Osteoporosis In Systemic Lupus Erythematosus Research Articles

Estimation of fracture risk by the FRAX tool in patients with systemic lupus erythematosus: a 10-year longitudinal validation study.

Background:The fracture risk assessment tool has been widely used to stratify the 10-year fracture risk to guide therapy. Using the actual fracture data of a 10-year longitudinal cohort of older patients with systemic lupus erythematosus, we reported an underestimation of the tool in predicting major symptomatic osteoporotic fractures. Treatment of osteoporosis in systemic lupus erythematosus should not be based on fracture risk estimation alone. Relevant time-dependent risk factors should be taken into account for an individualized decision.Objective:To compare the observed fracture incidence in a 10-year longitudinal cohort of patients with systemic lupus erythematosus (SLE) with the fracture risk prediction from the fracture risk assessment (FRAX) tool.Methods:Adult patients (⩾40 years) with SLE who had a first DEXA scan performed in 2005–2009 were studied. The 10-year rates of major osteoporotic and hip fractures were estimated by FRAX using clinical data at DEXA with adjustment for prednisolone dosage. The actual incidence of clinical fractures at 10 years was compared with the estimated rates. Factors associated with new fractures were studied by logistic regression.Results:A total of 229 SLE patients were studied (age: 50.2 ± 6.6 years, 93% women). Glucocorticoid was used in 148 (65%) patients at baseline (mean dose: 7.3 ± 6.9 mg/day; 34% ⩾ 7.5 mg/day). Osteoporosis (bone mineral density T score ⩽ –2.5) at the hip, femoral neck, or spine was present in 61 (27%) patients. The estimated 10-year risk of major osteoporotic and hip fractures by FRAX was 3.4 ± 4.5% and 0.95 ± 2.3%, respectively. After 10 years, three patients developed hip fracture, 6 patients had limb fractures and 20 patients had symptomatic vertebral fractures (major osteoporotic fracture 12.7%, hip fracture 1.3%). The actual major osteoporotic fracture rate was significantly higher than the FRAX estimation (12.7% vs 3.4%; p < 0.001). Logistic regression revealed that osteoporosis (odds ratio (OR): 4.07 [1.51–10.9]), previous fragility fracture (OR: 3.18 [1.02–9.90]), and a parental history of fracture (OR: 4.44 [1.16–17.0]) were independently associated with new clinical fractures at 10 years.Conclusion:The FRAX tool underestimates the major clinical fracture risk at 10 years in patients with SLE.

Predictors of decreased bone mineral density in childhood systemic lupus erythematosus: possible role of osteoprotegerin gene polymorphisms.

This study aims to explore effects of osteoprotegerin (OPG) gene polymorphisms and other possible factors on bone mineral density (BMD) in children with systemic lupus erythematosus (SLE). Osteoprotegerin gene rs2073617 and rs3134069 were evaluated in 74 SLE patients and 100 controls then genotypes, alleles and haplotypes' frequencies were compared between cases and controls and between patients with BMD z-scores above and below -2 evaluated by dual energy X-ray absorptiometry (DEXA). Disease activity was evaluated by SLE disease activity index (SLEDAI). The patients aged 14.01±2.6 years and included 57 (77%) females and 27 (36%) patients with BMD z-score below -2. Genotypes, alleles, and haplotypes frequencies did not differ between patients and controls (p>0.05 for all). Rs3134069 GG genotype and G allele (p=0.001, 0.002) and rs2073617 TT genotype and T allele (p=0.01, 0.006) were significantly higher in patients with BMD below -2. Cumulative glucocorticoids dose, disease duration, and SLEDAI scores were higher in patients with BMD below -2 (p=0.01, 0.01, <0.001, respectively). Regression analysis showed T allele of rs2073617, duration of illness (above 36 months), and cumulative SLEDAI (above 10) as independent predictors of decreased BMD (p 0.02, 0.003, and 0.002, respectively). This is the first study to demonstrate OPG gene influence on BMD in children with SLE. The studied SNPs are not risk for developing SLE but, rs2073617T allele is a possible predictor for reduced BMD in SLE. Other predictors include long disease duration and high activity supporting that osteoporosis in SLE is multifactorial.

A meta-analysis of secondary osteoporosis in systemic lupus erythematosus: prevalence and risk factors.

This study aimed to evaluate the prevalence and risk factors of secondary osteoporosis (OP) in patients with systemic lupus erythematosus (SLE) and provide a theoretical basis for clinical prevention and treatment of SLE. Take systematic review and meta-analysis of relevant studies. Data sources are CINAHL databases, PubMed, Embase, Wan Fang, Weipu, and CNKI databases. Eligibility criteria are cross-sectional or case-control studies which analyzed the prevalence and risk factors of OP in SLE. Two authors independently screened all studies; a third author verified and identify controversial studies. The quality of the included articles was evaluated. Stata 11 and Rev-Man 5.2 software were used for data processing. Thirty-one articles were included, with a total sample size of 3089 SLE, including 529 OP cases and 2560 non-OP cases. Meta-analysis showed that the prevalence of OP among SLE was 16% (95% CI (0.12, 0.19)). The risk of OP in SLE cases compared with controls was significantly greater with OR of 2.03 (95% CI 1.33-3.10, P = 0.001). Age, disease duration, cumulative glucocorticoid dose, duration of glucocorticoid therapy, SLICC, and menopause had significant differences between two groups. No statistical differences of daily glucocorticoid dose, SLEDAI, and BMI were found between OP and non-OP cases. Our study found a statistically significant increased risk of OP in SLE patients compared with controls. SLE patients should be actively screened for OP and its consequences. Larger longitudinal studies are needed to confirm this possible association. The prevalence of OP in SLE was 16%. Compared with controls, the risk of OP in SLE was 2.03. There were significant differences of age, disease duration, cumulative glucocorticoid dose, time of glucocorticoid, SLICC, and menopause, while daily glucocorticoid dose, SLEDAI, and BMI had no statistical differences between OP and non-OP cases.

Serum RANKL, osteoprotegerin (OPG) and RANKL/OPG ratio in children with systemic lupus erythematosus.

Systemic lupus erythematosus (SLE) patients have lower bone mineral density (BMD) compared with healthy individuals because of general, genetic, disease and medication-related factors. The disturbance of the receptor activator of nuclear factor-κB ligand (RANKL)/osteoprotegerin (OPG) ratio has been reported to be associated with low BMD in many disorders in adults and children alike. The objectives of this study were (i) to assess serum OPG, RANKL and RANKL/OPG ratio levels in SLE children and controls, (ii) to determine whether the cumulative glucocorticoid (CGCS) dose had any effect on the concentration of serum RANKL, OPG and RANKL/OPG ratio, and (iii) to determine the relation of these parameters to BMD. We evaluated 50 SLE children and 50 age- and sex-matched healthy controls. RANKL and OPG were assessed in serum and compared between patients and controls. For SLE patients, a univariate followed by multivariable analysis were carried out to detect the possible predictors of the changes in RANKL, OPG and RANKL/OPG ratio levels. Lumbar BMD for all patients was assessed by dual-energy X-ray absorptiometry (DXA) scan and then correlated to different probable correlated factors. RANKL, OPG and RANKL/OPG ratio were significantly higher in SLE patients (p ≤ 0.001). Univariate analysis showed significant correlations of RANKL with CGCS (p ≤ 0.001) and with DXA scan z-score (p = 0.007): OPG was significantly correlated to Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) score (p = 0.001) and anti-double-stranded DNA (p = 0.001), whereas RANKL/OPG was significantly correlated to duration of illness and DXA z-score (p = 0.002). The multivariable analysis showed that DXA z-score was an independent predictor of RANKL and RANKL/OPG ratio (p = 0.019 and 0.008, respectively), whereas SLEDAI score was an independent predictor of OPG levels. BMD was negatively correlated to disease duration (p = 0.008) and CGCS dose (p = 0.015), but no significant correlation has been found between BMD and cumulative SLEDAI score (p = 0.29). Serum RANKL/OPG ratio is elevated in Egyptian children with SLE and is considered a risk factor for reduced bone mass in these children. Other risk factors for low BMD include high CGCS dose and disease duration, supporting that osteoporosis in SLE is multifactorial.

Glucocorticoid-induced osteoporosis in systemic lupus erythematosus

Improvement in survival of systemic lupus erythematosus has been brought about with new advancement in treatment. However, glucocorticoids remain the sole cornerstone and as patients live longer, there is a need to address long-term complications brought by long-term glucocorticoid use such as osteoporosis. In this review, glucocorticoid-induced osteoporosis in systemic lupus erythematosus will be extensively discussed. This would include prevalence of osteoporosis in systemic lupus erythematosus patients, the difficulties in measuring fracture risk and pitfalls in using conventional methods such as bone mineral density. In addition, the mechanism of actions of glucocorticoids and evidence for glucocorticoids in the treatment of specific systemic lupus erythematosus manifestations would be explored and we also discussed specific pathophysiological mechanisms in the development of glucocorticoid-induced osteoporosis in systemic lupus erythematosus. We also reviewed the latest guidelines in the treatment of glucocorticoid-induced osteoporosis and the evidence for various osteoporosis medications. Finally, we recommend an approach in monitoring bone health and the treatment of osteoporosis specifically in systemic lupus erythematosus patients.

Beyond Hit-and-Run: Stem Cells Leave a Lasting Memory

While mesenchymal stem cells (MSCs) are rapidly cleared from the body following systemic transplantation, their therapeutic benefits typically persist. In this issue, Liu et al. (2015) reveal that the ability of transplanted MSCs to alleviate osteoporosis in systemic lupus erythematosus is maintained through epigenetic changes conferred by secretory action of the MSCs.

Transplantation of mesenchymal stem cells ameliorates secondary osteoporosis through interleukin-17-impaired functions of recipient bone marrow mesenchymal stem cells in MRL/lpr mice.

IntroductionSecondary osteoporosis is common in systemic lupus erythematosus and leads to a reduction in quality of life due to fragility fractures, even in patients with improvement of the primary disorder. Systemic transplantation of mesenchymal stem cells could ameliorate bone loss and autoimmune disorders in a MRL/lpr mouse systemic lupus erythematosus model, but the detailed therapeutic mechanism of bone regeneration is not fully understood. In this study, we transplanted human bone marrow mesenchymal stem cells (BMMSCs) and stem cells from exfoliated deciduous teeth (SHED) into MRL/lpr mice and explored their therapeutic mechanisms in secondary osteoporotic disorders of the systemic lupus erythematosus model mice.MethodsThe effects of systemic human mesenchymal stem cell transplantation on bone loss of MRL/lpr mice were analyzed in vivo and ex vivo. After systemic human mesenchymal stem cell transplantation, recipient BMMSC functions of MRL/lpr mice were assessed for aspects of stemness, osteogenesis and osteoclastogenesis, and a series of co-culture experiments under osteogenic or osteoclastogenic inductions were performed to examine the efficacy of interleukin (IL)-17-impaired recipient BMMSCs in the bone marrow of MRL/lpr mice.ResultsSystemic transplantation of human BMMSCs and SHED recovered the reduction in bone density and structure in MRL/lpr mice. To explore the mechanism, we found that impaired recipient BMMSCs mediated the negative bone metabolic turnover by enhanced osteoclastogenesis and suppressed osteoblastogenesis in secondary osteoporosis of MRL/lpr mice. Moreover, IL-17-dependent hyperimmune conditions in the recipient bone marrow of MRL/lpr mice damaged recipient BMMSCs to suppress osteoblast capacity and accelerate osteoclast induction. To overcome the abnormal bone metabolism, systemic transplantation of human BMMSCs and SHED into MRL/lpr mice improved the functionally impaired recipient BMMSCs through IL-17 suppression in the recipient bone marrow and then maintained a regular positive bone metabolism via the balance of osteoblasts and osteoclasts.ConclusionsThese findings indicate that IL-17 and recipient BMMSCs might be a therapeutic target for secondary osteoporosis in systemic lupus erythematosus.Electronic supplementary materialThe online version of this article (doi:10.1186/s13287-015-0091-4) contains supplementary material, which is available to authorized users.

Osteoporosis in Systemic Lupus Erythematosus - Correlations with Disease Activity and Organ Damage.

Purpose: to assess the incidence of osteoporosis in a cohort of SLE patients and to determine the possible correlations with disease activity, organ damage and glucocorticoid therapy. Material and methods: We analyzed a cohort that included 25 consecutive SLE patients, diagnosed according to ACR revised criteria, and 21 controls, with the same demographic characteristics. We assessed demographic, life style related, clinical, biologic and immunologic data; also, we registered information about the treatment and calculated disease activity and damage scores. Bone mineral density was measured both in lumbar spine and total hip, using dual-energy X-ray absorptiometry. Results: Evaluation of T score profile, both in lumbar spine and total hip, established a percentage of 36 (9) patients with osteoporosis, 40 (10) patients with osteopenia and 24 (6) cases with normal values. Mean T score in lumbar spine was -1.28+1.31 SD and for the total hip -1.21+1.34 SD. Analysis of correlation between T score, both in lumbar spine and total hip, and SLEDAI, established a moderate, negative correlation; for SDI we obtained a moderate correlation, both for lumbar spine and total hip, statistically significant. Conclusions: our results show an increased percentage of osteoporosis among SLE patients and a relation to disease and treatment variables, imposing a periodic evaluation, in order to establish an early diagnosis, the proper therapeutic measures, and to prevent the major consequence, vertebral and non-vertebral fractures.

SP0183 Multifactorial Pathogenesis of Osteoporosis in Sle

Systemic Lupus Erythematosus (SLE) is a chronic multisystem autoimmune disease that usually affects women during the childbearing ages. Because survival of SLE patients has improved dramatically over the last decades,...

FRI0405 The Association between FOK-I Vitamin D Receptor Gene Polymorphisms and Bone Mineral Density in Patients with Systemic Lupus Erythematosus

BackgroundLow bone mineral density (BMD) is highly prevalent in patients with systemic lupus erythematosus (SLE). In different studies, lower vitamin D levels were associated with BMD loss [1, 2]. Also,...

THU0158 Six year follow-up study of bone mineral density in patients with systemic lupus erythematosus

BackgroundLow bone mineral density (BMD) is highly prevalent in patients with systemic lupus erythematosus (SLE). However, the determinants of long-term BMD changes in SLE are still largely unknown, since the...

Six-year follow-up study of bone mineral density in patients with systemic lupus erythematosus

Long-term bone mineral density (BMD) changes and the associated factors in systemic lupus erythematosus (SLE) patients were assessed. Despite the remarkably low overall bone loss, significant spine bone loss was associated with the use of glucocorticoids, use of antimalarials, and lower 25-hydroxyvitamin D levels, stressing the importance of prevention of osteoporosis and vitamin D deficiency in SLE patients. The aim of this study is to assess the BMD changes in patients with SLE and to identify the associated factors. Demographic and clinical data of 126 SLE patients were collected, and BMD measurements of the lumbar spine and the total hip were performed by dual-energy X-ray absorptiometry at baseline and follow-up. Statistical analyses were performed using independent Mann-Whitney U tests and linear regression analyses. At baseline, 39.7% of the patients (90% female, mean age 39 ± 12.2years) had osteopenia, and 6.3% had osteoporosis. The median follow-up duration was 6.7years (range 1.9-9.3years). Mean changes in BMD at the lumbar spine (-0.08%/year) and the hip (-0.20%/year) were not significant. During follow-up, 70% of the patients used glucocorticoids. The mean ± SD daily glucocorticoid dose was 5.0 ± 5.0mg. In multiple regression analysis, BMD loss at the spine was significantly associated with higher daily glucocorticoid dose and lower baseline 25-hydroxyvitamin D levels. BMD loss at the hip was associated with lower 25-hydroxyvitamin D levels at baseline, reduction of body mass index, and baseline use of antimalarials. In this 6-year follow-up study, bone loss was remarkably low. A dose-dependent relationship between glucocorticoid use and spinal bone loss was found. In addition, the use of antimalarials and lower 25-hydroxyvitamin D levels at baseline were associated with BMD loss. These findings underline the importance of prevention and treatment of vitamin D deficiency and osteoporosis in SLE, especially in patients using glucocorticoids or antimalarials.

Systemic Correlative Study between Systemic Lupus Erythematosus, Osteoporoses And Dehydroepiandrosterone-S(DHEA-S)level In Premenoposal Egyptian Women

Systemic Lupus Erythematosus (SLE) is an autoimmune disease commonly occurs in of childbearing age, with connective tissue inflammation particularly joints and causes characteristic rashes. Subjects & Methods: the present study includs30 premenopausal females, they were divided into 3 groups. Group I consists o ten premenopausal females without SLE, Group II include ten premenopausal females had SLE,disease duration less than three years, Group III include ten premenopausal females had SLE,disease duration more than three years. Bone mineral density (BMD) in the heel of right foot by Achilles Express in all groups had been performed. Estimation of the serum level of Dehydroepiandrosterone Sulphate (DHEA-S) hormone and serum level of calcium, phosphorous ,sodium and potassium. Results: the results of the present study showed that in group II the BMD was 10% with osteoporotic , 40% with osteopenic and 50% with normal BMD, group III the BMD was 10% with osteoporotic , 60% with osteopenic and 30% with normal BMD. The correlations were done between BMD and serum minerals calcium, phosphorous, sodium and potassium in SLE patients ( Group II&III). Statistically high significant increase was found among osteopenic versus control women. Moreover a significant increase of serum calcium and sodium while there was a significant decrease in serum DHEA-S, phosphorous and potassium. Conclusions: There is a relationship between level of DHEA and the progression of SLE. Moreover there is relation between the decline in serum levels of DHEA-S and phosphorous , and the elevation of serum levels of calcium and the occurrence of osteoporosis in SLE. Treatment with DHE is beneficial in controlling of the disease activity in LES patients.

Osteoporosis in systemic lupus erythematosus: factors associated with referral for bone mineral density studies, prevalence of osteoporosis and factors associated with reduced bone density

The purpose of this study was to evaluate the clinical characteristics of women with systemic lupus erythematosus (SLE) sent for a dual energy X-ray absorptiometry (DEXA) study, and to analyse the factors associated with a lower bone mineral density in these patients. Women with SLE who had a DEXA done between 1 January 1995 and 31 December 2000 were compared with those who did not have DEXA scans performed. SLE patients with osteoporosis (OP) were compared with those with a normal bone density. Of 516 women with SLE, 205 had a DEXA done. These patients had more traditional risk factors for osteoporosis, higher lupus disease activity, renal involvement, increased damage, higher mean steroid dose, increased use of immunosuppressants and occurrence of avascular necrosis. Of the 205 patients with DEXA, 18% had osteoporosis, 48.8% had osteopenia and 33.2% had normal bone mineral density. The two statistically significant predictors of a low bone density were a higher age at time of DEXA (P = 0.0003) and a higher SDI score (P = 0.0019). Osteoporosis is a significant comorbidity in SLE. Lupus patients referred for a DEXA have more traditional risk factors and use more corticosteroids. The main factors associated with a low bone density were however found to be age and increased damage. Interestingly, disease activity and corticosteroid use were not associated with osteoporosis in this study which may suggest other potential causes such as decreased physical activity associated with damage.

Osteoporosis screening in systemic lupus erythematosus: impact of disease duration and organ damage.

The aim of the present study was to assess the effects of disease severity and demonstrable organ damage as risk factors for the development of osteoporosis in systemic lupus erythematosus (SLE). Sixty-four SLE patients were included. Mean disease duration was 7.7 +/- 5.7 y. Thirty-two patients had persistent organ damage, defined as SLICC-ACR damage score > or = 1. Disease activity measured by SLAM-2 ranged from 3 to 27. Bone mineral density (BMD) measurements were performed with dual X-ray absorptiometry. In addition, biochemical markers of bone metabolism were studied. BMD was inversely correlated with disease duration, damage score and cumulative glucocorticoid intake, but no correlation was found for current glucocortioid use or with markers of bone metabolism. In a multivariate analysis, body weight, disease duration and damage index fitted best for the prediction of BMD at both lumbar spine and femoral neck. Seven out of 64 patients had osteoporosis according to WHO criteria. In conclusion, severe osteoporosis is uncommon in lupus patients. Disease activity and severity were no major risk factors for loss of BMD in this study, but persistent non-bone-related organ damage was significantly linked to the presence of osteoporosis measured as decreased BMD. Our data suggest that, in addition to patients receiving glucocorticoids, patients with an SLICC-ACR > or = 1 or a disease duration > or = 7 y might benefit from regular monitoring of BMD as secondary prevention of damage.

Osteoporosis in systemic lupus erythematosus: prevention and treatment.

The patient with systemic lupus erythematosus (SLE) is at risk of osteoporosis through several factors: the inflammatory disease itself, disease-related co-morbidity, and its treatment. Bone loss is apparent early in the disease and this may be confounded primarily by treatment with corticosteroids. Patients should be assessed for additional risk factors for osteoporosis and general lifestyle measures adopted. Bone mineral density measurement should be considered in SLE patients at high risk of osteoporosis, particularly those starting corticosteroids and in postmenopausal women. Calcium and vitamin D supplementation provide general prophylaxis and are a suitable first-line option. Hormone replacement should be used in hypogondal subjects unless contra-indicated. In subjects at high fracture risk, particularly in postmenopausal women, bisphosphonate therapy should be considered as these agents have been shown to significantly reduce vertebral fracture risk. These measures should reduce the burden of osteoporosis and fracture in patients with lupus.