M. Meroni
University of Genoa
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Annals of the Rheumatic Diseases | 2015
M. Meroni; Carmen Pizzorni; Sabrina Paolino; D. Gerbaldo; C. Gustavino; Bruno Seriolo; Maurizio Cutolo
Background TNF alpha (TNFα) has a dual role during pregnancy course: in its first phase, promotes embryo implantation and endometrial vascular differentiation via cyclo-oxygenase and subsequent prostaglandins production; at the end of the third trimester, it contributes to the labor onset by regulating uterine contractions [1]. TNFα increased levels, although, have been associated to pregnancy complications. Among anti-TNFα agents indicated for RA treatment is included certolizumab pegol (CTZ). A double peak of incidence of RA in the female gender is linked to the hormonal status changes: the majority of women becomes ill during the post-menopausal age, but a percentage around 10% experiences the disease during the reproductive age [2]. Even if pregnancy has always been considered having a positive impact on RA symptoms [3], disease flares are occasionally observed, raising the challenge of RA management before/in the early stages of pregnancy. Objectives To assess the CTZ use safety during RA pregnancies. Methods In cooperation with the Obstetrics and Gynecology Division, we retrospectively considered, since 2010, 7 RA patients, diagnosed according to the 2010 ACR/EULAR criteria and exposed to CTZ just at the beginning (1st trimester) or during the whole pregnancy. Local ethic committee previously approved this rescue treatment and all patients signed an informed consent regarding the potential risk of biologic agents on fetus. Results The totality of patients was free from taking any potentially teratogenic drug like methotrexate or leflunomide, that were been stopped in the view of pregnancy. In 5/7 patients, thanks to an improvement of RA symptoms and laboratory tests, CTZ treatment was stopped during the first trimester of pregnancy. In 2 cases, on the opposite, the high disease activity required a prosecution of biologic administration until the end of the second trimester. All patients were treated by low-dose of oral prednisone (average 5±2.5 mg daily); two subjects were on sulfasalazine administration (both on 500 mg three times daily) and two others on hydroxychloroquine (200 mg, twice daily). Mean maternal age at conception was 31.6±3.4 years; mean disease duration dated of 51±26 months. Mean gestation period was 39±0.8 weeks and mean birth weight 3.037±0.58 grams. Three patients deliveries required cesarean section, while the others experienced a normal vaginal delivery (2 labor were induced by intravenous oxytocin). Mean APGAR scores after 1, 5 and 10 minutes from delivery were, respectively, 8±2; 8±1 and 9±1. No obstetric, perinatal or neonatal complications were observed. No relevant side effects were detected in relation to the CTZ treatment. However, none of the newborn was breastfed, due to the lack of data about CTZ safety. Conclusions Our data seem to suggest an overall safety of CTZ administration even during pregnancy in RA patients requiring intensive treatment. Further large data collection perspective, controlled studies are absolutely needed to confirm this pilot survey. References Marchioni RM. World JJ Gastroenterol 2013;19:2591-602. Cutolo M, et al. Expert Rev Clin Immunol 2014;10:31-9. Østensen M, et al. Autoimmun Rev 2012;11:A437-46. Disclosure of Interest None declared
Annals of the Rheumatic Diseases | 2015
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
Amelia Chiara Trombetta; Alberto Sulli; C. Pizzorni; M. Meroni; C. Cariti; Sabrina Paolino; Barbara Ruaro; M. Cutolo
Background Nailfold Video Capillaroscopy (NVC) is a reliable and safe method to qualitatively differentiate Primary (PRP) from Secondary Raynaud Phenomenon (SRP) allowing early diagnosis of systemic sclerosis (SSc) SRP-associated (“early” scleroderma pattern)1,2. Quantitative evaluation by NVC was demonstrated to be of great value for the analysis of abnormal capillary parameters2. Objectives To investigate the presence of diameter abnormalities, i.e. dilations >20μm, and their localization at level of capillaries, during the NVC follow up of PRP subjects, before their transition to SRP. Methods We performed a case-control study, over a total population of 191 PRP subjects (mean RP duration: 7.70 years), with a NVC follow-up of 42.77±35.80 months (3.56±2.98 years). PRP subjects were then classified as SSc SRP-associated, based on the appearance of the “early” scleroderma pattern and/or ANA positivity. Concomitant therapies and comorbidities were evaluated to avoid confounding factors3. A single operator performed the NVC and results were separately checked by three experts (PC,SA,CM), in blind. Practically, the observer (TAC), using a dedicated software (Videocap, DS MediGroup, Milan, Italy), measured on NVC images the major dilation of capillary loops branches (arterial, venous, apical). The mean diameter value for each enlarged branch (arterial, venous, apical) and therefore the total mean diameter value of all observed dilations, were calculated in each PRP subject. Mean diameter values were then correlated with all the considered clinical variables. Mann Whitney U and χ2 tests were used to calculate the differencies in the observed values between the two populations. Results A significant presence of abnormal dilations for both arterial and venous branches, was found in PRP subjects before their transition to SRP, compared to stable PRP subjects (p<0.0001), with a mean time of 29.19±26.94 months for transition. No significant differences were observed for apical dilations (p=0.07) (table). No significant correlations between the rate of dilations and clinical characteristics were detected. Total population = 191 PRP PRP = 143 SRP = 48 p Gender (%) M=4 (2)/F=187 (98) M=3 (2)/F=140 (98) M=1 (2)/F=47 (98) Age (years) 49.97±6.90 50.00±16.14 49.70±17.52 0.94 RP duration (years) 7.70±6.98 7.68±7.04 7.75±6.87 0.98 Arterial dilations (μm) 29.88±7.35 27.84±5.52 35.30±8.79 <0.0001 Venous dilations (μm) 31.16±6.34 28.86±4.48 37.19±6.58 <0.0001 Apical dilations (μm) 31.31±6.23 30.81±6.35 32.64±5.77 0.07 Conclusions The study shows that abnormal dilations of capillary diameter at the level of arterial and/or venous branches, are detectable by NVC, and are significantly expressed in PRP subjects that will develop a SRP associated to SSc. Therefore, the progressive presence of abnormal capillary dilations in PRP subjects, over at least 3.56 years of follow up, should be considered as a possible very early NVC signal of transition to the “early” scleroderma pattern. References Cutolo M et al. 2000;27:155–60. Cutolo M et al. Best Pract Res Clin Rheumatol. 2013;27(2):237-48. Smith V at al. J Rheumatol. 2013;40:2023-8. Disclosure of Interest None declared
Annals of the Rheumatic Diseases | 2014
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 | 2013
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
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
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
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
Annals of the Rheumatic Diseases | 2013
Bruno Seriolo; Sabrina Paolino; G. Botticella; A. Casabella; Luigi Molfetta; Alberto Sulli; M. Meroni; Maurizio Cutolo
Background It has been suggest a link between circulating levels of 25 hydroxyvitamin D [25(OH)D] and metabolic risk factors. It is know that metabolic syndrome (MetS) is strongly predictive of cardiovascular disease(CVD) and in rheumatoid arthritisRA there is an increased risk for CVD due to atherosclerosis resulting from systemic inflammation, medications and insulin resistance. Objectives The aim of this study is to look at the relations from 25(OH)D levels and the risk factors of MetS and the influence of 25(OH)D levels on insulin resistance Methods Fiftyfive RA patients (treated with a stable dose of Methotrexate and free of glucocorticoids theraphy from at least three months) were enrolled [mean age 52.3±5.4 years; median disease duration 75±28 months) after informed consent and Ethical Committee approval. Forthy percent of them were positive for the IgM Rheumatoid Factor (>20 IU/ml); 56% were positive for the anti CCP (12.5-20 U/ml]: 29 age- matched subject served as controls. All the patients fulfilled the ACR criteria for the diagnosis of RA and MetS. The Homoeostasis Model Assessment (HOMA) index was used to measure insulin resistance and the Quantitative Insulin Sensitivity Check Index (QUICKI) to measure insulin sensitivity. 25(OH)D was assayed by radioimmunoassay (DiaSorin). Vitamin D levels were classified as normal (>30 ng/ml), insufficient (<30, >10 ng/ml) or deficient (<10 ng/ml). Peripheral blood was collected after a 12 h fasting period. Subjects were classified as MetS positive according to the Adult Treatment Panel III Criteria(1)whenever at least three out of five of the following risk factors were present: increased waist circumference (WC) <102 cm in men and <88 cm in women, elevated serum triglycerides >150 mg/dL, reduced serum high density lipoprotein (HDL-cholesterol) <50 mg/dL in men and 50 mg/dL in womenfasting plasma glucose (FGP) >109 mg/dL, elevated systolic blood pressure (SBP) >130 mmHg and/or diastolic blood pressure (DBP) >85 mmHg. Results The mean levels of 25(OH)D in RA patients were found significantly lower compared with the control group (74.2±30.9 ng/ml vs 96.8±39.3 ng/ml; p<0.001). 25(OH)D levels in RA patients were inversely correlated with HOMA (p=0.02), Triglycerides (p=0.03), Systolic Blood pressure (p=0.02), HDL-cholesterol (p=0.005), and positively correlated with QUICKI (p=0.02) and Insulin serum levels (p=0.003). However, no relationship was observed between 25(OH)D levels and BMI or Waist circumference. Conclusions We observed a significant relationship between low levels of 25(OH)D and several metabolic risk factors for MetS in RA patients. Further research is need to elucidate possible relationship between 25(OH)D and the development of MetS. References National Cholesterol Education Program (NCEP) Circulation 2002;106:3143-3421 Disclosure of Interest None Declared
Annals of the Rheumatic Diseases | 2017
M. Meroni; C. Pizzorni; Alberto Sulli; M. Limonta; M. Cutolo