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Liu J, Ji F, Lee H, Kim JH. Association between the appendicular skeletal muscle mass-to-visceral fat area ratio and bone mineral density and osteoporosis: A cross-sectional study. Exp Gerontol 2025; 206:112772. [PMID: 40339765 DOI: 10.1016/j.exger.2025.112772] [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: 01/12/2025] [Revised: 04/28/2025] [Accepted: 05/01/2025] [Indexed: 05/10/2025]
Abstract
OBJECTIVE This cross-sectional study investigated the association between appendicular skeletal muscle mass-to-visceral fat area ratio (SVR), bone mineral density (BMD), and osteoporosis in U.S. adults using NHANES data. METHODS Data from the 2013-2014 and 2017-2018 NHANES cycles were analyzed. Multivariable regression models assessed associations between SVR, BMD, and osteoporosis, adjusting for demographic, lifestyle, metabolic, and comorbidity variables. Generalized Additive Models with smooth curve fitting and likelihood ratio tests evaluated model fit. Subgroup analyses explored effect modifications. RESULTS The study included 2325 individuals with a mean age of 50.66 ± 5.55 years. In fully adjusted models, the highest SVR tertile was associated with a 0.05 g/cm2 higher BMD (β = 0.05, 95 % CI: 0.03-0.08, P = 0.002) and 57 % lower odds of osteoporosis (OR = 0.43, 95 % CI: 0.24-0.78, P = 0.028) than the lowest tertile. As a continuous variable, SVR remained significantly associated with BMD (β = 0.03, 95 % CI: 0.02-0.04, P = 0.002) and osteoporosis (OR = 0.67, 95 % CI: 0.50-0.91, P = 0.033). Stronger associations were found in individuals with diabetes (β = 0.09, 95 % CI: 0.06-0.12, P < 0.01) and BMI ≥ 30 (β = 0.07, 95 % CI: 0.05-0.09, P < 0.01). CONCLUSION Higher SVR was significantly associated with increased BMD and lower odds of osteoporosis, suggesting its potential as a marker for bone health assessment. However, the cross-sectional design limits causal inference. Further longitudinal and mechanistic studies are warranted to confirm these findings and explore clinical applicability.
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Affiliation(s)
- Jiao Liu
- Major in Sport Science, Division of Sport Industry and Science, College of Performing Arts and Sport, Hanyang University, 222 Wangsimni-ro, Seongdong-gu, Seoul 04763, Republic of Korea
| | - Fujue Ji
- Major in Sport Science, Division of Sport Industry and Science, College of Performing Arts and Sport, Hanyang University, 222 Wangsimni-ro, Seongdong-gu, Seoul 04763, Republic of Korea; BK21 FOUR Human-Tech Convergence Program, Hanyang University, 222 Wangsimni-ro, Seongdong-gu, 004763, Republic of Korea
| | - Haesung Lee
- Major in Sport Science, Division of Sport Industry and Science, College of Performing Arts and Sport, Hanyang University, 222 Wangsimni-ro, Seongdong-gu, Seoul 04763, Republic of Korea; BK21 FOUR Human-Tech Convergence Program, Hanyang University, 222 Wangsimni-ro, Seongdong-gu, 004763, Republic of Korea
| | - Jong-Hee Kim
- Major in Sport Science, Division of Sport Industry and Science, College of Performing Arts and Sport, Hanyang University, 222 Wangsimni-ro, Seongdong-gu, Seoul 04763, Republic of Korea; BK21 FOUR Human-Tech Convergence Program, Hanyang University, 222 Wangsimni-ro, Seongdong-gu, 004763, Republic of Korea.
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Zhang Y, Cui Y, Sun C, Guo J, Li M. ED-71 ameliorates OVX-induced osteoporosis by regulating calcium homeostasis and SIRT1-mediated mitochondrial function, alleviating osteoblast senescence and suppressing osteoclastogenesis. Cell Signal 2025; 131:111713. [PMID: 40049265 DOI: 10.1016/j.cellsig.2025.111713] [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: 11/27/2024] [Revised: 02/12/2025] [Accepted: 03/02/2025] [Indexed: 04/15/2025]
Abstract
Osteoporosis arising from estrogen deficiency is characterized by oxidative stress and cellular senescence accompanied by calcium loss and disrupted bone metabolism. The paracrine interaction between osteoblasts and osteoclasts, along with the ratio of receptor activator of nuclear factor-κB ligand (RANKL) to osteoprotegerin (OPG), play a pivotal role in maintaining bone homeostasis. Eldecalcitol (ED-71), a novel active form of vitamin D, can reduce the ratio of RANKL to OPG in osteoblasts. In this study, an ovariectomized (OVX) rat model was established in vivo, and a cell model was constructed in vitro using H₂O₂ to explore the specific mechanism by which ED-71 improved the release of RANKL/OPG in senescent osteoblasts. Mitochondrial dysfunction and calcium imbalance were identified as significant factors. Under oxidative stress conditions, ED-71 alleviated endoplasmic reticulum (ER) stress by decreasing the ratio of phosphorylated protein kinase R-like ER kinase (P-PERK/PERK), and augmented the expression levels of sarcoplasmic reticulum/endoplasmic reticulum calcium ATPase 2 (SCERA2) thereby promoting calcium uptake by the ER, enhancing ER calcium influx, and effectively ameliorating calcium homeostasis between the ER and mitochondria. Consequently, it mitigates mitochondrial calcium overload and associated dysfunction. In contrast, ED-71 increased the expression of silent information regulator 1 (SIRT1) and phosphorylated AMP-activated protein kinase (P-AMPK). This alleviates mitochondrial dysfunction and promotes adenosine triphosphate (ATP). The combined effects of these two factors synergistically contribute to the improvement in osteoblast senescence.
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Affiliation(s)
- Yaoguang Zhang
- Department of Bone Metabolism, School and Hospital of Stomatology, Cheeloo College of Medicine, Shandong University & Shandong Key Laboratory of Oral Tissue Regeneration & Shandong Engineering Research Center of Dental Materials and Oral Tissue Regeneration & Shandong Provincial Clinical Research Center for Oral Diseases, China; Department of Orthodontics, School and Hospital of Stomatology, Cheeloo College of Medicine, Shandong University, China; Center of Osteoporosis and Bone Mineral Research, Shandong University, China
| | - Yajun Cui
- Department of Bone Metabolism, School and Hospital of Stomatology, Cheeloo College of Medicine, Shandong University & Shandong Key Laboratory of Oral Tissue Regeneration & Shandong Engineering Research Center of Dental Materials and Oral Tissue Regeneration & Shandong Provincial Clinical Research Center for Oral Diseases, China; Center of Osteoporosis and Bone Mineral Research, Shandong University, China
| | - Changyun Sun
- Department of Bone Metabolism, School and Hospital of Stomatology, Cheeloo College of Medicine, Shandong University & Shandong Key Laboratory of Oral Tissue Regeneration & Shandong Engineering Research Center of Dental Materials and Oral Tissue Regeneration & Shandong Provincial Clinical Research Center for Oral Diseases, China; Department of Orthodontics, School and Hospital of Stomatology, Cheeloo College of Medicine, Shandong University, China; Center of Osteoporosis and Bone Mineral Research, Shandong University, China.
| | - Jie Guo
- Department of Bone Metabolism, School and Hospital of Stomatology, Cheeloo College of Medicine, Shandong University & Shandong Key Laboratory of Oral Tissue Regeneration & Shandong Engineering Research Center of Dental Materials and Oral Tissue Regeneration & Shandong Provincial Clinical Research Center for Oral Diseases, China; Department of Orthodontics, School and Hospital of Stomatology, Cheeloo College of Medicine, Shandong University, China.
| | - Minqi Li
- Department of Bone Metabolism, School and Hospital of Stomatology, Cheeloo College of Medicine, Shandong University & Shandong Key Laboratory of Oral Tissue Regeneration & Shandong Engineering Research Center of Dental Materials and Oral Tissue Regeneration & Shandong Provincial Clinical Research Center for Oral Diseases, China; Department of Orthodontics, School and Hospital of Stomatology, Cheeloo College of Medicine, Shandong University, China; Center of Osteoporosis and Bone Mineral Research, Shandong University, China; School of Clinical Medicine, Jining Medical University, Jining, China.; Institute of Oral Basic Research, School and Hospital of Stomatology, Cheeloo College of Medicine, Shandong University, China
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Kuang C, Shang J, Ma M, Huang S, Yan B, Zhong Y, Guan B, Gong J, Liu F, Chen L. Risk factors and clinical prediction models for osteoporosis in pre-dialysis chronic kidney disease patients. Ren Fail 2024; 46:2361802. [PMID: 38874080 PMCID: PMC11182074 DOI: 10.1080/0886022x.2024.2361802] [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: 10/06/2023] [Accepted: 05/24/2024] [Indexed: 06/15/2024] Open
Abstract
BACKGROUND Osteoporosis in pre-dialysis chronic kidney disease (CKD) patients has been overlooked, and the risk factors of osteoporosis in these patients have not been adequately studied. OBJECTIVE To identify risk factors for osteoporosis in pre-dialysis CKD patients and develop predictive models to estimate the likelihood of osteoporosis. METHODS Dual-energy X-ray absorptiometry was used to measure bone mineral density, and clinical examination results were collected from 326 pre-dialysis CKD patients. Binary logistic regression was employed to explore the risk factors associated with osteoporosis and develop predictive models. RESULTS In this cohort, 53.4% (n = 174) were male, 46.6% (n = 152) were female, and 21.8% (n = 71) were diagnosed with osteoporosis. Among those diagnosed with osteoporosis, 67.6% (n = 48) were female and 32.4% (n = 23) were male. Older age and low 25-(OH)-Vitamin D levels were identified as risk factors for osteoporosis in males. For females, older age, being underweight, higher bone alkaline phosphatase (NBAP), and advanced CKD (G5) were significant risk factors, while higher iPTH was protective. Older age, being underweight, and higher NBAP were risk factors for osteoporosis in the G1-4 subgroup. In the G5 subgroup, older age and higher NBAP increased the risk, while high 25-(OH)-Vitamin D or iPTH had protective effects. Nomogram models were developed to assess osteoporosis risk in pre-dialysis patients based on gender and renal function stage. CONCLUSION Risk factors for osteoporosis vary by gender and renal function stages. The nomogram clinical prediction models we constructed may aid in the rapid screening of patients at high risk of osteoporosis.
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Affiliation(s)
- Chaoying Kuang
- Nephrology Department, The First Affiliated Hospital of Jinan University, Jinan University, Guangzhou, Guangdong, China
| | - Jingjie Shang
- Nuclear Medicine, The First Affiliated Hospital of Jinan University, Jinan University, Guangzhou, Guangdong, China
| | - Mingming Ma
- Nephrology Department, The First Affiliated Hospital of Jinan University, Jinan University, Guangzhou, Guangdong, China
| | - Shengling Huang
- Nephrology Department, The First Affiliated Hospital of Jinan University, Jinan University, Guangzhou, Guangdong, China
| | - Bing Yan
- Nephrology Department, The First Affiliated Hospital of Jinan University, Jinan University, Guangzhou, Guangdong, China
| | - Yuzhen Zhong
- Nephrology Department, The First Affiliated Hospital of Jinan University, Jinan University, Guangzhou, Guangdong, China
| | - Baozhang Guan
- Nephrology Department, The First Affiliated Hospital of Jinan University, Jinan University, Guangzhou, Guangdong, China
| | - Jian Gong
- Nuclear Medicine, The First Affiliated Hospital of Jinan University, Jinan University, Guangzhou, Guangdong, China
| | - Fanna Liu
- Nephrology Department, The First Affiliated Hospital of Jinan University, Jinan University, Guangzhou, Guangdong, China
| | - Liangmei Chen
- Nephrology Department, The First Affiliated Hospital of Jinan University, Jinan University, Guangzhou, Guangdong, China
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Essibayi MA, Mortezaei A, Azzam AY, Bangash AH, Eraghi MM, Fluss R, Brook A, Altschul DJ, Yassari R, Chandra RV, Cancelliere NM, Pereira VM, Jennings JW, Gilligan CJ, Bono CM, Hirsch JA, Dmytriw AA. Risk of adjacent level fracture after percutaneous vertebroplasty and kyphoplasty vs natural history for the management of osteoporotic vertebral compression fractures: a network meta-analysis of randomized controlled trials. Eur Radiol 2024; 34:7185-7196. [PMID: 38811388 DOI: 10.1007/s00330-024-10807-3] [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: 03/08/2024] [Revised: 03/08/2024] [Accepted: 04/06/2024] [Indexed: 05/31/2024]
Abstract
OBJECTIVES Percutaneous vertebroplasty and kyphoplasty are common interventions for osteoporotic vertebral compression fractures. However, there is concern about an increased risk of adjacent-level fractures after treatment. This study aimed to compare the risk of adjacent-level fractures after vertebroplasty and kyphoplasty with the natural history after osteoporotic vertebral compression fractures. MATERIALS AND METHODS A network meta-analysis of randomized controlled trials (RCTs) was conducted to evaluate the risk of adjacent-level fractures after vertebroplasty and kyphoplasty compared to the natural history after osteoporotic vertebral compression fractures. Frequentist network meta-analysis was conducted using the "netmeta" package, and heterogeneity was assessed using Q statistics. The pooled risk ratio (RR) and 95% confidence intervals (CI) were calculated using random effects. RESULTS Twenty-three RCTs with a total of 2838 patients were included in the analysis. The network meta-analysis showed comparable risks of adjacent-level fractures between vertebroplasty, kyphoplasty, and natural history after osteoporotic vertebral compression fractures with a mean follow-up of 21.2 (range: 3-49.4 months). The pooled RR for adjacent-level fractures after kyphoplasty compared to natural history was 1.35 (95% CI, 0.78-2.34, p = 0.23) and for vertebroplasty compared to natural history was 1.16 (95% CI, 0.62-2.14) p = 0.51. The risk of bias assessment showed a low to moderate risk of bias among included RCTs. CONCLUSION There was no difference in the risk of adjacent-level fractures after vertebroplasty and kyphoplasty compared to natural history after osteoporotic vertebral compression fractures. The inclusion of a large patient number and network meta-analysis of RCTs serve evidence-based clinical practice. CLINICAL RELEVANCE STATEMENT The risk of adjacent-level fracture following percutaneous vertebroplasty or kyphoplasty is similar to that observed in the natural history after osteoporotic vertebral compression fractures. KEY POINTS RCTs have examined the risk of adjacent-level fracture after intervention for osteoporotic vertebral compression fractures. There was no difference between vertebroplasty and kyphoplasty patients compared to the natural disease history for adjacent compression fractures. This is strong evidence that interventional treatments for these fractures do not increase the risk of adjacent fractures.
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Affiliation(s)
- Muhammed Amir Essibayi
- Department of Neurological Surgery, Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, NY, USA
- Department of Radiology, Mayo Clinic, Rochester, NY, USA
- Montefiore-Einstein Cerebrovascular Research Lab, Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, NY, USA
| | - Ali Mortezaei
- Montefiore-Einstein Cerebrovascular Research Lab, Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, NY, USA
| | - Ahmed Y Azzam
- Montefiore-Einstein Cerebrovascular Research Lab, Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, NY, USA
| | - Ali Haider Bangash
- Montefiore-Einstein Cerebrovascular Research Lab, Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, NY, USA
| | - Mohammad Mirahmadi Eraghi
- Montefiore-Einstein Cerebrovascular Research Lab, Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, NY, USA
| | - Rose Fluss
- Department of Neurological Surgery, Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, NY, USA
| | - Allan Brook
- Department of Neuroradiology, Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, NY, USA
| | - David J Altschul
- Department of Neurological Surgery, Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, NY, USA
- Montefiore-Einstein Cerebrovascular Research Lab, Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, NY, USA
| | - Reza Yassari
- Department of Neurological Surgery, Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, NY, USA
- Montefiore Spine Research Group, Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, NY, USA
| | - Ronil V Chandra
- Department of Interventional Neuroradiology, Monash Health, Clayton, VIC, Australia
- Department of Image, Monash University Faculty of Medicine Nursing and Health Sciences, Clayton, VIC, Australia
| | - Nicole M Cancelliere
- Neurovascular Centre, Divisions of Therapeutic Neuroradiology & Neurosurgery, St. Michael's Hospital, University of Toronto, Toronto, ON, Canada
| | - Vitor Mendes Pereira
- Neurovascular Centre, Divisions of Therapeutic Neuroradiology & Neurosurgery, St. Michael's Hospital, University of Toronto, Toronto, ON, Canada
| | - Jack W Jennings
- Musculoskeletal Radiology, Mallinckrodt Institute of Radiology, Washington University St. Louis School of Medicine, St. Louis, MO, USA
| | | | - Christopher M Bono
- Department of Orthopedics, Massachusetts General Hospital & Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA
| | - Joshua A Hirsch
- Neuroendovascular Program, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA
- Senior affiliate research fellow, The Harvey L. Neiman Health Policy Institute, Reston, Virginia, USA
| | - Adam A Dmytriw
- Neurovascular Centre, Divisions of Therapeutic Neuroradiology & Neurosurgery, St. Michael's Hospital, University of Toronto, Toronto, ON, Canada.
- Neuroendovascular Program, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
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Hong G, Tang L, Zhou T, Xie Y, Wang J, Ge D, Dong Q, Sun P. Fufang Zhenshu Tiaozhi capsule enhances bone formation and safeguards against glucocorticoid-induced osteoporosis through innovative Mekk2-mediated β-catenin deubiquitination. J Bone Miner Metab 2024; 42:516-528. [PMID: 38755327 DOI: 10.1007/s00774-024-01516-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/15/2024] [Accepted: 04/29/2024] [Indexed: 05/18/2024]
Abstract
INTRODUCTION Bone homeostasis depends on the regulation of β-catenin in osteoblasts. Glucocorticoids (GCs) are known to diminish β-catenin activity via Wnt pathway signaling, leading to osteoporosis. Conversely, activating β-catenin in osteoblasts through mitogen-activated protein kinase kinase kinase 2 (Mekk2) offers an innovative approach to combat GC-induced osteoporosis (GIOP). Fufang Zhenshu Tiaozhi (FTZ) capsules have shown effectiveness in treating GIOP, but the mechanisms behind this are still unclear. MATERIALS AND METHODS In this study, Mekk2 knockout mice (Mekk2-/-) was generated by CRISPR/Cas9. These mice were then subjected to Alcian Blue-Alizarin Red staining and immunofluorescence to assess their bone and cartilage development. To establish models of GIOP, both Mekk2-/- and wild-type (WT) mice were treated with dexamethasone (DXMS) and subsequently given FTZ capsules. We analyzed the resulting phenotypic changes in these mice using Micro-CT scans and histomorphological studies. Primary osteoblasts, isolated from both Mekk2-/- and WT mice, underwent qRT-PCR to measure key osteogenesis markers, including Runx2, Sp7, Bgalp, Col1a1 and Alp. Cells were then exposed to treatments with either FTZ or Wnt3a and the phosphorylation levels of β-catenin and Mekk2, along with the protein expression of Runx2, were evaluated using Western blotting and immunoprecipitation. Additionally, C3H10T1/2 cells transfected with TOPflash-luciferase and Renilla luciferase reporters were treated with FTZ and Wnt3a to measure β-catenin activity. RESULTS In our study, administering FTZ in vivo effectively prevented bone loss typically induced by GCs. However, it's important to note that this protective effect was substantially reduced in mice lacking Mekk2. Additionally, FTZ showed a significant ability to enhance osteogenic differentiation in primary osteoblasts, doing so by altering the expression of Mekk2. Intriguingly, the impact of FTZ on Mekk2 appears to function through a pathway separate from the traditional Wnt signaling route. Furthermore, our findings indicate that FTZ also promotes the deubiquitination of β-catenin, contributing further to its positive effects on bone health. CONCLUSIONS This study suggests that FTZ plays a significant role in protecting bone mass in cases of GIOP. The mechanism through which FTZ confers this benefit involves the activation of Mekk2/β-catenin signaling pathways, which represents a promising alternative strategy to counteract the deleterious effects of GIOP by augmenting osteoblastogenesis.
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Affiliation(s)
- Guoju Hong
- Department of Orthopaedic Surgery, The Third Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, 510000, People's Republic of China
- The Third Medical Collage, Guangzhou University of Chinese Medicine, Guangzhou, 510000, People's Republic of China
| | - Lin Tang
- Department of Endocrinology, The First Affiliated Hospital of Guangdong Pharmaceutical University, Guangzhou, 510378, People's Republic of China
| | - Tianyu Zhou
- Department of Endocrinology, The First Affiliated Hospital of Guangdong Pharmaceutical University, Guangzhou, 510378, People's Republic of China
| | - Youhong Xie
- Department of Endocrinology, The First Affiliated Hospital of Guangdong Pharmaceutical University, Guangzhou, 510378, People's Republic of China
| | - Jiangyan Wang
- Department of Endocrinology, The First Affiliated Hospital of Guangdong Pharmaceutical University, Guangzhou, 510378, People's Republic of China
| | - Dongdong Ge
- Department of Orthopedic, The First Affiliated Hospital of Guangdong Pharmaceutical University, Guangzhou, 510378, People's Republic of China
| | - Qunwei Dong
- Department of Orthopedic, The First Affiliated Hospital of Guangdong Pharmaceutical University, Guangzhou, 510378, People's Republic of China.
- Department of Orthopedic, Yunfu Hospital of Traditional Chinese Medicine, Yunfu, 527300, People's Republic of China.
| | - Ping Sun
- Department of Endocrinology, The First Affiliated Hospital of Guangdong Pharmaceutical University, Guangzhou, 510378, People's Republic of China.
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Kang J, Zhao S, Wu X, Wang C, Jiang Z, Wang S. The association of lipid metabolism with bone metabolism and the role of human traits: a Mendelian randomization study. Front Endocrinol (Lausanne) 2023; 14:1271942. [PMID: 38125793 PMCID: PMC10731031 DOI: 10.3389/fendo.2023.1271942] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/03/2023] [Accepted: 11/15/2023] [Indexed: 12/23/2023] Open
Abstract
Background The impact of lipid metabolism on bone metabolism remains controversial, and the extent to which human traits mediate the effects of lipid metabolism on bone metabolism remains unclear. Objective This study utilized mendelian randomization to investigate the effects of blood lipids on bone mineral density (BMD) at various skeletal sites and examined the mediating role of human traits in this process. Methods We leveraged genetic data from large-scale genome-wide association studies on blood lipids (n=1,320,016), forearm bone mineral density (FA-BMD) (n=10,805), lumbar spine bone mineral density (LS-BMD) (n=44,731), and femoral neck bone mineral density (FN-BMD) (n=49,988) to infer causal relationships between lipid and bone metabolism. The coefficient product method was employed to calculate the indirect effects of human traits and the proportion of mediating effects. Results The results showed that a 1 standard deviation(SD) increase in HDL-C, LDL-C and TC was associated with a decrease in LS-BMD of 0.039 g/cm2, 0.045 g/cm2 and 0.054 g/cm2, respectively. The proportion of mediating effects of systolic blood pressure (SBP) on HDL-C to LS-BMD was 3.17%, but suppression effects occurred in the causal relationship of LDL-C and TC to LS-BMD. Additionally, the proportion of mediating effects of hand grip strength (HGS) on the TC to LS-BMD pathway were 6.90% and 4.60% for the left and right hands, respectively. Conclusion In conclusion, a negative causal relationship was established between lipid metabolism and bone metabolism. Our results indicated that SBP and HGS served as mediators for the effects of lipid metabolism on bone metabolism.
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Affiliation(s)
- Jian Kang
- Graduate School, Liaoning University of Traditional Chinese Medicine, Shenyang, China
| | - Shuangli Zhao
- Orthopedics and Traumatology, The Second Hospital of Liaoning University of Chinese Medicine, Shenyang, China
| | - Xize Wu
- Department of Critical Care Medicine, Nantong Hospital of Traditional Chinese Medicine, Nantong, China
| | - Can Wang
- Clinical College, Jinzhou Medical University, Jinzhou, China
| | - Zongkun Jiang
- Orthopedics and Traumatology, The Second Hospital of Liaoning University of Chinese Medicine, Shenyang, China
| | - Shixuan Wang
- Orthopedics and Traumatology, The Second Hospital of Liaoning University of Chinese Medicine, Shenyang, China
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Jha SS, Srivastava A, Kambhampati SBS, Elhence A. Introduction to Osteoporosis, Osteomalacia, and Fragility Fractures. Indian J Orthop 2023; 57:25-32. [PMID: 38107821 PMCID: PMC10721584 DOI: 10.1007/s43465-023-01015-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/11/2023] [Accepted: 09/28/2023] [Indexed: 12/19/2023]
Abstract
Background Osteoporosis is a disease of the bones leading to decreased bone mineral density, leading to fragility fractures. This article is an overview of osteoporosis, osteomalacia and fragility fractures and serves as an introductory article for this special issue on osteoporosis. Methods This is a short, comprehensive account of the given conditions with concepts and a review from the recent literature. The authors provide relevant references from the literature in the bibliography. The sections herein have also been deliberated in the meetings of experts of osteoporosis. Results An overview of osteoporosis, osteomalacia and fragility fractures is provided, including definitions and summaries of aetiology, pathophysiology, diagnosis, prevention, and management. A detailed account of some of these topics will be provided in subsequent chapters. Conclusion Osteoporosis is a silent disease with the potential to cause significant morbidity and mortality if not detected early. It is important to differentiate from and diagnose associated osteomalacia to provide accurate therapy. It is also important to identify the type of fragility fractures and initiate treatment for bone strengthening to prevent subsequent fractures.
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Nguyen DK, Vanden-Bossche A, Laroche N, Thomas M, Linossier MT, Peyroche S, Farlay D, Follet H, Laquerrière P, Lafage-Proust MH, Thomas T, Vico L, Marotte H, Rousseau M. Dietary supplementation with nacre reduces cortical bone loss in aged female mice. Exp Gerontol 2023; 184:112337. [PMID: 38006949 DOI: 10.1016/j.exger.2023.112337] [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: 05/04/2023] [Revised: 08/17/2023] [Accepted: 11/22/2023] [Indexed: 11/27/2023]
Abstract
Aging is associated with detrimental bone loss leading to fragility fractures in both men and women. Notably, a majority of bone loss with aging is cortical, as well as a large number of fractures are non-vertebral and at the non-hip sites. Nacre is a product of mollusks composed of calcium carbonate embedded in organic components. As our previous study demonstrated the protective effect of nacre supplementation on trabecular bone loss in ovariectomized rats, we sought to evaluate the effect of dietary nacre on bone loss related to aging in female mice which do not suffer true menopause as observed in women. The current study compared the effect of a 90-day long nacre-supplemented diet to that of Standard or CaCO3 diets on both bone mass and strength in 16-month-old C57BL/6 female mice. Multiple approaches were performed to assess the microarchitecture and mechanical properties of long bones, analyze trabecular histomorphometry, and measure bone cell-related gene expressions, and bone turnover markers. In the cortex, dietary nacre improved cortical bone strength in line with lower expression levels of genes reflecting osteoclasts activity compared to Standard or CaCO3 diets (p < 0.05). In the trabeculae, nacre-fed mice were characterized by a bone remodeling process more active than the other groups as shown by greater histomorphometric parameters and osteoblast-related gene expressions (p < 0.05). But these differences were not exhibited at the level of the trabecular microarchitecture at this age. Collectively, these data suggest that dietary nacre should be a potential candidate for reducing aging-associated cortical bone loss in the elderly.
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Affiliation(s)
- Dung Kim Nguyen
- Université Jean Monnet Saint-Étienne, INSERM, Mines Saint Etienne, SAINBIOSE U1059, F-42023 Saint-Étienne, France.
| | - Arnaud Vanden-Bossche
- Université Jean Monnet Saint-Étienne, INSERM, Mines Saint Etienne, SAINBIOSE U1059, F-42023 Saint-Étienne, France
| | - Norbert Laroche
- Université Jean Monnet Saint-Étienne, INSERM, Mines Saint Etienne, SAINBIOSE U1059, F-42023 Saint-Étienne, France
| | - Mireille Thomas
- Université Jean Monnet Saint-Étienne, INSERM, Mines Saint Etienne, SAINBIOSE U1059, F-42023 Saint-Étienne, France
| | - Marie-Thérèse Linossier
- Université Jean Monnet Saint-Étienne, INSERM, Mines Saint Etienne, SAINBIOSE U1059, F-42023 Saint-Étienne, France
| | - Sylvie Peyroche
- Université Jean Monnet Saint-Étienne, INSERM, Mines Saint Etienne, SAINBIOSE U1059, F-42023 Saint-Étienne, France
| | - Delphine Farlay
- INSERM, LYOS UMR 1033, Université Claude Bernard Lyon 1, 69008 Lyon, France
| | - Hélène Follet
- INSERM, LYOS UMR 1033, Université Claude Bernard Lyon 1, 69008 Lyon, France
| | - Patrice Laquerrière
- Université de Strasbourg, Strasbourg, France; CNRS, Institut Pluridisciplinaire Hubert Curien UMR 7178, Strasbourg, France
| | - Marie-Hélène Lafage-Proust
- Université Jean Monnet Saint-Étienne, INSERM, Mines Saint Etienne, SAINBIOSE U1059, F-42023 Saint-Étienne, France; Université Jean Monnet Saint-Étienne, Department of Rheumatology, CHU Saint-Etienne, INSERM, Mines Saint Etienne, SAINBIOSE U1059, F-42023, F-42055 Saint-Étienne, France
| | - Thierry Thomas
- Université Jean Monnet Saint-Étienne, INSERM, Mines Saint Etienne, SAINBIOSE U1059, F-42023 Saint-Étienne, France; Université Jean Monnet Saint-Étienne, Department of Rheumatology, CHU Saint-Etienne, INSERM, Mines Saint Etienne, SAINBIOSE U1059, F-42023, F-42055 Saint-Étienne, France
| | - Laurence Vico
- Université Jean Monnet Saint-Étienne, INSERM, Mines Saint Etienne, SAINBIOSE U1059, F-42023 Saint-Étienne, France
| | - Hubert Marotte
- Université Jean Monnet Saint-Étienne, INSERM, Mines Saint Etienne, SAINBIOSE U1059, F-42023 Saint-Étienne, France; Université Jean Monnet Saint-Étienne, Department of Rheumatology, CHU Saint-Etienne, INSERM, Mines Saint Etienne, SAINBIOSE U1059, F-42023, F-42055 Saint-Étienne, France
| | - Marthe Rousseau
- Université Jean Monnet Saint-Étienne, INSERM, Mines Saint Etienne, SAINBIOSE U1059, F-42023 Saint-Étienne, France; UMR5510 MATEIS, CNRS, Lyon University, INSA-Lyon, Lyon, France
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9
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Aude M, Jean-Jacques B, Laura I, Felicia B, Alexia C, Serge R, Mureille S, Pierre B, Florence B. Fracture distribution in postmenopausal women: a FRISBEE sub-study. Arch Osteoporos 2022; 18:3. [PMID: 36469184 DOI: 10.1007/s11657-022-01191-w] [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: 05/20/2022] [Accepted: 11/14/2022] [Indexed: 12/12/2022]
Abstract
We registered 1336 incident-validated fractures in a prospective cohort of 3560 postmenopausal (60-85 years) Belgian women (mean follow-up of 9.1 years). The increase of fracture incidence with age varied widely depending on the fracture site and was significantly steeper for central than for peripheral fractures (e.g., not significant for the ankle). INTRODUCTION The epidemiology of fracture sites other than MOFs has been less studied. We examined the incidence of fractures according to their sites in a prospective cohort of postmenopausal Belgian women. METHODS Three thousand five hundred sixty postmenopausal women, aged 60-85 years old, were recruited from 2007 to 2013 and surveyed yearly (FRISBEE). The number of validated incident fractures was recorded and analyzed in relation to age and the fracture site. RESULTS One thousand three hundred thirty-six fractures were recorded after a mean follow-up of 9.1 years. Seven hundred fifty-six fractures (57%) were MOFs and 580 (43%) non-MOFs, while 813 (61%) were central and 523 (39%) peripheral. The increase of fracture incidence with age differed between fracture sites and was steeper for central than for peripheral fractures. The ratio of MOFs to non-MOFs increased significantly with age, from 1.10 (95% CI: 0.83-1.45) for the 60-69 to 1.69 [1.42-2.01] for the 80-89-year subgroup (P = 0.017). This was also true for central versus peripheral fracture. We differentiated three groups of fracture incidence evolution with age: fractures with a mean increase/decade (compared to the 60-69 age group) of less than 1.5, 1.5-2.0, and 2.0-3.0. The lowest increase was seen for most peripheral fractures, whereas the greatest increase included hip, scapula, pelvis, ribs, and spine fractures. CONCLUSION The increase of fracture incidence with age varied widely depending on the fracture site, and the ratio of MOFs to non-MOFs rose significantly with age. Some peripheral fractures, such as the ankle, did not increase significantly with age, suggesting that bone fragility does not play a major role in their occurrence.
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Affiliation(s)
- Mugisha Aude
- Department of Geriatrics, CHU Brugmann, Université Libre de Bruxelles, Place van Gehuchten 4, 1020, Laeken, Brussels, Belgium.
| | - Body Jean-Jacques
- Department of Endocrinology, CHU Brugmann, Université Libre de Bruxelles, Brussels, Belgium
- Department of Internal Medicine, CHU Brugmann, Université Libre de Bruxelles, Brussels, Belgium
- Laboratory of Translational Medicine, CHU Brugmann, Université Libre de Bruxelles, Brussels, Belgium
| | - Iconaru Laura
- Department of Endocrinology, CHU Brugmann, Université Libre de Bruxelles, Brussels, Belgium
| | - Baleanu Felicia
- Department of Endocrinology, CHU Brugmann, Université Libre de Bruxelles, Brussels, Belgium
| | - Charles Alexia
- Department of Internal Medicine, CHU Brugmann, Université Libre de Bruxelles, Brussels, Belgium
| | - Rozenberg Serge
- Department of Gynecology-Obstetrics, CHU Saint-Pierre, Université Libre de Bruxelles, Brussels, Belgium
| | - Surquin Mureille
- Department of Geriatrics, CHU Brugmann, Université Libre de Bruxelles, Place van Gehuchten 4, 1020, Laeken, Brussels, Belgium
- Department of Internal Medicine, CHU Brugmann, Université Libre de Bruxelles, Brussels, Belgium
| | - Bergmann Pierre
- Laboratory of Translational Medicine, CHU Brugmann, Université Libre de Bruxelles, Brussels, Belgium
- Department of Nuclear Medicine, CHU Brugmann, Université Libre de Bruxelles, Brussels, Belgium
| | - Benoit Florence
- Department of Geriatrics, CHU Brugmann, Université Libre de Bruxelles, Place van Gehuchten 4, 1020, Laeken, Brussels, Belgium
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10
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Coco Martín MB, Leal Vega L, Blázquez Cabrera JA, Navarro A, Moro MJ, Arranz García F, Amérigo MJ, Sosa Henríquez M, Vázquez MÁ, Montoya MJ, Díaz Curiel M, Olmos JM, Pérez Castrillón JL, Filgueira Rubio J, Sánchez Molini P, Aguado Caballero JM, Armengol Sucarrats D, Calero Bernal ML, de Escalante Yanguas B, Hernández de Sosa N, Hernández JL, Jareño Chaumel J, Miranda García MJ, Giner García M, Miranda Díaz C, Cotos Canca R, Cobeta García JC, Rodero Hernández FJ, Tirado Miranda R. Comorbidity and osteoporotic fracture: approach through predictive modeling techniques using the OSTEOMED registry. Aging Clin Exp Res 2022; 34:1997-2004. [PMID: 35435583 PMCID: PMC9464169 DOI: 10.1007/s40520-022-02129-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/18/2022] [Accepted: 03/24/2022] [Indexed: 11/30/2022]
Abstract
Purpose To examine the response to anti-osteoporotic treatment, considered as incident fragility fractures after a minimum follow-up of 1 year, according to sex, age, and number of comorbidities of the patients. Methods For this retrospective observational study, data from baseline and follow-up visits on the number of comorbidities, prescribed anti-osteoporotic treatment and vertebral, humerus or hip fractures in 993 patients from the OSTEOMED registry were analyzed using logistic regression and an artificial network model. Results Logistic regression showed that the probability of reducing fractures for each anti-osteoporotic treatment considered was independent of sex, age, and the number of comorbidities, increasing significantly only in males taking vitamin D (OR = 7.918), patients without comorbidities taking vitamin D (OR = 4.197) and patients with ≥ 3 comorbidities taking calcium (OR = 9.412). Logistic regression correctly classified 96% of patients (Hosmer–Lemeshow = 0.492) compared with the artificial neural network model, which correctly classified 95% of patients (AUC = 0.6). Conclusion In general, sex, age and the number of comorbidities did not influence the likelihood that a given anti-osteoporotic treatment improved the risk of incident fragility fractures after 1 year, but this appeared to increase when patients had been treated with risedronate, strontium or teriparatide. The two models used classified patients similarly, but predicted differently in terms of the probability of improvement, with logistic regression being the better fit.
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11
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Clausen A, Möller S, Skjødt MK, Bech BH, Rubin KH. Evaluating the performance of the Charlson Comorbidity Index (CCI) in fracture risk prediction and developing a new Charlson Fracture Index (CFI): a register-based cohort study. Osteoporos Int 2022; 33:549-561. [PMID: 34993562 DOI: 10.1007/s00198-021-06293-8] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/16/2021] [Accepted: 12/29/2021] [Indexed: 10/19/2022]
Abstract
UNLABELLED The Charlson Comorbidity Index (CCI) may be applicable for predicting fracture risk since several diagnoses from the index are predictors of fracture. Main results were that the CCI was updated to predict risk of hip fracture with fair precision and that the index could be useful in detecting high-risk individuals. PURPOSE Several of the Charlson Comorbidity Index (CCI) diagnoses are validated predictors of fracture. The purpose of this study was to evaluate the performance of the CCI 1987 by Charlson et al. and of the CCI 2011 by Quan et al. in predicting major osteoporotic fracture (MOF) and hip fracture (HF). Furthermore, it was examined whether the index could be modified to improve fracture risk prediction. METHODS The study population included the entire Danish population aged 45 + years as per January 1, 2018. The cohort was split randomly 50/50 into a development and a validation cohort. CCI diagnoses and fracture outcomes were identified from hospital diagnoses. The weighting of diagnoses was updated in a new Charlson Fracture Index (CFI) using multivariable logistic regression. Predictive capabilities of the CCI 1987, the updated CCI 2011 and the new Charlson Fracture index were evaluated in the validation cohort by receiver operating characteristics (ROC) curves and area under the curve (AUC). RESULTS In the validation cohort, the 1987 and 2011 CCIs resulted in AUCs below or around 0.7 in prediction of MOF and HF in both sexes. The CFI resulted in AUCs < 0.7 in prediction of MOF in both sexes. In prediction of HF, the CFI resulted in AUC of 0.755 (95% CI 0.749; 0.761) in women and 0.782 (95% CI 0.772; 0.793) in men. CONCLUSION The 1987 and 2011 CCIs showed overall poor accuracy in fracture risk prediction. The CFI showed fair accuracy in prediction of HF in women and in men.
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Affiliation(s)
- A Clausen
- OPEN - Open Patient Data Explorative Network, Odense University Hospital, Odense, Denmark
| | - S Möller
- OPEN - Open Patient Data Explorative Network, Odense University Hospital, Odense, Denmark
- Research Unit OPEN, Department of Clinical Research, University of Southern Denmark, Odense, Denmark
| | - M K Skjødt
- Research Unit OPEN, Department of Clinical Research, University of Southern Denmark, Odense, Denmark
- Department of Medicine, Holbæk Hospital, Holbæk, Denmark
| | - B H Bech
- Department of Public Health - Department of Epidemiology, Aarhus University, Aarhus, Denmark
| | - K H Rubin
- OPEN - Open Patient Data Explorative Network, Odense University Hospital, Odense, Denmark.
- Research Unit OPEN, Department of Clinical Research, University of Southern Denmark, Odense, Denmark.
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12
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Ma TL, Zhu P, Ke ZR, Chen JX, Hu YH, Xie J. Focusing on OB-OC-MΦ Axis and miR-23a to Explore the Pathogenesis and Treatment Strategy of Osteoporosis. Front Endocrinol (Lausanne) 2022; 13:891313. [PMID: 35909545 PMCID: PMC9329542 DOI: 10.3389/fendo.2022.891313] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/07/2022] [Accepted: 06/20/2022] [Indexed: 11/27/2022] Open
Abstract
Osteoporosis is a bone metabolic disorder characterized by decreased bone density and deteriorated microstructure, which increases the risk of fractures. The imbalance between bone formation and bone resorption results in the occurrence and progression of osteoporosis. Osteoblast-mediated bone formation, osteoclast-mediated bone resorption and macrophage-regulated inflammatory response play a central role in the process of bone remodeling, which together maintain the balance of the osteoblast-osteoclast-macrophage (OB-OC-MΦ) axis under physiological conditions. Bone formation and bone resorption disorders caused by the imbalance of OB-OC-MΦ axis contribute to osteoporosis. Many microRNAs are involved in the regulation of OB-OC-MΦ axis homeostasis, with microRNA-23a (miR-23a) being particularly crucial. MiR-23a is highly expressed in the pathological process of osteoporosis, which eventually leads to the occurrence and further progression of osteoporosis by inhibiting osteogenesis, promoting bone resorption and inflammatory polarization of macrophages. This review focuses on the role and mechanism of miR-23a in regulating the OB-OC-MΦ axis to provide new clinical strategies for the prevention and treatment of osteoporosis.
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Affiliation(s)
- Tian-Liang Ma
- Department of Orthopedics, Xiangya Hospital, Central South University, Changsha, China
- Hunan Engineering Research Center of Biomedical Metal and Ceramic Implants, Xiangya Hospital, Central South University, Changsha, China
- XiangYa School of Medicine, Central South University, Changsha, China
| | - Peng Zhu
- XiangYa School of Medicine, Central South University, Changsha, China
| | - Zhuo-Ran Ke
- XiangYa School of Medicine, Central South University, Changsha, China
| | - Jing-Xian Chen
- XiangYa School of Medicine, Central South University, Changsha, China
| | - Yi-He Hu
- Department of Orthopedics, Xiangya Hospital, Central South University, Changsha, China
- Hunan Engineering Research Center of Biomedical Metal and Ceramic Implants, Xiangya Hospital, Central South University, Changsha, China
- *Correspondence: Yi-He Hu, ; Jie Xie,
| | - Jie Xie
- Department of Orthopedics, Xiangya Hospital, Central South University, Changsha, China
- Hunan Engineering Research Center of Biomedical Metal and Ceramic Implants, Xiangya Hospital, Central South University, Changsha, China
- *Correspondence: Yi-He Hu, ; Jie Xie,
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13
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17 β-Estradiol alleviates oxidative damage in osteoblasts by regulating miR-320/RUNX2 signaling pathway. J Biosci 2021. [DOI: 10.1007/s12038-021-00236-5] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/20/2023]
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14
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Halvachizadeh S, Stalder AL, Bellut D, Hoppe S, Rossbach P, Cianfoni A, Schnake KJ, Mica L, Pfeifer R, Sprengel K, Pape HC. Systematic Review and Meta-Analysis of 3 Treatment Arms for Vertebral Compression Fractures: A Comparison of Improvement in Pain, Adjacent-Level Fractures, and Quality of Life Between Vertebroplasty, Kyphoplasty, and Nonoperative Management. JBJS Rev 2021; 9:01874474-202110000-00006. [PMID: 34695056 DOI: 10.2106/jbjs.rvw.21.00045] [Citation(s) in RCA: 29] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/29/2022]
Abstract
BACKGROUND Osteoporotic vertebral fractures (OVFs) have become increasingly common, and previous nonrandomized and randomized controlled trials (RCTs) have compared the effects of cement augmentation versus nonoperative management on the clinical outcome. This meta-analysis focuses on RCTs and the calculated differences between cement augmentation techniques and nonsurgical management in outcome (e.g., pain reduction, adjacent-level fractures, and quality of life [QOL]). METHODS A systematic review was performed according to the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines, and the following scientific search engines were used: MEDLINE, Embase, Cochrane, Web of Science, and Scopus. The inclusion criteria included RCTs that addressed different treatment strategies for OVF. The primary outcome was pain, which was determined by a visual analog scale (VAS) score; the secondary outcomes were the risk of adjacent-level fractures and QOL (as determined by the EuroQol-5 Dimension [EQ-5D] questionnaire, the Oswestry Disability Index [ODI], the Quality of Life Questionnaire of the European Foundation for Osteoporosis [QUALEFFO], and the Roland-Morris Disability Questionnaire [RDQ]). Patients were assigned to 3 groups according to their treatment: vertebroplasty (VP), kyphoplasty (KP), and nonoperative management (NOM). The short-term (weeks), midterm (months), and long-term (>1 year) effects were compared. A random effects model was used to summarize the treatment effect, including I2 for assessing heterogeneity and the revised Cochrane risk-of-bias 2 (RoB 2) tool for assessment of ROB. Funnel plots were used to assess risk of publication bias. The log of the odds ratio (OR) between treatments is reported. RESULTS After screening of 1,861 references, 53 underwent full-text analysis and 16 trials (30.2%) were included. Eleven trials (68.8%) compared VP and NOM, 1 (6.3%) compared KP and NOM, and 4 (25.0%) compared KP and VP. Improvement of pain was better by 1.31 points (95% confidence interval [CI], 0.41 to 2.21; p < 0.001) after VP when compared with NOM in short-term follow-up. Pain effects were similar after VP and KP (midterm difference of 0.0 points; 95% CI, -0.25 to 0.25). The risk of adjacent-level fractures was not increased after any treatment (log OR, -0.16; 95% CI, -0.83 to 0.5; NOM vs. VP or KP). QOL did not differ significantly between the VP or KP and NOM groups except in the short term when measured by the RDQ. CONCLUSIONS This meta-analysis provides evidence in favor of the surgical treatment of OVFs. Surgery was associated with greater improvement of pain and was unrelated to the development of adjacent-level fractures or QOL. Although improvements in sagittal balance after surgery were poorly documented, surgical treatment may be warranted if pain is a relevant problem. LEVEL OF EVIDENCE Therapeutic Level I. See Instructions for Authors for a complete description of levels of evidence.
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Affiliation(s)
- Sascha Halvachizadeh
- Department of Trauma, University Hospital Zurich, Zurich, Switzerland
- Harald-Tscherne Laboratory for Orthopedic and Trauma Research, University of Zurich, Zurich, Switzerland
| | | | - David Bellut
- Department of Neurosurgery, University Hospital Zurich, Zurich, Switzerland
| | - Sven Hoppe
- Department of Orthopedic Surgery, Inselspital University Hospital of Bern, Bern, Switzerland
| | - Philipp Rossbach
- Department of Rheumatology, University Hospital Zurich, Zurich, Switzerland
| | - Alessandro Cianfoni
- Department of Neuroradiology, Neurocenter of Southern Switzerland, Ospedale Regionaledi Lugano, Lugano, Switzerland
- Department of Interventional and Diagnostic Neuroradiology, Inselspital University Hospital of Bern, Bern, Switzerland
| | - Klaus John Schnake
- Center for Spinal and Scoliosis Surgery, Malteser Waldkrankenhaus St. Marien, Erlangen, Germany
- Department of Orthopedics and Traumatology, Paracelsus Private Medical University Nuremberg, Nuremberg, Germany
| | - Ladislav Mica
- Department of Trauma, University Hospital Zurich, Zurich, Switzerland
- Harald-Tscherne Laboratory for Orthopedic and Trauma Research, University of Zurich, Zurich, Switzerland
| | - Roman Pfeifer
- Department of Trauma, University Hospital Zurich, Zurich, Switzerland
- Harald-Tscherne Laboratory for Orthopedic and Trauma Research, University of Zurich, Zurich, Switzerland
| | - Kai Sprengel
- Department of Trauma, University Hospital Zurich, Zurich, Switzerland
- Harald-Tscherne Laboratory for Orthopedic and Trauma Research, University of Zurich, Zurich, Switzerland
| | - Hans-Christoph Pape
- Department of Trauma, University Hospital Zurich, Zurich, Switzerland
- Harald-Tscherne Laboratory for Orthopedic and Trauma Research, University of Zurich, Zurich, Switzerland
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15
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Migliorini F, Giorgino R, Hildebrand F, Spiezia F, Peretti GM, Alessandri-Bonetti M, Eschweiler J, Maffulli N. Fragility Fractures: Risk Factors and Management in the Elderly. MEDICINA-LITHUANIA 2021; 57:medicina57101119. [PMID: 34684156 PMCID: PMC8538459 DOI: 10.3390/medicina57101119] [Citation(s) in RCA: 115] [Impact Index Per Article: 28.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 08/19/2021] [Revised: 10/05/2021] [Accepted: 10/13/2021] [Indexed: 02/08/2023]
Abstract
Given the progressive ageing of Western populations, the fragility fractures market has a growing socioeconomic impact. Fragility fractures are common in the elderly, negatively impacting their quality of life, limiting autonomy, increasing disability, and decreasing life expectancy. Different causes contribute to the development of a fractures in frail individuals. Among all, targeting fragile patients before the development of a fracture may represent the greatest challenge, and current diagnostic tools suffer from limitations. This study summarizes the current evidence on the management of fragility fractures, discussing risk factors, prevention, diagnosis, and actual limitations of the clinical therapeutic options, putting forward new ideas for further scientific investigation.
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Affiliation(s)
- Filippo Migliorini
- Department of Orthopaedics, Trauma and Reconstructive Surgery, RWTH Aachen University, 52074 Aachen, Germany; (F.M.); (F.H.); (J.E.)
| | - Riccardo Giorgino
- Residency Program in Orthopedics and Traumatology, University of Milan, 20122 Milan, Italy;
| | - Frank Hildebrand
- Department of Orthopaedics, Trauma and Reconstructive Surgery, RWTH Aachen University, 52074 Aachen, Germany; (F.M.); (F.H.); (J.E.)
| | - Filippo Spiezia
- Department of Orthopaedic and Trauma Surgery, Ospedale San Carlo Potenza, Via Potito Petrone, 85100 Potenza, Italy;
| | - Giuseppe Maria Peretti
- Department of Biomedical Sciences for Health, University of Milan, 20133 Milan, Italy;
- IRCCS Orthopedic Institute Galeazzi, 20161 Milan, Italy
| | | | - Jörg Eschweiler
- Department of Orthopaedics, Trauma and Reconstructive Surgery, RWTH Aachen University, 52074 Aachen, Germany; (F.M.); (F.H.); (J.E.)
| | - Nicola Maffulli
- Department of Medicine, Surgery and Dentistry, University of Salerno, 84081 Baronissi, Italy
- School of Pharmacy and Bioengineering, Keele University Faculty of Medicine, Thornburrow Drive, Stoke-on-Trent ST4 7QB, UK
- Centre for Sports and Exercise Medicine, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, Mile End Hospital, London E1 4DG, UK
- Correspondence:
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16
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Peng CH, Lin WY, Yeh KT, Chen IH, Wu WT, Lin MD. The molecular etiology and treatment of glucocorticoid-induced osteoporosis. Tzu Chi Med J 2021; 33:212-223. [PMID: 34386357 PMCID: PMC8323641 DOI: 10.4103/tcmj.tcmj_233_20] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/07/2020] [Revised: 11/19/2020] [Accepted: 12/30/2020] [Indexed: 12/30/2022] Open
Abstract
Glucocorticoid-induced osteoporosis (GIOP) is the most common form of secondary osteoporosis, accounting for 20% of osteoporosis diagnoses. Using glucocorticoids for >6 months leads to osteoporosis in 50% of patients, resulting in an increased risk of fracture and death. Osteoblasts, osteocytes, and osteoclasts work together to maintain bone homeostasis. When bone formation and resorption are out of balance, abnormalities in bone structure or function may occur. Excess glucocorticoids disrupt the bone homeostasis by promoting osteoclast formation and prolonging osteoclasts' lifespan, leading to an increase in bone resorption. On the other hand, glucocorticoids inhibit osteoblasts' formation and facilitate apoptosis of osteoblasts and osteocytes, resulting in a reduction of bone formation. Several signaling pathways, signaling modulators, endocrines, and cytokines are involved in the molecular etiology of GIOP. Clinically, adults ≥40 years of age using glucocorticoids chronically with a high fracture risk are considered to have medical intervention. In addition to vitamin D and calcium tablet supplementations, the major therapeutic options approved for GIOP treatment include antiresorption drug bisphosphonates, parathyroid hormone N-terminal fragment teriparatide, and the monoclonal antibody denosumab. The selective estrogen receptor modulator can only be used under specific condition for postmenopausal women who have GIOP but fail to the regular GIOP treatment or have specific therapeutic contraindications. In this review, we focus on the molecular etiology of GIOP and the molecular pharmacology of the therapeutic drugs used for GIOP treatment.
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Affiliation(s)
- Cheng-Huan Peng
- Department of Orthopedics, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Hualien, Taiwan.,Institute of Medical Sciences, Tzu Chi University, Hualien, Taiwan.,School of Medicine, Tzu Chi University, Hualien, Taiwan
| | - Wen-Ying Lin
- Department of Orthopedics, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Hualien, Taiwan
| | - Kuang-Ting Yeh
- Department of Orthopedics, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Hualien, Taiwan.,School of Medicine, Tzu Chi University, Hualien, Taiwan
| | - Ing-Ho Chen
- Department of Orthopedics, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Hualien, Taiwan.,School of Medicine, Tzu Chi University, Hualien, Taiwan
| | - Wen-Tien Wu
- Department of Orthopedics, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Hualien, Taiwan.,Institute of Medical Sciences, Tzu Chi University, Hualien, Taiwan.,School of Medicine, Tzu Chi University, Hualien, Taiwan
| | - Ming-Der Lin
- Institute of Medical Sciences, Tzu Chi University, Hualien, Taiwan.,Department of Molecular Biology and Human Genetics, Tzu Chi University, Hualien, Taiwan
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17
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Li L, Zhou J, Xu Y, Huang Z, Zhang N, Qiu X, Wang L. C-C chemokine receptor type 6 modulates the biological function of osteoblastogenesis by altering the expression levels of Osterix and OPG/RANKL. Biosci Trends 2021; 15:240-248. [PMID: 34248133 DOI: 10.5582/bst.2021.01199] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/05/2022]
Abstract
Circulating inflammatory factors affect osteoblast and osteoclast formation and activity in osteoporosis. Estrogen affects the migration of Th17 cells via the C-C chemokine receptor type 6 (CCR6) and C-C chemokine ligand 20 (CCL20) signaling pathways to modulate bone metabolism; however, it is unclear whether and how CCR6 modulates bone homeostasis. In the present study, CCR6 knockout (CCR6-/-) mice were selected to investigate the effects of CCR6 in the regulation of homeostasis of osteoblasts and osteoclasts. Primary osteoblasts were isolated from the calvarium of newborn CCR6-/- or wild-type mice, followed by osteoblastic differentiation culture in vitro. CCR6 deletion reduced osteoblast activity in terms of alkaline phosphatase (ALP) activity and inhibited osteoblast mineralization according to the results of Alizarin Red S staining, whereas it did not affect the proliferation of osteoblasts. CCR6 deletion inhibited Osterix mRNA expression in osteoblasts during the late stage of mineralization in vitro, while it did not affect mRNA expression levels of runt-related transcription factor 2 (Runx2) and Collagen-1. The ratio of osteoprotegerin (OPG) /receptor activator of nuclear factor κ-Β ligand (RANKL) mRNA level in osteoblasts was decreased by CCR6 deficiency in the culture treated with 1,25(OH)2D3/PGE2, while there was no effect observed in the normal culture environment. The results provide novel insights, such as that CCR6 deletion suppresses osteoblast differentiation by downregulating the expression levels of the transcription factor Osterix, and indirectly promotes osteoclast production by increasing transcription of RANKL. This may be one of the mechanisms via which CCR6 deletion regulates bone metabolism.
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Affiliation(s)
- Lisha Li
- Obstetrics and Gynecology Hospital of Fudan University, Shanghai, China.,The Academy of Integrative Medicine of Fudan University, Shanghai, China.,Shanghai Key Laboratory of Female Reproductive Endocrine-related Diseases, Shanghai, China
| | - Jing Zhou
- Obstetrics and Gynecology Hospital of Fudan University, Shanghai, China.,The Academy of Integrative Medicine of Fudan University, Shanghai, China.,Shanghai Key Laboratory of Female Reproductive Endocrine-related Diseases, Shanghai, China
| | - Yingping Xu
- Reproductive Medicine Centre, Taizhou Hospital Affiliated to Wenzhou Medical University, Linhai, Zhejiang, China
| | - Zengshu Huang
- Obstetrics and Gynecology Hospital of Fudan University, Shanghai, China.,The Academy of Integrative Medicine of Fudan University, Shanghai, China.,Shanghai Key Laboratory of Female Reproductive Endocrine-related Diseases, Shanghai, China
| | - Na Zhang
- Obstetrics and Gynecology Hospital of Fudan University, Shanghai, China.,The Academy of Integrative Medicine of Fudan University, Shanghai, China.,Shanghai Key Laboratory of Female Reproductive Endocrine-related Diseases, Shanghai, China
| | - Xuemin Qiu
- Obstetrics and Gynecology Hospital of Fudan University, Shanghai, China.,The Academy of Integrative Medicine of Fudan University, Shanghai, China.,Shanghai Key Laboratory of Female Reproductive Endocrine-related Diseases, Shanghai, China
| | - Ling Wang
- Obstetrics and Gynecology Hospital of Fudan University, Shanghai, China.,The Academy of Integrative Medicine of Fudan University, Shanghai, China.,Shanghai Key Laboratory of Female Reproductive Endocrine-related Diseases, Shanghai, China
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18
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Liu M, Ding H, Wang H, Wang M, Wu X, Gan L, Cheng L, Li X. Moringa oleifera leaf extracts protect BMSC osteogenic induction following peroxidative damage by activating the PI3K/Akt/Foxo1 pathway. J Orthop Surg Res 2021; 16:150. [PMID: 33610167 PMCID: PMC7896384 DOI: 10.1186/s13018-021-02284-x] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/28/2020] [Accepted: 02/08/2021] [Indexed: 12/28/2022] Open
Abstract
Objective We aimed to investigate the therapeutic effects of Moringa oleifera leaf extracts on osteogenic induction of rat bone marrow mesenchymal stem cells (BMSCs) following peroxidative damage and to explore the underlying mechanisms. Methods Conditioned medium was used to induce osteogenic differentiation of BMSCs, which were treated with H2O2, Moringa oleifera leaf extracts-containing serum, or the phosphatidyl inositol-3 kinase (PI3K) inhibitor wortmannin, alone or in combination. Cell viability was measured using the MTT assay. Cell cycle was assayed using flow cytometry. Expression levels of Akt, phosphorylated (p)Akt, Foxo1, and cleaved caspase-3 were analyzed using western blot analysis. The mRNA levels of osteogenesis-associated genes, including alkaline phosphatase (ALP), collagen І, osteopontin (OPN), and Runx2, were detected using qRT-PCR. Reactive oxygen species (ROS) and malondialdehyde (MDA) levels, as well as superoxide dismutase (SOD), glutathione peroxidase (GSH-PX), and ALP activity were detected using commercially available kits. Osteogenic differentiation capability was determined using alizarin red staining. Results During osteogenic induction of rat BMSCs, H2O2 reduced cell viability and proliferation, inhibited osteogenesis, increased ROS and MDA levels, and decreased SOD and GSH-PX activity. H2O2 significantly reduced pAkt and Foxo1 expression, and increased cleaved caspase-3 levels in BMSCs. Additional treatments with Moringa oleifera leaf extracts partially reversed the H2O2-induced changes. Wortmannin partially attenuated the effects of Moringa oleifera leaf extracts on protein expression of Foxo1, pAkt, and cleaved caspase-3, as well as mRNA levels of osteogenesis-associated genes. Conclusion Moringa oleifera leaf extracts ameliorate peroxidative damage and enhance osteogenic induction of rat BMSCs by activating the PI3K/Akt/Foxo1 pathway.
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Affiliation(s)
- Meiling Liu
- Department of Geriatrics, Second Affiliated Hospital of Harbin Medical University, 246 Xuefu Road, Nangang District, Harbin, 150086, China
| | - Haifeng Ding
- Department of Geriatrics, Second Affiliated Hospital of Harbin Medical University, 246 Xuefu Road, Nangang District, Harbin, 150086, China
| | - Hongzhi Wang
- Department of Geriatrics, Second Affiliated Hospital of Harbin Medical University, 246 Xuefu Road, Nangang District, Harbin, 150086, China
| | - Manfeng Wang
- Department of Geriatrics, Second Affiliated Hospital of Harbin Medical University, 246 Xuefu Road, Nangang District, Harbin, 150086, China
| | - Xiaowei Wu
- Department of Geriatrics, Second Affiliated Hospital of Harbin Medical University, 246 Xuefu Road, Nangang District, Harbin, 150086, China.
| | - Lu Gan
- Department of Geriatrics, Second Affiliated Hospital of Harbin Medical University, 246 Xuefu Road, Nangang District, Harbin, 150086, China.
| | - Luyang Cheng
- Department of Geriatrics, Second Affiliated Hospital of Harbin Medical University, 246 Xuefu Road, Nangang District, Harbin, 150086, China
| | - Xianglu Li
- Department of Geriatrics, Second Affiliated Hospital of Harbin Medical University, 246 Xuefu Road, Nangang District, Harbin, 150086, China
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19
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Radeva M, Predel D, Winzler S, Teichgräber U, Pfeil A, Malich A, Papageorgiou I. Reliability of a Risk-Factor Questionnaire for Osteoporosis: A Primary Care Survey Study with Dual Energy X-ray Absorptiometry Ground Truth. INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH 2021; 18:1136. [PMID: 33525339 PMCID: PMC7908374 DOI: 10.3390/ijerph18031136] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 12/22/2020] [Revised: 01/22/2021] [Accepted: 01/25/2021] [Indexed: 12/24/2022]
Abstract
(1) Purpose: Predisposing factors to osteoporosis (OP) as well as dual-source x-ray densitometry (DXA) steer therapeutic decisions by determining the FRAX index. This study examines the reliability of a standard risk factor questionnaire in OP-screening. (2) Methods: n = 553 eligible questionnaires encompassed 24 OP-predisposing factors. Reliability was assessed using DXA as a gold standard. Multiple logistic regression and Spearman's correlations, as well as the confounding influence of age and body mass index, were analyzed in SPSS (IBM Corporation, Armonk, NY, USA). (3) Results: Our study revealed low patient self-awareness regarding OP and its risk factors. One out of every four patients reported a positive history for osteoporosis not confirmed by DXA. The extraordinarily high incidence of rheumatoid arthritis and thyroid disorders likely reflect confusion with other diseases or health anxiety. FRAX-determining risk factors such as malnutrition, liver insufficiency, prior fracture without trauma, and glucocorticoid therapy did not correlate with increased OP incidence, altogether demonstrating how inaccurate survey information could influence therapeutic decisions on osteoporosis. (4) Conclusions: Contradictive results and a low level of patient self-awareness suggest a high degree of uncertainty and low reliability of the current OP risk factor survey.
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Affiliation(s)
- Maria Radeva
- Institute of Diagnostic and Interventional Radiology, Jena University Hospital—Friedrich Schiller University Jena, Am Klinikum 1, 07747 Jena, Germany; (M.R.); (U.T.)
| | - Dorothee Predel
- Institute of Radiology, Suedharz Hospital Nordhausen, Dr.-Robert-Koch-Str. 39, 99734 Nordhausen, Germany; (D.P.); (S.W.); (A.M.)
| | - Sven Winzler
- Institute of Radiology, Suedharz Hospital Nordhausen, Dr.-Robert-Koch-Str. 39, 99734 Nordhausen, Germany; (D.P.); (S.W.); (A.M.)
| | - Ulf Teichgräber
- Institute of Diagnostic and Interventional Radiology, Jena University Hospital—Friedrich Schiller University Jena, Am Klinikum 1, 07747 Jena, Germany; (M.R.); (U.T.)
| | - Alexander Pfeil
- Department of Internal Medicine III, Jena University Hospital—Friedrich Schiller University Jena, Am Klinikum 1, 07747 Jena, Germany;
| | - Ansgar Malich
- Institute of Radiology, Suedharz Hospital Nordhausen, Dr.-Robert-Koch-Str. 39, 99734 Nordhausen, Germany; (D.P.); (S.W.); (A.M.)
| | - Ismini Papageorgiou
- Institute of Diagnostic and Interventional Radiology, Jena University Hospital—Friedrich Schiller University Jena, Am Klinikum 1, 07747 Jena, Germany; (M.R.); (U.T.)
- Institute of Radiology, Suedharz Hospital Nordhausen, Dr.-Robert-Koch-Str. 39, 99734 Nordhausen, Germany; (D.P.); (S.W.); (A.M.)
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20
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Song J, Zhang R, Lv L, Liang J, Wang W, Liu R, Dang X. The Relationship Between Body Mass Index and Bone Mineral Density: A Mendelian Randomization Study. Calcif Tissue Int 2020; 107:440-445. [PMID: 32989491 DOI: 10.1007/s00223-020-00736-w] [Citation(s) in RCA: 42] [Impact Index Per Article: 8.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/18/2020] [Accepted: 07/21/2020] [Indexed: 01/28/2023]
Abstract
Body mass index (BMI) is closely associated with bone mineral density (BMD) in both men and women. However, the relationship between BMI and BMD varies according to different studies. Using SNPs strongly associated with BMI in 336,107 individuals, we conducted a two-sample Mendelian randomization study to identify whether and to what extent BMD at different skeletal sites was affected by BMI. A power calculation was also performed. We found that BMI may causally increase lumbar BMD (β 0.087; 95% CI 0.025 to 0.149; P = 0.006) and heel calcaneus BMD (β 0.120; 95% CI 0.082 to 0.157; P = 1 × 10-7). The associations of BMI with forearm and femoral neck BMD were not statistically significant. Our study suggested that higher BMI plays a causal role in increasing BMD and the effects are similar across the skeleton. BMI was causally and positively associated with lumbar and heel calcaneus BMD. However, no statistically significant effects were observed for BMI on femoral neck or forearm BMD.
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Affiliation(s)
- Jidong Song
- Department of Orthopaedics, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an Jiaotong University, No.157, Xiwu Road, Xi'an, 710004, Shaanxi, China
| | - Rupeng Zhang
- Department of Orthopaedics, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an Jiaotong University, No.157, Xiwu Road, Xi'an, 710004, Shaanxi, China
| | - Leifeng Lv
- Department of Orthopaedics, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an Jiaotong University, No.157, Xiwu Road, Xi'an, 710004, Shaanxi, China
| | - Jialin Liang
- Department of Orthopaedics, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an Jiaotong University, No.157, Xiwu Road, Xi'an, 710004, Shaanxi, China
| | - Wei Wang
- Department of Orthopaedics, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an Jiaotong University, No.157, Xiwu Road, Xi'an, 710004, Shaanxi, China
| | - Ruiyu Liu
- Department of Orthopaedics, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an Jiaotong University, No.157, Xiwu Road, Xi'an, 710004, Shaanxi, China
| | - Xiaoqian Dang
- Department of Orthopaedics, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an Jiaotong University, No.157, Xiwu Road, Xi'an, 710004, Shaanxi, China.
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21
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Zheng J, Guo H, Qin Y, Liu Z, Ding Z, Zhang L, Wang W. SNHG5/miR-582-5p/RUNX3 feedback loop regulates osteogenic differentiation and apoptosis of bone marrow mesenchymal stem cells. J Cell Physiol 2020. [PMID: 33111341 DOI: 10.1002/jcp.29527] [Citation(s) in RCA: 22] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/26/2019] [Accepted: 01/08/2020] [Indexed: 12/21/2022]
Abstract
Osteoporosis is one of the most prevailing orthopedic diseases that causes a heavy burden on public health. Given that bone marrow-derived mesenchymal stem cells (BMSCs) are of immense importance in osteoporosis development, it is necessary to expound the mechanisms underlying BMSC osteoblastic differentiation. Although mounting research works have investigated the role of small nucleolar RNA host gene 5 (SNHG5) in various diseases, elucidations on its function in osteoporosis are still scarce. It was observed that SNHG5 and RUNX family transcription factor 3 (RUNX3) were remarkably elevated during osteogenic differentiation of human bone marrow mesenchymal stem cells (hBMSCs). Further, we disclosed that the silencing of SNHG5 suppressed osteogenic differentiation and induced apoptosis of hBMSCs. What's more, SNHG5 acted as a competing endogenous RNA to affect RUNX3 expression via competitively binding with microRNA (miR)-582-5p. RUNX3 was also confirmed to simulate the transcriptional activation of SNHG5. Finally, our findings manifested that the positive feedback loop of SNHG5/miR-582-5p/RUNX3 executed the promoting role in the development of osteoporosis, which shed light on specific molecular mechanism governing SNHG5 in osteogenic differentiation and apoptosis of hBMSCs and indicated that SNHG5 may represent a novel target for the improvement of osteoporosis therapy.
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Affiliation(s)
- Jiwei Zheng
- School of Stomatology, Xuzhou Medical University, Xuzhou, Jiangsu, China
- Department of Stomatology, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu, China
| | - Hongliang Guo
- Department of Repair Section, The Affiliated Stomatology Hospital of Xuzhou Medical University, Xuzhou, Jiangsu, China
| | - Ying Qin
- School of Stomatology, Xuzhou Medical University, Xuzhou, Jiangsu, China
- Department of Stomatology, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu, China
| | - Zongxiang Liu
- Department of Stomatology, The Affiliated Stomatology Hospital of Xuzhou Medical University, Xuzhou, Jiangsu, China
| | - Zhijiang Ding
- School of Stomatology, Xuzhou Medical University, Xuzhou, Jiangsu, China
- Department of Stomatology, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu, China
| | - Lei Zhang
- Department of Stomatology, The Affiliated Stomatology Hospital of Xuzhou Medical University, Xuzhou, Jiangsu, China
| | - Wanqing Wang
- School of Stomatology, Xuzhou Medical University, Xuzhou, Jiangsu, China
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22
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Ogliari G, Lunt E, Ong T, Marshall L, Sahota O. The impact of lockdown during the COVID-19 pandemic on osteoporotic fragility fractures: an observational study. Arch Osteoporos 2020; 15:156. [PMID: 33026586 PMCID: PMC7539555 DOI: 10.1007/s11657-020-00825-1] [Citation(s) in RCA: 37] [Impact Index Per Article: 7.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/13/2020] [Accepted: 09/15/2020] [Indexed: 02/03/2023]
Abstract
We investigated whether osteoporotic fractures declined during lockdown, among adults aged 50 years and older. We showed that fewer outpatients attended the Fracture Clinic, for non-hip fractures, during lockdown; in contrast, no change in admissions for hip fractures was observed. This could be due to fewer outdoors falls, during lockdown. PURPOSE Many countries implemented a lockdown to control the spread of the COVID-19 pandemic. We explored whether outpatient attendances to the Fracture Clinic for non-hip fragility fracture and inpatient admissions for hip fracture declined during lockdown, among adults aged 50 years and older, in a large secondary care hospital. METHODS In our observational study, we analysed the records of 6681 outpatients attending the Fracture Clinic, for non-hip fragility fractures, and those of 1752 inpatients, admitted for hip fracture, during the time frames of interest. These were weeks 1st to 12th in 2020 ("prior to lockdown"), weeks 13th to 19th in 2020 ("lockdown") and corresponding periods over 2015 to 2019. We tested for differences in mean numbers (standard deviation (SD)) of outpatients and inpatients, respectively, per week, during the time frames of interest, across the years. RESULTS Prior to lockdown, in 2020, 63.1 (SD 12.6) outpatients per week attended the Fracture Clinic, similar to previous years (p value 0.338). During lockdown, 26.0 (SD 7.3) outpatients per week attended the Fracture Clinic, fewer than previous years (p value < 0.001); similar findings were observed in both sexes and age groups (all p values < 0.001). During lockdown, 16.1 (SD 5.6) inpatients per week were admitted for hip fracture, similar to previous years (p value 0.776). CONCLUSION During lockdown, fewer outpatients attended the Fracture Clinic, for non-hip fragility fractures, while no change in inpatient admissions for hip fracture was observed. This could reflect fewer non-hip fractures and may inform allocation of resources during pandemic.
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Affiliation(s)
- Giulia Ogliari
- Department of Health Care for Older People (HCOP), Queen's Medical Centre, Nottingham University Hospitals NHS Trust, Derby Road, Nottingham, Nottinghamshire, NG7 2UH, UK.
| | - Eleanor Lunt
- Department of Health Care for Older People (HCOP), Queen's Medical Centre, Nottingham University Hospitals NHS Trust, Derby Road, Nottingham, Nottinghamshire, NG7 2UH, UK
| | - Terence Ong
- Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia
| | - Lindsey Marshall
- Department of Trauma & Orthopaedics, Queen's Medical Centre, Nottingham University Hospitals NHS Trust, Nottingham, UK
| | - Opinder Sahota
- Department of Health Care for Older People (HCOP), Queen's Medical Centre, Nottingham University Hospitals NHS Trust, Derby Road, Nottingham, Nottinghamshire, NG7 2UH, UK
- University of Nottingham , Nottingham, UK
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23
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Martínez-Martínez A, Muñoz-Islas E, Ramírez-Rosas MB, Acosta-González RI, Torres-Rodríguez HF, Jiménez-Andrade JM. Blockade of the colony-stimulating factor-1 receptor reverses bone loss in osteoporosis mouse models. Pharmacol Rep 2020; 72:1614-1626. [PMID: 32222915 DOI: 10.1007/s43440-020-00091-5] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/20/2019] [Revised: 01/27/2020] [Accepted: 02/19/2020] [Indexed: 12/26/2022]
Abstract
BACKGROUND Mice lacking either colony-stimulating factor-1 (CSF-1) or its receptor, CSF-1R, display osteopetrosis. Accordingly, genetic deletion or pharmacological blockade of CSF-1 prevents the bone loss associated with estrogen deficiency. However, the role of CSF-1R in osteoporosis models of type-1 diabetes (T1D) and ovariectomy (OVX) has not been examined. Thus, we evaluated whether CSF-1R blockade would relieve the bone loss in a model of primary osteoporosis (female mice with OVX) and a model of secondary osteoporosis (female with T1D) using micro-computed tomography. METHODS Female ICR mice at 10 weeks underwent OVX or received five daily administrations of streptozotocin (ip, 50 mg/kg) to induce T1D. Four weeks after OVX and 14 weeks after first injection of streptozotocin, mice received an anti-CSF-1R (2G2) antibody (10 mg/kg, ip; once/week for 6 weeks) or vehicle. At the last day of antibody administration, mice were sacrificed and femur and tibia were harvested for micro-computed tomography analysis. RESULTS Mice with OVX had a significant loss of trabecular bone at the distal femoral and proximal tibial metaphysis. Chronic treatment with anti-CSF-1R significantly reversed the trabecular bone loss at these anatomical sites. Streptozotocin-induced T1D resulted in significant loss of trabecular bone at the femoral neck and cortical bone at the femoral mid-diaphysis. Chronic treatment with anti-CSF-1R antibody significantly reversed the bone loss observed in mice with T1D. CONCLUSION Our results demonstrate that blockade of CSF-1R signaling reverses bone loss in two different mouse models of osteoporosis.
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Affiliation(s)
- Arisaí Martínez-Martínez
- Laboratorio de Farmacología, Unidad Académica Multidisciplinaria Reynosa-Aztlán, Universidad Autónoma de Tamaulipas, Calle 16 y Lago de Chapala, Col. Aztlán, 88740, Reynosa, TAMPS, México
| | - Enriqueta Muñoz-Islas
- Laboratorio de Farmacología, Unidad Académica Multidisciplinaria Reynosa-Aztlán, Universidad Autónoma de Tamaulipas, Calle 16 y Lago de Chapala, Col. Aztlán, 88740, Reynosa, TAMPS, México
| | - Martha B Ramírez-Rosas
- Laboratorio de Farmacología, Unidad Académica Multidisciplinaria Reynosa-Aztlán, Universidad Autónoma de Tamaulipas, Calle 16 y Lago de Chapala, Col. Aztlán, 88740, Reynosa, TAMPS, México
| | - Rosa I Acosta-González
- Laboratorio de Farmacología, Unidad Académica Multidisciplinaria Reynosa-Aztlán, Universidad Autónoma de Tamaulipas, Calle 16 y Lago de Chapala, Col. Aztlán, 88740, Reynosa, TAMPS, México
| | - Héctor F Torres-Rodríguez
- Laboratorio de Farmacología, Unidad Académica Multidisciplinaria Reynosa-Aztlán, Universidad Autónoma de Tamaulipas, Calle 16 y Lago de Chapala, Col. Aztlán, 88740, Reynosa, TAMPS, México
| | - Juan M Jiménez-Andrade
- Laboratorio de Farmacología, Unidad Académica Multidisciplinaria Reynosa-Aztlán, Universidad Autónoma de Tamaulipas, Calle 16 y Lago de Chapala, Col. Aztlán, 88740, Reynosa, TAMPS, México.
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24
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Zhong Z, Qian Z, Zhang X, Chen F, Ni S, Kang Z, Zhang F, Li D, Yu B. Tetrandrine Prevents Bone Loss in Ovariectomized Mice by Inhibiting RANKL-Induced Osteoclastogenesis. Front Pharmacol 2020; 10:1530. [PMID: 31998129 PMCID: PMC6967024 DOI: 10.3389/fphar.2019.01530] [Citation(s) in RCA: 29] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/16/2019] [Accepted: 11/26/2019] [Indexed: 12/21/2022] Open
Abstract
Postmenopausal osteoporosis (PMOP) is a metabolic bone disease characterized by decreased bone density and strength due to the imbalance between osteogenesis and osteoclastogenesis. Postmenopausal estrogen withdrawal increases proinflammatory cytokines and increases the serum level of Receptor activator of NF-kB ligand (RANKL)/Osteoprotegerin (OPG), which then leads to the overactivation of osteoclastogenesis. Tetrandrine, a bis-benzylisoquinoline alkaloid, has been widely used in the treatment of rheumatoid arthritis clinically in China. Here, we demonstrate that tetrandrine significantly prevented ovariectomy-induced bone loss and inhibited RANKL-induced osteoclastogenesis. In vivo, we found that intraperitoneal injection of tetrandrine (30 mg/kg) every other day markedly reduced bone loss in ovariectomized mice and the serum levels of TRAcp5b, TNF-a, IL-6, CTX-I, and RANKL/OPG were significantly decreased. In vitro, we found that tetrandrine significantly inhibited osteoclast differentiation in bone marrow monocytes (BMMs) and RAW264.7 cells according to the results of osteoclastogenesis-related gene expression, tartrate-resistant acid phosphatase (TRAP) staining and actin-ring formation as well as bone resorption assay. Mechanistically, tetrandrine inhibited RANKL-induced osteoclastogenesis by suppressing NF-kB, Ca2+, PI3K/AKT, and MAPKs signaling pathways. Taken together, our findings suggest that tetrandrine suppresses osteoclastogenesis through modulation of multiple pathways and has potential value as a therapeutic agent for PMOP, especially for those suffering from RA and PMOP at the same time.
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Affiliation(s)
- Zeyuan Zhong
- Department of Orthopedics, Shanghai Pudong Hospital, Fudan University Pudong Medical Center, Shanghai, China
| | - Zhi Qian
- Department of Orthopedics, Shanghai Pudong Hospital, Fudan University Pudong Medical Center, Shanghai, China
| | - Xu Zhang
- Department of Orthopedics, Shanghai Pudong Hospital, Fudan University Pudong Medical Center, Shanghai, China
| | - Fancheng Chen
- Shanghai Medical College, Fudan University, Shanghai, China
| | - Shuo Ni
- Department of Orthopedics, Shanghai Pudong Hospital, Fudan University Pudong Medical Center, Shanghai, China
| | - Zhanrong Kang
- Department of Orthopedics, Shanghai Pudong Hospital, Fudan University Pudong Medical Center, Shanghai, China
| | - Fangxue Zhang
- Department of Orthopedics, Shanghai Pudong Hospital, Fudan University Pudong Medical Center, Shanghai, China
| | - Dejian Li
- Department of Orthopedics, Shanghai Pudong Hospital, Fudan University Pudong Medical Center, Shanghai, China
| | - Baoqing Yu
- Department of Orthopedics, Shanghai Pudong Hospital, Fudan University Pudong Medical Center, Shanghai, China
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25
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Deal CL, Mitlak BH, Wang Y, Fitzpatrick LA, Miller PD. Response rates for hip, femoral neck, and lumbar spine bone mineral density in patients treated with abaloparatide followed by alendronate: Results from phase 3 ACTIVExtend. Bone Rep 2019; 11:100230. [PMID: 31799340 PMCID: PMC6883300 DOI: 10.1016/j.bonr.2019.100230] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/17/2019] [Revised: 10/28/2019] [Accepted: 10/29/2019] [Indexed: 12/13/2022] Open
Abstract
A significantly greater proportion of abaloparatide/alendronate patients had BMD increases over 0, 3 and 6 percent versus placebo/alendronate. BMD responses were higher at all anatomic sites and for all thresholds assessed for abaloparatide/alendronate versus placebo/alendronate This study provides further evidence of cumulative benefit from sequential treatment with an anabolic agent followed by an antiresorptive. Abaloparatide is a selective activator of the parathyroid hormone type 1 receptor signaling pathway that favors the stimulation of bone formation. Here, we report a prospective, exploratory analysis of bone mineral density (BMD) response rates comparing sequential abaloparatide/alendronate vs placebo/alendronate across the ACTIVE and ACTIVExtend studies. BMD was measured at the lumbar spine, total hip, and femoral neck from the beginning of ACTIVE to the end of ACTIVExtend (18 months of abaloparatide or placebo followed by about 1 month for re-consent, followed by 24 months of alendronate treatment for a total of 43 months). Responders were defined as those patients who had improvements in BMD at 3 anatomic sites—the lumbar spine, total hip, and femoral neck. Three response thresholds, >0%, >3%, and >6%, were evaluated. Five hundred fifty-eight patients in the abaloparatide/alendronate group and 581 patients in the placebo/alendronate group from ACTIVExtend were included in the analysis. At Month 43, a significantly greater proportion of those in the abaloparatide/alendronate group compared with the placebo/alendronate group responded with BMD changes from ACTIVE baseline of >0%, >3%, and >6% at all 3 anatomic sites (p < 0.001 for each comparison). At the>3% threshold, 60.7% (307/506) vs 24.0% (121/505) of patients experienced BMD increases at all 3 sites in the abaloparatide/alendronate vs placebo/alendronate groups, respectively (p < 0.001). A significantly greater proportion of the abaloparatide/alendronate group experienced BMD increases of>0%, >3%, and >6% at each individual anatomic site compared with the placebo/alendronate group at 43 months (p < 0.001). Additionally, at each visit in ACTIVExtend, there was a significantly greater proportion of patients in the abaloparatide/alendronate group above the 3% threshold at each anatomic site compared with the placebo/alendronate group. Results are consistent with the significant BMD response with abaloparatide vs placebo observed in ACTIVE and with the continued fracture risk reduction with sequential abaloparatide/alendronate compared with placebo/alendronate treatment observed in ACTIVE through ACTIVExtend.
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Affiliation(s)
| | | | | | | | - Paul D Miller
- Colorado Center for Bone Research at Panorama Orthopedics & Spine Center, Golden, CO, USA
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26
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Vargas‐Muñoz VM, Martínez‐Martínez A, Muñoz‐Islas E, Ramírez‐Rosas MB, Acosta‐González RI, Jiménez‐Andrade JM. Chronic administration of Cl‐amidine, a pan‐peptidylarginine deiminase inhibitor, does not reverse bone loss in two different murine models of osteoporosis. Drug Dev Res 2019; 81:93-101. [DOI: 10.1002/ddr.21608] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/23/2019] [Revised: 09/24/2019] [Accepted: 09/26/2019] [Indexed: 12/11/2022]
Affiliation(s)
- Virginia M. Vargas‐Muñoz
- Unidad Académica Multidisciplinaria Reynosa‐Aztlán, Universidad Autónoma de Tamaulipas Reynosa Tamaulipas Mexico
| | - Arisai Martínez‐Martínez
- Unidad Académica Multidisciplinaria Reynosa‐Aztlán, Universidad Autónoma de Tamaulipas Reynosa Tamaulipas Mexico
| | - Enriqueta Muñoz‐Islas
- Unidad Académica Multidisciplinaria Reynosa‐Aztlán, Universidad Autónoma de Tamaulipas Reynosa Tamaulipas Mexico
| | - Martha B. Ramírez‐Rosas
- Unidad Académica Multidisciplinaria Reynosa‐Aztlán, Universidad Autónoma de Tamaulipas Reynosa Tamaulipas Mexico
| | - Rosa I. Acosta‐González
- Unidad Académica Multidisciplinaria Reynosa‐Aztlán, Universidad Autónoma de Tamaulipas Reynosa Tamaulipas Mexico
| | - Juan M. Jiménez‐Andrade
- Unidad Académica Multidisciplinaria Reynosa‐Aztlán, Universidad Autónoma de Tamaulipas Reynosa Tamaulipas Mexico
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Jing Y, Wang X, Yu J, Wang X, Zhou Y, Tao B, Sun L, Liu J, Zhao H. Associations of serum sex hormone binding globulin with bone mineral densities and higher 10-year probability of fractures in postmenopausal women with type 2 diabetes mellitus. ANNALS OF TRANSLATIONAL MEDICINE 2019; 7:457. [PMID: 31700893 DOI: 10.21037/atm.2019.08.46] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Abstract
Background Postmenopause and type 2 diabetes mellitus (T2DM) are associated with higher fracture risk. Sex hormones are important in maintaining woman skeleton health. The relationships of sex hormone(s) with bone mineral density (BMD) and fracture risk are still unclear in diabetic-postmenopausal women. This study aimed to investigate the relationships of sex hormones with BMDs and fracture risk in postmenopausal women with T2DM. Methods Two hundred and fourteen postmenopausal women with T2DM were included. BMDs at lumbar spine (L2-4), femoral neck (FN) and total hip (TH) were measured by dual-energy X-ray absorptiometry (DXA). The 10-year probability of fractures was accessed by modified fracture risk algorithm (FRAX) tool. Serum concentrations of sex hormones were measured. Results Sex hormone binding globulin (SHBG) was a determinant of BMDs at L2-4 (β=-0.199, P<0.05), TH (β=-0.233, P<0.05), major osteoporotic fracture (MOF) (β=0.253, P<0.001) and hip fracture (HF) (β=0.262, P<0.001). Per SD increase in SHBG caused a 2% increase in the risk of osteoporosis/osteopenia. SHBG in quartile-4 was associated with 4.21 higher risk of osteoporosis/osteopenia compared with SHBG in quartile-1. Conclusions In postmenopausal women with T2DM, higher serum SHBG tended to be associated with lower BMDs, and increased the risk of osteoporosis/osteopenia and the fracture risk.
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Affiliation(s)
- Yixuan Jing
- Department of Endocrine and Metabolic Diseases, Rui Jin Hospital, Shanghai Jiao-tong University School of Medicine, Shanghai Institute of Endocrine and Metabolic Diseases, Shanghai Clinical Center for Endocrine and Metabolic Diseases, Shanghai 200025, China
| | - Xiaofeng Wang
- Department of Endocrine and Metabolic Diseases, Rui Jin Hospital, Shanghai Jiao-tong University School of Medicine, Shanghai Institute of Endocrine and Metabolic Diseases, Shanghai Clinical Center for Endocrine and Metabolic Diseases, Shanghai 200025, China.,Currently at Tong Ren Hospital, Shanghai Jiao-tong University School of Medicine, Shanghai 200336, China
| | - Jingjia Yu
- Department of Endocrine and Metabolic Diseases, Rui Jin Hospital, Shanghai Jiao-tong University School of Medicine, Shanghai Institute of Endocrine and Metabolic Diseases, Shanghai Clinical Center for Endocrine and Metabolic Diseases, Shanghai 200025, China
| | - Xiaojing Wang
- Department of Endocrine and Metabolic Diseases, Rui Jin Hospital, Shanghai Jiao-tong University School of Medicine, Shanghai Institute of Endocrine and Metabolic Diseases, Shanghai Clinical Center for Endocrine and Metabolic Diseases, Shanghai 200025, China
| | - Yanman Zhou
- Department of Endocrine and Metabolic Diseases, Rui Jin Hospital, Shanghai Jiao-tong University School of Medicine, Shanghai Institute of Endocrine and Metabolic Diseases, Shanghai Clinical Center for Endocrine and Metabolic Diseases, Shanghai 200025, China
| | - Bei Tao
- Department of Endocrine and Metabolic Diseases, Rui Jin Hospital, Shanghai Jiao-tong University School of Medicine, Shanghai Institute of Endocrine and Metabolic Diseases, Shanghai Clinical Center for Endocrine and Metabolic Diseases, Shanghai 200025, China
| | - Lihao Sun
- Department of Endocrine and Metabolic Diseases, Rui Jin Hospital, Shanghai Jiao-tong University School of Medicine, Shanghai Institute of Endocrine and Metabolic Diseases, Shanghai Clinical Center for Endocrine and Metabolic Diseases, Shanghai 200025, China
| | - Jianmin Liu
- Department of Endocrine and Metabolic Diseases, Rui Jin Hospital, Shanghai Jiao-tong University School of Medicine, Shanghai Institute of Endocrine and Metabolic Diseases, Shanghai Clinical Center for Endocrine and Metabolic Diseases, Shanghai 200025, China
| | - Hongyan Zhao
- Department of Endocrine and Metabolic Diseases, Rui Jin Hospital, Shanghai Jiao-tong University School of Medicine, Shanghai Institute of Endocrine and Metabolic Diseases, Shanghai Clinical Center for Endocrine and Metabolic Diseases, Shanghai 200025, China
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28
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Costantini S, Conte C. Bone health in diabetes and prediabetes. World J Diabetes 2019; 10:421-445. [PMID: 31523379 PMCID: PMC6715571 DOI: 10.4239/wjd.v10.i8.421] [Citation(s) in RCA: 56] [Impact Index Per Article: 9.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/06/2019] [Revised: 06/03/2019] [Accepted: 07/20/2019] [Indexed: 02/05/2023] Open
Abstract
Bone fragility has been recognized as a complication of diabetes, both type 1 diabetes (T1D) and type 2 diabetes (T2D), whereas the relationship between prediabetes and fracture risk is less clear. Fractures can deeply impact a diabetic patient's quality of life. However, the mechanisms underlying bone fragility in diabetes are complex and have not been fully elucidated. Patients with T1D generally exhibit low bone mineral density (BMD), although the relatively small reduction in BMD does not entirely explain the increase in fracture risk. On the contrary, patients with T2D or prediabetes have normal or even higher BMD as compared with healthy subjects. These observations suggest that factors other than bone mass may influence fracture risk. Some of these factors have been identified, including disease duration, poor glycemic control, presence of diabetes complications, and certain antidiabetic drugs. Nevertheless, currently available tools for the prediction of risk inadequately capture diabetic patients at increased risk of fracture. Aim of this review is to provide a comprehensive overview of bone health and the mechanisms responsible for increased susceptibility to fracture across the spectrum of glycemic status, spanning from insulin resistance to overt forms of diabetes. The management of bone fragility in diabetic patient is also discussed.
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Affiliation(s)
- Silvia Costantini
- Department of Immunology, Transplantation and Infectious Diseases, Vita-Salute San Raffaele University, Milan 20123, Italy
- Epatocentro Ticino, Lugano 6900, Switzerland
| | - Caterina Conte
- Department of Immunology, Transplantation and Infectious Diseases, Vita-Salute San Raffaele University, Milan 20123, Italy
- IRCCS Ospedale San Raffaele, Internal Medicine and Transplantation, Milan 20123, Italy
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29
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Yeh PS, Lee YW, Chang WH, Wang W, Wang JL, Liu SH, Chen RM. Biomechanical and tomographic differences in the microarchitecture and strength of trabecular and cortical bone in the early stage of male osteoporosis. PLoS One 2019; 14:e0219718. [PMID: 31393911 PMCID: PMC6687113 DOI: 10.1371/journal.pone.0219718] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/18/2019] [Accepted: 06/28/2019] [Indexed: 01/09/2023] Open
Abstract
Osteoporosis is a continuous process of loss of bone tissue. Compared to women, osteoporosis in men is associated with greater morbidity and mortality. In this study, we conducted tomographic and biomechanical evaluations of trabecular and cortical bone in the early stage of male osteoporosis. Male Wistar rats were subjected to orchiectomy and sham operation. Four weeks after being castrated, decreased levels of testosterone in plasma were found and resulted in concurrent bone loss. Separately, the orchiectomy led to significant tomographic alterations in the trabecular bone number, trabecular separation, and trabecular pattern factor. Data of a mechanistic compression test further showed that the orchiectomy diminished the maximum loading force, displacement at maximum load, energy at maximum load, and ultimate stress. Interestingly, orchiectomy-triggered changes in the maximum loading force and tomographic parameters were highly correlated. In contrast, tomographic and biomechanical analyses showed that 4 weeks after rats were orchiectomized, the thickness, area, maximum loading force, bone stiffness, energy at maximum load, and ultimate stress of the cortical bone were not changed. Taken together, this study showed specific differences in the microarchitecture and strength of trabecular bone in the early stage of male osteoporosis.
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Affiliation(s)
- Poh-Shiow Yeh
- Department of Neurology, Chi Mei Medical Center, Tainan, Taiwan
- Graduate Institute of Medical Sciences, College of Medicine, Taipei Medical University, Taipei, Taiwan
| | - Yuan-Wen Lee
- Department of Anesthesiology, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan
- Anesthesiology and Health Policy Research Center and Department of Anesthesiology, Taipei Medical University Hospital, Taipei, Taiwan
| | - Wei-Hui Chang
- Graduate Institute of Medical Sciences, College of Medicine, Taipei Medical University, Taipei, Taiwan
| | - Weu Wang
- Division of General Surgery, Department of Surgery, Taipei Medical University Hospital, Taipei, Taiwan
| | - Jaw-Lin Wang
- Institute of Biomedical Engineering, National Taiwan University, Taipei, Taiwan
| | - Shing-Hwa Liu
- Institute of Toxicology, College of Medicine, National Taiwan University, Taipei, Taiwan
| | - Ruei-Ming Chen
- Graduate Institute of Medical Sciences, College of Medicine, Taipei Medical University, Taipei, Taiwan
- Anesthesiology and Health Policy Research Center and Department of Anesthesiology, Taipei Medical University Hospital, Taipei, Taiwan
- Cell Physiology and Molecular Image Research Center, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan
- * E-mail:
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30
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Chlorpyrifos Exposure Induces Parkinsonian Symptoms and Associated Bone Loss in Adult Swiss Albino Mice. Neurotox Res 2019; 36:700-711. [PMID: 31367921 DOI: 10.1007/s12640-019-00092-0] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/10/2019] [Revised: 07/15/2019] [Accepted: 07/18/2019] [Indexed: 12/14/2022]
Abstract
Prenatal and early life exposure of chlorpyrifos (CPF), a widely used pesticide, is known to cause neuronal deficits and Parkinson's disease (PD). However, data about the effect of its exposure at adult stages on PD-like symptoms and associated bone loss is scanty. In the present study, we investigated the impact of CPF on the behavioral alterations seen in PD using adult Swiss albino mice. PD is often associated with bone loss. Hence, skeletal changes were also evaluated using micro-computed tomography and histology. MPTP was used as a positive control. Cell culture studies using MC3T3E-1, SHSY5Y, and primary osteoclast cultures were done to understand the cellular mechanism for the behavioral and skeletal changes. Our results showed that CPF treatment leads to PD-like symptoms due to the loss of dopaminergic neurons. Moreover, CPF has a deleterious effect on the trabecular bone through both indirect changes in circulating factors and direct stimulation of multinucleate osteoclast cell formation. The impact on the bone mass was even stronger than MPTP. In conclusion, this is the first report demonstrating that CPF induces parkinsonian features in adult Swiss albino mice and it is accompanied by loss of trabecular bone.
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31
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Unwarranted regional variation in vertebroplasty and kyphoplasty in Switzerland: A population-based small area variation analysis. PLoS One 2018; 13:e0208578. [PMID: 30532141 PMCID: PMC6287855 DOI: 10.1371/journal.pone.0208578] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/07/2017] [Accepted: 11/20/2018] [Indexed: 12/30/2022] Open
Abstract
Background Percutaneous vertebroplasty (VP) and balloon kyphoplasty (BKP) for treating painful osteoporotic vertebral fractures are controversial. Objective We assessed the regional variation in the use of VP/BKP in Switzerland. Methods We conducted a population-based small area variation analysis using patient discharge data for VP/BKP from all Swiss hospitals and Swiss census data for calendar years 2012/13. We derived hospital service areas (HSAs) by analyzing patient flows, assigning regions from which most residents were discharged to the same VP/BKP specific HSA. We calculated age-/sex-standardized mean VP/BKP-rates and measures of regional variation (extremal quotient [EQ], systematic component of variation [SCV]). We estimated the reduction in variation of VP/BKP rates using negative binomial regression, with adjustment for patient demographic and regional socioeconomic factors (socioeconomic status, urbanization, and language region). We considered the residual, unexplained variation most likely to be unwarranted. Results Overall, 4955 VP/BKPs were performed in Switzerland in 2012/13. The age-/sex-standardized mean VP/BKP rate was 4.6/10,000 persons and ranged from 1.0 to 10.1 across 26 HSAs. The EQ was 10.2 and the SCV 57.6, indicating a large variation across VP/BKP specific HSAs. After adjustment for demographic and socioeconomic factors, the total reduction in variance was 32.2% only, with the larger part of the variation remaining unexplained. Conclusions We found a 10-fold variation in VP/BKP rates across Swiss VP/BKP specific HSAs. As only one third of the variation was explained by differences in patient demographics and regional socioeconomic factors, VP/BKP in the highest-use areas may, at least partially, represent overtreatment.
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Chen S, Jia L, Zhang S, Zheng Y, Zhou Y. DEPTOR regulates osteogenic differentiation via inhibiting MEG3-mediated activation of BMP4 signaling and is involved in osteoporosis. Stem Cell Res Ther 2018; 9:185. [PMID: 29973283 PMCID: PMC6033203 DOI: 10.1186/s13287-018-0935-9] [Citation(s) in RCA: 46] [Impact Index Per Article: 6.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/13/2018] [Revised: 05/02/2018] [Accepted: 06/18/2018] [Indexed: 02/07/2023] Open
Abstract
Background The mammalian target of rapamycin (mTOR) pathway plays a significant role in osteogenic differentiation and bone maintenance. As the only known endogenous inhibitor of mTOR function, DEP domain containing mTOR interacting protein (DEPTOR) is potentially involved in stem cell differentiation, although the pathophysiological significance and its molecular mechanisms remain unclear. The present study aimed to elucidate the effects of DEPTOR on the progress of osteoporosis and investigate the underlying molecular mechanisms of osteogenic regulation. Methods An ovariectomy mouse model with decreased bone formation and osteogenic induction with bone marrow mesenchymal stem cells (BMSCs) were used to investigate the relationship between DEPTOR and osteogenic events. A loss-of-function investigation was then performed to explore the role of DEPTOR in the osteogenic differentiation of BMSCs both in vitro and in vivo. Finally, long noncoding RNA (lncRNA) and mRNA sequences were investigated to reveal the underlying mechanisms of DEPTOR in osteogenic regulation. RNA interference, western blotting, and chromatin immunoprecipitation assays were performed for further mechanistic determination. Results The results indicated that DEPTOR contributes to the progress of osteoporosis, and higher expression of Deptor was observed in osteoporotic bones. The expression of DEPTOR was reduced during the osteogenic differentiation of BMSCs, and knockdown of DEPTOR promoted BMSC osteogenesis in vitro and in vivo. lncRNA and mRNA sequences indicated that knockdown of DEPTOR upregulated the expression of maternally expressed 3 (nonprotein coding) (MEG3), which subsequently activated bone morphogenetic protein 4 (BMP4) signaling. Furthermore, DEPTOR could bind to a specific region (− 1000 bp ~ 0) of the MEG3 promoter to regulate its transcription, and inhibition of MEG3 reduced BMP4 activation triggered by DEPTOR knockdown. Conclusions Taken together, our study revealed a novel function of DEPTOR in osteogenic differentiation by inhibiting MEG3-mediated activation of BMP4 signaling, which suggested that DEPTOR could be a therapeutic target for bone loss diseases and skeletal tissue regeneration. Electronic supplementary material The online version of this article (10.1186/s13287-018-0935-9) contains supplementary material, which is available to authorized users.
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Affiliation(s)
- Si Chen
- Department of Prosthodontics, Peking University School and Hospital of Stomatology, 22 Zhongguancun South Avenue, Haidian District, Beijing, 100081, China
| | - Lingfei Jia
- Department of Oral and Maxillofacial Surgery, Peking University School and Hospital of Stomatology, 22 Zhongguancun South Avenue, Haidian District, Beijing, 100081, China.,Central Laboratory, Peking University School and Hospital of Stomatology, 22 Zhongguancun South Avenue, Haidian District, Beijing, 100081, China.,National Clinical Research Center for Oral Diseases, 22 Zhongguancun South Avenue, Haidian District, Beijing, 100081, China
| | - Shan Zhang
- Central Laboratory, Peking University School and Hospital of Stomatology, 22 Zhongguancun South Avenue, Haidian District, Beijing, 100081, China
| | - Yunfei Zheng
- Department of Orthodontics, Peking University School and Hospital of Stomatology, 22 Zhongguancun South Avenue, Haidian District, Beijing, 100081, China. .,National Clinical Research Center for Oral Diseases, 22 Zhongguancun South Avenue, Haidian District, Beijing, 100081, China.
| | - Yongsheng Zhou
- Department of Prosthodontics, Peking University School and Hospital of Stomatology, 22 Zhongguancun South Avenue, Haidian District, Beijing, 100081, China. .,National Engineering Lab for Digital and Material Technology of Stomatology, Peking University School and Hospital of Stomatology, 22 Zhongguancun South Avenue, Haidian District, Beijing, 100081, China. .,National Clinical Research Center for Oral Diseases, 22 Zhongguancun South Avenue, Haidian District, Beijing, 100081, China.
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Danila MI, Outman RC, Rahn EJ, Mudano AS, Redden DT, Li P, Allison JJ, Anderson FA, Wyman A, Greenspan SL, LaCroix AZ, Nieves JW, Silverman SL, Siris ES, Watts NB, Miller MJ, Curtis JR, Warriner AH, Wright NC, Saag KG. Evaluation of a Multimodal, Direct-to-Patient Educational Intervention Targeting Barriers to Osteoporosis Care: A Randomized Clinical Trial. J Bone Miner Res 2018; 33:763-772. [PMID: 29377378 PMCID: PMC6016546 DOI: 10.1002/jbmr.3395] [Citation(s) in RCA: 23] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/20/2017] [Revised: 12/14/2017] [Accepted: 01/10/2018] [Indexed: 11/06/2022]
Abstract
Osteoporosis treatment rates are declining, even among those with past fractures. Novel, low-cost approaches are needed to improve osteoporosis care. We conducted a parallel group, controlled, randomized clinical trial evaluating a behavioral intervention for improving osteoporosis medication use. A total of 2684 women with self-reported fracture history after age 45 years not using osteoporosis therapy from US Global Longitudinal Study of Osteoporosis in Women (GLOW) sites were randomized 1:1 to receive a multimodal, tailored, direct-to-patient, video intervention versus usual care. The primary study outcome was self-report of osteoporosis medication use at 6 months. Other outcomes included calcium and vitamin D supplementation, bone mineral density (BMD) testing, readiness for behavioral change, and barriers to treatment. In intent-to-treat analyses, there were no significant differences between groups (intervention versus control) in osteoporosis medication use (11.7% versus 11.4%, p = 0.8), calcium supplementation (31.8% versus 32.6%, p = 0.7), vitamin D intake (41.3% versus 41.9%, p = 0.8), or BMD testing (61.8% versus 57.1%, p = 0.2). In the intervention group, fewer women were in the precontemplative stage of behavior change, more women reported seeing their primary care provider, had concerns regarding osteonecrosis of the jaw, and difficulty in taking/remembering to take osteoporosis medications. We found differences in BMD testing among the subgroup of women with no prior osteoporosis treatment, those who provided contact information, and those with no past BMD testing. In per protocol analyses, women with appreciable exposure to the online intervention (n = 257) were more likely to start nonbisphosphonates (odds ratio [OR] = 2.70; 95% confidence interval [CI] 1.26-5.79) compared with the usual care group. Although our intervention did not increase the use of osteoporosis therapy at 6 months, it increased nonbisphosphonate medication use and BMD testing in select subgroups, shifted participants' readiness for behavior change, and altered perceptions of barriers to osteoporosis treatment. Achieving changes in osteoporosis care using patient activation approaches alone is challenging. © 2018 American Society for Bone and Mineral Research.
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Affiliation(s)
- Maria I Danila
- University of Alabama at Birmingham, Birmingham, AL, USA
| | - Ryan C Outman
- University of Alabama at Birmingham, Birmingham, AL, USA
| | | | - Amy S Mudano
- University of Alabama at Birmingham, Birmingham, AL, USA
| | - David T Redden
- University of Alabama at Birmingham, Birmingham, AL, USA
| | - Peng Li
- University of Alabama at Birmingham, Birmingham, AL, USA
| | | | - Fred A Anderson
- University of Massachusetts Medical School, Worcester, MA, USA
| | - Allison Wyman
- University of Massachusetts Medical School, Worcester, MA, USA
| | | | - Andrea Z LaCroix
- Group Health Cooperative, Seattle, WA, USA.,University of California San Diego, La Jolla, CA, USA
| | | | | | - Ethel S Siris
- Columbia University Medical Center, New York, NY, USA
| | - Nelson B Watts
- Mercy Health Osteoporosis and Bone Health Services, Cincinnati, OH, USA
| | - Michael J Miller
- Department of Pharmaceutical Sciences, Irma Lerma Rangel College of Pharmacy, Texas A&M University, College Station, TX, USA
| | | | - Amy H Warriner
- University of Alabama at Birmingham, Birmingham, AL, USA
| | | | - Kenneth G Saag
- University of Alabama at Birmingham, Birmingham, AL, USA
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Paine A, Woeller CF, Zhang H, de la Luz Garcia-Hernandez M, Huertas N, Xing L, Phipps RP, Ritchlin CT. Thy1 is a positive regulator of osteoblast differentiation and modulates bone homeostasis in obese mice. FASEB J 2018; 32:3174-3183. [PMID: 29401595 DOI: 10.1096/fj.201701379r] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/14/2023]
Abstract
Thy1 (CD90), a glycosylated, glycophosphatidylinositol-anchored membrane protein highly expressed by subsets of mesenchymal stem cells and fibroblasts, inhibits adipogenesis. The role of Thy1 on bone structure and function has been poorly studied and represents a major knowledge gap. Therefore, we analyzed the long bones of wild-type (WT) and Thy1 knockout (KO) mice with micro-computed tomography (micro-CT) and histomorphometry to compare changes in bone architecture and overall bone structure. micro-CT analysis of long bones revealed Thy1 KO and WT mice fed a high-fat diet demonstrated bone structural parameters at 4 mo that differed significantly between WT and KO mice. A significant reduction in trabecular bone volume was noted in Thy1 KO mice. The most prominent differences were observed in trabecular bone volume ratio and trabecular bone connectivity density. Consistent with micro-CT measurements, histomorphometric analysis also showed decreased bone volume in the obese Thy1 KO mice compared to obese WT mice. In vitro assays revealed that osteogenic conditions increased Thy1 expression during OB differentiation and absence of Thy1 attenuated osteoblastogenesis. Together, these findings support the concept that Thy1 serves as a major mechanistic link to regulate bone formation and negatively regulate adipogenesis.-Paine, A., Woeller, C. F., Zhang, H., Garcia-Hernandez, M. L., Huertas, N., Xing, L., Phipps, R. P., Ritchlin, C. T. Thy1 is a positive regulator of osteoblast differentiation and modulates bone homeostasis in obese mice.
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Affiliation(s)
- Ananta Paine
- Division of Allergy, Immunology, and Rheumatology, School of Medicine and Dentistry, University of Rochester, Rochester, New York, USA
| | - Collynn F Woeller
- Department of Environmental Medicine, School of Medicine and Dentistry, University of Rochester, Rochester, New York, USA
| | - Hengwei Zhang
- Center for Musculoskeletal Research, University of Rochester Medical Center, University of Rochester, Rochester, New York, USA; and.,Department of Pathology and Laboratory Medicine, School of Medicine and Dentistry, University of Rochester, Rochester, New York, USA
| | - Maria de la Luz Garcia-Hernandez
- Division of Allergy, Immunology, and Rheumatology, School of Medicine and Dentistry, University of Rochester, Rochester, New York, USA
| | - Nelson Huertas
- Division of Allergy, Immunology, and Rheumatology, School of Medicine and Dentistry, University of Rochester, Rochester, New York, USA
| | - Lianping Xing
- Center for Musculoskeletal Research, University of Rochester Medical Center, University of Rochester, Rochester, New York, USA; and.,Department of Pathology and Laboratory Medicine, School of Medicine and Dentistry, University of Rochester, Rochester, New York, USA
| | - Richard P Phipps
- Department of Environmental Medicine, School of Medicine and Dentistry, University of Rochester, Rochester, New York, USA
| | - Christopher T Ritchlin
- Division of Allergy, Immunology, and Rheumatology, School of Medicine and Dentistry, University of Rochester, Rochester, New York, USA
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Francesco L, Elisa B, Raffaella M, Alessandro P, Iacopo C, Giampiero M, Bruno F, Daniel PA, Luisa BM, Claudio C. Assessing Risk of Osteoporotic Fractures in Primary Care: Development and Validation of the FRA-HS Algorithm. Calcif Tissue Int 2017; 100:537-549. [PMID: 28160026 DOI: 10.1007/s00223-016-0230-7] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/07/2016] [Accepted: 12/26/2016] [Indexed: 12/19/2022]
Abstract
We aimed to develop and validate the FRActure Health Search (FRA-HS) score for prediction of risk of osteoporotic fractures in primary care in Italy. We selected a cohort of patients aged 40 years between 1999 and 2002. They were followed until the occurrence of osteoporotic fracture, death, end of data registration, or end of data availability (December 31, 2012). Age, sex, history of osteoporotic fractures, secondary osteoporosis, long-term use of corticosteroids, rheumatoid arthritis, body mass index, smoking, and alcohol abuse/alcohol-related diseases, and the interaction terms sex*use of corticosteroids and age*secondary osteoporosis were entered in a competing-risk regression (Fine and Gray method) to predict the risk of hip/femur or overall major osteoporotic fractures. The coefficients were combined to obtain the FRA-HS for individual patients. Explained variance, discrimination, and calibration measures were computed to evaluate the models accuracy. The final model was tested using an independent data source. The FRA-HS explained 47.36 and 20.6% of the variation for occurrence of hip/femur and overall major osteoporotic fractures, respectively. Area Under Curve was 0.77 and 0.73, respectively. Predicted/observed ratios revealed a margin of error lower than 30% in the 80% of the population. After stratifying by sex, prediction models for hip/femur fractures confirmed acceptable accuracy in both sexes, while poor explained variance (<20%) was observed for overall major fractures. These findings indicate that FRA-HS might be implemented in primary care for risk prediction of hip/femur fractures. General practitioners could be therefore supported by this tool in clinical decision making.
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Affiliation(s)
- Lapi Francesco
- Health Search, Italian College of General Practitioners and Primary Care, Via Sestese 61, 50141, Florence, Italy.
| | - Bianchini Elisa
- Health Search, Italian College of General Practitioners and Primary Care, Via Sestese 61, 50141, Florence, Italy
| | - Michieli Raffaella
- Italian College of General Practitioners and Primary Care, Florence, Italy
| | - Pasqua Alessandro
- Health Search, Italian College of General Practitioners and Primary Care, Via Sestese 61, 50141, Florence, Italy
| | - Cricelli Iacopo
- Health Search, Italian College of General Practitioners and Primary Care, Via Sestese 61, 50141, Florence, Italy
| | - Mazzaglia Giampiero
- Health Search, Italian College of General Practitioners and Primary Care, Via Sestese 61, 50141, Florence, Italy
| | - Frediani Bruno
- Department of Rheumatology, Policlinico Le Scotte, University of Siena, Siena, Italy
| | - Prieto-Alhambra Daniel
- Oxford NIHR Musculoskeletal Biomedical Research Unit, Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, Oxford, UK
- GREMPAL Research Group, Institut Universitari d'Investigació en Atenció Primària Jordi Gol (IDIAP Jordi Gol), Universitat Autònoma de Barcelona, Barcelona, Spain
| | - Brandi Maria Luisa
- Metabolic Bone Diseases Unit, Department of Surgery and Translational Medicine, University of Florence, Florence, Italy
| | - Cricelli Claudio
- Italian College of General Practitioners and Primary Care, Florence, Italy
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Lorbergs AL, Noseworthy MD, MacIntyre NJ. Magnetic Resonance Imaging and Spectroscopy to Assess Leg Muscle Macrostructure and Microstructure in Healthy Older Women: A Feasibility Assessment. J Med Imaging Radiat Sci 2017; 48:43-54. [PMID: 31047210 DOI: 10.1016/j.jmir.2016.09.004] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/24/2015] [Revised: 08/25/2016] [Accepted: 09/22/2016] [Indexed: 11/27/2022]
Abstract
BACKGROUND Advanced magnetic resonance (MR) scanning techniques, such as diffusion tensor imaging (DTI) and proton MR spectroscopy (1H-MRS) permit microstructural evaluation of water diffusivity and intramyocellular lipid content, respectively. We aimed to determine the feasibility of performing advanced MR scanning (proton density [PD] weighted imaging, DTI, and 1H-MRS) to evaluate properties of leg muscles in older women with respect to: (1) participant recruitment using three community-based strategies; (2) participant tolerance to the MRI scan acquisition protocol; and (3) scan acquisition and analyses protocols. METHODS Recruitment feasibility was evaluated based on the number of participants enrolled using various strategies. Participant tolerance was feasible if the scanning session was uninterrupted and image artifacts were absent. Optimal PD imaging, DTI, and 1H-MRS acquisition and analyses protocols were established. RESULTS Nine women (mean age = 71 years) were recruited over four months. The acquisition protocol was well tolerated by all participants. Adaptations were required for women with short stature and vertebral fracture risk. PD-weighted image analyses were improved by using the phased array uniformity enhancement filter to increase tissue contrast. CONCLUSIONS It is feasible to use a combination of MR scanning methods to evaluate muscle macrostructure and microstructure in the leg of older women. Our findings suggest that advanced MR scanning methods can be used for future studies interested in quantifying components of muscle structure in older women, but prospective studies are needed to confirm whether change in microstructure can be detected in response to an intervention.
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Affiliation(s)
- Amanda L Lorbergs
- Institute for Aging Research, Hebrew SeniorLife and Harvard Medical School, Boston, Massachusetts, USA; School of Rehabilitation Science, McMaster University, Hamilton, Ontario, Canada
| | - Michael D Noseworthy
- Department of Electrical and Computer Engineering, McMaster University, Hamilton, Ontario, Canada; School of Biomedical Engineering, McMaster University, Hamilton, Ontario, Canada
| | - Norma J MacIntyre
- School of Rehabilitation Science, McMaster University, Hamilton, Ontario, Canada.
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Almeida M, Laurent MR, Dubois V, Claessens F, O'Brien CA, Bouillon R, Vanderschueren D, Manolagas SC. Estrogens and Androgens in Skeletal Physiology and Pathophysiology. Physiol Rev 2017; 97:135-187. [PMID: 27807202 PMCID: PMC5539371 DOI: 10.1152/physrev.00033.2015] [Citation(s) in RCA: 548] [Impact Index Per Article: 68.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/25/2022] Open
Abstract
Estrogens and androgens influence the growth and maintenance of the mammalian skeleton and are responsible for its sexual dimorphism. Estrogen deficiency at menopause or loss of both estrogens and androgens in elderly men contribute to the development of osteoporosis, one of the most common and impactful metabolic diseases of old age. In the last 20 years, basic and clinical research advances, genetic insights from humans and rodents, and newer imaging technologies have changed considerably the landscape of our understanding of bone biology as well as the relationship between sex steroids and the physiology and pathophysiology of bone metabolism. Together with the appreciation of the side effects of estrogen-related therapies on breast cancer and cardiovascular diseases, these advances have also drastically altered the treatment of osteoporosis. In this article, we provide a comprehensive review of the molecular and cellular mechanisms of action of estrogens and androgens on bone, their influences on skeletal homeostasis during growth and adulthood, the pathogenetic mechanisms of the adverse effects of their deficiency on the female and male skeleton, as well as the role of natural and synthetic estrogenic or androgenic compounds in the pharmacotherapy of osteoporosis. We highlight latest advances on the crosstalk between hormonal and mechanical signals, the relevance of the antioxidant properties of estrogens and androgens, the difference of their cellular targets in different bone envelopes, the role of estrogen deficiency in male osteoporosis, and the contribution of estrogen or androgen deficiency to the monomorphic effects of aging on skeletal involution.
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Affiliation(s)
- Maria Almeida
- Division of Endocrinology and Metabolism, Center for Osteoporosis and Metabolic Bone Diseases, University of Arkansas for Medical Sciences and the Central Arkansas Veterans Healthcare System, Little Rock, Arkansas; Departments of Cellular and Molecular Medicine and Clinical and Experimental Medicine, KU Leuven, Leuven, Belgium; Center for Metabolic Bone Diseases, University Hospitals Leuven, Leuven, Belgium; and Institut National de la Santé et de la Recherche Médicale UMR1011, University of Lille and Institut Pasteur de Lille, Lille, France
| | - Michaël R Laurent
- Division of Endocrinology and Metabolism, Center for Osteoporosis and Metabolic Bone Diseases, University of Arkansas for Medical Sciences and the Central Arkansas Veterans Healthcare System, Little Rock, Arkansas; Departments of Cellular and Molecular Medicine and Clinical and Experimental Medicine, KU Leuven, Leuven, Belgium; Center for Metabolic Bone Diseases, University Hospitals Leuven, Leuven, Belgium; and Institut National de la Santé et de la Recherche Médicale UMR1011, University of Lille and Institut Pasteur de Lille, Lille, France
| | - Vanessa Dubois
- Division of Endocrinology and Metabolism, Center for Osteoporosis and Metabolic Bone Diseases, University of Arkansas for Medical Sciences and the Central Arkansas Veterans Healthcare System, Little Rock, Arkansas; Departments of Cellular and Molecular Medicine and Clinical and Experimental Medicine, KU Leuven, Leuven, Belgium; Center for Metabolic Bone Diseases, University Hospitals Leuven, Leuven, Belgium; and Institut National de la Santé et de la Recherche Médicale UMR1011, University of Lille and Institut Pasteur de Lille, Lille, France
| | - Frank Claessens
- Division of Endocrinology and Metabolism, Center for Osteoporosis and Metabolic Bone Diseases, University of Arkansas for Medical Sciences and the Central Arkansas Veterans Healthcare System, Little Rock, Arkansas; Departments of Cellular and Molecular Medicine and Clinical and Experimental Medicine, KU Leuven, Leuven, Belgium; Center for Metabolic Bone Diseases, University Hospitals Leuven, Leuven, Belgium; and Institut National de la Santé et de la Recherche Médicale UMR1011, University of Lille and Institut Pasteur de Lille, Lille, France
| | - Charles A O'Brien
- Division of Endocrinology and Metabolism, Center for Osteoporosis and Metabolic Bone Diseases, University of Arkansas for Medical Sciences and the Central Arkansas Veterans Healthcare System, Little Rock, Arkansas; Departments of Cellular and Molecular Medicine and Clinical and Experimental Medicine, KU Leuven, Leuven, Belgium; Center for Metabolic Bone Diseases, University Hospitals Leuven, Leuven, Belgium; and Institut National de la Santé et de la Recherche Médicale UMR1011, University of Lille and Institut Pasteur de Lille, Lille, France
| | - Roger Bouillon
- Division of Endocrinology and Metabolism, Center for Osteoporosis and Metabolic Bone Diseases, University of Arkansas for Medical Sciences and the Central Arkansas Veterans Healthcare System, Little Rock, Arkansas; Departments of Cellular and Molecular Medicine and Clinical and Experimental Medicine, KU Leuven, Leuven, Belgium; Center for Metabolic Bone Diseases, University Hospitals Leuven, Leuven, Belgium; and Institut National de la Santé et de la Recherche Médicale UMR1011, University of Lille and Institut Pasteur de Lille, Lille, France
| | - Dirk Vanderschueren
- Division of Endocrinology and Metabolism, Center for Osteoporosis and Metabolic Bone Diseases, University of Arkansas for Medical Sciences and the Central Arkansas Veterans Healthcare System, Little Rock, Arkansas; Departments of Cellular and Molecular Medicine and Clinical and Experimental Medicine, KU Leuven, Leuven, Belgium; Center for Metabolic Bone Diseases, University Hospitals Leuven, Leuven, Belgium; and Institut National de la Santé et de la Recherche Médicale UMR1011, University of Lille and Institut Pasteur de Lille, Lille, France
| | - Stavros C Manolagas
- Division of Endocrinology and Metabolism, Center for Osteoporosis and Metabolic Bone Diseases, University of Arkansas for Medical Sciences and the Central Arkansas Veterans Healthcare System, Little Rock, Arkansas; Departments of Cellular and Molecular Medicine and Clinical and Experimental Medicine, KU Leuven, Leuven, Belgium; Center for Metabolic Bone Diseases, University Hospitals Leuven, Leuven, Belgium; and Institut National de la Santé et de la Recherche Médicale UMR1011, University of Lille and Institut Pasteur de Lille, Lille, France
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Danila MI, Outman RC, Rahn EJ, Mudano AS, Thomas TF, Redden DT, Allison JJ, Anderson FA, Anderson JP, Cram PM, Curtis JR, Fraenkel L, Greenspan SL, LaCroix AZ, Majumdar SR, Miller MJ, Nieves JW, Safford MM, Silverman SL, Siris ES, Solomon DH, Warriner AH, Watts NB, Yood RA, Saag KG. A multi-modal intervention for Activating Patients at Risk for Osteoporosis (APROPOS): Rationale, design, and uptake of online study intervention material. Contemp Clin Trials Commun 2016; 4:14-24. [PMID: 27453960 PMCID: PMC4955389 DOI: 10.1016/j.conctc.2016.06.010] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/11/2016] [Revised: 06/09/2016] [Accepted: 06/22/2016] [Indexed: 02/04/2023] Open
Abstract
OBJECTIVE To develop an innovative and effective educational intervention to inform patients about the need for osteoporosis treatment and to determine factors associated with its online uptake. METHODS Postmenopausal women with a prior fracture and not currently using osteoporosis therapy were eligible to be included in the Activating Patients at Risk for OsteoPOroSis (APROPOS). Four nominal groups with a total of 18 racially/ethnically diverse women identified osteoporosis treatment barriers. We used the Information, Motivation, Behavior Skills conceptual model to develop a direct-to-patient intervention to mitigate potentially modifiable barriers to osteoporosis therapy. The intervention included videos tailored by participants' race/ethnicity and their survey responses: ranked barriers to osteoporosis treatment, deduced barriers to treatment, readiness to behavior change, and osteoporosis treatment history. Videos consisted of "storytelling" narratives, based on osteoporosis patient experiences and portrayed by actresses of patient-identified race/ethnicity. We also delivered personalized brief phone calls followed by an interactive voice-response phone messages aimed to promote uptake of the videos. RESULTS To address the factors associated with online intervention uptake, we focused on participants assigned to the intervention arm (n = 1342). These participants were 92.9% Caucasian, with a mean (SD) age 74.9 (8.0) years and the majority (77.7%) had some college education. Preference for natural treatments was the barrier ranked #1 by most (n = 130; 27%), while concern about osteonecrosis of the jaw was the most frequently reported barrier (at any level; n = 322; 67%). Overall, 28.1% (n = 377) of participants in the intervention group accessed the videos online. After adjusting for relevant covariates, the participants who provided an email address had 6.07 (95% CI 4.53-8.14) higher adjusted odds of accessing their online videos compared to those who did not. CONCLUSION We developed and implemented a novel tailored multi-modal intervention to improve initiation of osteoporosis therapy. An email address provided on the survey was the most important factor independently associated with accessing the intervention online. The design and uptake of this intervention may have implications for future studies in osteoporosis or other chronic diseases.
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Affiliation(s)
| | - Ryan C. Outman
- University of Alabama at Birmingham, Birmingham, AL, USA
| | | | - Amy S. Mudano
- University of Alabama at Birmingham, Birmingham, AL, USA
| | | | | | - Jeroan J. Allison
- University of Massachusetts Medical School, Worcester, MA 01655, USA
| | - Fred A. Anderson
- University of Massachusetts Medical School, Worcester, MA 01655, USA
| | | | | | | | | | | | - Andrea Z. LaCroix
- Group Health Cooperative, Seattle, WA 98112, USA
- University of California San Diego, La Jolla, CA 92093, USA
| | | | - Michael J. Miller
- The University of Oklahoma Health Sciences Center, Tulsa, OK 74135, USA
| | | | - Monika M. Safford
- University of Alabama at Birmingham, Birmingham, AL, USA
- Weill Cornell Medical Center, New York, NY 10065, USA
| | | | - Ethel S. Siris
- Columbia University Medical Center, New York, NY 10032, USA
| | | | | | - Nelson B. Watts
- Mercy Health Osteoporosis and Bone Health Services, Cincinnati, OH 45236, USA
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Binks S, Dobson R. Risk Factors, Epidemiology and Treatment Strategies for Metabolic Bone Disease in Patients with Neurological Disease. Curr Osteoporos Rep 2016; 14:199-210. [PMID: 27525980 DOI: 10.1007/s11914-016-0320-5] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Abstract
Metabolic bone disease is a major public health concern, especially when it manifests as hip fracture which carries significant morbidity and mortality. Individuals with neurological disease are at higher risk of osteopenia, osteoporosis and fragility fracture compared to age-matched controls, yet this is under-appreciated by these patients. Clinician attention to this topic is therefore of importance and should address the bone health of men as well as women, a group in whom it may be an under-recognised problem. Evidence for optimal management of bone health in neurological disease remains to be defined, but a growing literature provides some useful guidance. This review focuses on two conditions, multiple sclerosis and Parkinson's disease, where research has been active over recent years. In neuroinflammation, shared immunological pathways between bone and brain are a current domain of interest and it will be intriguing to interrogate the action of emerging immunotherapies on these dual compartments.
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Affiliation(s)
- S Binks
- Nuffield Department of Clinical Neurosciences, John Radcliffe Hospital, University of Oxford, Oxford, OX3 9DU, UK
| | - R Dobson
- Blizard Institute, Queen Mary University, 4 Newark St, London, E1 2AT, UK.
- St Georges Hospital, Blackshaw Rd, London, SW17 0QT, UK.
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Ding Q, Zhou H, Yun B, Zhou L, Zhang N, Yin G, Fan J. Interleukin-13 Inhibits Expression of cyp27b1 in Peripheral CD14+ Cells That Is Correlated With Vertebral Bone Mineral Density of Patients With Ulcerative Colitis. J Cell Biochem 2016; 118:376-381. [PMID: 27381199 DOI: 10.1002/jcb.25646] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/06/2016] [Accepted: 07/05/2016] [Indexed: 12/19/2022]
Abstract
Osteoporosis is a common problem in aged people and those with related diseases, such as inflammatory bowel diseases. Deregulation of vitamin D metabolism plays a role in the pathogenesis of osteoporosis. Micro RNA (miR) can regulate cytokine expression in cells. This study test a hypothesis that inflammatory cytokine interleukin (IL)-13 increases miR-19a to compromise cyp27b1 (a vitamin D hydroxylase) in peripheral CD14+ cells. Bone mineral density of L2-L4 was measured in 20 patients with ulcerative colitis (UC) and 20 healthy subjects. Peripheral CD14+ cells were isolated from healthy people and patients with UC. Expression of cyp27b1 by CD14+ cells was analyzed in the presence or absence of IL-13 in the culture. We observed that bone mineral density (BMD) in UC patients was significantly lower than healthy subjects. The BMD is negatively correlated with miR-19a in peripheral CD14+ cells. MiR-19a in peripheral CD14+ cell was correlated with serum IL-13 in UC patients. Expression of cyp27b1 in peripheral CD14+ cells was correlated with miR-19a and serum IL-13 in UC patients. IL-13 suppressed cyp27b1 expression in CD14+ cells. IL-13 increased expression of miR-19a in CD14+ cells. IL-13 suppresses cyp27b1 expression in peripheral CD14+ cells via up regulating miR-19a expression. J. Cell. Biochem. 118: 376-381, 2017. © 2016 Wiley Periodicals, Inc.
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Affiliation(s)
- Qingfeng Ding
- Orthopaedic Department, The First Affiliated Hospital of Nanjing Medical University, Jiangsu, China
| | - Hao Zhou
- Emergency Department, The First Affiliated Hospital of Nanjing Medical University, Jiangsu, China
| | - Bo Yun
- Orthopaedic Department, The First Affiliated Hospital of Nanjing Medical University, Jiangsu, China
| | - Lingjie Zhou
- Orthopaedic Department, The First Affiliated Hospital of Nanjing Medical University, Jiangsu, China
| | - Ning Zhang
- Orthopaedic Department, The First Affiliated Hospital of Nanjing Medical University, Jiangsu, China
| | - Guoyong Yin
- Orthopaedic Department, The First Affiliated Hospital of Nanjing Medical University, Jiangsu, China
| | - Jin Fan
- Orthopaedic Department, The First Affiliated Hospital of Nanjing Medical University, Jiangsu, China
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BMI and BMD: The Potential Interplay between Obesity and Bone Fragility. INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH 2016; 13:ijerph13060544. [PMID: 27240395 PMCID: PMC4924001 DOI: 10.3390/ijerph13060544] [Citation(s) in RCA: 139] [Impact Index Per Article: 15.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 03/27/2016] [Revised: 05/12/2016] [Accepted: 05/19/2016] [Indexed: 01/05/2023]
Abstract
Recent evidence demonstrating an increased fracture risk among obese individuals suggests that adipose tissue may negatively impact bone health, challenging the traditional paradigm of fat mass playing a protective role towards bone health. White adipose tissue, far from being a mere energy depot, is a dynamic tissue actively implicated in metabolic reactions, and in fact secretes several hormones called adipokines and inflammatory factors that may in turn promote bone resorption. More specifically, Visceral Adipose Tissue (VAT) may potentially prove detrimental. It is widely acknowledged that obesity is positively associated to many chronic disorders such as metabolic syndrome, dyslipidemia and type 2 diabetes, conditions that could themselves affect bone health. Although aging is largely known to decrease bone strength, little is yet known on the mechanisms via which obesity and its comorbidities may contribute to such damage. Given the exponentially growing obesity rate in recent years and the increased life expectancy of western countries it appears of utmost importance to timely focus on this topic.
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Tarride JE, Burke N, Leslie WD, Morin SN, Adachi JD, Papaioannou A, Bessette L, Brown JP, Pericleous L, Muratov S, Hopkins RB. Loss of health related quality of life following low-trauma fractures in the elderly. BMC Geriatr 2016; 16:84. [PMID: 27093957 PMCID: PMC4837505 DOI: 10.1186/s12877-016-0259-5] [Citation(s) in RCA: 50] [Impact Index Per Article: 5.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/17/2015] [Accepted: 04/13/2016] [Indexed: 12/05/2022] Open
Abstract
BACKGROUND To estimate the long-term change in health related quality of life (HRQoL) following low-trauma fractures among individuals receiving home care (HC) services or living in long-term care (LTC) facilities using linked healthcare administrative data from Ontario, Canada. METHODS HRQoL was estimated using the Health Utility Index (HUI-2) with the InterRai Minimum Data Set (MDS), a mandatory questionnaire for LTC and HC in the province of Ontario (population 14 million). The HUI-2, a validated HRQoL instrument, allows the calculation of health utility where 0 represents death and 1 the best imaginable health state. For reference, the HUI-2 utility value for Canadians aged 80-84 years is 0.61 and the minimal clinically important difference is 0.03. The MDS was linked to Ontario acute care databases for fiscal years 2007-2011 to identify low-trauma fractures using ICD-10-CA codes. Regression models were used to identify predictors of change in HRQoL from pre-fracture levels to 3 years post fracture for several populations. Low-trauma fractures included hip, humerus, vertebral, wrist, multiple and other. RESULTS Twenty-three thousand six-hundred fifty-five unique patients with low-trauma fractures were identified with pre- and post-fracture HRQoL assessments, of which 5057 individuals had at least 3 years of follow-up. Compared to patients receiving HC services (N = 3303), individuals residing in LTC (N = 1754) were older, taking more medications, and had more comorbidities. LTC patients had more hip fractures (49 % of total versus 29 %). For all fracture types, HRQoL decreased immediately following fracture. Although levels rebounded after the first month, HRQoL up to 36 months never returned to pre-fracture levels even for non-hip fracture. For both HC and LTC cohorts, clinically important and statistically significant decreases in HUI-2 utility scores were observed 36 months post fracture. Of the 6 HUI-2 domains, mobility had the largest impact on change in HRQoL. Regression analysis indicated that living with a musculoskeletal disorder or a neurological condition and living in LTC were associated with greater decrements in utility following a fracture. CONCLUSIONS Based on the analysis of one of the largest studies on HRQoL to date, among individuals living in LTC facilities or receiving HC services, fractures have a significant permanent impact on HRQoL up to 3 years following fracture.
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Affiliation(s)
- Jean-Eric Tarride
- />Programs for Assessment of Technology in Health (PATH), St. Joseph’s Healthcare Hamilton, 25 Main Street West, Suite 2000, Hamilton, ON L8P 1H1 Canada
- />Department of Clinical Epidemiology and Biostatistics, McMaster University, Hamilton, Ontario Canada
| | - Natasha Burke
- />Programs for Assessment of Technology in Health (PATH), St. Joseph’s Healthcare Hamilton, 25 Main Street West, Suite 2000, Hamilton, ON L8P 1H1 Canada
- />Department of Clinical Epidemiology and Biostatistics, McMaster University, Hamilton, Ontario Canada
| | - William D. Leslie
- />Department of Medicine, University of Manitoba, Winnipeg, Manitoba Canada
| | - Suzanne N. Morin
- />Department of Medicine, McGill University, Montréal, Quebec Canada
| | | | - Alexandra Papaioannou
- />Department of Clinical Epidemiology and Biostatistics, McMaster University, Hamilton, Ontario Canada
- />Department of Medicine, McMaster University, Hamilton, Ontario Canada
| | - Louis Bessette
- />Department of Medicine, Laval University, Quebec City, Quebec Canada
| | - Jacques P. Brown
- />Department of Medicine, Laval University, Quebec City, Quebec Canada
| | | | - Sergei Muratov
- />Programs for Assessment of Technology in Health (PATH), St. Joseph’s Healthcare Hamilton, 25 Main Street West, Suite 2000, Hamilton, ON L8P 1H1 Canada
- />Department of Clinical Epidemiology and Biostatistics, McMaster University, Hamilton, Ontario Canada
| | - Robert B. Hopkins
- />Programs for Assessment of Technology in Health (PATH), St. Joseph’s Healthcare Hamilton, 25 Main Street West, Suite 2000, Hamilton, ON L8P 1H1 Canada
- />Department of Clinical Epidemiology and Biostatistics, McMaster University, Hamilton, Ontario Canada
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Hull B, Smith NR. Diabetes and Bone. Am J Med Sci 2016; 351:356-60. [DOI: 10.1016/j.amjms.2016.02.010] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/18/2015] [Revised: 02/01/2016] [Accepted: 02/05/2016] [Indexed: 12/30/2022]
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Maravic M, Ostertag A, Urena P, Cohen-Solal M. Dementia is a major risk factor for hip fractures in patients with chronic kidney disease. Osteoporos Int 2016; 27:1665-1669. [PMID: 26588907 DOI: 10.1007/s00198-015-3429-y] [Citation(s) in RCA: 25] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/17/2015] [Accepted: 11/13/2015] [Indexed: 11/25/2022]
Abstract
UNLABELLED Chronic kidney disease increases the risk of hip fractures which can be promoted by dementia. We here showed that dementia increased the risk of hip fractures in dialysis patients, but in a similar manner than without dialysis. Attention should be paid to dementia to prevent hip fractures. INTRODUCTION Hip fractures (HF) are associated with significant morbidity and is further increased in patients with chronic kidney disease (CKD). Dementia, frequent in CKD, might be a risk factor for HF. We here aimed to assess if dementia increased the risk of hip fracture in CKD. METHODS The study was derived from the French National Database of Hospitalization. Data were obtained over the period 2011-2013. Three populations of subjects >60 years were extracted. Hip fractures, dialysis, and dementia were the main studied factors. The three populations were crossed to estimate the fracture risk based on dementia or dialysis, adjusted for age and gender. The fracture risk was calculated using a multiple logistic regression model. RESULTS Over this period, 213,180 patients experienced a HF, 660,434 patients were diagnosed for dementia, and 47,430 patients were on dialysis. There was an effect of age and gender on the incidence of HF and dementia. In CKD patients, the risk of HF was significantly higher in demented patients compared to those without dementia: OR 2.0 [95 % CI 1.7-2.4], this being the same for men (OR 2.4 [1.8-3.1]) and women (OR 2.6 [2.0-3.3]) and at any age. However, the adjusted risk for HF in demented patients on dialysis therapy is not different than in demented patients without CKD (OR 1.3 [1.0-1.6]). CONCLUSIONS Dementia significantly increases the risk of HF in patients on dialysis, but this risk in demented patients is equally high whether receiving dialysis therapy or not. These results highlight dementia as a major risk factor for HF in dialysis and indicate that reduction of fracture risk should include dementia as a risk factor.
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Affiliation(s)
- M Maravic
- Department of Rheumatology, Lariboisière Hospital, Paris, France
| | - A Ostertag
- Inserm U1132 and University Paris-Diderot, Department of Rheumatology, Lariboisière Hospital, 2 rue Ambroise Paré, 75010, Paris, France
| | - P Urena
- Department of Dialysis, Clinique du Landy, Saint-Ouen, France
- Department of Renal Physiology, Necker Hospital, University of Paris Descartes, Paris, France
| | - M Cohen-Solal
- Inserm U1132 and University Paris-Diderot, Department of Rheumatology, Lariboisière Hospital, 2 rue Ambroise Paré, 75010, Paris, France.
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Dostal AM, Arikawa A, Espejo L, Kurzer MS. Long-Term Supplementation of Green Tea Extract Does Not Modify Adiposity or Bone Mineral Density in a Randomized Trial of Overweight and Obese Postmenopausal Women. J Nutr 2016; 146:256-64. [PMID: 26701796 PMCID: PMC4725430 DOI: 10.3945/jn.115.219238] [Citation(s) in RCA: 54] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/22/2015] [Accepted: 11/17/2015] [Indexed: 12/31/2022] Open
Abstract
BACKGROUND Green tea extract (GTE) consumption has been linked to favorable changes in adiposity and bone mineral density (BMD), although it is unknown if these effects are due to green tea catechins or caffeine. The catechol-O-methyltransferase (COMT) genotype may also modify these associations. OBJECTIVE We examined the impact of decaffeinated GTE on body composition (using dual-energy X-ray absorptiometry) and obesity-associated hormones. METHODS The Minnesota Green Tea Trial was a 12-mo randomized, double-blind, placebo-controlled clinical trial in 937 postmenopausal women (aged 50-70 y) assigned to receive either GTE containing 843 mg (-)-epigallocatechin-3-gallate or placebo. This substudy was conducted in 121 overweight/obese participants [body mass index (BMI) (kg/m(2)) ≥25.0]. RESULTS There were no differences in changes in BMI (-0.13 ± 0.11 compared with -0.05 ± 0.11; P = 0.61), total fat mass (-0.30 ± 0.16 compared with -0.12 ± 0.15 kg; P = 0.40), percentage of body fat (-0.15% ± 0.17% compared with -0.15% ± 0.16%; P = 0.99), or BMD (-0.006 ± 0.002 compared with -0.003 ± 0.002 g/cm(2); P = 0.49) over 12 mo between women taking GTE (n = 61) and those taking a placebo (n = 60). Interactions were observed between treatment and time for gynoid percentage of fat (%fat) and tissue %fat. Gynoid %fat increased from baseline to month 12 in the placebo group as baseline BMI increased and decreased over time as baseline BMI increased in the GTE group (P-interaction = 0.02). Tissue %fat increased from baseline to month 12 in the placebo group as baseline BMI increased. In the GTE group, tissue %fat decreased during the intervention as baseline BMI increased (P-interaction = 0.04). No changes were seen in circulating leptin, ghrelin, adiponectin, or insulin concentrations. COMT genotype did not modify the effect of GTE on any variable. CONCLUSIONS Decaffeinated GTE was not associated with overall reductions in adiposity or improvements in BMD in overweight/obese postmenopausal women. However, GTE may be beneficial for reduction in tissue and gynoid %fat in individuals with higher BMI. This clinical trial was registered at www.clinicaltrials.gov as NCT00917735.
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Affiliation(s)
- Allison M Dostal
- Department of Food Science and Nutrition, University of Minnesota, St. Paul, MN; and
| | - Andrea Arikawa
- Department of Nutrition and Dietetics, University of North Florida, Jacksonville, FL
| | - Luis Espejo
- Department of Food Science and Nutrition, University of Minnesota, St. Paul, MN; and
| | - Mindy S Kurzer
- Department of Food Science and Nutrition, University of Minnesota, St. Paul, MN; and
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Klop C, Welsing PMJ, Leufkens HGM, Elders PJM, Overbeek JA, van den Bergh JP, Bijlsma JWJ, de Vries F. The Epidemiology of Hip and Major Osteoporotic Fractures in a Dutch Population of Community-Dwelling Elderly: Implications for the Dutch FRAX® Algorithm. PLoS One 2015; 10:e0143800. [PMID: 26633011 PMCID: PMC4669166 DOI: 10.1371/journal.pone.0143800] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/09/2015] [Accepted: 11/10/2015] [Indexed: 11/18/2022] Open
Abstract
Background Incidence rates of non-hip major osteoporotic fractures (MOF) remain poorly characterized in the Netherlands. The Dutch FRAX® algorithm, which predicts 10-year probabilities of hip fracture and MOF (first of hip, humerus, forearm, clinical vertebral), therefore incorporates imputed MOF rates. Swedish incidence rate ratios for hip fracture to MOF (Malmo 1987–1996) were used to perform this imputation. However, equality of these ratios between countries is uncertain and recent evidence is scarce. Aims were to estimate incidence rates of hip fracture and MOF and to compare observed MOF rates to those predicted by the imputation method for the Netherlands. Methods Using hospitalisation and general practitioner records from the Dutch PHARMO Database Network (2002–2011) we calculated age-and-sex-specific and age-standardized incidence rates (IRs) of hip and other MOFs (humerus, forearm, clinical vertebral) and as used in FRAX®. Observed MOF rates were compared to those predicted among community-dwelling individuals ≥50 years by the standardized incidence ratio (SIR; 95% CI). Results Age-standardized IRs (per 10,000 person-years) of MOF among men and women ≥50 years were 25.9 and 77.0, respectively. These numbers were 9.3 and 24.0 for hip fracture. Among women 55–84 years, observed MOF rates were significantly higher than predicted (SIR ranged between 1.12–1.50, depending on age). In men, the imputation method performed reasonable. Conclusion Observed MOF incidence was higher than predicted for community-dwelling women over a wide age-range, while it agreed reasonable for men. As miscalibration may influence treatment decisions, there is a need for confirmation of results in another data source. Until then, the Dutch FRAX® output should be interpreted with caution.
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Affiliation(s)
- Corinne Klop
- Utrecht Institute for Pharmaceutical Sciences, Division of Pharmacoepidemiology and Clinical Pharmacology, Utrecht University, Utrecht, Netherlands
| | - Paco M. J. Welsing
- Department of Rheumatology and Clinical Immunology, University Medical Center, Utrecht, Netherlands
- Julius Center for Health Sciences and Primary Care, University Medical Center, Utrecht, Netherlands
| | - Hubert G. M. Leufkens
- Utrecht Institute for Pharmaceutical Sciences, Division of Pharmacoepidemiology and Clinical Pharmacology, Utrecht University, Utrecht, Netherlands
| | - Petra J. M. Elders
- Department of General Practice and Elderly Care, VU University Medical Centre, Amsterdam, Netherlands
| | | | - Joop P. van den Bergh
- Department of Internal Medicine, Viecuri Medical Centre, Venlo, Netherlands
- Department of Internal Medicine, Maastricht University Medical Centre+, Maastricht, Netherlands
- Biomedical Research Institute, University Hasselt, Hasselt, Belgium
| | - Johannes W. J. Bijlsma
- Department of Rheumatology and Clinical Immunology, University Medical Center, Utrecht, Netherlands
| | - Frank de Vries
- Utrecht Institute for Pharmaceutical Sciences, Division of Pharmacoepidemiology and Clinical Pharmacology, Utrecht University, Utrecht, Netherlands
- Department of Clinical Pharmacy and Toxicology, Maastricht University Medical Centre+, Maastricht, Netherlands
- MRC Lifecourse Epidemiology Unit, Southampton General Hospital, Southampton, United Kingdom
- * E-mail:
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Abstract
During the last decades, obesity and osteoporosis have become important global health problems, and the belief that obesity is protective against osteoporosis has recently come into question. In fact, some recent epidemiologic and clinical studies have shown that a high level of fat mass might be a risk factor for osteoporosis and fragility fractures. Several potential mechanisms have been proposed to explain the complex relationship between adipose tissue and bone. Indeed, adipose tissue secretes various molecules, named adipokines, which are thought to have effects on metabolic, skeletal and cardiovascular systems. Moreover, fat tissue is one of the major sources of aromatase, an enzyme that synthesizes estrogens from androgen precursors, hormones that play a pivotal role in the maintenance of skeletal homeostasis, protecting against osteoporosis. Moreover, bone cells express several specific hormone receptors and recent observations have shown that bone-derived factors, such as osteocalcin and osteopontin, affect body weight control and glucose homeostasis. Thus, the skeleton is considered an endocrine target organ and an endocrine organ itself, likely influencing other organs as well. Finally, adipocytes and osteoblasts originate from a common progenitor, a pluripotential mesenchymal stem cell, which has an equal propensity for differentiation into adipocytes or osteoblasts (or other lines) under the influence of several cell-derived transcription factors. This review will highlight recent insights into the relationship between fat and bone, evaluating both potential positive and negative influences between adipose and bone tissue. It will also focus on the hypothesis that osteoporosis might be considered the obesity of bone.
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Affiliation(s)
- Emanuela A. Greco
- Department of Experimental Medicine, Section of Medical Pathophysiology, Endocrinology and Nutrition, ‘Sapienza’ University of Rome, Rome, Italy
| | - Andrea Lenzi
- Department of Experimental Medicine, Section of Medical Pathophysiology, Endocrinology and Nutrition, ‘Sapienza’ University of Rome, Rome, Italy
| | - Silvia Migliaccio
- Unit of Endocrinology, Department of Movement, Human and Health Sciences, Section of Health Sciences, ‘Foro Italico’ University of Rome, Largo Lauro De Bosis 15, 00195 Rome, Italy
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Green tea supplementation benefits body composition and improves bone properties in obese female rats fed with high-fat diet and caloric restricted diet. Nutr Res 2015; 35:1095-105. [PMID: 26525915 DOI: 10.1016/j.nutres.2015.09.014] [Citation(s) in RCA: 23] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/02/2015] [Revised: 09/18/2015] [Accepted: 09/21/2015] [Indexed: 12/15/2022]
Abstract
This study investigated the effects of green tea polyphenols (GTP) supplementation on body composition, bone properties, and serum markers in obese rats fed a high-fat diet (HFD) or a caloric restricted diet (CRD). Forty-eight female rats were fed an HFD ad libitum for 4 months, and then either continued on the HFD or the CRD with or without 0.5% GTP in water. Body composition, bone efficacy, and serum markers were measured. We hypothesized that GTP supplementation would improve body composition, mitigate bone loss, and restore bone microstructure in obese animals fed either HFD or CRD. CRD lowered percent fat mass; bone mass and trabecular number of tibia, femur and lumbar vertebrae; femoral strength; trabecular and cortical thickness of tibia; insulin-like growth factor-I and leptin. CRD also increased percent fat-free mass; trabecular separation of tibia and femur; eroded surface of tibia; bone formation rate and erosion rate at tibia shaft; and adiponectin. GTP supplementation increased femoral mass and strength (P = .026), trabecular thickness (P = .012) and number (P = .019), and cortical thickness of tibia (P < .001), and decreased trabecular separation (P = .021), formation rate (P < .001), and eroded surface (P < .001) at proximal tibia, and insulin-like growth factor-I and leptin. There were significant interactions (diet type × GTP) on osteoblast surface/bone surface, mineral apposition rate at periosteal and endocortical bones, periosteal bone formation rate, and trabecular thickness at femur and lumbar vertebrate (P < .05). This study demonstrates that GTP supplementation for 4 months benefited body composition and improved bone microstructure and strength in obese rats fed with HFD or HFD followed by CRD diet.
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Lorbergs AL, Noseworthy MD, Adachi JD, Stratford PW, MacIntyre NJ. Fat Infiltration in the Leg is Associated with Bone Geometry and Physical Function in Healthy Older Women. Calcif Tissue Int 2015; 97:353-63. [PMID: 26071112 DOI: 10.1007/s00223-015-0018-1] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/20/2015] [Accepted: 06/01/2015] [Indexed: 12/22/2022]
Abstract
The objective of this study was to estimate the associations between muscular fat infiltration, tibia bone mineral quantity and distribution, and physical function in healthy older women. Thirty-five women (aged 60-75 years, mean 70 years) were recruited from the community. Percent intramuscular fat (%IntraMF) within the right leg tibialis anterior, soleus, and gastrocnemius muscles and total intermuscular fat (IMF) were segmented from magnetic resonance imaging scans at the mid-calf. Intramyocellular lipid (IMCL) content in the right tibialis anterior was measured with proton magnetic resonance spectroscopy. Right tibia bone content, area, and strength were measured at the 4, 14, and 66% sites using peripheral quantitative computed tomography. Physical function was assessed by gait speed on the 20 m walking test. After adjusting for age, body size, and activity level, %IntraMF had a negative association with bone content and area at all tibia sites (r = -0.31 to -0.03). Conversely, greater IMF was associated with increased bone content and area (r = 0.04-0.32). Correlation coefficients for the association between IMCL and bone were negative (r = -0.44 to -0.03). All measures of fat infiltration had a negative association with observed physical function (r = -0.42 to -0.04). Our findings suggest that muscular fat infiltration in the leg of healthy postmenopausal women has a compartment-specific relationship with bone status and physical function. Minimizing fat accumulation within and between muscle compartments may prevent bone fragility and functional decline in women.
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Affiliation(s)
- Amanda L Lorbergs
- Institute for Aging Research, Hebrew SeniorLife and Harvard Medical School, 1200 Centre St., Rm. 620, Boston, MA, 02131, USA.
- School of Rehabilitation Science, McMaster University, 1400 Main Street West, IAHS 403, Hamilton, ON, L8S 1C7, Canada.
| | - Michael D Noseworthy
- School of Biomedical Engineering, McMaster University, 1280 Main Street West, ETB 406, Hamilton, ON, L8S 4K1, Canada.
- Department of Electrical and Computer Engineering, McMaster University, Hamilton, ON, Canada.
| | - Jonathan D Adachi
- Department of Medicine, McMaster University, 501-25 Charlton Ave East, Hamilton, ON, L8N 1Y2, Canada.
| | - Paul W Stratford
- School of Rehabilitation Science, McMaster University, 1400 Main Street West, IAHS 403, Hamilton, ON, L8S 1C7, Canada.
| | - Norma J MacIntyre
- School of Rehabilitation Science, McMaster University, 1400 Main Street West, IAHS 403, Hamilton, ON, L8S 1C7, Canada.
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Wang L, Qiu XM, Gui YY, Xu YP, Gober HJ, Li DJ. Bu-Shen-Ning-Xin decoction: inhibition of osteoclastogenesis by abrogation of the RANKL-induced NFATc1 and NF-κB signaling pathways via selective estrogen receptor α. DRUG DESIGN DEVELOPMENT AND THERAPY 2015; 9:3755-66. [PMID: 26229438 PMCID: PMC4516212 DOI: 10.2147/dddt.s88512] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 01/23/2023]
Abstract
INTRODUCTION Bu-Shen-Ning-Xin decoction (BSNXD) is a traditional Chinese medicinal composition that has been used as a remedy for postmenopausal osteoporosis, but the mechanisms affecting bone metabolism are not fully understood. PURPOSE We investigated the molecular mechanism and signaling pathway underlying the effect of BSNXD on osteoclastogenesis. MATERIALS AND METHODS A postmenopausal osteoporosis animal model generated by ovariectomy was administered BSNXD and drug-derived serum was prepared. An enzyme immunoassay was conducted to measure the 17-β-estradiol (E2) concentration in the drug-derived serum. Bone marrow-derived monocyte/macrophage precursor cells were treated with drug-derived serum, and tartrate-resistance acid phosphatase staining was conducted to observe osteoclastogenesis. A bone resorption assay was performed to analyze the effect on osteoclastic resorptive function. Real-time PCR, flow cytometry, Western blotting, transfection, and luciferase assays were conducted to explore the related mechanism. RESULTS E2 was not elevated in BSNXD-derived serum. BSNXD-derived serum suppressed receptor activation of nuclear factor κB ligand (RANKL)-activated osteoclastogenesis in a dose-dependent manner; this effect could be reversed by estrogen receptor α antagonist methyl-piperidino-pyrazole. The serum suppressed RANKL-induced NF-κB transcription and inhibited the accumulation of nuclear factor of activated T-cells, cytoplasmic 1 in osteoclast precursor cells; the inhibitory effect was abolished by methyl-piperidino-pyrazole but not the estrogen receptor β antagonist or androgen receptor antagonist. CONCLUSION These results collectively suggest that administration of BSNXD presents inhibitory effects on osteoclast differentiation by abrogating the RANKL-induced nuclear factor of activated T-cells, cytoplasmic 1 and NF-κB signaling pathways downstream of estrogen receptor α, thereby contributing to the inhibitory effect on bone resorption.
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Affiliation(s)
- Ling Wang
- Laboratory for Reproductive Immunology, Hospital and Institute of Obstetrics and Gynecology, IBS, Fudan University Shanghai Medical College, Shanghai, People's Republic of China ; Shanghai Key Laboratory of Female Reproductive Endocrine Related Diseases, Shanghai, People's Republic of China
| | - Xue-Min Qiu
- Laboratory for Reproductive Immunology, Hospital and Institute of Obstetrics and Gynecology, IBS, Fudan University Shanghai Medical College, Shanghai, People's Republic of China ; Shanghai Key Laboratory of Female Reproductive Endocrine Related Diseases, Shanghai, People's Republic of China
| | - Yu-Yan Gui
- Laboratory for Reproductive Immunology, Hospital and Institute of Obstetrics and Gynecology, IBS, Fudan University Shanghai Medical College, Shanghai, People's Republic of China ; Shanghai Key Laboratory of Female Reproductive Endocrine Related Diseases, Shanghai, People's Republic of China
| | - Ying-Ping Xu
- Laboratory for Reproductive Immunology, Hospital and Institute of Obstetrics and Gynecology, IBS, Fudan University Shanghai Medical College, Shanghai, People's Republic of China ; Shanghai Key Laboratory of Female Reproductive Endocrine Related Diseases, Shanghai, People's Republic of China
| | - Hans-Jürgen Gober
- Department of Pharmacy, Wagner Jauregg Hospital and Children's Hospital, Wagner Jauregg Weg, Linz, Austria
| | - Da-Jin Li
- Laboratory for Reproductive Immunology, Hospital and Institute of Obstetrics and Gynecology, IBS, Fudan University Shanghai Medical College, Shanghai, People's Republic of China
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