V. W. Y. Hung

Osteopenia: A New Prognostic Factor of Curve Progression in Adolescent Idiopathic Scoliosis

BACKGROUND Studies have shown that 27% to 38% of girls with adolescent idiopathic scoliosis have systemic osteopenia. The aim of this study was to investigate whether osteopenia could serve as one of the important prognostic factors in predicting curve progression. METHODS A prospective study was performed in 324 adolescent girls with adolescent idiopathic scoliosis who had a mean age of thirteen and a half years. Bone mineral density of the spine and both hips was measured at the time of the clinical diagnosis of scoliosis. All patients were followed longitudinally until skeletal maturity or until the curve had progressed > or =6 degrees . The univariate chi-square test and stepwise logistic regression were used to predict the prevalence of curve progression, and a receiver operating characteristic curve was plotted. RESULTS The overall prevalence of curve progression was 50%. The prevalence of osteopenia at the spine and hips was 27.5% and 23.1%, respectively. A larger initial Cobb angle (odds ratio = 4.6), a lower Risser grade (odds ratio = 4.7), premenarchal status (odds ratio = 2.5), osteopenia in the femoral neck of the hip on the side of the concavity (odds ratio = 2.3), and a younger age at the time of diagnosis (odds ratio = 2.1) were identified as risk factors in predicting curve progression. A predictive model was established, and the area under the receiver operating characteristic curve of the model was 0.80 (p < 0.01). CONCLUSION Osteopenia may be an important risk factor in curve progression. The measurement of bone mineral density at the time of diagnosis may serve as an additional objective measurement in predicting curve progression in adolescent idiopathic scoliosis. The bone mineral density-inclusive predictive model may be used in treatment planning for patients with adolescent idiopathic scoliosis who are at high risk of curve progression.

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.

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

Lifelong bound feet in China: a quantitative ultrasound and lifestyle questionnaire study in postmenopausal women

Objective The phenomenon of foot binding, also known as ‘lotus feet’, has an enduring and influential history in China. To achieve a man-made smaller foot size, lifelong foot binding may have had adverse effects on the skeleton. We investigated bone properties in postmenopausal women with bound feet, which may provide new information for developing countermeasures for prevention of fragility fractures. Design Population-based cohort study. Participants This study involved 254 postmenopausal women aged 65–80, including 172 with bound feet and 82 age- and gender-matched control subjects, living in a remote region of China. Outcomes Anthropometric, SF-36 Lifestyle Questionnaire and heel quantitative ultrasound (QUS) data were collected for the whole study population. A small subset of two cases was also invited for assessment of bone mineral density and microarchitecture at the distal tibia using high-resolution peripheral quantitative CT (HR-pQCT) and gait and balance tests. Results Women with bound feet had significantly lower QUS values than age-matched women with normal feet; this was supported by HR-pQCT data. However, SF-36 Questionnaire results did not reveal any statistically significant differences in any categorical responses, including physical functioning, general health vitality and physical component summary score, and number of previous fractures. No impairment of body balance was found in the small subset. Conclusions The man-made changes caused by foot binding led to reduced physical activity, making the subjects prone to osteoporosis. Women with bound feet and osteoporosis did not have a higher incidence of fragility fractures than controls. This might be explained by compensation in physical activity to improve body balance, implying the importance of improving or maintaining body balance in overall prevention strategies against fragility fractures.

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

FRI0666 Circulating mir-99b-5p as a predictor of erosion progression in early rheumatoid arthritis: a 1-year follow-up study by hr-pqct

Background: Bone erosion is a key feature of RA reflecting both disease severity and progression. HR-pQCT is an in-vivo clinical imaging system allowing detailed analysis of bone structure, including bone erosion. Several circulating microRNAs have already been suggested as potential biomarkers in RA. Objectives: To determine whether plasma cell-free circulating miRNAs are 1) associated with bone erosion at presentation and 2) predictive of erosion progression at 12 months as determined by HR-pQCT in patients with early rheumatoid arthritis (ERA). Methods: In this prospective study, 124 ERA patients were treated with a tight control protocol aiming at remission by using conventional synthetic disease modifying anti-rheumatic drugs (csDMARDs). The second metacarpophalangeal joint (MCP2) was assessed for erosions by HR-pQCT at baseline and after 12 months. Plasma cell-free circulating miRNAs at baseline were identified by microRNA array in 10 treatment-naïve ERA patients with maximal erosion volume at MCP2; in 10 treatment-naïve ERA patients without erosion; and in 6 age- and sex-matched healthy controls. The 4 most dysregulated miRNAs were identified by TaqMan® qRT-PCR in these same 20 ERA patients. Thereafter, the expression of these 4 selected miRNAs was validated in all 124 ERA patients at baseline. Results Of the 377 screened miRNAs, 155 miRNAs were detectable. 94 (60.6%) of these detectable miRNAs were upregulated in ERA patient with erosions, with 13 (8.4%) upregulated more than twofold. 61 (39.4%) miRNAs were downregulated in ERA patients with erosions, with 6 (3.9%) downregulated more than twofold. A total of 16 miRNAs were differentially expressed (P<0.05) and 4 were possibly differentially expressed (P ≤0.1) between ERA patients with and without erosions. At baseline, expressions of miR-143–3p, miR-145–5p and miR-99b-5p were significantly higher in ERA patients with erosions than those without erosions (P<0.05 for all). After 12 months of csDMARDs treatment, 31.7%, 47.7%, and 20.6% of the ERA patients had erosion progression, stable erosion and partial erosion repair respectively. Logistic regression analysis revealed baseline expression of miR-99b-5p to be an independent predictor of erosion progression at 12 months (Exp [B]= 4.203, 95% CI 1.166–15.147, P=0.028) (table 1). Univariate Multivariate P value Exp (B) 95% CI P value Exp (B) 95% CI Depth 0.068 0.479 0.217–1.056 0.085 0.177 0.025–1.269 Width 0.108 0.746 0.522–1.067 0.871 1.069 0.481–2.373 RF+ 0.102 3.833 0.764–19.224 0.087 5.407 0.784–37.317 ACPA>250U 0.062 3.281 0.941–11.439 0.084 4.238 0.822–21.843 miR99b-5p 0.075 2.512 0.913–6.905 0.028 4.203 1.166–15.147 Conclusions: Increased level of cell-free circulating miR-99b-5p was associated with erosions at presentation in ERA patients and could predict erosion progression as assessed by HR-pQCT over a period of 12 months, indicating that it may well serve as a biomarker of poor response to csDMARDs. Whether early biologic DMARDs use in these miR-99b-5p positive patients could reduce or prevent progression of erosion will need to be addressed in future studies. Acknowledgements: This study was partly supported by the Health and Medical Research Fund (project no 10110071). 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

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

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