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Annals of the Rheumatic Diseases | 2015

FRI0232 Evaluations of Bone Microarchitectural Status of the Lumbar Spine in Ankylosing Spondylitis Patients by Trabecular Bone Score Assessment

Sabrina Paolino; G. Botticella; A. Casabella; D. Fasciolo; Alberto Sulli; M. Cutolo; Bruno Seriolo

Background Inflammation and immobility due to pain and stiffness are responsible for bone loss and even vertebral fractures in patients affected by ankylosing spondylitis (AS). Diagnosis of vertebral osteoporosis and the assessment of risk fracture can be difficult in these patients (pts) because the lumbar bone mineral density (BMD) is overestimated by the presence of sindesmophytes. Trabecular bone score (TBS) is a new noninvasively measurement for assessing skeletal microstructure that gives informations about bone quality. 1 Objectives The aim of the study was to investigate the relationship between skeletal microarchitecture, bone density as well as between vertebral fractures, disease activity and functional ability in AS patients Methods 9 male pts fulfilling ASAS criteria2 for AS (mean age 42±9.2 years, disease duration 8±2.5 years, BASFI 5.8±1.9, BASDAI 6.3±1.4) and 18 controls, sex and age-matched were enrolled in the study during routine screening programs. All pts were negative for causes of secondary osteoporosis. The BMD (g/cm2) of the lumbar spine (L1-L4) was analyzed by dual-energy X-ray absorptiometry (DXA) scan (Lunar Prodigy) and using the same machine were performed anteroposterior spine analysis to evaluate TBS for L1-L4 using TBS iNsight Medimaps software (Lunar Prodigy). For definition of normal microarchitecture was considered TBS>1.350 units. Finally, lateral radiographs of the spinal column were taken in order to show the presence of vertebral fractures in the thoracic and lumbar spine. Disease activity of pts was measure by Bath Ankylosing Spondylitis Disease Activity (BASDAI) and functional status was assessed using Bath Ankylosing Spondylitis Functional Index (BASFI). Results The mean values of BMD and TBS resulted significantly highest in patients with AS than in the control group (1.231±0.16 gr/cm2 vs 1.152±0.17 gr/cm2; p<0.04 and 1.070±0.18 units vs 1.332±0.13 units; p<0.05, respectively). Interestingly, a positive correlation was found between TBS and BASFI (r=0.6, p=0.005). On the contrary, a negative correlations was found between TBS values and BMD (r= -0,5 p<0.02). No correlation was found between TBS and BASDAI. Then the AS patients were divided according to the presence or not of vertebral fractures; in the fractured group (5 pts, 26%) was observed an highest BMD (1.257±0.04 gr/cm2 vs 1.207±0.05 gr/cm2; p=0.02) and a lower TBS value (1.055±0.01 units vs 1.084±0.02 units; p<0.01) in comparison with non fractured group. Conclusions This study showed a higher BMD value in AS but a poor quality of bone microarchitecture that represents the bone “paradox” of the disease. Trabecular bone score (TBS) is a novel clinical tool/marker that reflects the trabecular bone structure and could provide skeletal informations, that are not captured from the standard BMD measurement at least in AS with vertebral fractures References Roux JP et al. Osteoporosis Int. 2013; 24(9):2455-60. Sieper J et al. Ann Rheum Dis 2009;68 (6):784-8 Disclosure of Interest None declared


Annals of the Rheumatic Diseases | 2016

OP0104 Bone Quality, as Measured by Trabecular Bone Score, in Female Postmenopausal Patients with Systemic Sclerosis and Rheumatoid Arthritis

A. Casabella; C. Seriolo; G. Botticella; Luigi Molfetta

Background Patients affected by Systemic Sclerosis (SSc) and Rheumatoid Arthritis (RA) might present an increased risk of low bone mass as a result of multisystemic disorder including treatment, low vitamin D levels and physical inactivity[1]. Trabecular Bone Score (TBS) is an index extracted from the dual-energy X-ray absorptiometry (DXA) that provides an indirect measurement of bone axial microarchitecture and allows to get informations about bone quality[2]. Objectives The aim of this study was to assess bone quality in SSc patients using TBS in comparison with a “high-risk” population with RA. Methods 74 patients (mean age 65±9 years) affected by SSc, 98 RA patients (mean age 61±8 years) and 60 age-matched healthy controls (mean age 64±11 years) were studied. Bone Mineral Density (BMD, g/cm2) of the lumbar spine (L1-L4) was analyzed using DXA scan (Lunar Prodigy). Lumbar spine TBS was derived for each spine DXA examination blinded to clinical parameters and outcomes using TBS iNsight Medimaps (Lunar Prodigy). TBS value >1.350 is considered normal whereas TBS value <1.200 indicates a degraded bone microarchitecture. Results Out of 74 enrolled patients with SSc, 56 (76%) presented bone loss; in particular 32 (43%) showed osteoporosis and 24 (32%) osteopenia. In RA patients bone loss was observed in 78 patients (80%); in particular 52 osteoporosis (53%) and 41 (42%) osteopenia. BMD was found significantly lower in SSc and RA patients compared with matched control group (respectively, Lumbar spine: 0.998±0.161 g/cm2 and 0.862±0.194 g/cm2 vs 1.240±0.932 g/cm2; Femoral neck: 0.784±0.212 g/cm2 and 0.668±0.141 g/cm2 vs 0.845±0.164 g/cm2; Ward 0.563±0.173 g/cm2 and 0.486±0.221 g/cm2 vs 0.657±0.106 g/cm2; Trochanter: 0.666 ±0.104 g/cm2 and 0.598±0.231 g/cm2 vs 0.725±0.143 g/cm2; Total hip: 0.827±0.182 g/cm2 and 0.764±0.244 g/cm2 vs 1.033±0.161 g/cm2, all p<0.001). Lumbar spine TBS was found significantly lower in SSc and RA patients compared with matched control group (respectively, 1.032±0.163 and 0.904±0.148 vs 1.361±0.126, both p<0.001). There was no significant difference in mean lumbar spine TBS between patients with SSc and RA (p=0.238). Conclusions This detailed study shows a decreased BMD and TBS values in SSc and RA patients when compared to healthy controls. In addition TBS, evaluated at the lumbar spine, with lumbar and femoral BMD, could discriminate patients with alterated bone microstructure and could become a new clinical tool in the general diagnosis of osteoporosis in inflammatory rheumatic diseases, such as SSc and RA. References Cutolo M et al. Autoimmun Rev 2011:12;84–7 Roux JP et al. Osteoporosis Int 2013; 24(9):2455–60. Disclosure of Interest None declared


Annals of the Rheumatic Diseases | 2015

OP0254 Association Between Dickkopf-1 Levels, 25-Hydroxyvitamin D Status and Bone Mineral Density in Postmenopausal Patients with Systemic Sclerosis

Bruno Seriolo; A. Casabella; Sabrina Paolino; G. Botticella; M. Meroni; C. Seriolo; Luigi Molfetta

Background Patients affected by systemic sclerosis (SSc) might present an increased risk of low bone mass as a result of multisystemic disorder such as gut malabsorption or malnutrition and decreased activation of vitamin D in the altered fibrotic skin1. Dickkopf-1 (Dkk-1) is recognized as a key regulator of bone remodeling by inhibition of the Wnt signalling requiare for new bone formattino and is increased in postmenopausal patients. Objectives In this study, bone mineral density (BMD), 25-hydroxyvitamin D [25(OH) D] status and Dkk-1 levels were evaluated in order to investigate in SSc patients the incidence of osteoporosis and/or osteopenia, in according to their different nailfold videocapillaroscopic (NVC) microangiopathy pattern (namely “Early”, “Active”, and “Late”). Methods Seventy-four postmenopausal patients (mean age 64±3 years) affected by SSc (“early” n=12; “active” n=21 and “late” pattern n=41) and 63 age-matched healthy controls (mean age 63±5 years) were studied. BMD (g/cm2) of the lumbar spine (L1-L4) and of the proximal femur (femoral neck, and total hip) was analyzed using dual-energy X-ray absorptiometry (DXA) scan (Lunar Prodigy, GE, USA). Dkk-1 serum levels were measured using an enzyme-linked immunosorbent assay and 25(OH)D serum levels were evaluated by radioimmunoassay. Vitamin D levels were classified as normal (>30 ng/ml), insufficient (<30 and >10 ng/ml), and deficient <10 ng/ml) The statistical analysis was performed by non-parametric tests. Results Out of 74 enrolled patients with SSc, 56 (76%) presented bone loss; in particular 32 (43%) showed osteoporosis and 24 (32%) osteopenia. BMD was found significantly lower in SSc patients than in control group (lumbar spine: 0.890±0.21 g/cm2 vs 1.028±0.26 g/cm2; femoral neck 0.698±0.21 g/cm2 vs 0.855±0.23 g/cm2; total hip 0.801±0.14 g/cm2 vs 0.922±0.19 g/cm2, overall significance p<0.001). DKK-1 levels were significantly higher in SSc patients than in control group (2734±894 pg/mL vs 2044±692 pg/mL, p<0.007). Vitamin D levels were found lower in SSc patients than in controls (18.6+ 31 ng/ml vs 42.8+ 23 ng/ml). Interestingly, BMD (lumbar spine 0.870±0.150 g/cm2 vs 1.077±0.165 g/cm2; total hip 0.660±0.246 g/cm2 vs 0.783±0.113 g/cm2) and 25(OH)D levels (9.3±2.3 ng/ml vs 16.8±3.6 ng/ml) were found lower and Dkk-1 levels (3265±666 pg/mL vs 2033±697 pg/mL) higher in patients with “late” pattern than “early”/“active” NVC patterns. Conclusions This study showed a significant increase in serum levels of Dkk-1, associated with osteopenia/osteoporosis and deficient Vitamin D status in SSc patients with late NVC pattern when compared to healthy postmenopausal subjects. Interestingly, since Dkk-1 blocks activation and proliferation of established myofibroblasts in vitro and blocks pericyte proliferation to PDGF, pericyte migration, gene activation, and cytoskeletal reorganization to TGF-Î2 or connective tissue growth factor (all activated in SSc), its increase observed in SSc patients is matter of further investigations2,3. References Cutolo M et al. Autoimmun Rev 2011:12;84-7 Ren S et al. Proc Natl Acad Sci U S A 2013;110:1440-5 Dees C et al. Ann Rheum Dis 2014:6;1232-9 Disclosure of Interest None declared


Annals of the Rheumatic Diseases | 2015

SAT0454 Relationship Between Trabecular Bone Score and Bone Mineral Density in Systemic Sclerosis

G. Botticella; Sabrina Paolino; A. Casabella; D. Fasciolo; Bruno Seriolo; M. Cutolo

Background Patients affected by Systemic Sclerosis (SSc) present an increased risk of osteoporosis or osteopenia and fractures as a result of many factors including chronic inflammatory state, malabsorption, low vitamin D levels, physical inactivity (1). The Trabecular Bone Score (TBS) is a index extracted from the dual-energy X-ray absorptiometry (DXA) that provides an indirect measurement of bone axial microarchitecture and allows to get informations about bone quality (2). Objectives The aim of this study is to investigate bone quality using TBS in SSc patients according to their different nailfold videocapillaroscopic (NVC) patterns of microangiopathy (“Early”, “Active”, “Late”) in order to evaluate the possible association between BMD and TBS. Methods 74 female postmenopausal patients (mean age 65±9 years) affected by SSc (“early” n=16, “active” n=12 and “late” n=46, NVC pattern) and 60 age-matched healthy controls (mean age 64±11 years) were studied. BMD (g/cm2) of the lumbar spine (L1-L4) was analyzed using DXA scan (Lunar Prodigy). Lumbar spine TBS was derived for each spine DXA examination blinded to clinical parameters and outcomes using TBS iNsight Medimaps (Lunar Prodigy). TBS value >1.350 is considered normal whereas TBS value <1.200 indicates a degraded bone microarchitecture (2) NVC patterns were analyzed according to the previous reported methods (3) Results BMD was found significantly lower in SSc patients than in matched control group (respectively, Lumbar spine: 0.984±0.191 g/cm2 vs 1.240±0.932 g/cm2; Femoral neck: 0.764±0.212 g/cm2 vs 0.845±0.164 g/cm2; Ward 0.583±0.173 g/cm2 vs 0.657±0.106 g/cm2; Trocanther: 0.666±0.104 g/cm2 vs 0.725±0.143 g/cm2; Total hip: 0.827±0.182 g/cm2 vs 1.033±0.161 g/cm2, all p<0.001). Lumbar spine TBS was found significantly lower in SSc patients than in matched control group (respectively, 1.092±0.163 vs 1.261±0.126, p<0.001). Interestingly, a positive correlation was found between BMD and TBS (Lumbar spine: r=0.4, p<0.01; Femoral neck: r=0.3, p<0.01; Ward: r=0.4, p<0.05; Trocanther: r=0.4 p<0.01; Total hip: r=0.3, p<0.01) in SSc patients. In particular, decreased BMD and TBS were found in “late” SSc patients vs “early”/“active” patients (Lumbar spine 0.892±0.142 g/cm2 vs 1.122±0.205 g/cm2; Femoral neck: 0.647±0.241 g/cm2 vs 0.775±0.243 g/cm2; Ward 0.596±0.141 g/cm2 vs 0.673±0.138 g/cm2; Trocanther: 0.641±0.115 g/cm2 vs 0.763±0.135 g/cm2; Total hip: 0.696±0.160 g/cm2 vs 0.791±0.164 g/cm2; TBS 1.121±0.121 VS 1.29±0.103 all p<0.01) Conclusions This detailed study shows a decreased BMD and TBS value in SSc patients when compared to healthy controls. In addition TBS, evaluated at the lumbar spine, with lumbar and femoral BMD, could discriminate patients with alterated bone microstructure and could become a new clinical tool in the general diagnosis of osteoporosis. In particular, the association with the “late” NVC scleroderma pattern of microvascular damage, may suggest that low vascular perfusion related to microangiopathy probably might further influence bone mass and quality of skeleton. References Cutolo M et al. Autoimmun Rev 2011;12:84-87. Roux JP et al. Osteoporosis Int 2013; 24(9):2455-60. Cutolo M et al. J Rheumatol 2000; 27 (1):155-60 Disclosure of Interest None declared


Annals of the Rheumatic Diseases | 2014

SAT0490 Vitamin D Serum Levels Correlate with Bone Mass Values in Postmenopausal Systemic Sclerosis Patients

Sabrina Paolino; Bruno Seriolo; A. Casabella; Alberto Sulli; C. Pizzorni; G. Botticella; M. Meroni; M. Cutolo

Background Vitamin D is involved in both innate and adaptive immunity and in the regulation of bone turnover1. High prevalence of vitamin D deficiency has been reported in autoimmune disease including Systemic Sclerosis (SSc)2. Vitamin D is recognized as one of the important causal factor for low bone mass due to its action on bone formation and mineralization3,4. Moreover SSc is characterized by vascular damage, immune and fibrotic changes that are further risk factors for bone mass loss. Objectives The aim of this study was to evaluate possible correlation between 25(OH)D3 serum concentration and further bone mass loss in postmenopausal women with SSc in winter season. Methods After informed consent 54 female SSc patients and 42 healthy controls (mean age 68.5±9.5 years), were enrolled in the study during routine screening programs, in winter time. The mean age of patients was 66.5±11 years, the mean disease duration calculated from onset of Raynaud phenomenon was 12±10 years. 25(OH)D3 serum levels were evaluated by radioimmunoassay. The Bone Mineral Density (BMD) of the lumbar spine and hip was measured by dual energy X-ray absorptiometry using a Lunar Prodigy (GE, USA) Results 25(OH)D3 resulted significantly lower in SSc patients in comparison with controls (mean ± SD 16.1±11.7 vs 25.1±4.1 ng/ml p<0.01); whereas several bone metabolism markers like calcium (p=0.2), phosphorus (p=0.1) and bone alkaline phosphatase (p=0.1) serum levels were similar in both groups. BMD was significantly lower in SSc patients compared to control group at the level of femoral neck (mean ± SD 0.766±0.13 g/cm3 vs 0.896±0.3 g/cm3, p<0.001) and total femur (0.826±0.163 g/cm3 vs 0.948±0.136 g/cm3 p<0.002). Significantly lower BMD at lumbar spine was also observed in SSc patients (1.033±0.151 g/cm3 vs 1.132±0.200 g/cm3 p<0.003). Both BMD of femoral neck and total femur positively correlated with 25(OH)D3 concentrations (r=0.39, p<0.002; r=0.46, p<0.003, respectively). Conclusions 25(OH)D3 serum concentration and BMD values are significantly lower in SSc postmenopausal patients than in postmenopausal controls, at least in winter time. A positive correlation between 25(OH)D3 serum levels and bone mass seem evident in SSc patients and deserve further analysis. References Cutolo M. et al. Autoimmun Rev 2011;11:84-87. Caramaschi P. et al. Clin Rheumatol 2010;12:1419-25. Lips P. et al. Journal of Internal Medicine 2006; 260:245–254. Pelajo CF et al Autoimmun Rev 2010 9(7):507-510. Disclosure of Interest None declared DOI 10.1136/annrheumdis-2014-eular.4087


Annals of the Rheumatic Diseases | 2014

SAT0460 Low Bone Mass in Patients with Systemic Sclerosis: Relationships with Dickkopf-1 Levels and 25-Hydroxyvitamin D Status

Bruno Seriolo; Renata Brizzolara; Stefano Soldano; A. Casabella; Luigi Molfetta; Sabrina Paolino; Marco A. Cimmino; G. Botticella; M. Cutolo

Background Patients (pts) affected by systemic sclerosis (SSc) show increased risk of bone loss as a result of the chronic inflammatory state, physical inactivity, gut malabsorption or malnutrition, decrease activation of vitamin D in the altered fibrotic skin1. Dickkopf-1 (Dkk-1) is recognized as a key regulator of bone remodeling by inhibition of the Wnt signalling required for new bone formation and is increased in postmenopausal pts. Objectives In this study, bone mineral density (BMD), 25-hydroxyvitamin D [25(OH) D] status and Dkk-1 serum levels were evaluated in order to investigate in SSc pts a possible association between systemic osteoporosis and/or osteopenia, and Dkk-1 concentrations, based on different 25(OH) D status Methods 64 postmenopausal pts (mean age 63±7 ys) affected by SSc (mean disease duration 6±3 ys) and 43 age-matched healthy controls (mean age 62±5 ys) were evaluated during their regular screenings and after informed consent in different periods of the year. Pts were not treated with vitamin D addiction or bone remodelling drugs. BMD (g/cm2) of the lumbar spine (L1-L4) and total hip was analyzed using dual-energy X-ray absorptiometry (DXA) scan (Lunar Prodigy, GE, USA). Dkk-1 serum levels were measured using an enzyme-linked immunosorbent assay and 25(OH)D3 serum levels were evaluated by radioimmunoassay. Vitamin D levels were classified as normal (>30 ng/ml), insufficient (<30 and >10 ng/ml), and deficient <10 ng/ml) Results 47 of the SSc pts enrolled (73%) presented bone loss, in particular 24 pts (51%) showed osteoporosis and 23 osteopenia. BMD was found significantly lower in the SSc pts than in control group (lumbar spine: 0.990±0.192 g/cm2 vs 1.039±0.18 g/cm2 and total hip 0.809±0.125 g/cm2 vs 0.903±0.11 g/cm2, both p<0.001). Dkk-1 levels were significantly higher in SSc pts than in control group (2,702±910 pg/mL vs 2,164±662 pg/mL, p<0.007). Vitamin D levels were found lower in SSc patients than in controls (22.6+ 11 ng/ml vs 49.8+ 10 ng/ml). Interestingly, BMD at lumbar spine and Dkk-1 levels were found, respectively, significantly lower and higher in pts with deficient (n=14) and insufficient (n=30) vitamin D status when compared to pts with normal vitamin D status (lumbar spine 0.868±0.151 g/cm2 vs 1.077±0.165 g/cm2; total hip 0.662±0.266 g/cm2 vs 0.788±0.121 g/cm2, and Dkk-1 levels 3,258±672 pg/mL and 3,098+586 pg/ml vs 2,033±697 pg/mL, respectively, all p<0.01). Conclusions This study showed a significant increase in serum levels of Dkk-1, associated with osteopenia/osteoporosis in pts affected by SSc and deficient or insufficient vitamin D status, when compared to healthy postmenopausal subjects. Interestingly, since Dkk-1 blocks activation and proliferation of established myofibroblasts in vitro and blocks pericyte proliferation to PDGF, pericyte migration, gene activation, and cytoskeletal reorganization to TGF-β or connective tissue growth factor (all activated in SSc), its increase observed in SSc pts is matter of further investigations2. In addition, Dkk-1 should be considered a further marker of disease activity in SSc patients. References Cutolo M et al. Autoimmun Rev 2011:12;84-7. Ren S et al. Proc Natl Acad Sci U S A.2013;110:1440-5. Disclosure of Interest None declared DOI 10.1136/annrheumdis-2014-eular.4246


Annals of the Rheumatic Diseases | 2013

FRI0392 Relationships between bone loss and dickkopf-1 (DKK-1) serum levels in patients with systemic sclerosis.

Bruno Seriolo; Renata Brizzolara; Stefano Soldano; A. Casabella; Sabrina Paolino; G. Botticella; M. Meroni; L. Molfetta; Alberto Sulli; Maurizio Cutolo

Background Systemic sclerosis (SSc) patients might present an increased risk of osteoporosis as a result of the chronic inflammatory state, immobilization, use of glucocorticoids and other causes. The Wnt/β-catenin pathway is an ancient and evolutionarily conserved signaling pathway that has recently been identified a key promoters of the osteoblastogenesis hence of the new bone formation in inflammatory conditions. Dickkopf-1 (DKK-1) is a natural inhibitor of Wnt signaling pathway that could be involved in promoting osteoclastogenesis through suppression of osteoprotegerin.1 In this study, bone mineral density (BMD) and DKK-1 levels were evaluated in SSc patients in order to investigate possible associations between bone loss and Dkk-1 concentrations, according to their different nailfold videocapillaroscopic (NVC) patterns of microangiopathy (“Early”, “Active”, and “Late”).2 Methods Sixty-one postmenopausal patients (mean age 63±7 years) affected by SSc (“early” n=15; “active” n=14 and “late” pattern n=32) and 43 age-matched healthy controls (mean age 62±5 years) were studied. BMD (g/cm2) of the lumbar spine (L1-L4) and of the proximal femur was analyzed using dual-energy X-ray absorptiometry (DXA) scan (Lunar Prodigy). DKK-1 serum levels were measured by ELISA methods (DKK-1 Immunoassay R&D System). NVC patterns were analyzed according to the previous reported methods. 2 Statistical analysis was performed by non-parametric tests. Results Out of 61 enrolled SSc patients, 44 (72%) presented bone loss; in particular 21 (34%) showed osteoporosis and 23 (28%) osteopenia. BMD was found significantly lower in SSc patients than in matched control group (lumbar spine: 0.990±0.192 g/cm2 vs 1.039±0.18 g/cm2; femoral neck 0.715±0.203 g/cm2 vs 0.823±0.09 g/cm2; ward 0.559±0.175 g/cm2 vs 0.639±0.10 g/cm2; trocanther 0.660±0.09 g/cm2 vs 0.719±0.11 g/cm2; total hip 0.809±0.125 g/cm2 vs 0.903±0.11 g/cm2, overall significance p<0.001). T and Z scores showed lower values in SSc patients compared to healthy controls (lumbar spine: T=-1.56±0.62 vs -0.72±1.19, p<0.001; Z=0.19±1.45 vs 0.65±1.06, p<0.05 and total hip: T=-2.01±1.07 vs -0.80±0.89, p<0.001; Z=-0.63±0.64 vs -0.01±0.75, p<0.03, respectively). DKK-1 levels were found significantly higher in SSc patients than in control group (2691±909 pg/mL vs 2164±662 pg/mL, p<0.007). Interestingly, decreased BMD at lumbar spine/hip and increased Dkk-1 levels were found in patients with “late” pattern vs “early”/“active” NVC patterns (lumbar spine 0.870±0.150 g/cm2 vs 1.077±0.165 g/cm2; total hip 0.660±0.246 g/cm2 vs 0.783±0.113 g/cm2, all p<0.05, and Dkk-1 levels 3265±666 pg/mL vs 2033±697 pg/mL p< 0.001, respectively). Conclusions Increased DKK-1 serum concentrations together with decreased bone mass seem present in SSc patients compared to healthy controls. The association with the “late” NVC pattern of microvascular damage (advanced disease), may suggest that diffuse hypoxia/ischemia related to the diffuse microangiopathy might be a promoting factor for osteoclastogenesis and bone loss. References: Krishnan V et al. J Clin Invest 2006 Cutolo M et al. Clin Exp Rheumatol 2007 Disclosure of Interest: None Declared


Annals of the Rheumatic Diseases | 2013

SAT0204 Fetal Placental Thrombotic Abnormalities Correlate with Anti-Centromeric Anti-Nuclear Antibody Pattern in Systemic Sclerosis Pregnancies

M. Meroni; Bruno Seriolo; Sabrina Paolino; G. Botticella; D. Gerbaldo; L. Gabbi; E. Fulcheri; Maurizio Cutolo

Background Systemic sclerosis (SSc) is an autoimmune condition characterized by microvascular, skin and multi-organ involvement. As it usual arises in the reproductive years, a number of these patients plans (or achieves) a pregnancy. Several studies (1,2) showed increased sterility, risk of preterm delivery and fetal growth complications in these pregnancies, but less is known about the patophysiological mechanisms underlying these phenomena, neither the potentially pathogenetic role of certain anticorpal patterns (3). Objectives To assess the outcome and the relationship between anti-centromere pattern and placental structural abnormalities in a group of SSc with recent labor. Methods We retrospectively enrolled 20 SSc patients (mean age 34±7 years) who delivered in our University Hospital within 48 months. For each patient we performed focused visits collecting clinical and laboratory data. After delivery, placentas were analyzed according to a validated villous tree alterations score (presence of sclerotic/fibrotic villi; dilated chorionic plate vessels), used as a thrombotic index in extended protocols (4). The placental features were subsequently compared by a Student t-test. To establish a correlation between the SSc subtype and the placental abnormalities, we assessed the obtained data by a non-parametric X2 test. Results The mean gestational duration was 37±4 weeks. The incidence of preterm delivery, 15%; baby delivered small for gestational age, 10%; no intra-uterine growth retardation was detected. Among the SSc women, 30% showed a diffuse subset of SSc disease with anti-Scl70 positivity, whereas 70% had a lcSSc subtype with anti-centromere pattern. None was positive for anticardiolipin antibodies, nor for other thrombofilic conditions. Placental abnormal findings were noticed in the totality of lcSSc patient (sclerotic 93% and fibrotic 86%villi; dilated vessels 71%), as opposed to the dcSSc patients (respectively, 17%, 33% and 50%) (p<0.01). Assuming the anti-centromere positivity linked to the placental thrombotic findings, the X2 overall analysis showed a p<0.01 (6 dof). The statistical significance was kept even after the lcSSc comparison with the three placental abnormalities subgroups (p<0.05). Conclusions Anti Scl-70 is generally associated to a more severe kind of SSc disease, but in many papers the anti-centromere pattern has been indicated as a negative pronostic factor regarding the microvascular damage (5) and, potentially, the placental effectiveness (3). Placental histologic findings of our cohort could reflect the microvascular remodeling, strongly associated to the centromeric antibodies pattern. The pathophysiologic role of these antibodies is still unknown, but an interaction with several centromeric proteins, thus preventing the physiological mitotic process, has been described. In this study, anti-centromere antibodies appear strictly related to typical thrombotic changes in placental tissue: to our knowledge, this association has not been previously reported. References Merav L. Autoimm Rev 2012;11:A515–9 Chakravarty EF. Int J Rheumatol 2010;2010:287248 Taraborelli M. Arthritis Rheum 2012;64(6):1970–7 Stanek J. Placenta 2011;(32):373-9 Meyer O. Joint Bone Spine 2006;73:490–4 Disclosure of Interest None Declared


Annals of the Rheumatic Diseases | 2013

THU0421 Rheumatoid Versus Psoriatic Arthritis: Similar or Different Bone Loss?

Sabrina Paolino; G. Botticella; A. Casabella; M. Meroni; Luigi Molfetta; Maurizio Cutolo; Bruno Seriolo

Background Rheumatoid (RA) and psoriatic (PsA) arthritis are chronic diseases characterized by inflammation, often common therapies and prolonged joint immobilization are possible risk factors of bone loss and fragility fractures.1 Vitamin D is a key regulator of calcium homeostasis and skeletal health, but also seem to play an important role as risk factor for RA and PsA Objectives to determine bone mineral density (BMD) and 25-dihydroxyvitaminD3 [25(OH)D3 ] serum concentrationin RA and PsA patients Methods The study included 61 postmenopausal patients (mean age 65±8 years) affected by RA, 45 PSA symmetrical type (mean age 63±4 years) and 31 age-matched healthy controls. BMD at the lumbar spine (L1-L4) and at the proximal femur was analyzed using dual-energy X-ray absorptiometry (DXA) scan (Lunar Prodigy, GE, USA). The results of BMD were expressed in g/cm2 and the diagnosis of osteoporosis was defined according to WHO guidelines as T-score less -2.5 whereas osteopenia as T-score between -1.0 and -2.5 at any site. Laboratory assessment included quantitative determination of 25(OH)D3 concentration performed by DiaSorin radioimmunoassay kit and the cut-off defined according to international guidelines2. Results Among the 45 patients with PsA, 5 (11%) presented osteoporosis and 15 (33%) osteopenia. Fifteen RA patients(25%) showed an osteoporotic condition and 14 (23%) an osteopenic status. BMD, T and Z scores at lumbar spine and at all site of femur were found significantly lower in RA and PsA patients than in control group. 25(OH)D3concentration were (RA: 13.9±8.0 ng/mL vs PsA: 15.9±7.4 ng/mL vs 44.8±4.7 ng/mL p<0.001). BMD was significantly lower in the RA than in PsA patients (femoral neck: BMD 0.781±0.11 g/cm2 vs 0.823±0.10 g/cm2 p=0.02; ward: BMD 0.582±0.13 g/cm2 vs 0.663±0.11 g/cm2 p=0.02; trocanther: BMD 0.668±0.13 g/cm2 vs 0.714±0.08 g/cm2 p=0.01). Similarly, the T-score value in all site determined were lower in RA versus PsA patients (femoral neck: -1.6 ±1.0 vs-1.2±0.88 p=0.01; ward:-2.4 ±1.0 vs -1.9±0.9 p=0.02; trocanther: - 1.1 ±1.2 vs -0.8± 0.8 p=0.03; total hip: T-score -1.4±1.2 vs-0.88±1.0 p=0.03). A significant positive correlation was found between T and Z scores at lumbar spine in RA and 25(OH)D3concentration (r=0.28 p=0.02 and r=0.27 p=0.03); as well in PsA group 25(OH)D3 was related to BMD, T-score and Z-score at all site of evaluation of femur. (Femoral neck BMD: r=0.69 p<0.001, T-score: r=0.68 p<0.001, Z-score: r=0.63 p<0.001; Ward BMD r=0.54 p=0.001, T-score:r=0.54 p=0.001, Z-score: r=0.54 p<0.001; Trocanther: BMD: r=0.42 p=0.03; T-score: r=0.59 p<0.001, Z-score:r=0.42 p=0.003;Total hip: BMD:r=0.67 p<0.001, T-score: r=0.52 p=0.002) Conclusions This study reports that bone loss occurs both in RA and in PsA patients, but overall BMD decrease was less evident in PsA patients. In both diseases insufficient/deficient levels of vitamin D are correlated with BMD decrease. The most intensive chronic inflammation in RA patients might partially explain their most evident systemic bone loss versus PsA patients. References Simeon Grazio et al. Osteoporosis in psoriatic arthritis:is there any? Wien Klin Wochenschr 2001;123:743-750 Holick MF. Vitamin D deficiency. N.Engl J Med 2007;357:266-281 Disclosure of Interest None Declared


Annals of the Rheumatic Diseases | 2013

THU0382 Bone Mineral Density in Psoriatic Arthritis Patients with or Without Bone Erosions

G. Botticella; Sabrina Paolino; M. Meroni; A. Casabella; Maurizio Cutolo; Bruno Seriolo

Background Osteoporosis (OP) is considered a common features in patients with inflammatory rheumatic disease[1]. Psoriatic arthritis (PsA) is a chronic inflammatory arthritis of unknown aetiology and joint bone erosions are frequent, but the relationship between their presence and systemic OP has been rarely investigated. Objectives The aim of this cross-sectional study is to analyze bone mineral density (BMD), T and Z scores in PsA patients as well as to investigate its possible association with the presence of joint bone erosions. Methods A total of 65 patients (mean age 61.4±11.8 years) affected by PsA and 30 age-matched healthy controls (mean age 64.0±6.5 years) were studied. The presence or absence of joint bone erosions was evaluated by hands and feet x-ray. BMD of lumbar spine (L₁-L₄) and the proximal femur (total hip) was analyzed using dual-energy X-ray absorptiometry (DXA) scan (Lunar Prodigy, GE, USA). The results of BMD were expressed in g/cm² and according to the WHO definition, osteoporosis was diagnosed at T score less -2.5 and osteopenia at T-score between -1.0 and -2.5 at any site. The statistical analysis was performed on 2 separate group: group A (32 patients with bone erosions) and group B (33 patients without bone erosions). Results Out of 65 patients enrolled 27 (41.5%) presented generalized bone loss, in particular 21 (32.3%) showed osteopenia and 6 (9.2%) osteoporosis. BMD was found significantly lower in the PsA patients than controls at lumbar spine and total hip (lumbar spine: 1.114±0.19 g/cm² vs 1.229±0.08 g/cm², p<0.000; total hip: 0.927±0.17 g/cm² vs 1.033±0.17 g/cm², p<0.05). Accordingly, T and Z-scores showed lower values in PsA compared to controls at lumbar spine and total hip (lumbar spine: T score -0.860±1.66 vs 0.145±0.64, p<0.0001; Z score: -1.707±3.70 vs 0.358±0.68, p<0.0001. Total hip: T score -1.186±1.25 vs 0.284±0.96, p=0,008; Z score: -0.586±1.15 vs 0.293±0.89, p=0.01). Group A was affected by osteopenia and osteoporosis in 59.4% and 12.5%, respectively. There was no difference in sex distribution in patients with osteopenia while 75% of subject with osteoporosis were female. In group B, 36.4% of patients showed osteopenia and 6% osteoporosis; all patients with osteoporosis were female. BMD, T and Z scores measured at lumbar spine were significantly lower in group A compared with group B (BMD: 1.048±0.12 g/cm² vs 1.185±0.2 g/cm², p =0.003; T score: -1.263±0.9 vs -0.094±1.74, p=0.003; Z score -1.519±3.46 vs 1.697±4.45, p=0.001). The comparison between the two groups showed no significance differences in total hip mineral density, T and Z scores. Conclusions PsA patients appear be at significantly higher risk of osteoporosis than controls and patients with joint erosions show significantly increased bone loss at any level of the skeleton. The high bone turnover, due to the action of the inflammatory cytokines might partially explain the reason for the observed differences. References Bultink IE, Vis M. Inflammatory Rheumatic Disorders and bone. Curr Rheumatol Rep. 2012;14(3):224-30. Review Disclosure of Interest None Declared

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M. Cutolo

Istituto Superiore di Sanità

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C. Pizzorni

Istituto Superiore di Sanità

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