X.-L. Tang

Structure and strength of the distal radius in female patients with rheumatoid arthritis: A case-control study

The purpose of this work was to investigate the volumetric bone mineral density (vBMD), bone microstructure, and mechanical indices of the distal radius in female patients with rheumatoid arthritis (RA). We report a cross‐sectional study of 66 middle‐aged female RA patients and 66 age‐matched healthy females. Areal BMD (aBMD) of the hip, lumbar spine, and distal radius was measured by dual‐energy X‐ray absorptiometry (DXA). High‐resolution peripheral quantitative computed tomography (HR‐pQCT) was performed at the distal radius, yielding vBMD, bone microstructure, and mechanical indices. Cortical and trabecular vBMD were 3.5% and 10.7% lower, respectively, in RA patients than controls, despite comparable aBMD. Trabecular microstructural indices were –5.7% to –23.1% inferior, respectively, in RA patients compared to controls, with significant differences in trabecular bone volume fraction, separation, inhomogeneity, and structural model index. Cortical porosity volume and percentage were 128% and 93% higher, respectively, in RA patients, with stress being distributed more unevenly. Fourteen RA patients had exaggerated periosteal bone apposition primarily affecting the ulnovolar aspect of the distal radius. These particular patients were more likely to have chronic and severe disease and coexisting wrist deformity. The majority of the differences in density and microstructure between RA patients and controls did not depend on menstrual status. Recent exposure to glucocorticoids did not significantly affect bone density and microstructure. HR‐pQCT provides new insight into inflammation‐associated bone fragility in RA. It detects differences in vBMD, bone microstructure, and mechanical indices that are not captured by DXA. At the distal radius, deterioration in density and microstructure in RA patients involved both cortical and trabecular compartments. Excessive bone resorption appears to affect cortical more than trabecular bone at distal radius, particularly manifested as increased cortical porosity. Ulnovolar periosteal apposition of the distal radius is a feature of chronic, severe RA with wrist deformity.

SLE disease per se contributes to deterioration in bone mineral density, microstructure and bone strength

Objective The objective of this report is to assess the effect of systemic lupus erythematosus (SLE) disease itself on deterioration of bone mineral density (BMD), microstructure and bone strength. Method Thirty age-matched SLE patients on long-term glucocorticoids (GC) (SLE/GC), 30 SLE patients without GC (SLE/non-GC) and 60 healthy controls were examined. Areal BMD (aBMD) was measured by dual-energy X-ray absorptiometry. Bone geometry, volumetric BMD (vBMD), and architectural parameters at the nondominant distal radius were assessed by high-resolution peripheral quantitative computed tomography (HR-pQCT). Bone strength was estimated by HR-pQCT-based micro-finite element analysis. Results Adjusted for menopausal status and adjusted calcium level, when compared with controls, SLE/non-GC patients had significantly lower aBMD at femoral neck and total hip, and diminished radial total vBMD, cortical area, vBMD and thickness, respectively, by 8.3%, 8%, 2.7% and 9.2%, as well as significant compromised bone strength (stiffness, failure load and apparent modulus) by 8.3%, 9.1% and 9.5%, respectively. Similar alterations were also found in SLE/GC patients when compared to controls. In the premenopausal subgroup analysis, when compared with controls, total hip aBMD and radial cortical area were significantly lower in SLE/non-GC patients, and cortical area and thickness were significantly deficit in SLE/GC patients. However, no significant difference in any bone variables was present between SLE/GC and SLE/non-GC patients in the entire cohort or in the premenopausal subgroup. Conclusion SLE disease per se contributes to the deterioration in bone density, cortical microstructure and bone strength. This might help to explain the considerably higher fracture risk seen in SLE patients.

Increased Organ Damage Associated with Deterioration in Volumetric Bone Density and Bone Microarchitecture in Patients with Systemic Lupus Erythematosus on Longterm Glucocorticoid Therapy

Objective. To evaluate bone quality in patients with systemic lupus erythematosus (SLE) who were undergoing longterm glucocorticoid (GC) therapy, and to focus on the correlation between bone quality and organ damage. Methods. Seventy-eight female patients with SLE and organ damage taking longterm GC, and 72 age-matched SLE patients without damage taking longterm GC were recruited for study. Clinical variables of interest included disease activity, cumulative organ damage (by Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index; SDI), major organ involvement (musculoskeletal damage and neuropsychiatric damage, etc.), and use of medication. Areal bone mineral density (aBMD) was measured by dual-energy X-ray absorptiometry. Bone geometry, volumetric BMD (vBMD), microarchitecture, and biomechanical properties were measured by high-resolution peripheral quantitative computed tomography (HR-pQCT). Results. Patients were mean age of 45 years (SD 10) and 54% were postmenopausal. The median SDI score of the cohort was 1 (interquartile range 1−2, range 1−5). Compared with patients without damage, the prevalence of osteopenia at either total hip or lumbar spine was significantly higher, and there were trends of deterioration of bone geometry, vBMD, microarchitecture, and biomechanical properties in patients with organ damage. Potential risk factors for bone quality in patients with damage were screened by univariate analysis. During multiple regression analysis, SDI was the only clinical variable consistently associated with deterioration of vBMD and microarchitecture. Conclusion. Cumulative organ damage consistently correlated with deterioration of vBMD and bone microarchitecture in SLE patients with damage on longterm GC therapy. HR-pQCT provides an insight into the underlying mechanism of bone loss in SLE.

Incidence of and risk factors for non-vertebral and vertebral fracture in female Chinese patients with systemic lupus erythematosus: a five-year cohort study:

Objective The objective of this paper is to investigate the incidence of both non-vertebral and vertebral fracture in female patients with systemic lupus erythematosus (SLE) and to identify risk factors for incident fracture. Methods In a five-year prospective study of 127 female Chinese SLE patients with an average age of 46.9 years (SD: 10.1 years), information on potential risk factors, including demographics, clinical data and bone mineral density (BMD) at lumbar spine and hip by dual-energy X-ray absorptiometry was collected at baseline. At follow-up, participants reported incident non-vertebral fracture during the study period. Semi-quantitative analysis was used to determine incident vertebral fracture on lateral thoracic and lumbar radiographs, defined as any vertebral body graded normal at baseline and at least mildly deformed (20%–25% reduction or more in any vertebral height) at follow-up. Results Nine incident non-vertebral fractures occurred in eight patients during the study period. Six patients had one or more incident vertebral fractures. The incidence of non-vertebral and vertebral fracture was 1.26 and 0.94 per 100 patient-years, respectively. In multivariate logistic analyses, independent variables associated with incident non-vertebral fracture were duration of glucocorticoid use and prevalent lumbar spine osteoporosis, while risk factors associated with incident vertebral fracture were higher organ damage and prevalent lumbar spine osteoporosis. Conclusions The incidence of fracture in SLE patients is lower than the prevalence reported in cross-sectional studies. Lumbar spine BMD appears to have a stronger relationship with incident fracture than hip BMD. This warrants further investigation regarding the optimal site of BMD measurement when predicting fracture risk in SLE patients.

SAT0095 Periarticular Bone Loss in Female Patients with Rheumatoid Arthritis: A Case-Control Study Using HR-PQCT

Background Periarticular bone loss is an early sign of bone involvement in rheumatoid arthritis (RA) and a predictor of subsequent radiographic erosion. High-resolution peripheral quantitative computed tomography (HR-pQCT) is a non-invasive 3D imaging technique capable of independent evaluation of cortical and trabecular components and their respective microstructural features. Objectives To investigate loss of cortical and trabecular volumetric bone mineral density (vBMD) and changes in microstructure at the second metacarpal bone in RA patients in comparison with healthy controls Methods For this cross-sectional study, images of the second metacarpal bone were obtained using HR-pQCT in a group of 56 middle-aged RA females (age: 48.5±8.1yrs, disease duration: 10.4±7.8yrs) and a group of 56 matched healthy females (age: 49.5±8.1yrs). HR-pQCT data acquisition yielded a series of 110CT slices proximal to the distal articular surface of the metacarpal head, providing measures of vBMD as well as cortical and trabecular microstructure. Results There were no significant differences between RA patients and controls in age, body height, body weight, menstrual status, and smoking and drinking habit. Cortical area was decreased significantly in RA patients (-21%, p=0.022) with preserved trabecular area (2.6%, p=0.242). RA patients had significantly decreased cortical (-9%, p=0.001) and trabecular vBMD (-11%, p<0.0001), thinner cortices (-23%, p=0.011), decreased trabecular bone volume fraction (-11%, p<0.0001), and thinner trabeculae (-10%, p=0.002). Trabecular number (-1%, p=0.848) and separation (4%, p=0.347) were comparable between the two groups. Decreases in trabecular vBMD and bone volume fraction in RA patients significantly correlated with increased disease activity, as reflected by higher C-reaction protein levels and Disease Activity Score in 28 Joints scores. On the other hand, increased functional disability, as reflected by higher Health Assessment Questionnaire score, significantly correlated with a decrease in cortical area, cortical vBMD and cortical thickness. Conclusions Periarticular bone loss in RA is both cortical and trabecular in origin and correlates with increased disease activity and severity. Particularly prominent in RA patients was a decrease in both cortical area and cortical thinning reflecting how periarticular cortical bone loss in RA patients occurs at both the periosteal and endocortical bone sites. References Fouque-Aubert A, Boutroy S, Marotte H, Vilayphiou N, Bacchetta J, Miossec P, Delmas PD, Chapurlat RD. Assessment of hand bone loss in rheumatoid arthritis by high-resolution peripheral quantitative CT. Ann Rheum Dis 2010;69(9):1671-6. Disclosure of Interest None Declared

SAT0413 A Case-Control Study of Density and Microstructure at the Distal Radius in Patients with Psoriatic Arthritis

Background Psoriatic arthritis (PsA) is a chronic progressive destructive arthritis characterized by joint inflammation affecting both cartilage and bone. High-resolution peripheral quantitative computed tomography (HR-pQCT) is a noninvasive imaging technique capable of quantitative assessment of volumetric bone mineral density (vBMD) and bone microstructure independently for both cortical and trabecular compartments. Objectives The objective of the study was to investigate vBMD and bone microstructure at the distal radius in PsA patients. Methods This cross-sectional study involved 65 PsA patients (30 males and 35 females, age: 54.7±10.4 years; disease duration: 13.8±7.1 years), and 65 age- and gender-matched healthy controls (30 males and 35 females, age: 54.4±10.8). Areal BMD (aBMD) of hip, lumbar spine and ultradistal radius was measured by dual-energy X-ray absorptiometry (DXA). HR-pQCT was performed at the distal radius. Comparisons of density and microstructure indices were performed by analyses of variances with Bonferroni adjustment in post-hoc analyses. Results PsA patients did not differ significantly from controls in age, body weight and body height. Areal BMD at all measurement sites were similar in PsA patients and controls. Compared to controls, PsA patients had significantly lower cortical volumetric BMD (% between-group difference: -3.93%, p=0.001). Trabecular volumetricBMD and microstructure, including trabecular bone volume fraction, number, thickness and separation, were similar in PsA patients to controls. The only measures indicating compromised bone quality in PsA patients were related to cortical porosity with cortical pore volume (94.9%, p=0.028), porosity index (67.4%, p=0.002) and pore diameter (8.9%, p<0.0001) all significantly higher in PsA patients than in controls. Male and female patients were equally affected although the increase in cortical pore volume (113.4% vs. 84.6%) and cortical porosity index (94.5% vs. 48.8%) was greater in female than male patients. Conclusions Compromised bone quality in PsA patients is primarily related to increased cortical porosity. This emphasizes the inability of standard areal BMD to explain bone fragility in PsA. References Zhu TY, Griffith JF, Qin L, Hung VWY Fong TN, Au SK, Tang XL, Kwok AW, Leung PC, Li EK, Tam LS. Structure and strength of the distal radius in female patients with rheumatoid arthritis: A case-control study. J Bone Miner Res 2013; 28(4):794-806. Disclosure of Interest None declared DOI 10.1136/annrheumdis-2014-eular.1843

FRI0325 Sle disease per se, rather than glucocorticoid treatment, contributes more to deterioration in bone density, microstructure and strength

Background The disparity between fracture prevalence and areal bone mineral density (aBMD) measured by dual-energy x-ray absorptiometry (DXA) has become a well-recognized feature in senile osteoporosis, glucorticoid (GC) use and systemic lupus erythematosus (SLE). Bone microstructure, a key component for bone strength, was measured by invasive histomorphometry of biopsy specimens. The recent development of high-resolution peripheral quantitative computed tomography (HR-pQCT) has allowed this information to be obtained non-invasively through acquisition of detailed 3D image datasets of the distal radius and tibia. In addition, in vivo HR-pQCT-based micro-finite element analysis (μFEA) allows accurate prediction of bone strength. Using HR-pQCT our group had demonstrated that low cortical volumetric BMD can reliably discriminate SLE patients on long-term GC with and without vertebral fracture; and SLE patients had deteriorated cortical bone density and microarchitecture and compromised bone strength compared with age-matched controls. Since all these studies involved SLE patients on long-term GC therapy, the effect of SLE disease per se on bone quality could not be ascertained. Objectives The aim of this study is therefore to compare BMD, bone microstructure and bone strength in SLE patients with and without treatment with GC and healthy controls. Methods Thirty age-and sex-matched SLE patients on long-term GC (SLE/GC), 30 SLE patients without GC (SLE/non-GC) and 60 healthy controls were examined. Areal BMD (aBMD) of the femoral neck, total hip, lumbar spine and non-dominant distal radius were measured by DXA. Bone geometry, volumetric BMD (vBMD), and architectural parameters at the non-dominant distal radius were assessed by HR-pQCT. Bone strength was estimated by μFEA. Results The mean age of the whole cohort was 46 years old and the mean disease duration for patients was over 10 years. Compared with healthy controls, aBMD at femoral neck and total hip were significantly lower, and using HR-pQCT, radial average vBMD, cortical area, vBMD and thickness were significantly reduced by 8.3%, 8%, 2.7% and 9.2% respectively in SLE/non-GC patients. Bone strength (i.e. stiffness, failure load and apparent modulus) in SLE/non-GC patients was inferior to that of controls by 8.3%, 9.1% and 9.5% respectively. Similar alterations were found in SLE/GC patients when compared to controls. However, no significant difference in any bone density, microstructure or strength variables was present between SLE/GC and SLE/non-GC patients. Conclusions SLE disease per se seems to contribute more to the deterioration in bone density, microstructure and strength seen in SLE patients than treatment with GC. HR-pQCT can provide an insightful analysis of the bone changes occurring in SLE, show the specific peripheral component of bone affected and improves our understanding of the mechanisms behind SLE-related bone loss, which at least partly contributes to the higher fracture risk in SLE patients. Disclosure of Interest: None Declared

SAT0210 Comparisons of bone microarchitecture and mechanical properties between childhood- and adult-onset patients with systemic lupus erythematosus

Background Systemic lupus erythematosus (SLE) patients are prone to osteoporosis and fracture due to disease itself and its therapies. Many studies of bone quality have involved in patients with adult-onset SLE (a-SLE), but only a few have concerned childhood-onset SLE (c-SLE) patients, who were at special risk of loss of bone mass. This is because they have developed the disease before achieving peak bone mass[1], which was reached in late teens or early adulthood after a gradual increase of bone mass throughout childhood and adolescence. Lilleby reported a high prevalence of osteopenia (41%) in young patients with a history of c-SLE[2]. However the information of the alterations of bone quality in this kind of patients is still scant. Objectives To study alterations of bone geometry, density and microarchitecture in women with SLE on long-term GCs according to disease onset. Methods 179 Chinese women with SLE who were receiving prednisone at least 5 mg/d for at least 1 year before study entry were selected, among whom, 18 were c-SLE (diagnostic age <18 years), 161 were a-SLE (diagnostic age ≥18 years). aBMD at femoral neck, total hip and lumbar spine were measured by DXA. Bone microarchitecture at the non-dominant distal radius was measured by high-resolution peripheral quantitative CT (HR-pQCT) and bone mechanical properties were analyzed by finite element (FE). Results Compared with a-SLE patients, patients with c-SLE were significantly younger (28yr vs.44yr), with longer GCs duration (14yr vs.11yr). All of the c-SLE patients were premenopausal, while 69 (42.9%) a-SLE patients were postmenopausal. NPLE, musculoskeletal damage and photosensitivity were more common in c-SLE patients, but no significant difference was in the prevalence of other clinical manifestations, such as nephritis or renal damage. Although aBMD at all measured sites were not significantly different between two groups, osteopenia and osteoporosis at either one site was more common in c-SLE than a-SLE (56% vs. 44%). Measured by HR-pQCT and FE, significantly lower cortical bone area (p<0.001), density (p=0.004) and thickness (p=0.003), smaller trabecular separation (p<0.001), more trabecular number (p=0.003), lower bone stiffness (p=0.03) and failure load (p=0.05) were detected in c-SLE patients. Lower cortical area, density, thickness, bone stiffness and failure load persisted in c-SLE patients even after adjusted for age, menstrual status, body mass index, duration of GCs use, highest GCs dose, disease duration, total and mean SLEDAI, disease damage (SDI), smoking, alcohol drinking, physical activities and diabetes. Conclusions C-SLE is an independent risk factor for deterioration of bone microarchitecture and mechanical properties. Early use of GCs-sparing therapies which may preserve bone quality should be applied on c-SLE patients. References Matkovic V, Jelic T, et al. Timing of peak bone mass in Caucasian females and its implication for the prevention of osteoporosis. Inference from a cross-sectional model. J Clin Invest 1994;93:799-808. Lilleby V, Lien G, et al. Frequency of osteopenia in children and young adults with childhood-onset systemic lupus erythematosus. Arthritis Rheum 2005;52:2051-9. Disclosure of Interest None Declared

THU0196 Bone microarchitecture and biomechanical properties in chinese female patients with systemic lupus erythematosus damage

Background Many studies using dual-energy X-ray absorptiometry (DXA) have shown that cumulative organ damage (SDI) of SLE is a risk factor for decreased areal bone mineral density (aBMD)[1], but without indicating respective contributions of disease- and therapy-related SDI on BMD. As a 2-dimensional projectional imaging technique, DXA measures integral aBMD of cortical and trabecular bone and is confounded by bone geometry which limited its ability in predicting fracture. The high-resolutinon peripheral quantitative CT (HR-pQCT) capable of distinguishing trabecular and cortical bone compartment with low radiation has now been available in studies of bone microarchitecture[2]. Objectives To evaluate bone quality in Chinese female patients with SLE who were on long-term glucocorticoids (GCs) and to focus on the correlation between bone quality and organ damage, including damage related to disease itself and treatment. Methods Seventy eight Chinese female patients with SLE damage on long-term GCs, were recruited in the cross-sectional study. Clinical parameters of interest included disease activity, SDI, major organ involvement and use of GCs and immunosuppressant were recorded. Bone microarchitecture at the non-dominant distal radius was measured by HR-pQCT. Results Patients were with mean age (SD) of 45 (10) and 54% being postmenopausal. The median SDI score of the cohort was 1 (interquartile range: 1-2, range 1-5). In univariate analysis, body height and weight correlated with bone geometry; age, postmenopausal status and SDI negatively associated with volumetric bone mineral density (vBMD), microarchitecture. During multiple regression analysis, SDI was the only clinical variable constantly associated with deterioration of vBMD and microarchitecture. We further distinguished 2 categories of disease damage, the therapy-related damage including cataract, osteoporotic fracture, avascular necrosis and premature gonadal failure, and SLE-related damage including the organ damages listed on the SDI other than the therapy-related damage. The SDI score was then divided as 2 scores, the therapy-related SDI score (sum of the scores of therapy-related damage) and the disease-related SDI score (sum of the scores of disease-related damage). In each multivariate analysis, the coefficient for therapy-related SDI score were at least 33% larger than the one for disease-related SDI score, suggesting therapy-related damage contributed more to the deterioration of bone density and microarchitecture compared with disease-related SDI damage. Conclusions Cumulative organ damage negatively correlated with vBMD, microarchitecture in female patients with SLE damage on long-term GCs. Therapies, such as GCs-sparing therapies or therapies without deleterious effect on bone, which can effectively control disease inflammation and, at the same time, prevent organ damage are potential in preserving bone quality in patients with SLE. References Becker A, Fischer R, Scherbaum WA, et al. Osteoporosis screening in systemic lupus erythematosus: impact of disease duration and organ damage. Lupus 2001;10:809-14. Sornay-Rendu E, Boutroy S, et al. Alterations of cortical and trabecular architecture are associated with fractures in postmenopausal women, partially independent of decreased BMD measured by DXA: the OFELY study. J Bone Miner Res 2007;22:425-33. Disclosure of Interest None Declared

FRI0324 Dkk-1 and rankl/opg predict changes in bone mineral density and bone microstructure in sle on long-term glucocorticoid: a prospective study

Background Inflammation in SLE is associated with an increase in circulating levels of pro-inflammatory cytokines including receptor activator for nuclear factor-κB ligand (RANKL), inducing osteoclasts differentiation and bone resorption. On the other hand, glucocorticoid (GC)can increase osteoclast lifespan by upregulating RANKL and suppressing osteoprotegrin (OPG). Inflammation and the use of GC in SLE may also inhibit bone formation by inducing the expression of an antagonist of the Wnt pathway - dickkopt-1 (Dkk-1), preventing osteoblast differentiation. Increased RANKL/OPG ratio and Dkk-1 expression had been described in SLE. Objectives 1) to evaluate the changes of volumetric BMD (vBMD) and bone microstructure by high resolution peripheral quantitative CT (HR-pQCT) over time in SLE patients on long-term GC and 2) to determine whether imbalance between RANKL/OPG and Dkk-1 level can predict changes in vBMD and bone microstructure. Methods This was a one-year prospective observational study in female SLE patients on long-term GC. Changes in bone geometry, vBMD and microstructure at distal radius were evaluated by HR-pQCT; and changes in aBMD were measured by dual energy x-ray absorptiometry (DXA) at total hip, lumbar spine and distal radius. Serum levels of RANKL, OPG and Dkk-1 were measured by ELISA. Potential risk factor of bone loss including age, menopausal status and other variables were analyzed using multiple regression analysis. Results A total of 180 consecutive SLE patients were recruited at baseline, and 165 completed the study. After 12 months, no significant change in aBMD at the three measured sites was observed. Using HR-pQCT, trabecular area and cortical microstructure (cortical area, perimeter and thickness [CtTh]) decreased significantly, while trabecular vBMD and meta-trabecular vBMD (adjacent to endocortical bone) significantly improved, respectively. Subgroup analysis revealed that aBMD at all measured sites and CtTh reduced significantly in postmenopausal patients. In contrast, aBMD and CtTh did not alter significantly but vBMD of cortical and trabecular bone significantly increased in premenopausal patients. Multiple regression analysis showed baseline Dkk-1 and the ratio of RANKL/OPG were independent predictors for the change in cortical area (β=-0.0003 and β=-33.1, respectively) and in CtTh (β=-0.0003 and β=-35.8, respectively). RANKL/OPG was independent predictor for percentage change in cortical vBMD (β=-12.85). Conclusions Deteriorated cortical bone geometry and mirostructure presenting as cortical bone ‘trabecularization’ were in SLE patients on long-term GC, while both cortical and trabecular bone were preserved in premenopausal subgroup, suggesting estrogen may reserve bone loss in SLE with GC. Dkk-1 and RANKL/OPG are independent predictors for changes in cortical density and structure, suggesting that bone loss in SLE with GC both by increasing osteoclastic resorption and by reducing osteoblastic formation. Disclosure of Interest: None Declared