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Li S, Zou J, Ran J, Wang L, Nie G, Liu Y, Tian C, Yang X, Liu Y, Wan J, Peng W. Advances in the Study of Denosumab Treatment for Osteoporosis and Sarcopenia in the Chinese Middle-Aged and Elderly Population. Int J Gen Med 2024; 17:6089-6099. [PMID: 39678680 PMCID: PMC11646433 DOI: 10.2147/ijgm.s494759] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/17/2024] [Accepted: 11/22/2024] [Indexed: 12/17/2024] Open
Abstract
Osteosarcopenia (OS) is a geriatric syndrome characterized by the concurrent presence of osteoporosis and sarcopenia, predominantly affecting the elderly population. Osteoporosis (OP) is a systemic skeletal disorder characterized by decreased bone mass, compromised bone microarchitecture, and heightened bone fragility, substantially elevating fracture risk. Sarcopenia (SP) is defined by decreased muscle mass, strength, and/or functional capacity. Both conditions are age-related degenerative diseases with overlapping pathophysiological mechanisms, commonly co-occurring in elderly individuals and substantially increasing fracture risk. Denosumab, a targeted anti-osteoporotic agent, mediates therapeutic effects by inhibiting bone resorption through the RANK-RANKL-OPG (RRO) pathway, consequently enhancing bone mineral density. International studies indicate that Denosumab not only treats osteoporosis but also improves sarcopenia-related metrics, suggesting its potential as a sarcopenia treatment. However, research focusing on the Chinese population remains limited. Additionally, the pathophysiological mechanisms of sarcopenia and the pathways through which Denosumab ameliorates sarcopenia are not yet fully understood, warranting further experimental investigation. In summary, Denosumab's therapeutic efficacy in osteoporosis treatment and its potential impact on sarcopenia are of substantial research interest. However, research and literature on these topics in China remain notably scarce. This article aims to offer a systematic review and critical analysis of these topics.
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Affiliation(s)
- Shaotian Li
- General Practice Department, Union Hospital TongJi Medical College HuaZhong University of Science and Technology, Wuhan, People’s Republic of China
| | - Jingfeng Zou
- General Practice Department, Union Hospital TongJi Medical College HuaZhong University of Science and Technology, Wuhan, People’s Republic of China
| | - Jiajia Ran
- General Practice Department, Union Hospital TongJi Medical College HuaZhong University of Science and Technology, Wuhan, People’s Republic of China
| | - Liping Wang
- General Practice Department, Union Hospital TongJi Medical College HuaZhong University of Science and Technology, Wuhan, People’s Republic of China
| | - Guqiao Nie
- General Practice Department, Union Hospital TongJi Medical College HuaZhong University of Science and Technology, Wuhan, People’s Republic of China
| | - Yiting Liu
- General Practice Department, Union Hospital TongJi Medical College HuaZhong University of Science and Technology, Wuhan, People’s Republic of China
| | - Chunhui Tian
- General Practice Department, Union Hospital TongJi Medical College HuaZhong University of Science and Technology, Wuhan, People’s Republic of China
| | - Xin Yang
- General Practice Department, Union Hospital TongJi Medical College HuaZhong University of Science and Technology, Wuhan, People’s Republic of China
| | - Yun Liu
- General Practice Department, Union Hospital TongJi Medical College HuaZhong University of Science and Technology, Wuhan, People’s Republic of China
| | - Jingjing Wan
- General Practice Department, Union Hospital TongJi Medical College HuaZhong University of Science and Technology, Wuhan, People’s Republic of China
| | - Wen Peng
- General Practice Department, Union Hospital TongJi Medical College HuaZhong University of Science and Technology, Wuhan, People’s Republic of China
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Mostafa SM, Elebrashy I, Haddad HE, Shaker O, Razek NA, Fayed A. Association between bone turnover markers, bone mineral density, and serum osteoglycine in middle-aged men with Type 2 Diabetes mellitus. Diabetol Metab Syndr 2024; 16:155. [PMID: 38982537 PMCID: PMC11232153 DOI: 10.1186/s13098-024-01388-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/24/2024] [Accepted: 06/24/2024] [Indexed: 07/11/2024] Open
Abstract
BACKGROUND Patients with Type 2 diabetes mellitus (T2DM) have decreased bone health. We aimed to investigate serum levels of bone turnover markers (BTMs) (markers of bone formation and bone resorption) and bone mineral density (BMD) at three sites (lumber, neck femur, and total femur) in middle-aged men with type 2 diabetes and to analyze the relationship between them. Also to evaluate serum osteoglycin as a novel marker and its relation to BTMs, BMD, and diabetic status. METHODS We recruited seventy-eight patients with T2DM and thirteen non-diabetic, male volunteers as a control group. BMD was measured using a DEXA scan. BTMs (carboxy-terminal crosslinking telopeptide of type 1 collagen [CTX] and procollagen type 1 N propeptide [P1NP]), osteoglycin, PTH, and vitamin D were estimated. Data was compared among subjects and statistical analysis was performed. RESULTS Most of the patients were having normal BMD with no significant difference between patients and the controls. BTMs and osteoglycin were significantly higher and vitamin D was significantly lower in the diabetic patients. Serum osteoglycin was positively correlated with DEXA Neck Femur (r = 0.233; p-value < 0.05). CONCLUSION Body mass index and Serum osteoglycin have a significant positive effect on BMD. Both markers of bone formation and bone resorption were increased indicating a state of increased bone turnover in T2DM.
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Affiliation(s)
- Salma Mohamed Mostafa
- Endocrinology Unit, Internal Medicine Department, Kasr Alainy School of Medicine, Cairo University, Giza, Egypt
| | - Ibrahim Elebrashy
- Endocrinology Unit, Internal Medicine Department, Kasr Alainy School of Medicine, Cairo University, Giza, Egypt
| | - Hemmat El Haddad
- Endocrinology Unit, Internal Medicine Department, Kasr Alainy School of Medicine, Cairo University, Giza, Egypt
| | - Olfat Shaker
- Medical Biochemistry and Molecular Biology Department, Kasr Alainy School of Medicine, Cairo University, Giza, Egypt
| | - Naglaa Abdel Razek
- Diagnostic and Interventional Radiology Department, Kasr Alainy School of Medicine, Cairo University, Giza, Egypt
| | - Ahmed Fayed
- Nephrology Unit, Internal Medicine Department, Kasr Alainy School of Medicine, Cairo University, Giza, Egypt.
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Wang Z, Zhou YB, Wang L, Wang L, Wang Z, Chen PB. Two-sample Mendelian randomization studies revealed a causal relationship between insulin use and osteoporosis: An observational study. Medicine (Baltimore) 2024; 103:e38535. [PMID: 38941431 PMCID: PMC11466163 DOI: 10.1097/md.0000000000038535] [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: 03/26/2024] [Accepted: 05/20/2024] [Indexed: 06/30/2024] Open
Abstract
OBJECTIVE To investigate causal associations between diabetes, insulin treatment and osteoporosis using LDSC analysis with a 2-way Mendelian randomization study. METHODS LDSC analysis was used to estimate the likelihood-scale heritability of the genome-wide association study used with genetic correlation between the 2 genome-wide association study used. Then a 2-sample Mendelian randomization study was performed using 3 methods including inverse variance weighted, MR Egger, and weighted median. RESULTS The genetic correlation between diabetes, insulin treatment (h2_Z = 3.70, P = 2.16e-4), osteoporosis (h2_Z = 4.93, h2_p = 8.13e-7) and genes was significant. There was a significant genetic correlation (rg = 0.122, P = 0.0211). There was a causal association between diabetes, insulin treatment and osteoporosis [P = 0.003754, OR (95%CI) = 0.998876 (0.998116-0.999636)], while no causal association existed between osteoporosis and insulin use (P = 0.998116-0.999636) causal association existed (P = 0.333244). CONCLUSION There was a strong genetic correlation between diabetes, insulin treatment and osteoporosis, a causal association between diabetes, insulin treatment and osteoporosis, and no causal association between osteoporosis and diabetes, insulin treatment.
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Affiliation(s)
- Zhan Wang
- Department of Orthopaedics, Xinjiang Uygur Autonomous Region Hospital of Traditional Chinese Medicine, Urumqi, Xinjiang, China
| | - Yu-bo Zhou
- Department of Orthopaedics, Xinjiang Uygur Autonomous Region Hospital of Traditional Chinese Medicine, Urumqi, Xinjiang, China
| | - Long Wang
- Department of Orthopaedics, Xinjiang Uygur Autonomous Region Hospital of Traditional Chinese Medicine, Urumqi, Xinjiang, China
| | - Lei Wang
- Department of Orthopaedics, Xinjiang Uygur Autonomous Region Hospital of Traditional Chinese Medicine, Urumqi, Xinjiang, China
| | - Zhenbin Wang
- Department of Orthopaedics, Xinjiang Uygur Autonomous Region Hospital of Traditional Chinese Medicine, Urumqi, Xinjiang, China
| | - Ping-bo Chen
- Department of Orthopaedics, Xinjiang Uygur Autonomous Region Hospital of Traditional Chinese Medicine, Urumqi, Xinjiang, China
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Gao L, Liu Y, Li M, Wang Y, Zhang W. Based on HbA1c Analysis: Bone Mineral Density and Osteoporosis Risk in Postmenopausal Female with T2DM. J Clin Densitom 2024; 27:101442. [PMID: 38039558 DOI: 10.1016/j.jocd.2023.101442] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/17/2023] [Accepted: 11/01/2023] [Indexed: 12/03/2023]
Abstract
INTRODUCTION This study aims to investigate association between glycosylated hemoglobin (HbA1c) with bone mineral density (BMD) and osteoporosis-risk in postmenopausal female with type 2 diabetes mellitus (T2DM). METHODOLOGY HbA1c values, BMD of L3 vertebra and basic clinical data of 152 postmenopausal females with T2DM and 326 postmenopausal females without T2DM were retrospectively analyzed. The propensity score matching was used to match the T2DM and the non-T2DM group at a ratio of 1:1. Restricted cubic spline (RCS) analysis and piecewise linear regression were used to evaluate the relationship between HbA1c and BMD. Univariable and multivariable logistic regression were utilized to evaluate the effect of HbA1c on the risk of osteoporosis in matched diabetes population. RESULTS After matching, the BMD (66.60 (46.58, 93.23) vs. 63.50 (36.70, 83.33), P < 0.05), HbA1c value (7.50 (6.72, 8.80) vs 5.30 (5.14, 5.50), P < 0.05) in the T2DM group were significantly higher than that of non-T2DM group. We found a nonlinear relation between HbA1c value and BMD, which showing a U-shaped curve with the cutoff value around 7.5 % (Poverall < 0.001, Pnonliearity < 0.05). The prevalence of osteoporosis in T2DM group was similar to that in controls (64.9 % vs 73.6 %, P = 0.102). Age-adjusted HbA1c value was not risk factor of osteoporosis in postmenopausal females with T2DM. CONCLUSION In postmenopausal females with T2DM, high BMD and similar risk of osteoporosis were confirmed; HbA1c was a contributing factor to BMD when values exceed 7.5 %. However, HbA1c does not seem to be associated with osteoporosis risk.
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Affiliation(s)
- Lei Gao
- Department of Radiology, Hebei Medical University Third Hospital, No.139 ziqiang road, Qiaoxi District, Shijiazhuang, Hebei 050051, China
| | - Ying Liu
- Department of Radiology, Hebei Medical University Third Hospital, No.139 ziqiang road, Qiaoxi District, Shijiazhuang, Hebei 050051, China
| | - Min Li
- Department of Endocrinology, Hebei Medical University Third Hospital, No.139 ziqiang road, Qiaoxi District, Shijiazhuang, Hebei 050051, China
| | - Yan Wang
- Department of Endocrinology, Hebei Medical University Third Hospital, No.139 ziqiang road, Qiaoxi District, Shijiazhuang, Hebei 050051, China.
| | - Wei Zhang
- Department of Radiology, Hebei Medical University Third Hospital, No.139 ziqiang road, Qiaoxi District, Shijiazhuang, Hebei 050051, China.
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Vachliotis ID, Polyzos SA. Osteoprotegerin/Receptor Activator of Nuclear Factor-Kappa B Ligand/Receptor Activator of Nuclear Factor-Kappa B Axis in Obesity, Type 2 Diabetes Mellitus, and Nonalcoholic Fatty Liver Disease. Curr Obes Rep 2023:10.1007/s13679-023-00505-4. [PMID: 37208545 DOI: 10.1007/s13679-023-00505-4] [Citation(s) in RCA: 11] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 03/29/2023] [Indexed: 05/21/2023]
Abstract
PURPOSE OF REVIEW To summarize evidence on the potential involvement of the osteoprotegerin (OPG)/receptor activator of nuclear factor-kappa B (NF-κΒ) ligand (RANKL)/receptor activator of NF-κΒ (RANK) axis in the pathogenesis of metabolic diseases. RECENT FINDINGS The OPG-RANKL-RANK axis, which has been originally involved in bone remodeling and osteoporosis, is now recognized as a potential contributor in the pathogenesis of obesity and its associated comorbidities, i.e., type 2 diabetes mellitus and nonalcoholic fatty liver disease. Besides bone, OPG and RANKL are also produced in adipose tissue and may be involved in the inflammatory process associated with obesity. Metabolically healthy obesity has been associated with lower circulating OPG concentrations, possibly representing a counteracting mechanism, while elevated serum OPG levels may reflect an increased risk of metabolic dysfunction or cardiovascular disease. OPG and RANKL have been also proposed as potential regulators of glucose metabolism and are potentially involved in the pathogenesis of type 2 diabetes mellitus. In clinical terms, type 2 diabetes mellitus has been consistently associated with increased serum OPG concentrations. With regard to nonalcoholic fatty liver disease, experimental data suggest a potential contribution of OPG and RANKL in hepatic steatosis, inflammation, and fibrosis; however, most clinical studies showed reduction in serum concentrations of OPG and RANKL. The emerging contribution of the OPG-RANKL-RANK axis to the pathogenesis of obesity and its associated comorbidities warrants further investigation by mechanistic studies and may have potential diagnostic and therapeutic implications.
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Affiliation(s)
- Ilias D Vachliotis
- First Department of Pharmacology, Medical School, Aristotle University of Thessaloniki, Thessaloniki, 54124, Greece.
- Second Department of Internal Medicine, 424 General Military Hospital, Thessaloniki, 56429, Greece.
| | - Stergios A Polyzos
- First Department of Pharmacology, Medical School, Aristotle University of Thessaloniki, Thessaloniki, 54124, Greece
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Ledoux C, Boaretti D, Sachan A, Müller R, Collins CJ. Clinical Data for Parametrization of In Silico Bone Models Incorporating Cell-Cytokine Dynamics: A Systematic Review of Literature. Front Bioeng Biotechnol 2022; 10:901720. [PMID: 35910035 PMCID: PMC9335409 DOI: 10.3389/fbioe.2022.901720] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/22/2022] [Accepted: 06/13/2022] [Indexed: 11/13/2022] Open
Abstract
In silico simulations aim to provide fast, inexpensive, and ethical alternatives to years of costly experimentation on animals and humans for studying bone remodeling, its deregulation during osteoporosis and the effect of therapeutics. Within the varied spectrum of in silico modeling techniques, bone cell population dynamics and agent-based multiphysics simulations have recently emerged as useful tools to simulate the effect of specific signaling pathways. In these models, parameters for cell and cytokine behavior are set based on experimental values found in literature; however, their use is currently limited by the lack of clinical in vivo data on cell numbers and their behavior as well as cytokine concentrations, diffusion, decay and reaction rates. Further, the settings used for these parameters vary across research groups, prohibiting effective cross-comparisons. This review summarizes and evaluates the clinical trial literature that can serve as input or validation for in silico models of bone remodeling incorporating cells and cytokine dynamics in post-menopausal women in treatment, and control scenarios. The GRADE system was used to determine the level of confidence in the reported data, and areas lacking in reported measures such as binding site occupancy, reaction rates and cell proliferation, differentiation and apoptosis rates were highlighted as targets for further research. We propose a consensus for the range of values that can be used for the cell and cytokine settings related to the RANKL-RANK-OPG, TGF-β and sclerostin pathways and a Levels of Evidence-based method to estimate parameters missing from clinical trial literature.
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Affiliation(s)
- Charles Ledoux
- Institute for Biomechanics, ETH Zurich, Zurich, Switzerland
| | | | - Akanksha Sachan
- Institute for Biomechanics, ETH Zurich, Zurich, Switzerland
- Department of Chemical Engineering, Indian Institute of Technology Bombay, Mumbai, India
| | - Ralph Müller
- Institute for Biomechanics, ETH Zurich, Zurich, Switzerland
| | - Caitlyn J. Collins
- Institute for Biomechanics, ETH Zurich, Zurich, Switzerland
- Department for Biomedical Engineering and Mechanics, Virginia Tech, Blacksburg, VI,United States
- *Correspondence: Caitlyn J. Collins,
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Romero-Díaz C, Duarte-Montero D, Gutiérrez-Romero SA, Mendivil CO. Diabetes and Bone Fragility. Diabetes Ther 2021; 12:71-86. [PMID: 33185853 PMCID: PMC7843783 DOI: 10.1007/s13300-020-00964-1] [Citation(s) in RCA: 50] [Impact Index Per Article: 12.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/06/2020] [Accepted: 10/29/2020] [Indexed: 02/08/2023] Open
Abstract
Diabetes is a highly prevalent disease with complications that impact most bodily systems. However, the impact of diabetes on bone health is frequently ignored or underestimated. Both type 1 (T1D) and type 2 diabetes (T2D) are associated with a higher risk of fractures, albeit through different mechanisms. T1D is characterized by near total insulinopenia, which affects the anabolic tone of bone and results in reduced bone mineral density (BMD). Meanwhile, patients with T2D have normal or high BMD, but carry an increased risk of fractures due to alterations of bone microarchitecture and a local humoral environment that stimulates osteoclast activity. Chronic hyperglycemia induces non-enzymatic glycation of collagen in both types of diabetes. Epidemiological evidence confirms a largely increased fracture risk in T1D and T2D, but also that it can be substantially reduced by opportune monitoring of fracture risk and appropriate treatment of both diabetes itself and osteopenia or osteoporosis if they are present. In this review, we summarize the mechanistic, epidemiological, and clinical evidence that links diabetes and bone fragility, and describe the impact of available diabetes treatments on bone health.
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Affiliation(s)
| | | | | | - Carlos O Mendivil
- School of Medicine, Universidad de los Andes, Bogotá, Colombia.
- Department of Internal Medicine, Endocrinology Section, Fundación Santa Fe de Bogotá, Bogotá, Colombia.
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Cipriani C, Colangelo L, Santori R, Renella M, Mastrantonio M, Minisola S, Pepe J. The Interplay Between Bone and Glucose Metabolism. Front Endocrinol (Lausanne) 2020; 11:122. [PMID: 32265831 PMCID: PMC7105593 DOI: 10.3389/fendo.2020.00122] [Citation(s) in RCA: 100] [Impact Index Per Article: 20.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/02/2019] [Accepted: 02/24/2020] [Indexed: 12/13/2022] Open
Abstract
The multiple endocrine functions of bone other than those related to mineral metabolism, such as regulation of insulin sensitivity, glucose homeostasis, and energy metabolism, have recently been discovered. In vitro and murine studies investigated the impact of several molecules derived from osteoblasts and osteocytes on glucose metabolism. In addition, the effect of glucose on bone cells suggested a mutual cross-talk between bone and glucose homeostasis. In humans, these mechanisms are the pivotal determinant of the skeletal fragility associated with both type 1 and type 2 diabetes. Metabolic abnormalities associated with diabetes, such as increase in adipose tissue, reduction of lean mass, effects of hyperglycemia per se, production of the advanced glycation end products, diabetes-associated chronic kidney disease, and perturbation of the calcium-PTH-vitamin D metabolism, are the main mechanisms involved. Finally, there have been multiple reports of antidiabetic drugs affecting the skeleton, with differences among basic and clinical research data, as well as of anti-osteoporosis medication influencing glucose metabolism. This review focuses on the aspects linking glucose and bone metabolism by offering insight into the most recent evidence in humans.
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Bonnet N, Bourgoin L, Biver E, Douni E, Ferrari S. RANKL inhibition improves muscle strength and insulin sensitivity and restores bone mass. J Clin Invest 2019; 129:3214-3223. [PMID: 31120440 PMCID: PMC6668701 DOI: 10.1172/jci125915] [Citation(s) in RCA: 183] [Impact Index Per Article: 30.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/31/2018] [Accepted: 05/14/2019] [Indexed: 12/13/2022] Open
Abstract
Receptor activator of Nfkb ligand (RANKL) activates, while osteoprotegerin (OPG) inhibits, osteoclastogenesis. In turn a neutralizing Ab against RANKL, denosumab improves bone strength in osteoporosis. OPG also improves muscle strength in mouse models of Duchenne's muscular dystrophy (mdx) and denervation-induce atrophy, but its role and mechanisms of action on muscle weakness in other conditions remains to be investigated. We investigated the effects of RANKL inhibitors on muscle in osteoporotic women and mice that either overexpress RANKL (HuRANKL-Tg+), or lack Pparb and concomitantly develop sarcopenia (Pparb-/-). In women, denosumab over 3 years improved appendicular lean mass and handgrip strength compared to no treatment, whereas bisphosphonate did not. HuRANKL-Tg+ mice displayed lower limb force and maximal speed, while their leg muscle mass was diminished, with a lower number of type I and II fibers. Both OPG and denosumab increased limb force proportionally to the increase in muscle mass. They markedly improved muscle insulin sensitivity and glucose uptake, and decrease anti-myogenic and inflammatory gene expression in muscle, such as myostatin and protein tyrosine phosphatase receptor-γ. Similarly, in Pparb-/-, OPG increased muscle volume and force, while also normalizing their insulin signaling and higher expression of inflammatory genes in skeletal muscle. In conclusions, RANKL deteriorates, while its inhibitor improves, muscle strength and insulin sensitivity in osteoporotic mice and humans. Hence denosumab could represent a novel therapeutic approach for sarcopenia.
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Affiliation(s)
- Nicolas Bonnet
- Division of Bone Diseases, Department of Internal Medicine Specialties, Geneva University Hospital & Faculty of Medicine, Geneva, Switzerland
| | - Lucie Bourgoin
- Division of Bone Diseases, Department of Internal Medicine Specialties, Geneva University Hospital & Faculty of Medicine, Geneva, Switzerland
| | - Emmanuel Biver
- Division of Bone Diseases, Department of Internal Medicine Specialties, Geneva University Hospital & Faculty of Medicine, Geneva, Switzerland
| | - Eleni Douni
- Biomedical Sciences Research Center “Alexander Fleming,” Athens, Greece
- Department of Biotechnology, Agricultural University of Athens, Athens, Greece
| | - Serge Ferrari
- Division of Bone Diseases, Department of Internal Medicine Specialties, Geneva University Hospital & Faculty of Medicine, Geneva, Switzerland
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Hur S, Cho SH, Song BK, Cho BJ. Effect of Resistance Exercise on Serum Osteoprotegerin Levels and Insulin Resistance in Middle-Aged Women with Metabolic Syndrome. Med Sci Monit 2018; 24:9385-9391. [PMID: 30582576 PMCID: PMC6320661 DOI: 10.12659/msm.911548] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022] Open
Abstract
Background Osteoprotegerin (OPG) is a soluble glycoprotein that belongs to the tumor necrosis factor (TNF) receptor superfamily. OPG is mainly secreted by bone. The relationship between acute resistance training, serum OPG levels and metabolic syndrome, including insulin resistance, remains unclear. The purpose of this study was to determine the effect of resistance exercise on serum OPG levels and insulin resistance in middle-aged women with metabolic syndrome. Material/Methods Twenty-four middle-aged women were divided into those with metabolic syndrome (n=12) and a normal control group without metabolic syndrome or insulin resistance (n=12). Metabolic syndrome was diagnosed according to the National Cholesterol Education Program Adult Treatment Panel III (NCEP-ATP III) criteria. The quantitative insulin-sensitivity check index (QUICKI) and the homeostatic model assessment (HOMA) index for assessing beta-cell function and insulin resistance were used. The intensity of the resistance exercise was 60–70% of the repetition maximum, for 40 minutes with 10–12 repetitions, performed three times per week. Venous blood samples were tested using standard laboratory procedures. Results Before exercise, the metabolic syndrome group showed a significant increase in waist circumference (P=0.030) and serum triglyceride (TG) (P=0.014), and lower high-density lipoprotein-cholesterol (HDL-C) (P=0.010) compared with the control group. After the eight-week resistance exercise program, waist circumference, and the QUICKI decreased and OPG levels were significantly increased in the metabolic syndrome group compared with the normal control group. Conclusions A resistance exercise program was effective in reducing factors associated with metabolic syndrome including insulin resistance and increases serum levels of OPG in middle-aged women.
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Affiliation(s)
- Sun Hur
- Department of Sports Science, College of Art and Culture, Kangwon National University, Kangwon, South Korea
| | - Sung-Hyoun Cho
- Department of Physical Therapy, Nambu University, Gwangju, South Korea
| | - Bo-Kyung Song
- Department of Occupational Therapy, Kangwon National University, Kangwon, South Korea
| | - Byung-Jun Cho
- Department of Emergency Medical Technology, Kangwon National University, Kangwon, South Korea
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Pacifico L, Andreoli GM, D’Avanzo M, De Mitri D, Pierimarchi P. Role of osteoprotegerin/receptor activator of nuclear factor kappa B/receptor activator of nuclear factor kappa B ligand axis in nonalcoholic fatty liver disease. World J Gastroenterol 2018; 24:2073-2082. [PMID: 29785076 PMCID: PMC5960813 DOI: 10.3748/wjg.v24.i19.2073] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/29/2018] [Revised: 05/03/2018] [Accepted: 05/11/2018] [Indexed: 02/06/2023] Open
Abstract
Concomitantly with the increase in the prevalences of overweight/obesity, nonalcoholic fatty liver disease (NAFLD) has worldwide become the main cause of chronic liver disease in both adults and children. Patients with fatty liver display features of metabolic syndrome (MetS), like insulin resistance (IR), glucose intolerance, hypertension and dyslipidemia. Recently, epidemiological studies have linked obesity, MetS, and NAFLD to decreased bone mineral density and osteoporosis, highlighting an intricate interplay among bone, adipose tissue, and liver. Osteoprotegerin (OPG), an important symbol of the receptor activator of nuclear factor-B ligand/receptor activator of nuclear factor kappa B/OPG system activation, typically considered for its role in bone metabolism, may also play critical roles in the initiation and perpetuation of obesity-related comorbidities. Clinical data have indicated that OPG concentrations are associated with hypertension, left ventricular hypertrophy, vascular calcification, endothelial dysfunction, and severity of liver damage in chronic hepatitis C. Nonetheless, the relationship between circulating OPG and IR as a key feature of MetS as well as between OPG and NAFLD remains uncertain. Thus, the aims of the present review are to provide the existent knowledge on these associations and to discuss briefly the underlying mechanisms linking OPG and NAFLD.
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Affiliation(s)
- Lucia Pacifico
- Policlinico Umberto I Hospital, Sapienza University of Rome, Rome 00161, Italy
| | - Gian Marco Andreoli
- Policlinico Umberto I Hospital, Sapienza University of Rome, Rome 00161, Italy
| | - Miriam D’Avanzo
- Policlinico Umberto I Hospital, Sapienza University of Rome, Rome 00161, Italy
| | - Delia De Mitri
- Policlinico Umberto I Hospital, Sapienza University of Rome, Rome 00161, Italy
| | - Pasquale Pierimarchi
- Institute of Translational Pharmacology, National Research Council, Rome 00083, Italy
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