musculoskeletal Sciences (NDORMS), University of Oxford, Windmill Road, Oxford, UK
| | - D Prieto-Alhambra
- Grupo de Investigación GREMPAL, IDIAP Jordi Gol and CIBERFes, Universitat Autònoma de Barcelona and Instituto de Salud Carlos III, Barcelona, Spain.
- Centre for Statistics in Medicine, Nuffield Department of Orthopaedics, Rheumatology, and Musculoskeletal Sciences (NDORMS), University of Oxford, Windmill Road, Oxford, UK.
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Nomura S, Kitami A, Takao-Kawabata R, Takakura A, Nakatsugawa M, Kono R, Maeno A, Tokuda A, Isogai Y, Ishizuya T, Utsunomiya H, Nakamura M. Teriparatide Improves Bone and Lipid Metabolism in a Male Rat Model of Type 2 Diabetes Mellitus. Endocrinology 2019; 160:2339-2352. [PMID: 31504411 PMCID: PMC6760306 DOI: 10.1210/en.2019-00239] [Citation(s) in RCA: 20] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/25/2019] [Accepted: 07/17/2019] [Indexed: 01/22/2023]
Abstract
Osteoporosis is a complication of diabetes mellitus (DM). The pathology of diabetic osteoporosis is distinct from postmenopausal osteoporosis, and there are no specific treatment guidelines for diabetic osteoporosis. In the current study, this issue was addressed by evaluating the effect of osteoporosis medications, such as the anabolic agent PTH [teriparatide (TPTD)] and the antiresorptive agents calcitonin [elcatonin (ECT)] and bisphosphonate [risedronate (RIS)], on bone metabolism as well as on glucose and lipid metabolism in spontaneously diabetic Torii (SDT) fatty rats, which are a model of type 2 DM (T2DM). The medicines were injected subcutaneously into 8-week-old male SDT fatty rats three times weekly for 8 weeks. TPTD treatment in SDT fatty rats increased the osteoblast number and function on trabecular bone in vertebrae, and increased the trabecular bone mass, bone mineral density (BMD), and mechanical strength of vertebrae. Additionally, TPTD improved cortical bone structure and increased BMD. RIS decreased the osteoclast number and function, which led to an increase in vertebral bone mineral content and BMD in the femoral diaphysis, and mechanical strength was increased in the vertebrae. ECT showed no clear effects on bone mass or metabolism. Similar to diabetic lesions, all of the drugs had no effects on hyperglycemia, pancreas morphology, or serum insulin and glucagon levels. However, triglyceride levels and lipid droplets in fatty liver were decreased in the TPTD group. These results suggest that TPTD may be useful for treating fatty liver in addition to osteoporosis in T2DM.
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Affiliation(s)
- Sachiko Nomura
- Department of Strategic Surveillance for Functional Food and Comprehensive Traditional Medicine, Wakayama Medical University, Wakayama, Japan
| | - Akihiro Kitami
- Clinical Development Center, Asahi Kasei Pharma Corporation, Chiyoda-ku, Tokyo, Japan
| | - Ryoko Takao-Kawabata
- Pharmaceuticals Research Center, Asahi Kasei Pharma Corporation, Izunokuni, Shizuoka, Japan
- Correspondence: Ryoko Takao-Kawabata, PhD, Pharmaceuticals Research Center, Asahi Kasei Pharma Corporation, 632-1 Mifuku, Izunokuni, Shizuoka 410-2321, Japan. E-mail: ; or Misa Nakamura, PhD, Department of Rehabilitation, Osaka Kawasaki Rehabilitation University, 158 Mizuma, Kaizuka, Osaka 597-0104, Japan. E-mail:
| | - Aya Takakura
- Pharmaceuticals Research Center, Asahi Kasei Pharma Corporation, Izunokuni, Shizuoka, Japan
| | - Momoko Nakatsugawa
- Pharmaceuticals Research Center, Asahi Kasei Pharma Corporation, Izunokuni, Shizuoka, Japan
| | - Ryohei Kono
- Department of Strategic Surveillance for Functional Food and Comprehensive Traditional Medicine, Wakayama Medical University, Wakayama, Japan
| | - Akihiro Maeno
- Department of Medical Chemistry, Kansai Medical University, Hirakata, Osaka, Japan
| | - Akihiko Tokuda
- Department of Strategic Surveillance for Functional Food and Comprehensive Traditional Medicine, Wakayama Medical University, Wakayama, Japan
| | - Yukihiro Isogai
- Corporate Planning and Coordination Division, Asahi Kasei Pharma Corporation, Chiyoda-ku, Tokyo, Japan
| | - Toshinori Ishizuya
- Pharmaceuticals Research Center, Asahi Kasei Pharma Corporation, Izunokuni, Shizuoka, Japan
| | - Hirotoshi Utsunomiya
- Department of Strategic Surveillance for Functional Food and Comprehensive Traditional Medicine, Wakayama Medical University, Wakayama, Japan
| | - Misa Nakamura
- Department of Rehabilitation, Osaka Kawasaki Rehabilitation University, Kaizuka, Osaka, Japan
- Correspondence: Ryoko Takao-Kawabata, PhD, Pharmaceuticals Research Center, Asahi Kasei Pharma Corporation, 632-1 Mifuku, Izunokuni, Shizuoka 410-2321, Japan. E-mail: ; or Misa Nakamura, PhD, Department of Rehabilitation, Osaka Kawasaki Rehabilitation University, 158 Mizuma, Kaizuka, Osaka 597-0104, Japan. E-mail:
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Rossi M, Battafarano G, Pepe J, Minisola S, Del Fattore A. The Endocrine Function of Osteocalcin Regulated by Bone Resorption: A Lesson from Reduced and Increased Bone Mass Diseases. Int J Mol Sci 2019; 20:ijms20184502. [PMID: 31514440 PMCID: PMC6769834 DOI: 10.3390/ijms20184502] [Citation(s) in RCA: 28] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/28/2019] [Revised: 09/10/2019] [Accepted: 09/10/2019] [Indexed: 02/06/2023] Open
Abstract
Bone is a peculiar tissue subjected to a continuous process of self-renewal essential to assure the integrity of the skeleton and to explicate the endocrine functions. The study of bone diseases characterized by increased or reduced bone mass due to osteoclast alterations has been essential to understand the great role played by osteocalcin in the endocrine functions of the skeleton. The ability of osteoclasts to regulate the decarboxylation of osteocalcin and to control glucose metabolism, male fertility, and cognitive functions was demonstrated by the use of animal models. In this review we described how diseases characterized by defective and increased bone resorption activity, as osteopetrosis and osteoporosis, were essential to understand the involvement of bone tissue in whole body physiology. To translate this knowledge into humans, recently published reports on patients were described, but further studies should be performed to confirm this complex hormonal regulation in humans.
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Affiliation(s)
- Michela Rossi
- Bone Physiopathology Group, Multifactorial Disease and Complex Phenotype Research Area, Bambino Gesù Children's Hospital, IRCCS, 00146 Rome, Italy.
| | - Giulia Battafarano
- Bone Physiopathology Group, Multifactorial Disease and Complex Phenotype Research Area, Bambino Gesù Children's Hospital, IRCCS, 00146 Rome, Italy.
| | - Jessica Pepe
- Department of Internal Medicine and Medical Disciplines, Sapienza University of Rome, 00186 Rome, Italy.
| | - Salvatore Minisola
- Department of Internal Medicine and Medical Disciplines, Sapienza University of Rome, 00186 Rome, Italy.
| | - Andrea Del Fattore
- Bone Physiopathology Group, Multifactorial Disease and Complex Phenotype Research Area, Bambino Gesù Children's Hospital, IRCCS, 00146 Rome, Italy.
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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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Henderson S, Ibe I, Cahill S, Chung YH, Lee FY. Bone Quality and Fracture-Healing in Type-1 and Type-2 Diabetes Mellitus. J Bone Joint Surg Am 2019; 101:1399-1410. [PMID: 31393433 DOI: 10.2106/jbjs.18.01297] [Citation(s) in RCA: 30] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Affiliation(s)
- Shasta Henderson
- Department of Orthopaedics, Pennsylvania State University, Hershey, Pennsylvania
| | - Izuchukwu Ibe
- Department of Orthopaedics and Rehabilitation (I.I.), Yale School of Medicine (S.C., Y.-H.C., and F.Y.L.), New Haven, Connecticut
| | - Sean Cahill
- Department of Orthopaedics and Rehabilitation (I.I.), Yale School of Medicine (S.C., Y.-H.C., and F.Y.L.), New Haven, Connecticut
| | - Yeon-Ho Chung
- Department of Orthopaedics and Rehabilitation (I.I.), Yale School of Medicine (S.C., Y.-H.C., and F.Y.L.), New Haven, Connecticut
| | - Francis Y Lee
- Department of Orthopaedics and Rehabilitation (I.I.), Yale School of Medicine (S.C., Y.-H.C., and F.Y.L.), New Haven, Connecticut
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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: 49] [Impact Index Per Article: 8.2] [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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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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Black DM, Abrahamsen B, Bouxsein ML, Einhorn T, Napoli N. Atypical Femur Fractures: Review of Epidemiology, Relationship to Bisphosphonates, Prevention, and Clinical Management. Endocr Rev 2019; 40:333-368. [PMID: 30169557 DOI: 10.1210/er.2018-00001] [Citation(s) in RCA: 126] [Impact Index Per Article: 21.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/03/2018] [Accepted: 05/08/2018] [Indexed: 12/18/2022]
Abstract
Bisphosphonates (BPs) are highly effective in treating osteoporosis and reducing hip, vertebral, and other fractures by as much as 50% to 70%. However, since 2006, atypical femur fractures (AFFs) emerged as potential side effects of BPs and other treatments. These fractures have unusual radiologic features and occur with little trauma. Public concern has led to a >50% decrease in BP usage. AFFs are rare: for each AFF, >1200 fractures, including 135 hip fractures, are prevented. Case definition criteria were updated by the American Society of Bone and Mineral Research in 2014. Many epidemiologic studies have been reported, and although methodologically challenging, generally support a BP-AFF association. However, the magnitude of the association between BPs and AFFs is uncertain: estimates of relative risk for AFFs among BP users vs nonusers range from 1 to 65 with a meta-analysis estimate of 1.7. Although mechanistic studies have proposed several hypotheses explaining how BPs might decrease bone strength, AFF pathogenesis remains uncertain and cannot explain the paradox of efficacy of reduction of common fractures while increasing risk for rare fractures at one site. There are several consistent risk factors, including Asian race (in North America), femoral bowing, and glucocorticoid use, whereas others remain unclear. Consensus is emerging about strategies to prevent AFFs in BP users (including drug holidays after 5 years' use in some patients). In conclusion, AFFs can be devastating, but even under the most pessimistic assumptions, the benefit/risk ratio is highly positive for BPs, particularly during 3 to 5 years of use. As understanding of AFFs increases, it is becoming increasingly possible to maximize BP benefits while minimizing AFF risk.
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Affiliation(s)
- Dennis M Black
- University of California, San Francisco, San Francisco, California
| | | | | | | | - Nicola Napoli
- Università Campus Bio-Medico di Roma, Rome, Italy.,IRCCS Istituto Ortopedico Galeazzi, Milan, Italy
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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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Lee YS, Gupta R, Kwon JT, Cho DC, Seo YJ, Seu SY, Park EK, Han I, Kim CH, Sung JK, Kim KT. Effect of a bisphosphonate and selective estrogen receptor modulator on bone remodeling in streptozotocin-induced diabetes and ovariectomized rat model. Spine J 2018; 18:1877-1887. [PMID: 29793000 DOI: 10.1016/j.spinee.2018.05.020] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/19/2018] [Revised: 04/26/2018] [Accepted: 05/16/2018] [Indexed: 02/03/2023]
Abstract
BACKGROUND CONTEXT Diabetes and menopause can cause severe osteoporosis. In general, menopause and diabetes can lead to an imbalance in bone turnover, which results in secondary osteoporosis. However, the efficacy of antiresorptive drugs against this form of osteoporosis has not been extensively evaluated. OBJECTIVE The aim of this study was to determine the changes in vertebral bone remodeling when postmenopausal osteoporosis is accompanied by diabetes and to compare the efficacy of bisphosphonates and selective estrogen-receptor modulators (SERMs) against these outcomes. STUDY DESIGN Streptozotocin-induced diabetic, ovariectomized Sprague-Dawley rats were used as the disease model. Alendronate and raloxifene were used as the bisphosphonate and SERM, respectively. METHODS We divided 62 female rats into five groups: (1) control (n=14), (2) DM (diabetes) (n=12), (3) DM+OVX (diabetes+ovariectomy) (n=12), (4) DM+OVX+A (diabetes+ovariectomy+alendronate) (n=12), and (5) DM+OVX+R (diabetes+ovariectomy+raloxifene) (n=12). Serum biochemical markers of bone turnover, including osteocalcin and the C-telopeptide of type I collagen (CTX-1), were analyzed. We measured histomorphometric parameters of the fourth lumbar vertebrae using microcomputed tomography. Mechanical strength was evaluated by a compression test. RESULTS In the DM and DM+OVX group, only the levels of osteocalcin significantly decreased compared with those of the control group at 8 weeks after OVX. At 12 weeks, the serum CTX-1 levels in the DM+OVX+A and DM+OVX+R groups were significantly lower than those of the DM+OVX group, but there were no changes in the levels of osteocalcin. Bone mineral density and mechanical strength were higher in the DM+OVX+A and DM+OVX+R groups than in the DM and DM+OVX groups (p<.05). CONCLUSIONS Even if postmenopausal osteoporosis is accompanied by diabetes in this animal model, both alendronate and raloxifene seem to show antiresorptive effects, decreased bone turnover rates, and improved bone mechanical strength. Therefore, alendronate and raloxifene are effective in the treatment of osteoporosis even for bone loss caused by DM and postmenopausal osteoporosis.
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Affiliation(s)
- Young-Seok Lee
- Department of Neurosurgery, Gyeongsang National University, Gyeongsang National University Hospital, 79, Gangnam-ro, Jinju-si, Gyeongsangnam-do, 52727, Republic of Korea
| | - Rishab Gupta
- International Collaboration On Repair Discoveries (ICORD), University of British Columbia, 818 W 10th Ave, Vancouver, British Columbia V5Z1M9 Canada
| | - Jeong-Taik Kwon
- Department of Neurosurgery, Chung-Ang University College of Medicine, 102, Heukseok-ro, Dongjak-gu, Seoul, 06973, Republic of Korea
| | - Dae-Chul Cho
- Department of Neurosurgery, Kyungpook National University, Kyungpook National University Hospital, 130 Dongdeok-ro, Jung-gu, Daegu 700-721, Republic of Korea
| | - Ye Jin Seo
- Department of Neurosurgery, Kyungpook National University, Kyungpook National University Hospital, 130 Dongdeok-ro, Jung-gu, Daegu 700-721, Republic of Korea
| | - Sung Young Seu
- Department of Neurosurgery, Kyungpook National University, Kyungpook National University Hospital, 130 Dongdeok-ro, Jung-gu, Daegu 700-721, Republic of Korea
| | - Eui Kyun Park
- Department of Pathology and Regenerative Medicine, School of Dentistry, Kyungpook National University, 2175, Dalgubeol-daero, Jung-gu, Daegu, 41950, Republic of Korea
| | - Inbo Han
- Department of Neurosurgery, CHA University, CHA Bundang Medical Center, Seongnam-si, 59, Yatap-ro, Bundang-gu, Seongnam-si, Gyeonggi-do, 3496, Republic of Korea
| | - Chi-Heon Kim
- Department of Neurosurgery, Seoul National University Hospital, Seoul National University College of Medicine, 101, Daehak-ro, Jongno-gu, Seoul, 03080, Republic of Korea
| | - Joo-Kyung Sung
- Department of Neurosurgery, Kyungpook National University, Kyungpook National University Hospital, 130 Dongdeok-ro, Jung-gu, Daegu 700-721, Republic of Korea
| | - Kyoung-Tae Kim
- Department of Neurosurgery, Kyungpook National University, Kyungpook National University Hospital, 130 Dongdeok-ro, Jung-gu, Daegu 700-721, Republic of Korea.
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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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Abstract
PURPOSE OF REVIEW This article reviews recent publications on the effect of type 1 diabetes (T1D) on fracture risk, bone mineral density (BMD), bone structure, and bone tissue quality. Possible fracture prevention strategies for patients with T1D have also been reviewed. RECENT FINDINGS T1D is associated with substantially elevated fracture risk and modestly low BMD at the femoral neck. However, BMD alone does not explain higher observed fracture risk in T1D. T1D also affects bone macro- and microstructure, characterized by thinner cortices and trabecular bone changes such as thinner and more widely spaced trabeculae. Structural bone deficit is pronounced in the presence of microvascular complications. Tissue-level changes, such as accumulation of advanced glycation endproducts, detrimental alterations of the mineral phase because of low bone turnover, and occlusion of vascular channels in bone by mineralized tissue, are implicated in pathophysiology of bone fragility in T1D. There are no guidelines on screening and prevention of osteoporotic fractures in T1D. SUMMARY More studies are needed to understand the influence of T1D on structural bone quality and tissue material properties. There is a need for a prospective study to evaluate better screening strategies for diagnosis and treatment of osteoporosis in T1D.
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Affiliation(s)
- Viral N. Shah
- Barbara Davis Center for Diabetes, University of Colorado Anschutz Medical Campus, Aurora, CO
| | - R. Dana Carpenter
- Department of Mechanical Engineering, University of Colorado Denver, San Francisco, California, USA
| | - Virginia L. Ferguson
- Department of Mechanical Engineering, University of Colorado Boulder, San Francisco, California, USA
| | - Ann V. Schwartz
- Department of Epidemiology and Biostatistics, University of California San Francisco, San Francisco, California, USA
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Lenchik L, Register TC, Hsu FC, Xu J, Smith SC, Carr JJ, Freedman BI, Bowden DW. Bone Mineral Density of the Radius Predicts All-Cause Mortality in Patients With Type 2 Diabetes: Diabetes Heart Study. J Clin Densitom 2018; 21:347-354. [PMID: 29284565 PMCID: PMC5984132 DOI: 10.1016/j.jocd.2017.11.003] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/21/2017] [Revised: 11/09/2017] [Accepted: 11/16/2017] [Indexed: 12/21/2022]
Abstract
This study aimed to determine the association between areal and volumetric bone mineral density (BMD) with all-cause mortality in patients with type 2 diabetes (T2D). Associations between BMD and all-cause mortality were examined in 576 women and 517 men with T2D in the Diabetes Heart Study. Volumetric BMD in the thoracic and lumbar spine was measured with quantitative computed tomography. Areal BMD (aBMD) in the lumbar spine, total hip, femoral neck, ultradistal radius, mid radius, and whole body was measured using dual X-ray absorptiometry. Association of BMD with all-cause mortality was determined using sequential models, stratified by sex: (1) unadjusted; (2) adjusted for age, race, smoking, alcohol, estrogen use; (3) model 2 plus history of cardiovascular disease, hypertension, and coronary artery calcification; (4) model 3 plus lean mass; and (5) model 3 plus fat mass. At baseline, mean age was 61.2 years for women and 62.7 years for men. At mean 11.0 ± 3.7 years' follow-up, 221 (36.4%) women and 238 (43.6%) men were deceased. In women, BMD at all skeletal sites (except spine aBMD and whole body aBMD) was inversely associated with all-cause mortality in the unadjusted model. These associations remained significant in the mid radius (hazard ratio per standard deviation = 0.79; p = 0.0057) and distal radius (hazard ratio per standard deviation = 0.76; p = 0.0056) after adjusting for all covariates, including lean mass. In men, volumetric BMD measurements but not aBMD were inversely associated with mortality and only in the unadjusted model. In this longitudinal study, lower baseline aBMD in the radius was associated with increased all-cause mortality in women with T2D, but not men, independent of other risk factors for death.
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Affiliation(s)
- Leon Lenchik
- Department of Radiology, Wake Forest School of Medicine, Winston-Salem, NC, USA.
| | - Thomas C Register
- Department of Pathology, Wake Forest School of Medicine, Winston-Salem, NC, USA
| | - Fang-Chi Hsu
- Department of Biostatistical Sciences, Division of Public Health Sciences, Wake Forest School of Medicine, Winston-Salem, NC, USA
| | - Jianzhao Xu
- Department of Biochemistry, Wake Forest School of Medicine, Winston-Salem, NC, USA
| | - S Carrie Smith
- Department of Biochemistry, Wake Forest School of Medicine, Winston-Salem, NC, USA
| | - J Jeffrey Carr
- Department of Radiology, Vanderbilt University School of Medicine, Nashville, TN, USA
| | - Barry I Freedman
- Department of Internal Medicine, Section on Nephrology, Wake Forest School of Medicine, Winston-Salem, NC, USA
| | - Donald W Bowden
- Department of Biostatistical Sciences, Division of Public Health Sciences, Wake Forest School of Medicine, Winston-Salem, NC, USA
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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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Effect of Zishen Jiangtang Pill, a Chinese Herbal Product, on Rats with Diabetic Osteoporosis. EVIDENCE-BASED COMPLEMENTARY AND ALTERNATIVE MEDICINE 2018; 2018:7201914. [PMID: 29670661 PMCID: PMC5833190 DOI: 10.1155/2018/7201914] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 08/31/2017] [Revised: 11/13/2017] [Accepted: 12/24/2017] [Indexed: 01/19/2023]
Abstract
Diabetic osteoporosis (DO) is a complication of diabetes. Zishen Jiangtang Pill (ZJP) is a Chinese herbal product which has been used in clinic to maintain blood glucose level and bone density for decades. However, the evidence about its mechanism on diabetes and osteoporosis is still unknown. The aim of this study is to investigate therapeutic effect of ZJP on DO in streptozotocin- (STZ-) induced rats. Rats were randomly assigned to 4 groups: one control group (CON), one model group (MOD), and two ZJP treatment groups (1.5 and 3.0 g/kg/d). All rats were treated for 8 weeks. Results showed that ZJP decreased the blood glucose level during OGTT and prevented the changes of FBG and Fins. Similarly, ZJP inhibited the changes of BCa, P, TRACP-5b, CTX-1, BALP, and BGP and the reduction of BMD. In parallel, 1H-NMR metabolomic studies showed that ZJP significantly altered the metabolic fingerprints of blood and urine level. These findings suggest that ZJP can effectively improve glucose metabolism, abnormal bone metabolism, and metabolic disorders in DO rats, which may be a useful alternative medicine for DO therapy.
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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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Fixen CW, Fixen DR. Managing and maintaining bone mineral density in diabetes patients with pharmacotherapy. Expert Opin Pharmacother 2017; 18:2001-2006. [PMID: 29172834 DOI: 10.1080/14656566.2017.1410539] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/18/2022]
Abstract
INTRODUCTION The population of patients with osteoporosis and diabetes is increasing as the aging population increases. Loss of bone mineral density occurs in patients with diabetes, but is not always a priority in the practice setting. The aim of this review is to discuss clinical considerations when managing osteoporosis in patients with diabetes. Areas covered: The pathophysiology of decreased bone mineral density in patients with diabetes is discussed. Additionally, diabetic risk factors for fracture, such as hypoglycemia, the National Osteoporosis Foundation recommendations for osteoporosis, and secondary causes of osteoporosis, including disease and medication related causes, are discussed. Furthermore, recommendations for antihyperglycemic agents, thiazolidinediones, canagliflozin, insulin, metformin, and sitagliptin are discussed due to their effects on bone mineral density. Expert opinion: Even though diabetes is an important risk factor for osteoporosis, assessing bone health in diabetic patients is often overlooked. Ensuring adequate prevention and treatment strategies for osteoporosis is vitally important with our diabetic patients as the population ages. T-scores and FRAX scores likely underrepresent a diabetic patients risk for fracture, and this should be taken into consideration in treatment decisions. Future studies are needed to determine optimal pharmacologic treatment of hyperglycemia in this population.
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Affiliation(s)
- Cy W Fixen
- a Denver Veterans Affairs Medical Center , Denver , CO , USA
| | - Danielle R Fixen
- b Department of Clinical Pharmacy , University of Colorado Skaggs School of Pharmacy and Pharmaceutical Sciences , Aurora , USA
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Rubin MR. Skeletal fragility in diabetes. Ann N Y Acad Sci 2017; 1402:18-30. [PMID: 28926113 DOI: 10.1111/nyas.13463] [Citation(s) in RCA: 29] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/03/2017] [Revised: 08/07/2017] [Accepted: 08/07/2017] [Indexed: 02/06/2023]
Abstract
Fracture risk is heightened in patients with both type 1 diabetes (T1D) and type 2 diabetes (T2D). Although bone mineral density by dual-energy X-ray absorptiometry is decreased in T1D, it is paradoxically increased with T2D. To predict fracture risk, the Fracture Risk Assessment Tool (FRAX) can be used in diabetes patients, albeit with refinement. Skeletal abnormalities in diabetes include alterations in microarchitecture in T1D and T2D as well as compromised impact microindentation in T2D. Changes in bone microvasculature, advanced glycation end product accumulation, and bone formation may underlie these findings. When fractures occur in T1D and T2D, consequences are worse than in nondiabetic patients with regard to both morbidity and mortality. With regard to treatment, antiresorptive osteoporosis therapies appear to be effective in the setting of diabetes.
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Affiliation(s)
- Mishaela R Rubin
- Metabolic Bone Disease Unit, Columbia University, New York, New York
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Chandran M. Clinical aspects and management of osteoporosis and fragility fractures in patients with diabetes. Osteoporos Sarcopenia 2017; 3:123-127. [PMID: 30775516 PMCID: PMC6372781 DOI: 10.1016/j.afos.2017.08.101] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/19/2017] [Accepted: 08/21/2017] [Indexed: 01/11/2023] Open
Abstract
Both diabetes and osteoporosis are assuming epidemic proportions throughout the world. Accumulating data suggest that both types 1 and 2 diabetes are associated with an increased risk of fragility fractures. This increased risk appears to be largely independent of bone mineral density (BMD) which is most often noted to be low in type 1 diabetes and normal or increased in type 2 diabetes. This review explores the clinical characteristics of bone fragility in patients with diabetes and highlights studies that have evaluated BMD and fracture prediction tools in these patients. It also briefly reviews the current management principles of osteoporosis in diabetes, with special emphasis on the impact of diabetes medications on bone health as well as explores the efficacy of currently available antiosteoporosis pharmacotherapy in the diabetic population.
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Affiliation(s)
- Manju Chandran
- Osteoporosis and Bone Metabolism Unit, Department of Endocrinology, Singapore General Hospital, Singapore
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