A. W. Kwok

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.

Relationship between grip strength and bone mineral density in healthy Hong Kong adolescents

SummaryThis study evaluated the magnitude of the correlations among grip strength, bone mineral density (BMD) and bone mineral content (BMC), after controlling for weight, height, pubertal development, weight-bearing activities and calcium intake. The results lead to the conclusion that grip strength is an independent predictor of bone mass in both sexes. The relationship between muscle strength and bone mass is systemic.IntroductionPrevious studies had shown a site-specific relationship between muscle strength and bone in pubertal children. This study evaluated the magnitude of the correlations among grip strength, bone mineral density (BMD) and bone mineral content (BMC) at distant bone.MethodsCross-sectional data of 169 11- to 12-year-old boys and 173 10- to 11-year-old girls came from the baseline result of a cohort study. Grip strength, BMD, BMC, weight, height, pubertal development, weight-bearing activities and calcium intake were measured. Pearson correlations and multiple regressions were used to calculate univariate and adjusted associations among grip strength and bone mass at distant bone.ResultsSignificant correlations were shown between grip strength and bone mass at hip, spine and whole body (boys: BMC:0.72–0.74, BMD:0.38–0.60; girls: BMC:0.71–0.72, BMD:0.44–0.63; p<0.0001). Multiple regressions with all covariates showed that about 70% and 50%, respectively, of the variations in BMC and BMD could be explained but not for whole body BMD. Grip strength was an independent predictor of bone mass, except hip BMD in boys and whole body BMD in girls. Stepwise regression showed that grip strength was a robust predictor in both sexes. Prediction models by grip strength and weight explained about 60% and 40% of the variations in BMC of different sites and in BMD of hip and spine, respectively.ConclusionsWe found that grip strength is an independent predictor of bone mass in both sexes. The relationship between muscle strength and bone mass is systemic.

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

SAT0094 Density, Microstructure and Strength of the Distal Radius in Male Patients with Rheumatoid Arthritis: A Case-Control Study Using HR-PQCT

Background Studies investigating risk of osteoporosis in rheumatoid arthritis (RA) have mainly been conducted in female patients. Bone health in male RA patients is less well studied. High-resolution peripheral quantitative computed tomography (HR-pQCT) is an in vivo imaging technique capable of assessing volumetric bone mineral density BMD (vBMD) and bone microstructure of the peripheral skeleton. Objectives To investigate bone density, microstructure and biomechanical competence at distal radius in male RA patients using HR-pQCT Methods This cross-sectional study involved 23 male RA patients (age: 57.5±7.0 years; disease duration: 16.0±11.1 years) with mild disease activity (DAS28 score: 3.3±1.9) and 23 age-matched male healthy controls (age: 58.2±7.1 years). Areal BMD (aBMD) of femoral neck, total hip, lumbar spine (L1-4) and ultradistal radius was measured by dual-energy X-ray absorptiometry (DXA). HR-pQCT at distal radius and micro-finite element (µFE) analysis were performed to assess cortical and trabecular vBMD, microstructure and bone biomechanical properties. Results RA patients had significantly lower body weight (62.3±10.1kg vs. 68.0±7.3kg, p=0.033). aBMD at femoral and total hip were -10% (p=0.019) and -11% (p=0.037) respectively lower in RA patients. aBMD at lumbar spine (-3%, p=0.447) or ultradistal radius (-8%, p=0.133) did not differ significantly between patients and controls. In contrast, at distal radius, trabecular vBMD was -22% (p=0.002) significantly lower in patients. Indices related to trabecular microstructure, such as trabecular bone volume fraction (-22%, p=0.002), number (-10%, p=0.041), thickness (-15%, p=0.003), separation (-20%, p=0.011), and network inhomogeneity (-33%, p=0.031), were significantly worse in RA patients. Cortical vBMD and cortical thickness were comparable between patients and controls. Indices related to cortical porosity, including pore volume (55%, p= 0.026), pore diameter (6%, p=0.030) and porosity index (57%, p=0.011) were significantly higher in patients. µFE analysis showed that whole bone stiffness and modulus were preserved but failure load (-13%, p=0.031) significantly decreased in patients. Trabecular stress (-17%, p<0.0005) and strain (-14%, p<0.0005) were significantly lower in patients with stress distributed more unevenly. After adjusted for age, disease duration and disease activity, compared with those without wrist deformity (n=12), patients with wrist deformity (n=11) had significantly increased trabecular network inhomogeneity, cortical pore diameter and cortical stress being more unevenly distributed. There was no correlation between use of oral glucocorticoids 6 months prior and vBMD or microstructure. Conclusions This study shows for the first time a significant deficit in density, cortical and trabecular microstructure and strength at distal radius in male RA patients. Increased cortical porosity is particularly noticeable in RA patients. This structural deterioration is most likely an effect of chronic inflammation rather than steroid therapy. Disclosure of Interest None Declared

Perfusion study on Modic changes of spine based on DCE-MRI

This study utilizes dynamic contrast enhancement scan by MRI to investigate the perfusion characteristics in bone marrow with Modic changes in spine. Three types of Modic change show different features in perfusion compared to normal vertebra. When the perfusion characteristics were quantified by the maximum enhancement (Smax) and enhancement slope (Slope), type II showed a slightly decreased perfusion while type I, III showed an enhanced perfusion. Besides, the normal bone marrow area in a vertebrae which has Modic change showed abnormal perfusion features when compared to that from subject with no Modic change at lumbar spine. The results suggest that the histological changes in Modic change are accompanied by vascular variation. By perfusion investigation, the inherent changes in vascular property in bone marrow can be reflected and quantified.

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

THU0083 Abnormal volumetric density and microarchitecture at the radius in chinese female patients with rheumatoid arthritis: A case-control study

Background Generalized bone loss at axial and peripheral bone is a common feature of rheumatoid arthritis (RA) and is one of the determinants of the fracture risk. The relationship between decreased areal bone mineral density (aBMD) and fracture is less clear in RA than in postmenopausal osteoporosis. High-resolution peripheral quantitative computed tomography (HR-pQCT) is an in vivo imaging technique capable of assessing volumetric BMD (vBMD) and microarchitecture of cortical and trebecular bone at the distal radius. Objectives To assess volumetric density, microarchitecture and bone strength at the distal radius in female patients with RA in comparison to healthy controls with HR-pQCT. Methods This cross-sectional study involved 66 female RA patients (age 48.9±8.2 years; disease duration 10.7±8.2 years) and 66 age-matched healthy females (age 48.8±8.2 years). aBMD of femoral neck, total hip, lumbar spine (L1-4) and forearm was measured by dual-energy X-ray absorptiometry (DXA). HR-pQCT at distal radius and image-based finite-element analyses (FEA) were performed to assess cortical and trabecular vBMD, microarchitecture and bone strength. Results There was no difference in age, body height and percentage of postmenopause between RA patients and controls. RA patients had significantly lower body weight (55.0±10.5kg vs. 58.3±7.3kg, p=0.038). aBMD at femoral neck, total hip, lumbar spine and forearm did not differ significantly between the 2 groups. However, at distal radius, compared with controls, RA patients had significantly lower volumetric cortical (p=0.004) and trabecular bone density (p=0.024), lower bone/tissue volume (p=0.023), higher trabecular separation (p=0.025), increased inhomogeneity of trabecular network (p=0.039), and increased structure model index (SMI). These alterations were independent of menstrual status. After adjusted for age, body weight, body height and aBMD of forearm by DXA, differences between RA and controls remained significant for cortical vBMD, trabecular separation, inhomogeneity of the trabecular network and SMI. Using FEA, there was no significant difference in stiffness, failure load and apparent modulus between RA and controls. Percentage difference in cortical and trabecular vBMD between RA and controls significantly correlated with disease activity (C-reactive protein, erythrocyte sedimentation rate, Disease Activity Score in 28 joints) and severity parameters (Health Assessment Questionnaire score and disease duration), while percentage difference in trabecular microarchitecture correlated with disease duration. Use of glucocorticoids did not influence vBMD or microarchitecture or bone strength in RA patients. Conclusions Patients with RA are associated with low vBMD and microarchitectural alterations of both cortical and trabecular bone at distal radius that are partially independent of demographics and aBMD assessed by DXA. Results from our study may increase understanding of the role of microarchitectural deterioration in bone fragility in patients with RA. References Haugeberg G et al. Bone mineral density and frequency of osteoporosis in female patients with rheumatoid arthritis: results from 394 patients in the Oslo County Rheumatoid Arthritis register. Arthritis Rheum 2000;43(3):522-30. Disclosure of Interest None Declared