Osteoporosis in a murine model of postmenopausal lupus

Lupus ◽  
2019 ◽  
Vol 29 (1) ◽  
pp. 58-66
Author(s):  
J Nordqvist ◽  
M K Lagerquist ◽  
L Grahnemo ◽  
A Koskela ◽  
U Islander ◽  
...  
Keyword(s):  
Risk Factors ◽  
Computed Tomography ◽  
Systemic Lupus Erythematosus ◽  
Experimental Model ◽  
Lupus Erythematosus ◽  
Mineral Density ◽  
Systemic Lupus ◽  
New Therapies ◽  
Increased Risk ◽  
Bone Remodeling Markers

Background/objective Postmenopausal women with systemic lupus erythematosus have an increased risk of osteoporosis and associated fractures. Their increased osteoporosis risk is probably caused by a high level of inflammation, use of glucocorticoids, impaired kidney function, and early menopause as these are known risk factors for osteoporosis. Due to these risk factors and the lack of safe and effective treatments, new therapies for the treatment of osteoporosis in this group of patients are needed. Ovariectomized MRL/ lpr mice constitute a well-established model for studies of postmenopausal systemic lupus erythematosus; however, it is not clear to what extent this experimental model is associated with the development of osteoporosis. Thus, the aim of this study was to characterize the skeleton of ovariectomized MRL/ lpr mice to determine the suitability of this model in studies of prospective new therapies for osteoporosis in postmenopausal systemic lupus erythematosus patients. Methods Skeletal parameters were measured in MRL/ lpr mice and MRL/++ control mice, using peripheral quantitative computed tomography, high-resolution micro-computed tomography and biomechanical analyses. mRNA expression of bone-remodeling markers was measured by quantitative polymerase chain reaction and serological markers of lupus disease were evaluated using ELISA. Results Total bone mineral density was reduced in MRL/ lpr mice compared with MRL/++ mice and MRL/ lpr mice had reduced cortical and trabecular bone thickness compared with MRL/++ mice. In line with the low bone mass of MRL/ lpr mice, gene expression analysis of cortical bone from these mice indicated an increased osteoclast activity as well as a decreased osteoblastogenesis and osteoblast activity, compared with MRL/++ mice. Conclusion Ovariectomized MRL/ lpr mice constitute a valuable experimental model for studies of osteoporosis development in postmenopausal systemic lupus erythematosus and this model is thus suitable for future studies of osteoporosis treatment in systemic lupus erythematosus.

Cardiovascular Disease in Systemic Lupus Erythematosus: Recent Data on Epidemiology, Risk Factors and Prevention

2020 ◽  
Vol 18 (6) ◽  
pp. 549-565 ◽  
Author(s):  
Myrto Kostopoulou ◽  
Dionysis Nikolopoulos ◽  
Ioannis Parodis ◽  
George Bertsias
Keyword(s):  
Risk Factors ◽  
Systemic Lupus Erythematosus ◽  
Lupus Erythematosus ◽  
Statin Treatment ◽  
Type I Interferons ◽  
Type I ◽  
Lifestyle Modifications ◽  
Systemic Lupus ◽  
Increased Risk ◽  
Atherogenic Dyslipidaemia

Systemic Lupus Erythematosus (SLE) is associated with increased risk for accelerated atherosclerosis and cardiovascular (CV) events including coronary heart disease, cerebrovascular and peripheral artery disease. CV events occur both early and late during the disease course, with younger patients being at much higher risk than age-matched counterparts. The risk cannot be fully accounted for by the increased prevalence of traditional atherosclerotic factors and may be due to pathophysiologic intermediates such as type I interferons and other inflammatory cytokines, oxidative stress, activated granulocytes and production of extracellular chromatin traps, antiphospholipid and other autoantibodies causing dysfunction of lipoproteins, altogether resulting in endothelial injury and pro-atherogenic dyslipidaemia. These mechanisms may be further aggravated by chronic intake of prednisone (even at doses <7.5 mg/day), whereas immunomodulatory drugs, especially hydroxychloroquine, may exert antiatherogenic properties. To date, there is a paucity of randomized studies regarding the effectiveness of preventative strategies and pharmacological interventions specifically in patients with SLE. Nevertheless, both the European League Against Rheumatism recommendations and extrapolated evidence from the general population emphasize that SLE patients should undergo regular monitoring for atherosclerotic risk factors and calculation of the 10-year CV risk. Risk stratification should include diseaserelated factors and accordingly, general (lifestyle modifications/smoking cessation, antihypertensive and statin treatment, low-dose aspirin in selected cases) and SLE-specific (control of disease activity, minimization of glucocorticoids, use of hydroxychloroquine) preventive measures be applied as appropriate. Further studies will be required regarding the use of non-invasive tools and biomarkers for CV assessment and of risk-lowering strategies tailored to SLE.

scholarly journals Prevalence and Possible Risk Factors of Low Bone Mineral Density in Untreated Female Patients with Systemic Lupus Erythematosus

2015 ◽  
Vol 2015 ◽  
pp. 1-7 ◽  
Author(s):  
Yi-Ning Sun ◽  
Xiu-Yuan Feng ◽  
Lan He ◽  
Ling-Xia Zeng ◽  
Zhi-Ming Hao ◽  
...  
Keyword(s):  
Risk Factors ◽  
Bone Mineral Density ◽  
Systemic Lupus Erythematosus ◽  
Lumbar Spine ◽  
Lupus Erythematosus ◽  
Mineral Density ◽  
Systemic Lupus ◽  
Total Hip ◽  
Female Patients ◽  
Untreated Female

Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by chronic inflammation. Different studies have shown decreased bone mineral density (BMD) in patients with SLE. The objective of this study was to investigate the prevalence and possible risk factors of low BMD in untreated female patients with SLE in Chinese population. A total of 119 untreated female patients with SLE were included. BMD was measured at lumbar spine and at total hip by dual-energy X-ray absorptiometry. The associations between decreased BMD and demographic variables, clinical variables, and bone metabolism variables were analyzed. These SLE patients had the following characteristics: mean age was32.6±11.9years, mean disease duration was22.1±34.5months, and mean SLEDAI was11.4±5.4. Osteopenia was present in 31.1% of the patients and osteoporosis in 8.5%. A significant negative association between low density lipoprotein cholesterol (LDL-c) and BMD at the lumbar spine (correlation coefficient= −0.242;P=0.023) and total hip (correlation coefficient= −0.259;P=0.019) was shown. These results seem to indicate that increased LDL-c may be an important risk factor for low BMD at lumbar spine and total hip in untreated female SLE patients.

scholarly journals Imaging Assessment of Cardiovascular Disease in Systemic Lupus Erythematosus

2012 ◽  
Vol 2012 ◽  
pp. 1-7 ◽  
Author(s):  
Sara C. Croca ◽  
Anisur Rahman
Keyword(s):  
Risk Factors ◽  
Systemic Lupus Erythematosus ◽  
Cardiovascular Disease ◽  
Cardiovascular Risk ◽  
Lupus Erythematosus ◽  
Current Status ◽  
Systemic Lupus ◽  
Cardiovascular Morbidity And Mortality ◽  
Increased Risk ◽  
Cardiovascular Assessment

Systemic lupus erythematosus is a multisystem, autoimmune disease known to be one of the strongest risk factors for atherosclerosis. Patients with SLE have an excess cardiovascular risk compared with the general population, leading to increased cardiovascular morbidity and mortality. Although the precise explanation for this is yet to be established, it seems to be associated with the presence of an accelerated atherosclerotic process, arising from the combination of traditional and lupus-specific risk factors. Moreover, cardiovascular-disease associated mortality in patients with SLE has not improved over time. One of the main reasons for this is the poor performance of standard risk stratification tools on assessing the cardiovascular risk of patients with SLE. Therefore, establishing alternative ways to identify patients at increased risk efficiently is essential. With recent developments in several imaging techniques, the ultimate goal of cardiovascular assessment will shift from assessing symptomatic patients to diagnosing early cardiovascular disease in asymptomatic patients which will hopefully help us to prevent its progression. This review will focus on the current status of the imaging tools available to assess cardiac and vascular function in patients with SLE.

Cardiovascular disease in systemic lupus erythematosus

2021 ◽  
Vol 2 (3) ◽  
pp. 157-172
Author(s):  
Maureen McMahon ◽  
Richard Seto ◽  
Brian J. Skaggs
Keyword(s):  
Risk Factors ◽  
Systemic Lupus Erythematosus ◽  
Cardiovascular Disease ◽  
Lupus Erythematosus ◽  
Cardiovascular Events ◽  
Subclinical Atherosclerosis ◽  
Cardiac Risk ◽  
Systemic Lupus ◽  
Cardiac Risk Factors ◽  
Increased Risk

Abstract There is a well-known increased risk for cardiovascular disease that contributes to morbidity and mortality in systemic lupus erythematosus (SLE). Major adverse cardiovascular events and subclinical atherosclerosis are both increased in this patient population. While traditional cardiac risk factors do contribute to the increased risk that is seen, lupus disease-related factors, medications, and genetic factors also impact the overall risk. SLE-specific inflammation, including oxidized lipids, cytokines, and altered immune cell subtypes all are likely to play a role in the pathogenesis of atherosclerotic plaques. Research is ongoing to identify biomarkers that can help clinicians to predict which SLE patients are at the greatest risk for cardiovascular disease (CVD). While SLE-specific treatment regimens for the prevention of cardiovascular events have not been identified, current strategies include minimization of traditional cardiac risk factors and lowering of overall lupus disease activity.

scholarly journals Prevalence of and risk factors for low bone mineral density and vertebral fractures in patients with systemic lupus erythematosus

2005 ◽  
Vol 52 (7) ◽  
pp. 2044-2050 ◽  
Author(s):  
Irene E. M. Bultink ◽  
Willem F. Lems ◽  
Piet J. Kostense ◽  
Ben A. C. Dijkmans ◽  
Alexandre E. Voskuyl
Keyword(s):  
Risk Factors ◽  
Bone Mineral Density ◽  
Systemic Lupus Erythematosus ◽  
Bone Mineral ◽  
Vertebral Fractures ◽  
Lupus Erythematosus ◽  
Mineral Density ◽  
Systemic Lupus ◽  
Low Bone Mineral Density

Synergistic effect of cumulative corticosteroid dose and immunosuppressants on avascular necrosis in patients with systemic lupus erythematosus

Lupus ◽  
2018 ◽  
Vol 27 (10) ◽  
pp. 1644-1651 ◽  
Author(s):  
H H Kwon ◽  
S Y Bang ◽  
S Won ◽  
Y Park ◽  
J H Yi ◽  
...  
Keyword(s):  
Risk Factors ◽  
Systemic Lupus Erythematosus ◽  
Avascular Necrosis ◽  
Lupus Erythematosus ◽  
Clinical Manifestations ◽  
Individual Risk ◽  
High Dose ◽  
Systemic Lupus ◽  
Corticosteroid Dose ◽  
Increased Risk

Objectives Avascular necrosis (AVN) is one of the most common causes of organ damage in patients with systemic lupus erythematosus (SLE) and often causes serious physical disability. The aims of this study were to investigate clinical risk factors associated with symptomatic AVN and to analyze their synergistic effects in a large SLE cohort in Korea. Methods Patients with SLE were enrolled and followed from 1998 to 2014 in the Hanyang BAE Lupus cohort, and damage was measured annually according to the Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index (SDI). AVN was confirmed by imaging study if patients had symptoms. To determine risk factors for AVN, clinical, laboratory and therapeutic variables were analyzed by logistic regression. Relative excess risk due to interaction (RERI), attributable proportion (AP), and synergy index (S) were calculated to measure interactions between significant variables. Results Among 1219 SLE patients, symptomatic AVN was the most common type of musculoskeletal damage (10.8%, n = 132). SLE patients with AVN showed an earlier onset age, demonstrated AVN more commonly in conjunction with certain other clinical manifestations such as renal and neuropsychiatric disorders, and received significantly higher total cumulative corticosteroid dose and immunosuppressive agents than did patients without AVN. However, in multivariable analysis, only two variables including use of a cumulative corticosteroid dose greater than 20 g (odds ratio (OR) 3.62, p = 0.015) and use of immunosuppressants including cyclophosphamide or mycophenolate mofetil (OR 4.51, p < 0.001) remained as significant risk factors for AVN. Patients with cumulative corticosteroid dose > 20 g and immunosuppressant use had a 15.44-fold increased risk for AVN, compared with patients without these risk factors ( p < 0.001). RERI, AP and S, which define the strength of interactions between two risk factors, were 9.01 (95% confidence interval (CI) 1.30–16.73), 0.58 (95% CI 0.36–0.81) and 2.66 (95% CI 1.42–4.99), respectively, supporting the presence of synergistic interactions in the development of symptomatic AVN in our Korean lupus cohort. Conclusions An individual risk assessment for AVN development should be made prior to and during treatment for SLE, especially in patients with high-dose corticosteroid and immunosuppressant use regardless of clinical manifestations and disease activity.

scholarly journals Incidence and risk factors of osteomyelitis in adult and pediatric systemic lupus erythematosus: a nationwide, population-based cohort study

Lupus ◽  
2018 ◽  
Vol 28 (1) ◽  
pp. 19-26
Author(s):  
Y.F. Huang ◽  
Y.S. Chang ◽  
W.S. Chen ◽  
Y.P. Tsao ◽  
W.H. Wang ◽  
...  
Keyword(s):  
Risk Factors ◽  
Systemic Lupus Erythematosus ◽  
Cohort Study ◽  
Incidence Rate ◽  
Bone Fracture ◽  
Lupus Erythematosus ◽  
Cox Proportional Hazards ◽  
Control Group ◽  
Systemic Lupus ◽  
Increased Risk

Objective The objective of this paper is to investigate the incidence rate, risk factors and outcome of osteomyelitis among patients with systemic lupus erythematosus (SLE). Materials and methods We conducted a cohort study using data for patients enrolled in the Taiwan National Health Insurance Database from 2000 to 2012. Patients with SLE and age- and sex-matched controls without SLE were enrolled. Primary endpoint was the first occurrence of osteomyelitis. Risks of osteomyelitis in SLE patients were analyzed with Cox proportional hazards regression models, including age, sex, comorbidities and medications. Results Among 24,705 SLE patients (88.4% women, mean age 35.8 years) with a median follow-up of 9.1 years, 386 patients had osteomyelitis. The incidence rate ratio (IRR) of osteomyelitis in the SLE group vs the control group was 8.52 (95% confidence interval (CI) 7.24–10.05). The SLE group had higher incidence rates of osteomyelitis than the control group, especially in pediatric subgroups (IRR 41.1 95% CI 18.57–107.35). Compared to controls, SLE patients experienced osteomyelitis at a younger age (42.3 vs 58.1 years) but did not have an increased risk of mortality (hazard ratio 0.7; 95% CI 0.21–2.38). Age >60 years, male gender, malignancy within five years, prior bone fracture and higher daily prednisolone dose (>7.5 mg) cumulatively for >180 days increased risk for osteomyelitis. Conclusions SLE patients have a higher IRR of osteomyelitis than controls. Pediatric and elder SLE patients, patients with a history of bone fracture, malignancy within five years and higher-dose glucocorticoid use have a higher risk of osteomyelitis and should be carefully monitored.

scholarly journals Asymptomatic Coronary Artery Calcifications in Men with Systemic Lupus Erythematosus

2018 ◽  
Vol 45 (5) ◽  
pp. 663-670 ◽  
Author(s):  
Juanita Romero-Díaz ◽  
Roberto Iván Acosta-Hernández ◽  
Sergio Criales-Vera ◽  
Erick Kimura-Hayama ◽  
Maricruz Domínguez-Quintana ◽  
...  
Keyword(s):  
Risk Factors ◽  
Systemic Lupus Erythematosus ◽  
Coronary Artery ◽  
Cumulative Dose ◽  
Lupus Erythematosus ◽  
Coronary Artery Calcification ◽  
Systemic Lupus ◽  
Increased Risk ◽  
Coronary Artery Atherosclerosis ◽  
Age And Sex

Objective.To determine whether the prevalence and extent of asymptomatic coronary artery atherosclerosis are increased in men with systemic lupus erythematosus (SLE) compared with age- and sex-matched controls, and to define the associated risk factors.Methods.Ninety-five patients with SLE (mean ± SD age, 34.7 ± 10.1 yrs) and 100 control subjects (age 34.8 ± 9.7 yrs) with no history of coronary artery disease were screened for coronary artery calcification using multidetector computed tomography. The extent of calcification was measured using the Agatston score. The frequency of risk factors for calcification was compared between patients and controls, and the relationship between clinical and immunological characteristics and the presence of coronary artery calcification was investigated.Results.Coronary artery calcification was more frequent in patients than controls [18% vs 7%, respectively (OR 2.89, 95% CI 1.07–8.65)]. These factors were independently associated with the presence of calcifications: age (OR 1.12, 95% CI 1.04–1.20), SLE diagnosis (OR 3.38, 95% CI 1.07–10.64), diabetes mellitus (OR 6.88, 95% CI 1.50–31.62), Framingham risk score (OR 1.12, 95% CI 1.00–1.23), and glomerular filtration rate (OR 0.98, 95% CI 0.96–1.00). Among patients with SLE, coronary artery calcifications were observed starting at age 32 years, within 2.3 years of diagnosis. Increasing age (OR 1.18, 95% CI 1.06–1.31), Systemic Lupus International Collaborating Clinics score (OR 2.85, 95% CI 1.21–6.73), and cumulative dose of prednisone (OR 1.04, 95% CI 1.01–1.08) were independent risk factors.Conclusion.Men with SLE are at an increased risk of coronary artery calcifications than age- and sex-matched controls. Among patients with SLE, the increased risk is associated to older age, increasing chronic damage, and cumulative dose of corticosteroids.

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