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Stefanakis K, Upadhyay J, Ramirez-Cisneros A, Patel N, Sahai A, Mantzoros CS. Leptin physiology and pathophysiology in energy homeostasis, immune function, neuroendocrine regulation and bone health. Metabolism 2024; 161:156056. [PMID: 39481533 DOI: 10.1016/j.metabol.2024.156056] [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: 10/04/2024] [Revised: 10/28/2024] [Accepted: 10/28/2024] [Indexed: 11/02/2024]
Abstract
Since its discovery and over the past thirty years, extensive research has significantly expanded our understanding of leptin and its diverse roles in human physiology, pathophysiology and therapeutics. A prototypical adipokine initially identified for its critical function in appetite regulation and energy homeostasis, leptin has been revealed to also exert profound effects on the hypothalamic-pituitary-gonadal, thyroid, adrenal and growth hormone axis, differentially between animals and humans, as well as in regulating immune function. Beyond these roles, leptin plays a pivotal role in significantly affecting bone health by promoting bone formation and regulating bone metabolism both directly and indirectly through its neuroendocrine actions. The diverse actions of leptin are particularly notable in leptin-deficient animal models and in conditions characterized by low circulating leptin levels, such as lipodystrophies and relative energy deficiency. Conversely, the effectiveness of leptin is attenuated in leptin-sufficient states, such as obesity and other high-adiposity conditions associated with hyperleptinemia and leptin tolerance. This review attempts to consolidate 30 years of leptin research with an emphasis on its physiology and pathophysiology in humans, including its promising therapeutic potential. We discuss preclinical and human studies describing the pathophysiology of energy deficiency across organ systems and the significant role of leptin in regulating neuroendocrine, immune, reproductive and bone health. We finally present past proof of concept clinical trials of leptin administration in leptin-deficient subjects that have demonstrated positive neuroendocrine, reproductive, and bone health outcomes, setting the stage for future phase IIb and III randomized clinical trials in these conditions.
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Affiliation(s)
- Konstantinos Stefanakis
- Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA
| | - Jagriti Upadhyay
- Department of Medicine, Lahey Hospital and Medical Center, Burlington, MA, USA
| | - Arantxa Ramirez-Cisneros
- Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA
| | - Nihar Patel
- Department of Medicine, Lahey Hospital and Medical Center, Burlington, MA, USA
| | - Akshat Sahai
- Vassar Brothers Medical Center, Poughkeepsie, NY, USA
| | - Christos S Mantzoros
- Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA; Department of Medicine, Boston VA Healthcare System, Boston, MA, USA.
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James R, Subramanyam KN, Payva F, E AP, Tv VK, Sivaramakrishnan V, Ks S. In-silico analysis predicts disruption of normal angiogenesis as a causative factor in osteoporosis pathogenesis. BMC Genom Data 2024; 25:85. [PMID: 39379846 PMCID: PMC11460074 DOI: 10.1186/s12863-024-01269-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/22/2024] [Accepted: 09/27/2024] [Indexed: 10/10/2024] Open
Abstract
Angiogenesis-osteogenesis coupling is critical for proper functioning and maintaining the health of bones. Any disruption in this coupling, associated with aging and disease, might lead to loss of bone mass. Osteoporosis (OP) is a debilitating bone metabolic disorder that affects the microarchitecture of bones, gradually leading to fracture. Computational analysis revealed that normal angiogenesis is disrupted during the progression of OP, especially postmenopausal osteoporosis (PMOP). The genes associated with OP and PMOP were retrieved from the DisGeNET database. Hub gene analysis and molecular pathway enrichment were performed via the Cytoscape plugins STRING, MCODE, CytoHubba, ClueGO and the web-based tool Enrichr. Twenty-eight (28) hub genes were identified, eight of which were transcription factors (HIF1A, JUN, TP53, ESR1, MYC, PPARG, RUNX2 and SOX9). Analysis of SNPs associated with hub genes via the gnomAD, I-Mutant2.0, MUpro, ConSurf and COACH servers revealed the substitution F201L in IL6 as the most deleterious. The IL6 protein was modeled in the SWISS-MODEL server and the substitution was analyzed via the YASARA FoldX plugin. A positive ΔΔG (1.936) of the F201L mutant indicates that the mutated structure is less stable than the wild-type structure is. Thirteen hub genes, including IL6 and the enriched molecular pathways were found to be profoundly involved in angiogenesis/endothelial function and immune signaling. Mechanical loading of bones through weight-bearing exercises can activate osteoblasts via mechanotransduction leading to increased bone formation. The present study suggests proper mechanical loading of bone as a preventive strategy for PMOP, by which angiogenesis and the immune status of the bone can be maintained. This in silico analysis could be used to understand the molecular etiology of OP and to develop novel therapeutic approaches.
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Affiliation(s)
- Remya James
- Department of Zoology, St. Joseph's College for Women, Alappuzha, Kerala, 688001, India.
- School of Biosciences, Department of Zoology, Avinashilingam Institute for Home Science and Higher Education for Women, Coimbatore, Tamil Nadu, 614043, India.
| | - Koushik Narayan Subramanyam
- Department of Orthopaedics, Sri Sathya Sai Institute of Higher Medical Sciences, Prasanthigram, Puttaparthi, Andhra Pradesh, 515134, India
| | - Febby Payva
- Department of Zoology, St. Joseph's College for Women, Alappuzha, Kerala, 688001, India
- School of Biosciences, Department of Zoology, Avinashilingam Institute for Home Science and Higher Education for Women, Coimbatore, Tamil Nadu, 614043, India
| | - Amrisa Pavithra E
- Department of Zoology, St. Joseph's College for Women, Alappuzha, Kerala, 688001, India
| | - Vineeth Kumar Tv
- Department of Zoology, The Cochin College, Kochi, Kerala, 682002, India.
| | - Venketesh Sivaramakrishnan
- School of Biosciences, Sri Sathya Sai Institute of Higher Learning, Prasanthinilayam, Puttaparthi, Andhra Pradesh, 515134, India
| | - Santhy Ks
- School of Biosciences, Department of Zoology, Avinashilingam Institute for Home Science and Higher Education for Women, Coimbatore, Tamil Nadu, 614043, India.
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Cho S, Shin S, Lee S, Rhee Y, Kim HI, Hong N. Differential Impact of Subcutaneous and Visceral Fat on Bone Changes after Gastrectomy. Endocrinol Metab (Seoul) 2024; 39:632-640. [PMID: 39015029 PMCID: PMC11375306 DOI: 10.3803/enm.2024.1956] [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: 02/07/2024] [Accepted: 05/27/2024] [Indexed: 07/18/2024] Open
Abstract
BACKGRUOUND Osteoporosis and fragility fractures are crucial musculoskeletal complications in long-term survivors of gastric cancer. However, the relationship between changes in body composition after gastrectomy and bone loss has not been investigated. Therefore, this study aimed to explore whether computed tomography (CT)-derived body composition parameters are associated with bone loss after gastrectomy in patients with gastric cancer. METHODS We retrospectively reviewed medical records and abdomen CT scans of patients who underwent gastrectomy at Yonsei University Severance Hospital between 2009 and 2018. Patients with non-metastatic gastric adenocarcinoma and preoperative and postoperative non-contrast CT scans were analyzed. Section area of skeletal muscle (SMA), visceral fat (VFA), and subcutaneous fat (SFA) were assessed using semi-automatic segmentation software. Changes in trabecular bone attenuation of L1 mid-vertebra level (L1 Hounsfield units [HU]) were measured. RESULTS Fifty-seven patients (mean age, 65.5±10.6; 70.2% males) were analyzed, and the median duration was 31 months. Fortyseven patients (82.5%) lost weight after gastrectomy. Baseline SMA and VFA did not differ between the bone loss and preserved groups; however, baseline SFA was significantly higher in the bone preserved group than in the bone loss group (P=0.020). In a multivariable linear regression model adjusted for confounding factors, one standard deviation higher VFA at baseline was associated with greater annualized L1 HU loss (%) (P=0.034). However, higher preoperative SFA was associated with protection against bone loss after gastrectomy (P=0.025). CONCLUSION Higher preoperative SFA exhibited a protective effect against bone loss after gastrectomy in patients with non-metastatic gastric cancer, whereas VFA exhibited a negative effect.
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Affiliation(s)
- Sungjoon Cho
- Department of Internal Medicine, Severance Hospital, Endocrine Research Institute, Yonsei University College of Medicine, Seoul, Korea
| | - Sungjae Shin
- Division of Endocrinology and Metabolism, Department of Internal Medicine, National Health Insurance Service Ilsan Hospital, Goyang, Korea
| | - Seunghyun Lee
- Department of Internal Medicine, Wonju Severance Christian Hospital, Yonsei University Wonju College of Medicine, Wonju, Korea
| | - Yumie Rhee
- Department of Internal Medicine, Severance Hospital, Endocrine Research Institute, Yonsei University College of Medicine, Seoul, Korea
| | - Hyoung-Il Kim
- Department of Surgery, Yonsei University College of Medicine, Seoul, Korea
- Gastric Cancer Center, Yonsei Cancer Center, Seoul, Korea
| | - Namki Hong
- Department of Internal Medicine, Severance Hospital, Endocrine Research Institute, Yonsei University College of Medicine, Seoul, Korea
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Gruneisen E, Kremer R, Duque G. Fat as a Friend or Foe of the Bone. Curr Osteoporos Rep 2024; 22:245-256. [PMID: 38416274 DOI: 10.1007/s11914-024-00864-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 02/12/2024] [Indexed: 02/29/2024]
Abstract
PURPOSE OF REVIEW The objective of this review is to summarize the literature on the prevalence and diagnosis of obesity and its metabolic profile, including bone metabolism, focusing on the main inflammatory and turnover bone mediators that better characterize metabolically healthy obesity phenotype, and to summarize the therapeutic interventions for obesity with their effects on bone health. RECENT FINDINGS Osteoporosis and fracture risk not only increase with age and menopause but also with metabolic diseases, such as diabetes mellitus. Thus, patients with high BMI may have a higher bone fragility and fracture risk. However, some obese individuals with healthy metabolic profiles seem to be less at risk of bone fracture. Obesity has become an alarming disease with growing prevalence and multiple metabolic comorbidities, resulting in a significant burden on healthcare and increased mortality. The imbalance between increased food ingestion and decreased energy expenditure leads to pathological adipose tissue distribution and function, with increased secretion of proinflammatory markers and harmful consequences for body tissues, including bone tissue. However, some obese individuals seem to have a healthy metabolic profile and may not develop cardiometabolic disease during their lives. This healthy metabolic profile also benefits bone turnover and is associated with lower fracture risk.
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Affiliation(s)
- Elodie Gruneisen
- Division of Endocrinology & Metabolism, Department of Medicine, McGill University Health Centre, Montréal, QC, Canada
| | - Richard Kremer
- Division of Endocrinology & Metabolism, Department of Medicine, McGill University Health Centre, Montréal, QC, Canada
- Bone, Muscle & Geroscience Group, Research Institute of the McGill University Health Centre, Montreal, QC, Canada
| | - Gustavo Duque
- Bone, Muscle & Geroscience Group, Research Institute of the McGill University Health Centre, Montreal, QC, Canada.
- Dr. Joseph Kaufmann Chair in Geriatric Medicine, Department of Medicine, McGill University, Montreal, QC, Canada.
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Patil JD, Fredericks S. The role of adipokines in osteoporosis management: a mini review. Front Endocrinol (Lausanne) 2024; 15:1336543. [PMID: 38516409 PMCID: PMC10956128 DOI: 10.3389/fendo.2024.1336543] [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: 11/10/2023] [Accepted: 02/22/2024] [Indexed: 03/23/2024] Open
Abstract
The prevalence of osteoporosis has been on the rise globally. With ageing populations, research has sought therapeutic solutions in novel areas. One such area is that of the adipokines. Current literature points to an important role for these chemical mediators in relation to bone metabolism. Well-established adipokines have been broadly reported upon. These include adiponectin and leptin. However, other novel adipokines such as visfatin, nesfatin-1, meteorin-like protein (Metrnl), apelin and lipocalin-2 are starting to be addressed pre-clinically and clinically. Adipokines hold pro-inflammatory and anti-inflammatory properties that influence the pathophysiology of various bone diseases. Omentin-1 and vaspin, two novel adipokines, share cardioprotective effects and play essential roles in bone metabolism. Studies have reported bone-protective effects of omentin-1, whilst others report negative associations between omentin-1 and bone mineral density. Lipocalin-2 is linked to poor bone microarchitecture in mice and is even suggested to mediate osteoporosis development from prolonged disuse. Nesfatin-1, an anorexigenic adipokine, has been known to preserve bone density. Animal studies have demonstrated that nesfatin-1 treatment limits bone loss and increases bone strength, suggesting exogenous use as a potential treatment for osteopenic disorders. Pre-clinical studies have shown adipokine apelin to have a role in bone metabolism, mediated by the enhancement of osteoblast genesis and the inhibition of programmed cell death. Although many investigations have reported conflicting findings, sufficient literature supports the notion that adipokines have a significant influence on the metabolism of bone. This review aims at highlighting the role of novel adipokines in osteoporosis while also discussing their potential for treating osteoporosis.
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Affiliation(s)
| | - Salim Fredericks
- The Royal College of Surgeons in Ireland – Medical University of Bahrain, Al Sayh, Bahrain
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Lopez N, Cohen SM, Emanuele M. Type 2 Diabetes and Bone Disease. Clin Rev Bone Miner Metab 2023; 21:21-31. [DOI: 10.1007/s12018-023-09288-7] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 04/10/2023] [Indexed: 01/05/2025]
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Walowski CO, Herpich C, Enderle J, Braun W, Both M, Hasler M, Müller MJ, Norman K, Bosy-Westphal A. Determinants of bone mass in older adults with normal- and overweight derived from the crosstalk with muscle and adipose tissue. Sci Rep 2023; 13:5030. [PMID: 36977715 PMCID: PMC10050471 DOI: 10.1038/s41598-023-31642-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/05/2022] [Accepted: 03/15/2023] [Indexed: 03/30/2023] Open
Abstract
Lower bone mass in older adults may be mediated by the endocrine crosstalk between muscle, adipose tissue and bone. In 150 community-dwelling adults (59-86 years, BMI 17-37 kg/m2; 58.7% female), skeletal muscle mass index, adipose tissue and fat mass index (FMI) were determined. Levels of myokines, adipokines, osteokines, inflammation markers and insulin were measured as potential determinants of bone mineral content (BMC) and density (BMD). FMI was negatively associated with BMC and BMD after adjustment for mechanical loading effects of body weight (r-values between -0.37 and -0.71, all p < 0.05). Higher FMI was associated with higher leptin levels in both sexes, with higher hsCRP in women and with lower adiponectin levels in men. In addition to weight and FMI, sclerostin, osteocalcin, leptin × sex and adiponectin were independent predictors of BMC in a stepwise multiple regression analysis. Muscle mass, but not myokines, showed positive correlations with bone parameters that were weakened after adjusting for body weight (r-values between 0.27 and 0.58, all p < 0.01). Whereas the anabolic effect of muscle mass on bone in older adults may be partly explained by mechanical loading, the adverse effect of obesity on bone is possibly mediated by low-grade inflammation, higher leptin and lower adiponectin levels.
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Affiliation(s)
- Carina O Walowski
- Institute for Human Nutrition and Food Science, Christian-Albrechts-University, Düsternbrooker Weg 17, 24105, Kiel, Germany
| | - Catrin Herpich
- Institute of Nutritional Science, University of Potsdam, Potsdam, Germany
- Department of Geriatrics and Medical Gerontology, Charité Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany
- Department of Nutrition and Gerontology, German Institute of Human Nutrition, Potsdam-Rehbrücke, Nuthetal, Germany
| | - Janna Enderle
- Institute for Human Nutrition and Food Science, Christian-Albrechts-University, Düsternbrooker Weg 17, 24105, Kiel, Germany
| | - Wiebke Braun
- Institute for Human Nutrition and Food Science, Christian-Albrechts-University, Düsternbrooker Weg 17, 24105, Kiel, Germany
| | - Marcus Both
- Department of Radiology and Neuroradiology, University Medical Center Schleswig-Holstein, Campus Kiel, Germany
| | - Mario Hasler
- Applied Statistics, Faculty of Agricultural and Nutritional Sciences, Christian-Albrechts-University, Kiel, Germany
| | - Manfred J Müller
- Institute for Human Nutrition and Food Science, Christian-Albrechts-University, Düsternbrooker Weg 17, 24105, Kiel, Germany
| | - Kristina Norman
- Institute of Nutritional Science, University of Potsdam, Potsdam, Germany
- Department of Geriatrics and Medical Gerontology, Charité Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany
- Department of Nutrition and Gerontology, German Institute of Human Nutrition, Potsdam-Rehbrücke, Nuthetal, Germany
- German Center for Cardiovascular Research (DZHK), Partner Site Berlin, Berlin, Germany
| | - Anja Bosy-Westphal
- Institute for Human Nutrition and Food Science, Christian-Albrechts-University, Düsternbrooker Weg 17, 24105, Kiel, Germany.
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Lee S, Kim JH, Jeon YK, Lee JS, Kim K, Hwang SK, Kim JH, Goh TS, Kim YH. Effect of adipokine and ghrelin levels on BMD and fracture risk: an updated systematic review and meta-analysis. Front Endocrinol (Lausanne) 2023; 14:1044039. [PMID: 37181034 PMCID: PMC10171108 DOI: 10.3389/fendo.2023.1044039] [Citation(s) in RCA: 9] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/14/2022] [Accepted: 03/29/2023] [Indexed: 05/16/2023] Open
Abstract
Context Circulating adipokines and ghrelin affect bone remodeling by regulating the activation and differentiation of osteoblasts and osteoclasts. Although the correlation between adipokines, ghrelin, and bone mineral density (BMD) has been studied over the decades, its correlations are still controversial. Accordingly, an updated meta-analysis with new findings is needed. Objective This study aimed to explore the impact of serum adipokine and ghrelin levels on BMD and osteoporotic fractures through a meta-analysis. Data sources Studies published till October 2020 in Medline, Embase, and the Cochrane Library were reviewed. Study selection We included studies that measured at least one serum adipokine level and BMD or fracture risk in healthy individuals. We excluded studies with one or more of the following: patients less than 18 years old, patients with comorbidities, who had undergone metabolic treatment, obese patients, patients with high physical activities, and a study that did not distinguish sex or menopausal status. Data extraction We extracted the data that include the correlation coefficient between adipokines (leptin, adiponectin, and resistin) and ghrelin and BMD, fracture risk by osteoporotic status from eligible studies. Data synthesis A meta-analysis of the pooled correlations between adipokines and BMD was performed, demonstrating that the correlation between leptin and BMD was prominent in postmenopausal women. In most cases, adiponectin levels were inversely correlated with BMD. A meta-analysis was conducted by pooling the mean differences in adipokine levels according to the osteoporotic status. In postmenopausal women, significantly lower leptin (SMD = -0.88) and higher adiponectin (SMD = 0.94) levels were seen in the osteoporosis group than in the control group. By predicting fracture risk, higher leptin levels were associated with lower fracture risk (HR = 0.68), whereas higher adiponectin levels were associated with an increased fracture risk in men (HR = 1.94) and incident vertebral fracture in postmenopausal women (HR = 1.18). Conclusions Serum adipokines levels can utilize to predict osteoporotic status and fracture risk of patients. Systematic review registration https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42021224855, identifier CRD42021224855.
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Affiliation(s)
- Seoyul Lee
- Department of Physiology, School of Medicine, Pusan National University, Yangsan, Republic of Korea
| | - Jeong Hun Kim
- Biomedical Research Institute, Pusan National University Hospital, Busan, Republic of Korea
- College of Nursing, Pusan National University, Yangsan, Republic of Korea
| | - Yun Kyung Jeon
- Biomedical Research Institute, Pusan National University Hospital, Busan, Republic of Korea
- Department of Internal Medicine, School of Medicine, Pusan National University, Yangsan, Republic of Korea
| | - Jung Sub Lee
- Biomedical Research Institute, Pusan National University Hospital, Busan, Republic of Korea
- Department of Orthopaedic Surgery, School of Medicine, Pusan National University, Yangsan, Republic of Korea
| | - Keunyoung Kim
- Biomedical Research Institute, Pusan National University Hospital, Busan, Republic of Korea
- Department of Nuclear Medicine, School of Medicine, Pusan National University, Yangsan, Republic of Korea
| | - Sun-Kyung Hwang
- College of Nursing, Pusan National University, Yangsan, Republic of Korea
| | - Jae Ho Kim
- Department of Physiology, School of Medicine, Pusan National University, Yangsan, Republic of Korea
- Research Institute for Convergence of Biomedical Science and Technology, Pusan National University Yangsan Hospital, Yangsan, Republic of Korea
| | - Tae Sik Goh
- Biomedical Research Institute, Pusan National University Hospital, Busan, Republic of Korea
- Department of Orthopaedic Surgery, School of Medicine, Pusan National University, Yangsan, Republic of Korea
- *Correspondence: Yun Hak Kim, ; Tae Sik Goh,
| | - Yun Hak Kim
- Research Institute for Convergence of Biomedical Science and Technology, Pusan National University Yangsan Hospital, Yangsan, Republic of Korea
- Department of Anatomy, School of Medicine, Pusan National University, Yangsan, Republic of Korea
- Department of Biomedical Informatics, School of Medicine, Pusan National University, Yangsan, Republic of Korea
- *Correspondence: Yun Hak Kim, ; Tae Sik Goh,
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Xu Q, Li D, Chen J, Yang J, Yan J, Xia Y, Zhang F, Wang X, Cao H. Crosstalk between the gut microbiota and postmenopausal osteoporosis: Mechanisms and applications. Int Immunopharmacol 2022; 110:108998. [PMID: 35785728 DOI: 10.1016/j.intimp.2022.108998] [Citation(s) in RCA: 31] [Impact Index Per Article: 10.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/23/2022] [Revised: 06/08/2022] [Accepted: 06/21/2022] [Indexed: 12/14/2022]
Abstract
Postmenopausal osteoporosis (PMO) results from a reduction in bone mass and microarchitectural deterioration in bone tissue due to estrogen deficiency, which may increase the incidence of fragility fractures. The number of people suffering from PMO has increased over the years because of the rapidly aging population worldwide. However, several pharmacological agents for the treatment of PMO have many safety risks and impose a heavy financial burden to patients and society. In recent years, the "gut-bone" axis has been proposed as a new approach in the prevention and treatment of PMO. This paper reviews the relationship between the gut microbiota and PMO, which mainly includes the underlying mechanisms between hormones, immunity, nutrient metabolism, metabolites of the gut microbiota and intestinal permeability, and explores the possible role of the gut microbiota in these processes. Finally, we discuss the therapeutic effects of diet, prebiotics, probiotics, and fecal microbiota transplantation on the gut microbiota.
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Affiliation(s)
- Qin Xu
- Nutrition Department, Affiliated Hospital of Jiangnan University, Wuxi, Jiangsu, China; Wuxi School of Medicine, Jiangnan University, Wuxi, Jiangsu, China
| | - Dan Li
- Nutrition Department, Affiliated Hospital of Jiangnan University, Wuxi, Jiangsu, China; Wuxi School of Medicine, Jiangnan University, Wuxi, Jiangsu, China; Clinical Assessment Center of Functional Food, Affiliated Hospital of Jiangnan University, Wuxi, Jiangsu, China
| | - Jing Chen
- Wuxi School of Medicine, Jiangnan University, Wuxi, Jiangsu, China; Nursing Department, Affiliated Hospital of Jiangnan University, Wuxi, Jiangsu, China
| | - Ju Yang
- Nutrition Department, Affiliated Hospital of Jiangnan University, Wuxi, Jiangsu, China; Wuxi School of Medicine, Jiangnan University, Wuxi, Jiangsu, China; Clinical Assessment Center of Functional Food, Affiliated Hospital of Jiangnan University, Wuxi, Jiangsu, China
| | - Jiai Yan
- Nutrition Department, Affiliated Hospital of Jiangnan University, Wuxi, Jiangsu, China; Wuxi School of Medicine, Jiangnan University, Wuxi, Jiangsu, China; Clinical Assessment Center of Functional Food, Affiliated Hospital of Jiangnan University, Wuxi, Jiangsu, China
| | - Yanping Xia
- Nutrition Department, Affiliated Hospital of Jiangnan University, Wuxi, Jiangsu, China; Clinical Assessment Center of Functional Food, Affiliated Hospital of Jiangnan University, Wuxi, Jiangsu, China
| | - Feng Zhang
- Nutrition Department, Affiliated Hospital of Jiangnan University, Wuxi, Jiangsu, China; Wuxi School of Medicine, Jiangnan University, Wuxi, Jiangsu, China; Clinical Assessment Center of Functional Food, Affiliated Hospital of Jiangnan University, Wuxi, Jiangsu, China
| | - Xuesong Wang
- Nutrition Department, Affiliated Hospital of Jiangnan University, Wuxi, Jiangsu, China; Wuxi School of Medicine, Jiangnan University, Wuxi, Jiangsu, China; Clinical Assessment Center of Functional Food, Affiliated Hospital of Jiangnan University, Wuxi, Jiangsu, China; Department of Orthopedics, Affiliated Hospital of Jiangnan University, Wuxi, Jiangsu, China
| | - Hong Cao
- Nutrition Department, Affiliated Hospital of Jiangnan University, Wuxi, Jiangsu, China; Wuxi School of Medicine, Jiangnan University, Wuxi, Jiangsu, China; Clinical Assessment Center of Functional Food, Affiliated Hospital of Jiangnan University, Wuxi, Jiangsu, China; Department of Endocrinology, Affiliated Hospital of Jiangnan University, Wuxi, Jiangsu, China.
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Avilkina V, Chauveau C, Ghali Mhenni O. Sirtuin function and metabolism: Role in pancreas, liver, and adipose tissue and their crosstalk impacting bone homeostasis. Bone 2022; 154:116232. [PMID: 34678494 DOI: 10.1016/j.bone.2021.116232] [Citation(s) in RCA: 16] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/29/2021] [Revised: 10/07/2021] [Accepted: 10/08/2021] [Indexed: 12/12/2022]
Abstract
Mammalian sirtuins (SIRT1-7) are members of the nicotine adenine dinucleotide (NAD+)-dependent family of enzymes critical for histone deacetylation and posttranslational modification of proteins. Sirtuin family members regulate a wide spectrum of biological processes and are best known for maintaining longevity. Sirtuins are well characterized in metabolic tissues such as the pancreas, liver and adipose tissue (AT). They are regulated by a diverse range of stimuli, including nutrients and metabolic changes within the organism. Indeed, nutrient-associated conditions, such as obesity and anorexia nervosa (AN), were found to be associated with bone fragility development in osteoporosis. Interestingly, it has also been demonstrated that sirtuins, more specifically SIRT1, can regulate bone activity. Various studies have demonstrated the importance of sirtuins in bone in the regulation of bone homeostasis and maintenance of the balance between bone resorption and bone formation. However, to understand the molecular mechanisms involved in the negative regulation of bone homeostasis during overnutrition (obesity) or undernutrition, it is crucial to examine a wider picture and to determine the pancreatic, liver and adipose tissue pathway crosstalk responsible for bone loss. Particularly, under AN conditions, sirtuin family members are highly expressed in metabolic tissue, but this phenomenon is reversed in bone, and severe bone loss has been observed in human subjects. AN-associated bone loss may be connected to SIRT1 deficiency; however, additional factors may interfere with bone homeostasis. Thus, in this review, we focus on sirtuin activity in the pancreas, liver and AT in cases of over- and undernutrition, especially the regulation of their secretome by sirtuins. Furthermore, we examine how the secretome of the pancreas, liver and AT affects bone homeostasis, focusing on undernutrition. This review aims to lead to a better understanding of the crosstalk between sirtuins, metabolic organs and bone. In long term prospective it should contribute to promote improvement of therapeutic strategies for the prevention of metabolic diseases and the development of osteoporosis.
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Affiliation(s)
- Viktorija Avilkina
- Marrow Adiposity and Bone Lab (MABLab) ULR4490, Univ. Littoral Côte d'Opale, F-62200, Boulogne-sur-Mer, Univ. Lille F-59000 Lille, CHU Lille, F-59000 Lille, France
| | - Christophe Chauveau
- Marrow Adiposity and Bone Lab (MABLab) ULR4490, Univ. Littoral Côte d'Opale, F-62200, Boulogne-sur-Mer, Univ. Lille F-59000 Lille, CHU Lille, F-59000 Lille, France
| | - Olfa Ghali Mhenni
- Marrow Adiposity and Bone Lab (MABLab) ULR4490, Univ. Littoral Côte d'Opale, F-62200, Boulogne-sur-Mer, Univ. Lille F-59000 Lille, CHU Lille, F-59000 Lille, France.
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E Hassan N, A El-Masry S, A El Banna R, Al-Tohamy M, El-Lebedy D, Adel Abdelhalim D, Amin D, Megahed S, Khalil A. Bone Health and its Relation to Energy Intake, Fat Mass and its Distribution. Pak J Biol Sci 2020; 23:1075-1085. [PMID: 32700859 DOI: 10.3923/pjbs.2020.1075.1085] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/15/2022]
Abstract
BACKGROUND AND OBJECTIVES Osteoporosis and obesity are two of the most important inter-related diseases worldwide. This study aimed to investigate impact of fat mass and its distribution on bone health in relation to energy intake among sample of Egyptian women. MATERIALS AND METHODS A cross-sectional study included 116 Egyptian women with age range 25-65 years old. They were classified according to the menopause into 2 groups: Pre-menopausal (n = 51) and post menopausal (n = 65). All participants have undergone anthropometric measurements, body composition, DEXA and laboratory investigations. RESULTS Among overweight/obese women, pre-menopausal women had significant higher values of BMR and BMD at both lumbar spines, neck of femur and significant lower values of central obesity (waist/hip ratio, waist/height ratio, visceral fat) and C-terminal peptides than postmenopausal ones. Among pre and post-menopausal women, BMD at both sites had significant positive correlations with obesity markers (BMI, waist and hip circumferences), fat mass, BMR, in addition to fat distribution, visceral fat, leptin among pre-menopausal women and C-terminal peptide among postmenopausal women. Among pre-menopausal women, BMR significantly explained 56% of the variations in BMD at neck of femur, while at lumbar spines the best model was BMI, BMR and waist circumference, which significantly explain 33% of the variations in BMD. CONCLUSION Bone health positively correlated with BMI, fat mass and its distribution and BMR, particularly at femur neck, among pre and post-menopausal Egyptian women. Overweight/obesity can be considered as a protective factor for bone health.
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Wang CH, Lai YH, Lin YL, Kuo CH, Syu RJ, Chen MC, Hsu BG. Increased Serum Leptin Level Predicts Bone Mineral Density in Hemodialysis Patients. Int J Endocrinol 2020; 2020:8451751. [PMID: 32565794 PMCID: PMC7290877 DOI: 10.1155/2020/8451751] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/20/2019] [Revised: 05/10/2020] [Accepted: 05/20/2020] [Indexed: 12/25/2022] Open
Abstract
BACKGROUND Leptin acts through the adipose-bone axis to regulate bone mineral density (BMD). This study evaluated the relationship between BMD and serum leptin levels in patients on hemodialysis. METHODS In this cross-sectional study including 98 hemodialysis patients, BMD was measured using dual energy X-ray absorptiometry of the lumbar vertebrae (L2-L4), and serum leptin levels were determined using an enzyme immunoassay. RESULTS There were 25 (25.5%), 13 (13.3%), and 60 (61.2%) patients with osteopenia, osteoporosis, and normal BMD, respectively. Advanced age (P=0.017); decreased body mass index (BMI, P < 0.001); body height (P < 0.001); prehemodialysis body weight (BW, P < 0.001); post-hemodialysis BW (P < 0.001); waist circumference (P < 0.001); and triglyceride (P=0.015), albumin (P=0.004), and leptin levels (P=0.017) were associated with lower lumbar T scores, whereas increased urea reduction rate (URR, P=0.004) and fractional clearance index for urea (Kt/V, P=0.004) were associated with lower lumbar T scores. The multivariable forward stepwise linear regression analysis with adjustment for sex; age; body height; prehemodialysis BW; BMI; waist circumference; logarithmically transformed triglycerides (log-triglycerides), albumin, creatinine, and leptin (log-leptin) levels; URR; and Kt/V indicated that high serum level of log-leptin (R 2 change = 0.184; P < 0.001), increased prehemodialysis BW (R 2 change = 0.325; P=0.008), male sex (R 2 change = 0.048; P=0.001), young age (R 2 change = 0.044; P=0.012), and increased serum albumin level (R 2 change = 0.017; P=0.044) were significantly and independently associated with lumbar BMD. CONCLUSIONS Advanced age and female sex were associated with poor BMD, whereas increased BW, serum albumin, and leptin levels were positively associated with BMD in patients on hemodialysis.
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Affiliation(s)
- Chih-Hsien Wang
- Division of Nephrology, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Hualien, Taiwan
- School of Medicine, Tzu Chi University, Hualien, Taiwan
| | - Yu-Hsien Lai
- Division of Nephrology, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Hualien, Taiwan
| | - Yu-Li Lin
- Division of Nephrology, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Hualien, Taiwan
- School of Medicine, Tzu Chi University, Hualien, Taiwan
| | - Chiu-Huang Kuo
- Division of Nephrology, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Hualien, Taiwan
| | - Ru-Jiang Syu
- Division of Nephrology, Department of Internal Medicine, Dalin Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Chiayi 62247, Taiwan
| | - Ming-Chun Chen
- School of Medicine, Tzu Chi University, Hualien, Taiwan
- Department of Pediatric, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Hualien, Taiwan
| | - Bang-Gee Hsu
- Division of Nephrology, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Hualien, Taiwan
- School of Medicine, Tzu Chi University, Hualien, Taiwan
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Kawao N, Ishida M, Kaji H. Roles of leptin in the recovery of muscle and bone by reloading after mechanical unloading in high fat diet-fed obese mice. PLoS One 2019; 14:e0224403. [PMID: 31648235 PMCID: PMC6812756 DOI: 10.1371/journal.pone.0224403] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/22/2019] [Accepted: 10/11/2019] [Indexed: 01/31/2023] Open
Abstract
Muscle and bone masses are elevated by the increased mechanical stress associated with body weight gain in obesity. However, the mechanisms by which obesity affects muscle and bone remain unclear. We herein investigated the roles of obesity and humoral factors from adipose tissue in the recovery phase after reloading from disuse-induced muscle wasting and bone loss using normal diet (ND)- or high fat diet (HFD)-fed mice with hindlimb unloading (HU) and subsequent reloading. Obesity did not affect decreases in trabecular bone mineral density (BMD), muscle mass in the lower leg, or grip strength in HU mice. Obesity significantly increased trabecular BMD, muscle mass in the lower leg, and grip strength in reloading mice over those in reloading mice fed ND. Among the humoral factors in epididymal and subcutaneous adipose tissue, leptin mRNA levels were significantly higher in reloading mice fed HFD than in mice fed ND. Moreover, circulating leptin levels were significantly higher in reloading mice fed HFD than in mice fed ND. Leptin mRNA levels in epididymal adipose tissue or serum leptin levels positively correlated with the increases in trabecular BMD, total muscle mass, and grip strength in reloading mice fed ND and HFD. The present study is the first to demonstrate that obesity enhances the recovery of bone and muscle masses as well as strength decreased by disuse after reloading in mice. Leptin may contribute to the recovery of muscle and bone enhanced by obesity in mice.
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Affiliation(s)
- Naoyuki Kawao
- Department of Physiology and Regenerative Medicine, Kindai University Faculty of Medicine, Osakasayama, Japan
| | - Masayoshi Ishida
- Department of Physiology and Regenerative Medicine, Kindai University Faculty of Medicine, Osakasayama, Japan
| | - Hiroshi Kaji
- Department of Physiology and Regenerative Medicine, Kindai University Faculty of Medicine, Osakasayama, Japan
- * E-mail:
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Meng XH, Tan LJ, Xiao HM, Tang BS, Deng HW. Examining the causal role of leptin in bone mineral density: A Mendelian randomization study. Bone 2019; 125:25-29. [PMID: 31077850 PMCID: PMC6686663 DOI: 10.1016/j.bone.2019.05.006] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/20/2018] [Revised: 04/26/2019] [Accepted: 05/07/2019] [Indexed: 01/08/2023]
Abstract
Leptin, a small polypeptide hormone secreted by the adipocytes, controls body weight and gonadal function by binding to a special receptor located in the hypothalamus. Observational studies have demonstrated a controversial association between leptin and bone mineral density (BMD), and functional studies of the relationship between leptin and BMD still largely vary by different studies. Using SNPs strongly associated with leptin levels in 52,140 individuals, we conducted a two-sample Mendelian randomization study to identify whether genetically lowered leptin levels were associated with BMD by using an inverse-variance weighted method, a weighted median method, MR-Egger and Robust Adjusted Profile Score. We found that circulating leptin levels may causally decrease lumbar spine BMD (effect size = -0.45, 95% CI: -0.82, -0.083; p value = 0.016). The association estimates of circulating leptin levels on femoral neck, forearm and total body BMD were not significant. Our study suggests that genetically predicted higher circulating leptin was associated with lower LS-BMD.
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Affiliation(s)
- Xiang-He Meng
- Laboratory of Molecular and Statistical Genetics, College of Life Sciences, Hunan Normal University, Changsha, Hunan 410081, China; Center of Bioinformatics and Genomics, School of Public Health and Tropical Medicine, Tulane University, New Orleans, LA 70112, USA
| | - Li-Jun Tan
- Laboratory of Molecular and Statistical Genetics, College of Life Sciences, Hunan Normal University, Changsha, Hunan 410081, China
| | - Hong-Mei Xiao
- School of Basic Medical Science, National Clinical Research Center for Geriatric Diseases, Xiangya Hospital, Central South University, Changsha, Hunan 410013, China
| | - Bei-Sha Tang
- School of Basic Medical Science, National Clinical Research Center for Geriatric Diseases, Xiangya Hospital, Central South University, Changsha, Hunan 410013, China
| | - Hong-Wen Deng
- Laboratory of Molecular and Statistical Genetics, College of Life Sciences, Hunan Normal University, Changsha, Hunan 410081, China; Center of Bioinformatics and Genomics, School of Public Health and Tropical Medicine, Tulane University, New Orleans, LA 70112, USA; School of Basic Medical Science, National Clinical Research Center for Geriatric Diseases, Xiangya Hospital, Central South University, Changsha, Hunan 410013, China.
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Liang M, Zhang B, Deng L, Xu R, Wu H, Chen J. Effects of Olanzapine on Bone Mineral Density, Glucose, and Lipid Metabolism in Schizophrenia Patients. Int J Endocrinol 2019; 2019:1312804. [PMID: 31019532 PMCID: PMC6451798 DOI: 10.1155/2019/1312804] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/29/2018] [Revised: 01/25/2019] [Accepted: 02/15/2019] [Indexed: 11/17/2022] Open
Abstract
AIM To explore whether olanzapine alters bone mineral density (BMD), glucose, and lipid metabolism in schizophrenia patients. METHODS This study enrolled 150 patients diagnosed with schizophrenia according to Diagnostic and Statistical Manual of Mental Disorders (DSM-IV), including 101 patients who had over 6-month history of olanzapine use (olanzapine-treated group) and 49 patients who had no history of antipsychotic use (first episode drug-naïve group). 71 subjects with age- and gender-matched healthy volunteers (healthy control group) were also enrolled. All study subjects were from the Chinese Han population recruited in the Second Xiangya Hospital from January 2015 to January 2016. Demographic and physical examination data were collected from all subjects. BMD measurements of the radius+ulna, lumbar spine (L1-4), and left hip were performed via a dual-energy X-ray absorptiometry test. Serum lipid, glucose, and insulin levels were analyzed. Psychopathology profiles in all enrolled schizophrenia patients were assessed by the positive and negative syndrome scale (PANSS). RESULTS There was no significant difference in age, gender, activity intensity, smoking, or drinking among the three groups. In the majority of evaluated bone areas, the BMD values in olanzapine-treated or drug-naïve patients were lower than those in the control group. However, BMD values in the drug-naïve group showed no difference or even decreased as compared with those in the olanzapine-treated group. Among the olanzapine-treated group, although not observed in every tested region, a positive correlation was found of BMI or HOMA-IR with BMD. Stepwise multiple linear regression analysis revealed independent predictive factors associated with BMD in groups/subgroups of schizophrenia patients or healthy controls, including gender, TG, BMI, body weight, HOMA-IR, and FBG. CONCLUSIONS Schizophrenia, but not the long-term use of olanzapine, correlates with BMD loss in schizophrenia patients. Elevated BMI, TG, FBG, and insulin levels might protect these patients against bone degradation. Our work provides new information to improve the understanding, prevention, and treatment of osteoporosis in schizophrenia patients.
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Affiliation(s)
- Mining Liang
- Clinical Nursing Teaching and Research Section, The Second Xiangya Hospital, Central South University, Changsha, Hunan Province, China
- Department of Psychiatry, The Second Xiangya Hospital, Central South University, Changsha, Hunan 410011, China
- Mental Health Institute of the Second Xiangya Hospital, Central South University, Changsha, Hunan 410011, China
- Chinese National Clinical Research Center for Mental Disorder (Xiangya), Chinese National Technology Institute on Mental Disorders, Hunan Key Laboratory of Psychiatry and Mental Health, Changsha, Hunan 410011, China
| | - Beibei Zhang
- Brain Hospital of Hunan Province, Changsha, Hunan Province, China
| | - Lu Deng
- Clinical Nursing Teaching and Research Section, The Second Xiangya Hospital, Central South University, Changsha, Hunan Province, China
| | - Rong Xu
- Clinical Nursing Teaching and Research Section, The Second Xiangya Hospital, Central South University, Changsha, Hunan Province, China
- Institute of Metabolism and Endocrinology, The Second Xiangya Hospital, Central South University, Changsha, China
| | - Haishan Wu
- Department of Psychiatry, The Second Xiangya Hospital, Central South University, Changsha, Hunan 410011, China
- Mental Health Institute of the Second Xiangya Hospital, Central South University, Changsha, Hunan 410011, China
- Chinese National Clinical Research Center for Mental Disorder (Xiangya), Chinese National Technology Institute on Mental Disorders, Hunan Key Laboratory of Psychiatry and Mental Health, Changsha, Hunan 410011, China
- Department of Neurosurgery, Xiangya Hospital, Central South University, Changsha, China
| | - Jindong Chen
- Department of Psychiatry, The Second Xiangya Hospital, Central South University, Changsha, Hunan 410011, China
- Mental Health Institute of the Second Xiangya Hospital, Central South University, Changsha, Hunan 410011, China
- Chinese National Clinical Research Center for Mental Disorder (Xiangya), Chinese National Technology Institute on Mental Disorders, Hunan Key Laboratory of Psychiatry and Mental Health, Changsha, Hunan 410011, China
- Department of Neurosurgery, Xiangya Hospital, Central South University, Changsha, China
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16
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Reid IR, Baldock PA, Cornish J. Effects of Leptin on the Skeleton. Endocr Rev 2018; 39:938-959. [PMID: 30184053 DOI: 10.1210/er.2017-00226] [Citation(s) in RCA: 120] [Impact Index Per Article: 17.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/11/2017] [Accepted: 06/26/2018] [Indexed: 12/12/2022]
Abstract
Leptin originates in adipocytes, including those in bone marrow, and circulates in concentrations 20 to 90 times higher than those in the cerebrospinal fluid. It has direct anabolic effects on osteoblasts and chondrocytes, but it also influences bone indirectly, via the hypothalamus and sympathetic nervous system, via changes in body weight, and via effects on the production of other hormones (e.g., pituitary). Leptin's role in bone physiology is determined by the balance of these conflicting effects. Reflecting this inconsistency, the leptin-deficient mouse has reduced length and bone mineral content of long bones but increased vertebral trabecular bone. A consistent bone phenotype in human leptin deficiency has not been established. Systemic leptin administration in animals and humans usually exerts a positive effect on bone mass, and leptin administration into the cerebral ventricles usually normalizes the bone phenotype in leptin-deficient mice. Reflecting the role of the sympathetic nervous system in mediating the central catabolic effects of leptin on the skeleton, β-adrenergic agonists and antagonists have major effects on bone in mice, but this is not consistently seen in humans. The balance of the central and peripheral effects of leptin on bone remains an area of substantial controversy and might vary between species and according to other factors such as body weight, baseline circulating leptin levels, and the presence of specific pathologies. In humans, leptin is likely to contribute to the positive relationship observed between adiposity and bone density, which allows the skeleton to respond appropriately to changes in soft tissue mass.
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Affiliation(s)
- Ian R Reid
- University of Auckland, Auckland, New Zealand.,Department of Endocrinology, Auckland District Health Board, Auckland, New Zealand
| | - Paul A Baldock
- Garvan Institute of Medical Research, Sydney, New South Wales, Australia
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Bilha SC, Branisteanu D, Buzduga C, Constantinescu D, Cianga P, Anisie E, Gavrilovici C, Covic A, Ungureanu MC. Modifications in the spectrum of bone mass predictive factors with menopausal status. Endocr Res 2018. [PMID: 29528762 DOI: 10.1080/07435800.2018.1448991] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/30/2023]
Abstract
PURPOSE Fat mass (FM) is a source of adipocytokines, with both positive and negative bone consequences. We aimed to investigate the role of body composition and adipokines as predictive factors for bone mass in women. METHODOLOGY This cross-sectional study included 93 women (38 premenopausal and 55 postmenopausal). Bone mineral density (BMD) and body composition were assessed by dual-energy X-ray absorptiometry. Serum levels of leptin, adiponectin, resistin, and also of the phosphocalcic markers parathormone and vitamin D were measured. RESULTS Only lean mass (LM) was an independent predictor of BMD in premenopausal women (r2 = 0.381, p < 0.001 for femoral neck BMD, r2 = 0.2, p < 0.01 for whole-body BMD) in both unadjusted and age-adjusted models. The effect of total FM upon BMD became nonsignificant when LM was added to the models assessed. In postmenopausal women, although LM, trunk-to-leg fat ratio, and resistin were initially associated with BMD in unadjusted models, only the trunk-to-leg fat ratio independently predicted BMD at various sites (r2 = 0.171, p < 0.01 for lumbar BMD, r2 = 0.078, p < 0.05 for radius BMD, r2 = 0.094, p < 0.05 for whole-body BMD) after adjusting for age. CONCLUSIONS While in premenopausal women the effect of LM upon bone is prevalent, after menopause, the fat distribution reflected by trunk-to-leg fat ratio is a major determinant of bone mass at different sites. Our study also stresses that the relationship between total FM and BMD is not mediated by adipokines in women irrespective of menopausal status and body composition, but it is largely mediated by LM only in young premenopausal women.
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Affiliation(s)
- Stefana Catalina Bilha
- a Endocrinology Department, "St. Spiridon" Hospital , "Grigore T. Popa" University of Medicine and Pharmacy , Iasi , Romania
- d Nephrology Department, Dialysis and Renal Transplant Centre, "C.I. Parhon" University Hospital , "Grigore T. Popa" University of Medicine and Pharmacy , Iasi , Romania
| | - Dumitru Branisteanu
- a Endocrinology Department, "St. Spiridon" Hospital , "Grigore T. Popa" University of Medicine and Pharmacy , Iasi , Romania
| | - Catalin Buzduga
- a Endocrinology Department, "St. Spiridon" Hospital , "Grigore T. Popa" University of Medicine and Pharmacy , Iasi , Romania
| | - Daniela Constantinescu
- b Immunology Department, "St. Spiridon" Hospital , "Grigore T. Popa" University of Medicine and Pharmacy , Iasi , Romania
| | - Petru Cianga
- b Immunology Department, "St. Spiridon" Hospital , "Grigore T. Popa" University of Medicine and Pharmacy , Iasi , Romania
| | - Ecaterina Anisie
- b Immunology Department, "St. Spiridon" Hospital , "Grigore T. Popa" University of Medicine and Pharmacy , Iasi , Romania
| | - Cristina Gavrilovici
- c Centre for Ethics and Health Policy , "Grigore T. Popa" University of Medicine and Pharmacy , Iasi , Romania
| | - Adrian Covic
- d Nephrology Department, Dialysis and Renal Transplant Centre, "C.I. Parhon" University Hospital , "Grigore T. Popa" University of Medicine and Pharmacy , Iasi , Romania
| | - Maria Christina Ungureanu
- a Endocrinology Department, "St. Spiridon" Hospital , "Grigore T. Popa" University of Medicine and Pharmacy , Iasi , Romania
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Abstract
The interaction between obesity and bone metabolism is complex. The effects of fat on the skeleton are mediated by both mechanical and biochemical factors. Though obesity is characterized by higher bone mineral density, studies conducted on bone microarchitecture have produced conflicting results. The majority of studies indicate that obesity has a positive effect on skeletal strength, even though most likely the effects are site-dependent and, in fact, obese individuals might be at risk of certain types of fractures. Mechanical loading and higher lean mass are associated with improved outcomes, whereas systemic inflammation, observed especially with abdominal obesity, may exert negative effects. Weight loss interventions likely lead to bone loss over time. Pharmacological treatment options seem to be safe in terms of skeletal health; however, the skeletal effects of bariatric surgery are dependent on the type of surgical procedure. Malabsorptive procedures are associated with higher short-term adverse effects on bone health. In this narrative review, we discuss the effects of obesity and weight loss interventions on skeletal health.
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Affiliation(s)
- Christos Savvidis
- Department of Endocrinology, Hippokrateion General Hospital, Athens, Greece
| | - Symeon Tournis
- Laboratory for Research of the Musculoskeletal System "Th. Garofalidis", KAT hospital, Medical school, Athens, Greece
| | - Anastasia D Dede
- Laboratory for Research of the Musculoskeletal System "Th. Garofalidis", KAT hospital, Medical school, Athens, Greece.
- Department of Endocrinology and Diabetes, Chelsea and Westminster Hospital, 369 Fulham Road, London, SW10 9NH, UK.
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High-refined carbohydrate diet promotes detrimental effects on alveolar bone and femur microarchitecture. Arch Oral Biol 2018; 86:101-107. [DOI: 10.1016/j.archoralbio.2017.11.013] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/06/2017] [Revised: 11/14/2017] [Accepted: 11/27/2017] [Indexed: 01/27/2023]
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Ponti F, Guerri S, Sassi C, Battista G, Guglielmi G, Bazzocchi A. Imaging of diabetic bone. Endocrine 2017; 58:426-441. [PMID: 28293856 DOI: 10.1007/s12020-017-1278-5] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/01/2016] [Accepted: 02/24/2017] [Indexed: 01/02/2023]
Abstract
Diabetes is an important concern in terms of medical and socioeconomic costs; a high risk for low-trauma fractures has been reported in patients with both type 1 and type 2 diabetes. The mechanism involved in the increased fracture risk from diabetes is highly complex and still not entirely understood; obesity could play an important role: recent evidence suggests that the influence of fat on bone is mainly dependent on the pattern of regional fat deposition and that an increased amount of visceral adipose tissue negatively affects skeletal health.Correct and timely individuation of people with high fracture risk is critical for both prevention and treatment: Dual-energy X-ray Absorptiometry (currently the "gold standard" for diagnosis of osteoporosis) underestimates fracture risk in diabetic patients and therefore is not sufficient by itself to investigate bone status. This paper is focused on imaging, covering different modalities involved in the evaluation of skeletal deterioration in diabetes, discussing the limitations of conventional methods and exploring the potential of new tools and recent high-resolution techniques, with the intent to provide interesting insight into pathophysiology and fracture risk.
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Affiliation(s)
- Federico Ponti
- Diagnostic and Interventional Radiology, The "Rizzoli" Orthopaedic Institute, Via G. C. Pupilli 1, 40136, Bologna, Italy
- Department of Experimental, Diagnostic and Specialty Medicine (DIMES), Division of Radiology S.Orsola-Malpighi Hospital, University of Bologna, Via G. Massarenti 9, 40138, Bologna, Italy
| | - Sara Guerri
- Department of Experimental, Diagnostic and Specialty Medicine (DIMES), Division of Radiology S.Orsola-Malpighi Hospital, University of Bologna, Via G. Massarenti 9, 40138, Bologna, Italy
| | - Claudia Sassi
- Department of Experimental, Diagnostic and Specialty Medicine (DIMES), Division of Radiology S.Orsola-Malpighi Hospital, University of Bologna, Via G. Massarenti 9, 40138, Bologna, Italy
| | - Giuseppe Battista
- Department of Experimental, Diagnostic and Specialty Medicine (DIMES), Division of Radiology S.Orsola-Malpighi Hospital, University of Bologna, Via G. Massarenti 9, 40138, Bologna, Italy
| | - Giuseppe Guglielmi
- Department of Radiology, University of Foggia, Viale Luigi Pinto 1, 71100, Foggia, Italy
- Department of Radiology, Scientific Institute "Casa Sollievo della Sofferenza" Hospital, Viale Cappuccini 1, 71013, San Giovanni Rotondo, Foggia, Italy
| | - Alberto Bazzocchi
- Diagnostic and Interventional Radiology, The "Rizzoli" Orthopaedic Institute, Via G. C. Pupilli 1, 40136, Bologna, Italy.
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Hwang JA, Kim YS, Leem AY, Park MS, Kim SK, Chang J, Jung JY. Clinical Implications of Sarcopenia on Decreased Bone Density in Men With COPD. Chest 2017; 151:1018-1027. [DOI: 10.1016/j.chest.2016.12.006] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/06/2016] [Revised: 10/28/2016] [Accepted: 12/05/2016] [Indexed: 01/16/2023] Open
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Tariq S, Baig M, Tariq S, Shahzad M. Association of serum leptin with bone mineral density in postmenopausal osteoporotic females. Gynecol Endocrinol 2017; 33:287-291. [PMID: 28010139 DOI: 10.1080/09513590.2016.1261103] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/13/2023] Open
Abstract
OBJECTIVE Present study was designed to find out whether leptin is a predictor of bone mass density (BMD) in premenopausal women (PMW) and postmenopausal osteoporotic women (PMOPW) or it has no association with BMD. METHODS One hundred and ninety two women (98 PMOPW and 94 PMW) were recruited for this study. The control group was BMI matched with osteoporotic subjects. BMD assessment was done on calcaneus by peripheral ultrasound bone densitometry and T scores were determined. Serum leptin levels were measured by enzyme-linked immunosorbent assay (ELISA). RESULTS Serum leptin and BMD values were significantly different in both groups (leptin, 18.56 ± 8.65 ng/ml versus 21.64 ± 9.80 ng/ml, p = 0.02) and (BMD, -0.70 ± 0.19 versus -3.17 ± 0.59, p = 0.000), respectively. In PMOPW serum leptin and BMD were considerably correlated with weight (lep, r = 0.53, p = <0.001; BMD, r = -0.21, p = 0.02), BMI (lep, r = 0.52, p = <0.001; BMD, r = -0.27, p = 0.005), waist circumference (lep, r = 0.61, p = <0.001; BMD, r = 0.18, p = 0.04), hip circumference (lep, r = 0.58, p = <0.001). Multivariate linear stepwise regression analysis showed that weight and BMI in PMW and PMOPW were independent predictors of BMD. Serum leptin level was not found to be the predictor of BMD in both groups. CONCLUSION The present results indicate that body weight and BMI have an impact on BMD while serum leptin is not associated with BMD in PMW and PMOPW.
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Affiliation(s)
- Saba Tariq
- a Department of Pharmacology , University Medical and Dental College , Faisalabad , Pakistan
- b Department of Pharmacology , University of Health Sciences , Lahore , Pakistan
| | - Mukhtiar Baig
- c Department of Clinical Biochemistry , Faculty of Medicine, Rabigh, King Abdulaziz University , Jeddah , Saudi Arabia
| | - Sundus Tariq
- d Department of Physiology , University Medical and Dental College , Faisalabad , Pakistan , and
- e Department of Physiology , University of Health Sciences , Lahore , Pakistan
| | - Muhammad Shahzad
- b Department of Pharmacology , University of Health Sciences , Lahore , Pakistan
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Abstract
Background Leptin plays a crucial role in bone metabolism, and its level is related to bone callus formation in the fracture repair process. The objective of this study was to evaluate the effect of recombinant leptin on the healing process of femoral fractures in rats. Material/Methods Forty-eight male Sprague Dawley (SD) rats with an average body weight of 389 g (range: 376–398 g) and an average age of 10 weeks were included in this animal research, and all rats were randomly divided into two major groups. Then standardized femur fracture models were implemented in all SD rats. Rats in the control group were treated with only 0.5 mL of physiological saline, and rats in the experimental group were treated with recombinant leptin 5 μg/kg/d along with the same 0.5 mL of physiological saline for 42 days intraperitoneally. At the same time, each major group was evenly divided into three parallel subgroups for each parallel bone evaluation separately at the second, fourth, and sixth weeks. Each subgroup included eight rats. Results The total radiological evaluation results showed that the healing progress of femoral fracture in the experimental group was superior to that in the control group from the fourth week. At the sixth week, experimental group rats began to present significantly better femoral fracture healing progress than that of the control group rats. Results of biomechanics show the ultimate load (N) and deflection ultimate load (mm) of the experimental group rats was significantly increased compared with that of the control group rats from the fourth week. Conclusions Our results suggest that leptin may have a positive effect on SD rat femur fracture healing.
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Affiliation(s)
- Pengcheng Liu
- Department of Orthopedics, Shanghai Tenth People's Hospital, School of Medicine, Tongji University, Shanghai, China (mainland)
| | - Ming Cai
- Department of Orthopedics, Shanghai Tenth People's Hospital, School of Medicine, Tongji University, Shanghai, China (mainland)
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Ho-Pham LT, Lai TQ, Nguyen UDT, Bui QV, Nguyen TV. Delineating the Relationship Between Leptin, Fat Mass, and Bone Mineral Density: A Mediation Analysis. Calcif Tissue Int 2017; 100:13-19. [PMID: 27722770 DOI: 10.1007/s00223-016-0196-5] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/04/2016] [Accepted: 10/01/2016] [Indexed: 11/26/2022]
Abstract
To test the hypothesis that the relationship between fat mass (FM) and bone mineral density (BMD) is mediated by leptin. The study involved 611 individuals aged 20-89 years who were randomly sampled from Ho Chi Minh City (Vietnam). BMD at the femoral neck (FN), lumbar spine (LS), and whole body (WB) was measured by DXA. Lean mass and FM were derived from the WB DXA scan. Leptin was measured by ELISA (DRG Diagnostics, Germany). The regression method was used to partition the variance of leptin and FM on BMD. The mediated effect of leptin was analyzed by the mediation analysis model. In the multiple linear regression, leptin, FM, and age collectively accounted for ~34 % variation in FNBMD in men and women. However, only 0.5 % of this explained variance was due to leptin. Of the total effect of FM on FNBMD, the mediated effect of leptin accounted for 6.1 % (P = 0.38) in men and 7.1 % (P = 0.99) in women. The same trend was observed for LS and WBBMD. These data suggest that greater FM is associated with greater BMD, but the association is not mediated by leptin, and that leptin has a non-significant influence on bone mass.
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Affiliation(s)
- Lan T Ho-Pham
- Bone and Muscle Research Group, Ton Duc Thang University, 19 Nguyen Huu Tho Street, Tan Phong Ward, Ho Chi Minh City, Vietnam.
| | - Thai Q Lai
- Department of Rheumatology, People's Hospital 115, Ho Chi Minh City, Vietnam
| | - Uyen D T Nguyen
- Department of Internal Medicine, Pham Ngoc Thach University of Medicine, Ho Chi Minh City, Vietnam
| | - Quoc V Bui
- Department of Internal Medicine, Pham Ngoc Thach University of Medicine, Ho Chi Minh City, Vietnam
| | - Tuan V Nguyen
- Garvan Institute of Medical Research, Darlinghurst, Australia
- School of Public Health and Community Medicine, UNSW Australia, Sydney, Australia
- University of Technology Sydney, Ultimo, Australia
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25
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Sharma A, Ma Y, Scherzer R, Wheeler AL, Cohen M, Gustafson DR, Keating SM, Yin MT, Tien PC. Brief Report: Association of Adipokines With Bone Mineral Density in HIV-Infected and HIV-Uninfected Women. J Acquir Immune Defic Syndr 2016; 73:433-437. [PMID: 27792683 PMCID: PMC5098807 DOI: 10.1097/qai.0000000000001118] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
Abstract
BACKGROUND HIV infection is associated with low bone mineral density (BMD) and alterations in adipokines, which may mediate the relationship between fat and bone. OBJECTIVE To evaluate the relationship of adiponectin and leptin with BMD in HIV-infected and uninfected women. METHODS We measured BMD over 5 years at the lumbar spine, total hip (TH), and femoral neck (FN) using dual-energy X-ray absorptiometry in 318 HIV-infected and 122 HIV-uninfected participants of the multicenter Women's Interagency HIV Study (WIHS). Total adiponectin and leptin were assayed on stored sera. Multivariable linear mixed models assessed the effects of adipokines and HIV status on BMD. RESULTS HIV-infected women had higher adiponectin (median 6.2 vs. 5.6 μg/mL,) but lower leptin (11.7 vs. 19.8 ng/mL) levels at baseline (both P < 0.05) compared with HIV-uninfected women. HIV infection was associated with lower BMD at the lumbar spine (-0.074 g/cm), FN (-0.049 g/cm), and TH (-0.047 g/cm) (all P < 0.05) after adjusting for demographic, behavioral, and metabolic factors. HIV infection remained associated with lower BMD at each site, with little change in the effect sizes after additional adjustment for adiponectin or leptin. Among HIV-infected women, higher adiponectin was associated with lower TH BMD (-0.025 g/cm per 10-fold increase, P = 0.035), whereas higher leptin was associated with higher BMD at FN (+0.027 g/cm per 10-fold increase, P = 0.005) and TH (+0.019 g/cm, P = 0.028). After multivariable adjustment, the adipokines showed little association with BMD at any site (P > 0.8 for adiponectin; P > 0.2 for leptin). CONCLUSIONS Alterations in serum adiponectin and leptin do not explain low BMD in HIV-infected women.
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Affiliation(s)
- Anjali Sharma
- Department of Medicine, Albert Einstein College of Medicine, Bronx, NY
| | - Yifei Ma
- Department of Pediatrics, University of California, San Francisco, CA
| | - Rebecca Scherzer
- Department of Medicine, University of California, San Francisco, CA
| | - Amber L. Wheeler
- Department of Medicine, San Francisco Veterans Affairs Medical Center, San Francisco, CA
| | - Mardge Cohen
- Department of Medicine, John H. Stroger, Jr. Hospital of Cook County, Chicago, IL
| | | | | | - Michael T. Yin
- Department of Medicine, Columbia University, New York, NY
| | - Phyllis C. Tien
- Department of Medicine, University of California, San Francisco, CA
- Department of Medicine, San Francisco Veterans Affairs Medical Center, San Francisco, CA
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26
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Liu P, Liu J, Xia K, Chen L, Wu X. Effect of leptin combined with CoCl2 on healing in Sprague Dawley Rat fracture model. Sci Rep 2016; 6:30754. [PMID: 27468656 PMCID: PMC4965822 DOI: 10.1038/srep30754] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/14/2016] [Accepted: 07/08/2016] [Indexed: 12/17/2022] Open
Abstract
To evaluate the effect of leptin combined with CoCl2 on rat femur fracture healing. 48 male Sprague Dawley rats were randomly divided into two main groups. Then standardized femur fractures were created to all rats. Control group rats were treated with 0.5 mL physiological saline, and experimental group rats were treated with 5 μg/Kg.d leptin and 15 mg/Kg.d CoCl2 along with 0.5 mL physiological saline for 42 days intraperitoneally. Each main group was divided into three subgroups for each evaluation at second, fourth and sixth weeks, each subgroup included eight rats. The radiological evaluation showed that the fracture healing progress of experimental group was superior to control group from second week. At fourth week, experimental group had better fracture healing progress than control group significantly. Results of biomechanics show the ultimate load (N) and deflection ultimate load (mm) of experimental group was significantly increased than that in control group from fourth week. The present result demonstrated that leptin combined with CoCl2 significantly increased the mRNA expression levels of HIF1A, Vegfa, Runx2, Bmp2, Bglap and Alpl. It suggested that leptin combined with CoCl2 have a positive effect on rat femur fracture healing by activating the HIF1A pathway.
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Affiliation(s)
- Pengcheng Liu
- Department of Orthopedics, Shanghai Tenth People's Hospital, School of Medicine, Tongji University, Shanghai 200072, P.R. China
| | - Junfeng Liu
- Department of Orthopedics, Shanghai Tenth People's Hospital, School of Medicine, Tongji University, Shanghai 200072, P.R. China
| | - Kuo Xia
- Department of Orthopedics, Shanghai Tenth People's Hospital, School of Medicine, Tongji University, Shanghai 200072, P.R. China
| | - Liyang Chen
- Department of Orthopedics, Shanghai Tenth People's Hospital, School of Medicine, Tongji University, Shanghai 200072, P.R. China
| | - Xing Wu
- Department of Orthopedics, Shanghai Tenth People's Hospital, School of Medicine, Tongji University, Shanghai 200072, P.R. China
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Mpalaris V, Anagnostis P, Anastasilakis AD, Goulis DG, Doumas A, Iakovou I. Serum leptin, adiponectin and ghrelin concentrations in post-menopausal women: Is there an association with bone mineral density? Maturitas 2016; 88:32-6. [PMID: 27105694 DOI: 10.1016/j.maturitas.2016.03.004] [Citation(s) in RCA: 25] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/31/2015] [Revised: 01/29/2016] [Accepted: 03/03/2016] [Indexed: 12/29/2022]
Abstract
OBJECTIVE Adipokines and ghrelin exert well-documented effects on energy expenditure and glucose metabolism. Experimental data also support a role in bone metabolism, although data from clinical studies are conflicting. The purpose of this cross-sectional study was to investigate the association of serum concentrations of leptin, adiponectin and ghrelin with bone mineral density (BMD) in post-menopausal women. METHODS BMD in lumbar spine and femoral neck, and circulating leptin, adiponectin and ghrelin concentrations were measured in 110 healthy post-menopausal women. Patients with secondary causes of osteoporosis were excluded. RESULTS Osteoporosis was diagnosed in 30 (27%) women and osteopenia in 54 (49%). Serum leptin concentrations were positively correlated with both lumbar spine (r=0.343, p<0.01) and femoral neck BMD (r=0.370, p<0.01). Adiponectin concentrations were negatively associated with BMD at both sites (r=-0.321, p<0.01 and r=-0.448, p<0.01 respectively). No significant correlation between ghrelin concentrations and BMD was found. Osteoporotic women had lower body weight, body mass index (BMI) and leptin concentrations, but higher adiponectin concentrations compared with non-osteoporotic women. In multivariate stepwise regression analysis, the association of adiponectin concentrations with BMD remained significant only for femoral neck, after adjustment for body weight or BMI. CONCLUSIONS An inverse association between adiponectin and femoral neck BMD was found in post-menopausal women, independently of body weight. The positive association between leptin and BMD was dependent on body weight, whereas no effect of ghrelin on BMD was evident.
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Affiliation(s)
- V Mpalaris
- Department of Nuclear Medicine, Aristotle University, Papageorgiou Hospital, 56403 Thessaloniki, Greece
| | - P Anagnostis
- Unit of Reproductive Endocrinology, 1st Department of Obstetrics and Gynecology, Medical School, Aristotle University of Thessaloniki, Greece
| | - A D Anastasilakis
- Department of Endocrinology, 424 General Military Hospital, Thessaloniki, Greece
| | - D G Goulis
- Unit of Reproductive Endocrinology, 1st Department of Obstetrics and Gynecology, Medical School, Aristotle University of Thessaloniki, Greece
| | - A Doumas
- Department of Nuclear Medicine, Aristotle University, Papageorgiou Hospital, 56403 Thessaloniki, Greece
| | - I Iakovou
- Department of Nuclear Medicine, Aristotle University, Papageorgiou Hospital, 56403 Thessaloniki, Greece.
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Kim JH, Choi HJ, Ku EJ, Hong AR, Kim KM, Kim SW, Cho NH, Shin CS. Regional body fat depots differently affect bone microarchitecture in postmenopausal Korean women. Osteoporos Int 2016; 27:1161-1168. [PMID: 26475286 DOI: 10.1007/s00198-015-3329-1] [Citation(s) in RCA: 37] [Impact Index Per Article: 4.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/12/2015] [Accepted: 09/16/2015] [Indexed: 12/25/2022]
Abstract
SUMMARY In a prospective community-based cohort study, we investigated the relationship between trabecular bone score (TBS) and regional fat depots in 1474 Korean postmenopausal women. TBS was positively related with subcutaneous fat and negatively related with visceral fat. INTRODUCTION The effect of fat distribution (visceral/subcutaneous) on bone quality or microarchitecture has rarely been investigated due to measurement difficulty. We aimed to investigate the relationship between TBS reflecting bone microarchitecture and regional fat depots in Korean women. METHODS Cross-sectional data evaluation was made from subjects participating in an ongoing prospective community-based cohort study since 2001. A total of 1474 postmenopausal women in the Ansung cohort were analyzed. Regional body fat mass, bone mineral density (BMD) at the lumbar spine, and total hip and lumbar spine TBS were measured by dual energy X-ray absorptiometry (DXA). RESULTS In an age-adjusted partial correlation analysis, TBS was not associated with total fat mass, but negatively associated with trunk fat mass. However, TBS was positively related with leg (r = 0.102, P < 0.05) and gynoid fat mass (r = 0.086, P < 0.05) and negatively related with android fat mass (r = -0.106; P < 0.05). In linear regression models controlling age, BMI, and physical activity, android fat was inversely associated with TBS (β = -0.595, P < 0.001), whereas gynoid fat was positively associated with TBS (β = 0.216, P < 0.001). Lumbar spine and total hip BMDs revealed positive associations with total and all regional fat depots regardless of fat distribution. CONCLUSION Our findings suggest that relatively large visceral fat and small subcutaneous fat may have a detrimental effect on TBS, a bone microarchitecture index.
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Affiliation(s)
- J H Kim
- Department of Internal Medicine, Seoul National University College of Medicine, Seoul, South Korea
| | - H J Choi
- Department of Anatomy, Seoul National University College of Medicine, Seoul, South Korea
| | - E J Ku
- Department of Internal Medicine, Chungbuk National University College of Medicine, Cheongju Si, South Korea
| | - A R Hong
- Department of Internal Medicine, Seoul National University College of Medicine, Seoul, South Korea
| | - K M Kim
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, South Korea
| | - S W Kim
- Department of Internal Medicine, Seoul National University College of Medicine, Seoul, South Korea
| | - N H Cho
- Department of Preventive Medicine, Ajou University School of Medicine, Suwon, South Korea.
| | - C S Shin
- Department of Internal Medicine, Seoul National University College of Medicine, Seoul, South Korea.
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Greco EA, Lenzi A, Migliaccio S. The pathophysiological basis of bone tissue alterations associated with eating disorders. Horm Mol Biol Clin Investig 2016; 28:121-132. [DOI: 10.1515/hmbci-2016-0006] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/18/2016] [Accepted: 02/09/2016] [Indexed: 12/13/2022]
Abstract
AbstractAnorexia nervosa (AN) and obesity are two major eating disorders present nowadays in Western countries. They are both characterized by striking body composition variations and hormonal alterations, which impact on skeletal metabolism, inducing bone tissue modifications and, thus, often cause an increased risk for fractures. AN and obesity are characterized by a severe reduction in fat mass and a high expression of it, respectively, and in both conditions hormones secreted or modulated by body fat content are important determinants of low bone density, impaired bone structure and reduced bone strength. In addition, in both AN and obesity, increased marrow adiposity, which correlates with low bone density, has been observed. This review will discuss the pathophysiological basis of bone alterations associated with AN and obesity, conditions of extreme energy deficiency and excess, respectively.
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30
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Kanazawa I. Osteocalcin as a hormone regulating glucose metabolism. World J Diabetes 2015; 6:1345-1354. [PMID: 26722618 PMCID: PMC4689779 DOI: 10.4239/wjd.v6.i18.1345] [Citation(s) in RCA: 61] [Impact Index Per Article: 6.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/21/2015] [Revised: 10/23/2015] [Accepted: 12/02/2015] [Indexed: 02/05/2023] Open
Abstract
The number of patients with osteoporosis and diabetes is rapidly increasing all over the world. Bone is recently recognized as an endocrine organ. Accumulating evidence has shown that osteocalcin, which is specifically expressed in osteoblasts and secreted into the circulation, regulates glucose homeostasis by stimulating insulin expression in pancreas and adiponectin expression in adipocytes, resulting in improving glucose intolerance. On the other hand, insulin and adiponectin stimulate osteocalcin expression in osteoblasts, suggesting that positive feedforward loops exist among bone, pancreas, and adipose tissue. In addition, recent studies have shown that osteocalcin enhances insulin sensitivity and the differentiation in muscle, while secreted factors from muscle, myokines, regulate bone metabolism. These findings suggest that bone metabolism and glucose metabolism are associated with each other through the action of osteocalcin. In this review, I describe the role of osteocalcin in the interaction among bone, pancreas, brain, adipose tissue, and muscle.
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31
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Chen XX, Yang T. Roles of leptin in bone metabolism and bone diseases. J Bone Miner Metab 2015; 33:474-85. [PMID: 25777984 DOI: 10.1007/s00774-014-0569-7] [Citation(s) in RCA: 65] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/24/2013] [Accepted: 01/16/2014] [Indexed: 02/05/2023]
Abstract
Adipose tissue has been more accepted as an active contributor to whole body homeostasis, rather than just a fat depot, since leptin, a 16 kDa protein, was discovered as the product of the obese gene in 1994. With more and more studies conducted on this hormone, it has been shown that there is a close relationship between adipose tissue and bone, which have important effects on each other. Bone is the source of many hormones, such as osteocalcin, that can affect energy metabolism and then the anabolism or catabolism of fat tissue. In contrast, the adipose tissue synthesizes and releases a series of adipokines, which are involved in bone metabolism through direct or indirect effects on bone formation and resorption. Interestingly, leptin, one of the most important cytokines derived from fat tissue, seems to account for the largest part of effects on bone, through direct or indirect involvement in bone remodeling and by playing a significant role in many bone diseases, such as osteoporosis, osteoarthritis, rheumatic arthritis, bone tumors and even fractures. In this review, we will discuss the progress in leptin research, particularly focusing on the roles of leptin in bone diseases.
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Affiliation(s)
- Xu Xu Chen
- Department of Orthopedic Surgery, West China Hospital, Sichuan University, 37# Guo Xue Xiang, Chengdu, 610041, Sichuan, People's Republic of China
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Migliaccio S, Greco EA, Wannenes F, Donini LM, Lenzi A. Adipose, bone and muscle tissues as new endocrine organs: role of reciprocal regulation for osteoporosis and obesity development. Horm Mol Biol Clin Investig 2015; 17:39-51. [PMID: 25372729 DOI: 10.1515/hmbci-2013-0070] [Citation(s) in RCA: 22] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/31/2013] [Accepted: 02/14/2014] [Indexed: 02/07/2023]
Abstract
The belief that obesity is protective against osteoporosis has recently been revised. In fact, the latest epidemiologic and clinical studies show that a high level of fat mass, but also reduced muscle mass, might be a risk factor for osteoporosis and fragility fractures. Furthermore, increasing evidence seems to indicate that different components such as myokines, adipokines and growth factors, released by both fat and muscle tissues, could play a key role in the regulation of skeletal health and in low bone mineral density and, thus, in osteoporosis development. This review considers old and recent data in the literature to further evaluate the relationship between fat, bone and muscle tissue.
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Liu K, Liu P, Liu R, Wu X, Cai M. Relationship between serum leptin levels and bone mineral density: a systematic review and meta-analysis. Clin Chim Acta 2015; 444:260-3. [PMID: 25748037 DOI: 10.1016/j.cca.2015.02.040] [Citation(s) in RCA: 29] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/07/2015] [Revised: 02/22/2015] [Accepted: 02/23/2015] [Indexed: 11/19/2022]
Abstract
BACKGROUND The association between leptin and bone mineral density (BMD) is controversial because of conflicting findings from previous studies. METHODS This meta-analysis aimed to provide an overview of the serum leptin levels and BMD in a healthy population. We reviewed the PubMed, Embase, and Cochrane Library databases until July 2014 for research on the association between leptin levels and BMD in healthy people. RESULTS We included and analyzed 45 studies in this systematic review and meta-analysis. The pooled correlations between leptin and BMD were analyzed by using the method of the inverse of the variance. Leptin was positively associated with BMD and the bone mineral content (BMC), especially in postmenopausal women (pooled r: 0.13-0.49). Overall, high serum leptin levels were associated with higher BMD levels. CONCLUSIONS This meta-analysis suggests that serum leptin levels are positively associated with BMD and BMC, especially in postmenopausal women.
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Affiliation(s)
- Kuan Liu
- Department of Orthopedics, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, China
| | - Pengcheng Liu
- Department of Orthopedics, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, China
| | - Run Liu
- Department of Orthopedics, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, China
| | - Xing Wu
- Department of Orthopedics, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, China.
| | - Ming Cai
- Department of Orthopedics, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, China.
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Mpalaris V, Anagnostis P, Goulis DG, Iakovou I. Complex association between body weight and fracture risk in postmenopausal women. Obes Rev 2015; 16:225-33. [PMID: 25586664 DOI: 10.1111/obr.12244] [Citation(s) in RCA: 48] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/07/2014] [Revised: 10/09/2014] [Accepted: 11/03/2014] [Indexed: 11/27/2022]
Abstract
Osteoporosis is a common disease, characterized by low bone mass with micro-architectural disruption and skeletal fragility, resulting in an increased risk of fracture. A substantial number of studies has examined the possible relationship between body weight, bone mineral density and fracture risk in post-menopausal women, with the majority of them concluding that low body weight correlates with increased risk of fracture, especially hip fracture. Controversies about the potential protective effect of obesity on osteoporosis and consequent fracture risk still exist. Several recent studies question the concept that obesity exerts a protective effect against fractures, suggesting that it stands as a risk factor for fractures at specific skeletal sites, such as upper arm. The association between body weight and fracture risk is complex, differs across skeletal sites and body mass index, and is modified by the interaction between body weight and bone mineral density. Some potential explanations that link obesity with increased fracture risk may be the pattern of falls and impaired mobility in obese individuals, comorbidities, such as asthma, diabetes and early menopause, as well as, increased parathyroid hormone and reduced 25-hydroxy-vitamin D concentrations.
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Affiliation(s)
- V Mpalaris
- Third Department of Nuclear Medicine, Medical School, Aristotle University of Thessaloniki, Thessaloniki, Greece
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Abstract
Bone metabolism is regulated by the action of two skeletal cells: osteoblasts and osteoclasts. This process is controlled by many genetic, hormonal and lifestyle factors, but today more and more studies have allowed us to identify a neuronal regulation system termed 'bone-brain crosstalk', which highlights a direct relationship between bone tissue and the nervous system. The first documentation of an anatomic relationship between nerves and bone was made via a wood cut by Charles Estienne in Paris in 1545. His diagram demonstrated nerves entering and leaving the bones of a skeleton. Later, several studies were conducted on bone innervation and, as of today, many observations on the regulation of bone remodeling by neurons and neuropeptides that reside in the CNS have created a new research field, that is, neuroskeletal research.
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Affiliation(s)
- Alessia Metozzi
- a 1 Department of Surgery and Translational Medicine, Metabolic Bone Diseases Unit, University of Florence, Largo Palagi 1, 50138 Florence, Italy
| | - Lorenzo Bonamassa
- a 1 Department of Surgery and Translational Medicine, Metabolic Bone Diseases Unit, University of Florence, Largo Palagi 1, 50138 Florence, Italy
| | - Gemma Brandi
- b 2 Public Mental Health system 1-4 of Florence, Florence, Italy
| | - Maria Luisa Brandi
- c 3 Department of Surgery and Translational Medicine, Metabolic Bone Diseases Unit, AOUC Careggi, University of Florence, Largo Palagi 1, 50138 Florence, Italy
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36
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Sabour H, Norouzi Javidan A, Latifi S, Shidfar F, Vafa MR, Emami Razavi SH, Larijani B, Heshmat R. Relationship between leptin and adiponectin concentrations in plasma and femoral and spinal bone mineral density in spinal cord-injured individuals. Spine J 2015; 15:1-9. [PMID: 24948038 DOI: 10.1016/j.spinee.2014.06.009] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/01/2014] [Revised: 05/11/2014] [Accepted: 06/09/2014] [Indexed: 02/03/2023]
Abstract
BACKGROUND CONTEXT Previously, the associations between leptin and adiponectin levels with bone mineral density (BMD) have been reported in different populations, and occasionally, controversial results have been demonstrated. Until now, these relationships in spinal cord-injured individuals have not yet been described. PURPOSE We tried to investigate the correlation between leptin and adiponectin concentrations in plasma and BMD in Iranian patients with spinal cord injury (SCI). STUDY DESIGN/SETTING Cross-sectional investigation. PATIENT SAMPLE Referred patients with SCI who did not meet our exclusion criteria such as pregnancy, lactation, amputation, history of diabetes, cancer, endocrinology disease, and use of special medications entered the study. OUTCOME MEASURES Bone mineral density of femoral neck, trochanter, intertrochanteric zone, total hip, and lumbar vertebrae assessed by dual-energy X-ray absorptiometry and serum leptin and adiponectin levels measured by blood sample analysis using immunoassay techniques. METHODS Patient demographic characteristics were measured during face-to-face visits. Injury level and Spinal cord Injury Association (ASIA) score were assessed by clinical examination and were confirmed by imaging aids. Measured levels of leptin and adiponectin and dual-energy X-ray absorptiometry results were analyzed with partial correlation analysis method after adjustment for weight, body mass index (BMI), and age. RESULTS Total of 104 patients (19 females and 85 males) entered this investigation. Higher leptin concentration was significantly associated with higher BMD in femoral neck (p=.006, r=0.73), femoral intertrochanteric zone (p=.001, r=0.83), and hip (p=.001, r=0.81) only in female patients, whereas no such association was detected in male participants after adjusting for BMI and age. Leptin and adiponectin levels were not associated with lumbar spine BMD in both genders. Neither injury level nor ASIA score and plegia type (paraplegia or tetraplegia) influenced on leptin and adiponectin concentrations. CONCLUSIONS We found no association between leptin concentration and BMD in male individuals, whereas a positive correlation between leptin and BMD of femoral neck, intertrochanter, and hip was observed in female patients that shows a sexual polymorphism in this relationship. However, by considering the low number of female participants, these results should be interpreted cautiously. Lumbar spine BMD was associated with neither leptin nor adiponectin level in both genders.
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Affiliation(s)
- Hadis Sabour
- Brain and Spinal Injury Research Center (BASIR), Tehran University of Medical Sciences, Keshavarz Blvd, Tehran, Iran
| | - Abbas Norouzi Javidan
- Brain and Spinal Injury Research Center (BASIR), Tehran University of Medical Sciences, Keshavarz Blvd, Tehran, Iran
| | - Sahar Latifi
- Brain and Spinal Injury Research Center (BASIR), Tehran University of Medical Sciences, Keshavarz Blvd, Tehran, Iran
| | - Farzad Shidfar
- Department of Nutrition, Iran University of Medical Sciences, Hemat Highway, Tehran, Iran
| | - Mohammad Reza Vafa
- Department of Nutrition, Iran University of Medical Sciences, Hemat Highway, Tehran, Iran
| | - Seyed-Hassan Emami Razavi
- Brain and Spinal Injury Research Center (BASIR), Tehran University of Medical Sciences, Keshavarz Blvd, Tehran, Iran
| | - Bagher Larijani
- Endocrinology and Metabolism Research Institute (EMRI), Tehran University of Medical Sciences, Shariati Hospital, North Kargar Avenue, Tehran, Iran
| | - Ramin Heshmat
- Endocrinology and Metabolism Research Institute (EMRI), Tehran University of Medical Sciences, Shariati Hospital, North Kargar Avenue, Tehran, Iran; Chronic Diseases Research Center, Endocrinology and Metabolism Population Sciences Institute, Tehran University of Medical Sciences, No. 111, 19th St, North Karegar, Tehran 14579-65597, Iran.
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Lacerda DR, Serakides R, de Melo Ocarino N, Ferreira AVM, Moraes MM, Boeloni JN, Silva JF, de Oliveira MC, de Barcellos LAM, Rodrigues LOC, Soares DD. Osteopetrosis in obese female rats is site-specifically inhibited by physical training. Exp Physiol 2014; 100:44-56. [PMID: 25557730 DOI: 10.1113/expphysiol.2014.082511] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/14/2014] [Accepted: 10/17/2014] [Indexed: 11/08/2022]
Abstract
NEW FINDINGS What is the central question of this study? Clinical studies suggest that obesity 'protects' against osteoporosis. However, these studies used only bone densitometry and assessed only one bone site, which is insufficient to enable conclusions to be drawn about the response of the whole skeleton. Furthermore, the effects of exercise on bone responses in obesity have not been explored previously. What is the main finding and what is its importance? We show that obesity causes osteopetrosis. Therefore, the classical perspective of 'protective effects of obesity' needs to be reviewed, and exercise is an important tool to avoid these alterations and to maintain the homeostasis of bone. A sedentary lifestyle and obesity induce systemic inflammatory responses. Although the effects of physical inactivity on osseous tissue have been well established, the effects of obesity on bone tissue remain controversial. Furthermore, the effects of physical training on bone tissue responses in the presence of diet-induced obesity are unknown. Our aim was to investigate the effects of obesity and physical training at multiple bone sites in rats. Female Wistar rats were divided into the following four groups: (i) control diet, non-trained (C-NT); (ii) high-refined carbohydrate-containing diet, non-trained (HC-NT); (iii) control diet, trained (C-T); and (iv) high-refined carbohydrate-containing diet, trained (HC-T). At 5 months of age, the rats were submitted to daily exercise for 30 min day(-1). After 13 weeks, blood samples, adipose and skeletal tissues were harvested. Two-way ANOVA was applied to detect differences (significance accepted when P ≤ 0.05). The HC-NT group exhibited increased body mass, adiposity, serum leptin, serum insulin, insulin resistance index and concentrations of tumour necrosis factor-α and interleukin-6. Obese rats (HC-NT) exhibited thickening of nasal bones, trabecular bones in the lumbar vertebrae and long bones in a site-dependent manner. The HC-T group exhibited similar adiposity and inflammatory results. Morphological analysis of the lumbar vertebrae in rats fed the HC diet revealed characteristics of osteopetrosis that were inhibited by exercise. In conclusion, the HC diet induced obesity and inflammatory/hormonal alterations and increased the trabecular bone in a site-dependent manner. However, obesity caused osteopetrosis in the lumbar vertebrae, which could be inhibited by physical training. Although exercise inhibited the development of bone alterations, physical training did not inhibit the HC diet-induced obesity responses.
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Tonge DP, Pearson MJ, Jones SW. The hallmarks of osteoarthritis and the potential to develop personalised disease-modifying pharmacological therapeutics. Osteoarthritis Cartilage 2014; 22:609-21. [PMID: 24632293 DOI: 10.1016/j.joca.2014.03.004] [Citation(s) in RCA: 109] [Impact Index Per Article: 9.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/07/2013] [Revised: 02/03/2014] [Accepted: 03/04/2014] [Indexed: 02/07/2023]
Abstract
Osteoarthritis (OA) is an age-related condition and the leading cause of pain, disability and shortening of adult working life in the UK. The incidence of OA increases with age, with 25% of the over 50s population having OA of the knee. Despite promising preclinical data covering various molecule classes, there is regrettably at present no approved disease-modifying OA drugs (DMOADs). With the advent of next generation sequencing technologies, other therapeutic areas, in particular oncology, have experienced a paradigm shift towards defining disease by its molecular composition. This paradigm shift has enabled high resolution patient stratification and supported the emergence of personalised or precision medicines. In this review we evaluate the potential for the development of OA therapeutics to undergo a similar paradigm shift given that OA is increasingly being recognised as a heterogeneous disease affecting multiple joint tissues. We highlight the evidence for the role of these tissues in OA pathology as different "hallmarks" of OA biology and review the opportunities to identify and develop targeted disease-modifying pharmacological therapeutics. Finally, we consider whether it is feasible to expect the emergence of personalised disease-modifying medicines for patients with OA and how this might be achieved.
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Affiliation(s)
- D P Tonge
- Faculty of Computing, Engineering and Sciences, Staffordshire University, Stoke-on-Trent ST4 2DF, UK.
| | - M J Pearson
- MRC-ARUK Centre for Musculoskeletal Ageing Research, School of Immunity and Infection, University of Birmingham, Birmingham B15 2WB, UK
| | - S W Jones
- MRC-ARUK Centre for Musculoskeletal Ageing Research, School of Immunity and Infection, University of Birmingham, Birmingham B15 2WB, UK.
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Abstract
Marrow adipose tissue (MAT) is functionally distinct from both white and brown adipose tissue and can contribute to systemic and skeletal metabolism. MAT formation is a spatially and temporally defined developmental event, suggesting that MAT is an organ that serves important functions and, like other organs, can undergo pathologic change. The well-documented inverse relationship between MAT and bone mineral density has been interpreted to mean that MAT removal is a possible therapeutic target for osteoporosis. However, the bone and metabolic phenotypes of patients with lipodystrophy argues that retention of MAT may actually be beneficial in some circumstances. Furthermore, MAT may exist in two forms, regulated and constitutive, with divergent responses to hematopoietic and nutritional demands. In this review, we discuss the role of MAT in lipodystrophy, bone loss, and metabolism, and highlight our current understanding of this unique adipose tissue depot.
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Affiliation(s)
- Erica L Scheller
- Department of Molecular and Integrative Physiology, University of Michigan, Ann Arbor, Michigan
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Kocyigit H, Bal S, Atay A, Koseoglu M, Gurgan A. Plasma leptin values in postmenopausal women with osteoporosis. Bosn J Basic Med Sci 2014; 13:192-6. [PMID: 23988172 DOI: 10.17305/bjbms.2013.2361] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022] Open
Abstract
Obesity has a protective effect against osteoporosis and this effect has been attributed to a high body fat content. It has been shown that the leptin concentration is higher in obese patients. Leptin, the protein product of obesity gene, is a hormone produced in adipose tissue. Some studies suggest that endogenous leptin might influence bone metabolism in postmenopausal women. In this study, we investigated plasma leptin concentrations in postmenopausal women with osteoporosis and also analyzed the relationship between plasma leptin levels and bone mineral density (BMD) in order to understand the potential role of leptin in maintaining bone mass. Forty-two postmenopausal women with osteoporosis and thirty seven age and BMI-matched healthy postmenopausal women were included in the study. The mean femoral neck BMD value in the patient group was significantly lower than that in the control group (0.691±0.1 g/cm2 and 0.863±0.1 g/cm2, respectively; p<0.001). The mean plasma leptin concentration in the patient group was not significantly different from that in the control group (p>0.05). Plasma leptin levels were correlated with BMI in both groups (p<0.001 in the patient group and p=0.001 in controls). There was also a strong positive correlation between plasma leptin levels and %fat in both groups (p<0.001 in the patient group and p<0.001 in controls). But there was no correlation between plasma leptin levels and femoral neck BMD values in both groups. Our results do not support the hypothesis that leptin itself plays an important role in maintaining bone mass in postmenopausal women.
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Affiliation(s)
- Hikmet Kocyigit
- Department of Physical Medicine and Rehabilitation, Izmir Katip Celebi University, Atatürk Training and Research Hospital, Basın Sitesi 35360, Izmir, Turkey.
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de Albuquerque Maia L, Lisboa PC, de Oliveira E, da Silva Lima N, Lima ICB, Lopes RT, Ruffoni LDG, Nonaka KO, de Moura EG. Bone metabolism in obese rats programmed by early weaning. Metabolism 2014; 63:352-64. [PMID: 24355624 DOI: 10.1016/j.metabol.2013.11.010] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/25/2013] [Revised: 11/11/2013] [Accepted: 11/12/2013] [Indexed: 01/24/2023]
Abstract
OBJECTIVE Obesity and osteoporosis seem to have a common pathogenesis, especially because bone and adipose tissue have common origins. Since early weaning (EW) decreases adipogenesis and osteogenesis in neonate, further programming for obesity and hyperleptinemia, we hypothesized that these changes in adipogenesis could affect bone metabolism. MATERIALS/METHODS Lactating rats were separated into 3 groups: control - dams whose pups ate milk throughout lactation; mechanical EW (MEW) - dams were involved with a bandage interrupting suckling in the last 3days of lactation; pharmacological EW (PEW) - dams were bromocriptine-treated (0.5mg/twice a day via intraperitoneal injection) 3days before weaning. The adult offspring was subjected to dual-energy X-ray absorptiometry and bone tissue was also evaluated by computed tomography, microcomputed tomography and biomechanical tests, beyond serum analyses. RESULTS MEW and PEW presented higher total bone mineral density (BMD), total bone mineral content, spine BMD and bone area in postnatal day 150 (PN150). In PN180, both groups also presented increase of these parameters and higher femur BMD and fourth lumbar vertebra (LV4) BMD, femoral head radiodensity and LV4 vertebral body radiodensity, trabecular number, stiffness and break load; lower trabecular separation, maximal deformation and break deformation, and also hyperleptinemia and higher visceral fat mass and 25-hydroxivitamin D, whereas parathyroid hormone was unchanged. Serum C-terminal cross-linked telopeptide of type I collagen was lower for both groups. CONCLUSIONS Since both models program for obesity and increased bone mass, and leptin increases plasma vitamin D levels, probably leptin is the link between obesity and higher bone mass.
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Affiliation(s)
- Lígia de Albuquerque Maia
- Department of Physiological Sciences, State University of Rio de Janeiro, State University of Rio de Janeiro, Rio de Janeiro, RJ 20550-030, Brazil
| | - Patrícia Cristina Lisboa
- Department of Physiological Sciences, State University of Rio de Janeiro, State University of Rio de Janeiro, Rio de Janeiro, RJ 20550-030, Brazil
| | - Elaine de Oliveira
- Department of Physiological Sciences, State University of Rio de Janeiro, State University of Rio de Janeiro, Rio de Janeiro, RJ 20550-030, Brazil
| | - Natália da Silva Lima
- Department of Physiological Sciences, State University of Rio de Janeiro, State University of Rio de Janeiro, Rio de Janeiro, RJ 20550-030, Brazil
| | - Inaya Correa Barbosa Lima
- Nuclear Instrumentation Laboratory, COPPE-PEN, Federal University of Rio de Janeiro, Rio de Janeiro, RJ 21941-972, Brazil
| | - Ricardo Tadeu Lopes
- Nuclear Instrumentation Laboratory, COPPE-PEN, Federal University of Rio de Janeiro, Rio de Janeiro, RJ 21941-972, Brazil
| | | | - Keico Okino Nonaka
- Laboratory of Exercise Physiology, Federal University of São Carlos, São Carlos, São Paulo, SP 13565-905, Brazil
| | - Egberto Gaspar de Moura
- Department of Physiological Sciences, State University of Rio de Janeiro, State University of Rio de Janeiro, Rio de Janeiro, RJ 20550-030, Brazil.
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Jeon YK, Kim WJ, Shin MJ, Chung HY, Kim SS, Kim BH, Kim SJ, Kim YK, Kim IJ. Short-term caloric restriction does not reduce bone mineral density in rats with early type 2 diabetes. Endocrinol Metab (Seoul) 2014; 29:70-6. [PMID: 24741457 PMCID: PMC3970278 DOI: 10.3803/enm.2014.29.1.70] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/02/2013] [Accepted: 10/11/2013] [Indexed: 01/14/2023] Open
Abstract
BACKGROUND The effect of caloric restriction (CR) in the setting of diabetes on bone metabolism has not yet been fully studied. The aim of this study is to determine if short-term CR alters bone mass and metabolism in Otsuka Long-Evans Tokushima fatty (OLETF) rats, an animal model of type 2 diabetes. METHODS Four groups (n=5) were created: OLETF rats with food ad libitum (AL), OLETF rats with CR, Long-Evans Tokusima Otsuka (LETO) rats with food AL, and LETO rats with CR. The CR condition was imposed on 24-week-old male rats using a 40% calorie reduction for 4 weeks. The effect of CR on femoral bone mineral density (BMD) was assessed by dual-energy X-ray absorptiometry. Serum markers were measured by immunoassay. RESULTS After 4 weeks of CR, body weight decreased in both strains. The BMD decreased in LETO rats and was maintained in OLETF rats. After adjustment for body weight, BMD remained lower in LETO rats (P=0.017) but not OLETF rats (P=0.410). Bone-specific alkaline phosphatase levels decreased in LETO rats (P=0.025) but not in OLEFT rats (P=0.347). Serum leptin levels were reduced after CR in both strains, but hyperleptinemia remained in OLETF rats (P=0.009). CR increased 25-hydroxyvitamin D levels in OLETF rats (P=0.009) but not in LETO rats (P=0.117). Additionally, interleukin-6 and tumor necrosis factor-α levels decreased only in OLETF rats (P=0.009). CONCLUSION Short-term CR and related weight loss were associated with decreases of femoral BMD in LETO rats while BMD was maintained in OLETF rats. Short-term CR may not alter bone mass and metabolism in type 2 diabetic rats.
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Affiliation(s)
- Yun Kyung Jeon
- Department of Internal Medicine, Pusan National University School of Medicine, Busan, Korea
- Medical Research Institute, Pusan National University School of Medicine, Busan, Korea
| | - Won Jin Kim
- Department of Internal Medicine, Pusan National University School of Medicine, Busan, Korea
- Medical Research Institute, Pusan National University School of Medicine, Busan, Korea
| | - Myung Jun Shin
- Medical Research Institute, Pusan National University School of Medicine, Busan, Korea
- Department of Rehabilitation Medicine, Pusan National University School of Medicine, Busan, Korea
| | | | - Sang Soo Kim
- Department of Internal Medicine, Pusan National University School of Medicine, Busan, Korea
- Medical Research Institute, Pusan National University School of Medicine, Busan, Korea
| | - Bo Hyun Kim
- Department of Internal Medicine, Pusan National University School of Medicine, Busan, Korea
- Medical Research Institute, Pusan National University School of Medicine, Busan, Korea
| | - Seong-Jang Kim
- Department of Nuclear Medicine, Pusan National University School of Medicine, Busan, Korea
| | - Yong Ki Kim
- Kim Yong Ki Internal Medicine Clinic, Busan, Korea
| | - In Joo Kim
- Department of Internal Medicine, Pusan National University School of Medicine, Busan, Korea
- Medical Research Institute, Pusan National University School of Medicine, Busan, Korea
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Campos RM, de Mello MT, Tock L, Silva PL, Masquio DC, de Piano A, Sanches PL, Carnier J, Corgosinho FC, Foschini D, Tufik S, Dâmaso AR. Aerobic Plus Resistance Training Improves Bone Metabolism and Inflammation in Adolescents who Are Obese. J Strength Cond Res 2014; 28:758-66. [DOI: 10.1519/jsc.0b013e3182a996df] [Citation(s) in RCA: 42] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/24/2022]
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Napoli N, Strollo R, Paladini A, Briganti SI, Pozzilli P, Epstein S. The alliance of mesenchymal stem cells, bone, and diabetes. Int J Endocrinol 2014; 2014:690783. [PMID: 25140176 PMCID: PMC4124651 DOI: 10.1155/2014/690783] [Citation(s) in RCA: 60] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/30/2013] [Accepted: 06/11/2014] [Indexed: 12/15/2022] Open
Abstract
Bone fragility has emerged as a new complication of diabetes. Several mechanisms in diabetes may influence bone homeostasis by impairing the action between osteoblasts, osteoclasts, and osteocytes and/or changing the structural properties of the bone tissue. Some of these mechanisms can potentially alter the fate of mesenchymal stem cells, the initial precursor of the osteoblast. In this review, we describe the main factors that impair bone health in diabetic patients and their clinical impact.
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Affiliation(s)
- Nicola Napoli
- Division of Endocrinology and Diabetes, Università Campus Bio-Medico di Roma, Via Alvaro del Portillo 21, 00128 Rome, Italy
- Division of Bone and Mineral Diseases, Washington University in St Louis, St Louis, MO, USA
- *Nicola Napoli:
| | - Rocky Strollo
- Division of Endocrinology and Diabetes, Università Campus Bio-Medico di Roma, Via Alvaro del Portillo 21, 00128 Rome, Italy
| | - Angela Paladini
- Division of Endocrinology and Diabetes, Università Campus Bio-Medico di Roma, Via Alvaro del Portillo 21, 00128 Rome, Italy
| | - Silvia I. Briganti
- Division of Endocrinology and Diabetes, Università Campus Bio-Medico di Roma, Via Alvaro del Portillo 21, 00128 Rome, Italy
| | - Paolo Pozzilli
- Division of Endocrinology and Diabetes, Università Campus Bio-Medico di Roma, Via Alvaro del Portillo 21, 00128 Rome, Italy
- Centre for Diabetes, The Blizard Building, Barts and The London School of Medicine, Queen Mary, University of London, London, UK
| | - Sol Epstein
- Division of Endocrinology, Mount Sinai School of Medicine, New York, USA
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Abstract
Anorexia nervosa is a serious psychiatric disorder accompanied by high morbidity and mortality. It is characterized by emaciation due to self-starvation and displays a unique hormonal profile. Alterations in gonadal axis, growth hormone resistance with low insulin-like growth factor I levels, hypercortisolemia and low triiodothyronine levels are almost universally present and constitute an adaptive response to malnutrition. Bone metabolism is likewise affected resulting in low bone mineral density, reduced bone accrual and increased fracture risk. Skeletal deficits often persist even after recovery from the disease with serious implications for future skeletal health. The pathogenetic mechanisms underlying bone disease are quite complicated and treatment is a particularly challenging task.
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Affiliation(s)
- Anastasia D Dede
- Department of Endocrinology and Metabolism, Hippokrateion General Hospital, Athens, Greece
| | | | - Symeon Tournis
- Laboratory for Research of Musculoskeletal System "Theodoros Garofalidis", University of Athens, KAT Hospital; Athens, Greece
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Marwaha RK, Garg MK, Tandon N, Mehan N, Sastry A, Bhadra K. Relationship of body fat and its distribution with bone mineral density in Indian population. J Clin Densitom 2013; 16:353-359. [PMID: 23910719 DOI: 10.1016/j.jocd.2012.08.074] [Citation(s) in RCA: 20] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/20/2012] [Revised: 07/30/2012] [Accepted: 08/02/2012] [Indexed: 11/26/2022]
Abstract
Obesity has been associated with increased bone mineral density (BMD). There is evidence of differential effect of regional fat on BMD. Hence, we undertook this study to evaluate the correlation between total body fat and its distribution with BMD in nonobese (mean body mass index: 25.0 ± 4.7 kg/m²) Indian adult volunteers. A total of 2347 participants (men: 39.4% and women: 60.6%) included in this cross-sectional study were divided according to sex and age. Fasting blood samples were drawn for biochemical parameters. Percent total body, truncal, and leg fat and BMD at lumbar spine, femur, and forearm were measured by dual-energy X-ray absorptiometry. The BMD at all sites (radius, femur, and spine) increased from lowest to highest quartiles of percent body fat. Percent truncal fat was positively correlated with BMD at all sites in both sexes, except for femoral neck in men, where it had negative correlation. Percent leg fat was positively related with BMD at all sites in premenopausal women, and spine and radius BMD in postmenopausal women. However, in men, it had negative correlation with femoral neck BMD. On multiple regression analysis, regional fat had positive association with BMD at all sites after adjusting for age, sex, lean mass index, 25-hydroxyvitamin D, and intact parathyroid hormone levels. Leg-to-total body fat ratio was negatively associated with BMD at all sites in men and pre- and postmenopausal women. Percent total body and regional fat have positive association with BMD at all sites in men and women.
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Affiliation(s)
- Raman Kumar Marwaha
- Department of Endocrinology and Thyroid Research Centre, Institute of Nuclear Medicine & Allied Sciences, Timarpur, New Delhi 110054, India.
| | - Mahendra K Garg
- Department of Endocrinology and Metabolism, Army Hospital (Research & Referral), Delhi Cantonment, New Delhi, India
| | - Nikhil Tandon
- Department of Endocrinology and Metabolism, All India Institute of Medical Sciences, New Delhi, India
| | - Neena Mehan
- Department of Medicine, B. R. Sur Institute of Homeopathy, New Delhi, India
| | - Aparna Sastry
- Department of Endocrinology and Thyroid Research Centre, Institute of Nuclear Medicine & Allied Sciences, Timarpur, New Delhi 110054, India
| | - Kuntal Bhadra
- Department of Endocrinology and Thyroid Research Centre, Institute of Nuclear Medicine & Allied Sciences, Timarpur, New Delhi 110054, India
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Anagnostis P, Vakalopoulou S, Charizopoulou M, Kazantzidou E, Chrysopoulou T, Moka E, Agapidou A, Zournatzi V, Garipidou V. Is there any association between leptin levels and bone mineral density in haemophiliac men? Arch Med Sci 2013; 9:459-65. [PMID: 23847667 PMCID: PMC3701978 DOI: 10.5114/aoms.2013.35341] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/05/2012] [Revised: 07/21/2012] [Accepted: 08/01/2012] [Indexed: 11/25/2022] Open
Abstract
INTRODUCTION Conflicting data exist regarding the role of leptin in bone metabolism. The purpose of the present study was to investigate serum leptin concentrations in male patients with haemophilia A and B, a disease known to be associated with low bone mass. MATERIAL AND METHODS Eighty-one male patients, aged 45.4 ±15 years, were screened. Bone mineral density (BMD) was measured by dual-energy X-ray absorptiometry (DXA) in lumbar spine (LS), femoral neck (FN) and total hip (TH). RESULTS Low bone mass was diagnosed in 20 patients (24.7%). Serum leptin concentrations were strongly associated with body weight (r s = 0.457, p = 0.0001) and body mass index (BMI) (r s = 0.491, p = 0.0001). In unadjusted analysis leptin was inversely associated with BMD in LS (r s = -0.255, p = 0.023), but not in FN and TH (r s = -0.205, p = 0.068 and r s = -0.191, p = 0.090, respectively). However, after adjusting for BMI and body weight, leptin was inversely associated with BMD in FN (F 1,76 = 7.727, p = 0.007, β = -0.371, ΔR (2) = 0.089) and TH (F 1,76 = 4.533, p = 0.036, β = -0.290, ΔR (2) = 0.054), but not in LS (F 1,75 = 2.076, p = 0.154, β = -0.202, ΔR (2) = 0.026). No association was found between age, presence of HBV, HCV or HIV infection or alkaline phosphatase and leptin levels. CONCLUSIONS Our study showed a negative association between circulating leptin levels and bone mass in males, independently of body weight and BMI.
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Affiliation(s)
| | - Sofia Vakalopoulou
- Division of Haematology, 2 Propaedeutic Department of Internal Medicine, Aristotle University, Hippokration Hospital, Thessaloniki, Greece
| | - Maria Charizopoulou
- Department of Psychology, School of Philosophy, Aristotle University of Thessaloniki, Greece
| | | | | | - Eleni Moka
- Division of Haematology, 2 Propaedeutic Department of Internal Medicine, Aristotle University, Hippokration Hospital, Thessaloniki, Greece
| | - Alexandra Agapidou
- Division of Haematology, 2 Propaedeutic Department of Internal Medicine, Aristotle University, Hippokration Hospital, Thessaloniki, Greece
| | - Vassiliki Zournatzi
- 2 Department of Obstetrics and Gynaecology, Aristotle University, Hippokration General Hospital, Thessaloniki, Greece
| | - Vasilia Garipidou
- Division of Haematology, 2 Propaedeutic Department of Internal Medicine, Aristotle University, Hippokration Hospital, Thessaloniki, Greece
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Cohen A, Dempster DW, Recker RR, Lappe JM, Zhou H, Zwahlen A, Müller R, Zhao B, Guo X, Lang T, Saeed I, Liu XS, Guo XE, Cremers S, Rosen CJ, Stein EM, Nickolas TL, McMahon DJ, Young P, Shane E. Abdominal fat is associated with lower bone formation and inferior bone quality in healthy premenopausal women: a transiliac bone biopsy study. J Clin Endocrinol Metab 2013; 98:2562-72. [PMID: 23515452 PMCID: PMC3667251 DOI: 10.1210/jc.2013-1047] [Citation(s) in RCA: 157] [Impact Index Per Article: 13.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Abstract
CONTEXT The conventional view that obesity is beneficial for bone strength has recently been challenged by studies that link obesity, particularly visceral obesity, to low bone mass and fractures. It is controversial whether effects of obesity on bone are mediated by increased bone resorption or decreased bone formation. OBJECTIVE The objective of the study was to evaluate bone microarchitecture and remodeling in healthy premenopausal women of varying weights. DESIGN We measured bone density and trunk fat by dual-energy x-ray absorptiometry in 40 women and by computed tomography in a subset. Bone microarchitecture, stiffness, remodeling, and marrow fat were assessed in labeled transiliac bone biopsies. RESULTS Body mass index (BMI) ranged from 20.1 to 39.2 kg/m(2). Dual-energy x-ray absorptiometry-trunk fat was directly associated with BMI (r = 0.78, P < .001) and visceral fat by computed tomography (r = 0.79, P < .001). Compared with women in the lowest tertile of trunk fat, those in the highest tertile had inferior bone quality: lower trabecular bone volume (20.4 ± 5.8 vs 29.1 ± 6.1%; P = .001) and stiffness (433 ± 264 vs 782 ± 349 MPa; P = .01) and higher cortical porosity (8.8 ± 3.5 vs 6.3 ± 2.4%; P = .049). Bone formation rate (0.004 ± 0.002 vs 0.011 ± 0.008 mm(2)/mm · year; P = .006) was 64% lower in the highest tertile. Trunk fat was inversely associated with trabecular bone volume (r = -0.50; P < .01) and bone formation rate (r = -0.50; P < .001). The relationship between trunk fat and bone volume remained significant after controlling for age and BMI. CONCLUSIONS At the tissue level, premenopausal women with more central adiposity had inferior bone quality and stiffness and markedly lower bone formation. Given the rising levels of obesity, these observations require further investigation.
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Affiliation(s)
- Adi Cohen
- Department of Medicine, Columbia University, College of Physicians and Surgeons, PH8-864 630 West 168th Street, New York, New York 10032, USA.
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Montalcini T, Romeo S, Ferro Y, Migliaccio V, Gazzaruso C, Pujia A. Osteoporosis in chronic inflammatory disease: the role of malnutrition. Endocrine 2013; 43:59-64. [PMID: 23055015 DOI: 10.1007/s12020-012-9813-x] [Citation(s) in RCA: 56] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/12/2012] [Accepted: 10/01/2012] [Indexed: 01/09/2023]
Abstract
Osteoporosis is a metabolic bone disorder affecting million of people worldwide. Increased understanding of bone disease has led to a greater recognition of factors affecting bones, and consequently many secondary causes of osteoporosis were demonstrated. In this study, we aim to explore possible causes of bone loss and fractures in subjects affected by chronic inflammatory disease and to suggest new targets for intervention. In fact several studies, evaluated to perform this study, suggest that the patients with chronic inflammatory disease could be at high risk for fractures due to bone loss as consequence of malnutrition, caused by inflammation and hormonal change. Consequently, some actions could derive from the considerations of these mechanisms: a change in actual approach of chronic patients, that may include the investigation on the possible presence of osteoporosis, as well as further research on this topic to find a better therapy to prevent osteoporosis considering all the mechanisms described.
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Affiliation(s)
- Tiziana Montalcini
- Department of Medical and Surgical Science, University Magna Grecia, Catanzaro, Italy.
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Berry PA, Jones SW, Cicuttini FM, Wluka AE, Maciewicz RA. Temporal relationship between serum adipokines, biomarkers of bone and cartilage turnover, and cartilage volume loss in a population with clinical knee osteoarthritis. ACTA ACUST UNITED AC 2013; 63:700-7. [PMID: 21305502 DOI: 10.1002/art.30182] [Citation(s) in RCA: 102] [Impact Index Per Article: 8.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
OBJECTIVE The association of obesity with both hand and knee osteoarthritis (OA) is suggestive of a link between dysfunctional metabolism and joint integrity. Given the role of adipokines in mediating bone and cartilage homeostasis, we undertook this study to examine the relationship between adipokines and bone and cartilage biomarkers in a population of subjects with OA, and to determine whether adipokine levels predicted 2-year cartilage integrity. METHODS One hundred seventeen subjects underwent magnetic resonance imaging at baseline and at 2-year followup. Cartilage volume was assessed from these images. Serum adipokine levels were measured at baseline. Bone and cartilage biomarker levels were measured at baseline and at 2-year followup. Linear regression was used to examine the relationship between baseline levels of adipokines and adipokine receptors (leptin, soluble leptin receptor [sOB-Rb], resistin, and adiponectin) and changes in levels of bone biomarkers (osteocalcin, N-terminal type I procollagen propeptide [PINP], C-terminal crosslinking telopeptide of type I collagen, N-terminal crosslinking telopeptide of type I collagen, or C-terminal crosslinking telopeptide of type I collagen generated by matrix metalloproteinases), levels of cartilage biomarkers (cartilage oligomeric matrix protein, N-terminal type IIA procollagen propeptide [PIIANP], or C2C), cartilage defects score, and cartilage volume over 2 years. RESULTS Baseline leptin was associated with increased levels of bone formation biomarkers (osteocalcin and PINP) over 2 years, while sOB-Rb was associated with reduced levels of osteocalcin. Baseline sOB-Rb was associated with reduced levels of the cartilage formation biomarker PIIANP, an increased cartilage defects score, and increased cartilage volume loss over 2 years. All results were independent of age, sex, and body mass index. CONCLUSION The findings of this study support the concept that serum adipokines may provide a nonmechanical link between obesity and joint integrity (which may be mediated by bone and cartilage turnover) that subsequently results in changes to the cartilage defects score and cartilage volume loss. This may facilitate our understanding of the mechanisms by which obesity is involved in the pathogenesis of OA.
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Affiliation(s)
- Patricia A Berry
- Monash University Medical School and Alfred Hospital, Prahran, Victoria, Australia
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