INTRODUCTION:Bisphosphonates (BPs) have consistently yielded positive results in the treatment of Complex Regional Pain Syndrome (CRPS). However, biochemical and histopathological evidence suggests that osteoclasts, the primary pharmacological target of BPs, is not a key driver in the early pathogenetic steps of CRPS. METHODS:To critically review and integrate current evidence on pharmacological mechanisms of action of BPs in CRPS and to propose unifying hypotheses explaining their clinical efficacy beyond antiosteoclastic activity. Literature from in vitro studies, animal models, and randomized clinical trials was integrated. Approximately 80 primary and review articles were critically reviewed. EXPERT OPINION:BPs efficacy in CRPS is best explained by a bone-driven pharmacological model by which local drug accumulation is achieved in the site of disease. This enables modulation of inflammatory and nociceptive processes on adjacent non-bone cells, including macrophages, neutrophils, keratinocytes, and nociceptive fibers. Inhibition of the mevalonate pathway in these cells may reduce inflammatory cytokines, nerve growth factor (NGF), and reactive oxygen species (ROS), while modulating nociceptive signaling pathways. Additional mechanisms, including modulation of vascular tone and neuropeptide signaling, may further contribute to therapeutic effects. This hypothesis may inform optimal treatment strategies and together improve understanding of CRPS pathophysiology.

Background: Chronic nonbacterial osteomyelitis (CNO) is an autoinflammatory noninfectious disease of the bone that predominantly affects children and adolescents. Bisphosphonates (BPs) are used to treat of CNO with most clinical experience involving pamidronate. Neridronate (NER) is an amino BP with a chemical structure and potency close to pamidronate. Objectives: This study aims to evaluate the effectiveness and safety of NER in patients with CNO. Design: Monocentric retrospective cohort study. Methods: This is a retrospective cohort study conducted on patients included in the monocentric CAMELOT (Chronic non-bActerial osteoMyELitis: A mOnocentric regisTry) registry. Response to treatment was evaluated semiquantitatively based on clinical, laboratory, and radiological domains. Results: The cohort consisted of 27 subjects. Thirteen (48%) received NER alone. At baseline, patients receiving NER alone tended to have a higher rate of vertebral fractures than those treated with combination therapy (46% vs 29%; p = 0.4). The median number of peripheral lesions at magnetic resonance imaging was clearly lower in patients treated with NER alone (0 (interquartile range (IQR) 0–2) vs 2 (IQR 1–5); p = 0.01). An overall response (complete or partial) to NER was documented in all but one patient (96%). Six patients (22%) achieved a complete response in all the three domains, 83% of whom ( n = 5) received NER without any other concomitant treatments. Interestingly, using a Receiver Operating Characteristic-derived cutoff of 2 years from CNO diagnosis, all patients who achieved a complete response (100%) had received NER within the first 2 years from diagnosis, compared with 57% ( n = 12) of those who did not ( p = 0.07). No long-term NER complications were observed. Conclusion: Neridronate appears to be a safe and effective option for CNO, particularly in patients with recent-onset disease, spinal involvement, and fewer peripheral lesions. Early initiation may be associated with higher rates of complete response, though further studies are needed to confirm these findings.

This study aimed to investigate the relationship between Osteoporosis (OP) and Complex Regional Pain Syndrome type 1 (CRPS-1), in the hypothesis that OP can influence the epidemiological and clinical features of CRPS-1. From March 2013 to May 2024, consecutive patients newly diagnosed with CRPS-1 were recruited. Demographic and clinical variables were collected in a standardised fashion. Univariate analyses and multivariate linear regression models were used to investigate the sample. We enrolled 425 patients, mostly females (70.1

Background: Evidence on the safety of intravenous neridronate (IV NER) in children with conditions other than osteogenesis imperfecta (OI) remains limited. This retrospective study describes adverse events, including acute phase reactions (APR) and hypocalcemia, over a median follow-up of 20 months in a monocentric pediatric cohort with rheumatological conditions. Methods: Thirty-seven children with OI and other bone diseases undergoing infusion of IV NER were included. Clinical, demographic, and serologic data were recorded. Results: The most common side effect was APR (62%), which occurred less frequently in patients on chronic oral cholecalciferol supplementation: 43% of the 14 patients who did not experience APR were supplemented, while none of the 23 subjects who developed APR received supplementation ( p = 0.001). Conversely, pre-infusion 25-dihydroxycholecalciferol and calcium levels did not differ between patients who experienced APR and patients without APR (24.23 ± 12.96 vs 27.56 ± 11.81 ng/mL, respectively; p = 0.496). Premedication with prednisone does not seem to be effective in the prevention of APR. Hypocalcemia was rare and asymptomatic in all cases. Conclusion: NER appears safe across different pediatric conditions, with predictable first-infusion reactions. The role of vitamin D and premedication in children candidate to NER infusion should be further confirmed in larger cohorts.

Background:Chronic non-bacterial osteomyelitis (CNO) is a rare autoinflammatory disease characterized by bone pain and sterile bone inflammation. Objectives:This study aimed at describing clinical presentation, laboratory and imaging features, densitometric assessment, and therapeutic approaches in a monocentric CNO cohort. Design:Monocentric retrospective cohort study. Methods:Patients were included in the Chronic non-bActerial osteoMyELitis: A mOnocentric regisTry (CAMELOT) in case of (i) clinical diagnosis of CNO, (ii) the fulfilment of diagnostic/classification criteria, (iii) at least one medical visit at our institution between June 2004 and June 2024, and (iv) a follow-up of at least 3 months. Results:Fifty-one patients were included in the CAMELOT (mean age at onset 11.14 years, 68.6% females). A total of 39.2% of patients presented an autoimmune comorbidity. Bone pain was invariably present; joint involvement was demonstrated in 9.6% of patients. Most subjects (86.3%) had multifocal disease: the median number of bony lesions per patient was 4. Lumbar spine dual-energy X-ray absorptiometry (DXA) was performed in 14 patients (27.4%), showing a reduced bone mineral density (BMD) (-1.14 ± 1.21 Z-score). A total of 18 patients (35.3%) experienced a fracture on a bony lesional site; 14 patients (27.4%) presented vertebral fractures (VFs) at onset, with multiple VFs in 5 cases (35.7%). BMD Z-scores (-1.7 vs -0.5) were lower in patients with VFs, with a higher rate of "low BMD for age" (37.5% vs 16.7%) compared to patients without VFs. Conclusion:The high prevalence of VF observed in the CAMELOT cohort highlights the importance of enlisting CNO in the diagnostic approach to pediatric patients presenting with VF.

OBJECTIVE:To date, there is no shared national guideline in Italy for the management of reproductive health in rheumatic diseases (RHRD). The Italian Society for Rheumatology (SIR) has committed to developing clinical practice recommendations to provide guidance on both management and treatment regarding RHRD in Italy. METHODS:Using the GRADE-ADOLOPMENT methodology, a systematic literature review was conducted to update the scientific evidence that emerged after the publication of the reference recommendations from the American College of Rheumatology. A multidisciplinary group of 18 clinicians with specialist experience in rheumatology, allergy and clinical immunology, internal medicine, nephrology, gynecology and obstetrics, and neonatology, a professional nurse, a clinical psychologist, and a representative from the National Association of Rheumatic Patients discussed the recommendations in collaboration with the evidence review working group. Subsequently, a group of stakeholders was consulted to examine and externally evaluate the developed recommendations. RESULTS:Recommendations were formulated for each area of interest: contraception, assisted reproductive technology, preconception counseling, and use of drugs before, during, and after pregnancy and during breastfeeding, considering both paternal and maternal exposure. CONCLUSIONS:The new SIR recommendations provide the rheumatology community with a practical guide based on updated scientific evidence for the management of RHRD.

Contrary to popular belief, a recent study did not show increased osteoclastic activity in acute complex regional pain syndrome. Conversely, osteoblastic activity seems to be enhanced. The real meaning of diagnostic tools needs to be reassessed. Therefore, bisphosphonates act through mechanisms of action different from their anti-osteoclastic effect. INTRODUCTION:Bone tissue involvement is a widely acknowledged event in the course of complex regional pain syndrome (CRPS), and it is invariably depicted as "high turnover osteoporosis." This statement needs to be revised in light of a recent biochemical study on bone turnover markers and regulators in patients with early CRPS. METHODS:The real meaning of the findings arising from biochemical, radiological, and histopathological studies and the possible mechanism of action of parenteral bisphosphonates have been reviewed according to the bone metabolism derangement specific to this disease. RESULTS:Consistent with the results of the recent biochemical study, no reliable data emerge from diagnostic studies sustaining an increased osteoclastic activity. Conversely, osteoblastic activity seems to be enhanced for an increased Wnt signaling due to lower levels of Sclerostin and Dickkopf-1. These results may provide a different and alternative interpretation of previous diagnostic and therapeutic studies. CONCLUSIONS:For the emerging role of bone in CRPS pathogenesis, these remarks could be useful for improving knowledge of the pathophysiology of the disease.

Despite the advancements achieved in modern rheumatology, patients with pediatric-onset rheumatological diseases are still exposed to systemic and/or articular inflammation and corticosteroid treatment, all exerting detrimental effects on the growing skeleton together with the reduced body weight and scarce physical activity that rheumatological patients usually experience. The assessment of bone mass in pediatric subjects carries computational limitations: Dual energy X-ray Absiorptiometry (DXA) underestimates bone mineral density (BMD) especially in case of smaller bone, an instance that occurs frequently in children with rheumatologic conditions due to the high rate of short stature or pubertal delay. The rates of low BMD in juvenile idiopathic arthritis (JIA) patients range between 3 % and 34 %, being higher in systemic and polyarticular JIA; patients with juvenile onset systemic lupus erythematosus (jSLE) present a low BMD in approximately 1/3 of cases. Such reduction in BMD presents early on disease course, persists with aging but might be reversed by rheumatological treatment. In pediatric populations, the term osteoporosis should be reserved to children with clinically relevant fractures, favoring "low BMD for chronological age". The prevalence of vertebral fractures ranges between 10 % and 30 % in JIA, peaking in female JIA patients aged 10-15 years, and between 21.4 % and 52 % in jSLE. While calcium and vitamin D supplementation should be optimized in all pediatric patients with rheumatological conditions, bisphosphonates should be reserved to subjects with fragility fractures; the prescription for primary fracture prevention in glucocorticoid-treated children is recommended only in case of a dosage <0.1 mg/kg/day for at least 3 months.

Objective. In the absence of national and European guidelines on the treatment of rheumatoid arthritis (RA) with interstitial lung disease (ILD), the Italian Society of Rheumatology decided to develop national clinical practice guidelines on the management of patients with RA-ILD in accordance with the requirements of the National Guideline System of the National Institute of Health. Methods. The development process included a systematic review of the available evidence and its adaptability to the Italian context, followed by a consultation with experts in rheumatology, respiratory diseases, radiology, and representatives of the health professions and patients. Results. The panel decided to develop recommendations in three main scenarios. The first section of recommendations is focused on drugs indicated for RA to assess their safety and efficacy in RA-ILD. The second set of recommendations covered the drugs indicated for the treatment of ILD in patients with RA-ILD (to assess their efficacy and safety in patients with RA). The third part of these guidelines dealt with drugs indicated for the treatment of RA-ILD upon first-line failure. Moreover, the lack or absence of scientific evidence in literature on certain topics, such as the value of a multidisciplinary treatment approach and lung transplantation, led to the decision to proceed through expert consensus to develop good clinical practice guidelines. Conclusions. These guidelines represent a fundamental step towards improving the health management of patients with rheumatological diseases in Italy by providing specific and evidence-based guidelines for the management of RA-ILD. Their use is intended to promote health and reduce the burden of morbidity and mortality in this vulnerable population.

L’algodistrofia, attualmente denominata Complex Regional Pain Syndrome di tipo 1, è una patologia a distribuzione regionale caratterizzata da intensa sintomatologia dolorosa, sproporzionata per intensità e durata rispetto a quanto atteso rispetto all’evento scatenante, cui si associano alterazioni sensitive, motorie, vascolari e dei tessuti molli. La presenza e l’intensità di tali manifestazioni si configurano in modo variabile nei diversi pazienti e tendono tipicamente a modificarsi nel tempo. La diagnosi precoce e il trattamento farmacologico adeguato evitano i danni anatomici e funzionali irreversibili che ne possono derivare.

Background: Over the last two decades, treatment strategies for PsA have dramatically improved thanks to the application of treat-to-target and personalized medicine concepts and the introduction of new drug classes such as biologic and targeted-synthetic disease-modifying anti-rheumatic drugs (b/tsDMARDs). The clinical heterogeneity, the multiorgan involvement, and the comorbidities associated to psoriatic arthritis (PsA) are elements that contribute to the complexity of its management, despite the recent expansion in therapeutic options. To date, a true official definition of a D2T PsA has not yet been elaborated by the international scientific societies and the only attempt so far has been to translate the criteria established for D2T RA also to PsA, to produce a preliminary definition [1]. Objectives: The aim of our work is to identify the prevalence of difficult-to-treat (D2T) PsA patients from a monocentric cohort according to the definition proposed1 and to further characterize patients’ features associated with an increased difficultness of treatment. Methods: 267 consecutive, adult PsA patients treated with b/tsDMARDs were enrolled in our study. We collected demographic, clinical and clinimetrical data for each patient. According to the proposed definition1, we derived the prevalence of D2T PsA patients from our cohort. Then, we calculated the number of failed b/tsDMARDs normalized by the expected number of failed b/tsDMARDs considering the follow up time for each patient. Patients with a higher difficultness-to-treat were defined by a ratio of observed and expected failed drugs (OBS/EXP) > 1. Using the OBS/EXP ratio as the response variable and clinical and demographic characteristics as independent variables, a generalized linear model with Poisson distribution was applied to explore potential features associated with difficultness-to-treat. A univariate analysis with Wald statistics followed by a multivariate analysis highlightened the difficultness-to-treat prediction model according to patients’ features. To pursue the robustness of the selection of the covariates, a bagging procedure was applied. First, a backward variable selection based on the Akaike Information Criterion (AIC) was performed on a bootstrap of 1000 samples. Then, the regression coefficients’ mean from each sample was calculated to perform a sufficiently robust prediction of the OBS/EXP ratio for each patient. Results: Among the 267 enrolled patients, only 8 (2.9%) satisfied the proposed D2T PsA criteria1 (Table 1). Following the application of the predictive model to 177 patients, 46 of them (26%) showed a higher difficultness-to-treat (OBS/EXP>1). At the univariate analysis, female sex (p=0.037), psoriasis pattern (p=0.05), presence of fibromyalgia (p=0.01), and steroid therapy (p<0.001) were associated with higher difficultness. The association between fibromyalgia, nail and pustular psoriasis, and steroid use was confirmed at the multivariate analysis (Figure 1). Conclusion: The proposed definition of D2T PsA patients [1] seems to capture only a small proportion of the prevalent patients with a higher difficultness-to-treat, as defined by a statistical predictive model. These data may provide a clue for possible criteria in the definition of D2T PsA. REFERENCES: [1] Perrotta FM, Scriffignano S, Ciccia F, Lubrano E. Clinical Characteristics of Potential “Difficult-to-treat” Patients with Psoriatic Arthritis: A Retrospective Analysis of a Longitudinal Cohort. Rheumatol Ther. 2022;9(4):1193-1201. doi:10.1007/s40744-022-00461-w Acknowledgements: NIL. Disclosure of Interests: None declared.

Hypophosphatasia (HPP) is a rare disorder of the bone metabolism, characterized by genetically determined low alkaline phosphatase (ALP) activity. Low ALP may also be observed in some common causes of bone fragility, such as in osteoporosis treated with antiresorptive drugs. This study aimed to verify whether differences in bone turnover markers (BTMs) could help differentiate adult patients with HPP from those with osteoporosis undergoing antiresorptive treatment. In this multicenter study, we enrolled 23 adult patients with a diagnosis of HPP and compared them with 46 osteoporotic subjects previously treated with zoledronic acid or denosumab. BTMs such as CTX, N-terminal propeptide of type I procollagen (P1NP), total ALP, and bone ALP (bALP) were measured, and ratios between BTMs were also calculated. Considering that the control group included only females, in the primary analysis we compared their characteristics with that of the 16 female patients with HPP. Both individual BTMs (CTX and P1NP) and 4 BTM ratios (ALP/P1NP, bALP/P1NP, ALP/CTX, and bALP/CTX) showed satisfactory discriminatory power, outperforming ALP alone. P1NP, in particular, had an area under the curve (AUC) of 0.962 with a cut-off of 32 μg/L, while as for the BTMs ratios, the ALP/P1NP ratio had an AUC of 0.964 with a cut-off of 1.114. Similar results were confirmed when including male HPP patients, when adjusting for age and sex, and finally when performing a sensitivity analysis only in patients with ALP less than or equal to 32 U/L (ie, the median of the distribution of the entire population). In cases of low ALP and bone fragility, BTM and their ratios could help distinguish HPP patients from osteoporotic individuals treated with antiresorptive drugs, aiding in accurate diagnosis and reducing the risk of inappropriate treatment.

To explore serum levels of some bone turnover markers and the involvement of the Wnt signaling in CRPS-1. Query ID="Q1" Text="Please check and confirm whether the edit made to the article title is in order." We conducted an observational study on patients with early CRPS-1 recruited before any treatment. Clinical measures were assessed together with biochemical evaluation. Values of sclerostin, DKK1, CTX-I, and P1NP were compared with sex-age-matched healthy controls (HCs). We enrolled 34 patients diagnosed with CRPS-1 (mean age 59.3 ± 10.6 years, Male/Female 10/24), median disease duration = 2 weeks (IQR 1–5); median VAS score = 76 (IQR 68–80). Foot localization was slightly more frequent than hand localization (18/16). No statistically significant difference was found between CRPS-1 patients and HCs for CTX-I (0.3 ± 0.1 ng/ml vs 0.3 ± 0.1, p = 0.140), while mean serum values of P1NP were significantly higher in CRPS-1 patients compared to HCs (70.0 ± 38.8 ng/ml vs 50.1 ± 13.6, p = 0.005). Mean levels of sclerostin and DKK1 were lower in CRPS-1 patients vs HCs (sclerostin 28.4 ± 10.8 pmol/l vs 34.1 ± 11.6, p = 0.004; DKK1 12.9 ± 10.8 pmol/l vs 24.1 ± 11.9, p = 0.001). No statistically significant difference was found for all biochemical assessments in a subgroup of fracture-induced CRPS-1. No statistically significant differences were observed according to disease localization, disease duration, presence of hyperalgesia, allodynia, sudomotor alterations, and mild or moderate/severe swelling. No significant correlation emerged between sclerostin, DKK1 levels, baseline VAS score, or McGill Pain Questionnaire score. Bone involvement in early CRPS-1 does not seem to rely on increased osteoclast activity. Conversely, a serum marker of bone formation resulted increased. Both Sclerostin and DKK1 showed decreased values, probably suggesting a widespread osteocyte loss of function. Trial registration number: Eudract Number: 2014-001156-28

Background: Complex Regional Pain Syndrome type 1 (CRPS-1) is severely debilitating and painful disease that is difficult to treat. Objective: The objective was to evaluate the long-term residual disability of patients with CRPS-1 following parenteral neridronate treatment. Design: This is real-life retrospective observational study. Methods: Patients affected by CRPS-1 of the upper limb were treated with neridronate infusions (400 mg over 10 days) between February 2017 and December 2021 for whom clinical and demographic information was collected. From November 2022, patients treated >= 1 year previously were recalled for clinical evaluation. A dedicated instrument (DASH questionnaire, Disabilities of the Arm, Shoulder and Hand) was employed to assess residual disability. Multivariate logistic regression analysis was used to investigate predictors of disability. Results: Forty-nine patients aged 61.1 +/- 11.5 years and 73.5% female with CRPS-1 of the upper limb were included. Disease duration before treatment was 9.9 +/- 8.0 weeks, and the mean length of follow-up was 4 years (47.7 +/- 22.0 months). The disease had fully resolved in 46 patients (93.9%) for whom the diagnostic criteria were no longer recognized. According to the DASH score, 38 patients (77.6%) resulted free of functional limitations, whereas 11 patients (22.4%) were still suffering from disability. The DASH score was positively correlated with residual visual analogue scale (VAS; Spearman's Rho = 0.61; P < .001). Predictors of residual disability were younger age (odds ratio [OR]: 0.77, 95% CI: 0.63-0.93; P = .012) and delay between disease onset and treatment (OR: 1.45, 95% CI: 1.13-1.96; P = .004). Conclusions: In this real-life study, neridronate parenteral treatment provided a full recovery of CRPS-1 in over 3 quarters of patients, provided they are treated early.

Background: Early induced surgical menopause due to bilateral oophorectomy (OPX) is considered a risk factor for the occurrence of osteoporosis (OP). Namely, it is a result of acute and remarkable reduction in ovarian function. There may be differences between induced surgical menopause and spontaneous menopause regarding the residual ovarian function in producing hormones with estrogenic activity. Objectives: In this monocentric, cross-sectional, retrospective study we evaluate if surgical menopause could be considered an additional risk factor compared with spontaneous menopause toward OP and fragility fractures (FFx). Methods: We retrospectively included patients from January 2016 to December 2023. Surgically induced menopausal female were compared using randomized-selection case-control methodology with a control group consisting of women matched for age (±1 yr) -Group 1- and age (±1 yr) and age of spontaneous menopause (±1 yr) -Group 2- in 1/3 ratio. All included subjects had never taken any anti-osteoporotic drugs or were taking drugs interfering bone metabolism. Densitometric evaluation was performed at lumbar level (L1-L4, Hologic DelphiW). Comparisons were performed by T test and chi-square test. Logistic regression analysis was used to analyze variables influencing the odd of OP and FFx. All patients have signed informed consent. Results: From a sample of 1018 surgical induced menopause women, 531 women who had OPX induced menopause at their first lumbar densitometric evaluation were selected (mean age 55.0±5.8 yrs; mean age at menopause 45.5±4.4 yrs) and compared to 1593 controls. Women who had taken osteometabolic therapies (n=128), hormone replacement therapy (n=246), women who had OPX for tumor or with missing data certifying bilateral OPX or taking other drugs which interfere with bone metabolism (n= 113) were excluded. OPX group and control group were homogeneous for ages of estrogen exposure, calcium intake, parity, physical activity, BMI, and smoke. 200 FFx were reported among groups, and distal radius Fx and vertebral Fx were the most frequent FFx among all groups. OPX group had significantly more Fx at forearm (p<0.001), rib (p=0.04), other (humerus, tibia, foot, pelvis, p<0.001).Comparing OPX patients with Group 1, OPX patient had significantly more OP and Fx (p=0.001). Stepwise multiple logistic regression analyses for OP showed that in addition to age, BMI, and calcium intake, OPX exerted a statistically significant risk for OP (OR 2.19 confidence interval (CI) 1.94-2.47) and FFx (OR 1.64, CI 1.33-2.01). The age at which OPX occurs significantly influences the risk of OP (9% for each year less of estrogenic exposure) than the risk of FX (10% for each year less of estrogenic exposure). Univariate analysis comparing OPX patients with Group 2, did not found any significantly differences among variables influencing bone mass (i.e. age of menarche, parity, BMI, physical activity, calcium intake, smoke). Prevalence of OP (37.5%) and FFx (9.9%) were similar among OPX and Group 2. Stepwise multiple logistic regression analyses for OP and FFx risk did not confirm OPX as independent predictive factor. Conclusion: The results of this study show that OPX is definitely a risk factor for OP and FFx, but it is not an additional risk factor to spontaneous premature menopause. In the absence of adequate therapeutic treatment represented by HRT, the age at which subjects undergo OPX is the variable that best correlates with the risk of OP and FFx. REFERENCES: NIL. Acknowledgements: NIL. None Disclosure of Interests: None declared.

Background: Patients with psoriatic arthritis (PsA) have a higher risk of cardiovascular disease compared to the general population. This is due to the higher prevalence of traditional cardiovascular risk factors, including hypertension, obesity, metabolic syndrome, and dyslipidemia, as well as chronic inflammation, treatment with nonsteroidal anti-inflammatory drugs, and glucocorticoids. Thus, evaluating an appropriate cardiovascular risk score in this population is crucial. Nonetheless, a calculating tool specific to PsA is not available, and international societies recommend using general population-derived CV risk scores. Risk calculation also plays a central role in patient-specific treatment guidelines, as per the latest European Medicines Agency (EMA) restrictions on the Janus kinase inhibitors (JAKi) use. Objectives: To evaluate the impact of the Expanded Cardiovascular Risk Score (ERS), originally developed for rheumatoid arthritis (ERS-RA), to assess and identify patients with PsA at high cardiovascular risk, and to determine its effect on the eligibility for JAKi treatment according to EMA recommendations. Methods: We conducted a monocentric retrospective analysis of an Italian single-center cohort of patients recruited from September 2022 to June 2023 with PsA treated with second-line therapies. Patients were considered ineligible for JAKi if they met the EMA criteria, which include being over 65 years, having a current or past smoking history, having an increased risk of major adverse cardiovascular events (MACE), or having malignancy risk factors. The MACE risk was defined according to ORAL Surveillance trial inclusion criteria fulfillment (ORALSURV) or as >10% in 10 years by ERS score (ERS-PsA), alternatively. As a surrogate for disease activity, in the ERS score we replaced the Clinical Disease Activity Index/Simple Disease Activity Index (CDAI/SDAI) used in RA with the Disease Activity in Psoriatic Arthritis (DAPSA) score. Results: Out of the 369 adult patients with PsA, 163 were identified as having an increased cardiovascular risk based on the ORALSURV inclusion criteria and 98 based on the ERS-PsA criteria. Using these definitions of cardiovascular risk, 229 patients would have been ineligible for JAKi therapy according to EMA-ORALSURV and 174 to EMA-ERS-PsA. Among these 174 patients, most (n=92, 52.9%) were ineligible for only one risk factor, while a minority for 2 (n=62, 35.6%) or 3 or more (n=20, 11.5%) risk factors. Evaluating patients with a single risk factor, 54 (58.7%) were smokers, 18 (19.6%) had an increased cardiovascular risk, 15 (16.3%) were over 65 and 5 (5.4%) had a history of malignancy. Using EMA-ORALSURV criteria, patients ineligible for JAKi therapy for only one risk factor were 134 (58.5%), and among these 73 (31.9%) only for the cardiovascular risk. At the time of our analysis, 9 patients were on JAKi therapy, with one as first-line and 5 refractory to more than two previous mechanisms of action. Five patients were ineligible for JAKi therapy according to PRAC-ORALSURV, and 4 according to PRAC-ERS-PsA (Figure 1, Table 1). Conclusion: In our cohort, only a small percentage of patients were treated with JAKi therapy at the time of recruitment, regardless of cardiovascular risk. This may be attributed to the recent approval of JAKi use in psoriatic arthritis and the impact of the EMA recommendations on drug prescription in February 2022. However, when applying the ERS-PsA criteria instead of the ORALSURV criteria to calculate cardiovascular risk, the proportion of patients who are ineligible for JAKi therapy decreases. This could be explained by the more stringent criteria in the latter. Considering the absence of a designated CV score for PsA, ERS-PsA could potentially be a viable alternative that warrants validation and implementation in clinical settings. REFERENCES: NIL. Acknowledgements: NIL. Disclosure of Interests: None declared.

Background Prevalence of osteoporosis (OP) and fractures (Fx) in spondyloarthritis (SpA) is frequently overlooked[1]. Axial (ax-) involvement, particularly in ankylosing spondylitis (AS), is associated with seeming increased lumbar spine bone mineral density (BMD) while vertebral fractures are present in up to 43% of patients with AS. Bone densitometry is considered the gold standard for osteoporosis diagnosis and fracture risk assessment. Objectives To investigate predictors of OP and prevalence of Fx in a population of ax-SpA patients. Methods Data were cross-sectionally extracted from a monocentric registry including SpA patients with axial involvement [AS, ax- Psoriatic Arthritis (ax-PsA), non-radiographic ax-SpA (nr-axSPA), IBD associated-SpA] at their last evaluation in a tertiary rheumatology center between August and December 2022. Comparisons were performed by T test and chi-square test; logistic regression was used to analyze the predictors of OP screening assessed by dual-energy x-ray absorptiometry (DXA) and other collected variables. Results The overall population included 385 patients (35.6% female; mean age±SD 48.5±12.7 yrs; 42.9% AS, 33% nr-axSpA, 20.5% ax-PsA, 3.6% IBD-SpA; 43.9% HLAB27 positive; 42.3% postmenopausal females; 7.8% patients with previous diagnosis of OP). Almost 10% of the entire population experienced Fx (n=38): 16 vertebral Fx, 2 femoral Fx, and 24 non-vertebral/non femoral Fx. The presence of previous fragility Fx was significantly associated with menopause (39% vs 12.4%, p<0.001), older age (56.6±10.11 vs 47.6±12.65, p<0.001), elevated ESR (median 13 mm/h (IQR 7-24) vs 9 (5-19), p=0.04) and higher ASDAS-CRP (median 1.28 (1-2.6) vs 1.05 (0.6-1.7), p=0.03), and previous OP diagnosis (50% vs 3.1%, p<0.001). DXA was performed only in 11.7% of the population. DXA was mainly performed in females (64.5% vs 31.8%, p<0.001), post-menopausal women (57.8% vs 9.4%, p< 0.001), older patients (58.6±12.5 vs 47.2±8.9, p<0.001), patients with previous diagnosis of disthyroidism (11.1% vs 4.7%, p=0.08), OP (53.4% vs 1.8%, p<0.001), patients with previous Fx (46.7% vs 5%, p<0.001), both vertebral Fx (26.7% vs 1.2%, p<0.001) and non-vertebral/non femoral Fx (24.5% vs 3.9%, p<0.001). DXA was significantly more frequently performed in patients supplemented with vitamin D (86.7% vs 29.4%, p<0.001), calcium (53.4% vs 4.1%, p<0.001), and receiving bisphosphonate therapy (26.7% vs 1.8%, p<0.001) or on bone loss inducing drugs (44.4% vs 21.3, p=0.001). DXA was significantly less frequently evaluated in current smokers (1.5% vs 24.7%, p=0.04) and ax-PsA subtype (8.9% vs 22%, p=0.04). Factors associated with OP screening by DXA were menopause [OR 17.8, 95% CI 2.3-135, p=0.005], and bone loss inducing drugs (OR 3.2, 95% CI 1.12-9.16, p=0.030). Predictor of Fx was the presence of elevated disease burden expressed as ASDASCRP (OR 1.9, 95% CI 1.2-3.2, p=0.012). Conclusion Our data confirm that OP is an underestimated comorbidity in axSpA patients, particularly males or younger patients. Fragility Fx is related with disease burden, confirming that inflammation mostly triggers bone loss. Not all risk factors for OP are correctly addressed, such as active smoke. We should aim to better evaluate OP as a SpA comorbidity to early detect patients at high risk of fragility Fx to treat them properly. References [1]Magrey MN et al, Curr Rheumatol Rep. 2017;19:17. [2]Walsh JA et al, Clin Rheumatol. 2018;37:1869–1878. Acknowledgements: NIL. Disclosure of Interests None Declared.

Background The multifaceted nature of psoriatic disease can potentially make its skin, articular, and extra-articular manifestation complex to manage.Biologic disease modifying anti-rheumatic drugs (bDMARDs) have dramatically improved the outcome of patients affected by chronic inflammatory arthritis. However, a satisfactory disease control is not achieved in a proportion of patients.While a “difficult-to-treat” (D2T) definition has been validated in rheumatoid arthritis (RA), it was only recently suggested for psoriatic arthritis (PsA) [1]. Objectives Based on the proposed definition, we aimed to assess prevalence and characteristics of D2T-PsA in a single-center cohort. Methods We conducted a single-center, cross-sectional study. 269 consecutive, adult PsA patients receiving bDMARDs at a tertiary care, dedicated outpatient clinic were enrolled.Demographic, clinical, and clinimetric data, and the Health Assessment Questionnaire (HAQ) were gathered and depicted in Table 1.According to the aforementioned definition, D2T patients were identified as: 1) failure of ≥ 2 b/tsDMARDs (with different mechanisms of action- MoA) after failing csDMARD therapy; 2) signs suggestive of active/progressive disease (defined either as a DAPSA >14 or not achieving MDA; signs or symptoms suggestive of active disease; a rapid radiographic progression; a reduction of quality of life due to PsA symptoms); 3) disease management perceived as problematic by rheumatologists or patients (all three criteria must be met to define D2T patients).Comparison between D2T and non-D2T patients was performed with univariate analyses. Results Among 269 PsA patients, only 8 (2.9%) fulfilled D2T definition. In bivariate analysis, D2T patients presented higher rate of osteoarthritis (62.5% vs 24.9%; p=0.03), fibromyalgia (62.5% vs 14.94%; p<0.004), and therapy with steroids (50% vs 12.1%; p=0.008). Furthermore, D2T patients presented significantly higher patient global assessment (PGA 0-10) (7.5 vs 2.00; p<0.001) and VAS pain 0-10 (8.00 vs 2.00; p<0.001). Among non-D2T patients, 24 were in moderate disease activity (9.19%).Due to the unbalance between the groups numerosity, multivariate analysis was not feasible. Conclusion Only few patients satisfied the PsA-D2T definition in our cohort; application of a RA-like D2T definition to a heterogeneous disease as PsA should be discussed more broadly in the future. Reference [1]Perrotta FM, Rheumatol Ther 2021 Aug;9(4):1193-1201 Acknowledgements: NIL. Disclosure of Interests Gilberto Cincinelli: None declared, Matteo Ferrito: None declared, Marco Pandolfi: None declared, Martina Biggioggero Speakers bureau: Galapagos, Silvia Casari: None declared, Martina Cornalba: None declared, Chiara Crotti: None declared, Francesca Desiati: None declared, Ennio Giulio Favalli Speakers bureau: AbbVie, BMS, Celltrion, Galapagos, Janssen, Lilly, MSD, Novartis, Pfizer, UCB, Consultant of: AbbVie, BMS, Celltrion, Galapagos, Janssen, Lilly, MSD, Novartis, Pfizer, UCB, Maria Manara Speakers bureau: Novartis, Angelini, Consultant of: Lilly, MSD, Roberto Caporali Speakers bureau: AbbVie, Amgen, BMS, Celltrion, Fresenius, Galapagos, Janssen, Lilly, Novartis, Pfizer, UCB, Consultant of: AbbVie, Fresenius, Galapagos, Lilly, Novartis, Pfizer, UCB.Table 1Study population (N=269)Gender (male)140 (52.0%)Age (years)52.63 ± 11.87Smokers68 (25.3%)BMI22.49 (CI 20.27 – 22.91)Disease duration (months)154.5 (CI 88.25 – 251,75)Disease subsetAxial29 (10.8%)Peripheral194 (72.1%)Axial+peripheral37 (13.8%)Enthesitic9 (3.3%)Skin psoriasis205 (76.2%)Vulgaris167 (81.5%)Scalp37 (18.0%)Nail31 (15.1%)Palmo-plantar17 (8.3%)Extra-articular manifestationsIBD4 (1.5%)Uveitis6 (2.2%)Dactilitis40 (14.9%)Charlson Comorbidity Index1 (CI 1 - 2)Fibromyalgia44 (16.4%)DAPSA (median)Remission4.21 (CI 1.11 – 9.89)120 (44.6%)LDA237 (88.1%)MDA238 (88.5%)BSA>3%9 (3.3%)LEI <1255 (94.8%)HAQ (median)0.125 (CI 0 – 0,375)HAQ>0,559 (21.9%)Steroid use32 (11.9%)csDMARD failure178 (66.2%)>2 previous bDMARDs45 (16.7%)>2 previous MoA27 (10.0%)

In this study, we investigated how the COVID-19 pandemic involved osteoporosis care in patients treated with denosumab. Almost a third of patients missed the prescription renewal, mandatory to obtain the subsidized drug. Among patients who suspended denosumab, more than half reported fragility fractures. This study aimed to evaluate persistence on denosumab (Dmab) treatment during the COVID-19 pandemic and the clinical effects of possible discontinuation. We retrospectively assessed patients affected by osteoporosis and treated with Dmab, scheduled to have the yearly renewal of prescription between March 9, 2020, and May 9, 2021, 2 months after the second pandemic wave. In June 2022, a telephone survey started, by calling all patients who missed the yearly renewal of Dmab. Predictors of missed renewal and fragility fracture occurrence were assessed by logistic analyses. Patients scheduled to have a renewal of Dmab prescription during the observational period were 538 (age 75.5 ± 9.3 years, female 511). A total of 152 (28.2

Several rheumatologic diseases are primarily distinguished by their involvement of bone tissue, which not only serves as a mere target of the condition but often plays a pivotal role in its pathogenesis. This scenario is particularly prominent in chronic inflammatory arthritis such as rheumatoid arthritis (RA) and spondyloarthritis (SpA). Given the immunological and systemic nature of these diseases, in this review, we report an overview of the pathogenic mechanisms underlying specific bone involvement, focusing on the complex interactions that occur between bone tissue's own cells and the molecular and cellular actors of the immune system, a recent and fascinating field of interest defined as osteoimmunology. Specifically, we comprehensively elaborate on the distinct pathogenic mechanisms of bone erosion seen in both rheumatoid arthritis and spondyloarthritis, as well as the characteristic process of aberrant bone formation observed in spondyloarthritis. Lastly, chronic inflammatory arthritis leads to systemic bone involvement, resulting in systemic bone loss and consequent osteoporosis, along with increased skeletal fragility.