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Liew JW, Johnston JD, Bacon K, Wang N, Lynch J, Lewis C, Torner J, Neogi T. Relationship between knee pain and depth-specific measures of proximal tibial subchondral bone density. Osteoarthritis Cartilage 2025; 33:625-632. [PMID: 40089263 PMCID: PMC12034474 DOI: 10.1016/j.joca.2025.02.781] [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: 09/18/2024] [Revised: 01/20/2025] [Accepted: 02/11/2025] [Indexed: 03/17/2025]
Abstract
BACKGROUND Altered subchondral bone mineral density (BMD) may be a possible contributor to osteoarthritis (OA) pain. We evaluated the relation of compartment-specific proximal tibial BMD, at varying depths beneath the subchondral surface, to knee pain. METHODS Multicenter Osteoarthritis (MOST) study participants with knee CTs were included. A 3D imaging tool measuring BMD in relation to depth from the subchondral surface was used to assess proximal tibial subchondral BMD at depths of 0-2.5, 2.5-5.0, and 5-10 mm. Knee pain in the past 30 days was scored on a numeric rating scale (range 0-100), dichotomized at 40/100 to define the presence of at least moderate pain. We cross-sectionally evaluated the relation of subchondral BMD to the presence of knee pain using binomial regression with generalized estimating equations (to account for correlations between two knees per individual) for each compartment and depth in separate models and adjusted for age, sex, and body mass index (BMI). RESULTS We included 2082 participants (mean age: 61 years, 56.5% female, mean BMI: 29 kg/m2). The prevalence of moderate pain was significantly lower for each SD unit increase in average subchondral BMD, after confounder adjustment, in each compartment. The magnitude of association did not differ for increasing depths beneath the subchondral surface or between compartments. CONCLUSION Lower subchondral proximal tibial BMD measures were associated with the prevalence of moderate knee pain in individuals with or at risk for knee OA, without differences by depth or compartment. These findings suggest bone remodeling responses throughout subchondral bone contribute to the knee pain experience.
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Affiliation(s)
- Jean W Liew
- Section of Rheumatology, Boston University Chobanian & Avedisian School of Medicine, Boston, MA, USA
| | - James D Johnston
- Department of Mechanical Engineering, University of Saskatchewan, Saskatoon, Canada
| | - Kathy Bacon
- Section of Rheumatology, Boston University Chobanian & Avedisian School of Medicine, Boston, MA, USA
| | - Na Wang
- School of Public Health, Boston University, Boston, MA, USA
| | - John Lynch
- University of California, San Francisco, San Francisco, CA, USA
| | - Cora Lewis
- Department of Epidemiology, University of Alabama at Birmingham, Birmingham, AL, USA
| | | | - Tuhina Neogi
- Section of Rheumatology, Boston University Chobanian & Avedisian School of Medicine, Boston, MA, USA.
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2
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Lyu X, Wang J, Su J. Intelligent Manufacturing for Osteoarthritis Organoids. Cell Prolif 2025:e70043. [PMID: 40285592 DOI: 10.1111/cpr.70043] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/05/2025] [Revised: 03/22/2025] [Accepted: 04/07/2025] [Indexed: 04/29/2025] Open
Abstract
Osteoarthritis (OA) is the most prevalent degenerative joint disease worldwide, imposing a substantial global disease burden. However, its pathogenesis remains incompletely understood, and effective treatment strategies are still lacking. Organoid technology, in which stem cells or progenitor cells self-organise into miniature tissue structures under three-dimensional (3D) culture conditions, provides a promising in vitro platform for simulating the pathological microenvironment of OA. This approach can be employed to investigate disease mechanisms, carry out high-throughput drug screening and facilitate personalised therapies. This review summarises joint structure, OA pathogenesis and pathological manifestations, thereby establishing the disease context for the application of organoid technology. It then examines the components of the arthrosis organoid system, specifically addressing cartilage, subchondral bone, synovium, skeletal muscle and ligament organoids. Furthermore, it details various strategies for constructing OA organoids, including considerations of cell selection, pathological classification and fabrication techniques. Notably, this review introduces the concept of intelligent manufacturing of OA organoids by incorporating emerging engineering technologies such as artificial intelligence (AI) into the organoid fabrication process, thereby forming an innovative software and hardware cluster. Lastly, this review discusses the challenges currently facing intelligent OA organoid manufacturing and highlights future directions for this rapidly evolving field. By offering a comprehensive overview of state-of-the-art methodologies and challenges, this review anticipates that intelligent, automated fabrication of OA organoids will expedite fundamental research, drug discovery and personalised translational applications in the orthopaedic field.
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Affiliation(s)
- Xukun Lyu
- Department of Orthopedics, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China
- Trauma Orthopedics Center, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China
- Institute of Musculoskeletal Injury and Translational Medicine of Organoids, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China
- Department of Clinical Medicine, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Jian Wang
- Department of Orthopedics, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China
- Trauma Orthopedics Center, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China
- Institute of Musculoskeletal Injury and Translational Medicine of Organoids, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China
- Institute of Translational Medicine, Shanghai University, Shanghai, China
- National Center for Translational Medicine SHU Branch, Shanghai University, Shanghai, China
| | - Jiacan Su
- Department of Orthopedics, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China
- Trauma Orthopedics Center, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China
- Institute of Musculoskeletal Injury and Translational Medicine of Organoids, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China
- Institute of Translational Medicine, Shanghai University, Shanghai, China
- National Center for Translational Medicine SHU Branch, Shanghai University, Shanghai, China
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3
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Duong V, Abdel Shaheed C, Ferreira ML, Narayan SW, Venkatesha V, Hunter DJ, Zhu J, Atukorala I, Kobayashi S, Goh SL, Briggs AM, Cross M, Espinosa-Morales R, Fu K, Guillemin F, Keefe F, Stefan Lohmander L, March L, Milne GJ, Mei Y, Mobasheri A, Namane M, Peat G, Risberg MA, Sharma S, Sit R, Telles RW, Zhang Y, Cooper C. Risk factors for the development of knee osteoarthritis across the lifespan: A systematic review and meta-analysis. Osteoarthritis Cartilage 2025:S1063-4584(25)00860-X. [PMID: 40174718 DOI: 10.1016/j.joca.2025.03.003] [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: 09/20/2024] [Revised: 03/17/2025] [Accepted: 03/19/2025] [Indexed: 04/04/2025]
Abstract
OBJECTIVE To identify and quantify risk factors for incident knee osteoarthritis (KOA) across the lifespan. METHODS This systematic review and meta-analysis identified eligible studies from seven electronic databases and three registries. Longitudinal cohort studies or randomised controlled trials evaluating participants who developed incident symptomatic and/or radiographic KOA were included. Two independent reviewers completed data screening and extraction. Estimates were pooled using a random effects model and reported as odds ratio (OR), hazard ratio, or risk ratio and corresponding 95% confidence intervals (95% CI). Grading of Recommendations, Assessment, Development and Evaluation was used to determine the certainty of evidence. Population attributable fractions were calculated, including risk factors significantly associated with radiographic KOA based on the pooled meta-analysis and where we could determine communality scores using existing clinical datasets. RESULTS We identified 131 studies evaluating > 150 risk factors. Previous knee injury, older age and high bone mineral density were associated with an increased risk of incident radiographic KOA based on the pooled analysis [OR (95% CI): 2.67 (1.41, 5.05), 1.15 (1.00, 1.33) and 1.82 (1.12, 2.94), respectively], with moderate-to-high certainty. Two risk factors (overweight/obesity and previous knee injury) accounted for 14% of incident radiographic KOA. Other modifiable risk factors, including occupational physical activity, also contribute to radiographic or symptomatic KOA. CONCLUSION Novel strategies addressing known modifiable risk factors including overweight/obesity, knee injuries and occupational physical activity are needed to reduce overall burden of KOA. SYSTEMATIC REVIEW REGISTRATION PROSPERO ID: CRD42023391187.
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Affiliation(s)
- Vicky Duong
- Sydney Musculoskeletal Health, Kolling Institute, Faculty of Medicine and Health, University of Sydney, Level 10, St Leonards, Sydney 2065, New South Wales, Australia.
| | - Christina Abdel Shaheed
- Sydney Musculoskeletal Health, Kolling Institute, Faculty of Medicine and Health, University of Sydney, Level 10, St Leonards, Sydney 2065, New South Wales, Australia; Faculty of Medicine and Health, School of Public Health, University of Sydney, Level 10N, King George V Building, Royal Prince Alfred Hospital, Sydney 2050, New South Wales, Australia.
| | - Manuela L Ferreira
- The George Institute for Global Health, Faculty of Medicine and Health, The University of New South Wales, Level 18, International Towers 3, 300 Barangaroo Ave, Barangaroo, Sydney 2000, New South Wales, Australia
| | - Sujita W Narayan
- Sydney Musculoskeletal Health, Kolling Institute, Faculty of Medicine and Health, University of Sydney, Level 10, St Leonards, Sydney 2065, New South Wales, Australia; Faculty of Medicine and Health, School of Public Health, University of Sydney, Level 10N, King George V Building, Royal Prince Alfred Hospital, Sydney 2050, New South Wales, Australia
| | - Venkatesha Venkatesha
- Northern Sydney Local Health District Executive, Royal North Shore Hospital, The Kolling Institute, Level 10, St Leonards, Sydney 2065, New South Wales, Australia
| | - David J Hunter
- Sydney Musculoskeletal Health, Kolling Institute, Faculty of Medicine and Health, University of Sydney, Level 10, St Leonards, Sydney 2065, New South Wales, Australia; Department of Rheumatology, Royal North Shore Hospital, Clinical Administration 7C, St Leonards, Sydney 2065, New South Wales, Australia
| | - Jimmy Zhu
- Department of Rheumatology, Royal North Shore Hospital, Clinical Administration 7C, St Leonards, Sydney 2065, New South Wales, Australia; Liverpool Hospital, Sydney, New South Wales, Australia
| | - Inoshi Atukorala
- Department of Clinical Medicine, University of Colombo, Colombo, Sri Lanka
| | - Sarah Kobayashi
- Sydney Musculoskeletal Health, Kolling Institute, Faculty of Medicine and Health, University of Sydney, Level 10, St Leonards, Sydney 2065, New South Wales, Australia
| | - Siew Li Goh
- Centre for Epidemiology and Evidence-Based Practice, Universiti Malaya, Kuala Lumpur, Malaysia; Sports and Exercise Medicine Research and Education Group, Faculty of Medicine, Universiti Malaya, Kuala Lumpur, Malaysia
| | - Andrew M Briggs
- Curtin School of Allied Health, Curtin University, Perth 6845, Western Australia, Australia
| | - Marita Cross
- Sydney Musculoskeletal Health, Kolling Institute, Faculty of Medicine and Health, University of Sydney, Level 10, St Leonards, Sydney 2065, New South Wales, Australia; Department of Rheumatology, Royal North Shore Hospital, Clinical Administration 7C, St Leonards, Sydney 2065, New South Wales, Australia
| | - Rolando Espinosa-Morales
- National Institute of Rehabilitation, National University Autonomous of Mexico, Mexico City, Mexico
| | - Kai Fu
- Department of Orthopedic Surgery, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, No. 600 Yishan Road, Xuhui District, Shanghai 200233, China
| | | | - Francis Keefe
- Duke Pain Prevention and Treatment Research Program, Department of Psychiatry and Behavioral Sciences, Duke University School of Medicine, Durham, NC, USA
| | - L Stefan Lohmander
- Department of Clinical Sciences Lund, Orthopedics, Lund University, PO Box 117, Lund 22100, Sweden
| | - Lyn March
- Sydney Musculoskeletal Health, Kolling Institute, Faculty of Medicine and Health, University of Sydney, Level 10, St Leonards, Sydney 2065, New South Wales, Australia; Department of Rheumatology, Royal North Shore Hospital, Clinical Administration 7C, St Leonards, Sydney 2065, New South Wales, Australia
| | - George J Milne
- Marshall Centre for Infectious Disease Research and Department of Computer Science and Software Engineering, University of Western Australia, 35 Stirling Highway, Crawley 6009, Western Australia, Australia
| | - Yifang Mei
- Department of Rheumatology and Immunology, The Second Affiliated Hospital of Southern University of Science and Technology/The Third People's Hospital of Shenzhen, 29 Bulan Road, Longgang District, Shenzhen 518000, China
| | - Ali Mobasheri
- Research Unit of Health Sciences and Technology, Faculty of Medicine, University of Oulu, Oulu, Finland; State Research Institute Centre for Innovative Medicine, Vilnius, Lithuania; Department of Joint Surgery, First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China; World Health Organization Collaborating Center for Public Health Aspects of Musculoskeletal Health and Aging, Université de Liège, Liège, Belgium
| | - Mosedi Namane
- Division of Family Medicine, Department of Family, Community and Emergency Medicine, University of Cape Town, Cape Town, South Africa
| | - George Peat
- Centre for Applied Health & Social Care Research (CARe), Sheffield Hallam University, Robert Winston Building, Collegiate Campus, Sheffield, United Kingdom
| | - May Arna Risberg
- Department of Sport Medicine, Norwegian School Sport Sciences, P. Box 4014 Ullevaal Stadion, 0806 Oslo, Norway; Division of Orthopaedic Surgery, Oslo University Hospital, Oslo, Norway
| | - Saurab Sharma
- Pain Management and Research Centre, Royal North Shore Hospital, Northern Sydney Local Health District, Douglas Building, St Leonards, Sydney 2065, New South Wales, Australia; School of Health Sciences, Faculty of Medicine and Health, University of New South Wales, Sydney, New South Wales, Australia; Pain Management Research Institute, Kolling Institute, Faculty of Medicine and Health, the University of Sydney and Northern Sydney Local Health District, St Leonard's, NSW, Australia
| | - Regina Sit
- The Jockey Club School of Public Health and Primary Care, The Chinese University of Hong Kong, Hong Kong
| | - Rosa Weiss Telles
- Department of Internal Medicine, Faculty of Medicine, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil; Rheumatology Service, Hospital das Clínicas da UFMG/Ebserh, Belo Horizonte, Brazil
| | - Yuqing Zhang
- Division of Rheumatology, Allergy and Immunology, Massachusetts General Hospital, Harvard Medical School, 55 Fruit Street, Bulfinch 165, Boston, MA 02114, USA
| | - Cyrus Cooper
- University of Southampton, Southampton, United Kingdom; Institute of Musculoskeletal Science, University of Oxford, Oxfordshire, United Kingdom
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Zhu R, Xing X, Bian J, Zhang X, Ge L, Cai G. Causal association between bone mineral density and the risk of joint replacement in patients with osteoarthritis: a Mendelian randomization study. Clin Rheumatol 2025; 44:823-830. [PMID: 39738847 DOI: 10.1007/s10067-024-07289-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/27/2024] [Revised: 12/15/2024] [Accepted: 12/18/2024] [Indexed: 01/02/2025]
Abstract
Population-based studies have been inconsistent in terms of the relationship between bone mineral density (BMD) and the progression of osteoarthritis. This study aimed to evaluate the causal relationship between BMD and the risk of joint replacement in patients with osteoarthritis. We performed a two-sample Mendelian randomization (MR) analysis to determine the association of BMD of the total body, femoral neck, and lumbar spine with the risk of hip and knee replacements. Inverse variance weighting (IVW) was used as the main analysis method. Heterogeneity and horizontal pleiotropy were checked. Multivariable MR analysis was performed by adjusting for hip/knee pain, body mass index (BMI), estrogen levels, BMI-based sex hormone-binding globulin (SHBG) levels, and physical activity. BMD of the total body and the lumbar spine were significantly associated with higher risks of both knee (IVW odds ratios (ORs) = 1.08-1.10, p = 4.62E-03) and hip replacements (IVW ORs = 1.19-1.37, P = 3.23E-09). Femoral neck BMD was significantly associated with the risk of hip but not knee replacement (IVW OR = 1.27, 95% confidence interval 1.13 to 1.43, p = 9.15E-05). Multivariable MR analyses produced similar results compared to the univariable analyses. No evidence of heterogeneity and horizontal pleiotropy were found, except that there was heterogeneity in the association between total body BMD and the risk of knee replacement. BMD is significantly associated with an increased risk of both knee and hip replacement, and the association is stronger for hip replacement. These findings suggest a causal relationship between BMD and the progression of osteoarthritis. Key Points • BMD is associated with an increased risk of hip and knee joint replacement. • BMD was more strongly associated with hip replacement risk.
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Affiliation(s)
- Rui Zhu
- Department of Epidemiology and Biostatistics, School of Public Health, Anhui Medical University, Hefei, 230032, Anhui, China
| | - Xing Xing
- Department of Epidemiology and Biostatistics, School of Public Health, Anhui Medical University, Hefei, 230032, Anhui, China
| | - Jingyuan Bian
- Department of General Surgery, Qingpu Branch of Zhongshan Hospital Affiliated to Fudan University, Shanghai, 201700, China
| | - Xiaoyue Zhang
- Department of Epidemiology and Biostatistics, School of Public Health, Anhui Medical University, Hefei, 230032, Anhui, China
| | - Liru Ge
- Department of Epidemiology and Biostatistics, School of Public Health, Anhui Medical University, Hefei, 230032, Anhui, China
| | - Guoqi Cai
- Department of Epidemiology and Biostatistics, School of Public Health, Anhui Medical University, Hefei, 230032, Anhui, China.
- Menzies Institute for Medical Research, University of Tasmania, Hobart, TAS, 7000, Australia.
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5
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Bonecka J, Turek B, Jankowski K, Borowska M, Jasiński T, Smyth G, Domino M. Relationship between Feline Knee Joint Osteoarthritis and Bone Mineral Density Quantified Using Computed Tomography and Computed Digital Absorptiometry. Animals (Basel) 2024; 14:2615. [PMID: 39272400 PMCID: PMC11394321 DOI: 10.3390/ani14172615] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/08/2024] [Revised: 09/04/2024] [Accepted: 09/04/2024] [Indexed: 09/15/2024] Open
Abstract
Osteoarthritis (OA), including knee joint OA, is a common chronic condition in cats. In both cats and humans, knee joint OA is characterized radiographically by the presence of osteophytes, enthesiophytes, subchondral sclerosis, and joint space narrowing. However, only in humans have these radiographic signs been reported to increase bone mineral density (BMD). Therefore, this study aims to quantify the volumetric (vBMD) and relative (rBMD) BMD measures of the feline knee joint and compare BMD measures between various severities of OA to test the hypothesized OA-BMD relationship in the knee joint in cats. The 46 feline knee joints were imaged using computed tomography (CT) and conventional radiography supported by the computed digital absorptiometry (CDA) method to obtain vBMD and rBMD, respectively. Both BMD measures were assessed in three regions of interest (ROIs): the distal femur (ROI 1), patella (ROI 2), and proximal tibia (ROI 3). In all locations, vBMD and rBMD showed moderate (ROI 2: r = 0.67, p < 0.0001) to strong (ROI 1: ρ = 0.96, p < 0.0001; ROI 3: r = 0.89, p < 0.0001) positive correlations. Due to differences (p < 0.0001) in the width of the distal femur (17.9 ± 1.21 mm), patella (8.2 ± 0.82 mm), and proximal tibia (19.3 ± 1.16 mm), the rBMD was corrected (corr rBMD) using the thickness coefficient of 0.46 ± 0.04 for ROI 2 and 1.08 ± 0.03 for ROI 3. Regardless of the quantification method used, BMD measures increased linearly from a normal knee joint to severe OA, with differences in BMD between normal and mild to severe knee joint OA. The OA-BMD relationship in the feline knee joint can be preliminarily confirmed.
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Affiliation(s)
- Joanna Bonecka
- Department of Small Animal Diseases and Clinic, Institute of Veterinary Medicine, Warsaw University of Life Sciences (WULS-SGGW), 02-787 Warsaw, Poland
| | - Bernard Turek
- Department of Large Animal Diseases and Clinic, Institute of Veterinary Medicine, Warsaw University of Life Sciences (WULS-SGGW), 02-787 Warsaw, Poland
| | - Krzysztof Jankowski
- Institute of Mechanics and Printing, Warsaw University of Technology, 02-524 Warsaw, Poland
| | - Marta Borowska
- Institute of Biomedical Engineering, Faculty of Mechanical Engineering, Białystok University of Technology, 15-351 Bialystok, Poland
| | - Tomasz Jasiński
- Department of Large Animal Diseases and Clinic, Institute of Veterinary Medicine, Warsaw University of Life Sciences (WULS-SGGW), 02-787 Warsaw, Poland
| | - Graham Smyth
- Menzies Health Institute Queensland, Griffith University School of Medicine, Southport, QLD 4222, Australia
| | - Małgorzata Domino
- Department of Large Animal Diseases and Clinic, Institute of Veterinary Medicine, Warsaw University of Life Sciences (WULS-SGGW), 02-787 Warsaw, Poland
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Kiliç SC, Durna D, Baygutalp F. Correlations with clinical and radiologic findings and prevalence of osteopenia/osteoporosis in the patients with bilateral temporomandibular joint osteoarthritis. JOURNAL OF STOMATOLOGY, ORAL AND MAXILLOFACIAL SURGERY 2024; 125:101869. [PMID: 38582351 DOI: 10.1016/j.jormas.2024.101869] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 02/08/2024] [Revised: 03/29/2024] [Accepted: 04/03/2024] [Indexed: 04/08/2024]
Abstract
This study aimed to evaluate the prevalence of osteopenia/osteoporosis in patients with bilateral temporomandibular joint osteoarthritis (TMJ-OA) and its correlations with clinical and radiological findings. A total of 95 patients with bilateral TMJ-OA diagnosed by CBCT were included in the study. Clinical and radiological findings and bone mineral density (BMD) scores were recorded. Descriptive statistics and the Spearman rho correlation tests were performed. Osteopenia/osteoporosis was found in 44 of 95 patients (46.32 %) (30, osteopenia; 14 osteoporosis). Osteopenia/osteoporosis is significantly associated with postmenopausal status and age over 40 years, but it is not associated with clinical and radiological findings of TMJ-OA. Patients with bilateral TMJ-OA have a high prevalence of osteopenia/osteoporosis.
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Affiliation(s)
- Songül Cömert Kiliç
- Department of Oral and Maxillofacial Surgery, Faculty of Dentistry, Atatürk University, Erzurum, Turkey.
| | - Doğan Durna
- Department of Oral and Maxillofacial Radiology, Faculty of Dentistry, Atatürk University, Erzurum, Turkey
| | - Fatih Baygutalp
- Department of Physical Therapy and Rehabilitation, Faculty of Medicine, Atatürk University, Erzurum, Turkey
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Szala D, Kopańska M, Trojniak J, Jabłoński J, Hanf-Osetek D, Snela S, Zawlik I. The Role of MicroRNAs in the Pathophysiology of Osteoarthritis. Int J Mol Sci 2024; 25:6352. [PMID: 38928059 PMCID: PMC11204066 DOI: 10.3390/ijms25126352] [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: 05/05/2024] [Revised: 06/04/2024] [Accepted: 06/06/2024] [Indexed: 06/28/2024] Open
Abstract
Worldwide, osteoarthritis (OA) is the most common cause of joint pain in older people. Many factors contribute to osteoarthritis' development and progression, including secondary osteoarthritis' underlying causes. It is important to note that osteoarthritis affects all four tissues: cartilage, bone, joint capsule, and articular apparatus. An increasingly prominent area of research in osteoarthritis regulation is microRNAs (miRNAs), a small, single-stranded RNA molecule that controls gene expression in eukaryotes. We aimed to assess and summarize current knowledge about the mechanisms of the action of miRNAs and their clinical significance. Osteoarthritis (OA) is affected by the interaction between miRNAs and inflammatory processes, as well as cartilage metabolism. MiRNAs also influence cartilage cell apoptosis, contributing to the degradation of the cartilage in OA. Studies have shown that miRNAs may have both an inhibitory and promoting effect on osteoporosis progression through their influence on molecular mechanisms. By identifying these regulators, targeted treatments for osteoarthritis may be developed. In addition, microRNA may also serve as a biomarker for osteoarthritis. By using these biomarkers, the disease could be detected faster, and early intervention can be instituted to prevent mobility loss and slow deterioration.
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Affiliation(s)
| | - Marta Kopańska
- Department of Pathophysiology, Institute of Medical Sciences, Medical College of Rzeszow University, 35-959 Rzeszow, Poland
| | - Julia Trojniak
- Student Research Club “Reh-Tech”, Medical College of Rzeszow University, 35-959 Rzeszow, Poland;
| | - Jarosław Jabłoński
- Faculty of Orthopaedic and Reumatology, Institute of Medical Sciences, Collegium Medicum, University of Rzeszow, 35-959 Rzeszow, Poland; (J.J.); (D.H.-O.); (S.S.)
- Orthopaedics and Traumatology Clinic, Clinical Hospital No. 2, 35-301 Rzeszow, Poland
| | - Dorota Hanf-Osetek
- Faculty of Orthopaedic and Reumatology, Institute of Medical Sciences, Collegium Medicum, University of Rzeszow, 35-959 Rzeszow, Poland; (J.J.); (D.H.-O.); (S.S.)
- Orthopaedics and Traumatology Clinic, Clinical Hospital No. 2, 35-301 Rzeszow, Poland
| | - Sławomir Snela
- Faculty of Orthopaedic and Reumatology, Institute of Medical Sciences, Collegium Medicum, University of Rzeszow, 35-959 Rzeszow, Poland; (J.J.); (D.H.-O.); (S.S.)
- Orthopaedics and Traumatology Clinic, Clinical Hospital No. 2, 35-301 Rzeszow, Poland
| | - Izabela Zawlik
- Department of General Genetics, Institute of Medical Sciences, Medical College of Rzeszow University, Kopisto 2a, 35-959 Rzeszow, Poland;
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8
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Tönük ŞB, Yorgancıoğlu ZR, Ramadan SU, Kocaoğlu S. Relationship between DXA measured systemic bone mineral density and subchondral bone cysts in postmenopausal female patients with knee osteoarthritis: a cross-sectional study : Osteoarthritis cysts and bone mineral density. BMC Musculoskelet Disord 2024; 25:50. [PMID: 38212780 PMCID: PMC10782551 DOI: 10.1186/s12891-023-07141-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/24/2023] [Accepted: 12/20/2023] [Indexed: 01/13/2024] Open
Abstract
BACKGROUND Individuals with high systemic bone mineral density (BMD) may have an increased risk of incident knee osteoarthritis (OA). Besides that, radiographic osteophytes are strongly associated with BMD. Because of these reasons, the aim of the study was to investigate the possible association between radiological subchondral bone cyst (SBC) grade and systemic BMD and vitamin D status in the postmenopausal female patients with knee OA in a crosss-sectional study. METHODS This study included of 48 osteoporosis treatment-free postmenopausal patients diagnosed with symptomatic medial compartment knee OA. BMD analysis was performed using dual-energy X-ray absorptiometry (DXA) and serum vitamin D levels were measured after recording patients' findings. Each knee was scanned using computed tomography (CT), and categorical SBC scores were graded for the medial and lateral tibiofemoral (TF) and patellofemoral (PF) compartments and further calculated as compartmental total, total TF and grand total of both TF compartments. SBC scores were analysed with correlation analysis. RESULTS The patient population was characterized by radiographic joint space narrowing, obesity and low vitamin D status. Median medial total and grand total TF SBC scores were significantly different between the patient groups according to the Kellgren-Lawrence (KL) radiographic grading (p = 0.006 and p = 0.007, respectively). There were no correlations between femoral BMD values and SBC scores. However, positive correlations were detected significantly between L1 - 4 DXA values and TF SBC scores, but not with PF SBC scores (p = 0.005 for the correlation between L1 - 4 BMD and medial compartments total TF SBC score, p = 0.021 for the correlation between L1 - 4 BMD and grand total TF SBC score). No significant correlations were found with Vitamin D levels. CONCLUSIONS Development of TF OA high-grade SBCs may be linked to systemic bone mass as represented by trabecular bone-rich lumbar vertebrae. The relationship might point to the importance of bone stiffness as an acting factor in knee OA possibly with mechanical energy transfer to the joint.
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Affiliation(s)
- Şükrü Burak Tönük
- Department of Physical Medicine and Rehabilitation, Bolu Abant Izzet Baysal University, Karacasu, Bolu, Turkey.
| | - Zeynep Rezan Yorgancıoğlu
- Department of Physical Medicine and Rehabilitation, Ministry of Health Ankara Training and Research Hospital, Ankara, Turkey
| | - Selma Uysal Ramadan
- Department of Radiology, Ministry of Health Kecioren Training and Research Hospital, Ankara, Turkey
| | - Seher Kocaoğlu
- Department of Physical Medicine and Rehabilitation, Ministry of Health Ankara Training and Research Hospital, Ankara, Turkey
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Qu Y, Chen S, Han M, Gu Z, Zhang Y, Fan T, Zeng M, Ruan G, Cao P, Yang Q, Ding C, Zhang Y, Zhu Z. Osteoporosis and osteoarthritis: a bi-directional Mendelian randomization study. Arthritis Res Ther 2023; 25:242. [PMID: 38093316 PMCID: PMC10717893 DOI: 10.1186/s13075-023-03213-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/21/2023] [Accepted: 11/09/2023] [Indexed: 12/17/2023] Open
Abstract
OBJECTIVE To investigate the causal relationship between low bone mineral density (BMD) and osteoarthritis (OA) using Mendelian randomization (MR) design. METHODS Two-sample bi-directional MR analyses were performed using summary-level information on OA traits from UK Biobank and arcOGEN. Sensitivity analyses including MR-Egger, simple median, weighted median, MR pleiotropy residual sum, and outlier approaches were utilized in conjunction with inverse variance weighting (IVW). Gene ontology (GO) enrichment analyses and expression quantitative trait locus (eQTL) colocalization analyses were used to investigate the potential mechanism and shared genes between osteoporosis (OP) and OA. RESULTS The IVW method revealed that genetically predicted low femoral neck BMD was significantly linked with hip (β = 0.105, 95% CI: 0.023-0.188) and knee OA (β = 0.117, 95% CI: 0.049-0.184), but not with other site-specific OA. Genetically predicted low lumber spine BMD was significantly associated with OA at any sites (β = 0.048, 95% CI: 0.011-0.085), knee OA (β = 0.101, 95% CI: 0.045-0.156), and hip OA (β = 0.150, 95% CI: 0.077-0.224). Only hip OA was significantly linked with genetically predicted reduced total bone BMD (β = 0.092, 95% CI: 0.010-0.174). In the reverse MR analyses, no evidence for a causal effect of OA on BMD was found. GO enrichment analysis and eQTL analysis illustrated that DDN and SMAD-3 were the most prominent co-located genes. CONCLUSIONS These findings suggested that OP may be causally linked to an increased risk of OA, indicating that measures to raise BMD may be effective in preventing OA. More research is required to determine the underlying processes via which OP causes OA.
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Affiliation(s)
- Yudun Qu
- Clinical Research Centre, Zhujiang Hospital, The Second School of Clinical Medicine, Southern Medical University, Guangzhou, Guangdong, China
| | - Shibo Chen
- Clinical Research Centre, Zhujiang Hospital, The Second School of Clinical Medicine, Southern Medical University, Guangzhou, Guangdong, China
- Department of Orthopedics, Zhujiang Hospital, Southern Medical University, Guangzhou, Guangdong, China
| | - Mengling Han
- Department of Rehabilitation, Zhujiang Hospital, Southern Medical University, Guangzhou, China
| | - Ziqi Gu
- Clinical Research Centre, Zhujiang Hospital, The Second School of Clinical Medicine, Southern Medical University, Guangzhou, Guangdong, China
| | - Yujie Zhang
- Department of Epidemiology, School of Public Health, Southern Medical University, Guangzhou, Guangdong, China
| | - Tianxiang Fan
- Clinical Research Centre, Zhujiang Hospital, The Second School of Clinical Medicine, Southern Medical University, Guangzhou, Guangdong, China
- Department of Orthopedics, Zhujiang Hospital, Southern Medical University, Guangzhou, Guangdong, China
| | - Muhui Zeng
- Clinical Research Centre, Zhujiang Hospital, The Second School of Clinical Medicine, Southern Medical University, Guangzhou, Guangdong, China
- Department of Orthopedics, Zhujiang Hospital, Southern Medical University, Guangzhou, Guangdong, China
| | - Guangfeng Ruan
- Department of Rheumatology, Guangzhou First People's Hospital, School of Medicine, South China University of Technology, Guangzhou, 510180, China
| | - Peihua Cao
- Clinical Research Centre, Zhujiang Hospital, The Second School of Clinical Medicine, Southern Medical University, Guangzhou, Guangdong, China
| | - Qian Yang
- MRC Integrative Epidemiology Unit at the University of Bristol, Bristol, UK
- Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, UK
| | - Changhai Ding
- Clinical Research Centre, Zhujiang Hospital, The Second School of Clinical Medicine, Southern Medical University, Guangzhou, Guangdong, China.
- Department of Rheumatology, Guangzhou First People's Hospital, School of Medicine, South China University of Technology, Guangzhou, 510180, China.
- Department of Orthopaedics, Affiliated Hospital of Youjiang Medical University for Nationalities, Baise, 533000, China.
| | - Yan Zhang
- Clinical Research Centre, Zhujiang Hospital, The Second School of Clinical Medicine, Southern Medical University, Guangzhou, Guangdong, China.
| | - Zhaohua Zhu
- Clinical Research Centre, Zhujiang Hospital, The Second School of Clinical Medicine, Southern Medical University, Guangzhou, Guangdong, China.
- Department of Orthopedics, Zhujiang Hospital, Southern Medical University, Guangzhou, Guangdong, China.
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10
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Chiba D, Sasaki E, Ota S, Oyama T, Ishibashi H, Kimura Y, Nakaji S, Ishibashi Y. Lower bone mineral density can be a risk for an enlarging bone marrow lesion: A longitudinal cohort study of Japanese women without radiographic knee osteoarthritis. Mod Rheumatol 2023; 33:1044-1051. [PMID: 35919930 DOI: 10.1093/mr/roac079] [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: 03/09/2022] [Revised: 05/15/2022] [Accepted: 07/24/2022] [Indexed: 11/14/2022]
Abstract
OBJECTIVES The aim is to elucidate the relationship between bone mineral density (BMD) at baseline and the change of bone marrow lesion (BML) during a 2-year follow-up (2YFU) period. METHODS Seventy-eight female participants (mean age: 54.9 ± 9.6 years) without radiographic knee osteoarthritis were eligible. Based on right-knee magnetic resonance imaging, maximum BML area (BMLa) was calculated by tracing the BML border. The change in BMLa was defined using the following formula: [2YFU] - [Baseline] = ΔBMLa. Positive ΔBMLa was defined as enlarged; negative ΔBMLa was defined as regressed. Dual-energy X-ray absorptiometry was performed to measure the BMD of distal radius. Young adult mean [YAM (%)] of the BMD was used for statistical analysis. Linear regression analysis was conducted with ΔBMLa as the dependent variable and YAM as the independent variable. Receiver operating characteristic curve and logistic regression analyses were conducted for YAM to predict the prevalence of BML enlargement or regression. RESULTS Twenty-six (33.3%) patients had enlarged BMLa, 12 (15.4%) participants showed regressing BMLa, and 40 (51.3%) patients remained stable. YAM was negatively associated with ΔBMLa (β: - 0.375, P = 0.046). The best predictor of BML enlargement risk was 85% (odds ratio: 8.383, P = 0.025). CONCLUSIONS Lower BMD could predict BML enlargement during a 2YFU period.
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Affiliation(s)
- Daisuke Chiba
- Department of Orthopaedic Surgery, Hirosaki University Graduate School of Medicine, Hirosaki, Aomori, Japan
| | - Eiji Sasaki
- Department of Orthopaedic Surgery, Hirosaki University Graduate School of Medicine, Hirosaki, Aomori, Japan
| | - Seiya Ota
- Department of Orthopaedic Surgery, Hirosaki University Graduate School of Medicine, Hirosaki, Aomori, Japan
| | - Tetsushi Oyama
- Department of Orthopaedic Surgery, Hirosaki University Graduate School of Medicine, Hirosaki, Aomori, Japan
| | - Hikaru Ishibashi
- Department of Orthopaedic Surgery, Hirosaki University Graduate School of Medicine, Hirosaki, Aomori, Japan
| | - Yuka Kimura
- Department of Orthopaedic Surgery, Hirosaki University Graduate School of Medicine, Hirosaki, Aomori, Japan
| | - Shigeyuki Nakaji
- Department of Social Medicine, Hirosaki University Graduate School of Medicine, Hirosaki, Aomori, Japan
| | - Yasuyuki Ishibashi
- Department of Orthopaedic Surgery, Hirosaki University Graduate School of Medicine, Hirosaki, Aomori, Japan
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11
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Davis S, Zekonyte J, Karali A, Roldo M, Blunn G. Early Degenerative Changes in a Spontaneous Osteoarthritis Model Assessed by Nanoindentation. Bioengineering (Basel) 2023; 10:995. [PMID: 37760097 PMCID: PMC10525236 DOI: 10.3390/bioengineering10090995] [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: 07/26/2023] [Revised: 08/15/2023] [Accepted: 08/18/2023] [Indexed: 09/29/2023] Open
Abstract
Understanding early mechanical changes in articular cartilage (AC) and subchondral bone (SB) is crucial for improved treatment of osteoarthritis (OA). The aim of this study was to develop a method for nanoindentation of fresh, unfixed osteochondral tissue to assess the early changes in the mechanical properties of AC and SB. Nanoindentation was performed throughout the depth of AC and SB in the proximal tibia of Dunkin Hartley guinea pigs at 2 months, 3 months, and 2 years of age. The contralateral tibias were either histologically graded for OA or analyzed using immunohistochemistry. The results showed an increase in the reduced modulus (Er) in the deep zone of AC during early-stage OA (6.0 ± 1.75 MPa) compared to values at 2 months (4.04 ± 1.25 MPa) (*** p < 0.001). In severe OA (2-year) specimens, there was a significant reduction in Er throughout the superficial and middle AC zones, which correlated to increased ADAMTS 4 and 5 staining, and proteoglycan loss in these regions. In the subchondral bone, a 35.0% reduction in stiffness was observed between 2-month and 3-month specimens (*** p < 0.001). The severe OA age group had significantly increased SB stiffness of 36.2% and 109.6% compared to 2-month and 3-month-old specimens respectively (*** p < 0.001). In conclusion, this study provides useful information about the changes in the mechanical properties of both AC and SB during both early- and late-stage OA and indicates that an initial reduction in stiffness of the SB and an increase in stiffness in the deep zone of AC may precede early-stage cartilage degeneration.
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Affiliation(s)
- Sarah Davis
- School of Pharmacy and Biomedical Science, University of Portsmouth, Portsmouth PO1 2DT, UK; (M.R.); (G.B.)
- School of Mechanical and Design Engineering, University of Portsmouth, Portsmouth PO1 3DJ, UK; (J.Z.); (A.K.)
| | - Jurgita Zekonyte
- School of Mechanical and Design Engineering, University of Portsmouth, Portsmouth PO1 3DJ, UK; (J.Z.); (A.K.)
| | - Aikaterina Karali
- School of Mechanical and Design Engineering, University of Portsmouth, Portsmouth PO1 3DJ, UK; (J.Z.); (A.K.)
| | - Marta Roldo
- School of Pharmacy and Biomedical Science, University of Portsmouth, Portsmouth PO1 2DT, UK; (M.R.); (G.B.)
| | - Gordon Blunn
- School of Pharmacy and Biomedical Science, University of Portsmouth, Portsmouth PO1 2DT, UK; (M.R.); (G.B.)
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12
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Herbst EC, Evans LAE, Felder AA, Javaheri B, Pitsillides AA. 3D profiling of mouse epiphyses across ages reveals new potential imaging biomarkers of early spontaneous osteoarthritis. J Anat 2023; 242:1037-1050. [PMID: 36772893 PMCID: PMC10184544 DOI: 10.1111/joa.13834] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/12/2022] [Revised: 10/24/2022] [Accepted: 01/16/2023] [Indexed: 02/12/2023] Open
Abstract
Worldwide research groups and funding bodies have highlighted the need for imaging biomarkers to predict osteoarthritis (OA) progression and treatment effectiveness. Changes in trabecular architecture, which can be detected with non-destructive high-resolution CT imaging, may reveal OA progression before apparent articular surface damage. Here, we analysed the tibial epiphyses of STR/Ort (OA-prone) and CBA (healthy, parental control) mice at different ages to characterise the effects of mouse age and strain on multiple bony parameters. We isolated epiphyseal components using a semi-automated method, and measured the total epiphyseal volume; cortical bone, trabecular bone and marrow space volumes; mean trabecular and cortical bone thicknesses; trabecular volume relative to cortical volume; trabecular volume relative to epiphyseal interior (trabecular BV/TV); and the trabecular degree of anisotropy. Using two-way ANOVA (significance level ≤0.05), we confirmed that all of these parameters change significantly with age, and that the two strains were significantly different in cortical and trabecular bone volumes, and trabecular degree of anisotropy. STR/Ort mice had higher cortical and trabecular volumes and a lower degree of anisotropy. As the two mouse strains reflect markedly divergent OA predispositions, these parameters have potential as bioimaging markers to monitor OA susceptibility and progression. Additionally, significant age/strain interaction effects were identified for total epiphyseal volume, marrow space volume and trabecular BV/TV. These interactions confirm that the two mouse strains have different epiphyseal growth patterns throughout life, some of which emerge prior to OA onset. Our findings not only propose valuable imaging biomarkers of OA, but also provide insight into ageing 3D epiphyseal architecture bone profiles and skeletal biology underlying the onset and development of age-related OA in STR/Ort mice.
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Affiliation(s)
- Eva C. Herbst
- Palaeontological Institute & MuseumUniversity of ZurichZurichSwitzerland
- Skeletal Biology Group, Comparative Biomedical SciencesRoyal Veterinary CollegeLondonUK
| | - Lucinda A. E. Evans
- Skeletal Biology Group, Comparative Biomedical SciencesRoyal Veterinary CollegeLondonUK
| | - Alessandro A. Felder
- Skeletal Biology Group, Comparative Biomedical SciencesRoyal Veterinary CollegeLondonUK
- Research Software Development Group, Advanced Research ComputingUniversity College LondonLondonUK
| | - Behzad Javaheri
- Skeletal Biology Group, Comparative Biomedical SciencesRoyal Veterinary CollegeLondonUK
| | - Andrew A. Pitsillides
- Skeletal Biology Group, Comparative Biomedical SciencesRoyal Veterinary CollegeLondonUK
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13
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Motta F, Barone E, Sica A, Selmi C. Inflammaging and Osteoarthritis. Clin Rev Allergy Immunol 2023; 64:222-238. [PMID: 35716253 DOI: 10.1007/s12016-022-08941-1] [Citation(s) in RCA: 155] [Impact Index Per Article: 77.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 04/18/2022] [Indexed: 12/15/2022]
Abstract
Osteoarthritis is a highly prevalent disease particularly in subjects over 65 years of age worldwide. While in the past it was considered a mere consequence of cartilage degradation leading to anatomical and functional joint impairment, in recent decades, there has been a more dynamic view with the synovium, the cartilage, and the subchondral bone producing inflammatory mediators which ultimately lead to cartilage damage. Inflammaging is defined as a chronic, sterile, low-grade inflammation state driven by endogenous signals in the absence of infections, occurring with aging. This chronic status is linked to the production of reactive oxygen species and molecules involved in the development of age-related disease such as cancer, diabetes, and cardiovascular and neurodegenerative diseases. Inflammaging contributes to osteoarthritis development where both the innate and the adaptive immune response are involved. Elevated systemic and local inflammatory cytokines and senescent molecules promote cartilage degradation, and antigens derived from damaged joints further trigger inflammation through inflammasome activation. B and T lymphocyte populations also change with inflammaging and OA, with reduced regulatory functions, thus implicating self-reactivity as an additional mechanism of joint damage. The discovery of the underlying pathogenic pathways may help to identify potential therapeutic targets for the management or the prevention of osteoarthritis. We will provide a comprehensive evaluation of the current literature on the role of inflammaging in osteoarthritis and discuss the emerging therapeutic strategies.
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Affiliation(s)
- Francesca Motta
- Division of Rheumatology and Clinical Immunology, IRCCS Humanitas Research Hospital, via Manzoni 56, 20089, Rozzano, Milan, Italy.,Department of Biomedical Sciences, Humanitas University, via Rita Levi Montalcini, 20090, Pieve Emanuele, Milan, Italy
| | - Elisa Barone
- Division of Rheumatology and Clinical Immunology, IRCCS Humanitas Research Hospital, via Manzoni 56, 20089, Rozzano, Milan, Italy.,Department of Biomedical Sciences, Humanitas University, via Rita Levi Montalcini, 20090, Pieve Emanuele, Milan, Italy
| | - Antonio Sica
- Division of Rheumatology and Clinical Immunology, IRCCS Humanitas Research Hospital, via Manzoni 56, 20089, Rozzano, Milan, Italy.,Department of Pharmaceutical Sciences, Università del Piemonte Orientale "Amedeo Avogadro", Largo Donegani 2, 28100, Novara, Italy
| | - Carlo Selmi
- Division of Rheumatology and Clinical Immunology, IRCCS Humanitas Research Hospital, via Manzoni 56, 20089, Rozzano, Milan, Italy. .,Department of Biomedical Sciences, Humanitas University, via Rita Levi Montalcini, 20090, Pieve Emanuele, Milan, Italy.
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14
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Yoo HJ, Jeong HW, Park SB, Shim SJ, Nam HS, Lee YS. Do Individualized Patient-Specific Situations Predict the Progression Rate and Fate of Knee Osteoarthritis? Prediction of Knee Osteoarthritis. J Clin Med 2023; 12:jcm12031204. [PMID: 36769856 PMCID: PMC9918059 DOI: 10.3390/jcm12031204] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/11/2022] [Revised: 01/16/2023] [Accepted: 01/31/2023] [Indexed: 02/05/2023] Open
Abstract
Factors affecting the progression rate and fate of osteoarthritis need to be analyzed when considering patient-specific situation. This study aimed to identify the rate of remarkable progression and fate of primary knee osteoarthritis based on patient-specific situations. Between May 2003 and May 2019, 83,280 patients with knee pain were recruited for this study from the clinical data warehouse. Finally, 2492 knees with pain that were followed up for more than one year were analyzed. For analyzing affecting factors, patient-specific information was categorized and classified as demographic, radiologic, social, comorbidity disorders, and surgical intervention data. The degree of contribution of factors to the progression rate and the fate of osteoarthritis was analyzed. Bone mineral density (BMD), Kellgren-Lawrence (K-L) grade, and physical occupational demands were major contributors to the progression rate of osteoarthritis. Hypertension, initial K-L grade, and physical occupational demands were major contributors to the outcome of osteoarthritis. The progression rate and fate of osteoarthritis were mostly affected by the initial K-L grade and physical occupational demands. Patients who underwent surgical intervention for less than five years had the highest proportion of initial K-L grade 2 (49.0%) and occupations with high physical demand (41.3%). In identifying several contributing factors, the initial K-L grade and physical occupational demands were the most important factors. BMD and hypertension were also major contributors to the progression and fate of osteoarthritis, and the degree of contribution was lower compared to the two major factors.
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Affiliation(s)
- Hyun Jin Yoo
- Department of Orthopaedic Surgery, Seoul National University College of Medicine, Seoul National University Bundang Hospital, Seoul 13620, Republic of Korea
- Department of Orthopedic Surgery, Konyang University College of Medicine, Daejeon 35365, Republic of Korea
| | - Ho Won Jeong
- Department of Orthopaedic Surgery, Seoul National University College of Medicine, Seoul National University Bundang Hospital, Seoul 13620, Republic of Korea
| | - Sung Bae Park
- Department of Orthopaedic Surgery, Seoul National University College of Medicine, Seoul National University Bundang Hospital, Seoul 13620, Republic of Korea
| | - Seung Jae Shim
- Department of Orthopaedic Surgery, Seoul National University College of Medicine, Seoul National University Bundang Hospital, Seoul 13620, Republic of Korea
| | - Hee Seung Nam
- Department of Orthopaedic Surgery, Seoul National University College of Medicine, Seoul National University Bundang Hospital, Seoul 13620, Republic of Korea
| | - Yong Seuk Lee
- Department of Orthopaedic Surgery, Seoul National University College of Medicine, Seoul National University Bundang Hospital, Seoul 13620, Republic of Korea
- Correspondence: or ; Tel.: +82-31-787-7199; Fax: +82-31-787-4056
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15
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Induced inactivation of Wnt16 in young adult mice has no impact on osteoarthritis development. PLoS One 2022; 17:e0277495. [DOI: 10.1371/journal.pone.0277495] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/13/2022] [Accepted: 10/28/2022] [Indexed: 11/13/2022] Open
Abstract
Osteoarthritis (OA) is a common disorder and a major cause of disability in the elderly population. WNT16 has been suggested to play important roles in joint formation, bone homeostasis and OA development, but the mechanism of action is not clear. Transgenic mice lacking Wnt16 expression (Wnt16-/-) have a more severe experimental OA than control mice. In addition, Wnt16-/- mice have a reduced cortical thickness and develop spontaneous fractures. Herein, we have used Cre-Wnt16flox/flox mice in which Wnt16 can be conditionally ablated at any age through tamoxifen-inducible Cre-mediated recombination. Wnt16 deletion was induced in 7-week-old mice to study if the Cre-Wnt16flox/flox mice have a more severe OA phenotype after destabilizing the medial meniscus (DMM surgery) than littermate controls with normal Wnt16 expression (Wnt16flox/flox). WNT16 deletion was confirmed in articular cartilage and cortical bone in Cre-Wnt16flox/flox mice, shown by immunohistochemistry and reduced cortical bone area compared to Wnt16flox/flox mice. After DMM surgery, there was no difference in OA severity in the articular cartilage in the knee joint between the Cre-Wnt16flox/flox and Wnt16flox/flox mice in neither female nor male mice. In addition, there was no difference in osteophyte size in the DMM-operated tibia between the genotypes. In conclusion, inactivation of Wnt16 in adult mice do not result in a more severe OA phenotype after DMM surgery. Thus, presence of WNT16 in adult mice does not have an impact on experimental OA development. Taken together, our results from Cre-Wnt16flox/flox mice and previous results from Wnt16-/- mice suggest that WNT16 is crucial during synovial joint establishment leading to limited joint degradation also later in life, after onset of OA. This may be important when developing new therapeutics for OA treatment.
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16
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Auroux M, Merle B, Fontanges E, Duvert F, Lespessailles E, Chapurlat R. The disability associated with hand osteoarthritis is substantial in a cohort of post-menopausal women: the QUALYOR study. Osteoarthritis Cartilage 2022; 30:1526-1535. [PMID: 35995128 DOI: 10.1016/j.joca.2022.07.010] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/03/2022] [Revised: 06/10/2022] [Accepted: 07/14/2022] [Indexed: 02/02/2023]
Abstract
OBJECTIVES Our primary aims were to assess current prevalence of HOA and the disability associated with this condition, in the group usually most affected, i.e., women older than 55. METHODS We performed hand radiographs, clinical examination, grip strength measurement, AUSCAN and COCHIN questionnaires in a cohort of postmenopausal women aged at least 55. Radiographic hand OA (RHOA) was defined as at least 2 affected joints among 30, grading 2 or more using the Kellgren Lawrence score but without any HOA symptom. Symptomatic HOA (OA ACR) was defined according to ACR criteria for hand OA. Moderate to severe symptomatic HOA was defined as having OA ACR and AUSCAN total score of >43/100. RESULTS We enrolled 1,189 participants. The mean age was 71.7 years. Inter-reader reliability of radiographs reading was good (ICC = 0.86) and intra-reader reliability was excellent (ICC = 0.97). Among the 1,189 women, 333 (28.0%) had RHOA, 482 (40.5%) patients fulfilled the ACR criteria for symptomatic HOA and 82 of these (17% of OA ACR population) had moderate to severe symptomatic HOA. The prevalence of symptomatic erosive osteoarthritis was 11.8%. Mean AUSCAN and Cochin scores were higher and grip strength lower in patients with symptomatic HOA compared to patient without HOA. Differences were more noticeable in patients with moderate to severe HOA. CONCLUSIONS We have assessed disability associated with HOA in greater detail than previously and found that a third of postmenopausal women had RHOA, two fifths had symptomatic HOA and one sixth of symptomatic patients had moderate to severe HOA related disability and a tenth had symptomatic erosive osteoarthritis, representing a substantial burden of disease in our population-based cohort.
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Affiliation(s)
- M Auroux
- Hôpital E Herriot, Hospices Civils de Lyon, 69437 Lyon Cedex 03 Lyon, France.
| | - B Merle
- INSERM UMR 1033, Université de Lyon, Hôpital E Herriot, 69437 Lyon Cedex 03, France
| | - E Fontanges
- Hôpital E Herriot, Hospices Civils de Lyon, 69437 Lyon Cedex 03 Lyon, France
| | - F Duvert
- Hôpital E Herriot, Hospices Civils de Lyon, 69437 Lyon Cedex 03 Lyon, France
| | - E Lespessailles
- Centre Hospitalier Régional d'Orléans, Université d'Orléans, Orléans, France
| | - R Chapurlat
- Hôpital E Herriot, Hospices Civils de Lyon, 69437 Lyon Cedex 03 Lyon, France; INSERM UMR 1033, Université de Lyon, Hôpital E Herriot, 69437 Lyon Cedex 03, France
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17
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Tang Q, Zhao XS, Guo A, Cui RT, Song HL, Qi ZY, Pan Y, Yang Y, Zhang FF, Jin L. Therapeutic applications of adipose-derived stromal vascular fractions in osteoarthritis. World J Stem Cells 2022; 14:744-755. [PMID: 36337155 PMCID: PMC9630988 DOI: 10.4252/wjsc.v14.i10.744] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/06/2022] [Revised: 07/08/2022] [Accepted: 09/12/2022] [Indexed: 02/07/2023] Open
Abstract
Osteoarthritis (OA) is considered to be a highly heterogeneous disease with progressive cartilage loss, subchondral bone remodeling, and low-grade inflammation. It is one of the world's leading causes of disability. Most conventional clinical treatments for OA are palliative drugs, which cannot fundamentally cure this disease. The stromal vascular fraction (SVF) from adipose tissues is a heterogeneous cell population. According to previous studies, it contains a large number of mesenchymal stem cells, which have been used to treat OA with good therapeutic results. This safe, simple, and effective therapy is expected to be applied and promoted in the future. In this paper, the detailed pathogenesis, diagnosis, and current clinical treatments for OA are introduced. Then, clinical studies and the therapeutic mechanism of SVF for the treatment of OA are summarized.
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Affiliation(s)
- Qi Tang
- School of Life Science and Technology, China Pharmaceutical University, Nanjing 211198, Jiangsu Province, China
| | - Xian-Sheng Zhao
- Department of Dermatology, Huashan Hospital, Fudan University, Shanghai 200040, China
| | - Ao Guo
- School of Life Science and Technology, China Pharmaceutical University, Nanjing 211198, Jiangsu Province, China
| | - Ruo-Tong Cui
- School of Life Science and Technology, China Pharmaceutical University, Nanjing 211198, Jiangsu Province, China
| | - Huai-Le Song
- School of Life Science and Technology, China Pharmaceutical University, Nanjing 211198, Jiangsu Province, China
| | - Zi-Yang Qi
- School of Life Science and Technology, China Pharmaceutical University, Nanjing 211198, Jiangsu Province, China
| | - Yi Pan
- School of Life Science and Technology, China Pharmaceutical University, Nanjing 211198, Jiangsu Province, China
| | - Yue Yang
- School of Life Science and Technology, China Pharmaceutical University, Nanjing 211198, Jiangsu Province, China
| | - Fang-Fang Zhang
- School of Life Science and Technology, China Pharmaceutical University, Nanjing 211198, Jiangsu Province, China
| | - Liang Jin
- School of Life Science and Technology, China Pharmaceutical University, Nanjing 211198, Jiangsu Province, China
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18
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Is Osteoarthritis Always Associated with Low Bone Mineral Density in Elderly Patients? MEDICINA (KAUNAS, LITHUANIA) 2022; 58:medicina58091207. [PMID: 36143883 PMCID: PMC9502981 DOI: 10.3390/medicina58091207] [Citation(s) in RCA: 13] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 07/21/2022] [Revised: 08/24/2022] [Accepted: 08/26/2022] [Indexed: 11/17/2022]
Abstract
Background and Objectives: The relationship between osteoarthritis (OA) and osteoporosis (OP) has been analysed for over four decades. However, this relationship has remained controversial. Numerous observational and longitudinal studies have shown an inverse association between the two diseases and a protective effect of one against the other. On the other hand, some studies show that patients with OA have impaired bone strength and are more prone to fractures. The study’s main objective was to determine the bone mineral density (BMD) of the spine and hip (femoral neck) of postmenopausal women of different ages, with radiologically determined OA of the hip and knee, as well as to determine the correlation between BMD values and age in the experimental group. Materials and Methods: The retrospective cohort study included 7018 patients with osteoarthritis of peripheral joints and the spine, examined by a rheumatologist in an outpatient rheumatology clinic at the Institute for Treatment and Rehabilitation, Niška Banja from July 2019 to March 2021. A nested anamnestic study was conducted within the cohort study of patients, and it included two groups: an experimental group composed of 60 postmenopausal women, and a control group composed of the same number of women. Out of 120 patients, 24 did not meet the criteria for the continuation of the study (due to technical errors—radiographic and/or densitometry artefacts). Fifty-six postmenopausal women (aged 45−77 years) with hip and knee radiological OA were examined as an experimental group. The participants were divided into two subgroups according to age (45−60 years and over 61 years). The control group included 40 healthy postmenopausal women of the same age range, without radiological OA, with normal BMD of the hip and spine. All patients with OA met the American College of Radiology (ACR) criteria. OA of the hip and knee was determined radiologically according to Kellgren and Lawrence (K&L) classification, and patients were included in the study if a K&L grade of at least ≥ 2 was present. Hip and spine BMD was measured by dual-energy X-ray absorptiometry (DXA). Results: Compared to the control group, we found statistically significantly lower BMD and T-scores of the spine in older postmenopausal women: BMD (g/cm2), p = 0.014; T-score, p = 0.007, as well as of the hip: BMD (g/cm2), p = 0.024; T-score p < 0.001. The values of BMD and T-score of the spine and hip are lower in more severe forms of OA (X-ray stage 3 and 4, according to K&L), p < 0.001. We found negative correlation between BMD and T-score and age only for the hip: BMD (g/cm2), ρ = 0.378, p = 0.005; T-score ρ = −0.349, p = 0.010. Conclusions: Older postmenopausal women with radiographic hip and knee OA had significantly lower BMD of the hip and spine as compared to the control group without OA, pointing to the need for the prevention and treatment of OA, as well as early diagnosis, monitoring, and treatment of low bone mineral density.
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Yang X, Liang X, Guo H, Ma L, Jian L, Zhao X, Wang J, Yang L, Meng Z, Jin Q. β2-Adrenergic receptor expression in subchondral bone of patients with varus knee osteoarthritis. Open Med (Wars) 2022; 17:1031-1044. [PMID: 35794997 PMCID: PMC9175016 DOI: 10.1515/med-2022-0498] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/28/2021] [Revised: 05/05/2022] [Accepted: 05/09/2022] [Indexed: 11/15/2022] Open
Abstract
Abstract
An important causative factor in osteoarthritis (OA) is the abnormal mechanical stress-induced bone remodeling of the subchondral bone. β2-adrenergic receptor (Adrb2) plays a major role in mechanical stresses that induce bone remodeling. The medial tibial plateau (MTP) and lateral tibial plateau (LTP) of patients with varus Knee osteoarthritis (KO) bear different mechanical stresses. The present study aimed to investigate the expression of Adrb2 in medial tibial plateau subchondral bone (MTPSB) and lateral tibial plateau subchondral bone (LTPSB) in patients with varus KO. A total of 30 tibial plateau samples from patients undergoing total knee arthroplasty for varus KO and MTPSB and LTPSB were studied. Statistical analysis was performed using paired sample t-tests. Safranin O-Fast Green staining and Micro-computed tomography showed significant differences in the bone structure between MTPSB and LTPSB. Tartrate-resistant acid phosphatase (TRAP)-positive cell density in MTPSB was higher than that in LTPSB. Immunohistochemistry, reverse transcription-quantitative polymerase chain reaction, and Western blot analysis revealed that compared to LTPSB, the levels of Adrb2, tyrosine hydroxylase (TH), and osteocalcin increased significantly in MTPSB. Double-labeling immunofluorescence showed Adrb2 was present in the majority of TRAP-positive multinuclear cells of the MTPSB. The expression of Adrb2 and TH was significantly higher in MTPSB than in LTPSB, confirming the involvement of these molecules in the development of OA.
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Affiliation(s)
- Xiaochun Yang
- Department of Orthopedics Ward 3, The General Hospital of Ningxia Medical University , Yinchuan , 750004, Ningxia , China
| | - Xuegang Liang
- Department of The General Hospital of Ningxia Medical University, Ningxia Medical University , Yinchuan , 750004, Ningxia , China
| | - Haohui Guo
- Department of Orthopedics Ward 3, The General Hospital of Ningxia Medical University , Yinchuan , 750004, Ningxia , China
| | - Long Ma
- Department of Orthopedics Ward 3, The General Hospital of Ningxia Medical University , Yinchuan , 750004, Ningxia , China
| | - Li Jian
- Department of Pathology, The General Hospital of Ningxia Medical University , Yinchuan , 750004, Ningxia , China
| | - Xin Zhao
- Department of Orthopedics Ward 3, The General Hospital of Ningxia Medical University , Yinchuan , 750004, Ningxia , China
| | - Jian Wang
- Department of Orthopedics Ward 3, The General Hospital of Ningxia Medical University , Yinchuan , 750004, Ningxia , China
| | - Lvlin Yang
- Department of The General Hospital of Ningxia Medical University, Ningxia Medical University , Yinchuan , 750004, Ningxia , China
| | - Zhiqiang Meng
- Department of The General Hospital of Ningxia Medical University, Ningxia Medical University , Yinchuan , 750004, Ningxia , China
| | - Qunhua Jin
- Department of Orthopedics Ward 3, The General Hospital of Ningxia Medical University , Yinchuan , 750004, Ningxia , China
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Ciliberti FK, Guerrini L, Gunnarsson AE, Recenti M, Jacob D, Cangiano V, Tesfahunegn YA, Islind AS, Tortorella F, Tsirilaki M, Jónsson H, Gargiulo P, Aubonnet R. CT- and MRI-Based 3D Reconstruction of Knee Joint to Assess Cartilage and Bone. Diagnostics (Basel) 2022; 12:279. [PMID: 35204370 PMCID: PMC8870751 DOI: 10.3390/diagnostics12020279] [Citation(s) in RCA: 12] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/07/2021] [Revised: 01/10/2022] [Accepted: 01/20/2022] [Indexed: 02/01/2023] Open
Abstract
For the observation of human joint cartilage, X-ray, computed tomography (CT) or magnetic resonance imaging (MRI) are the main diagnostic tools to evaluate pathologies or traumas. The current work introduces a set of novel measurements and 3D features based on MRI and CT data of the knee joint, used to reconstruct bone and cartilages and to assess cartilage condition from a new perspective. Forty-seven subjects presenting a degenerative disease, a traumatic injury or no symptoms or trauma were recruited in this study and scanned using CT and MRI. Using medical imaging software, the bone and cartilage of the knee joint were segmented and 3D reconstructed. Several features such as cartilage density, volume and surface were extracted. Moreover, an investigation was carried out on the distribution of cartilage thickness and curvature analysis to identify new markers of cartilage condition. All the extracted features were used with advanced statistics tools and machine learning to test the ability of our model to predict cartilage conditions. This work is a first step towards the development of a new gold standard of cartilage assessment based on 3D measurements.
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Affiliation(s)
- Federica Kiyomi Ciliberti
- Institute of Biomedical and Neural Engineering, Reykjavik University, 101 Reykjavik, Iceland; (F.K.C.); (L.G.); (A.E.G.); (M.R.); (D.J.); (V.C.); (R.A.)
- Department of Electrical, Information Engineering and Applied Mathematics, University of Salerno, 84084 Salerno, Italy;
| | - Lorena Guerrini
- Institute of Biomedical and Neural Engineering, Reykjavik University, 101 Reykjavik, Iceland; (F.K.C.); (L.G.); (A.E.G.); (M.R.); (D.J.); (V.C.); (R.A.)
- Laboratory of Cellular and Molecular Engineering “Silvio Cavalcanti”, Department of Electrical, Electronic and Information Engineering “Guglielmo Marconi” (DEI), University of Bologna, 47521 Cesena, Italy
| | - Arnar Evgeni Gunnarsson
- Institute of Biomedical and Neural Engineering, Reykjavik University, 101 Reykjavik, Iceland; (F.K.C.); (L.G.); (A.E.G.); (M.R.); (D.J.); (V.C.); (R.A.)
| | - Marco Recenti
- Institute of Biomedical and Neural Engineering, Reykjavik University, 101 Reykjavik, Iceland; (F.K.C.); (L.G.); (A.E.G.); (M.R.); (D.J.); (V.C.); (R.A.)
| | - Deborah Jacob
- Institute of Biomedical and Neural Engineering, Reykjavik University, 101 Reykjavik, Iceland; (F.K.C.); (L.G.); (A.E.G.); (M.R.); (D.J.); (V.C.); (R.A.)
| | - Vincenzo Cangiano
- Institute of Biomedical and Neural Engineering, Reykjavik University, 101 Reykjavik, Iceland; (F.K.C.); (L.G.); (A.E.G.); (M.R.); (D.J.); (V.C.); (R.A.)
| | | | | | - Francesco Tortorella
- Department of Electrical, Information Engineering and Applied Mathematics, University of Salerno, 84084 Salerno, Italy;
| | - Mariella Tsirilaki
- Department of Radiology, Landspitali, University Hospital of Iceland, 101 Reykjavik, Iceland;
| | - Halldór Jónsson
- Department of Orthopaedics, Landspitali, University Hospital of Iceland, 101 Reykjavik, Iceland;
- Medical Faculty, University of Iceland, 101 Reykjavik, Iceland
| | - Paolo Gargiulo
- Institute of Biomedical and Neural Engineering, Reykjavik University, 101 Reykjavik, Iceland; (F.K.C.); (L.G.); (A.E.G.); (M.R.); (D.J.); (V.C.); (R.A.)
- Department of Science, Landspitali, University Hospital of Iceland, 101 Reykjavik, Iceland
| | - Romain Aubonnet
- Institute of Biomedical and Neural Engineering, Reykjavik University, 101 Reykjavik, Iceland; (F.K.C.); (L.G.); (A.E.G.); (M.R.); (D.J.); (V.C.); (R.A.)
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Jiang L, Jiang Y, Wang A, Wu C, Shen Y. The causal association between bone mineral density and risk of osteoarthritis: A Mendelian randomization study. Front Endocrinol (Lausanne) 2022; 13:1021083. [PMID: 36714576 PMCID: PMC9874138 DOI: 10.3389/fendo.2022.1021083] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/06/2022] [Accepted: 12/16/2022] [Indexed: 01/12/2023] Open
Abstract
OBJECTIVES The causal direction and magnitude of the association between total body bone mineral density (TB-BMD) and osteoarthritis (OA) risk is uncertain owing to the susceptibility of observational studies to confounding and reverse causation. The study aimed to explore the relationships between TB-BMD concentration and OA using Mendelian randomization (MR). METHODS In this study, we used two-sample MR to obtain unconfounded estimates of the effect of TB-BMD on hip and knee OA. Single nucleotide polymorphisms (SNPs) strongly associated with TB-BMD in a large genome-wide association study (GWAS) were identified and selected as instrumental variables (IVs). In addition to the main analysis using inverse-variance weighted (IVW) method, we applied 2 additional methods to control for pleiotropy(MR-Egger regression, weighted median estimator) and compared the respective MR estimates. RESULTS MR analyses suggested that genetically predicted higher TB-BMD is associated with risks of hip OA (For IVW: OR=1.199, 95%CI: 1.02-1.42, P=0.032; for WM: OR=1.257, 95%CI: 1.09-1.45, P=0.002). There was no evidence that the observed causal effect between TB-BMD and the risk of hip OA was affected by genetic pleiotropy(P=0.618). Additionally, our study didn't support causal effects of a genetically increased TB-BMD risk on knee OA risk(OR=1.121, 95%CI: 0.99-1.28, P=0.084 using IVW; OR=1.132, 95%CI: 0.99-1.29, P=0.068 using WM; OR=1.274, 95%CI: 0.88-1.85, P=0.217 using MR-Egger). CONCLUSIONS Our findings support a causal effect that a genetic predisposition to systematically higher TB-BMD was associated with the risk of OA. And, TB-BMD likely exerts an effect on the risk of hip OA not knee OA.
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Affiliation(s)
- Liying Jiang
- Department of Prevention Medicine, College of Public health, Shanghai University of Medicine & Health Sciences, Shanghai, China
- Jiading Central Hospital, Shanghai University of Medicine & Health Sciences, Shanghai, China
| | - Ying Jiang
- Department of Health, Center for Disease Control and Prevention in Suqian, Suqian, Jiangsu Province, China
| | - Anqi Wang
- Department of Nursing, Shanghai University of Traditional Chinese Medicine, Shanghai, China
| | - Cui Wu
- Department of Non-communicable Disease, Baoshan District Center for Disease Control and Prevention in Shanghai, Shanghai, China
- *Correspondence: Yi Shen, ; Cui Wu,
| | - Yi Shen
- Department of Epidemiology, School of Public Health, Nantong University, Nantong, Jiangsu Province, China
- *Correspondence: Yi Shen, ; Cui Wu,
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Baker BS, Bozynski CC, Leary EV, Sherwood RJ, Keeney JA, Cook JL, Duren DL. Tibial Bone Quality in Former Bariatric Surgery Patients with Osteoarthritis. Obes Surg 2021; 31:5322-5329. [PMID: 34625891 DOI: 10.1007/s11695-021-05727-w] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/29/2021] [Revised: 09/10/2021] [Accepted: 09/22/2021] [Indexed: 12/14/2022]
Abstract
Downstream effects of bariatric weight-loss surgery have been associated with bone resorption, potentially jeopardizing total knee arthroplasty (TKA) implant fixation/ingrowth. PURPOSE This case-control study sought to determine if TKA patients with history of bariatric surgery exhibit altered microanatomy of subchondral bone quality in the tibial plateau compared to controls. MATERIALS AND METHODS With IRB approval, 41 bone samples were evaluated from 12 former bariatric surgery patients and 10 sex-, age-, weight-, height-, and BMI-matched controls. Patient-Reported Outcomes Measurement Information System (PROMIS) surveys were completed prior to TKA. Tibial plateau osteochondral tissues were recovered during the TKA procedure, and samples from the medial and lateral plateaus were dissected into 1 × 2 cm sections, scanned using microcomputed tomography (µCT), and plastic-embedded for histologic sectioning/staining of undecalcified bone. Paired t tests with Bonferroni correction were performed to assess group differences. RESULTS Female bariatric surgery patients had reduced osteoid/total area and greater osteoclast number asymmetry than female controls (p < 0.03). No differences were noted in µCT or histologic bone parameters between bariatric and control patients when the sexes were combined. Bariatric patients self-reported worse preoperative PROMIS pain interference and physical function scores than controls (p < 0.04). CONCLUSIONS Similarities of subchondral bone between former bariatric surgery patients and matched controls indicate OA disease progression dominates the bone landscape in both patient groups.
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Affiliation(s)
- Breanne S Baker
- Department of Orthopaedic Surgery and Thompson Laboratory for Regenerative Orthopaedics, Missouri Orthopaedic Institute, University of Missouri, Research 4th Floor, 1100 Virginia Avenue, Columbia, MO, 65212, USA
- School of Kinesiology, Applied Health, and Recreation, Oklahoma State University, Stillwater, OK, 74078, USA
| | - Chantelle C Bozynski
- Department of Orthopaedic Surgery and Thompson Laboratory for Regenerative Orthopaedics, Missouri Orthopaedic Institute, University of Missouri, Research 4th Floor, 1100 Virginia Avenue, Columbia, MO, 65212, USA
| | - Emily V Leary
- Department of Orthopaedic Surgery and Thompson Laboratory for Regenerative Orthopaedics, Missouri Orthopaedic Institute, University of Missouri, Research 4th Floor, 1100 Virginia Avenue, Columbia, MO, 65212, USA
| | - Richard J Sherwood
- Department of Orthopaedic Surgery and Thompson Laboratory for Regenerative Orthopaedics, Missouri Orthopaedic Institute, University of Missouri, Research 4th Floor, 1100 Virginia Avenue, Columbia, MO, 65212, USA
- Department of Pathology and Anatomical Sciences, Craniofacial Research Center, University of Missouri, Columbia, MO, 65212, USA
| | - James A Keeney
- Department of Orthopaedic Surgery and Thompson Laboratory for Regenerative Orthopaedics, Missouri Orthopaedic Institute, University of Missouri, Research 4th Floor, 1100 Virginia Avenue, Columbia, MO, 65212, USA
| | - James L Cook
- Department of Orthopaedic Surgery and Thompson Laboratory for Regenerative Orthopaedics, Missouri Orthopaedic Institute, University of Missouri, Research 4th Floor, 1100 Virginia Avenue, Columbia, MO, 65212, USA
| | - Dana L Duren
- Department of Orthopaedic Surgery and Thompson Laboratory for Regenerative Orthopaedics, Missouri Orthopaedic Institute, University of Missouri, Research 4th Floor, 1100 Virginia Avenue, Columbia, MO, 65212, USA.
- Department of Pathology and Anatomical Sciences, Craniofacial Research Center, University of Missouri, Columbia, MO, 65212, USA.
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Choi ES, Shin HD, Sim JA, Na YG, Choi WJ, Shin DD, Baik JM. Relationship of Bone Mineral Density and Knee Osteoarthritis (Kellgren-Lawrence Grade): Fifth Korea National Health and Nutrition Examination Survey. Clin Orthop Surg 2021; 13:60-66. [PMID: 33747379 PMCID: PMC7948046 DOI: 10.4055/cios20111] [Citation(s) in RCA: 21] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/07/2020] [Accepted: 07/01/2020] [Indexed: 11/28/2022] Open
Abstract
Background Osteoarthritis (OA) and osteoporosis (OP) are the 2 most common bone disorders associated with aging. We can simply assume that older patients have a higher incidence of OA and OP with more severity. Although several papers have conducted studies on the relationship between OA and OP, none of them has demonstrated a conclusive link. In this study, we used radiological knee OA and bone mineral density (BMD; T-score of the total hip and lumbar spine) to analyze the incidence of OA and OP in a large population. We aimed to determine the relationship between OA and OP and investigate the associated risk factors Methods This cross-sectional study used data extracted from the 2010–2012 Korea National Health and Nutrition Examination Survey. We evaluated a total of 4,250 participants aged ≥ 50 years who underwent knee radiography and dual-energy X-ray absorptiometry and their laboratory results. The relationship between radiological knee OA and BMD was assessed. The generalized linear model was used to evaluate the relationship between BMD and Kellgren-Lawrence (KL) grade. Results The higher KL grade was associated with older age, higher body mass index (BMI), female sex, and lower hemoglobin level (p < 0.001). No significant association was found between OA and the following variables: white blood cell, platelet, total cholesterol, vitamin D, alkaline phosphatase, parathyroid hormone, hypertension, diabetes, asthma, dyslipidemia, smoking status, alcohol consumption, and regular exercise (p > 0.05). After adjusting for confounding factors (age, BMI, diabetes, hypertension, smoking, and alcohol consumption), the average T-scores of total hip and lumbar spine were the highest in the mild OA group with KL grade 2 (−0.22 ± 1.08 and −0.89 ± 1.46, respectively, p < 0.001). The average T-scores of the total hip and lumbar spine significantly decreased as OA progressed from moderate (KL grade 3; −0.49 ± 1.05 and −1.33 ± 1.38, respectively, p < 0.001) to severe (KL grade 4; −0.73 ± 1.13 and −1.74 ± 1.75, respectively, p < 0.001). T-scores of the moderate-to-severe OA group were significantly lower than those of the non-OA group (KL grades 0 and 1, p < 0.001). Conclusions Compared with the non-OA group, BMD (T-scores of the total hip and lumbar spine) was higher in the mild OA group and lower in the moderate-to-severe OA group.
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Affiliation(s)
- Eun-Seok Choi
- Department of Orthopaedic Surgery, Chungnam National University Hospital, Daejeon, Korea
| | - Hyun Dae Shin
- Department of Orthopaedic Surgery, Chungnam National University Hospital, Daejeon, Korea
| | - Jae Ang Sim
- Department of Orthopaedic Surgery, Gil Medical Center, Gachon University College of Medicine, Incheon, Korea
| | - Young Gon Na
- Department of Orthopaedic Surgery, CM Hospital, Seoul, Korea
| | - Won-Jun Choi
- Department of Occupational and Environmental Medicine, Gil Medical Center, Gachon University College of Medicine, Incheon, Korea
| | - Dae-Do Shin
- Department of Orthopaedic Surgery, Gil Medical Center, Gachon University College of Medicine, Incheon, Korea
| | - Jong-Min Baik
- Department of Orthopaedic Surgery, Gil Medical Center, Gachon University College of Medicine, Incheon, Korea
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Kasher M, Williams FMK, Freidin MB, Cherny S, Livshits G. An in-depth study of the associations between osteoarthritis- and osteoporosis-related phenotypes at different skeletal locations. Osteoporos Int 2020; 31:2197-2208. [PMID: 32556517 DOI: 10.1007/s00198-020-05504-y] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/13/2020] [Accepted: 06/12/2020] [Indexed: 01/01/2023]
Abstract
UNLABELLED The relationship between OA and osteoporosis characteristics remains controversial. This study revealed that age-adjusted hand OA is associated with lower hand/arm BMD levels. Wrist fracture occurrence is associated with increased OA hand scores and low arm BMD. Conversely, age-adjusted knee and spine OA is associated with high spine, hip, and total BMDs. INTRODUCTION Osteoarthritis (OA) and osteoporosis are two common musculoskeletal diseases which contribute a high burden of disability, yet assessments of their relationship remains controversial. The aim of this study was to clarify the association between bone mineral densities (BMD) of the hand, arm, spine, hip, and total body, and OA of the hand and knee and lumbar disc degeneration in two different ethnic groups. METHODS Radiographic assessments of the hand, knee, and spine were collected and coded for joint space narrowing, osteophytes, and the Kellgren-Lawrence score from Chuvashian (n = 1504) and British (n = 2280) individuals. BMD measurements of standard skeletal sites were estimated by dual X-ray absorptiometry. Age- and familial-adjusted regression analyses were conducted to determine associations. RESULTS Knee OA affection was positively associated with elevated hip, spine, and total body BMD levels (p < 0.001). Additionally, disc degeneration phenotypes showed significant positive associations with the hip, spine, and total BMD (p < 0.001). However, increased hand OA scores was significantly negatively correlated with arm and hand BMD measurements in males and females in both samples (p < 0.001). Additionally, higher hand OA scores were significantly associated with wrist fracture. CONCLUSIONS We discovered a clear pattern of association between hand OA and low hand and arm BMD, with increased risk of wrist fracture, as well as reproducing previous associations between knee and spine OA and elevated spine, hip, and total body BMD. It appears that hand OA manifests differently in comparison to hip and knee OA.
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Affiliation(s)
- M Kasher
- Human Population Biology Research Unit, Department of Anatomy and Anthropology, Sackler Faculty of Medicine, Tel Aviv University, Ramat-Aviv, Tel Aviv, Israel
| | - F M K Williams
- Department of Twin Research and Genetic Epidemiology, School of Life Course Sciences, King's College London, London, UK
| | - M B Freidin
- Department of Twin Research and Genetic Epidemiology, School of Life Course Sciences, King's College London, London, UK
| | - S Cherny
- Human Population Biology Research Unit, Department of Anatomy and Anthropology, Sackler Faculty of Medicine, Tel Aviv University, Ramat-Aviv, Tel Aviv, Israel
- Department of Epidemiology and Preventive Medicine, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
| | - G Livshits
- Human Population Biology Research Unit, Department of Anatomy and Anthropology, Sackler Faculty of Medicine, Tel Aviv University, Ramat-Aviv, Tel Aviv, Israel.
- Department of Twin Research and Genetic Epidemiology, School of Life Course Sciences, King's College London, London, UK.
- Adelson Medical School, Ariel University, Ariel, Israel.
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Ren Y, Hu J, Tan J, Tang X, Li Q, Yang H, Liu C, He Q, Zou K, Sun X, Tan B. Incidence and risk factors of symptomatic knee osteoarthritis among the Chinese population: analysis from a nationwide longitudinal study. BMC Public Health 2020; 20:1491. [PMID: 33004017 PMCID: PMC7528331 DOI: 10.1186/s12889-020-09611-7] [Citation(s) in RCA: 27] [Impact Index Per Article: 5.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/07/2020] [Accepted: 09/25/2020] [Indexed: 02/08/2023] Open
Abstract
Background Knee osteoarthritis (OA) is a common disease condition associated with aging and a frequent cause of primary care consultations. Few longitudinal studies have been conducted to investigate the incidence of symptomatic knee osteoarthritis (OA) and to identify its risk factors among the Chinese population. Methods The China Health and Retirement Longitudinal Study (CHARLS) is a nationwide longitudinal survey of persons aged ≥45 years. Symptomatic knee OA was diagnosed when both self-reported knee pain and self-reported physician-diagnosis arthritis existed. Using the national survey data collected from the CHARLS, we estimated the incidence of symptomatic knee OA, taking into account the complex survey design and response rate. We applied weighted logistic regression analysis to identify its risk factors. Results In the 4-year follow-up, the cumulative incidence of symptomatic knee OA among middle-aged and older Chinese adults was 8.5%; the incidence was higher among females (11.2%) than males (5.6%). Female (odds ratio (OR) 1.98 [95% confidence interval (CI) 1.65–2.37]), rural area (OR 1.32 [95% CI 1.08–1.60]), and West region (OR 2.33 [95% CI 1.89–2.87]) were associated with a higher risk of incident symptomatic knee OA. Physical activities (OR 0.47 [95% CI 0.29–0.76]) and high education level (OR 0.60 [95% CI 0.41–0.88]) was associated with a lower risk of incident symptomatic knee OA, while histories of heart disease (OR 1.40 [95% CI 1.07–1.82]), kidney disease (OR 1.80 [95% CI 1.35–2.39]), and digestive disease (OR 1.54 [95% CI 1.30–1.82]) were associated with a higher risk of incident symptomatic knee OA. Conclusion The cumulative incidence of symptomatic knee OA over 4 years was relatively high, and varied by province and region. Lack of physical activities was confirmed to be risk factors of incident symptomatic knee OA. The presence of heart disease, kidney disease, and digestive disease may be associated with a higher risk of incident symptomatic knee OA, further research need to confirm these findings.
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Affiliation(s)
- Yan Ren
- Chinese Evidence-based Medicine Center and National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University, Chengdu, 610044, Sichuan, China
| | - Jiang Hu
- Department of Orthopedics, Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chengdu, 611731, Sichuan, China
| | - Jing Tan
- Chinese Evidence-based Medicine Center and National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University, Chengdu, 610044, Sichuan, China
| | - Xiaoming Tang
- Department of Orthopedics, Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chengdu, 611731, Sichuan, China
| | - Qianrui Li
- Chinese Evidence-based Medicine Center and National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University, Chengdu, 610044, Sichuan, China.,Department of Nuclear Medicine, West China Hospital, Sichuan University, Chengdu, Sichuan, China
| | - Huazhen Yang
- West China School of Public Health, Sichuan University, Chengdu, 610041, China
| | - Chunrong Liu
- Chinese Evidence-based Medicine Center and National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University, Chengdu, 610044, Sichuan, China
| | - Qiao He
- Chinese Evidence-based Medicine Center and National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University, Chengdu, 610044, Sichuan, China
| | - Kang Zou
- Chinese Evidence-based Medicine Center and National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University, Chengdu, 610044, Sichuan, China
| | - Xin Sun
- Chinese Evidence-based Medicine Center and National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University, Chengdu, 610044, Sichuan, China.
| | - Bo Tan
- Department of Orthopedics, Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chengdu, 611731, Sichuan, China.
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Hartley A, Hardcastle SA, Paternoster L, McCloskey E, Poole KES, Javaid MK, Aye M, Moss K, Granell R, Gregory J, Williams M, Tobias JH, Gregson CL. Individuals with high bone mass have increased progression of radiographic and clinical features of knee osteoarthritis. Osteoarthritis Cartilage 2020; 28:1180-1190. [PMID: 32417557 DOI: 10.1016/j.joca.2020.03.020] [Citation(s) in RCA: 20] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/24/2019] [Revised: 03/16/2020] [Accepted: 03/26/2020] [Indexed: 02/02/2023]
Abstract
OBJECTIVE High bone mass (HBM) is associated with an increased prevalence of radiographic knee OA (kOA), characterized by osteophytosis. We aimed to determine if progression of radiographic kOA, and its sub-phenotypes, is increased in HBM and whether observed changes are clinically relevant. DESIGN A cohort with and without HBM (L1 and/or total hip bone mineral density Z-score≥+3.2) had knee radiographs collected at baseline and 8-year follow-up. Sub-phenotypes were graded using the OARSI atlas. Medial/lateral tibial/femoral osteophyte and medial/lateral joint space narrowing (JSN) grades were summed and Δosteophytes, ΔJSN derived. Pain, function and stiffness were quantified using the WOMAC questionnaire. Associations between HBM status and sub-phenotype progression were determined using multivariable linear/poisson regression, adjusting for age, sex, height, baseline sub-phenotype grade, menopause, education and total body fat mass (TBFM). Generalized estimating equations accounted for individual-level clustering. RESULTS 169 individuals had repeated radiographs, providing 330 knee images; 63% had HBM, 73% were female, mean (SD) age was 58 (12) years. Whilst HBM was not clearly associated with overall Kellgren-Lawrence measured progression (RR = 1.55 [0.56.4.32]), HBM was positively associated with both Δosteophytes and ΔJSN individually (adjusted mean differences between individuals with and without HBM 0.45 [0.01.0.89] and 0.15 [0.01.0.29], respectively). HBM individuals had higher WOMAC knee pain scores (β = 7.42 [1.17.13.66]), largely explained by adjustment for osteophyte score (58% attenuated) rather than JSN (30% attenuated) or TBFM (16% attenuated). The same pattern was observed for symptomatic stiffness and functional limitation. CONCLUSIONS HBM is associated with osteophyte progression, which appears to contribute to increased reported pain, stiffness and functional loss.
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Affiliation(s)
- A Hartley
- Musculoskeletal Research Unit, Translational Health Sciences, Bristol Medical School, University of Bristol, Bristol, UK; MRC Integrative Epidemiology Unit, Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, UK.
| | - S A Hardcastle
- Musculoskeletal Research Unit, Translational Health Sciences, Bristol Medical School, University of Bristol, Bristol, UK; Royal National Hospital for Rheumatic Diseases, Royal United Hospitals Bath NHS Foundation Trust, Bath, UK
| | - L Paternoster
- MRC Integrative Epidemiology Unit, Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, UK
| | - E McCloskey
- Academic Unit of Bone Metabolism, Department of Oncology and Metabolism, The Mellanby Centre for Bone Research, University of Sheffield, Sheffield, UK; Centre for Metabolic Diseases, University of Sheffield Medical School, Sheffield, UK; Centre for Integrated Research Into Musculoskeletal Ageing, University of Sheffield Medical School, Sheffield, UK
| | - K E S Poole
- Cambridge NIHR Biomedical Research Centre and the Wellcome Trust Clinical Research Facility, Cambridge
| | - M K Javaid
- Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, Oxford, UK
| | - M Aye
- Department of Diabetes, Endocrinology and Metabolism, Hull and East Yorkshire Hospitals NHS Trust, Hull, UK
| | - K Moss
- Centre for Rheumatology, St George's Hospital, St George's Healthcare NHS Trust, London, UK
| | - R Granell
- MRC Integrative Epidemiology Unit, Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, UK
| | - J Gregory
- Institute of Medical Science, School of Medicine, University of Aberdeen, Aberdeen, UK
| | - M Williams
- Department of Radiology, Southmead Hospital, North Bristol NHS Trust, Bristol UK
| | - J H Tobias
- Musculoskeletal Research Unit, Translational Health Sciences, Bristol Medical School, University of Bristol, Bristol, UK; MRC Integrative Epidemiology Unit, Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, UK
| | - C L Gregson
- Musculoskeletal Research Unit, Translational Health Sciences, Bristol Medical School, University of Bristol, Bristol, UK
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Nevitt MC, Felson DT. High bone density and radiographic osteoarthritis: questions answered and unanswered. Osteoarthritis Cartilage 2020; 28:1151-1153. [PMID: 32417559 PMCID: PMC10411125 DOI: 10.1016/j.joca.2020.05.006] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/02/2020] [Accepted: 05/07/2020] [Indexed: 02/02/2023]
Affiliation(s)
- M C Nevitt
- Department of Epidemiology and Biostatistics, University of California, San Francisco, USA
| | - D T Felson
- Department of Rheumatology, Boston University School of Medicine, Boston, USA; University of Manchester Centre for Epidemiology, NIHR Manchester BRC, Manchester University NHS Trust, Manchester, UK.
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28
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Jeon SH, Lee KG, Kim MS. Association of bone mineral density with the development of knee osteoarthritis in men and women: a cross-sectional study using the fourth and fifth Korea National Health and Nutrition Examination Surveys. Arch Osteoporos 2020; 15:117. [PMID: 32720172 DOI: 10.1007/s11657-020-00793-6] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/21/2020] [Accepted: 07/21/2020] [Indexed: 02/03/2023]
Abstract
UNLABELLED Bone mineral density (BMD) and osteoarthritis (OA) were correlated but the relationship was varied according to sex. An association between lumbar spine and femur neck BMDs and OA showed a positive relation in women, while lumbar spine and pelvis BMDs in men were associated with OA with a negative relation. PURPOSE The purpose of this study was to evaluate the association of BMD in various body parts in conjunction with the presence or severity of radiographic knee osteoarthritis (KOA) in relation to sex. METHODS This study was a cross-sectional analysis using Korea National Health and Nutrition Examination Surveys. KOA was graded using the Kellgren-Lawrence (KL) grading system. Radiographic KOA was defined as a KL grade 2 or higher. The associations between KOA and BMD in certain body parts (femur, pelvis, lumbar, lower leg, and whole-body) were assessed. BMD was measured using dual-energy X-ray absorptiometry. The BMD of each body part was divided into quartiles and the relationship between KOA and BMD was examined according to sex. RESULTS BMD did not show a significant tendency according to KL grade in either sex. In men, the severity of KL grade have a statistically significant relationship with total femur (R2 = 0.303, p < 0.05), femur neck (R2 = 0.257, p < 0.05), lumbar (R2 = 0.137, p < 0.05), and pelvis BMD (R2 = 0.185, p < 0.05). In women, total femur (R2 = 0.466, p < 0.05), lumbar (R2 = 0.316, p < 0.05), pelvis (R2 = 0.343, p < 0.05), and lower leg BMD (R2 = 0.133, p < 0.05) were associated with the severity of KL grade. When the BMD was divided into quartiles, lumbar (p < 0.05) and pelvis BMD (p < 0.05) in men had statistically significant association with knee OA as BMD decreased. In women, femur neck (p < 0.05) and lumbar BMD (p < 0.05) were significantly associated with knee OA as BMD increased. CONCLUSION The relationship between BMD and OA severity varied according to sex. In women, there was a positive association between femur neck and lumbar BMD and OA, while BMD of the lumbar and pelvis in men was negatively correlated with OA. LEVEL OF EVIDENCE Cohort study, III.
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Affiliation(s)
- Sang Hyun Jeon
- Department of Orthopaedic Surgery, Incheon St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Incheon, South Korea
| | - Kyoung Geun Lee
- Department of Orthopaedic Surgery, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, 222 Banpo-Daero, Seocho-Gu, Seoul, 06591, South Korea
| | - Man Soo Kim
- Department of Orthopaedic Surgery, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, 222 Banpo-Daero, Seocho-Gu, Seoul, 06591, South Korea.
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Törnqvist AE, Grahnemo L, Nilsson KH, Funck-Brentano T, Ohlsson C, Movérare-Skrtic S. Wnt16 Overexpression in Osteoblasts Increases the Subchondral Bone Mass but has no Impact on Osteoarthritis in Young Adult Female Mice. Calcif Tissue Int 2020; 107:31-40. [PMID: 32140758 PMCID: PMC7270053 DOI: 10.1007/s00223-020-00682-7] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/17/2019] [Accepted: 02/21/2020] [Indexed: 12/22/2022]
Abstract
Epidemiological studies have shown that high bone mineral density (BMD) is associated with an increased risk of osteoarthritis (OA), but the causality of this relationship remains unclear. Both bone mass and OA have been associated with the WNT signaling pathway in genetic studies, there is thus an interest in studying molecular partners of the WNT signaling pathway and OA. Female mice overexpressing WNT16 in osteoblasts (Obl-Wnt16 mice) have an increased bone mass. We aimed to evaluate if the high bone mass in Obl-Wnt16 mice leads to a more severe experimental OA development than in WT control mice. We induced experimental OA in female Obl-Wnt16 and WT control mice by destabilizing the medial meniscus (DMM). The Obl-Wnt16 mice displayed thicker medial and lateral subchondral bone plates as well as increased subchondral trabecular bone volume/tissue volume (BV/TV) but un-altered thickness of articular cartilage compared to WT mice. After DMM surgery, there was no difference in OA severity in the articular cartilage in the knee joint between the Obl-Wnt16 and WT mice. Both the Obl-Wnt16 and WT mice developed osteophytes in the DMM-operated tibia to a similar extent. We conclude that although the Obl-Wnt16 female mice have a high subchondral bone mass due to increased WNT signaling, they do not exhibit a more severe OA phenotype than their WT controls. This demonstrates that high bone mass does not result in an increased risk of OA per se.
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Affiliation(s)
- Anna E Törnqvist
- Department of Internal Medicine and Clinical Nutrition, Centre for Bone and Arthritis Research, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, 413 45, Gothenburg, Sweden.
- Klin Farm Lab, Department of Internal Medicine and Clinical Nutrition, Centre for Bone and Arthritis Research, Sahlgrenska University Hospital, Vita Stråket 11, 41345, Gothenburg, Sweden.
| | - Louise Grahnemo
- Department of Internal Medicine and Clinical Nutrition, Centre for Bone and Arthritis Research, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, 413 45, Gothenburg, Sweden
| | - Karin H Nilsson
- Department of Internal Medicine and Clinical Nutrition, Centre for Bone and Arthritis Research, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, 413 45, Gothenburg, Sweden
| | - Thomas Funck-Brentano
- Department of Internal Medicine and Clinical Nutrition, Centre for Bone and Arthritis Research, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, 413 45, Gothenburg, Sweden
- BIOSCAR, Inserm, Université de Paris, 75010, Paris, France
- Department of Rheumatology, AP-HP, Hopital Lariboisière, 75010, Paris, France
| | - Claes Ohlsson
- Department of Internal Medicine and Clinical Nutrition, Centre for Bone and Arthritis Research, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, 413 45, Gothenburg, Sweden
| | - Sofia Movérare-Skrtic
- Department of Internal Medicine and Clinical Nutrition, Centre for Bone and Arthritis Research, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, 413 45, Gothenburg, Sweden
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Garriga C, Sánchez-Santos MT, Judge A, Hart D, Spector T, Cooper C, Arden NK. Predicting Incident Radiographic Knee Osteoarthritis in Middle-Aged Women Within Four Years: The Importance of Knee-Level Prognostic Factors. Arthritis Care Res (Hoboken) 2020; 72:88-97. [PMID: 31127870 DOI: 10.1002/acr.23932] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/11/2018] [Accepted: 05/21/2019] [Indexed: 12/20/2022]
Abstract
OBJECTIVE To develop and internally validate risk models and a clinical risk score tool to predict incident radiographic knee osteoarthritis (RKOA) in middle-aged women. METHODS We analyzed 649 women in the Chingford 1,000 Women study. The outcome was incident RKOA, defined as Kellgren/Lawrence grade 0-1 at baseline and ≥2 at year 5. We estimated predictors' effects on the outcome using logistic regression models. Two models were generated. The clinical model considered patient characteristics, medication, biomarkers, and knee symptoms. The radiographic model considered the same factors, plus radiographic factors (e.g., angle between the acetabular roof and the ilium's vertical cortex [hip α-angle]). The models were internally validated. Model performance was assessed using calibration and discrimination (area under the receiver characteristic curve [AUC]). RESULTS The clinical model contained age, quadriceps circumference, and a cartilage degradation marker (C-terminal telopeptide of type II collagen) as predictors (AUC = 0.692). The radiographic model contained older age, greater quadriceps circumference, knee pain, knee baseline Kellgren/Lawrence grade 1 (versus 0), greater hip α-angle, greater spinal bone mineral density, and contralateral RKOA at baseline as predictors (AUC = 0.797). Calibration tests showed good agreement between the observed and predicted incident RKOA. A clinical risk score tool was developed from the clinical model. CONCLUSION Two models predicting incident RKOA within 4 years were developed, including radiographic variables that improved model performance. First-time predictor hip α-angle and contralateral RKOA suggest OA origins beyond the knee. The clinical tool has the potential to help physicians identify patients at risk of RKOA in routine practice, but the tool should be externally validated.
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Affiliation(s)
| | | | - Andrew Judge
- University of Oxford, Oxford, University of Southampton and Southampton General Hospital, Southampton, and Bristol Medical School, University of Bristol, and Southmead Hospital, Bristol, UK
| | | | | | - Cyrus Cooper
- University of Oxford, Oxford, and University of Southampton and Southampton General Hospital, Southampton, UK
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31
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Cai G, Otahal P, Cicuttini F, Wu F, Munugoda IP, Jones G, Aitken D. The association of subchondral and systemic bone mineral density with osteoarthritis-related joint replacements in older adults. Osteoarthritis Cartilage 2020; 28:438-445. [PMID: 32119971 DOI: 10.1016/j.joca.2020.02.832] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/24/2019] [Revised: 02/12/2020] [Accepted: 02/18/2020] [Indexed: 02/02/2023]
Abstract
OBJECTIVE To describe the association of subchondral and systemic bone mineral density (BMD) with knee and hip replacements (KR and HR, respectively) due to osteoarthritis. DESIGN 1,095 participants (mean age 63 years, 51% female) were included. At baseline, subchondral BMD of the medial and lateral tibia in three regions of interest (ROI) for the right knee, and systemic BMD of the lumbar spine, femoral neck, total hip and whole-body, were measured using dual-energy X-ray absorptiometry. Subchondral BMD of the hip was not measured. Competing risk regression models were used to estimate sub-distribution hazard ratios (SHRs) of KR/HR per one standard deviation (SD) higher in BMD measures, with adjustment of potential confounders. RESULTS Over 12.2 years, 79 (7.2%) participants underwent a KR and 56 (5.1%) an HR due to osteoarthritis. For the right side, medial subchondral BMD in ROI-3 was associated with an increased risk of KR (SHR 1.95 per SD; 95% Confidence Interval [CI], 1.57 to 2.43). In contrast, systemic BMD was not associated with the risk of KR, but higher BMD at the lumbar spine (1.42, 1.07 to 1.88) and whole-body (1.29, 1.00 to 1.66) were associated with an increased risk of HR at both sides. CONCLUSIONS Subchondral BMD is positively associated with an increased risk of KR and systemic BMD with an increased risk of HR, suggesting a role of BMD in the progression of osteoarthritis.
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Affiliation(s)
- G Cai
- Menzies Institute for Medical Research, University of Tasmania, Hobart, Tasmania, Australia.
| | - P Otahal
- Menzies Institute for Medical Research, University of Tasmania, Hobart, Tasmania, Australia.
| | - F Cicuttini
- Department of Epidemiology and Preventive Medicine, Monash University Medical School, Melbourne, Victoria, Australia.
| | - F Wu
- Menzies Institute for Medical Research, University of Tasmania, Hobart, Tasmania, Australia.
| | - I P Munugoda
- Menzies Institute for Medical Research, University of Tasmania, Hobart, Tasmania, Australia.
| | - G Jones
- Menzies Institute for Medical Research, University of Tasmania, Hobart, Tasmania, Australia.
| | - D Aitken
- Menzies Institute for Medical Research, University of Tasmania, Hobart, Tasmania, Australia.
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32
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Shi J, Zhao W, Ying H, Du J, Chen J, Chen S, Shen B. The relationship of platelet to lymphocyte ratio and neutrophil to monocyte ratio to radiographic grades of knee osteoarthritis. Z Rheumatol 2019; 77:533-537. [PMID: 28681116 DOI: 10.1007/s00393-017-0348-7] [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] [Indexed: 12/26/2022]
Abstract
OBJECTIVE Accumulating data show that platelet to lymphocyte ratio (PLR) and neutrophil to monocyte ratio (NMR) undergo changes during inflammation in various diseases; however, the clinical features remain unclear in knee osteoarthritis (OA) patients. The purpose of our study was to evaluate PLR and NMR in knee OA patients, and assess their relationship to knee OA's radiographic grades. METHODS A retrospective study on 132 adult knee OA patients and 162 healthy controls (HC) was performed. All clinical characteristics of the knee OA patients were obtained from their medical records. PLR and NMR were compared between knee OA patients and HC by non-parametric tests. Correlations of PLR and NMR with Kellgren-Lawrence (KL) classification (KL grade 2, KL grade 3, and KL grade 4) were also analyzed through a Spearman correlation test. Ordinal polytomous logistic regression was used to determine independent factors influencing radiographic grades of knee OA patients. RESULTS PLR was increased significantly in knee OA patients, while a statistical difference in NMR was not observed. However, PLR was not relevant to KL grades, while NMR was negatively correlated with these (r = -0.330, P < 0.01) and was independently associated with KL grades of knee OA. CONCLUSION PLR could reflect the inflammation response of knee OA. NMR emerged as an independent factor and could be used as a potential marker indicating the severity of knee OA.
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Affiliation(s)
- J Shi
- Department of Clinical Laboratory, Taizhou Hospital of Zhejiang Province, Taizhou, Zhejiang Province, China
| | - W Zhao
- Wenzhou Medical University, Wenzhou, Zhejiang Province, China
| | - H Ying
- Wenzhou Medical University, Wenzhou, Zhejiang Province, China
| | - J Du
- Department of Clinical Laboratory, Taizhou Hospital of Zhejiang Province, Taizhou, Zhejiang Province, China
| | - J Chen
- Department of Clinical Laboratory, Taizhou Hospital of Zhejiang Province, Taizhou, Zhejiang Province, China
| | - S Chen
- Department of Clinical Laboratory, Taizhou Hospital of Zhejiang Province, Taizhou, Zhejiang Province, China
| | - B Shen
- Department of Clinical Laboratory, Taizhou Hospital of Zhejiang Province, Taizhou, Zhejiang Province, China.
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Bergink AP, Rivadeneira F, Bierma-Zeinstra SM, Zillikens MC, Ikram MA, Uitterlinden AG, van Meurs JBJ. Are Bone Mineral Density and Fractures Related to the Incidence and Progression of Radiographic Osteoarthritis of the Knee, Hip, and Hand in Elderly Men and Women? The Rotterdam Study. Arthritis Rheumatol 2019; 71:361-369. [PMID: 30264891 DOI: 10.1002/art.40735] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/11/2017] [Accepted: 09/18/2018] [Indexed: 01/06/2023]
Abstract
OBJECTIVE To examine the longitudinal relationship between bone mineral density (BMD) and the incidence and progression of knee, hip, and hand osteoarthritis (OA), and to examine the relationship between prevalent vertebral and nonvertebral fractures and the incidence and progression of OA in elderly men and women in the Rotterdam Study. METHODS Age- and sex-specific quartiles of baseline femoral neck BMD data were constructed for 4,154 subjects. Radiographs were scored for incidence and progression of knee and hip OA, and for incidence of hand OA. Prevalent vertebral fractures were scored using the McCloskey/Kanis method, and prevalent nonvertebral fractures were reported by baseline interview. RESULTS Subjects in the highest quartile of femoral neck BMD had an increased risk of incident radiographic knee OA (ROA) (odds ratio [OR] 1.58 [95% confidence interval (95% CI) 1.14-2.18]), and an increased risk of incident hip ROA (OR 1.57 [95% CI 1.06-2.32]), compared to the lowest quartile. No significant relationship was found between high femoral neck BMD and progression of knee or hip ROA or the incidence of hand ROA. Prevalent vertebral and nonvertebral fractures were not related to an increase in the incidence or progression of knee or hip ROA. However, vertebral fractures were associated with incident hand ROA (OR 1.74 [95% CI 1.02-2.98]). CONCLUSION Results from the present study confirm earlier findings and thus provide strong evidence that high femoral neck BMD is a prognostic risk factor for the development of knee and hip ROA. Vertebral fractures were found to be a risk factor for incident hand ROA.
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Affiliation(s)
- Arjan P Bergink
- Erasmus Medical Center, Rotterdam, The Netherlands, and Center for Orthopedic Surgery OCON, Hengelo, The Netherlands
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Song GG, Lee YH. Causal Association between Bone Mineral Density and Osteoarthritis: A Mendelian Randomization Study. JOURNAL OF RHEUMATIC DISEASES 2019. [DOI: 10.4078/jrd.2019.26.2.104] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/22/2022]
Affiliation(s)
- Gwan Gyu Song
- Department of Rheumatology, Korea University College of Medicine, Seoul, Korea
| | - Young Ho Lee
- Department of Rheumatology, Korea University College of Medicine, Seoul, Korea
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O'Neill TW, McCabe PS, McBeth J. Update on the epidemiology, risk factors and disease outcomes of osteoarthritis. Best Pract Res Clin Rheumatol 2018; 32:312-326. [PMID: 30527434 DOI: 10.1016/j.berh.2018.10.007] [Citation(s) in RCA: 263] [Impact Index Per Article: 37.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/05/2018] [Revised: 10/12/2018] [Accepted: 10/12/2018] [Indexed: 12/20/2022]
Abstract
Osteoarthritis (OA) is the most frequent form of arthritis and a leading cause of pain and disability worldwide. OA can affect any synovial joint, although the hip, knee, hand, foot and spine are the most commonly affected sites. Knowledge about the occurrence and risk factors for OA is important to define the clinical and public health burden of the disease to understand mechanisms of disease occurrence and may also help to inform the development of population-wide prevention strategies. In this article, we review the occurrence and risk factors for OA and also consider patient-reported outcome measures that have been used for the assessment of the disease.
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Affiliation(s)
- Terence W O'Neill
- Arthritis Research UK Centre for Epidemiology, The University of Manchester, Manchester, UK & NIHR Manchester Biomedical Research Centre, Manchester University NHS Foundation Trust, Manchester Academic Health Science Centre, Manchester, UK
| | - Paul S McCabe
- Royal Oldham Hospital, Pennine Acute NHS Trust, Rochdale Rd, Oldham OL1 2JH, UK
| | - John McBeth
- Arthritis Research UK Centre for Epidemiology, The University of Manchester, Manchester, UK & NIHR Manchester Biomedical Research Centre, Manchester University NHS Foundation Trust, Manchester Academic Health Science Centre, Manchester, UK.
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36
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Calce SE, Kurki HK, Weston DA, Gould L. Effects of osteoarthritis on age-at-death estimates from the human pelvis. AMERICAN JOURNAL OF PHYSICAL ANTHROPOLOGY 2018; 167:3-19. [DOI: 10.1002/ajpa.23595] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/02/2017] [Revised: 03/13/2018] [Accepted: 04/08/2018] [Indexed: 11/10/2022]
Affiliation(s)
- Stephanie E. Calce
- Department of Anthropology; University of Victoria; Victoria British Columbia, V8W 2Y2 Canada
| | - Helen K. Kurki
- Department of Anthropology; University of Victoria; Victoria British Columbia, V8W 2Y2 Canada
| | - Darlene A. Weston
- Department of Anthropology; University of British Columbia; British Columbia V6T 1Z1 Canada
| | - Lisa Gould
- Department of Anthropology; University of Victoria; Victoria British Columbia, V8W 2Y2 Canada
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Longitudinal Growth and pQCT Measures in Hutterite Children and Grandchildren Are Associated With Prevalence of Hip or Knee Replacement Resulting From Osteoarthritis in Parents and Grandparents. Clin Orthop Relat Res 2018; 476:1093-1103. [PMID: 29432264 PMCID: PMC5916627 DOI: 10.1007/s11999.0000000000000197] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/31/2023]
Abstract
BACKGROUND Osteoarthritis (OA) is one of the leading causes of disability in the world. Several genes are associated with the development of OA, and previous studies have shown adult children of individuals with OA have higher areal bone mineral density (BMD). Because childhood is an important period of growth and bone development, and body composition is known to be associated with BMD, we speculated that there may be differences in growth and bone measures among young children with a genetic predisposition to OA. QUESTIONS/PURPOSES (1) Do differences exist at baseline in anthropometric and peripheral quantitative CT (pQCT) measurements between children and grandchildren of individuals with OA and controls? (2) Do children and grandchildren of individuals with OA accrue bone longitudinally at a different rate than controls? METHODS Longitudinal anthropometric (height, weight) and bone (cortical and trabecular volumetric BMD and cross-sectional area) measurements by pQCT were obtained at baseline and 18 and 36 months on children (n = 178) and grandchildren (n = 230) of 23 individuals with hip or knee arthroplasty resulting from OA and 23 sex-matched controls (16 females each). Grandchildren (age, 8-30 years) were further categorized as growing (premenarcheal or male < 14 years, n = 99) or mature (≥ 2 years postmenarchal or males ≥ 18 years, n = 96). The remaining 35 grandchildren could not be categorized and were excluded. RESULTS Mature granddaughters and grandsons of individuals with OA had greater trabecular volumetric BMD than controls (236 ± 24 and 222 ± 26 mg/cm, respectively, for granddaughters, difference of 14 [95% confidence interval {CI}, 1-28] mg/cm, p = 0.041 and 270 ± 22 and 248 ± 30 mg/cm, respectively, for grandsons, difference of 22 [95% CI, 1-42] mg/cm, p = 0.040). Greater trabecular volumetric BMD was observed in daughters of individuals with OA compared with daughters of controls (228 ± 28 and 212 ± 33 mg/cm, respectively, difference of 18 [95% CI, 3-30] mg/cm, respectively [p = 0.021]). Growing granddaughters and grandsons of controls had greater decreases in cortical volumetric BMD than grandchildren of individuals with OA (time-by-group [TG] based on mixed model [± standard error] -9.7 ± 4.3 versus -0.8 ± 4.4 mg/cm/year, respectively, for granddaughters, difference of 9.0 [95% CI, 2.4-15.5] mg/cm/year, p = 0.007 and -6.8 ± 3.3 versus 4.5 ± 3.4 mg/cm/year, respectively, for grandsons, difference of 11.3 [95% CI, 4.3-18.3] mg/cm/year, p = 0.002). Cortical volumetric BMD was maintained in sons of individuals with OA, but decreased in sons of controls (-0.0 ± 1.5 versus -4.3 ± 1.0 mg/cm/year, respectively, difference of 4.3 [95% CI, 0.7-7.8] mg/cm/year, p = 0.019 [TG]). There was a greater apparent decrease in cross-sectional area among daughters of individuals with OA than in controls (-4.6 ± 0.9 versus -1.7 ± 0.9 mm/year, respectively, difference of -2.9 [95% CI, -5.3 to -0.6] mm/year, p = 0.015 [TG]). CONCLUSIONS Several anthropometric and bone differences exist between children and grandchildren of individuals with OA and controls. If these differences are confirmed in additional studies, it would be important to identify the mechanism so that preventive measures could be developed and implemented to slow or reduce OA development. CLINICAL RELEVANCE Differences in growth and bone development may lead to increased loads on cartilage that may predispose offspring to the development of OA. If these differences are confirmed in additional studies, it would be important to identify the mechanism so that preventive measures could be developed and implemented to slow or reduce OA development.
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Hackinger S, Trajanoska K, Styrkarsdottir U, Zengini E, Steinberg J, Ritchie GRS, Hatzikotoulas K, Gilly A, Evangelou E, Kemp JP, Evans D, Ingvarsson T, Jonsson H, Thorsteinsdottir U, Stefansson K, McCaskie AW, Brooks RA, Wilkinson JM, Rivadeneira F, Zeggini E. Evaluation of shared genetic aetiology between osteoarthritis and bone mineral density identifies SMAD3 as a novel osteoarthritis risk locus. Hum Mol Genet 2018; 26:3850-3858. [PMID: 28934396 PMCID: PMC5886098 DOI: 10.1093/hmg/ddx285] [Citation(s) in RCA: 33] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/09/2017] [Accepted: 07/15/2017] [Indexed: 01/20/2023] Open
Abstract
Osteoarthritis (OA) is a common complex disease with high public health burden and no curative therapy. High bone mineral density (BMD) is associated with an increased risk of developing OA, suggesting a shared underlying biology. Here, we performed the first systematic overlap analysis of OA and BMD on a genome wide scale. We used summary statistics from the GEFOS consortium for lumbar spine (n = 31,800) and femoral neck (n = 32,961) BMD, and from the arcOGEN consortium for three OA phenotypes (hip, ncases=3,498; knee, ncases=3,266; hip and/or knee, ncases=7,410; ncontrols=11,009). Performing LD score regression we found a significant genetic correlation between the combined OA phenotype (hip and/or knee) and lumbar spine BMD (rg=0.18, P = 2.23 × 10−2), which may be driven by the presence of spinal osteophytes. We identified 143 variants with evidence for cross-phenotype association which we took forward for replication in independent large-scale OA datasets, and subsequent meta-analysis with arcOGEN for a total sample size of up to 23,425 cases and 236,814 controls. We found robustly replicating evidence for association with OA at rs12901071 (OR 1.08 95% CI 1.05–1.11, Pmeta=3.12 × 10−10), an intronic variant in the SMAD3 gene, which is known to play a role in bone remodeling and cartilage maintenance. We were able to confirm expression of SMAD3 in intact and degraded cartilage of the knee and hip. Our findings provide the first systematic evaluation of pleiotropy between OA and BMD, highlight genes with biological relevance to both traits, and establish a robust new OA genetic risk locus at SMAD3.
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Affiliation(s)
- Sophie Hackinger
- Human Genetics, Wellcome Trust Sanger Institute, Hinxton CB10 1HH, UK
| | - Katerina Trajanoska
- Departments of Internal Medicine and Epidemiology, Erasmus University Medical Center, Rotterdam 3000 CA, The Netherlands
| | | | - Eleni Zengini
- Department of Oncology and Metabolism, University of Sheffield, Sheffield S10 2RX, UK.,5th Department, Dromokaiteio Psychiatric Hospital, Athens 124 61, Greece
| | - Julia Steinberg
- Human Genetics, Wellcome Trust Sanger Institute, Hinxton CB10 1HH, UK
| | | | | | - Arthur Gilly
- Human Genetics, Wellcome Trust Sanger Institute, Hinxton CB10 1HH, UK
| | - Evangelos Evangelou
- Department of Hygiene and Epidemiology, University of Ioannina Medical School, Ioannina 45110, Greece.,Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, UK
| | - John P Kemp
- MRC Integrative Epidemiology Unit, University of Bristol, Bristol, UK.,University of Queensland Diamantina Institute, Translational Research Institute, Brisbane, QLD, Australia
| | | | - David Evans
- MRC Integrative Epidemiology Unit, University of Bristol, Bristol, UK.,University of Queensland Diamantina Institute, Translational Research Institute, Brisbane, QLD, Australia
| | - Thorvaldur Ingvarsson
- Department of Orthopedic Surgery, Akureyri Hospital, 600 Akureyri, Iceland.,Faculty of Medicine, University of Iceland, 101 Reykjavik, Iceland.,Institution of Health Science, University of Akureyri, 600 Akureyri, Iceland
| | - Helgi Jonsson
- Faculty of Medicine, University of Iceland, 101 Reykjavik, Iceland.,Department of Medicine, Landspitali, The National University Hospital of Iceland, 101 Reykjavik, Iceland
| | - Unnur Thorsteinsdottir
- deCODE Genetics, Sturlugata 8, IS-101 Reykjavik, Iceland.,Faculty of Medicine, University of Iceland, 101 Reykjavik, Iceland
| | - Kari Stefansson
- deCODE Genetics, Sturlugata 8, IS-101 Reykjavik, Iceland.,Faculty of Medicine, University of Iceland, 101 Reykjavik, Iceland
| | - Andrew W McCaskie
- Division of Trauma & Orthopaedic Surgery, University of Cambridge, Box 180, Addenbrooke's Hospital, Cambridge CB2 0QQ, UK
| | - Roger A Brooks
- Division of Trauma & Orthopaedic Surgery, University of Cambridge, Box 180, Addenbrooke's Hospital, Cambridge CB2 0QQ, UK
| | - Jeremy M Wilkinson
- Department of Oncology and Metabolism, University of Sheffield, Sheffield S10 2RX, UK
| | - Fernando Rivadeneira
- Departments of Internal Medicine and Epidemiology, Erasmus University Medical Center, Rotterdam 3000 CA, The Netherlands
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Neogi T, Li S, Peloquin C, Misra D, Zhang Y. Effect of bisphosphonates on knee replacement surgery. Ann Rheum Dis 2018; 77:92-97. [PMID: 28988204 PMCID: PMC6374039 DOI: 10.1136/annrheumdis-2017-211811] [Citation(s) in RCA: 43] [Impact Index Per Article: 6.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/17/2017] [Revised: 08/11/2017] [Accepted: 09/08/2017] [Indexed: 11/03/2022]
Abstract
PURPOSE Bone remodelling as a therapeutic target in knee osteoarthritis (OA) has gained much interest, but the effects of antiresorptive agents on knee OA have been conflicting, with no studies to date examining the effects of bisphosphonate use on the clinically relevant endpoint of knee replacement (KR) surgery. METHODS We used data from The Health Improvement Network (THIN), a general practitioner electronic medical records representative of the general UK population. We identified older women who had initiated bisphosphonate use after their incident knee OA diagnosis. Each bisphosphonate initiator was propensity score-matched with a non-initiator within each 1-year cohort accrual block. The effect of bisphosphonates on the risk of KR was assessed using Cox proportional hazard regression. Sensitivity analyses to address residual confounding were also conducted. RESULTS We identified 2006 bisphosphonate initiators, who were matched to 2006 non-initiators(mean age 76, mean body mass index 27), with mean follow-up time of 3 years. The crude incidence rate of KR was 22.0 per 1000 person-years among the initiators, and 29.1 among the non-initiators. Bisphosphonate initiators had 26% lower risk of KR than non-initiators(HR 0.74, 95% CI 0.59 to 0.93); these results were similar when additionally adjusted for potential confounders in the propensity score (HR 0.76, 95% CI 0.60 to 0.95). Results of sensitivity analyses supported this protective effect. CONCLUSIONS In this population-based cohort of older women with incident knee OA, those with incident bisphosphonate users had lower risk of KR than non-users of bisphosphonates, suggesting a potential beneficial effect of bisphosphonates on knee OA.
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Affiliation(s)
- Tuhina Neogi
- Clinical Epidemiology Research and Training Unit, Boston University School of Medicine, Boston, Massachusetts, USA
| | - Shanshan Li
- Clinical Epidemiology Research and Training Unit, Boston University School of Medicine, Boston, Massachusetts, USA
| | - Christine Peloquin
- Clinical Epidemiology Research and Training Unit, Boston University School of Medicine, Boston, Massachusetts, USA
| | - Devyani Misra
- Clinical Epidemiology Research and Training Unit, Boston University School of Medicine, Boston, Massachusetts, USA
| | - Yuqing Zhang
- Clinical Epidemiology Research and Training Unit, Boston University School of Medicine, Boston, Massachusetts, USA
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Barbour KE, Murphy LB, Helmick CG, Hootman JM, Renner JB, Jordan JM. Bone Mineral Density and the Risk of Hip and Knee Osteoarthritis: The Johnston County Osteoarthritis Project. Arthritis Care Res (Hoboken) 2017; 69:1863-1870. [PMID: 28129489 DOI: 10.1002/acr.23211] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/07/2016] [Accepted: 01/24/2017] [Indexed: 01/08/2023]
Abstract
OBJECTIVE To address knowledge gaps regarding the relationship between bone mineral density (BMD) and incident hip or knee osteoarthritis (OA); specifically, lack of information regarding hip OA or symptomatic outcomes. METHODS Using data (n = 1,474) from the Johnston County Osteoarthritis Project's first (1999-2004) and second (2005-2010) followup of participants ages ≥45 years, we examined the association between total hip BMD and both hip and knee OA. Total hip BMD was measured using dual x-ray absorptiometry, and participants were classified into sex-specific quartiles (low, intermediate low, intermediate high, and high). Radiographic OA (ROA) was defined as development of Kellgren/Lawrence grade ≥2. Symptomatic ROA (sROA) was defined as onset of both ROA and symptoms. Weibull regression modeling was used to estimate hazard ratios (HRs) and 95% confidence intervals (95% CIs). RESULTS Median followup time was 6.5 years (range 4.0-10.2 years). In multivariate models, and compared with participants with low BMD, those with intermediate high and high BMD were less likely to develop hip sROA (HR 0.52 [95% CI 0.31-0.86] and 0.56 [95% CI 0.31-0.86], respectively; P = 0.024 for trend); high BMD was not associated (HR 0.69 [95% CI 0.45-1.06]) with risk of hip ROA. Compared with participants with low BMD, those with intermediate low and intermediate high total hip BMD were more likely to develop knee sROA (HR 2.15 [95% CI 1.40-3.30] and 1.65 [95% CI 1.02-2.67], respectively; P = 0.325 for trend); similar associations were seen with knee ROA. CONCLUSION Our findings suggest that higher BMD may reduce the risk of hip sROA, while intermediate levels may increase the risk of both knee sROA and ROA.
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Affiliation(s)
- Kamil E Barbour
- Centers for Disease Control and Prevention, Atlanta, Georgia
| | - Louise B Murphy
- Centers for Disease Control and Prevention, Atlanta, Georgia
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Associations between systemic bone mineral density and early knee cartilage changes in middle-aged adults without clinical knee disease: a prospective cohort study. Arthritis Res Ther 2017; 19:98. [PMID: 28521839 PMCID: PMC5437680 DOI: 10.1186/s13075-017-1314-0] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/17/2017] [Accepted: 05/02/2017] [Indexed: 01/12/2023] Open
Abstract
Background Osteoarthritis has a high prevalence in people with high bone mineral density (BMD). Nevertheless, whether high systemic BMD predates early structural features of knee osteoarthritis is unclear. This study examined the association between systemic BMD and knee cartilage defect progression and cartilage volume loss in middle-aged people without clinical knee disease. Methods Adults (n = 153) aged 25–60 years had total body, lumbar spine, and total hip BMD assessed by dual-energy X-ray absorptiometry at baseline (2005–2008), and tibial cartilage volume and tibiofemoral cartilage defects assessed by magnetic resonance imaging at baseline and follow up (2008–2010). Results Higher spine BMD was associated with increased risk for progression of medial (OR = 1.45, 95% CI 1.10, 1.91) and lateral (OR = 1.30, 95% CI 1.00, 1.67) tibiofemoral cartilage defects. Total hip BMD was also positively associated with the progression of medial (OR = 1.63, 95% CI 1.10, 2.41) and lateral (OR = 1.53, 95% CI 1.08, 2.18) tibiofemoral cartilage defects. Greater total body, spine, and total hip BMD were associated with increased rate of lateral tibial cartilage volume loss (for every 1 g/10 cm2 increase in total body BMD: B = 0.44%, 95% CI 0.17%, 0.71%; spine BMD: 0.17%, 95% CI 0.04%, 0.30%; total hip BMD: 0.29%, 95% CI 0.13%, 0.45%), with no significant associations for medial tibial cartilage volume loss. Conclusion In middle-aged people without clinical knee disease, higher systemic BMD was associated with increased early knee cartilage damage. Further work is needed to clarify the effect of systemic BMD at different stages of the pathway from health through to disease in knee osteoarthritis, as new therapies targeting bone are developed for the management of knee osteoarthritis.
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Gregson CL, Hardcastle SA, Murphy A, Faber B, Fraser WD, Williams M, Davey Smith G, Tobias JH. High Bone Mass is associated with bone-forming features of osteoarthritis in non-weight bearing joints independent of body mass index. Bone 2017; 97:306-313. [PMID: 28082078 PMCID: PMC5378151 DOI: 10.1016/j.bone.2017.01.005] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/16/2016] [Revised: 11/05/2016] [Accepted: 01/06/2017] [Indexed: 12/19/2022]
Abstract
OBJECTIVES High Bone Mass (HBM) is associated with (a) radiographic knee osteoarthritis (OA), partly mediated by increased BMI, and (b) pelvic enthesophytes and hip osteophytes, suggestive of a bone-forming phenotype. We aimed to establish whether HBM is associated with radiographic features of OA in non-weight-bearing (hand) joints, and whether such OA demonstrates a bone-forming phenotype. METHODS HBM cases (BMD Z-scores≥+3.2) were compared with family controls. A blinded assessor graded all PA hand radiographs for: osteophytes (0-3), joint space narrowing (JSN) (0-3), subchondral sclerosis (0-1), at the index Distal Interphalangeal Joint (DIPJ) and 1st Carpometacarpal Joint (CMCJ), using an established atlas. Analyses used a random effects logistic regression model, adjusting a priori for age and gender. Mediating roles of BMI and bone turnover markers (BTMs) were explored by further adjustment. RESULTS 314 HBM cases (mean age 61.1years, 74% female) and 183 controls (54.3years, 46% female) were included. Osteophytes (grade≥1) were more common in HBM (DIPJ: 67% vs. 45%, CMCJ: 69% vs. 50%), with adjusted OR [95% CI] 1.82 [1.11, 2.97], p=0.017 and 1.89 [1.19, 3.01], p=0.007 respectively; no differences were seen in JSN. Further adjustment for BMI failed to attenuate ORs for osteophytes in HBM cases vs. controls; DIPJ 1.72 [1.05, 2.83], p=0.032, CMCJ 1.76 [1.00, 3.06], p=0.049. Adjustment for BTMs (concentrations lower amongst HBM cases) did not attenuate ORs. CONCLUSIONS HBM is positively associated with OA in non-weight-bearing joints, independent of BMI. HBM-associated OA is characterised by osteophytes, consistent with a bone-forming phenotype, rather than JSN reflecting cartilage loss. Systemic factors (e.g. genetic architecture) which govern HBM may also increase bone-forming OA risk.
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Affiliation(s)
- C L Gregson
- Musculoskeletal Research Unit, School of Clinical Sciences, University of Bristol, UK.
| | - S A Hardcastle
- Musculoskeletal Research Unit, School of Clinical Sciences, University of Bristol, UK; MRC Integrative Epidemiology Unit, University of Bristol, Bristol, UK
| | - A Murphy
- Musculoskeletal Research Unit, School of Clinical Sciences, University of Bristol, UK
| | - B Faber
- Musculoskeletal Research Unit, School of Clinical Sciences, University of Bristol, UK
| | - W D Fraser
- Department of Medicine, Norwich Medical School, University of East Anglia, Norwich, UK
| | - M Williams
- Department of Radiology, North Bristol NHS Trust, Bristol, UK
| | - G Davey Smith
- MRC Integrative Epidemiology Unit, University of Bristol, Bristol, UK
| | - J H Tobias
- Musculoskeletal Research Unit, School of Clinical Sciences, University of Bristol, UK
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Sang W, Jiang Y, Cheng B, Ma J, Zhu L, Lu H, Wang C. [Expression of Sclerostin in medial and lateral subchondral bone of the varus osteoarthritic knee plateau]. ZHONGGUO XIU FU CHONG JIAN WAI KE ZA ZHI = ZHONGGUO XIUFU CHONGJIAN WAIKE ZAZHI = CHINESE JOURNAL OF REPARATIVE AND RECONSTRUCTIVE SURGERY 2017; 31:295-299. [PMID: 29806257 DOI: 10.7507/1002-1892.201610082] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Subscribe] [Scholar Register] [Indexed: 11/03/2022]
Abstract
Objective To study the expression difference of Sclerostin in the medial and lateral subchondral bone of the varus osteoarthritic knee plateau. Methods The tibial plateau was obtained from 20 patients with varus knee osteoarthritis receiving total knee arthroplasty from March to October 2015. There were 8 males and 12 females with an average age of 67.8 years (range, 61-78 years). The mean course of osteoarthritis was 3.2 years (range, 2-5 years). Before operation, the varus angle was 12.0-25.5° (mean, 17.6°) on the X-ray film. Five cases were rated as grade III and 15 cases as grade IV according to Kellgren-Lawrance classification. Micro-CT scan was performed on the medial and lateral subchondral bone to compare the changes of bone structure; bone volume/total volume (BV/TV), trabecular number (Tb.N), trabecular thickness (Tb.Th), structure model index (SMI), and the trabecular separation (Tb.Sp) were measured. Immunohistochemistry and real-time fluorescent quantitative PCR were used to test the expressions of Sclerostin protein and sost gene. Results Micro-CT showed that BV/TV, Tb.N, and Tb.Th significantly increased in the medial subchondral bone when compared with the lateral part ( P<0.05), but SMI and Tb.Sp significantly reduced ( P<0.05). Real-time fluorescent quantitative PCR detection showed that sost gene expression level in the medial subchondral bone (1.000) was significantly lower than that in the lateral part (4.157±2.790) ( t=2.371, P=0.040). The percentage of Sclerostin positive cells in the lateral subchondral bone (52.00%±0.19%) was significantly higher than that in the medial subchondral bone (7.20%±0.04%) ( t=5.094, P=0.005). Conclusion Sclerostin plays an important role in the subchondral bone remodeling of the varus osteoarthritic knee. And the low expression of Sclerostin may be an important factor to promote bone remodeling and aggravate knee deformity.
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Affiliation(s)
- Weilin Sang
- Department of Orthopedics, Clinical Medical School, Shanghai General Hospital of Nanjing Medical University, Shanghai, 201620, P.R.China
| | - Yafei Jiang
- Department of Orthopedics, Clinical Medical School, Shanghai General Hospital of Nanjing Medical University, Shanghai, 201620, P.R.China
| | - Biao Cheng
- Department of Orthopedics, Clinical Medical School, The Affiliated Shanghai No.10 People's Hospital, Nanjing Medical University, Shanghai, 200072,
| | - Jinzhong Ma
- Department of Orthopedics, Clinical Medical School, Shanghai General Hospital of Nanjing Medical University, Shanghai, 201620, P.R.China
| | - Libo Zhu
- Department of Orthopedics, Clinical Medical School, Shanghai General Hospital of Nanjing Medical University, Shanghai, 201620, P.R.China
| | - Haiming Lu
- Department of Orthopedics, Clinical Medical School, Shanghai General Hospital of Nanjing Medical University, Shanghai, 201620, P.R.China
| | - Cong Wang
- Department of Orthopedics, Clinical Medical School, Shanghai General Hospital of Nanjing Medical University, Shanghai, 201620, P.R.China
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Menopause is associated with articular cartilage degeneration: a clinical study of knee joint in 860 women. Menopause 2016; 23:1239-1246. [DOI: 10.1097/gme.0000000000000697] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/25/2023]
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Elwakil WA, Mohasseb D, Elkaffash D, Elshereef S, Elshafey M. Serum leptin and osteoporosis in postmenopausal women with primary knee osteoarthritis. EGYPTIAN RHEUMATOLOGIST 2016. [DOI: 10.1016/j.ejr.2016.02.002] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/29/2022]
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Obana KK, Davis J. Racial Disparities in the Prevalence of Arthritis among Native Hawaiians and Pacific Islanders, Whites, and Asians. HAWAI'I JOURNAL OF MEDICINE & PUBLIC HEALTH : A JOURNAL OF ASIA PACIFIC MEDICINE & PUBLIC HEALTH 2016; 75:155-61. [PMID: 27413625 PMCID: PMC4928514] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Subscribe] [Scholar Register] [Indexed: 06/06/2023]
Abstract
The health disparities of Native Hawaiians and Pacific Islanders (NHPI) are well established for diabetes and cardiovascular disease, but less is known about disparities in arthritis. This study examined possible disparities in the prevalence of arthritis by age, sex, and severity comparing NHPI, Whites, and Asians. The study population included adult Hawai'i participants in the 2013 Behavioral Risk Factor Surveillance Survey. NHPI males had a significantly higher prevalence of arthritis, which peaked twenty years earlier, than White and Asian males (P<.001). The prevalence of arthritis peaked at 65-79 years in males and females in all racial groups, except in NHPI males where it peaked at 45-54 years. The mean ages (years) for males with arthritis were 46.2 for NHPI, 59.1 for Whites, and 60.5 for Asians; the respective ages for females were 54.2, 60.5, and 58.8. NHPI males body mass index averaged 2.4 kg/m(2) greater than White males (P<.001), and obese NHPI males had twice the age-adjusted odds of arthritis than obese White males. Although NHPI females had a greater body mass index than White females (P=.05), the prevalence of arthritis was only slightly and not significantly higher. NHPI males and females reported high pain scores more frequently than Whites did, but the differences did not reach statistical significance. Diabetes was a comorbidity more than twice as often in NHPI and Asians of both sexes than among Whites. This study demonstrated racial disparities in the prevalence of arthritis among NHPI, Whites, and Asians.
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Affiliation(s)
- Kyle K Obana
- Amherst College, Amherst, MA; Department of Native Hawaiian Health, John A. Burns School of Medicine, University of Hawai'i, Honolulu, HI (KKO)
| | - James Davis
- Amherst College, Amherst, MA; Department of Native Hawaiian Health, John A. Burns School of Medicine, University of Hawai'i, Honolulu, HI (KKO)
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Abstract
PURPOSE OF REVIEW Increasing evidence show that bone is a key factor in the development of osteoarthritis. This article reviews the latest results of basic and clinical research on the role of the subchondral bone in osteoarthritis. RECENT FINDINGS Early changes in the subchondral bone can predict subsequent symptoms or disease structural progression. New tools may help clinicians to stratify different osteoarthritis phenotypes with regards to bone remodeling status. SUMMARY The involvement of bone in osteoarthritis has long been thought to be secondary to cartilage damage as an adaptation of the joint. Recent clinical studies with MRI have demonstrated that bone changes could be observed in early stages of the disease, even preceding cartilage lesions. Moreover, there is clear evidence of an association between subchondral bone mineral density and osteoarthritis. The level of bone remodeling plays a critical role under mechanical loading conditions as demonstrated by consistent experimental studies. Yet new clinical biomarkers are being developed to assess the bone phenotype of osteoarthritic patients. This stratification strategy is likely to better identify groups of patients who would benefit from bone-acting drugs to decrease disease progression and improve pain and disability.
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Asian Elm tree inner bark prevents articular cartilage deterioration in ovariectomized obese rats with monoiodoacetate-induced osteoarthritis. Menopause 2016; 23:197-208. [DOI: 10.1097/gme.0000000000000521] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/20/2023]
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Ho-Pham LT, Lai TQ, Mai LD, Doan MC, Nguyen TV. Body Composition in Individuals with Asymptomatic Osteoarthritis of the Knee. Calcif Tissue Int 2016; 98:165-71. [PMID: 26590808 DOI: 10.1007/s00223-015-0080-8] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/23/2015] [Accepted: 11/04/2015] [Indexed: 02/01/2023]
Abstract
Greater body mass index (BMI) is associated with a greater risk of osteoarthritis (OA). This study sought to investigate whether the association is mediated by fat mass or lean mass. The study involved 170 men and 488 women aged between 20 and 90 (average age: 55) who were randomly recruited from Ho Chi Minh City, Vietnam. The presence of knee OA was radiographically diagnosed based on the Kellgren-Lawrence criteria. Lean mass (LM) and fat mass (FM) were obtained from the DXA whole body scan (Hologic QDR-4500). The relationship between OA, LM, and FM was analyzed by a series of multiple linear regression models which take into account the effects of gender and age. As expected, men and women with knee OA were older than those without OA (65 vs 51 year in men, and 64 vs 52 year in women). After adjusting for age, OA was associated with greater FM and percent body fat (PBF), but the association was only observed in women, not in men. There was no statistically significant difference in LM between OA and non-OA individuals. Moreover, after adjusting for age and BMI or PBF, bone density in OA patients was not significantly different from non-OA individuals. Women with OA of the knee have greater fat mass than non-OA individuals, and that there is no significant difference in bone density between OA and non-OA individuals. Thus, the association between body mass index and OA is mainly mediated by fat mass.
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Affiliation(s)
- Lan T Ho-Pham
- Bone and Muscle Research Division, Faculty of Applied Sciences, Ton Duc Thang University, Nguyen Huu Tho Street, District 7, Ho Chi Minh City, Vietnam.
- Department of Internal Medicine, Pham Ngoc Thach University of Medicine, Ho Chi Minh City, Vietnam.
- Department of Rheumatology, People's Hospital 115, Ho Chi Minh City, Vietnam.
| | - Thai Q Lai
- Bone and Muscle Research Division, Faculty of Applied Sciences, Ton Duc Thang University, Nguyen Huu Tho Street, District 7, Ho Chi Minh City, Vietnam
- Department of Rheumatology, People's Hospital 115, Ho Chi Minh City, Vietnam
| | - Linh D Mai
- Department of Internal Medicine, Pham Ngoc Thach University of Medicine, Ho Chi Minh City, Vietnam
| | - Minh C Doan
- Department of Internal Medicine, Pham Ngoc Thach University of Medicine, Ho Chi Minh City, Vietnam
| | - Tuan V Nguyen
- Bone and Muscle Research Division, Faculty of Applied Sciences, Ton Duc Thang University, Nguyen Huu Tho Street, District 7, Ho Chi Minh City, Vietnam
- Osteoporosis and Bone Biology, Garvan Institute of Medical Research, Sydney, NSW, Australia
- School of Public Health and Community Medicine, UNSW Australia, Sydney, NSW, Australia
- Centre for Health Technologies, University of Technology, Sydney, NSW, Australia
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