|
1
|
Lao Z, Chen X, Chen X, Zhang H, Zhang Z, Bian Y, Zhou C, Tian K, Jin H, Fu F, Wu C, Gan K, Ruan H. Vertebral Osteoporosis in Systemic Lupus Erythematosus: A Possible Involvement of Inflammation-Related Osteoblast Ferroptosis. J Inflamm Res 2025; 18:5587-5599. [PMID: 40303004 PMCID: PMC12039848 DOI: 10.2147/jir.s523051] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/15/2025] [Accepted: 04/16/2025] [Indexed: 05/02/2025] Open
Abstract
Background Systemic lupus erythematosus (SLE) is a complex autoimmune disease characterized by immune system dysregulation and the production of autoantibodies, leading to widespread inflammation and multi-organ damage. Despite clinical observations have shown that approximately 1.4-68.7% of SLE patients develop vertebral osteoporosis (OP), the underlying mechanisms remain poorly defined. This study utilized the MRL/lpr mouse model, which effectively replicates human SLE manifestations, to investigate the impact of SLE on vertebral bone homeostasis. Methods Female MRL/lpr mice were employed to investigate SLE-induced bone loss. The study comprehensively evaluated bone structural changes through micro-CT analysis, histological assessment, and bone metabolic markers. Specifically, we analyzed trabecular parameters (TV, BV, BV/TV, Tb.Th), inflammatory cytokine profiles (TNF-α, IL-6, IL-1β, IL-18), osteogenic markers (RUNX2, OSTERIX, ALP, OPG), osteoclastogenic indicators (TRAP, RANKL, CTSK), and ferroptosis-related proteins (FACL4, FTH1, GPX4). Results SLE progression in MRL/lpr mice led to significant vertebral bone loss and OP phenotype, evidenced by reduced bone volume fraction (BV/TV) and trabecular thickness (Tb.Th). The inflammatory microenvironment was characterized by elevated TNF-α and IL-6 levels, which disrupted bone homeostasis by suppressing RUNX2, OSTERIX, and OPG expression while enhancing RANKL signaling. Mechanistically, SLE induced ferroptosis through increased FACL4 and FTH1 expression coupled with decreased GPX4 levels, leading to impaired osteoblast function and enhanced osteoclast activity. Conclusion SLE-associated vertebral OP is mediated by inflammation-driven ferroptosis, disrupting the balance between bone formation and resorption, offering novel insights into potential therapeutic strategies for managing bone loss in SLE patients.
Collapse
Affiliation(s)
- Zhaobai Lao
- Institute of Orthopaedics and Traumatology, The First Affiliated Hospital of Zhejiang Chinese Medical University (Zhejiang Provincial Hospital of Traditional Chinese Medicine), Hangzhou, Zhejiang, 310053, People’s Republic of China
| | - Xiaogang Chen
- Department of Orthopaedic Surgery, The Third Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, Zhejiang, 310005, People’s Republic of China
| | - Xin Chen
- Institute of Orthopaedics and Traumatology, The First Affiliated Hospital of Zhejiang Chinese Medical University (Zhejiang Provincial Hospital of Traditional Chinese Medicine), Hangzhou, Zhejiang, 310053, People’s Republic of China
| | - Helou Zhang
- Institute of Orthopaedics and Traumatology, The First Affiliated Hospital of Zhejiang Chinese Medical University (Zhejiang Provincial Hospital of Traditional Chinese Medicine), Hangzhou, Zhejiang, 310053, People’s Republic of China
| | - Zhiguo Zhang
- Institute of Orthopaedics and Traumatology, The First Affiliated Hospital of Zhejiang Chinese Medical University (Zhejiang Provincial Hospital of Traditional Chinese Medicine), Hangzhou, Zhejiang, 310053, People’s Republic of China
| | - Yishan Bian
- Institute of Orthopaedics and Traumatology, The First Affiliated Hospital of Zhejiang Chinese Medical University (Zhejiang Provincial Hospital of Traditional Chinese Medicine), Hangzhou, Zhejiang, 310053, People’s Republic of China
| | - Chengcong Zhou
- Institute of Orthopaedics and Traumatology, The First Affiliated Hospital of Zhejiang Chinese Medical University (Zhejiang Provincial Hospital of Traditional Chinese Medicine), Hangzhou, Zhejiang, 310053, People’s Republic of China
| | - Kun Tian
- Department of Orthopaedic Surgery, The Third Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, Zhejiang, 310005, People’s Republic of China
| | - Hongting Jin
- Institute of Orthopaedics and Traumatology, The First Affiliated Hospital of Zhejiang Chinese Medical University (Zhejiang Provincial Hospital of Traditional Chinese Medicine), Hangzhou, Zhejiang, 310053, People’s Republic of China
| | - Fangda Fu
- Institute of Orthopaedics and Traumatology, The First Affiliated Hospital of Zhejiang Chinese Medical University (Zhejiang Provincial Hospital of Traditional Chinese Medicine), Hangzhou, Zhejiang, 310053, People’s Republic of China
| | - Chengliang Wu
- Institute of Orthopaedics and Traumatology, The First Affiliated Hospital of Zhejiang Chinese Medical University (Zhejiang Provincial Hospital of Traditional Chinese Medicine), Hangzhou, Zhejiang, 310053, People’s Republic of China
| | - Kaifeng Gan
- Department of Orthopaedic Surgery, The Affiliated LiHuiLi Hospital of Ningbo University, Ningbo, Zhejiang, 315040, People’s Republic of China
| | - Hongfeng Ruan
- Institute of Orthopaedics and Traumatology, The First Affiliated Hospital of Zhejiang Chinese Medical University (Zhejiang Provincial Hospital of Traditional Chinese Medicine), Hangzhou, Zhejiang, 310053, People’s Republic of China
| |
Collapse
|
|
2
|
Hong Y, Yang Y, Yao Y. Prevalence and risk factors of osteoporosis in lupus nephritis patients in China: a cross-sectional study. BMC Nephrol 2024; 25:428. [PMID: 39604881 PMCID: PMC11604019 DOI: 10.1186/s12882-024-03882-7] [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: 06/21/2024] [Accepted: 11/22/2024] [Indexed: 11/29/2024] Open
Abstract
BACKGROUND Osteoporosis is a significant concern among individuals with lupus nephritis (LN), with reported prevalence rates exhibiting considerable variation. This study investigates the prevalence and identifies risk factors contributing to osteoporosis in premenopausal and postmenopausal LN patients, addressing the paucity of data specific to the Chinese population. METHODS This cross-sectional study enrolled patients with renal biopsy-proven LN, who underwent bone mineral density (BMD) measurements using dual X-ray absorptiometry at the lumbar spine, total hip, and femoral neck. The study was conducted at Tongji hospital from May 2011 to June 2018. RESULTS A total of 130 patients were evaluated, with a mean age of 46.2 ± 12.9 years, including 2 males and 128 females. A significant majority, 52.3% (n = 67) of the female patients, were identified as postmenopausal. BMD measurements revealed that 40.0% of patients had osteoporosis in at least one site. The spearman rank correlation of BMD with clinical characteristics indicated that age at menopause, weight, height, and body mass index were positively correlated with BMD, while age, age at diagnosis of LN, and menopause duration were negatively correlated with BMD in lumbar spine, total hip, and/or femoral neck. Multivariable linear regression analysis demonstrated that body mass index was positively associated with BMD, whereas disease duration and menopause duration were negatively associated with BMD in all and postmenopausal patients. Postmenopausal patients consistently had a higher prevalence of osteoporosis across all measured sites. Factors such as older age, lower weight, and the absence of bisphosphonates therapy were independently associated with an increased risk of osteoporosis in LN patients. CONCLUSION Our findings underscore a substantial prevalence of osteoporosis in LN patients, especially among postmenopausal individuals. The study identifies older age, lower weight, and absence of bisphosphonates treatment as risk factors for osteoporosis in this patient population.
Collapse
Affiliation(s)
- Yu Hong
- Department of Nephrology, Tongji hospital affiliated to Tongji medical college, Huazhong University of Science and Technology, Wuhan, Hubei, China
| | - Yi Yang
- Department of Nephrology, Tongji hospital affiliated to Tongji medical college, Huazhong University of Science and Technology, Wuhan, Hubei, China.
| | - Ying Yao
- Department of Nephrology, Tongji hospital affiliated to Tongji medical college, Huazhong University of Science and Technology, Wuhan, Hubei, China
- Department of Nutrition, Tongji hospital affiliated to Tongji medical college, Huazhong University of Science and Technology, Wuhan, Hubei, China
| |
Collapse
|
|
3
|
Patt YS, Ben-Shabat N, Fisher L, Sharif K, Arow M, Lassman S, Watad A, Skuja V, Shtewe AH, McGonagle D, Amital H. Increased risk of osteoporosis and femoral neck fractures in patients with familial Mediterranean fever-a large retrospective cohort study. Rheumatology (Oxford) 2024; 63:2128-2134. [PMID: 37769238 DOI: 10.1093/rheumatology/kead526] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/26/2023] [Revised: 08/21/2023] [Accepted: 09/21/2023] [Indexed: 09/30/2023] Open
Abstract
OBJECTIVES The direct impact of inflammatory conditions and their therapy with corticosteroids contribute to an increased risk of osteoporosis with associated fractures. Familial Mediterranean fever (FMF) is an autoinflammatory disorder not commonly treated with corticosteroids. Evidence regarding FMF association with osteoporosis and femur fractures is anecdotal. We aimed to evaluate the incidence and risk of osteoporosis and femoral neck fracture in FMF patients compared with the general population. METHODS A retrospective cohort study using the electronic database of Clalit Health Services of all FMF patients first diagnosed between 2000 and 2016 and controls was conducted including age- and sex-matched controls in a 1:1 ratio. Follow-up continued until the first diagnosis of osteoporosis or fracture. Risk for these conditions was compared using univariate and multivariate Cox regression models. RESULTS A total of 9769 FMF patients were followed for a median period of 12.5 years. Of these, 304 FMF patients were diagnosed with osteoporosis compared with 191 controls, resulting in an incidence rate (per 10 000 persons-years) of 28.8 and 17.8, respectively, and a crude hazard ratio of 1.62 (95% CI 1.35, 1.93; P < 0.001). Patients were diagnosed with osteoporosis at a considerably younger age than controls [60.1 (s.d. 12.4) vs 62.5 (s.d. 11.0) years; P = 0.028]. A total of 56 FMF patients were diagnosed with femoral neck fracture compared with 35 controls, resulting in an incidence rate of 5.3 and 3.3, respectively, and a crude HR of 1.60 (95% CI 1.05, 2.44; P < 0.05). CONCLUSION FMF patients are at increased risk for osteoporosis and consequently femur fracture. Our findings emphasize the importance of considering bone health in the management of FMF patients.
Collapse
Affiliation(s)
- Yonatan Shneor Patt
- Department of Internal Medicine B and Zabludowicz Center for Autoimmune Diseases, Sheba Medical Center, Tel-Hashomer, Israel
- Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel
| | - Niv Ben-Shabat
- Department of Internal Medicine B and Zabludowicz Center for Autoimmune Diseases, Sheba Medical Center, Tel-Hashomer, Israel
- Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel
| | - Lior Fisher
- Department of Internal Medicine B and Zabludowicz Center for Autoimmune Diseases, Sheba Medical Center, Tel-Hashomer, Israel
- Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel
| | - Kassem Sharif
- Department of Internal Medicine B and Zabludowicz Center for Autoimmune Diseases, Sheba Medical Center, Tel-Hashomer, Israel
- Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel
- Department of Gastroenterology, Sheba Medical Center, Tel-Hashomer, Israel
| | - Mohamad Arow
- Department of Internal Medicine B and Zabludowicz Center for Autoimmune Diseases, Sheba Medical Center, Tel-Hashomer, Israel
- Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel
| | - Simon Lassman
- Department of Internal Medicine B and Zabludowicz Center for Autoimmune Diseases, Sheba Medical Center, Tel-Hashomer, Israel
- St George's Hospital, University of London, London, UK
| | - Abdulla Watad
- Department of Internal Medicine B and Zabludowicz Center for Autoimmune Diseases, Sheba Medical Center, Tel-Hashomer, Israel
- Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel
- Leeds Institute of Rheumatic and Musculoskeletal Medicine, University of Leeds, Leeds, UK
| | - Vita Skuja
- Department of Internal Medicine, Riga Stradins University, Riga, Latvia
- Anti-Aging Institute, Health Center 4, Riga, Latvia
| | - Anan H Shtewe
- Department of Orthopedic Surgery, Spine Surgery Service, Sheba Medical Center, Tel-Hashomer, Israel
| | - Dennis McGonagle
- Leeds Institute of Rheumatic and Musculoskeletal Medicine, University of Leeds, Leeds, UK
- NIHR Leeds Musculoskeletal Biomedical Research Unit, Chapel Allerton, Leeds Teaching Hospital Trust, Leeds, UK
| | - Howard Amital
- Department of Internal Medicine B and Zabludowicz Center for Autoimmune Diseases, Sheba Medical Center, Tel-Hashomer, Israel
- Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel
| |
Collapse
|
|
4
|
Zhang S, Hao W, Chen D, Chen S, Li Z, Zhong F, Wang H, Wang J, Zheng Z, Zhan Z, Dai G, Liu H. Intermittent administration of PTH for the treatment of inflammatory bone loss does not enhance entheseal pathological new bone formation. Biochem Biophys Res Commun 2024; 711:149888. [PMID: 38603833 DOI: 10.1016/j.bbrc.2024.149888] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/18/2024] [Revised: 03/21/2024] [Accepted: 04/03/2024] [Indexed: 04/13/2024]
Abstract
OBJECTIVE To investigate the effect of intermittent parathyroid hormone (iPTH) administration on pathological new bone formation during treatment of ankylosing spondylitis-related osteoporosis. METHODS Animal models with pathological bone formation caused by hypothetical AS pathogenesis received treatment with iPTH. We determined the effects of iPTH on bone loss and the formation of pathological new bone with micro-computed tomography (micro-CT) and histological examination. In addition, the tamoxifen-inducible conditional knockout mice (CAGGCre-ERTM; PTHflox/flox, PTH-/-) was established to delete PTH and investigate the effect of endogenous PTH on pathological new bone formation. RESULTS iPTH treatment significantly improved trabecular bone mass in the modified collagen-induced arthritis (m-CIA) model and unbalanced mechanical loading models. Meanwhile, iPTH treatment did not enhance pathological new bone formation in all types of animal models. Endogenous PTH deficiency had no effects on pathological new bone formation in unbalanced mechanical loading models. CONCLUSION Experimental animal models of AS treated with iPTH show improvement in trabecular bone density, but not entheseal pathological bone formation，indicating it may be a potential treatment for inflammatory bone loss does in AS.
Collapse
Affiliation(s)
- Shuai Zhang
- Department of Spine Surgery, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510080, Guangdong, China; Guangdong Province Key Laboratory of Orthopaedics and Traumatology, Guangzhou, 510080, Guangdong, China
| | - Wenjun Hao
- Department of Spine Surgery, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510080, Guangdong, China; Guangdong Province Key Laboratory of Orthopaedics and Traumatology, Guangzhou, 510080, Guangdong, China
| | - Dongying Chen
- Department of Rheumatology and Immunology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510080, Guangdong, China
| | - Siwen Chen
- Department of Spine Surgery, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510080, Guangdong, China; Guangdong Province Key Laboratory of Orthopaedics and Traumatology, Guangzhou, 510080, Guangdong, China
| | - Zihao Li
- Department of Spine Surgery, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510080, Guangdong, China; Guangdong Province Key Laboratory of Orthopaedics and Traumatology, Guangzhou, 510080, Guangdong, China
| | - Fangling Zhong
- Department of Spine Surgery, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510080, Guangdong, China; Guangdong Province Key Laboratory of Orthopaedics and Traumatology, Guangzhou, 510080, Guangdong, China
| | - Haitao Wang
- Department of Spine Surgery, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510080, Guangdong, China; Guangdong Province Key Laboratory of Orthopaedics and Traumatology, Guangzhou, 510080, Guangdong, China
| | - Jianru Wang
- Department of Spine Surgery, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510080, Guangdong, China; Guangdong Province Key Laboratory of Orthopaedics and Traumatology, Guangzhou, 510080, Guangdong, China
| | - Zhaomin Zheng
- Department of Spine Surgery, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510080, Guangdong, China; Guangdong Province Key Laboratory of Orthopaedics and Traumatology, Guangzhou, 510080, Guangdong, China
| | - Zhongping Zhan
- Department of Rheumatology and Immunology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510080, Guangdong, China
| | - Guo Dai
- Department of Spine Surgery, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510080, Guangdong, China; Guangdong Province Key Laboratory of Orthopaedics and Traumatology, Guangzhou, 510080, Guangdong, China.
| | - Hui Liu
- Department of Spine Surgery, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510080, Guangdong, China; Guangdong Province Key Laboratory of Orthopaedics and Traumatology, Guangzhou, 510080, Guangdong, China.
| |
Collapse
|
|
5
|
Li B, Yang Z, Li Y, Zhang J, Li C, Lv N. Exploration beyond osteoarthritis: the association and mechanism of its related comorbidities. Front Endocrinol (Lausanne) 2024; 15:1352671. [PMID: 38779455 PMCID: PMC11110169 DOI: 10.3389/fendo.2024.1352671] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/08/2023] [Accepted: 03/12/2024] [Indexed: 05/25/2024] Open
Abstract
Osteoarthritis is the most prevalent age-related degenerative joint disease and a leading cause of pain and disability in aged people. Its etiology is multifaceted, involving factors such as biomechanics, pro-inflammatory mediators, genetics, and metabolism. Beyond its evident impact on joint functionality and the erosion of patients' quality of life, OA exhibits symbiotic relationships with various systemic diseases, giving rise to various complications. This review reveals OA's extensive impact, encompassing osteoporosis, sarcopenia, cardiovascular diseases, diabetes mellitus, neurological disorders, mental health, and even cancer. Shared inflammatory processes, genetic factors, and lifestyle elements link OA to these systemic conditions. Consequently, recognizing these connections and addressing them offers opportunities to enhance patient care and reduce the burden of associated diseases, emphasizing the need for a holistic approach to managing OA and its complications.
Collapse
Affiliation(s)
| | | | | | | | | | - Naishan Lv
- The Second Affiliated Hospital of Shandong University of Traditional Chinese Medicine (Shandong Hospital of integrated traditional Chinese and Western medicine), Jinan, China
| |
Collapse
|
|
6
|
Drapkina OM, Kontsevaya AV, Kalinina AM, Avdeev SN, Agaltsov MV, Alekseeva LI, Almazova II, Andreenko EY, Antipushina DN, Balanova YA, Berns SA, Budnevsky AV, Gainitdinova VV, Garanin AA, Gorbunov VM, Gorshkov AY, Grigorenko EA, Jonova BY, Drozdova LY, Druk IV, Eliashevich SO, Eliseev MS, Zharylkasynova GZ, Zabrovskaya SA, Imaeva AE, Kamilova UK, Kaprin AD, Kobalava ZD, Korsunsky DV, Kulikova OV, Kurekhyan AS, Kutishenko NP, Lavrenova EA, Lopatina MV, Lukina YV, Lukyanov MM, Lyusina EO, Mamedov MN, Mardanov BU, Mareev YV, Martsevich SY, Mitkovskaya NP, Myasnikov RP, Nebieridze DV, Orlov SA, Pereverzeva KG, Popovkina OE, Potievskaya VI, Skripnikova IA, Smirnova MI, Sooronbaev TM, Toroptsova NV, Khailova ZV, Khoronenko VE, Chashchin MG, Chernik TA, Shalnova SA, Shapovalova MM, Shepel RN, Sheptulina AF, Shishkova VN, Yuldashova RU, Yavelov IS, Yakushin SS. Comorbidity of patients with noncommunicable diseases in general practice. Eurasian guidelines. КАРДИОВАСКУЛЯРНАЯ ТЕРАПИЯ И ПРОФИЛАКТИКА 2024; 23:3696. [DOI: 10.15829/1728-8800-2024-3996] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/10/2024] Open
Abstract
Создание руководства поддержано Советом по терапевтическим наукам отделения клинической медицины Российской академии наук.
Collapse
|
|
7
|
Shi YK, Yuan KH, Fu ZM, Hu RR, Wang H. The Relationship Between Systemic Lupus Erythematosus and Osteoporosis Based on Different Ethnic Groups: a Two-Sample Mendelian Randomization Analysis. Calcif Tissue Int 2024; 114:386-396. [PMID: 38355832 DOI: 10.1007/s00223-024-01190-8] [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: 06/01/2023] [Accepted: 01/29/2024] [Indexed: 02/16/2024]
Abstract
The previous observational studies could not overcome the effects of confounding variables and reverse causality. We aimed to determine whether there is a causal relationship between systemic lupus erythematosus and osteoporosis in East Asian and European populations, respectively, by two-sample Mendelian Randomization analysis. We obtained and downloaded data from publicly available genome-wide association study databases and analyses for East Asian and European populations, including systemic lupus erythematosus (SLE), osteoporosis (OP), multisite bone mineral density (BMD), and OP with fracture. After screening for instrumental single-nucleotide polymorphisms (SNPs) significantly correlated to SLE, the inverse-variance weighted (IVW) method was used for calculating the ratio and 95% confidence interval, besides utilizing MR-Egger, weighted median, and weighted mode to assess the robustness of the primary outcome. Moreover, multiple analyses, including MR-PRESSO, MR-Egger intercept, Cochran's Q test, as well as "leave-one-out" sensitivity, were used for evaluating horizontal pleiotropy, heterogeneity, and stability. Finally, we exchanged exposure and outcome and performed a reverse MR analysis. IVW (OR = 1.05, 95% CI = 1.01-1.09, P = 0.009) indicated a significant positive correlation between genetically predicted SLE and OP in East Asians. Furthermore, neither heterogeneity nor horizontal pleiotropy was observed. In Europe, there was no significant genetically predicted causal relation between SLE and OP. Bi-directional MR analysis showed no reverse causality between SLE and OP. In the East Asian population, genetically predicted SLE may have had a positive causal relationship with OP. In Europe, there is insufficient evidence for a potential causal relation between SLE and OP or BMD and fracture, and the correlations currently observed may be attributed to a variety of confounder variables.
Collapse
Affiliation(s)
- Y K Shi
- Department of Nuclear Medicine, Hainan Hospital Of PLA General Hospital, 80 Jianglin Road, Sanya, China
| | - K H Yuan
- Department of Nuclear Medicine, Hainan Hospital Of PLA General Hospital, 80 Jianglin Road, Sanya, China
| | - Z M Fu
- Department of Nuclear Medicine, Hainan Hospital Of PLA General Hospital, 80 Jianglin Road, Sanya, China
| | - R R Hu
- Department of Nuclear Medicine, Hainan Hospital Of PLA General Hospital, 80 Jianglin Road, Sanya, China
| | - H Wang
- Department of Nuclear Medicine, Hainan Hospital Of PLA General Hospital, 80 Jianglin Road, Sanya, China.
| |
Collapse
|
|
8
|
Evenepoel P, Stenvinkel P, Shanahan C, Pacifici R. Inflammation and gut dysbiosis as drivers of CKD-MBD. Nat Rev Nephrol 2023; 19:646-657. [PMID: 37488276 DOI: 10.1038/s41581-023-00736-7] [Citation(s) in RCA: 18] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 06/19/2023] [Indexed: 07/26/2023]
Abstract
Two decades ago, Kidney Disease: Improving Global Outcomes coined the term chronic kidney disease-mineral and bone disorder (CKD-MBD) to describe the syndrome of biochemical, bone and extra-skeletal calcification abnormalities that occur in patients with CKD. CKD-MBD is a prevalent complication and contributes to the excessively high burden of fractures and cardiovascular disease, loss of quality of life and premature mortality in patients with CKD. Thus far, therapy has focused primarily on phosphate retention, abnormal vitamin D metabolism and parathyroid hormone disturbances, but these strategies have largely proved unsuccessful, thus calling for paradigm-shifting concepts and innovative therapeutic approaches. Interorgan crosstalk is increasingly acknowledged to have an important role in health and disease. Accordingly, mounting evidence suggests a role for both the immune system and the gut microbiome in bone and vascular biology. Gut dysbiosis, compromised gut epithelial barrier and immune cell dysfunction are prominent features of the uraemic milieu. These alterations might contribute to the inflammatory state observed in CKD and could have a central role in the pathogenesis of CKD-MBD. The emerging fields of osteoimmunology and osteomicrobiology add another level of complexity to the pathogenesis of CKD-MBD, but also create novel therapeutic opportunities.
Collapse
Affiliation(s)
- Pieter Evenepoel
- Laboratory of Nephrology, Department of Microbiology, Immunology, and Transplantation, KU Leuven, Herestraat, Leuven, Belgium.
| | - Peter Stenvinkel
- Department of Renal Medicine M99, Karolinska University Hospital, Stockholm, Sweden
| | - Catherine Shanahan
- British Heart Foundation Centre of Excellence, School of Cardiovascular and Metabolic Medicine and Sciences, King's College London, London, UK
| | - Roberto Pacifici
- Division of Endocrinology, Metabolism and Lipids, Department of Medicine, Emory Microbiome Research Center, and Immunology and Molecular Pathogenesis Program, Emory University, Atlanta, GA, USA
| |
Collapse
|
|
9
|
Shevchuk S, Marynych L, Malovana T, Denyshchych L. Vitamin D level in patients with systemic lupus erythematosus: its relationship to disease course and bone mineral density. Lupus Sci Med 2023; 10:e000968. [PMID: 37558268 PMCID: PMC10414063 DOI: 10.1136/lupus-2023-000968] [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: 06/12/2023] [Accepted: 07/28/2023] [Indexed: 08/11/2023]
Abstract
OBJECTIVE To determine vitamin D levels in patients with SLE and evaluate their relationship to bone mineral density (BMD) and the disease course. METHODS The study included 101 patients with SLE and 29 individuals in the control group. The study participants were tested for vitamin D level, erythrocyte sedimentation rate (ESR), C reactive protein (CRP), interleukin (IL)-6, osteocalcin (OC) and collagen type I C-terminal telopeptide (CTX), and the dual-energy X-ray absorptiometry was provided to assess BMD in the lumbar spine and the hip. RESULTS The mean serum vitamin D level was 18.98±0.88 ng/mL, and women had 25.42% lower vitamin D levels than men (p<0.05). There was no correlation between vitamin D levels and patient's age or disease course. There was a significant inverse correlation between vitamin D levels and cumulative dose of glucocorticoids (r=-0.26) and serum inflammatory markers, particularly CRP (r=-0.39), IL-6 (r=-0.37) and ESR (r=-0.15). Vitamin D level was associated with the bone turnover markers (BTMs). In women of reproductive age with vitamin D deficiency, BMD of the lumbar spine and the hip was 9.5-23.1% higher than in those with no vitamin deficiency, respectively, and the mean lumbar spine Z-score in women of reproductive age with vitamin D insufficiency and deficiency was significantly 2.0 and 2.9 times lower than in patients with normal vitamin D level. CONCLUSIONS Hypovitaminosis D is quite common in patients with SLE and is associated with high inflammatory activity (SLE Disease Activity Index, ESR, CRP, IL-6), severity of organ damage (Damage Index), cumulative dose of glucocorticoids, BTM changes (decrease in OC, increase in CTX) and BMD decline. Vitamin D status was not associated with the patient's age or disease course.
Collapse
Affiliation(s)
- Sergii Shevchuk
- Vinnytsia National Medical University, Vinnytsia, Ukraine
- Research Institute for Rehabilitation of Individuals with Disabilities (Educational and Scientific Treatment Facility) of Vinnytsia National Medical University, Vinnytsia, Ukraine
| | | | | | | |
Collapse
|
|
10
|
Gómez-Vaquero C, Hernández JL, Olmos JM, Cerdà D, Calleja CH, López JAM, Arboleya L, Del Rey FJA, Pardo SM, Vilamajó IR, Armangué XS, Grados D, Audera CB, Suero-Rosario E, Gracia IG, Chamizo AS, Martín-Esteve I, Florez H, Naranjo A, Castañeda S, Bruno SO, Carazo SG, Garcia-Vadillo A, Vives LL, Martínez-Ferrer À, Paños HB, Acín PA, Castellanos-Moreira R, Satorra P, Tebé C, Guañabens N. High incidence of clinical fragility fractures in postmenopausal women with rheumatoid arthritis. A case-control study. Bone 2023; 168:116654. [PMID: 36584785 DOI: 10.1016/j.bone.2022.116654] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/26/2022] [Revised: 12/20/2022] [Accepted: 12/21/2022] [Indexed: 12/29/2022]
Abstract
OBJECTIVES To estimate the incidence of clinical fragility fractures in postmenopausal women with rheumatoid arthritis (RA) and analyze risk factors for fracture. METHODS Incidence of clinical fragility fractures in 330 postmenopausal women with RA was compared to that of a control population of 660 age-matched postmenopausal Spanish women. Clinical fractures during the previous five years were recorded. We analyzed associations with risk factors for fracture in both populations and with disease-related variables in RA patients. RESULTS Median age of RA patients was 64 years; median RA duration was eight years. Sixty-nine percent were in remission or on low activity. Eighty-five percent had received glucocorticoids (GCs); 85 %, methotrexate; and 40 %, ≥1 biologic DMARD. Fifty-four patients and 47 controls had ≥1 major osteoporotic fracture (MOF). Incidence of MOFs was 3.55 per 100 patient-year in patients and 0.72 in controls (HR: 2.6). Risk factors for MOFs in RA patients were age, previous fracture, parental hip fracture, years since menopause, BMD, erosions, disease activity and disability, and cumulative dose of GCs. Previous fracture in RA patients was a strong risk for MOFs (HR: 10.37). CONCLUSION Of every 100 postmenopausal Spanish women with RA, 3-4 have a MOF per year. This is more than double that of the general population. A previous fracture poses a high risk for a new fracture. Other classic risk factors for fracture, RA disease activity and disability, and the cumulative dose of GCs are associated with fracture development.
Collapse
Affiliation(s)
- Carmen Gómez-Vaquero
- Department of Rheumatology, Hospital Universitari de Bellvitge, L'Hospitalet de Llobregat, University of Barcelona, Barcelona, Spain.
| | - José Luis Hernández
- Depto. de Medicina y Psiquiatría, Universidad de Cantabria, Servicio de Medicina Interna, Hospital Universitario Marqués de Valdecilla, Instituto de Investigación Valdecilla (IDIVAL), Santander, Spain
| | - José Manuel Olmos
- Depto. de Medicina y Psiquiatría, Universidad de Cantabria, Servicio de Medicina Interna, Hospital Universitario Marqués de Valdecilla, Instituto de Investigación Valdecilla (IDIVAL), Santander, Spain
| | - Dacia Cerdà
- Department of Rheumatology, Hospital Moisès Broggi, Sant Joan Despí, University of Barcelona, Barcelona, Spain
| | | | | | - Luis Arboleya
- Department of Rheumatology, University Hospital Central de Asturias, Oviedo, Spain
| | | | | | | | - Xavier Surís Armangué
- Department of Rheumatology, Hospital General de Granollers, Granollers, International University of Catalunya, Barcelona, Spain
| | - Dolors Grados
- Department of Rheumatology, Hospital d'Igualada, Igualada, Barcelona, Spain
| | | | | | | | | | | | - Helena Florez
- Department of Rheumatology, Hospital Clínic, CIBERehd, IDIBAPS, University of Barcelona, Barcelona, Spain
| | - Antonio Naranjo
- Department of Rheumatology, University Hospital de Gran Canaria Dr. Negrín, Las Palmas de Gran Canaria, Spain
| | - Santos Castañeda
- Department of Rheumatology, University Hospital La Princesa IIS-, IP, Madrid, Spain
| | - Soledad Ojeda Bruno
- Department of Rheumatology, University Hospital de Gran Canaria Dr. Negrín, Las Palmas de Gran Canaria, Spain
| | | | | | | | | | | | - Pilar Aguado Acín
- Department of Rheumatology, University Hospital La Paz, Madrid, Spain
| | - Raul Castellanos-Moreira
- Department of Rheumatology, Hospital Clínic, CIBERehd, IDIBAPS, University of Barcelona, Barcelona, Spain
| | - Pau Satorra
- Biostatistics Unit, Bellvitge Biomedical Research Institute (IDIBELL), L'Hospitalet de Llobregat, Barcelona, Spain
| | - Cristian Tebé
- Biostatistics Unit, Bellvitge Biomedical Research Institute (IDIBELL), L'Hospitalet de Llobregat, University of Barcelona, Barcelona, Spain
| | - Núria Guañabens
- Department of Rheumatology, Hospital Clínic, CIBERehd, IDIBAPS, University of Barcelona, Barcelona, Spain
| |
Collapse
|
|
11
|
Sulphurous Crenotherapy Is Effective at Reducing Pain and Disability in Overweight/Obese Patients Affected by Chronic Low Back Pain from Spine Osteoarthritis. Healthcare (Basel) 2022; 10:healthcare10091800. [PMID: 36141412 PMCID: PMC9498685 DOI: 10.3390/healthcare10091800] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/19/2022] [Revised: 09/09/2022] [Accepted: 09/13/2022] [Indexed: 11/24/2022] Open
Abstract
Crenotherapy is recognized as being effective in patients with osteoarthritis of the spine, but to date there is no indication if it is effective for patients who are overweight or obese. The aim of this study is to evaluate the efficacy of sulphurous crenotherapy on pain and disability in overweight/obese subjects affected by chronic low back pain from spine osteoarthritis. Forty-three patients (63 ± 8.8 years) affected by chronic low back pain from lumbar spine osteoarthritis were enrolled in this study. Subjects were treated with 2 weeks of sulphurous creno-treatments. Subjective pain was measured by a numerical rating scale score (NRS), and functional mobility of the lumbar spine was measured using the Oswestry Disability Index (ODI) before and after crenotherapy. Both crenotherapy groups (normal weight: A1; overweight/obese: A2) experienced significantly improved NRS and ODI scores (A1: p < 0.001 and p = 0.001; A2: p = 0.001 and p = 0.001). At end of the treatment, significant improvements were observed as a result of the crenotherapy in overweight/obese subjects in terms of pain reduction measured with NRS (p = 0.03) and in terms of function mobility of the lumbar spine measured with ODI (p = 0.006). This study highlights the beneficial effect of sulphurous crenotherapy on the painful symptomatology and disability in both normal weight and overweight/obese patients suffering from chronic low back pain associated with lumbar spine osteoarthritis.
Collapse
|
|
12
|
Bone Involvement in Systemic Lupus Erythematosus. Int J Mol Sci 2022; 23:ijms23105804. [PMID: 35628614 PMCID: PMC9143163 DOI: 10.3390/ijms23105804] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/30/2022] [Revised: 05/19/2022] [Accepted: 05/20/2022] [Indexed: 02/01/2023] Open
Abstract
Systemic lupus erythematosus (SLE) is a chronic autoimmune disease characterized by a wide variability of clinical manifestations due to the potential involvement of several tissues and internal organs, with a relapsing and remitting course. Dysregulation of innate and adaptive immune systems, due to genetic, hormonal and environmental factors, may be responsible for a broad spectrum of clinical manifestations, affecting quality of life, morbidity and mortality. Bone involvement represents one of the most common cause of morbidity and disability in SLE. Particularly, an increased incidence of osteoporosis, avascular necrosis of bone and osteomyelitis has been observed in SLE patients compared to the general population. Moreover, due to the improvement in diagnosis and therapy, the survival of SLE patient has improved, increasing long-term morbidities, including osteoporosis and related fractures. This review aims to highlight bone manifestations in SLE patients, deepening underlying etiopathogenetic mechanisms, diagnostic tools and available treatment.
Collapse
|
|
13
|
Lv F, Hu S, Lin C, Cai X, Zhu X, Ji L. Association between biologic therapy and fracture incidence in patients with selected rheumatic and autoimmune diseases: A systematic review and meta-analysis of randomized controlled trials. Pharmacol Res 2022; 181:106278. [DOI: 10.1016/j.phrs.2022.106278] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/21/2022] [Revised: 05/18/2022] [Accepted: 05/24/2022] [Indexed: 12/19/2022]
|
|
14
|
Abstract
Objective Denosumab, an anti-RANKL monoclonal antibody, was reported to improve bone mineral density (BMD) and reduce fracture risk, offering favorable efficacy against postmenopausal osteoporosis. However, some patients have experienced a reduced BMD despite denosumab therapy. Methods We performed an observational study to clarify the clinical efficacy of denosumab for osteoporosis in rheumatic disease patients. Serum levels of bone turnover markers and lumber BMD in 100 rheumatic disease patients were examined at baseline and 6 and 12 months after denosumab therapy. The independent influence of changes in the BMD was examined by multiple regression analyses adjusted for patient characteristics and bone turnover markers. Results As bone resorption markers, serum levels of N-telopeptide crosslinked of type I collagen (NTx) and tartrate-resistant acid phosphatase isoform 5b were statistically decreased after 12 months. As bone formation markers, serum levels of osteocalcin, procollagen type I N-terminal peptide, and bone alkaline phosphatase were significantly decreased after 12 months. The mean BMD was significantly increased after 12 months. However, in 10 patients, the BMD decreased. A multivariate analysis of factors related to BMD changes highlighted a young age, low prednisolone dosage, and reduction in NTx. Conclusions Denosumab increases the BMD to combat osteoporosis in rheumatic disease patients, and potential predictors of a better response to denosumab include a young age, reduction in bone turnover markers, and low-dose glucocorticoid use.
Collapse
Affiliation(s)
- Kaichi Kaneko
- Division of Rheumatology, Department of Internal Medicine, Toho University School of Medicine, Japan
| | - Kotaro Shikano
- Division of Rheumatology, Department of Internal Medicine, Toho University School of Medicine, Japan
| | - Mai Kawazoe
- Division of Rheumatology, Department of Internal Medicine, Toho University School of Medicine, Japan
| | - Shinichi Kawai
- Department of Inflammation and Pain Control Research, Toho University School of Medicine, Japan
| | - Toshihiro Nanki
- Division of Rheumatology, Department of Internal Medicine, Toho University School of Medicine, Japan
| |
Collapse
|
|
15
|
Assessment of Low Bone Mineral Density in Untreated Patients with Takayasu's Arteritis. BIOMED RESEARCH INTERNATIONAL 2021; 2021:6489631. [PMID: 34692838 PMCID: PMC8528581 DOI: 10.1155/2021/6489631] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 07/07/2021] [Revised: 09/16/2021] [Accepted: 09/17/2021] [Indexed: 12/13/2022]
Abstract
Chronic inflammation affects bone metabolism and accelerates bone loss. This study is aimed at analyzing the prevalence of low bone mineral density (LBMD) in patients with untreated Takayasu's arteritis (TA) and risk factors. Forty untreated TA patients were enrolled, including 38 premenopausal women and 2 men before 50 years old. The control group included 60 age- and gender-matched healthy persons. Bone mineral density (BMD) of lumbar vertebrae and hip in patients with TA and the control group was measured by the dual-energy X-ray method. Serum 25OHD and β-CTX were also measured. The lumbar BMD of TA patients (0.89 ± 0.11 g/cm2) was significantly lower than that of the healthy control (0.97 ± 0.11 g/cm2). The prevalence of LBMD at the lumbar spine (17.50%) was significantly higher than that of the control group (3.33%). However, there was no significant difference at the hip. The 25OHD of TA patients was lower than that of healthy controls, while the level of β-CTX was higher. The levels of total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C) in patients with LBMD were higher than those in patients with normal BMD. According to univariate correlation analysis, there was a significant negative correlation between LDL-C and lumbar BMD. Binary logistic regression analysis showed that LDL-C was an important factor affecting the occurrence of LBMD in patients with TA (OR = 25.269, P = 0.02). Our result reveals bone loss in TA patients, which hints the relationship among inflammation, lipid metabolism, and bone metabolism.
Collapse
|
|
16
|
Tahtabasi M, Kilicaslan N, Akin Y, Karaman E, Gezer M, Icen YK, Sahiner F. The Prognostic Value of Vertebral Bone Density on Chest CT in Hospitalized COVID-19 Patients. J Clin Densitom 2021; 24:506-515. [PMID: 34353732 PMCID: PMC8302819 DOI: 10.1016/j.jocd.2021.07.007] [Citation(s) in RCA: 29] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/17/2021] [Revised: 07/15/2021] [Accepted: 07/16/2021] [Indexed: 01/08/2023]
Abstract
The aim of this study is to evaluate the prognostic value of the vertebral bone mineral density (BMD) on chest computed tomography (CT) in COVID-19 patients. The chest CT of hospitalized patients with COVID-19 pneumonia were evaluated for Pneumonia Severity Score (PSS) as the ratio of the volume of involved lung parenchyma to the total lung volume. In addition, BMD was manually measured from the vertebral corpus using axial CT images. The relationships of clinical variables, PSS and vertebral BMD with patient outcomes, namely mortality, intensive care unit (ICU) admission and mechanical ventilation were investigated. Lower BMD was defined as ≤100 HU. The study included 209 patients (118 males, 56.4%). As a result of the univariate analysis, the rates of mortality, ICU admission and mechanical ventilation were 17.2% (n = 36), 24.8% (n = 52), and 20.6% (n = 43), respectively, and they were significantly higher among the patients with lower BMD (38.1 vs 13.0%, p < 0.001; 33.4 vs 21.2%, p = 0.002; and 38.1 vs 8.2%, p < 0.001, respectively). In the mortality group, PSS was significantly higher (median, 9 vs 5; p < 0.001) and vertebral BMD was significantly lower (median, 83 vs 139; p < 0.001). Severe clinical incidence was significantly higher in patients with lower BMD compared to those with higher BMD (39.7 vs 24.7% and p = 0.028). There was a significant correlation between clinical classification and lower BMD (r = 0.152 and p = 0.028). The multivariate analysis revealed vertebral BMD [odds ratio (OR), 1.028; 95% CI, 1.011-1.045, p = 0.001) and lower BMD (OR, 4.682; 95% CI, 1.784-12.287, p = 0.002) as significant independent predictors of mortality. Vertebral BMD is a strong independent predictor of mortality that is reproducible and can be easily evaluated on the chest CT images of COVID-19 patients.
Collapse
Affiliation(s)
- Mehmet Tahtabasi
- Department of Radiology, University of Health Sciences- Mehmet Akif Inan Education and Research Hospital, Sanliurfa, Turkey.
| | - Nihat Kilicaslan
- Department of Radiology, University of Health Sciences- Mehmet Akif Inan Education and Research Hospital, Sanliurfa, Turkey
| | - Yasin Akin
- Department of Radiology, University of Health Sciences- Mehmet Akif Inan Education and Research Hospital, Sanliurfa, Turkey
| | - Ergin Karaman
- Department of Radiology, University of Health Sciences- Mehmet Akif Inan Education and Research Hospital, Sanliurfa, Turkey
| | - Mehmet Gezer
- Department of Radiology, University of Health Sciences- Mehmet Akif Inan Education and Research Hospital, Sanliurfa, Turkey
| | - Yahya Kemal Icen
- Department of Cardiology, University of Health Sciences - Adana Health Practice and Research Center, Adana, Turkey
| | - Fatih Sahiner
- Department of Medical Microbiology, Gulhane Medical Faculty, University of Health Sciences, Ankara, Turkey
| |
Collapse
|
|
17
|
Hoff M, Skovlund E, Meyer HE, Langhammer A, Søgaard AJ, Syversen U, Holvik K, Abrahamsen B, Schei B. Does treatment with bisphosphonates protect against fractures in real life? The HUNT study, Norway. Osteoporos Int 2021; 32:1395-1404. [PMID: 33479844 PMCID: PMC8192327 DOI: 10.1007/s00198-021-05845-2] [Citation(s) in RCA: 3] [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: 09/04/2020] [Accepted: 01/11/2021] [Indexed: 12/02/2022]
Abstract
UNLABELLED Bisphosphonates reduce fractures in randomized controlled trials (RCT); however, there is less information from real life. In our population including 14,990 women and 13,239 men, use of bisphosphonates reduced risk of fractures in hip and forearm in women. The magnitude of the effect was comparable to results from RCT. INTRODUCTION The objective was to examine if treatment with bisphosphonates (BPs) was associated with reduced risk of fractures in the hip and forearm in women and men in the general population. METHODS In a cohort study based on data from the third wave of the population-based HUNT Study (HUNT3), the fracture registry in Nord-Trøndelag, and the Norwegian Prescription Database, 14,990 women and 13,239 men 50-85 years were followed from the date of participating in HUNT3 (2006-2008) until the date of first fracture in the hip or forearm, death, or end of study (31 December 2012). Hazard ratios with 95% confidence intervals for hip and forearm fracture according to use of BPs were estimated using Cox proportional hazards models with time-dependent exposure. Adjustment for individual FRAX® fracture risk assessment scores was included. RESULTS BPs, predominantly alendronate, were used by 9.4% of the women and 1.5% of the men. During a median of 5.2 years of follow-up, 265 women and 133 men had a hip fracture, and 662 women and 127 men had a forearm fracture. Compared with non-users of BPs, the hazard ratios with 95% confidence interval for a fracture among users of BPs adjusted for age and FRAX® were 0.67 (0.52-0.86) for women and 1.13 (0.50-2.57) for men. Among users of glucocorticoids, the corresponding figures were 0.35 (0.19-0.66) and 1.16 (0.33-4.09), respectively. CONCLUSIONS Use of BPs was associated with reduced risk of fractures in hip and forearm in women, and the magnitude of effect is comparable to results from RCTs.
Collapse
Affiliation(s)
- M Hoff
- Department of Neuromedicine and Movement Science, Norwegian University of Science and Technology, NTNU, Trondheim, Norway.
- Department of Public Health and Nursing, Norwegian University of Science and Technology, NTNU, Trondheim, Norway.
- Department of Rheumatology, St. Olavs hospital, Trondheim University Hospital, Trondheim, Norway.
| | - E Skovlund
- Department of Public Health and Nursing, Norwegian University of Science and Technology, NTNU, Trondheim, Norway
- Norwegian Institute of Public Health, Oslo, Norway
| | - H E Meyer
- Norwegian Institute of Public Health, Oslo, Norway
- Department of Community Medicine and Global Health, University of Oslo, Oslo, Norway
| | - A Langhammer
- HUNT Research Centre, Department of Public Health and Nursing, Norwegian University of Science and Technology, NTNU, Trondheim, Norway
- Levanger Hospital, Nord-Trøndelag Hospital Trust, Levanger, Norway
| | - A J Søgaard
- Norwegian Institute of Public Health, Oslo, Norway
| | - U Syversen
- Department of Endocrinology, St. Olavs hospital, Trondheim University Hospital, Trondheim, Norway
- Department of Clinical and Molecular Medicine, Norwegian University of Science and Technology, NTNU, Trondheim, Norway
| | - K Holvik
- Norwegian Institute of Public Health, Oslo, Norway
| | - B Abrahamsen
- Department of Medicine, Holbæk Hospital, Holbæk, Denmark
- Odense Patient Data Explorative Network, Institute of Clinical Research, University of Southern Denmark, Odense, Denmark
| | - B Schei
- Department of Public Health and Nursing, Norwegian University of Science and Technology, NTNU, Trondheim, Norway
- Department of Gynecology, St. Olavs hospital, Trondheim University Hospital, Trondheim, Norway
| |
Collapse
|
|
18
|
Zhang P, Zhou S, Chen Z, Tian Y, Wang Q, Li H, Zhang T, Guo Q, Wang M, Guo C. TNF Receptor: Fc Fusion Protein Downregulates RANKL/OPG Ratio by Inhibiting CXCL16/CXCR6 in Active Ankylosing Spondylitis. Curr Pharm Biotechnol 2021; 22:305-316. [PMID: 32116188 DOI: 10.2174/1389201021666200302104418] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/16/2019] [Revised: 12/20/2019] [Accepted: 02/09/2020] [Indexed: 11/22/2022]
Abstract
BACKGROUND Clinical studies indicate that recombinant tumor necrosis factor receptor:Fc fusion protein (rhTNFR:Fc) quickly alleviates symptoms and physical signs of active Ankylosing Spondylitis (AS), improving the manifestation of spinal inflammation on radiological imaging. However, the regulatory mechanism of rhTNFR:Fc in the chemokine pathway is unclear. Thus we study the mechanism of phlogogenic activity of CXCL16/CXCR6 in AS and the related mechanism of rhTNFR: Fc treatment. METHODS Thirty-two cases of active AS were treated with rhTNFR:Fc for 3 consecutive months. Clinical response was evaluated at baseline and after treatment. CXCL16/CXCR6 expression as well as Receptor Activator Of Nuclear Factor-Κb Ligand (RANKL)/Osteoprotegerin (OPG), essential molecules for osteoclast differentiation, were studied in AS before and after treatment. Further, the proliferation of lymphocytes and the RANKL level stimulated by recombinant human CXCL16 (rhCXCL16) were measured in vitro. RESULTS Thirty cases responded to rhTNFR:Fc treatment. The RANKL level, RANKL/OPG ratio, CXCLl6 level in serum, and CXCLl6 and CXCR6 mRNA levels in active AS were higher than those in controls and treated patients (P<0.001). rhCXCL16 treatment increased lymphocyte proliferation and RANKL level in active AS (P<0.001), but not in controls or treated patients (P>0.05). A positive linear correlation was noted between CXCL16 serum levels and RANKL/OPG ratio and between CXCL16 levels and C-reactive protein results (P<0.001). CONCLUSIONS Our findings suggest that rhTNFR:Fc suppresses inflammation and bone destruction of AS by reducing the RANKL/OPG ratio through inhibition of the CXCL16/CXCR6 pathway.
Collapse
Affiliation(s)
- Peiyi Zhang
- Department of Rheumatology and Immunology, Jinan Central Hospital Affiliated to Shandong University, Jinan 250013, China
| | - Shufen Zhou
- Department of Rheumatology and Immunology, Southern Medical University Affiliated Shenzhen Baoan Hospital, Shenzhen 518101, China
| | - Zhe Chen
- Department of Rheumatology and Immunology, Southern Medical University Affiliated Shenzhen Baoan Hospital, Shenzhen 518101, China
| | - Ye Tian
- Department of Rheumatology and Immunology, Southern Medical University Affiliated Shenzhen Baoan Hospital, Shenzhen 518101, China
| | - Qianqian Wang
- Department of Rheumatology and Immunology, Southern Medical University Affiliated Shenzhen Baoan Hospital, Shenzhen 518101, China
| | - Hui Li
- Department of Rheumatology and Immunology, Southern Medical University Affiliated Shenzhen Baoan Hospital, Shenzhen 518101, China
| | - Tiantian Zhang
- Department of Rheumatology and Immunology, Southern Medical University Affiliated Shenzhen Baoan Hospital, Shenzhen 518101, China
| | - Qin Guo
- Department of Rheumatology and Immunology, Southern Medical University Affiliated Shenzhen Baoan Hospital, Shenzhen 518101, China
| | - Meiying Wang
- Department of Rheumatology and Immunology, Peking University Shenzhen Hospital, Shenzhen 518000, China
| | - Chengshan Guo
- Department of Rheumatology and Immunology, Southern Medical University Affiliated Shenzhen Baoan Hospital, Shenzhen 518101, China
| |
Collapse
|
|
19
|
Structural and Functional Changes of Hands and Legs in Early Rheumatoid Arthritis. ACTA ACUST UNITED AC 2021; 57:medicina57040317. [PMID: 33800568 PMCID: PMC8066246 DOI: 10.3390/medicina57040317] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/28/2021] [Revised: 03/18/2021] [Accepted: 03/24/2021] [Indexed: 11/19/2022]
Abstract
Background and Objectives: The aim of this study was to assess if there are structural and functional changes of hands and legs already in early rheumatoid arthritis (ERA), compared with the population-based control group. Additionally, we aimed to identify if the changes are symmetrical in hands and legs and if there are factors that are associated with these changes. The study was conducted, and, thus far, the results have been controversial. Materials and Methods: The study group consisted of 83 consecutive patients with ERA and 321 control subjects. Dual-Energy X-Ray Absorptiometry (DXA) machine was used to measure bone, lean and fat mass. Inflammation and bone markers, smoking and nutritional habits were assessed, to evaluate the effects of different factors. The 30-Second Chair Stand Test (30-CST) and the Handgrip Strength Test (HST) were used to estimate muscle strength. Results: The presence of ERA was associated with lower arm, leg lean mass and higher fat mass of arm, compared with control subjects. ERA was also associated with lower mean handgrip in HST and worse muscle strength of legs in the 30-CST. Bone mass changes were not so evident both in arms and legs. Smoking habits did not seem to have relevant effect on bone mass, muscle structural and functional changes, both on hands and legs. In ERA, lean mass of arm and leg was negatively associated with C-reactive protein (CRP). The intake of proteins in ERA was not associated with lean mass changes both in hands and legs. Conclusions: Structural and functional changes of hands and legs are different in ERA. ERA patients had higher fat mass of arm, lower lean mass of arm and leg and, accordingly, decreased muscle function. The lowering of lean mass of arm and leg in ERA was associated with the elevation of CRP.
Collapse
|
|
20
|
Bone Loss, Osteoporosis, and Fractures in Patients with Rheumatoid Arthritis: A Review. J Clin Med 2020; 9:jcm9103361. [PMID: 33092162 PMCID: PMC7589399 DOI: 10.3390/jcm9103361] [Citation(s) in RCA: 35] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/28/2020] [Revised: 10/08/2020] [Accepted: 10/15/2020] [Indexed: 12/19/2022] Open
Abstract
Rheumatoid arthritis (RA) is often characterized by bone loss and fragility fractures and is a frequent comorbidity. Compared with a matched population, RA patients with fractures have more common risk factors of osteoporosis and fragility fractures but also risk factors resulting from the disease itself such as duration, intensity of the inflammation and disability, and cachexia. The inflammatory reaction in the synovium results in the production of numerous cytokines (interleukin-1, interleukin-6, tumor necrosis factor) that activate osteoclasts and mediate cartilage and bone destruction of the joints, but also have a systemic effect leading to generalized bone loss. Regular bone mineral density (BMD) measurement, fracture risk assessment using tools such as the FRAX algorithm, and vertebral fracture assessment (VFA) should be performed for early detection of osteoporosis and accurate treatment in RA patients.
Collapse
|
|
21
|
Vaamonde-García C, Burguera EF, Vela-Anero Á, Hermida-Gómez T, Filgueira-Fernández P, Fernández-Rodríguez JA, Meijide-Faílde R, Blanco FJ. Intraarticular Administration Effect of Hydrogen Sulfide on an In Vivo Rat Model of Osteoarthritis. Int J Mol Sci 2020; 21:ijms21197421. [PMID: 33050005 PMCID: PMC7582513 DOI: 10.3390/ijms21197421] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/14/2020] [Revised: 10/01/2020] [Accepted: 10/06/2020] [Indexed: 12/15/2022] Open
Abstract
Osteoarthritis (OA) is the most common articular chronic disease. However, its current treatment is limited and mostly symptomatic. Hydrogen sulfide (H2S) is an endogenous gas with recognized physiological activities. The purpose here was to evaluate the effects of the intraarticular administration of a slow-releasing H2S compound (GYY-4137) on an OA experimental model. OA was induced in Wistar rats by the transection of medial collateral ligament and the removal of the medial meniscus of the left joint. The animals were randomized into three groups: non-treated and intraarticularly injected with saline or GYY-4137. Joint destabilization induced articular thickening (≈5% increment), the loss of joint mobility and flexion (≈12-degree angle), and increased levels of pain (≈1.5 points on a scale of 0 to 3). Animals treated with GYY-4137 presented improved motor function of the joint, as well as lower pain levels (≈75% recovery). We also observed that cartilage deterioration was attenuated in the GYY-4137 group (≈30% compared with the saline group). Likewise, these animals showed a reduced presence of pro-inflammatory mediators (cyclooxygenase-2, inducible nitric oxide synthase, and metalloproteinase-13) and lower oxidative damage in the cartilage. The increment of the nuclear factor-erythroid 2-related factor 2 (Nrf-2) levels and Nrf-2-regulated gene expression (≈30%) in the GYY-4137 group seem to be underlying its chondroprotective effects. Our results suggest the beneficial impact of the intraarticular administration of H2S on experimental OA, showing a reduced cartilage destruction and oxidative damage, and supporting the use of slow H2S-producing molecules as a complementary treatment in OA.
Collapse
Affiliation(s)
- Carlos Vaamonde-García
- Grupo de Terapia Celular y Medicina Regenerativa, Universidad de A Coruña, Agrupación Estratégica CICA- INIBIC, Complexo Hospitalario Universitario A Coruña, Campus Oza, 15006 A Coruña, Spain; (C.V.-G.); (Á.V.-A.)
- Grupo de Investigación en Reumatología (GIR), INIBIC-Complexo Hospitalario Universitario A Coruña, Sergas, As Xubias, 15006 A Coruña, Spain; (E.F.B.); (T.H.-G.); (P.F.-F.)
| | - Elena F. Burguera
- Grupo de Investigación en Reumatología (GIR), INIBIC-Complexo Hospitalario Universitario A Coruña, Sergas, As Xubias, 15006 A Coruña, Spain; (E.F.B.); (T.H.-G.); (P.F.-F.)
- Centro de investigación biomédica en Red, Bioingeniería, Biomateriales y Nanomedicina (CIBER-BBN), 28029 Madrid, Spain
| | - Ángela Vela-Anero
- Grupo de Terapia Celular y Medicina Regenerativa, Universidad de A Coruña, Agrupación Estratégica CICA- INIBIC, Complexo Hospitalario Universitario A Coruña, Campus Oza, 15006 A Coruña, Spain; (C.V.-G.); (Á.V.-A.)
| | - Tamara Hermida-Gómez
- Grupo de Investigación en Reumatología (GIR), INIBIC-Complexo Hospitalario Universitario A Coruña, Sergas, As Xubias, 15006 A Coruña, Spain; (E.F.B.); (T.H.-G.); (P.F.-F.)
- Centro de investigación biomédica en Red, Bioingeniería, Biomateriales y Nanomedicina (CIBER-BBN), 28029 Madrid, Spain
| | - Purificación Filgueira-Fernández
- Grupo de Investigación en Reumatología (GIR), INIBIC-Complexo Hospitalario Universitario A Coruña, Sergas, As Xubias, 15006 A Coruña, Spain; (E.F.B.); (T.H.-G.); (P.F.-F.)
- Centro de investigación biomédica en Red, Bioingeniería, Biomateriales y Nanomedicina (CIBER-BBN), 28029 Madrid, Spain
| | - Jennifer A. Fernández-Rodríguez
- Grupo de Envejecimiento e Inflamación, Agrupación Estratégica CICA- INIBIC, Complexo Hospitalario Universitario A Coruña, Sergas, Universidad de A Coruña, As Xubias, 15006 A Coruña, Spain;
| | - Rosa Meijide-Faílde
- Grupo de Terapia Celular y Medicina Regenerativa, Universidad de A Coruña, Agrupación Estratégica CICA- INIBIC, Complexo Hospitalario Universitario A Coruña, Campus Oza, 15006 A Coruña, Spain; (C.V.-G.); (Á.V.-A.)
- Correspondence: (R.M.-F.); (F.J.B.); Tel.: +34-981167000 (ext. 5855) (R.M.-F.); +34-981176399 (F.J.B.)
| | - Francisco J. Blanco
- Grupo de Investigación en Reumatología (GIR), INIBIC-Complexo Hospitalario Universitario A Coruña, Sergas, As Xubias, 15006 A Coruña, Spain; (E.F.B.); (T.H.-G.); (P.F.-F.)
- Grupo de Investigación de Reumatología y Salud (GIR), Departamento de Fisioterapia, Medicina y Ciencias Biomédicas, Facultad de Fisioterapia, Agrupación Estrategica CICA-INIBIC, Universidade da Coruña, Campus de Oza, 15006 A Coruña, Spain
- Correspondence: (R.M.-F.); (F.J.B.); Tel.: +34-981167000 (ext. 5855) (R.M.-F.); +34-981176399 (F.J.B.)
| |
Collapse
|
|
22
|
Fratter A, Pellizzato M. Novel micellar system for Vitamin D3 oral delivery: Assessment of enteric absorption through a digestion-like in vitro model. J Drug Deliv Sci Technol 2020. [DOI: 10.1016/j.jddst.2020.101840] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/24/2022]
|
|
23
|
Okano I, Jones C, Salzmann SN, Miller CO, Shirahata T, Rentenberger C, Shue J, Carrino JA, Sama AA, Cammisa FP, Girardi FP, Hughes AP. Postoperative decrease of regional volumetric bone mineral density measured by quantitative computed tomography after lumbar fusion surgery in adjacent vertebrae. Osteoporos Int 2020; 31:1163-1171. [PMID: 32170396 DOI: 10.1007/s00198-020-05367-3] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/16/2019] [Accepted: 02/24/2020] [Indexed: 12/21/2022]
Abstract
UNLABELLED We investigated the effect of posterior lumbar fusion surgery on the regional volumetric bone mineral density (vBMD) measured by quantitative computed tomography. Surgery negatively affected the regional vBMD in adjacent levels. Interbody fusion was independently associated with vBMD decline and preoperative epidural steroid injections (ESIs) were associated with less postoperative vBMD decline. INTRODUCTION Few studies investigate postoperative BMD changes after lumbar fusion surgery utilizing quantitative computed tomography (QCT). Additionally, it remains unclear what preoperative and operative factors contribute to postoperative BMD changes. The purpose of this study is to investigate the effect of lumbar fusion surgery on regional volumetric bone mineral density (vBMD) in adjacent vertebrae and to identify potential modifiers for postoperative BMD change. METHODS The data of patients undergoing posterior lumbar fusion with available pre- and postoperative CTs were reviewed. The postoperative changes in vBMD in the vertebrae one or two levels above the upper instrumented vertebra (UIV+1, UIV+2) and one level below the lower instrumented vertebra (LIV+1) were analyzed. As potential contributing factors, history of ESI, and the presence of interbody fusion, as well as various demographic/surgical factors, were included. RESULTS A total of 90 patients were included in the study analysis. Mean age (±SD) was 62.1 ± 11.7. Volumetric BMD (±SD) in UIV+1 was 115.4 ± 36.9 mg/cm3 preoperatively. The percent vBMD change in UIV+1 was - 10.5 ± 12.9% (p < 0.001). UIV+2 and LIV+1 vBMD changes showed similar trends. After adjusting with the interval between surgery and the secondary CT, non-Caucasian race, ESI, and interbody fusion were independent contributors to postoperative BMD change in UIV+1. CONCLUSIONS Posterior lumbar fusion surgery negatively affected the regional vBMDs in adjacent levels. Interbody fusion was independently associated with vBMD decline. Preoperative ESIs were associated with less postoperative vBMD decline, which was most likely a result of a preoperative decrease in vBMD due to ESIs.
Collapse
Affiliation(s)
- I Okano
- Spine Care Institute, Hospital for Special Surgery, 535 East 70th Street, New York, NY, 10021, USA
| | - C Jones
- Spine Care Institute, Hospital for Special Surgery, 535 East 70th Street, New York, NY, 10021, USA
| | - S N Salzmann
- Spine Care Institute, Hospital for Special Surgery, 535 East 70th Street, New York, NY, 10021, USA
| | - C O Miller
- Spine Care Institute, Hospital for Special Surgery, 535 East 70th Street, New York, NY, 10021, USA
| | - T Shirahata
- Spine Care Institute, Hospital for Special Surgery, 535 East 70th Street, New York, NY, 10021, USA
- Department of Orthopaedic Surgery, Showa University School of Medicine, 1-5-8 Hatanodai, Shinagawa-ku, Tokyo, 142-8555, Japan
| | - C Rentenberger
- Spine Care Institute, Hospital for Special Surgery, 535 East 70th Street, New York, NY, 10021, USA
| | - J Shue
- Spine Care Institute, Hospital for Special Surgery, 535 East 70th Street, New York, NY, 10021, USA
| | - J A Carrino
- Department of Radiology and Imaging, Hospital for Special Surgery, 535 East 70th Street, New York, NY, 10021, USA
| | - A A Sama
- Spine Care Institute, Hospital for Special Surgery, 535 East 70th Street, New York, NY, 10021, USA
| | - F P Cammisa
- Spine Care Institute, Hospital for Special Surgery, 535 East 70th Street, New York, NY, 10021, USA
| | - F P Girardi
- Spine Care Institute, Hospital for Special Surgery, 535 East 70th Street, New York, NY, 10021, USA
| | - A P Hughes
- Spine Care Institute, Hospital for Special Surgery, 535 East 70th Street, New York, NY, 10021, USA.
| |
Collapse
|
|
24
|
Lai EL, Huang WN, Chen HH, Chen JP, Chen DY, Hsieh TY, Hung WT, Lai KL, Lin CT, Tang KT, Chen YM, Chen YH. Degraded microarchitecture by low trabecular bone score is associated with prevalent vertebral fractures in patients with systemic lupus erythematosus. Arch Osteoporos 2020; 15:54. [PMID: 32221755 DOI: 10.1007/s11657-020-00726-3] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/11/2019] [Accepted: 03/17/2020] [Indexed: 02/03/2023]
Abstract
PURPOSE Recently, trabecular bone score (TBS) has emerged as an important supplementary assessment tool in osteoporosis diagnosis and management. The high incidence of fragility fracture within the non-osteoporotic range of bone mineral density (BMD), among systemic lupus erythematosus (SLE) patients, highlights the crucial role of bone microarchitecture in osteoporosis. This study aimed to evaluate whether TBS identified existing vertebral fractures (VF) more accurately than BMD in SLE patients. METHODS This study enrolled 147 SLE patients from the Asia Pacific Lupus Collaboration (APLC) cohort, who had BMD and TBS assessed from January 2018 until December 2018. Twenty-eight patients sustaining VF and risk factors associated with increased fracture occurrence were evaluated. Independent risk factors and diagnostic accuracy of VF were analyzed by logistic regression and ROC curve, respectively. RESULT The prevalence of vertebral fracture among SLE patients was 19%. BMD, T-score, TBS, and TBS T-score were significantly lower in the vertebral fracture group. TBS exhibited higher positive predictive value and negative predictive value than L spine and left femur BMD for vertebral fractures. Moreover, TBS had a higher diagnostic accuracy than densitometric measurements (area under curve, 0.811 vs. 0.737 and 0.605). CONCLUSION Degraded microarchitecture by TBS was associated with prevalent vertebral fractures in SLE patients. Our result suggests that TBS can be a complementary tool for assessing vertebral fracture prevalence in this population.
Collapse
Affiliation(s)
- Ee-Ling Lai
- Rheumatology Unit, Department of Internal Medicine, Hospital Sultan Ismail, Johor Bahru, Malaysia.,Division of Allergy, Immunology and Rheumatology, Department of Internal Medicine, Taichung Veterans General Hospital, No. 1650, Sec. 4, Taiwan Boulevard, Taichung, 40705, Taiwan
| | - Wen-Nan Huang
- Division of Allergy, Immunology and Rheumatology, Department of Internal Medicine, Taichung Veterans General Hospital, No. 1650, Sec. 4, Taiwan Boulevard, Taichung, 40705, Taiwan.,Faculty of Medicine, National Yang-Ming University, Taipei, Taiwan
| | - Hsin-Hua Chen
- Division of Allergy, Immunology and Rheumatology, Department of Internal Medicine, Taichung Veterans General Hospital, No. 1650, Sec. 4, Taiwan Boulevard, Taichung, 40705, Taiwan.,Faculty of Medicine, National Yang-Ming University, Taipei, Taiwan.,Department of Medical Research, Taichung Veterans General Hospital, Taichung, Taiwan.,Rong Hsing Research Center for Translational Medicine, Chung Hsing University, Taichung, Taiwan.,Translational Medicine, National Chung Hsing University, Taichung, Taiwan.,Department of Industrial Engineering and Enterprise Information, Tunghai University, Taichung, Taiwan
| | - Jun-Peng Chen
- Department of Medical Research, Taichung Veterans General Hospital, Taichung, Taiwan
| | - Der-Yuan Chen
- Rheumatology and Immunology Center, Department of Medicine, China Medical University Hospital, Taichung, Taiwan.,College of Medicine, China Medical University, Taichung, Taiwan
| | - Tsu-Yi Hsieh
- Division of Allergy, Immunology and Rheumatology, Department of Internal Medicine, Taichung Veterans General Hospital, No. 1650, Sec. 4, Taiwan Boulevard, Taichung, 40705, Taiwan.,Department of Medical Education, Taichung Veterans General Hospital, Taichung, Taiwan
| | - Wei-Ting Hung
- Division of Allergy, Immunology and Rheumatology, Department of Internal Medicine, Taichung Veterans General Hospital, No. 1650, Sec. 4, Taiwan Boulevard, Taichung, 40705, Taiwan.,Department of Medical Education, Taichung Veterans General Hospital, Taichung, Taiwan
| | - Kuo-Lung Lai
- Division of Allergy, Immunology and Rheumatology, Department of Internal Medicine, Taichung Veterans General Hospital, No. 1650, Sec. 4, Taiwan Boulevard, Taichung, 40705, Taiwan
| | - Ching-Tsai Lin
- Division of Allergy, Immunology and Rheumatology, Department of Internal Medicine, Taichung Veterans General Hospital, No. 1650, Sec. 4, Taiwan Boulevard, Taichung, 40705, Taiwan
| | - Kuo-Tung Tang
- Division of Allergy, Immunology and Rheumatology, Department of Internal Medicine, Taichung Veterans General Hospital, No. 1650, Sec. 4, Taiwan Boulevard, Taichung, 40705, Taiwan
| | - Yi-Ming Chen
- Division of Allergy, Immunology and Rheumatology, Department of Internal Medicine, Taichung Veterans General Hospital, No. 1650, Sec. 4, Taiwan Boulevard, Taichung, 40705, Taiwan. .,Faculty of Medicine, National Yang-Ming University, Taipei, Taiwan. .,Department of Medical Research, Taichung Veterans General Hospital, Taichung, Taiwan. .,Rong Hsing Research Center for Translational Medicine, Chung Hsing University, Taichung, Taiwan. .,Translational Medicine, National Chung Hsing University, Taichung, Taiwan. .,Bioinformatics Section, National Institute of Neurological Disorder and Stroke, National Institutes of Health, Bethesda, MD, USA.
| | - Yi-Hsing Chen
- Division of Allergy, Immunology and Rheumatology, Department of Internal Medicine, Taichung Veterans General Hospital, No. 1650, Sec. 4, Taiwan Boulevard, Taichung, 40705, Taiwan.,Faculty of Medicine, National Yang-Ming University, Taipei, Taiwan
| |
Collapse
|
|
25
|
Vaamonde-García C, Vela-Anero Á, Hermida-Gómez T, Fernández-Burguera E, Filgueira-Fernández P, Goyanes N, Blanco FJ, Meijide-Faílde R. Effect of balneotherapy in sulfurous water on an in vivo murine model of osteoarthritis. INTERNATIONAL JOURNAL OF BIOMETEOROLOGY 2020; 64:307-318. [PMID: 31828429 DOI: 10.1007/s00484-019-01807-w] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/25/2019] [Revised: 09/12/2019] [Accepted: 09/16/2019] [Indexed: 06/10/2023]
Abstract
Osteoarthritis (OA) is a chronic joint disease that results in progressive cartilage destruction and subsequently joint dysfunction. Growing evidence indicates beneficial impact of balneological interventions in OA; however, their mechanisms of action are still unclear. Here, we evaluate the effect of balneotherapy in sulfurous water in an OA experimental model. Experimental OA was induced in Wistar rats by transection of the medial collateral ligament and removal of the medial meniscus of the left knee. Animals were randomized into three groups: non-treated (control) and balneotherapy using sulfurous water (SW) or tap water (TW). Macroscopic evaluation was performed, as well as evaluation of pain levels and analysis of motor function by rotarod test. Histopathological changes in articular cartilage and synovium were also evaluated. The presence of matrix metalloproteinase-13 (MMP-13) and oxidative damage markers was assessed by immunohistochemistry. Joint destabilization induced joint thickening, loss of joint flexion, and increased levels of pain. At day 40, animals from SW group presented lower pain levels than those from control group. Experimental OA also affected motor function. Balneotherapy in sulfur-rich water significantly improved joint mobility in relation to that in tap water. Besides, we observed that cartilage deterioration was lower in SW group than in the other two groups. Likewise, SW group showed reduced levels of MMP-13 in the cartilage. Conversely, we failed to observe any modulation on synovial inflammation. Finally, balneotherapy in sulfurous water diminished the presence of oxidative damage markers. Our results suggest the beneficial effect of balneotherapy in sulfur-rich water on an experimental model of OA, showing a reduced cartilage destruction and oxidative damage. Thus, these findings support the use of balneotherapy as a non-pharmacological treatment in OA.
Collapse
Affiliation(s)
- Carlos Vaamonde-García
- Facultad de Ciencias de la Salud, Grupo de Terapia Celular y Medicina Regenerativa, Agrupación Estratégica CICA-INIBIC, Complexo Hospitalario Universitario A Coruña, Campus de Oza, 15006, A Coruña, Spain.
| | - Ángela Vela-Anero
- Facultad de Ciencias de la Salud, Grupo de Terapia Celular y Medicina Regenerativa, Agrupación Estratégica CICA-INIBIC, Complexo Hospitalario Universitario A Coruña, Campus de Oza, 15006, A Coruña, Spain
- CIBER-BBN, Barcelona, Spain
| | - Tamara Hermida-Gómez
- Grupo de Investigación en Reumatología (GIR), Agrupación Estratégica CICA-INIBIC, Complexo Hospitalario Universitario A Coruña, Sergas, Universidad de A Coruña, As Xubias, 15006, A Coruña, Spain
| | - Elena Fernández-Burguera
- CIBER-BBN, Barcelona, Spain
- Grupo de Investigación en Reumatología (GIR), Agrupación Estratégica CICA-INIBIC, Complexo Hospitalario Universitario A Coruña, Sergas, Universidad de A Coruña, As Xubias, 15006, A Coruña, Spain
| | - Purificación Filgueira-Fernández
- Grupo de Investigación en Reumatología (GIR), Agrupación Estratégica CICA-INIBIC, Complexo Hospitalario Universitario A Coruña, Sergas, Universidad de A Coruña, As Xubias, 15006, A Coruña, Spain
| | - Noa Goyanes
- Grupo de Investigación en Reumatología (GIR), Agrupación Estratégica CICA-INIBIC, Complexo Hospitalario Universitario A Coruña, Sergas, Universidad de A Coruña, As Xubias, 15006, A Coruña, Spain
| | - Francisco J Blanco
- Grupo de Investigación de Reumatología, INIBIC-Hospital Universitario A Coruña, Departamento de Fisioterapia, Medicina y Ciencias Biomdicas, Universidad de A Coruña, A Coruña, Spain
| | - Rosa Meijide-Faílde
- Facultad de Ciencias de la Salud, Grupo de Terapia Celular y Medicina Regenerativa, Agrupación Estratégica CICA-INIBIC, Complexo Hospitalario Universitario A Coruña, Campus de Oza, 15006, A Coruña, Spain.
| |
Collapse
|
|
26
|
Abstract
Inflammatory rheumatic diseases are often associated with secondary osteoporosis, as many inflammatory messengers can interfere with bone metabolism and adversely affect it. In addition to a decrease in densitometric bone density, remodeling occurs in the trabecular bone, which can lead to a disturbed microarchitecture and increase the risk of fracture.Central to this is the close integration of bone metabolism and the immune system. Proinflammatory cytokines play an important role not only in the inflammatory process, but also as mediators of bone resorption because they stimulate osteoclastogenesis and induce further signal transduction cascades with negative influence on the bone. The understanding gained in recent years of the underlying immunological processes has led to the development of new and targeted treatment approaches.
Collapse
|
|
27
|
Fauny M, Albuisson E, Bauer E, Perrier-Cornet J, Chary-Valckenaere I, Loeuille D. Study of vertebral fracture and Scanographic Bone Attenuation Coefficient in rheumatoid arthritis and ankylosing spondylitis vs. controls. Sci Rep 2019; 9:13323. [PMID: 31527613 PMCID: PMC6746735 DOI: 10.1038/s41598-019-49712-x] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/03/2019] [Accepted: 08/16/2019] [Indexed: 01/14/2023] Open
Abstract
The objective of this study is to identify the prevalence of vertebral fractures (VFs) and to measure the scanographic bone attenuation coefficient of the first lumbar vertebra (SBAC-L1) based CT-scan, a biomarker of bone fragility in patients with rheumatoid arthritis (RA) and ankylosing spondylitis (AS) and in a control group. This monocentric and retrospective study included patients with RA and AS, based on ACR/EULAR or New-York criteria, respectively. A control group was constituted. All of the patients received a CT-scan. VFs were determined via CT-scans according to the Genant classification, and the SBAC-L1 was measured in Hounsfield units (HU). SBAC-L1 ≤145 HU (fracture threshold) defined patients at risk of VFs. 244 patients were included (105 RA, 83 AS, 56 controls). Of the 4.365 vertebrae studied, 66 osteoporotic VFs were found in 36 patients: 18 (17.1%) RA, 13 (15.7%) AS and 5 (8.9%) controls. The mean SBAC-L1 was 142.2 (±48.4) HU for RA, 142.8 (±48.2) for AS, both of which were significantly lower than that of the control group (161.8 (±42.7) HU). Of the 36 patients with VFs and rheumatism, 28% had a T-score ≤-2.5 SD and 71.4% a SBAC-L1 ≤145 HU. A T-score ≤-2.5 SD and a SBAC-L1 ≤145 HU were associated with VF (OR = 3.07 (CI 95%: 1.07; 8.81), and 2.31 (CI 95%: 1.06; 5.06)), respectively. The SBAC-L1 was significantly lower in the RA and AS groups than in the control group. Furthermore, SBAC-L1 ≤145 HU was associated with a higher risk of VFs, with an odds ratio similar to that of a DXA.
Collapse
Affiliation(s)
- Marine Fauny
- Department of Rheumatology, University Hospital, Nancy, France.
| | - Eliane Albuisson
- Pôle S2R, PARC, University Hospital, Vandoeuvre lès Nancy, France.,University of Lorraine, Faculty of Medicine, InSciDens, Vandoeuvre lès Nancy, France.,CNRS, Institute Elie Cartan de Lorraine, UMR 7502, Vandoeuvre-lès-Nancy, F-54506, France
| | - Elodie Bauer
- Department of Rheumatology, University Hospital, Nancy, France
| | | | | | - Damien Loeuille
- Department of Rheumatology, University Hospital, Nancy, France
| |
Collapse
|
|
28
|
Dogru A, Balkarli A, Karatay CC, Cobankara V, Sahin M. Bone mineral density and serum osteocalcin levels in patients with gout. Acta Clin Belg 2019; 74:252-257. [PMID: 30004299 DOI: 10.1080/17843286.2018.1495389] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
Objective: The objective of the study is to evaluate the relation of gout with osteoporosis and serum osteocalcin (OC) levels. Material and methods: Seventy-five patients diagnosed with gout and 55 controls were included in the study. Comorbid conditions and drugs associated with osteoporosis were excluded. The T and Z scores from lumbar spine (L2-L4) and femur (neck, ward, trochanter, total) were determined by dual-energy X-ray absorptiometry (DXA). OC levels were measured by enzyme-linked immunosorbent assay. Results: Osteoporosis according to T scores of lumbar vertebrae L2-L4 was found to be significantly higher in patients with gout compared to the control group (p = 0.02). Lumbar spine T-score was -1.6 in gout group and -1.0 in controls. OC level was 7.9 ng/mL in the gout group and 18.9 ng/mL in the control group. There was a significant difference (p < 0.001). In addition, mean OC level was 12.4 ± 6.9 ng/mL in the patients diagnosed with osteoporosis and 17.2 ± 10.6 ng/mL in the patients that were classified as normal and a significant difference was established between the two groups (p = 0.03). A significant negative correlation was found between OC level and body mass index, age, and age at first attack. Similarly, femoral T-score established a negative correlation with parathyroid hormone, age, age at first attack, and allopurinol dose. Conclusion: Serum OC level can be a useful marker in the assessment of bone turnover and clinicians should keep osteoporosis in mind in gout patients.
Collapse
Affiliation(s)
- Atalay Dogru
- Department of Internal Medicine, Division of Rheumatology, Dr. Ersin Arslan Training and Research Hospital, Gaziantep, Turkey
| | - Ayse Balkarli
- Department of Internal Medicine, Division of Rheumatology, Antalya Training and Research Hospital, Antalya, Turkey
| | | | - Veli Cobankara
- Department of Internal Medicine, Division of Rheumatology, Pamukkale University, Denizli, Turkey
| | - Mehmet Sahin
- Faculty of Medicine, Department of Internal Medicine, Division of Rheumatology, Suleyman Demirel University, Isparta, Turkey
| |
Collapse
|
|
29
|
Kim BY, Kim HA, Jung JY, Choi ST, Kim JM, Kim SH, Kwon SR, Suh CH, Kim SS. Clinical Impact of the Fracture Risk Assessment Tool on the Treatment Decision for Osteoporosis in Patients with Knee Osteoarthritis: A Multicenter Comparative Study of the Fracture Risk Assessment Tool and World Health Organization Criteria. J Clin Med 2019; 8:jcm8070918. [PMID: 31248035 PMCID: PMC6678257 DOI: 10.3390/jcm8070918] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/06/2019] [Revised: 06/19/2019] [Accepted: 06/22/2019] [Indexed: 11/23/2022] Open
Abstract
Background: To compare the frequency of high-risk osteoporotic fracture in patients with knee OA (OA) using the fracture risk assessment tool (FRAX) and the bone mineral density (BMD). Methods: We retrospectively assessed 282 Korean patients with knee OA who visited five medical centers and 1165 healthy controls (HCs) aged ≥50 years without knee OA. After matching for age, sex, and body mass index, 478 subjects (239 patients with knee OA and 239 HCs) were included. Results: Based on the BMD, the frequency of osteoporosis was 40.2% in patients with knee OA and 36.4% in HCs. The predicted mean FRAX major osteoporotic fracture probabilities calculated with or without femur neck BMD differed significantly between the knee OA and HCs (6.9 ± 3.8% versus 6.1 ± 2.8%, p = 0.000 and 8 ± 3.6% versus 6.8 ± 2.3%, p < 0.001, respectively). The mean FRAX hip fracture probabilities calculated with or without femur neck BMD differed significantly in the knee OA and HCs (2.1 ± 2.4% versus 1.7 ± 1.8%, p = 0.006 and 3 ± 2.3% versus 2.4 ± 1.6%, p < 0.001, respectively). Conclusion: Our study suggests that FRAX may have a clinical impact on treatment decisions to reduce osteoporotic facture in patients with knee OA.
Collapse
Affiliation(s)
- Bo Young Kim
- Division of Rheumatology, Department of Internal Medicine, Gangneung Asan Hospital, University of Ulsan College of Medicine, Gangneung 25440, Korea.
| | - Hyoun-Ah Kim
- Department of Rheumatology, Ajou University School of Medicine, Suwon 16449, Korea.
| | - Ju-Yang Jung
- Department of Rheumatology, Ajou University School of Medicine, Suwon 16449, Korea.
| | - Sang Tae Choi
- Division of Rheumatology, Department of Internal Medicine, Chung-Ang University College of Medicine, Seoul 06973, Korea.
| | - Ji-Min Kim
- Division of Rheumatology, Department of Internal Medicine, Keimyung University School of Medicine, Dongsan Medical Center, Daegu 42601, Korea.
| | - Sang Hyon Kim
- Division of Rheumatology, Department of Internal Medicine, Keimyung University School of Medicine, Dongsan Medical Center, Daegu 42601, Korea.
| | - Seong-Ryul Kwon
- Division of Rheumatology, Department of Internal Medicine, Rheumatism Center, Inha University Hospital, Incheon 22332, Korea.
| | - Chang-Hee Suh
- Department of Rheumatology, Ajou University School of Medicine, Suwon 16449, Korea.
| | - Sung-Soo Kim
- Division of Rheumatology, Department of Internal Medicine, Gangneung Asan Hospital, University of Ulsan College of Medicine, Gangneung 25440, Korea.
| |
Collapse
|
|
30
|
Coury F, Peyruchaud O, Machuca-Gayet I. Osteoimmunology of Bone Loss in Inflammatory Rheumatic Diseases. Front Immunol 2019; 10:679. [PMID: 31001277 PMCID: PMC6456657 DOI: 10.3389/fimmu.2019.00679] [Citation(s) in RCA: 62] [Impact Index Per Article: 10.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/08/2019] [Accepted: 03/12/2019] [Indexed: 12/14/2022] Open
Abstract
Over the past two decades, the field of osteoimmunology has emerged in response to a range of evidence demonstrating the reciprocal relationship between the immune system and bone. In particular, localized bone loss, in the form of joint erosions and periarticular osteopenia, as well as systemic osteoporosis, caused by inflammatory rheumatic diseases including rheumatoid arthritis, the prototype of inflammatory arthritis has highlighted the importance of this interplay. Osteoclast-mediated resorption at the interface between synovium and bone is responsible for the joint erosion seen in patients suffering from inflammatory arthritis. Clinical studies have helped to validate the impact of several pathways on osteoclast formation and activity. Essentially, the expression of pro-inflammatory cytokines as well as Receptor Activator of Nuclear factor κB Ligand (RANKL) is, both directly and indirectly, increased by T cells, stimulating osteoclastogenesis and resorption through a crucial regulator of immunity, the Nuclear factor of activated T-cells, cytoplasmic 1 (NFATc1). Furthermore, in rheumatoid arthritis, autoantibodies, which are accurate predictors both of the disease and associated structural damage, have been shown to stimulate the differentiation of osteoclasts, resulting in localized bone resorption. It is now also evident that osteoblast-mediated bone formation is impaired by inflammation both in joints and the skeleton in rheumatoid arthritis. This review summarizes the substantial progress that has been made in understanding the pathophysiology of bone loss in inflammatory rheumatic disease and highlights therapeutic targets potentially important for the cure or at least an alleviation of this destructive process.
Collapse
Affiliation(s)
- Fabienne Coury
- INSERM, UMR1033 LYOS, Lyon, France.,University Claude Bernard Lyon I, Lyon, France.,Department of Rheumatology, Lyon Sud Hospital, Lyon, France
| | - Olivier Peyruchaud
- INSERM, UMR1033 LYOS, Lyon, France.,University Claude Bernard Lyon I, Lyon, France
| | - Irma Machuca-Gayet
- INSERM, UMR1033 LYOS, Lyon, France.,University Claude Bernard Lyon I, Lyon, France
| |
Collapse
|
|
31
|
Abstract
Patients with Rheumatoid Arthritis (RA) commonly develop osteoporosis and fragility fractures. This fact cannot be explained only with the use of glucocorticoids, known to be detrimental for bone health. RA is characterized by a chronic inflammation caused by the continuous activation of innate and adaptive immunity with proinflammatory cytokines overproduction. This process is detrimental for several organs and physiological processes, including the impairment of bone remodeling. We will briefly review the pathogenesis of inflammation-related bone loss in RA, describing well-known and new molecular pathways and focusing on vitamin D and Parathyroid Hormone role.
Collapse
|
|
32
|
Herpes zoster and the risks of osteoporosis and fracture: a nationwide cohort study. Eur J Clin Microbiol Infect Dis 2018; 38:365-372. [PMID: 30460416 DOI: 10.1007/s10096-018-3436-y] [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: 10/04/2018] [Accepted: 11/14/2018] [Indexed: 10/27/2022]
Abstract
This study aimed to investigate the association between herpes zoster (HZ) and the risks of osteoporosis and fracture. We conducted a nationwide retrospective cohort study using the National Health Insurance Research Database of Taiwan. The study enrolled 63,786 patients: 31,893 diagnosed with HZ between 2000 and 2012 were included in the HZ cohort, and 31,893 matched controls without HZ were included in the non-HZ cohort, with 1:1 exact matching for age, sex, and index year. Hazard ratios (HRs) were calculated for the risks of osteoporosis and fracture according to the HZ status using the Cox proportional hazards regression models. During a mean follow-up period of 6.0 years, 5597 and 4639 patients in the HZ and non-HZ cohorts, respectively, developed osteoporosis or fractures (incidence rate: 29.8 vs. 23.8 per 1000 person-years). HZ diagnosis was significantly associated with an elevated risk of developing osteoporosis or fracture (adjusted HR [aHR] = 1.20, p < 0.001). On analyses for each individual event, the HZ cohort had significantly increased risks for all events, including osteoporosis (aHR = 1.32, p < 0.001), hip fracture (aHR = 1.34, p < 0.001), vertebral fracture (aHR = 1.38, p < 0.001), and other fractures (aHR = 1.10, p < 0.001) compared with the non-HZ cohort. Patients with postherpetic neuralgia had especially higher risks of osteoporosis and fracture. Age- and sex-stratified analyses also revealed similar patterns. In conclusion, HZ was independently associated with an increased risk of osteoporosis and fracture. Further studies are required to investigate its underlying mechanisms.
Collapse
|
|
33
|
Langdahl BL, Silverman S, Fujiwara S, Saag K, Napoli N, Soen S, Enomoto H, Melby TE, Disch DP, Marin F, Krege JH. Real-world effectiveness of teriparatide on fracture reduction in patients with osteoporosis and comorbidities or risk factors for fractures: Integrated analysis of 4 prospective observational studies. Bone 2018; 116:58-66. [PMID: 30021126 DOI: 10.1016/j.bone.2018.07.013] [Citation(s) in RCA: 63] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/01/2018] [Revised: 07/09/2018] [Accepted: 07/13/2018] [Indexed: 02/07/2023]
Abstract
INTRODUCTION Teriparatide significantly reduces fracture rates in clinical trials; however, those study populations were relatively restricted and included too few patients to analyze fracture outcomes within clinically important patient subgroups. We assessed fracture outcomes in subgroups of osteoporosis patients from 4 real-world teriparatide observational studies. METHODS Patients received teriparatide 20 μg/day for up to 24 months. Fracture rates were compared between 0 to 6 months versus >6 months using a piecewise exponential model for first fracture. Analyses included incident clinical vertebral fractures (CVF) and nonvertebral fractures (NVF), and clinical fractures (CVF and NVF) by subgroups of gender, age <75 or ≥75 years, diabetes, prior bisphosphonates use, rheumatoid arthritis (RA), glucocorticoid use, prior hip, and prior vertebral fracture. RESULTS The population included 8828 patients (8117 women, 92%) with mean (SD) age 71 (10.6) years and teriparatide treatment duration 17.4 (8.6) months. Overall, CVF, NVF, clinical fracture, and hip fracture rates decreased by 62%, 43%, 50%, and 56%, respectively (all p < .005) for >6 months versus 0 to 6 months. Subgroup analyses all showed significantly decreased rates after >6 months except for NVF reduction in males (n = 710, fracture rate low during months 0 to 6) and in patients using glucocorticoids, and CVF in patients with prior hip fracture. The effects of teriparatide on CVF, NVF, and clinical fractures over time were statistically consistent in all subgroups except age for CVF (p = .074, patients <75 years of age responded better), and diabetes for clinical fractures (p = .046, patients with diabetes responded better), although all of these subgroups experienced significant reductions over time. Glucocorticoids, prior bisphosphonate, and prior vertebral fracture were associated with increased CVF, NVF, and clinical fracture rates; RA, prior hip fracture and female gender were associated with higher NVF and clinical fracture rates; increased age was associated with higher CVF and clinical fracture rates. CONCLUSIONS Data from 4 real-world observational studies showed statistically significant reductions during teriparatide treatment in rates of CVF, NVF, and clinical fractures in clinically relevant patient subgroups. These results should be interpreted in the context of the non-controlled design of the source studies.
Collapse
Affiliation(s)
- Bente L Langdahl
- Department of Endocrinology and Internal Medicine, Aarhus University Hospital, Aarhus, Denmark.
| | - Stuart Silverman
- Cedars-Sinai/UCLA Medical Center and OMC Clinical Research Center, Beverly Hills, CA, USA.
| | - Saeko Fujiwara
- Health Management and Promotion Center, Hiroshima Atomic Bomb Casualty Council, Hiroshima, Japan
| | - Ken Saag
- Division of Clinical Immunology and Rheumatology, Center for Education and Research on Therapeutics University of Alabama at Birmingham, Birmingham, AL, USA.
| | - Nicola Napoli
- Division of Endocrinology and Diabetes, Campus Bio-Medico University of Rome, Rome, Italy; IRCCS Istituto Ortopedico Galeazzi, Milan, Italy
| | - Satoshi Soen
- Department of Orthopaedic Surgery and Rheumatology, Kindai University Nara Hospital, Ikoma, Japan.
| | | | | | | | | | | |
Collapse
|
|
34
|
Canella C, Costa F, Danowisk A, de Melo ASA, Marchiori E. Stress fracture and osteomyelitis in a patient with systemic lupus erythematosus. Radiol Bras 2018; 51:277-278. [PMID: 30202140 PMCID: PMC6124598 DOI: 10.1590/0100-3984.2017.0035] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 03/31/2024] Open
Affiliation(s)
- Clarissa Canella
- Clínica de Diagnóstico Por Imagem (CDPI), Rio de
Janeiro, RJ, e Universidade Federal Fluminense (UFF), Niterói, RJ,
Brazil
| | - Flavia Costa
- Clínica de Diagnóstico Por Imagem (CDPI), Rio de
Janeiro, RJ, Brazil
| | | | | | - Edson Marchiori
- Universidade Federal do Rio de Janeiro (UFRJ), Rio de Janeiro, RJ,
Brazil
| |
Collapse
|
|
35
|
Jin S, Hsieh E, Peng L, Yu C, Wang Y, Wu C, Wang Q, Li M, Zeng X. Incidence of fractures among patients with rheumatoid arthritis: a systematic review and meta-analysis. Osteoporos Int 2018; 29:1263-1275. [PMID: 29546507 DOI: 10.1007/s00198-018-4473-1] [Citation(s) in RCA: 82] [Impact Index Per Article: 11.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/23/2017] [Accepted: 03/01/2018] [Indexed: 12/17/2022]
Abstract
UNLABELLED This study is the first meta-analysis investigating the pooled incidence rates of fractures among patients with RA. Our results demonstrated that this population is at high risk of overall and fragility fractures. Consideration of vertebral imaging and RA-specific risk factor assessment may aid in fracture prevention for this vulnerable group. INTRODUCTION This systematic review and meta-analysis aims to estimate the incidence of fractures (overall and fragility) in patients with rheumatoid arthritis (RA). METHODS MEDLINE, EMBASE, and CENTRAL were searched for cohort studies reporting incidence of fractures among patients with RA. Two reviewers independently assessed all studies for inclusion and extracted data. Pooled analyses of incidence rates and relative risk of fractures were conducted using a random-effects model. Subgroup analyses investigated potential sources of heterogeneity, and predictors of fractures were summarized. RESULTS Twenty-five studies were included in total. The pooled incidence rates of overall and fragility fractures were 33.00 (95% CI 18.39-59.21) and 15.31 (95% CI 10.43-22.47) per 1000 person-years, respectively. Patients with RA had a higher risk of overall (RR 1.52, 95% CI 1.07-2.14) and fragility (RR 1.61, 95% CI 1.44-1.79) fractures. Subgroup analyses suggested a higher risk of fragility fractures among female patients (31.03 vs. 23.75 per 1000 person-years). The pooled site-specific incidence rates of vertebral, hip, forearm, and proximal humeral fractures were 7.51 (95% CI 3.27-17.23), 4.33 (95% CI 2.26-8.27), 3.40 (95% CI 2.27-5.10), and 1.86 (95% CI 1.36-2.53) per 1000 person-years, respectively. Clinical vertebral fractures were underestimated compared with radiographic screening (4.29 vs. 42.40 per 1000 person-years). Predictors of fractures included both traditional OP risk factors and RA-specific factors. CONCLUSIONS Patients with RA are at high risk of incident overall and fragility fractures. Consideration of vertebral imaging for patients with additional OP risk factors, including RA-specific risk factors, may help with early OP diagnosis and timely intervention.
Collapse
Affiliation(s)
- S Jin
- Department of Rheumatology, Peking Union Medical College Hospital, Peking Union Medical College & Chinese Academy of Medical Sciences, Key Laboratory of Rheumatology and Clinical Immunology, Ministry of Education, No.1 Shuaifuyuan, Wangfujing Ave, Beijing, 100730, China
| | - E Hsieh
- Section of Rheumatology, Yale School of Medicine, 300 Cedar Street, TAC S-525, P.O. Box 208031, New Haven, CT, 06520-8031, USA.
| | - L Peng
- Department of Rheumatology, Peking Union Medical College Hospital, Peking Union Medical College & Chinese Academy of Medical Sciences, Key Laboratory of Rheumatology and Clinical Immunology, Ministry of Education, No.1 Shuaifuyuan, Wangfujing Ave, Beijing, 100730, China
| | - C Yu
- Department of Rheumatology, Peking Union Medical College Hospital, Peking Union Medical College & Chinese Academy of Medical Sciences, Key Laboratory of Rheumatology and Clinical Immunology, Ministry of Education, No.1 Shuaifuyuan, Wangfujing Ave, Beijing, 100730, China
| | - Y Wang
- Department of Epidemiology and Bio-statistics, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, School of Basic Medicine, Peking Union Medical College, Beijing, China
| | - C Wu
- Department of Rheumatology, Peking Union Medical College Hospital, Peking Union Medical College & Chinese Academy of Medical Sciences, Key Laboratory of Rheumatology and Clinical Immunology, Ministry of Education, No.1 Shuaifuyuan, Wangfujing Ave, Beijing, 100730, China
| | - Q Wang
- Department of Rheumatology, Peking Union Medical College Hospital, Peking Union Medical College & Chinese Academy of Medical Sciences, Key Laboratory of Rheumatology and Clinical Immunology, Ministry of Education, No.1 Shuaifuyuan, Wangfujing Ave, Beijing, 100730, China
| | - M Li
- Department of Rheumatology, Peking Union Medical College Hospital, Peking Union Medical College & Chinese Academy of Medical Sciences, Key Laboratory of Rheumatology and Clinical Immunology, Ministry of Education, No.1 Shuaifuyuan, Wangfujing Ave, Beijing, 100730, China.
| | - X Zeng
- Department of Rheumatology, Peking Union Medical College Hospital, Peking Union Medical College & Chinese Academy of Medical Sciences, Key Laboratory of Rheumatology and Clinical Immunology, Ministry of Education, No.1 Shuaifuyuan, Wangfujing Ave, Beijing, 100730, China
| |
Collapse
|
|
36
|
Hauser B, Harre U. The Role of Autoantibodies in Bone Metabolism and Bone Loss. Calcif Tissue Int 2018; 102:522-532. [PMID: 29204673 DOI: 10.1007/s00223-017-0370-4] [Citation(s) in RCA: 8] [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: 09/04/2017] [Accepted: 11/27/2017] [Indexed: 12/20/2022]
Abstract
Many autoimmune diseases are associated with deranged bone metabolism. The resulting localized or systemic bone loss can compromise the quality of life of patients by causing local bone deformities or fragility fractures. There is emerging evidence that antibodies have a direct impact on key players of bone homeostasis, in particular osteoclasts. Clinical and pre-clinical studies provide insight into the function of autoantibodies related to Rheumatoid Arthritis (rheumatoid factor, anti-citrullinated protein antibodies, and anti-carbamylated protein antibodies) and their inflammation-independent interaction with bone cells. Furthermore, we summarize the current knowledge about neutralizing antibodies to the antiresorptive protein osteoprotegerin, which have been described in patients with Coeliac Disease, Rheumatoid Arthritis, and Spondyloarthritis.
Collapse
Affiliation(s)
- Barbara Hauser
- Centre for Genomics and Experimental Medicine, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, UK
| | - Ulrike Harre
- Department of Internal Medicine 3 - Rheumatology and Immunology, Friedrich-Alexander-University Erlangen-Nürnberg (FAU), Universitätsklinikum Erlangen, Ulmenweg 18, 91054, Erlangen, Germany.
| |
Collapse
|
|
37
|
Hafez EA, ElBakry SA, Ibrahim SI, Morad CS, Hamza SA, Abd El-Khalik DM. Assessment of fracture risk in a cohort of Egyptian female Systemic Lupus erythematosus patients. THE EGYPTIAN RHEUMATOLOGIST 2018; 40:85-91. [DOI: 10.1016/j.ejr.2017.07.006] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 09/02/2023]
|
|
38
|
Franceschi C, Garagnani P, Morsiani C, Conte M, Santoro A, Grignolio A, Monti D, Capri M, Salvioli S. The Continuum of Aging and Age-Related Diseases: Common Mechanisms but Different Rates. Front Med (Lausanne) 2018; 5:61. [PMID: 29662881 PMCID: PMC5890129 DOI: 10.3389/fmed.2018.00061] [Citation(s) in RCA: 548] [Impact Index Per Article: 78.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/11/2018] [Accepted: 02/20/2018] [Indexed: 12/11/2022] Open
Abstract
Geroscience, the new interdisciplinary field that aims to understand the relationship between aging and chronic age-related diseases (ARDs) and geriatric syndromes (GSs), is based on epidemiological evidence and experimental data that aging is the major risk factor for such pathologies and assumes that aging and ARDs/GSs share a common set of basic biological mechanisms. A consequence is that the primary target of medicine is to combat aging instead of any single ARD/GSs one by one, as favored by the fragmentation into hundreds of specialties and sub-specialties. If the same molecular and cellular mechanisms underpin both aging and ARDs/GSs, a major question emerges: which is the difference, if any, between aging and ARDs/GSs? The hypothesis that ARDs and GSs such as frailty can be conceptualized as accelerated aging will be discussed by analyzing in particular frailty, sarcopenia, chronic obstructive pulmonary disease, cancer, neurodegenerative diseases such as Alzheimer and Parkinson as well as Down syndrome as an example of progeroid syndrome. According to this integrated view, aging and ARDs/GSs become part of a continuum where precise boundaries do not exist and the two extremes are represented by centenarians, who largely avoided or postponed most ARDs/GSs and are characterized by decelerated aging, and patients who suffered one or more severe ARDs in their 60s, 70s, and 80s and show signs of accelerated aging, respectively. In between these two extremes, there is a continuum of intermediate trajectories representing a sort of gray area. Thus, clinically different, classical ARDs/GSs are, indeed, the result of peculiar combinations of alterations regarding the same, limited set of basic mechanisms shared with the aging process. Whether an individual will follow a trajectory of accelerated or decelerated aging will depend on his/her genetic background interacting lifelong with environmental and lifestyle factors. If ARDs and GSs are manifestations of accelerated aging, it is urgent to identify markers capable of distinguishing between biological and chronological age to identify subjects at higher risk of developing ARDs and GSs. To this aim, we propose the use of DNA methylation, N-glycans profiling, and gut microbiota composition to complement the available disease-specific markers.
Collapse
Affiliation(s)
- Claudio Franceschi
- Institute of Neurological Sciences, University of Bologna, Bellaria Hospital, Bologna, Italy
| | - Paolo Garagnani
- Department of Experimental, Diagnostic and Specialty Medicine (DIMES), University of Bologna, Bologna, Italy.,Clinical Chemistry, Department of Laboratory Medicine, Karolinska Institutet at Huddinge University Hospital, Stockholm, Sweden.,Applied Biomedical Research Center (CRBA), S. Orsola-Malpighi Polyclinic, Bologna, Italy.,CNR Institute of Molecular Genetics, Unit of Bologna, Bologna, Italy
| | - Cristina Morsiani
- Department of Experimental, Diagnostic and Specialty Medicine (DIMES), University of Bologna, Bologna, Italy
| | - Maria Conte
- Department of Experimental, Diagnostic and Specialty Medicine (DIMES), University of Bologna, Bologna, Italy
| | - Aurelia Santoro
- Department of Experimental, Diagnostic and Specialty Medicine (DIMES), University of Bologna, Bologna, Italy.,Interdepartmental Center "L. Galvani" (CIG), University of Bologna, Bologna, Italy
| | - Andrea Grignolio
- Unit and Museum of History of Medicine, Department of Molecular Medicine, Sapienza University of Rome, Rome, Italy
| | - Daniela Monti
- Department of Experimental and Clinical Biomedical Sciences "Mario Serio", University of Florence, Florence, Italy
| | - Miriam Capri
- Department of Experimental, Diagnostic and Specialty Medicine (DIMES), University of Bologna, Bologna, Italy.,Interdepartmental Center "L. Galvani" (CIG), University of Bologna, Bologna, Italy
| | - Stefano Salvioli
- Department of Experimental, Diagnostic and Specialty Medicine (DIMES), University of Bologna, Bologna, Italy.,Interdepartmental Center "L. Galvani" (CIG), University of Bologna, Bologna, Italy
| |
Collapse
|
|
39
|
Oo WM, Naganathan V, Bo MT, Hunter DJ. Clinical utilities of quantitative ultrasound in osteoporosis associated with inflammatory rheumatic diseases. Quant Imaging Med Surg 2018; 8:100-113. [PMID: 29541626 PMCID: PMC5835660 DOI: 10.21037/qims.2018.02.02] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/13/2017] [Accepted: 01/29/2018] [Indexed: 01/27/2023]
Abstract
Secondary osteoporosis is an important co-morbidity related to inflammatory rheumatic diseases that is attributed to several factors including inflammatory cytokines, inactivity and glucocorticoid treatment. Quantitative ultrasound (QUS) has been utilized in osteoporosis research due to its detectability of bone density as well as bone quality. The current narrative review is to address the potential utilities of QUS in secondary osteoporosis of inflammatory rheumatic diseases, focusing on the clinical aspects of QUS in these diseases, based on the conformity of QUS with dual emission X-ray absorptiometry (DXA), the relationship with disease characteristics, and its capability of fracture prediction. Although limited data demonstrate that QUS had moderate to strong correlation with DXA, and might be useful as a potential imaging tool to screen for osteoporosis, further research is still required for QUS to be utilized effectively for the best outcome in these patients with rheumatic diseases.
Collapse
Affiliation(s)
- Win Min Oo
- Rheumatology Department, Royal North Shore Hospital, and Institute of Bone and Joint Research, Kolling Institute, University of Sydney, Sydney, Australia
| | - Vasikaran Naganathan
- Centre for Education and Research on Ageing and the Ageing and Alzheimers Institute, Sydney Medical School, The University of Sydney and Concord Hospital, Sydney, Australia
| | - Myat Thae Bo
- University of Medicine-Mandalay, Mandalay, Myanmar
| | - David J. Hunter
- Rheumatology Department, Royal North Shore Hospital, and Institute of Bone and Joint Research, Kolling Institute, University of Sydney, Sydney, Australia
| |
Collapse
|
|
40
|
Mori Y, Baba K, Kogure A, Izumiyama T, Matsuda M, Mori N, Ishii T, Itoi E. Assessment of the risk of low bone mineral density in premenopausal Japanese female patients with systemic lupus erythematosus. J Orthop 2018; 15:89-93. [PMID: 29657446 DOI: 10.1016/j.jor.2018.01.029] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/28/2017] [Accepted: 01/14/2018] [Indexed: 11/19/2022] Open
Abstract
Background The aim of this study was to assess the relationships between clinical parameters and bone mineral density (BMD) in Japanese female patients with systemic lupus erythematosus (SLE). Methods A total of female 136 SLE patients without menopause were retrospectively assessed to identify associations between age, disease duration, body mass index (BMI), glucocorticoid usage and disease activity and BMD based on the treatment with or without bisphosphonate. There were 71 patients treated with bisphosphonate (bisphosphonate group) and 65 patients without (non-bisphosphonate group). We evaluated the impact of age, disease duration, BMI, serologic SLE markers, glucocorticoid use on BMD of the anterior-posterior (AP) and lateral lumbar spine, total hip and femoral neck using univariate and multivariate linear regression analyses of both bisphosphonate and non-bisphosphonate groups. Results Multivariate linear regression analyses showed that in non-bisphosphonate group disease duration was negatively associated with BMD of AP spine and femoral neck, whereas in bisphosphonate group these negative associations were not present. However, multivariate linear regression analyses showed a significant relationship between BMI and BMD of the AP spine, femoral neck and total hip, regardless of bisphosphonate treatment. Conclusions Bisphosphonate treatment eliminated the negative relationships between disease duration and the BMD of the spine and hip. AP spine and hip BMD in patients with SLE depend on BMI, regardless of bisphosphonate use. SLE serologic markers and glucocorticoid use were not negatively associated with generalized bone loss. SLE patients with low BMI have a high risk of generalized bone loss, and should be assessed and treated to prevent osteoporosis even before menopause.
Collapse
Affiliation(s)
- Yu Mori
- Department of Orthopaedic Surgery, Tohoku University Graduate School of Medicine, 1-1 Seiryo machi, Aobaku, Sendai, Miyagi, 980-8574, Japan
| | - Kazuyoshi Baba
- Department of Orthopaedic Surgery, Tohoku University Graduate School of Medicine, 1-1 Seiryo machi, Aobaku, Sendai, Miyagi, 980-8574, Japan
| | - Atsushi Kogure
- Department of Orthopaedic Surgery, Tohoku University Graduate School of Medicine, 1-1 Seiryo machi, Aobaku, Sendai, Miyagi, 980-8574, Japan
| | - Takuya Izumiyama
- Department of Orthopaedic Surgery, Tohoku University Graduate School of Medicine, 1-1 Seiryo machi, Aobaku, Sendai, Miyagi, 980-8574, Japan
| | - Michiharu Matsuda
- Department of Orthopaedic Surgery, Tohoku University Graduate School of Medicine, 1-1 Seiryo machi, Aobaku, Sendai, Miyagi, 980-8574, Japan
| | - Naoko Mori
- Department of Diagnostic Radiology, Tohoku University Graduate School of Medicine, 1-1 Seiryo machi, Aobaku, Sendai, Miyagi, 980-8574, Japan
| | - Tomonori Ishii
- Department of Hematology and Rheumatology, Tohoku University Graduate School of Medicine, 1-1 Seiryo machi, Aobaku, Sendai, Miyagi, 980-8574, Japan
| | - Eiji Itoi
- Department of Orthopaedic Surgery, Tohoku University Graduate School of Medicine, 1-1 Seiryo machi, Aobaku, Sendai, Miyagi, 980-8574, Japan
| |
Collapse
|
|
41
|
Sapir-Koren R, Livshits G. Postmenopausal osteoporosis in rheumatoid arthritis: The estrogen deficiency-immune mechanisms link. Bone 2017; 103:102-115. [PMID: 28666971 DOI: 10.1016/j.bone.2017.06.020] [Citation(s) in RCA: 54] [Impact Index Per Article: 6.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/26/2017] [Revised: 06/13/2017] [Accepted: 06/26/2017] [Indexed: 12/20/2022]
Abstract
Rheumatoid arthritis (RA) is characterized, among other factors, by systemic bone loss, reaching ~50% prevalence of osteoporosis in postmenopausal women. This is roughly a doubled prevalence in comparison with age-matched non-RA women. Postmenopausal RA women are more likely to be sero-positive for the anti-citrullinated peptide antibody (ACPA). Our extensive review of recent scientific literature enabled us to propose several mechanisms as responsible for the accelerated bone loss in ACPA(+) RA postmenopausal women. Menopause-associated estrogen deficiency plays a major role in these pathological mechanisms, as follows.
Collapse
Affiliation(s)
- Rony Sapir-Koren
- Human Population Biology Research Group, Department of Anatomy and Anthropology, Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel.
| | - Gregory Livshits
- Human Population Biology Research Group, Department of Anatomy and Anthropology, Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel; Lilian and Marcel Pollak Chair of Biological Anthropology, Department of Anatomy and Anthropology, Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel.
| |
Collapse
|
|
42
|
Kaneko T, Okamura K, Yonemoto Y, Okura C, Suto T, Tachibana M, Tamura Y, Inoue M, Chikuda H. Short-term daily teriparatide in patients with rheumatoid arthritis. Mod Rheumatol 2017; 28:468-473. [PMID: 28805099 DOI: 10.1080/14397595.2017.1362093] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/19/2022]
Abstract
OBJECTIVE The aim of this study was to compare the efficacy of six-month teriparatide treatment followed by six-month bisphosphonate therapy with 12-month bisphosphonate monotherapy in Japanese rheumatoid arthritis (RA) patients who had not been previously treated for osteoporosis. METHODS A total of 34 RA patients with osteoporosis were enrolled. Thirteen patients received six-month teriparatide prior to six-month minodronate therapy (PTH group), and 21 patients received 12-month minodronate therapy (BP group). Bone mineral density (BMD), and bone turnover markers were measured prior to and 6 and 12 months after the initiation of treatment. RESULTS Bone mineral density of the spine was significantly increased after 12 months of treatment in both groups. In the PTH group, the mean percent change of BMD of the spine was significantly higher at 12 months after the initiation of treatment, as compared to the BP group (PTH group: 9.9 ± 1.5%, BP group: 5.5 ± 0.7%). Femoral neck BMD was significantly increased only in the PTH group after 12 months. CONCLUSION Therapy involving six-month teriparatide followed by six-month minodronate therapy increased spine BMD to a greater degree than 12-month minodronate monotherapy. The strategy of short-term administration of teriparatide for RA patients with osteoporosis might be useful when additional bisphosphonate therapy is considered.
Collapse
Affiliation(s)
- Tetsuya Kaneko
- a Department of Orthopedic Surgery , Japan Redcross Society Fukaya Redcross Hospital , Fukaya , Saitama , Japan.,b Department of Orthopedic Surgery , Gunma University Graduate School of Medicine , Maebashi , Gunma , Japan.,c Department of Orthopedic Surgery , Fukaya Seikeigeka Clinic , Fukaya , Saitama , Japan.,d Department of Orthopedic Surgery , Inoue Hospital , Takasaki , Gunma , Japan
| | - Koichi Okamura
- b Department of Orthopedic Surgery , Gunma University Graduate School of Medicine , Maebashi , Gunma , Japan
| | - Yukio Yonemoto
- b Department of Orthopedic Surgery , Gunma University Graduate School of Medicine , Maebashi , Gunma , Japan
| | - Chisa Okura
- b Department of Orthopedic Surgery , Gunma University Graduate School of Medicine , Maebashi , Gunma , Japan
| | - Takahito Suto
- b Department of Orthopedic Surgery , Gunma University Graduate School of Medicine , Maebashi , Gunma , Japan
| | - Masahiro Tachibana
- b Department of Orthopedic Surgery , Gunma University Graduate School of Medicine , Maebashi , Gunma , Japan
| | - Yasuyuki Tamura
- d Department of Orthopedic Surgery , Inoue Hospital , Takasaki , Gunma , Japan
| | - Makoto Inoue
- d Department of Orthopedic Surgery , Inoue Hospital , Takasaki , Gunma , Japan
| | - Hirotaka Chikuda
- b Department of Orthopedic Surgery , Gunma University Graduate School of Medicine , Maebashi , Gunma , Japan
| |
Collapse
|
|
43
|
Chen YY, Feng JY, Ting WY, Yen YF, Chuang PH, Pan SW, Su VYF, Su WJ. Increased risk of incident osteoporosis and osteoporotic fracture in tuberculosis patients: a population-based study in a tuberculosis-endemic area. Osteoporos Int 2017; 28:1711-1721. [PMID: 28331966 DOI: 10.1007/s00198-017-3939-x] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/16/2016] [Accepted: 01/23/2017] [Indexed: 12/21/2022]
Abstract
UNLABELLED The occurrence of osteoporosis in tuberculosis, a chronic infection, has rarely been evaluated. In this study, we found significantly higher incidence rates of osteoporosis (Adjusted hazard ratio (AHR) 1.82) and osteoporotic fracture (AHR 2.33) in tuberculosis patients than matched cohorts, which suggest that osteoporosis screening should be considered in tuberculosis patients' follow-up program. The aim of this study is to determine the occurrence of incident osteoporosis in patients who completed anti-tuberculosis (TB) treatment. INTRODUCTION Chronic inflammatory disorders are associated with an increased risk of osteoporosis. Although TB is an infectious disease characterized by systemic inflammatory responses, the impact of active TB on incident osteoporosis is unclear. We used the Taiwan National Health Insurance Research Database to investigate the association between history of active TB and incident osteoporosis and osteoporotic fracture. METHODS In this nationwide retrospective cohort study, active TB patients and their age- and sex-matched controls were identified from the National Health Insurance Research Database in Taiwan during 2000-2012. The occurrence of incident osteoporosis, osteoporotic fractures, and risk factors associated with osteoporosis among TB patients and matched controls were analyzed. RESULTS We observed incident osteoporosis in 2.2% (n = 86) of the TB patients and in 1.1% (n = 162) of the matched controls. The incidence rate of osteoporosis was 4.31 and 1.80 per 1000 person-years, which was significantly higher in TB patients (p < 0.001). In multivariate analysis, TB was an independent risk factor for osteoporosis. The other independent factors associated with osteoporosis were older age, female sex, chronic obstructive pulmonary disease, asthma, and lower income. Moreover, we demonstrated that the occurrence of osteoporotic fracture was significantly higher in TB patients. CONCLUSIONS Patients with a history of active TB have a higher incidence rate of osteoporosis and osteoporotic fracture.
Collapse
Affiliation(s)
- Y-Y Chen
- Department of Chest Medicine, Taipei Veterans General Hospital, No. 201, Sec. 2, Shih-Pai Rd., Taipei, 11217, Taiwan
| | - J-Y Feng
- Department of Chest Medicine, Taipei Veterans General Hospital, No. 201, Sec. 2, Shih-Pai Rd., Taipei, 11217, Taiwan
- School of Medicine, National Yang-Ming University, Taipei, Taiwan
- Institute of Clinical Medicine, School of Medicine, National Yang-Ming University, Taipei, Taiwan
| | - W-Y Ting
- Department of Chest Medicine, Taipei Veterans General Hospital, No. 201, Sec. 2, Shih-Pai Rd., Taipei, 11217, Taiwan
| | - Y-F Yen
- School of Medicine, National Yang-Ming University, Taipei, Taiwan
- Section of Infectious Diseases, Taipei City Hospital, Taipei City Government, Taipei City, Taiwan
| | - P-H Chuang
- Center for prevention and treatment of occupational injury and diseases, Taipei Veterans General Hospital, Taipei, Taiwan
- Division of Clinical Toxicology and Occupational Medicine, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan
| | - S-W Pan
- Department of Chest Medicine, Taipei Veterans General Hospital, No. 201, Sec. 2, Shih-Pai Rd., Taipei, 11217, Taiwan
- School of Medicine, National Yang-Ming University, Taipei, Taiwan
- Institute of Physiology, National Yang-Ming University, Taipei, Taiwan
| | - V Y-F Su
- Department of Chest Medicine, Taipei Veterans General Hospital, No. 201, Sec. 2, Shih-Pai Rd., Taipei, 11217, Taiwan
- School of Medicine, National Yang-Ming University, Taipei, Taiwan
| | - W-J Su
- Department of Chest Medicine, Taipei Veterans General Hospital, No. 201, Sec. 2, Shih-Pai Rd., Taipei, 11217, Taiwan.
- School of Medicine, National Yang-Ming University, Taipei, Taiwan.
- Chest Department, Taipei Veterans General Hospital, Taipei, Taiwan.
| |
Collapse
|
|
44
|
Zerbini CAF, Clark P, Mendez-Sanchez L, Pereira RMR, Messina OD, Uña CR, Adachi JD, Lems WF, Cooper C, Lane NE. Biologic therapies and bone loss in rheumatoid arthritis. Osteoporos Int 2017; 28:429-446. [PMID: 27796445 DOI: 10.1007/s00198-016-3769-2] [Citation(s) in RCA: 128] [Impact Index Per Article: 16.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/02/2016] [Accepted: 09/07/2016] [Indexed: 12/20/2022]
Abstract
INTRODUCTION Rheumatoid arthritis (RA) is a common systemic autoimmune disease of unknown cause, characterized by a chronic, symmetric, and progressive inflammatory polyarthritis. One of the most deleterious effects induced by the chronic inflammation of RA is bone loss. During the last 15 years, the better knowledge of the cytokine network involved in RA allowed the development of potent inhibitors of the inflammatory process classified as biological DMARDs. These new drugs are very effective in the inhibition of inflammation, but there are only few studies regarding their role in bone protection. The principal aim of this review was to show the evidence of the principal biologic therapies and bone loss in RA, focusing on their effects on bone mineral density, bone turnover markers, and fragility fractures. METHODS Using the PICOST methodology, two coauthors (PC, LM-S) conducted the search using the following MESH terms: rheumatoid arthritis, osteoporosis, clinical trials, TNF- antagonists, infliximab, adalimumab, etanercept, certolizumab, golimumab, IL-6 antagonists, IL-1 antagonists, abatacept, tocilizumab, rituximab, bone mineral density, bone markers, and fractures. The search was conducted electronically and manually from the following databases: Medline and Science Direct. The search period included articles from 2003 to 2015. The selection included only original adult human research written in English. Titles were retrieved and the same two authors independently selected the relevant studies for a full text. The retrieved selected studies were also reviewed completing the search for relevant articles. The first search included 904 titles from which 253 titles were selected. The agreement on the selection among researchers resulted in a Kappa statistic of 0.95 (p < 0.000). Only 248 abstracts evaluated were included in the acronym PICOST. The final selection included only 28 studies, derived from the systematic search. Additionally, a manual search in the bibliography of the selected articles was made and included into the text and into the section of "small molecules of new agents." CONCLUSION Treatment with biologic drugs is associated with the decrease in bone loss. Studies with anti-TNF blocking agents show preservation or increase in spine and hip BMD and also a better profile of bone markers. Most of these studies were performed with infliximab. Only three epidemiological studies analyzed the effect on fractures after anti-TNF blocking agent's treatment. IL-6 blocking agents also showed improvement in localized bone loss not seen with anti-TNF agents. There are a few studies with rituximab and abatacept. Although several studies reported favorable actions of biologic therapies on bone protection, there are still unmet needs for studies regarding their actions on the risk of bone fractures.
Collapse
Affiliation(s)
- C A F Zerbini
- Centro Paulista de Investigação Clínica, Rua Moreira e Costa, 342-Ipiranga, São Paulo, SP, 04266-010, Brazil.
| | - P Clark
- Hospital Infantil Federico Gómez-Faculty of Medicine UNAM, Ciudad de México D.F, Mexico
| | - L Mendez-Sanchez
- Hospital Infantil Federico Gómez-Faculty of Medicine UNAM, Ciudad de México D.F, Mexico
| | - R M R Pereira
- Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil
| | - O D Messina
- IRO Clinical Research Center Buenos Aires, Buenos Aires, Argentina
| | - C R Uña
- IRO Clinical Research Center Buenos Aires, Buenos Aires, Argentina
| | - J D Adachi
- Actavis Chair for Better Bone Health in Rheumatology, Hamilton, ON, Canada
| | - W F Lems
- Amsterdam Rheumatology and Immunology Centre, VU University Medical Centre, Amsterdam, The Netherlands
| | - C Cooper
- MRC Lifecourse Epidemiology Unit, Southampton, UK
- Faculty of Medicine, University of Southampton, Southampton, UK
- University of Oxford, Oxford, UK
| | - N E Lane
- Center for Musculoskeletal Health, Sacramento, CA, USA
- UC Davis Health System, University of California, Sacramento, CA, USA
| | | |
Collapse
|
|
45
|
Bellan M, Sainaghi PP, Pirisi M. Role of Vitamin D in Rheumatoid Arthritis. ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY 2017; 996:155-168. [PMID: 29124698 DOI: 10.1007/978-3-319-56017-5_13] [Citation(s) in RCA: 22] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/31/2022]
Abstract
Vitamin D is a fat soluble hormone, with a well described role in bone health and calcium/phosphate metabolism. Recent evidences have related vitamin D to other physiological functions and pathological conditions. Specifically, vitamin D has widely proven activities on immune system and evidences suggest that it may be implicated in the pathogenesis of rheumatoid arthritis (RA). The relationship between vitamin D and RA is complex, also because a deficitary vitamin D status, which is very common in RA patients, can contribute to the increased risk of osteoporosis typical of RA. In this chapter, will be described and discussed the main aspects of the relationship between RA and vitamin D.
Collapse
Affiliation(s)
- Mattia Bellan
- Department of Translational Medicine, Università del Piemonte Orientale UPO, via Solaroli 17, 28100, Novara, Italy. .,Immunorheumatology Unit, Internal Medicine Division, AOU Maggiore della Carità, Novara, Italy.
| | - Pier Paolo Sainaghi
- Immunorheumatology Unit, Internal Medicine Division, AOU Maggiore della Carità, Novara, Italy
| | - Mario Pirisi
- Department of Translational Medicine, Università del Piemonte Orientale UPO, via Solaroli 17, 28100, Novara, Italy.,Immunorheumatology Unit, Internal Medicine Division, AOU Maggiore della Carità, Novara, Italy
| |
Collapse
|
|
46
|
Wu CH, Chai CY, Tung YC, Lu YY, Su YF, Tsai TH, Tzou RD, Lin CL. Herpes zoster as a risk factor for osteoporosis: A 15-year nationwide population-based study. Medicine (Baltimore) 2016; 95:e3943. [PMID: 27336887 PMCID: PMC4998325 DOI: 10.1097/md.0000000000003943] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/25/2023] Open
Abstract
The objective of this study was to investigate the risk of osteoporosis in patients with herpes zoster (HZ) infection using a nationwide population-based dataset. The Taiwan National Health Insurance Research Database was used to compare data between 11,088 patients aged 20 to 49 years diagnosed with HZ during 1996 to 2010 and a control group of 11,088 patients without HZ. Both cohorts were followed up until the end of 2010 to measure the incidence of osteoporosis. Cox proportional-hazards regression and Kaplan-Meier analyses were used to calculate hazard ratio and cumulative incidences of osteoporosis, respectively. The overall risk of osteoporosis was 4.55 times greater in the HZ group than in the control group (2.48 vs. 0.30 per 1000 person-years, respectively) after adjusting for age, gender, Charlson Comorbidity Index, and related comorbidities. Compared with controls, patients with HZ and subsequent postherpetic neuralgia had a 4.76-fold higher likelihood of developing osteoporosis (95% confidence interval: 2.44-9.29), which was a statistically significant difference (P <0.001). Osteoporosis risk factors included female gender, age, advanced Charlson Comorbidity Index, depression, and postherpetic neuralgia. This study identified HZ is associated with an increased osteoporosis risk. Further evaluation of the value of bone mineral density test in detecting osteoporosis after HZ may be suggested. HZ vaccination could also be evaluated to lower the incidence of HZ and possibly subsequent osteoporosis. Physicians should be alerted to this association to improve early identification of osteoporosis in patients with HZ.
Collapse
Affiliation(s)
- Chieh-Hsin Wu
- Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University
- Department of Neurosurgery, Kaohsiung Medical University Hospital, Kaohsiung Medical University
| | - Chee-Yin Chai
- Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University
- Department of Pathology, Kaohsiung Medical University Hospital, Kaohsiung Medical University
- Department of Pathology, Faculty of Medicine, College of Medicine, Kaohsiung Medical University
- Institute of Biomedical Sciences, National Sun Yat-Sen University
| | - Yi-Ching Tung
- Department of Public Health and Environmental Medicine, College of Medicine, Kaohsiung Medical University
| | - Ying-Yi Lu
- Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University
- Department of Dermatology, Kaohsiung Veterans General Hospital
- Cosmetic Applications and Management Department, Yuh-Ing Junior College of Health Care and Management
| | - Yu-Feng Su
- Department of Neurosurgery, Kaohsiung Medical University Hospital, Kaohsiung Medical University
| | - Tai-Hsin Tsai
- Department of Neurosurgery, Kaohsiung Medical University Hospital, Kaohsiung Medical University
| | - Rong-Dar Tzou
- Department of Neurosurgery, Kaohsiung Medical University Hospital, Kaohsiung Medical University
| | - Chih-Lung Lin
- Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University
- Department of Neurosurgery, Kaohsiung Medical University Hospital, Kaohsiung Medical University
- Department of Neurosurgery, Faculty of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
| |
Collapse
|
|
47
|
Carroll MB, Fields JH, Clerc PG. Rheumatoid arthritis in patients with HIV: management challenges. Open Access Rheumatol 2016; 8:51-59. [PMID: 27843370 PMCID: PMC5098761 DOI: 10.2147/oarrr.s87312] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/29/2022] Open
Abstract
Over the past few decades, HIV has been transformed from a once-uniformly fatal disease to now a manageable but complex multisystem illness. Before highly active antiretroviral therapy (HAART), reports suggested that HIV-infected patients with rheumatoid arthritis (RA) would experience remission of their disease. It has now become clear that RA can develop in HIV-infected patients at any time, independent of HAART. Choosing the right medication to treat symptoms related to RA while avoiding excess weakening of the immune system remains a clinical challenge. Agents such as hydroxychloroquine and sulfasalazine might best balance safety with efficacy, making them reasonable first choices for therapy in HIV-infected patients with RA. More immune suppressing agents such as methotrexate may balance safety with efficacy, but data are limited. Corticosteroids such as prednisone may also be reasonable but could increase the risk of osteonecrosis. Among biologic response modifiers, tumor necrosis factor α inhibitors may balance safety with efficacy, but perhaps when HIV replication is controlled with HAART. Monitoring RA disease activity remains challenging as only one retrospective study has been published in this area. Those with HIV infection and RA can experience comorbidities such as accelerated heart disease and osteoporosis, a consequence of the chronic inflammatory state that each illness generates. Although HIV-infected patients are at risk for developing the immune reconstitution inflammatory syndrome when starting HAART, it appears that immune reconstitution inflammatory syndrome has a minimal effect on triggering the onset or the worsening of RA.
Collapse
Affiliation(s)
- Matthew B Carroll
- Department of Rheumatology, Keesler Medical Center, Keesler Air Force Base, Biloxi, MS, USA
| | - Joshua H Fields
- Department of Rheumatology, Keesler Medical Center, Keesler Air Force Base, Biloxi, MS, USA
| | - Philip G Clerc
- Department of Rheumatology, Keesler Medical Center, Keesler Air Force Base, Biloxi, MS, USA
| |
Collapse
|
|
48
|
Abstract
PURPOSE OF REVIEW This manuscript will provide a review of recent publications, examining the correlation of systemic lupus erythematosus (SLE) with changes in bone health and associated osteoporosis, highlighting prevalence, etiology, diagnosis, and treatment. RECENT FINDINGS Studies suggest that bone loss and fractures are associated with SLE, related not only to the disease itself, but also with low vitamin D and treatment side-effects. Understanding the mechanisms of glucocorticoids on bone and the immunologic relationship of vitamin D, as well as recognizing the role of chronic inflammation on bone, allows for better understanding of skeletal side-effects. Further awareness of the association of poor bone health has led to an increased need for prevention and treatment. New imaging and treatment are emerging, although not recommended currently. SUMMARY Loss of bone density culminating in osteoporosis and fracture is a frequent comorbidity in SLE patients at any age and is multifactorial in etiology. Awareness and diagnosis is crucial because of its prevalence and morbidity. Prevention is safe and effective in this high-risk population where diagnostic measures and interventions are underutilized and guidelines are lacking.
Collapse
Affiliation(s)
- Cuoghi Edens
- aDepartment of Pediatrics, Division of Pediatric Infectious Diseases and Rheumatology, Rainbow Babies and Children's Hospital bDepartment of Internal Medicine, Division of Rheumatology, University Hospitals Case Medical Center, Cleveland, Ohio, USA
| | | |
Collapse
|
|
49
|
Bellan M, Pirisi M, Sainaghi PP. Osteoporose na artrite reumatoide: papel do sistema vitamina D/hormônio paratireóideo. REVISTA BRASILEIRA DE REUMATOLOGIA 2015; 55:256-63. [DOI: 10.1016/j.rbr.2014.10.007] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/25/2014] [Revised: 06/10/2014] [Accepted: 10/06/2014] [Indexed: 01/30/2023] Open
|
|
50
|
Straub RH, Cutolo M, Pacifici R. Evolutionary medicine and bone loss in chronic inflammatory diseases--A theory of inflammation-related osteopenia. Semin Arthritis Rheum 2015; 45:220-8. [PMID: 26044543 DOI: 10.1016/j.semarthrit.2015.04.014] [Citation(s) in RCA: 66] [Impact Index Per Article: 6.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/20/2014] [Revised: 03/02/2015] [Accepted: 04/24/2015] [Indexed: 12/22/2022]
Abstract
OBJECTIVE Bone loss is typical in chronic inflammatory diseases such as rheumatoid arthritis, psoriasis, ankylosing spondylitis, systemic lupus erythematosus, multiple sclerosis, inflammatory bowel diseases, pemphigus vulgaris, and others. It is also typical in transplantation-related inflammation and during the process of aging. While we recognized that bone loss is tightly linked to immune system activation or inflamm-aging in the form of acute, chronic active, or chronic smoldering inflammation, bone loss is typically discussed to be an "accident of inflammation." METHODS Extensive literature search in PubMed central. RESULTS Using elements of evolutionary medicine, energy regulation, and neuroendocrine regulation of homeostasis and immune function, we work out that bone waste is an adaptive, evolutionarily positively selected program that is absolutely necessary during acute inflammation. However, when acute inflammation enters a chronic state due to the inability to terminate inflammation (e.g., in autoimmunity or in continuous immunity against microbes), the acute program of bone loss is a misguided adaptive program. CONCLUSIONS The article highlights the complexity of interwoven pathways of osteopenia.
Collapse
Affiliation(s)
- Rainer H Straub
- Laboratory of Experimental Rheumatology and Neuroendocrine Immunology, Department of Internal Medicine I, University Hospital Regensburg, 93042 Regensburg, Germany.
| | - Maurizio Cutolo
- Department of Internal Medicine and Medical Specialties, University of Genova, Genova, Italy
| | - Roberto Pacifici
- Division of Endocrinology, Metabolism and Lipids, Department of Medicine, Emory University, Atlanta, GA
| |
Collapse
|