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Summary Long-term environmental air pollution exposure was associated with osteoporosis’ risk in a cohort of women at high risk of fracture. Cortical sites seemed to be more susceptible to the exposure’s effect. Introduction Environmental air pollution has been associated with disruption of bone health at a molecular level. Particulate matter (PM) exposure can simultaneously stimulate bone resorption and halt bone formation. The primary aim of the present study is to describe the association between long-term exposure to PM and osteoporosis in a large cohort of women at high risk of fracture. Methods Clinical, demographic, and densitometric data were extracted from the DeFRAcalc79 dataset, which gathers data on women at risk for osteoporosis. Data on the monitoring of PM10 and PM2.5 concentrations were retrieved from the Italian institute of environment protection and research (Istituto Superiore per la Protezione e la Ricerca Ambientale, ISPRA). Generalized linear models with robust estimators were employed to determine the relationship between BMD and PM long-term exposure. Results A total 59,950 women from 110 Italian provinces were included in the study. PM 2.5 exposure was negatively associated with T-score levels at the femoral neck (β −0.005, 95 CI −0.007 to −0.003) and lumbar spine (β −0.003, 95% CI −0.006 to −0.001). Chronic exposure to PM2.5 above 25 μg/m3 was associated with a 16% higher risk of having osteoporotic T-score at any site (aOR 1.161, 95% CI 1.105 to 1.220), and exposure to PM10 above 30 μg/m3 was associated with a 15% higher risk of having osteoporotic T-score at any site (aOR 1.148, 95% CI 1.098 to 1.200). Conclusion Long-term exposure to air pollution was associated with higher risk of osteoporosis. Femoral neck site seemed to be more susceptible to the detrimental effect of PM exposure than lumbar spine site. Key message Exposure to air pollution is associated with osteoporosis, mainly at femoral site.

Objectives Few data are available on the role of emotional distress as a possible mediator of the relationship between coping strategies and the Patient Global Assessment (PGA). This study aims to investigate, in a large cohort of patients affected by RA, the relationship between specific copying strategies and PGA, and the role of emotional distress as a mediator. Methods A total of 490 patients with RA completed a set of standardized assessments including the self-reported PGA, the Coping Orientation to the Problems Experienced (COPE-NVI) and the Hospital Anxiety and Depression Scale (HADS). A mediation analysis was conducted to investigate the role of emotional distress. Results The effect of coping strategies on the PGA score was significantly mediated by the emotional distress for religious (total effect mediated 42.0%), planning (total effect mediated 17.5%), behavioural disengagement (total effect mediated 10.5%), and focus on and venting of emotions (total effect mediated 9.8%). Seven coping strategies (acceptance, positive reinterpretation and growth, active coping, denial, humour, substance use-mental disengagement) resulted directly associated to PGA total score, but no mediation effect was found. The remaining four coping strategies were not associated to the PGA score. Conclusion This study suggests that coping strategies could be an important factor in the perceived disease severity. Consequently, in order to reduce PGA in patients with RA, a useful tool could be represented by the implementation of psychological interventions aiming to modify the specific coping styles. Moreover, to prevent or treat emotional distress seems to further reduce PGA.

Introduction Depression is a quite common comorbidity in patients with rheumatoid arthritis (RA) and is thought to influence its severity. This study aims to estimate, in a large cohort of Italian patients with RA, the prevalence of depression and to investigate the clinical correlates of depression in terms of disease activity and disability. Methods This is a cross-sectional study enrolling 490 outpatients with RA (80% female, mean age 59.5). The Hospital Anxiety and Depression Scale (HADS) was used to assess the presence of depression with a cut-off of 11. We collected data about disease activity and disability with DAS28, TJC-68, PhGA, PGA, VAS, DAS28, SDAI, CDAI and HAQ. Results Prevalence of depression was 14.3% (95% CI: 11-17%). Depressed patients, when compared with not depressed ones, were found to have higher scores for TJC-68 (p = 0.011), PhGA (p = 0.001), PGA (p = 0.001), VAS (p = 0.001), DAS28 (p = 0.007), SDAI (p = 0.001), CDAI (p = 0.001) and HAQ (p = 0.001). Out of the 70 depressed patients, 30 subjects, already known to be depressed in the past, were still depressed at the time of the assessment, with only 11 (15.7%) under antidepressants. A multivariate analysis showed that male sex, higher PGA score, use of antidepressants and higher HAQ score were significantly associated with an increased risk of depression. Conclusions Our study shows that depression is common in RA and may affect its activity mainly via an alteration in the perception of the disease. Although its important implications, depression is still under-diagnosed and its management is inadequate.

ObjectivesTo evaluate in a multicentric Italian cohort of patients with psoriatic arthritis (PsA) on secukinumab followed for 24 months: (1) the long-term effectiveness and safety of secukinumab, (2) the drug retention rate and minimal disease activity (MDA), (3) differences in the outcomes according to the biological treatment line: biologic-naïve patients (group A) versus multifailure (group B) patients.MethodsConsecutive patients with PsA receiving secukinumab were evaluated prospectively. Disease characteristics, previous/ongoing treatments, comorbidities and follow-up duration were collected. Disease activity/functional/clinimetric scores and biochemical values were recorded at baseline (T0), 6(T6), 12(T12) and 24(T24) months. Effectiveness was evaluated overtime with descriptive statistics; multivariate Cox and logistic regression models were used to evaluate predictors of drug-discontinuation and MDA at T6. Infections and adverse events were recorded.Results608 patients (41.28% men; mean (SD) age 52.78 (11.33)) were enrolled; secukinumab was prescribed as first-line biological treatment in 227 (37.34%) patients, as second (or more)-line biological treatment in 381 (62.66%). Effectiveness of secukinumab was shown with an improvement in several outcomes, such as Ankylosing Spondylitis Disease Activity Score (T0=3.26 (0.88) vs T24=1.60 (0.69) ;p=0.02) and Disease Activity Index for Psoriatic Arthritis (T0=25.29 (11.14) vs T24=7.69 (4.51); pgroup A showed lower Psoriasis Area Severity Index (p=0.04), erythrocyte sedimentation rate and C reactive protein (p=0.03 ;p=0.05) and joint count (p=0.03) compared with group B. At T24, MDA was achieved in 75.71% of group A and 70.37% of group B. Treatment was discontinued in 123 (20.23%) patients, mainly due to primary/secondary loss of effectiveness, and in 22 due to adverse events. Retention rate at T24 was 71% in the whole population, with some difference depending on secukinumab dosage (p=0.004) and gender (p=0.05).ConclusionsIn a real-life clinical setting, secukimumab proved safe and effective in all PsA domains, with notable drug retention rate.

BACKGROUND Inflammatory arthritis including rheumatoid arthritis (RA), ankylosing spondylitis (AS) and psoriatic arthritis (PsA) are disorders at increased risk of morbidity and mortality for which a validated prognostic tool for facilitating clinical management is needed. CHA2 DS2 -VASc (congestive heart failure/hypertension/age diabetes/stroke/vascular disease/age/sex category) score was initially conceived and used to estimate thromboembolic risk in non-valvular atrial fibrillation, and then successfully applied in community populations with sinus rhythm. We tested CHA2 DS2 -VASc-score as a prognosticator of adverse outcomes in patients in sinus rhythm with RA/AS/PsA. METHODS Between March 2014 and March 2015, 414 patients (214 RA, 75 AS, 125 PsA) in sinus rhythm without cardiac disease were consecutively analyzed and prospectively followed-up. Primary and co-primary end-points were a composite of all-cause death/all-cause hospitalization and CV death/CV hospitalization, respectively. RESULTS Patients were divided into LOWscore and HIGHscore groups if CHA2 DS2 -VASc was = 0/1 point or greater than 1 point, respectively. The HIGHscore group comprised 190 patients who were older with higher prevalence of CV risk factors and arthritis disease activity than 224 LOWscore patients. During a follow up of 36 months, the event rate for primary and co-primary end-point was 37% and 12% in the HIGHscore vs 22% and 4% in LOWscore group (P = .001 and .002 respectively). At multivariate Cox regression analysis CHA2 DS2 -VASc-score was related to primary end-point (hazards ratio [HR] 1.30 [1.07-1.59], P = .009) and co-primary end-point (HR 1.35 [1.01-1.79], P = .04) independently of traditional CV risk factors analyzed individually and indexes of inflammation or disease duration. CONCLUSION CHA2 DS2 -VASc-score accurately identifies in the mid-term patients in sinus rhythm with RA/AS/PsA at different risks for CV and non-CV mortality and hospitalization.

To evaluate the clinical effectiveness of golimumab in biologic inadequate responder (IR) patients with Rheumatoid arthritis (RA), Spondyloarthritis (SpA), and Psoriatic arthritis (PsA).We analyzed 1424 patients on golimumab from the GISEA registry. Drug survival was estimated by Kaplan-Meier analysis in biologic-naïve, 1-biologic IR, ≥2-biologics IR patients. Hazard ratios (HRs) of discontinuing golimumab at 2 years were assessed by multivariate Cox regression. Patients achieving CDAI based low disease activity (LDA) or BASDAI4 were calculated at 6 and 12 months.In RA (n.370), the 2-years survival on golimumab was 61.4% in 1-biologic IR, 51.9% in≥2-biologics IR, and 73.1% in biologic-naive patients (P=0.002 vs≥2-biologics IR). In SpA (n.502), the survival was similar among 1-biologic IR (80%), ≥2-biologics IR (76.5%), and biologic-naive (74.6%) patients (P0.05). In PsA (n.552) the survival was 72% in 1-biologic IR, 72.5% in≥2-biologics IR, and 71.8% in naïve-biologic (P0.05). Predictors of golimumab discontinuation were monotherapy (HR 1.65) for RA, female gender for SpA (HR 2.48) and PsA (HR 1.57). In RA, patients on CDAI-LDA were lower in 1-biologic IR (40%) or≥2 biologics IR (40%) than in biologic-naïve (60%) group at 6 months (P=0.02), but no difference was observed at 12 months. In PsA and SpA, the percentage of patients on CDAI-LDA or BASDAI4 at 6 months was almost identical across the subgroups.Golimumab had similar effectiveness in biologic-failure and biologic-naïve SpA and PsA, but seems to be less effective in multi-failure RA patients, especially as monotherapy. The best outcomes were seen in male patients.

Comparative pharmacodynamic (PD) analyses on different dosing schedules for cholecalciferol supplementation are limited. This was an open-label, randomized, parallel-group study involving 75 healthy individuals deficient in vitamin D (baseline 25OHD &lt, 20 ng/mL) receiving oral cholecalciferol with three different dosing regimens: Group A: 10,000 IU/day for 8 weeks followed by 1000 IU/day for 4 weeks, Group B: 50,000 IU/week for 12 weeks and Group C: 100,000 IU every other week for 12 weeks. Regulators of calcium and phosphate homeostasis, bone turnover markers and Wnt inhibitors were measured at baseline, Day 28, 53, 84, and 112. The 1,25OH2D increased at each time point. The increase was greater (p &lt, 0.05) for group A vs. B and C at Day 28, and vs. group B at Day 56. No significant difference among groups was observed for the other biomarkers. The 24,25OH2D remained stable over time. PTH decreased at Day 84 and FGF-23 increased at all time points. CTX-I and PINP increased slightly at Day 28. BALP decreased from Day 56 onward. Dkk-1 increased from Day 56 onward, while sclerostin did not show significant changes. In healthy individuals deficient in vitamin D, vitamin D supplementation exerted effects on multiple regulators of calcium, phosphate and bone metabolism, without marked differences using the three regimens.

Background:Many patients with rheumatoid arthritis (RA) and spondyloarthritis (SpA) are in their childbearing years. Concerns exist regarding the interplay between the rheumatic diseases and the pregnancy (1).Objectives:Actually, there are contradictory data regarding the pregnancy outcome in patients with RA and SpA (2). Thus, we performed this longitudinal retrospective study to evaluate the effect of RA and SpA on pregnancy outcome.Methods:The data of 78 pregnancies of 60 women followed from April 2017 to December 2020 at pregnancy clinic of Internal Medicine Unit, San Bortolo Hospital, Vicenza and Rheumatology Unit, University of Verona were reviewed. Fifty (64.1%) women were affected by RA and 28 (35.9%) by SpA. Information regarding demographic data, disease activity, drug exposure and maternal/foetal outcomes were collected in an electronic database. Details concerning pregnancy complications and congenital malformation were also collected. We compared pregnancy and foetal/neonatal outcome, medication use and disease activity between women affected by RA and SpA. Moreover, we evaluated the effect of disease activity on pregnancy outcome.Results:Overall, there were 70 (86.4%) live births, 10 (12.3%) miscarriages and 1 (1.2%) foetal death. There were three twin pregnancies. Even there was a higher rate of glucocorticoids and bDMARDs use in RA than in SpA group, respectively 40% vs 21% and 70% vs 57,1%, there were no statistical differences regarding drug exposure at conception. Moreover, there were no differences concerning disease activity at conception. Still, a higher rate of glucocorticoids and bDMARDs, respectively 26% vs 10.7% and 46% vs 39.3% were used in RA than in SpA patients during pregnancy. Furthermore, we did not find any statistical differences regarding maternal and foetal/neonatal outcome between pregnancies in the RA and those in the SpA groups. There were four (4.9%), congenital malformation, two (3.8%) in RA group and two (6.9%) in SpA group. About one-third of patients 24 (30.7%) presented a moderate disease activity at conception as evaluated by DAS28PCR and BASDAI. However, there were no significant differences, on maternal and foetal/neonatal outcome in patients with moderate activity disease with respect of those in clinical remission.Conclusion:Even a higher rate of glucocorticoids and bDMARDs were used in RA than in SpA patients, there was no differences on pregnancy outcome between them.References:[1]Ostensen M. Nat Rev Rheumatol. 2017;13:485-493. doi: 10.1038/nrrheum.2017.102.[2]Polachek et al. J Rheumatol 2020;47:161-163. doi: 10.3899/jrheum.190631.Disclosure of Interests:None declared

Bone loss in rheumatoid arthritis (RA) is a key feature both local and systemic. Anti-citrullinated protein antibodies (ACPA) have recently been found to directly induce differentiation and activation of osteoclasts and therefore contribute to periarticular bone loss. The aim of this study was to analyze the effect of ACPA on systemic bone mineral density (BMD) in patients with established RA. This is a cross-sectional study with a single-center RA population. BMD was measured with Dual X-ray absorptiometry at lumbar and femoral sites. ACPA were measured by EIA. Multivariate analysis was performed adjusting for the main confounding variables. One hundred twenty-seven RA patients were enrolled. In univariate analysis, ACPA-positive patients showed lower BMD Z-score (SD below the age- and gender-matched mean reference value) at femoral sites (p

Inflammatory arthritis including rheumatoid arthritis (RA), ankylosing spondylitis (AS) and psoriatic arthritis (PsA) are disorders at increased risk of morbidity and mortality for which a validated prognostic tool for facilitating clinical management is needed. CHABetween March 2014 and March 2015, 414 patients (214 RA, 75 AS, 125 PsA) in sinus rhythm without cardiac disease were consecutively analyzed and prospectively followed-up. Primary and co-primary end-points were a composite of all-cause death/all-cause hospitalization and CV death/CV hospitalization, respectively.Patients were divided into LOWscore and HIGHscore groups if CHACHA

Background Occult left ventricular (LV) systolic dysfunction (LVSD) is associated with worse cardiovascular outcomes in asymptomatic patients with arterial hypertension and/or diabetes mellitus. In these patients, LV systolic function may worsen or improve overtime. However, little is known about the changes in LV function during follow up of patients with rheumatoid arthritis (RA). Objectives This prospective study analyzed incidence and factors associated with changes in LV systolic function in patients with RA without known cardiovascular disease. Methods One-hundred-forty outpatients with RA without overt cardiac disease were recruited between March and December 2014. Patients underwent clinical and echocardiographic evaluation at baseline and after a median period [min-max] of 35 [23-47] months of follow up. Stress-corrected midwall fractional shortening (sc-MFS) was used as measure of LVSD and considered impaired if Results Impaired sc-MFS at follow up (sc-MFS-FU) was detected in 60/140 (43%) patients who were compared with 80 patients with normal sc-MFS-FU. Baseline sc-MFS did not differ significantly between the two groups, which appeared to diverge significantly soon after 1-year of follow up (figure). Baseline anti-citrullinated protein antibodies (ACPA) positivity, high disease activity (CDAI>10) and duration of RA were independently associated with impaired sc-MFS-FU at multiple logistic regression analysis. Among these parameters, ACPA had the highest sensitivity (80%) whereas high disease activity had the highest specificity (89%) for sc-MFS-FU. A predictive score including all three predictors (ACPA status, CDAI>10 and duration of RA) detected impaired sc-MFS-FU with a sensitivity of 78% and specificity of 82% (AUC 0.80 [IC 0.72-0.88], p Conclusion This study supports the hypothesis that changes overtime in LVSF in patients with RA are associated with ACPA, high disease activity and duration of disease. Disclosure of Interests: Alessandro Giollo: None declared, Giovanni Cioffi: None declared, Giovanni Orsolini Speakers bureau: Grunenthal, Luca Idolazzi: None declared, Antonio Carletto Speakers bureau: Roche, Novartis, MSD, Abbvie, Bristol, Jannsen, Celgene, Pfizer, Andrea Dalbeni: None declared, Federica Ognibeni: None declared, Elena Fracassi Speakers bureau: Novartis, Davide Gatti Speakers bureau: Abiogen, Amgen, Janssen-Cilag, Mundipharma, Pfeizer, Maurizio Rossini: None declared, Ombretta Viapiana Speakers bureau: Novartis, Abbvie, Eli-Lilly, Sanofi Genzyme

Background Given the data on efficacy and safety of biologic treatment in rheumatoid arthritis (RA), more and more patients older than 65 years are starting these drugs. Objectives This study aims to evaluate safety and efficacy of biologics in elderly patients. Methods: four-hundred and thirteen patients with RA were enrolled and divided in two group, i.e. older or younger than 65 years old. Data on disease characteristics, treatment and adverse reactions were collected. In addition, comorbidities were evaluated by the Rheumatic Disease Comorbidity index (RDCI). Results Seventy-seven patients were male and 87 were older than 65 years. The elderly patients had a higher RDCI as compared to those younger than 65 years (1.0 ± 3.0 vs. 0.0 ± 10 respectively, p Conclusion RA patients aged over 65 years have been found to have even a better retention rate at first biologic than youngers one, probably because of less strict targets in disease control and a more frequent follow up. In addition, safety has been found to be as good as in younger patients. Comorbidities do not seem to affect retention rate. Disclosure of Interests Cristian Caimmi: None declared, Federica Martinis: None declared, Ilaria Montanari: None declared, Alice Dellaidotti: None declared, Elena Fracassi Speakers bureau: Novartis, Ombretta Viapiana Speakers bureau: Novartis, Abbvie, Eli-Lilly, Sanofi Genzyme, Domenico Biasi: None declared, Maurizio Rossini: None declared, Antonio Carletto Speakers bureau: Roche, Novartis, MSD, Abbvie, Bristol, Jannsen, Celgene, Pfizer

Background: Secukinumab is a novel treatment for psoriatic arthritis (PsA) but data from real life are still missing. Objectives: The aim of this study is to evaluate a wide cohort of PsA patients on secukinumab followed in 7 Italian rheumatologic centers. Methods: Two-hundred and seventy-nine patients affected by PsA and on secukinumab were enrolled. Data on disease characteristics, previous and ongoing treatments, comorbidities and duration of follow-up were collected. In particular DAPSA and aSDAS were used to assess articular and axial disease activity. Results: Mean age of our cohort was 53±11 years and BMI 26.4±5.1 kg\m2 with the majority of patients being female (63.8%). Mean disease duration was 9.7±7.5 years and mean follow-up was 10.9±6.8 years. For 100 patients (35.8%) secukinumab was their first line biologic treatment and 41 (50.5%) were in monotherapy. DAPSA was 25.9±10.5 at baseline, 15.9±9.7 at M3, 12.9±8.4 at M6, 9.8±7.1 at M12 with a significant downward decrease at every visit as compared to baseline (p Forty patients (14.3%) stopped the treatment during the follow up mainly because of primary or secondary loss of efficacy (18 and 10, respectively). Only 9 patients suspended the treatment because of adverse events, of which 5 because of reactions at site of injection. The retention rate at 12 months was very good in the whole population (figure), and in particular in patients with entesitis at the baseline (10.5 vs, 11.2, p=0.038). No differences in survival were found when dividing patients accordingly to BMI, although overweight or obese patients showed a trend for a better retention rate (10.6 vs 10.9, p=0.089). Interestingly no differences were found between naive and non-naive patients (p=0.895) and between those in monotherapy or in combination therapy (p=0.925). Conclusion: This is one of the first real life studies on secukinumab and shows a very good efficacy and safety of this treatment in PsA patients, also for the articular manifestations, as shown by a significant decrease of DAPSA over a 12-months follow up. Disclosure of interests: Federica Martinis: None declared, Cristian Caimmi: None declared, Rosario Foti: None declared, Elisa Visalli: None declared, Giorgio amato: None declared, Roberta Ramonda: None declared, augusta Ortolan: None declared, Mariagrazia Lorenzin: None declared, angelo Semeraro: None declared, Leonardo Santo: None declared, Emanuela Praino: None declared, Maria Sole Chimenti: None declared, Roberto Perricone: None declared, Favia Sunzini: None declared, Raffaele Scarpa: None declared, Francesco Caso: None declared, Luisa Costa: None declared, Elena Fracassi Speakers bureau: Novartis, Maurizio Rossini: None declared, antonio Carletto Speakers bureau: Roche, Novartis, MSD, abbvie, Bristol, Jannsen, Celgene, Pfizer

Objective Patients with rheumatoid arthritis (RA) have an increased cardiovascular event rate, mainly due to the arterial stiffness which leads to coronary atherosclerosis and concentric left ventricular (LV) geometry. These conditions predispose to LV systolic dysfunction (LVSD), which can be detected by stress-corrected mid-wall shortening (sc-MS), an early prognosticator of cardiovascular events in asymptomatic patients with arterial hypertension and/or diabetes. In these subjects, sc-MS is frequently impaired even though LV ejection fraction (LVEF) is preserved. In this study, we analyzed the prevalence and the factors associated with asymptomatic LVSD measured by sc-MS among patients with RA and verified whether RA per se was independently related to LVSD. Methods We prospectively recruited 198 outpatients with RA without overt cardiac disease between January and June 2014 and compared them to 198 controls matched for age, gender, body mass index, and prevalence of hypertension and diabetes. sc-MS was taken as index of LVSD and considered impaired if

Background:Secukinumab (SEC) is a novel treatment for psoriatic arthritis (PsA),but data from real life are still missing.Objectives:1)to evaluate the effectiveness and safety of a wide cohort of PsA patients on SEC followed in 7 Italian rheumatologic centers for 24 months;2)to compare the features and disease activity indices of SEC-treated PsA patients subdivided in naïve biological drugs (group A) and in TNF-inhibitors (TNFi) failure patients (group B).Methods:Consecutive patients with moderate-severe PsA,who begun SEC treatment were evaluated prospectively.Data on disease characteristics,previous and ongoing treatments,comorbidities and duration of follow-up were collected.Disease activity,functional and clinimetric scores and biochemical values were recorded at baseline (t0),at 6 (t6),12 (t12),and 24 (t24) months.Anova (Kruskal Wallis) and generalized linear models were used to compare variables over time.Infections and adverse events were also collected.Results:PsA345patients [38.84% men;mean age 52.9 (11.27) years] were enrolled;mean treatment duration was 18.53 (9.97) years.SEC was prescribed as first line biologic treatment in 133 (38.55%) patients and as second or more line biological treatment in 212 (61.45%) patients. Enthesitis was present as a prominent manifestation in 61.44% of patients (Figure 1).In all population significant decrease in tender/swollen joints;Visual Analogue Scale of pain (VASp) and general health (VASgh);Psoriasis Area Severity Index (PASI);Leeds Enthesitis Index (LEI);number of dactylitis;Health Assessment Questionnaire modified for spondyloarthritis (HAQ-S);Bath Ankylosing Spondylitis Disease Activity Index (BASDAI);Bath Ankylosing Spondylitis Functional Index (BASFI);C-reactive protein (CRP) was achieved.Effectiveness of all PsA patients was associated to an improvement in Ankylosing Spondylitis disease activity score (ASDAS) [t0=3.45 (0.69) vs t24=1.48 (0.23);pgroup Bhad a more erosive (p=0.04) and polyarticular pattern (p=0.04),a longer disease duration (p=0.001),a greater prevalence (p=0.04) of psoriasis and dactylitis (p=0.01),a higher PASI score (p=0.01),while no significant difference was observed for uveitis,inflammatory bowel diseases,enthesitis.At t24group Ashowed better physical functioning and lower disease activity compared togroup B[HAQs A vs B=0.03 (0.16) vs 0.69 (0.73);BASDAI A vs B=2.37 (0.66) vs 4.27 (2.33);ASDAS A vs B=1.4 (0.62) vs 1.99 (0.86);CRP A vs B=2.03 (1.94) vs 3.11 (1.55) mg/L;DAPSA A vs B=7.03 (3.57) vs 12.41 (8.05)].After t24 of treatment 74.6% ofGroup Aand 72.8% ofGroup Barticular had an inactive\low disease activity (MDA),accordingly to ASDAS and DAPSA respectively.Forty-three patients (12.46%) stopped the treatment during the follow-up mainly because of primary or secondary loss of efficacy (29 and 24, respectively).Only 14 patients suspended SEC because of adverse events (of which 9 for reactions at site of injection).A low number of episodes of mild infections (16) occurred;SEC was instead permanently discontinued in 7 cases for:oral refractory mucositis (3);recurrent aphthosis (2);diverticulitis (2).The retention rate at t24 was good in the whole population.Interestingly no differences were found betweenGroup AandB(p=0.815).Conclusion:In a real life clinical setting,SEC was safe and effective in PsA. as shown by a significant decrease of DAPSA and ASDAS over a 24-months follow up.Disclosure of Interests:Mariagrazia Lorenzin: None declared, Antonio Carletto: None declared, Rosario Foti Consultant of: lilly, sanofi, MSD, Janssen, Abbvie, BMS, celgene, roche, Speakers bureau: lilly, sanofi, MSD, Janssen, Abbvie, BMS, celgene, roche, Maria Sole Chimenti: None declared, Angelo Semeraro: None declared, Luisa Costa: None declared, Leonardo Santo: None declared, Elena Fracassi: None declared, Ilaria Montanari: None declared, Mara Felicetti: None declared, Giulia Lavinia Fonti: None declared, Francesco Caso: None declared, Andrea Doria Consultant of: GSK, Pfizer, Abbvie, Novartis, Ely Lilly, Speakers bureau: UCB pharma, GSK, Pfizer, Janssen, Abbvie, Novartis, Ely Lilly, BMS, Augusta Ortolan: None declared, Roberta Ramonda Speakers bureau: Novartis, Celgene, Janssen, Pfizer, Abbvie, Lilly

Background Secukinumab has been approved for the treatment of active ankylosing spondilytis (AS) and psoriatic arthritis (PsA). Its efficacy has been demonstrated in phase III trials where eligibility criteria ensured a homogeneous population. Although this strategy reduces confounding factors, it does not guarantee the same results in the real world, where clinicians deal with advanced disease, comorbidities, adherence and persistence challenges. Objectives Aim of this study was to assess efficacy and safety of Secukinumab in real-world clinical practice. Methods Patients received Secukinumab (150 or 300 mg) at weeks 0,1,2,3 and 4 as induction therapy and then every 4 weeks as manteinance therapy. Assessment of disease acrivity was done at months 0,6 and 12 using DAPSA, ASDAS, BASDAI, BASFI, pain VAS. Results 61 patients affected by PsA (65% females, 35% males) and 29 affected by AS (70% males, 30% females) were included. 64% of patients reached 12 months follow up. Baseline characteristics of both groups are shown in the tables below. In the PsA cohort, the median DAPSA at baseline was 19.5 (IQR 9.6), at 6 months 9.09 (IQR 6.5, p In the AS cohort, the median BASDAI at baseline was 5.5 (IQR 2.2), at 6 months 3.6 (IQR 1.2, p 4 patients switched therapy at 6 months due to partial response, 1 patient experienced an expected adverse event (Candida infection). Overall, no serious side effects were observed and none resulted in Secukinimab discontinuation. Conclusions In this first real-world cohorts of patients with PsA and AS Secukinumab has proven to be effective, regardless of PsA subtype, radiographic progression in AS and previous exposure to biologic therapy. The safety profile was favourable and similar to previous studies. Reference [1] Baeten D, et al. Secukinumab, an Interleukin-17 A Inhibitor, in Ankylosing Spondylitis. NEJM2015; 373 (26): 2534–48. Disclosure of Interest None declared

Background Depression and anxiety disorders are more common in chronic inflammatory arthritides (CIA) than in the general population.1 In rheumatoid arthritis (RA), depressive and anxiety symptoms have been associated with disease activity and pain perception,1 physical disability,2 health care costs,3 and mortality.4 To our knowledge, data on the prevalence of depression in Italian patients with RA are scarce. Objectives To estimate the prevalence and factors associated with depression among patients affected by RA. Methods During an one year period, patients affected by RA have been consecutively enrolled. For each patient demographics and disease characteristics were recorded; the Hospital Anxiety and Depression Scale (HADS) was administered. HADS is a validate questionnaire to assess depressive and anxiety symptoms in patients affected by somatic disorders admitted to general hospital. An HADS ≥11 was considered diagnostic for depression. Results The table summarises the main results. We recruited 231 patients affected by RA, finding a prevalence of depression of 13.9% (95% CI 9.4%–18.3%). Overall, patients with depression, when compared with patients without, were older, more frequently females, with a lower education, higher physician global assessment and patient global assessment, more comorbidities. In particular, they had any cardiovascular, neurologic or musculoskeletal issue (p=0.018, p=0.032, p=0.014, respectively) and more often used glucocorticoids or NSAIDs. Conversely, no association was found between depressive symptoms and the use of biologic therapies or the presence of inflammatory markers. Interestingly, a positive history of depression was present only in few patients with an HADS ≥11. Conclusions These preliminary results suggest that more than one every seven patients with RA could suffer from depression, thus depression might be undiagnosed in a significant number of patients. Comorbidities, anti-inflammatory medications and both physician- and patient- driven evaluation of disease burden were the most striking factors associated with depression in this cohort of patients with RA. References [1] Kojima M, et al. Arthritis and rheumatism2009Aug 15;61(8):1018–24. [2] Peck JR, et al. Arthritis and rheumatism1989Sep;32(9):1100–6. [3] Joyce AT, et al. J Rheumatol2009Apr;36(4):743–52. [4] Ang DC, et al. J Rheumatol2005Jun;32(6):1013–9. Disclosure of Interest None declared

Objective.The duration of treatment with glucocorticoids (GC) in polymyalgia rheumatica (PMR) is often longterm. Amino bisphosphonates (N-BP) are used in PMR for the prevention of GC-induced osteoporosis, but they coulsd also have immunomodulatory properties. Whether they can be effective as an adjuvant treatment in PMR is unknown. We aimed to establish whether the use of N-BP in our PMR cohort may be associated with GC discontinuation.Methods.We conducted a retrospective review of all patients diagnosed with PMR recorded in our electronic medical notes. Cox regression analyses were used to examine the association between the use of N-BP and discontinuation of GC.Results.Data were retrieved for 385 patients (mean age 71 ± 10 yrs, 64% females, mean initial prednisone dose 19 ± 9 mg/day). The median followup time was 38 months (range 9–57); more than 60% of patients were exposed to N-BP. GC were discontinued in 47% of patients after a median time of 20 months (range 14–27), but subsequently restarted in 39%. Overall, 276/385 patients (72%) were actively treated at their last available evaluation (mean prednisone dose 4.9 ± 5.5 mg/day), while 123/205 (60%) were still receiving GC after 24 months of followup. The use of N-BP was associated with the discontinuation of GC (adjusted HR 0.66, 95% CI 0.50–0.88), independent of age, initial GC dose, and osteoporosis.Conclusion.Unlike current guidelines, longterm treatment with GC is often necessary. These preliminary data suggest that N-BP may be involved in the management of PMR.

Golimumab is an anti-TNF monoclonal antibody administred subcutaneously once a month and produced with an innovative technology that minimizes immunogenicity. This paper reviews and updates the main studies on the efficacy, safety and pharmacoeconomic aspects of treatment with golimumab of psoriatic arthritis, ankylosing spondylitis and rheumatoid arthritis.

Background Since 2013, in Veneto9s Region, data registration is mandatory for all patients affected by Rheumatoid arthritis (RA), Psoriatic Arthritis (PA), Ankylosing Spondylitis (AS) in treatment with biologic agents. The biologic DMARDs currently marketed in Italy are: anti-TNF (originator and biosimilar infliximab, etanercept, adalimumab, certolizumab and golimumab), anti-IL6 (tocilizumab), anti-CD20 (rituximab), CTLA-4 like (abatacept) and anti IL-12/23 (ustekinumab). Objectives The aim of this study was first to describe the characteristics of patients with RA, PA, AS under biologics and then, to extract and analyze real-life data regarding rheumatic treatments in Verona9s cohort. Methods The study has been carried out on behalf of Regione del Veneto, Giunta regionale- Ricerca Sanitaria Finalizzata-Venezia-Italy. Data used for analysis were retrieved from Veneto9s Region Biologics Register (VRBR). VRBR provides that core variables such as onset and type of disease, anthropometric characteristics (age, sex, body weight, height) are registered at the beginning. Furthermore, prior and concomitant rheumatic treatment (conventional and biologic DMARDs, corticosteroids, NSAIDs), disease activity indicators (DAS 28-PCR, ASDAS-PCR, pain-NRS), prognostic factors (positivity for rheumatoid factor and/ or anti-citrulline antibodies in AR, presence of radiological erosions) were assembled at baseline, every 6 months and at the time of biologic9s switch or swap. Results A total of 983 patients under biologics were examined; 543 (55,2%) with AR, 272 (27,7%) with AP and 168 (17,1%). Between these, 262 (27,2%) patients were naive to biologics, 128 with AR, 84 with AP, 50 with SA. Mean duration of disease was of 15,3, 10,7 and 12,6 years respectively for RA, PA and AS. Radiological erosions were present in 73% of RA-patients and the percentage was higher in those with positivity for rheumatoid factor and/ or anti-citrulline antibodies (84,4% versus 56,2%). More than half of the patients in this cohort were treated at least with one biologic agent; anti-TNFs were the main biologic used (RA:54,8%, PA:92,7%, AS: 100%) followed by Abatacept (25,4%), tocilizumab (12,3%) and rituximab (5,9%) in patients with RA. Methotrexate (MTX) was the prevalent associated c-DMARDs (41,8% in RA and 34,2% in PA) with mean dose of 11,9 mg/week in RA and 12,1 mg/week in PA. The optimal dose of methotrexate was not achieved prevalently because of drug intolerance. Conclusions Profile of both conventional and biological DMARDs looks very different according to the type of rheumatic disease. The first data show an underuse of MTX in patients with RA and PA under biologics with a low mean dosage due to intolerance. Next step is to evaluate long-term outcomes in clinical practice. Disclosure of Interest None declared

The coupling of bone formation to bone resorption during treatment of postmenopausal osteoporosis with antiresorbers might be related to changes in Wnt/b-catenin signaling. We compared the effects of two bisphosphonate treatments on two Wnt-inhibitors Sclerostin (SOST) and Dickkopf-related protein 1 (DKK1). The study population included 74 women with postmenopausal osteoporosis participating simultaneously in two multicenter, placebo controlled trials. The patients were randomized to: intramuscular clodronate 100mg/week (CLO) (N=36), and yearly intravenous therapy with 5mg zoledronate (ZOL) (N=18) and placebo (N=20). Bone turnover markers (intact N-propeptide of type I collagen [P1NP], C-terminal telopeptide of type I collagen [CTX]) remained unchanged in the placebo group while they significantly decreased during treatment with the two bisphosphonates, versus both placebo and baseline. In CLO treated patients serum DKK1 remained stable over the entire period of observation while serum SOST levels increased significantly after 12months of treatment both versus placebo group (p

Osteogenesis imperfecta (OI) is a hereditary disease characterized by low bone mass, increased bone fragility, short stature, and skeletal deformities. This study focuses on OI type I, the mildest form of the disease. Bisphosphonates represent the prevailing standard of care in patients with OI. Teriparatide (TPD) is a PTH analog with bone-anabolic actions which has been approved for osteoporosis treatment. Thirteen postmenopausal women with type I OI who had been on treatment with neridronate for at least 2 years and who incurred new vertebral fracture during treatment were treated with TPD for 18 months. Bone mineral density (BMD) increased significantly over 18 months up to 3.5 % at the lumbar spine (p = 0.001), while no significant changes were noted in hip BMD. Serum markers of bone formation and of bone resorption increased significantly during the treatment. The Wnt inhibitors serum dickkopf-1 (DKK1) and sclerostin were also measured. A nonsignificant increase was seen in serum sclerostin levels, while serum DKK1 rose gradually and significantly during TPD treatment. In patients affected by type I OI, TPD treatment is associated with a remarkable response in markers of bone formation. This suggests a normal osteoblastic response to TPD. However, the observed increases in BMD were somewhat lower than those in postmenopausal or senile osteoporosis treated with TPD for the same lag time. Our results open the possibility to develop TPD for the treatment of adult type I OI, but particularly for the lack of a control group, a properly designed controlled study is warranted.

Bone formation is influenced by the Wnt pathway through effects on osteoblast functionality, and these actions are opposed by two antagonists: sclerostin and Dickkopf-1 (DKK1). Decreased levels of serum sclerostin were found after treatment with the PTH analogue teriparatide and in patients with primary hyperparathyroidism (PHPT), while treatment with teriparatide of postmenopausal osteoporosis is associated with increases in serum DKK1. We studied mineral metabolism and Wnt pathway in 21 postmenopausal women affected by PHPT and in 42 age-matched healthy women. Mean serum calcium and PTH were significantly higher and serum phosphates significantly lower in the PHPT group compared with the control group. Serum 25-OH-vitamin D (25OHD) was lower in PHPT patients and 1,25 dihydroxy-vitamin D [1,25(OH)2D] was significantly higher. Patients with PHPT had significantly higher levels of bone alkaline phosphatase (BAP) and of serum C-terminal telopeptides of type I collagene (sCTX). Serum sclerostin in PHPT was significantly lower (−26 %) and serum DKK1 significantly higher (+57 %) than in healthy control subjects. Serum PTH was positively correlated with 1,25OH2D (p < 0.001), BAP (p = 0.036), sCTX (p = 0.003), and DKK1 (p = 0.007) and negatively with 25OHD (p = 0.002) and sclerostin (p = 0.02). In PHPT patients, serum sclerostin was negatively correlated with BAP (p = 0.038) and sCTX (p = 0.07). Patients with PHPT have significantly lower sclerostin and higher DKK1 levels compared with healthy postmenopausal control subjects. Further studies are warranted in order to verify whether the balance between these two opposite effects on Wnt function might help explain the variable bone involvement among patients with PHPT.

A number of effective therapies for the treatment of osteoporosis have become available in recent years. However, uncertainty exists regarding their long-term use and effectiveness. Bisphosphonate treatment, unlike hormone replacement, denosumab or teriparatide, is associated with benefits extended even after treatment discontinuation. The extended benefits are most apparent for alendronate (ALN) and zoledronate (ZOL). A drug holiday might be considered in patients at low-moderate risk and who have been fully compliant with treatment, and who have had a response to treatment. In patients at low-moderate risk of fractures the decision to consider a drug holiday should be balanced also with the safety profile of each treatment.

Conditions such as rheumatoid arthritis (RA) and spondyloarthritis (SpA, such as psoriatic arthritis, PsA, and ankylosing spondylitis, AS) are characterized by an imbalance between osteoclast (OC) bone resorption and osteoblast (OB) bone formation. The two conditions present substantial differences in bone involvement, which is probably related to the different expression of IL17 and TNFα, two cytokines that strongly promote osteoclastogenesis and focal bone erosions. TNFα is the major inflammatory cytokine in RA. It acts by both triggering OC bone erosion via the RANK-RANKL system, and suppressing OB bone formation through the overexpression of DKK1, a powerful inhibitor of the WNT bone anabolic signaling pathway. Differing from TNFα, IL17 promotes also osteogenesis, particularly at inflamed sites undergoing mechanical stress, such as entheses. Therefore, in RA, where overexpression of TNFα is higher than IL17, OC bone resorption largely prevails upon bone formation. In PsA and AS, the prevailing inflammatory cytokine is IL17, which promotes also osteogenesis. Given the prevalent involvement of entheses poor of OC, excess bone formation may even prevail over excess bone resorption. The results of clinical trials support the different pathophysiology of bone involvement in chronic arthritis. Inflammation control through anti-TNFα agents has not resulted in incomparable effects on radiographic progression and excess bone formation in both AS and PsA. Clinical trials investigating IL17 inhibitors, such as secukinumab, in patients with psoriatic disease are underway. The preliminary results on inflammation and symptoms appear positive, while long-term studies are required to demonstrate an effect on excess bone formation.

The bone mass benefits of antiresorbers in postmenopausal osteoporosis are limited by the rapid coupling of decreasing bone resorption with bone formation. Wnt signaling is involved in this coupling process during treatment with bisphosphonates, whereas its role during treatment with the anti-receptor activator of NF-κB ligand (RANKL) antibody denosumab is unknown. The study population includes patients participating in a placebo-controlled trial lasting 36 months: 19 women were on placebo and 24 on subcutaneous 60 mg denosumab every 6 months. All measured parameters (serum C-terminal telopeptide of type I collagen [sCTX], serum bone alkaline phosphatase [bAP], Dickkopf-1 [DKK1], and sclerostin) remained unchanged during the observation period in the placebo group. sCTX and bAP were significantly suppressed by denosumab treatment over the entire follow-up. Denosumab treatment was associated with significant (p

Context: Vitamin D deficiency is often treated or prevented by high intermittent doses of vitamin D to achieve a better treatment adherence, but treatment outcomes were contradictory, and even a transient increase in fracture and fall risk was reported. Objective: The objective of the study was to investigate the short-term effects on bone turnover markers of a single bolus of vitamin D3. Design, Setting, Patients, and Intervention: Twelve elderly subjects (eight women, four men; mean age 76 ± 3 yr) were given a single oral bolus of 600,000 IU vitamin D3. Blood samples were taken at baseline and 1, 3, 7, 14, 30, 60, and 90 d after vitamin D3 administration. Twenty-four subjects served as controls. Main Outcome Measures: Changes in serum levels of 25-hydroxyvitamin D (25OHD), 1,25-dihydroxyvitamin D, PTH, C-terminal-telopeptides of type I collagen, cross-linked N-telopeptide of type I collagen (sNTX), osteocalcin, and bone-specific alkaline phosphatase. Results: No relevant changes in 25OHD and bone turnov...

The benefits coming from long-term treatment of postmenopausal osteoporosis with bisphophonates are limited by a coupled decrease in bone formation. The objective of this study is to determine whether this decrease in bone formation is associated with changes in serum levels of the WNT signaling antagonist sclerostin or Dickkopf-1 (DKK1). This is an ancillary observation from patients participating in a 12 months, phase 2, randomized clinical trial. We analyzed 107 patients given either monthly intramuscular neridronate (12.5, 25 or 50 mg) or placebo. Serum C-terminal telopeptide of type I collagen (sCTX, a bone-resorption marker) decreased by 61%, 75% and 73% in the 12.5, 25 and 50 mg dose groups, respectively. Mean changes in bone alkaline phosphatase (bAP) at 12 months were -47%, -60.0% and -52.6% in the groups receiving 12.5, 25 or 50 mg neridronate, respectively. Serum DKK1 remained unchanged at all time points in the 3 groups. Serum sclerostin increased versus placebo group gradually and significantly only in patients treated with 25 or 50 mg neridronate monthly, reaching 138-148% of baseline values (P

In patients with primary hyperparathyroidism (PHPT) not suitable for surgical correction, a skeletal protection with bisphosphonates is considered a reasonable option, but the long-term effects after treatment discontinuation are not well known. Sixty postmenopausal women with PHPT were given 400-600 IU vitamin D(3) daily and 100 mg neridronate IV every 2 months for 2 years with 2 additional years of follow-up without antiresorptive therapies. Bone mineral density (BMD) progressively rose by 6.7 ± 7.6% (SD) and by 2.9 ± 4.5% at the spine and femoral neck, respectively. During follow-up, mean BMD progressively fell, but after 2 years it was still 3.9 ± 5.5% higher than baseline values at the spine. Bone alkaline phosphatase and serum C-telopeptide of type I collagen decreased significantly within 6 months (28 and 49% versus baseline, respectively) and rose to baseline values within 6-12 months during follow-up. Serum PTH significantly rose from baseline during treatment, but it remained significantly higher than baseline during follow-up. The PTH changes were significantly correlated with serum 25-hydroxyvitamin D (25OHD) levels. In conclusion, in this study we observed that in patients with mild PHPT treatment with bisphosphonates is associated with the expected changes in bone-turnover markers and that the significant increases of both hip and spine BMD are partially maintained for at least 2 years after treatment discontinuation at the vertebral site. The marked increases in serum PTH levels, particularly in subjects with low 25OHD levels, persist after treatment discontinuation and this raises the suspicion that this might reflect a worsening of PHPT.

Neridronic acid (6-amino-1-idroxyesilidene-1,1-bisphosphonate) is a nitrogen-containing bisphosphonate licensed in Italy for the treatment of osteogenesis imperfecta and Paget's disease of bone. The pharmacodynamic profile is similar to that of other nitrogen-containing bisphosphonates and is characterized by its high affinity for bone tissue particularly at sites undergoing a process of remodeling. In growing children affected by osteogenesis imperfect, neridronic acid rapidly increases bone mineral density as measured by dual X-ray absortiometry and this is associated with a significant decrease in fracture cumulative number. Similar results have been obtained also in newborns (12 month old) and in adult patients. In Paget's disease of bone, 200 mg intravenous neridronic acid is associated with a 65% rate of full remission and a biochemical response (decrease of75% of bone turnover markers) in 95% of the patients. Neridronic acid treatment has been reported to be effective also in other skeletal diseases such as osteoporosis, algodystrophy, hypercalcemia of malignancy and bone metastasis. Neridronic acid has been developed only for parenteral use, and it is the only one used as intramuscular injection. This avoids all the limitations of oral bisphosphonates and may be offered for a home treatment with simple nursing assistance.

Background Vitamin D deficiency is very common in elderly people while there are very few reports on its incidence, determinants and metabolic consequences in young subjects. Results In 608 young healthy premenopausal women participating in the BONTURNO study, levels of 25-hydroxyvitamin D [25(OH)D] below 20 ng/ml were found in almost a third of the women. Its levels were inversely ( P 2 ) and directly with sunlight exposure during the summer time, and latitude: i.e. the higher the latitude over Italy, the higher the 25(OH)D level. In women on contraceptive pill the mean 25(OH)D level was significantly increased even when the data were adjusted for age, BMI and sun exposure. 25(OH)D levels, adjusted for age and BMI, were significantly and positively related with serum C-telopeptide of type 1 collagen, serum phosphate and spine bone mineral density (BMD) and negatively with serum PTH, serum magnesium, serum bone alkaline phosphatase (bone AP). Conclusion Vitamin D deficiency is rather common in young otherwise healthy Italian women and particularly among those living in the Southern part of the country. The most close determinants of vitamin D deficiency were BMI and sunlight exposure. Vitamin D insufficiency is associated with low spine BMD and increased bone AP even in young individuals.

L’osteogenesi imperfetta comprende un gruppo di patologie ereditarie del collagene di tipo I che si esprime clinicamente con fragilita ossea e fratture ricorrenti. L’unica terapia che abbia dimostrato di essere in grado di ridurre significativamente l’incidenza di nuove fratture sono i bisfosfonati. Il neridronato e l’unico bisfosfonato registrato al momento in Italia per l’osteogenesi imperfetta.

Anorexia nervosa (AN) is a life-threatening eating disorder characterized by an inability to maintain a normal body weight and amenorrhoea, often associated with osteoporosis and increased risk of fragility fractures. Bone metabolism, including markers of bone turnover (serum total alkaline phosphatase, bone alkaline phosphatase [bone AP], osteocalcin [OC] and type I collagen C-telopeptide breakdown products [sCTX]) and bone mineral density (BMD) by dual energy X-ray absorptiometry (DXA) at the spine and at the hip, were evaluated in 55 consecutive women with AN undergoing a 3-month intensive nutritional rehabilitation program. The control group was constituted of 25 healthy young medical students. In AN patients body weight increased during the 3-month nutritional program from 37.8+/-5.1 (mean+/-SD) to 51.5+/-4.5 kg. The corresponding BMI rose to values17.5 kg/m(2) in all patients. Mean BMD significantly rose by 2.6+/-3.5% and 1.1+/-3.6% at the hip and at the spine, respectively. The markers of bone formation, serum bone AP and osteocalcin, significantly rose by two-folds, while sCTX decreased by 16%. The changes in hip BMD were positively related (p0.005) to changes in body weight and in bone AP (p0.02) while the changes in spine BMD were positively related to changes in serum osteocalcin (p0.05). In the 25 patients who attended the 12-month posttreatment control, mean body weight significantly decreased by 3.6+/-6.0 kg and this was not associated with any significant change in BMD values. In the patients in whom BMI fell again below 17.5 kg/m(2) hip BMD values decreased significantly. On the contrary, in the patients who maintained BMI17.5 kg/m(2), BMD values continued to rise up to values over the 15-month observation of 4.8+/-6.2 and 7.1+/-12.1 at the spine and hip, respectively. In conclusion, we have demonstrated that substantial gains in weight in women with chronic AN are associated with remarkable increases in BMD at both the hip and the spine. If weight is maintained, the overall improvement approach 1 SD within 1 year. The changes in both weight and BMD are correlated with improvements in bone formation markers and diminutions in a marker of bone resorption.