Romosozumab is a monoclonal antibody against sclerostin that initially exhibits potent anabolic effects in treating osteoporosis. However, its efficacy diminishes after 6 mo, with bone formation markers declining despite continued therapy. We hypothesized that increased levels of Dickkopf-1 (Dkk1), a Wnt pathway inhibitor, may contribute to this attenuation by suppressing osteoblast activity. We conducted a 12-mo prospective observational study on postmenopausal osteoporosis naïve to anti-osteoporosis treatment treated with romosozumab. Serum levels of Dkk1, procollagen type I N-terminal propeptide (P1NP), C-terminal telopeptide of type I collagen (CTX), and sclerostin were measured at baseline (M0) and at 3 (M3), 6 (M6), and 12 mo (M12). BMD at the LS, FN, and TH was assessed at M0, M6, and M12. Associations between Dkk1 and P1NP were analyzed using linear mixed-effects models. Dkk1 levels increased significantly from 38.9 pmol/L at M0 to 44.2 pmol/L at M12 (p = .003). P1NP increased from 89.4 ng/mL at M0 to 115.4 ng/mL at M3 (p = .004) but decreased to 61.5 ng/mL by M12 (p < .001). CTX decreased significantly throughout the study (p < .001). BMD increased significantly at all sites by M12 (LS + 13.8%, FN + 6.3%, TH + 4.7%; all p < .01). An inverse association was found between Dkk1 increase and P1NP decrease between M3 and M12 (estimate = -0.909; p = .032). Romosozumab treatment is associated with a significant rise in Dkk1 levels, which correlates with a decrease in bone formation markers over time. Dkk1 may attenuate the anabolic effects of romosozumab by inhibiting Wnt signaling.

Key advances from the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA) pilot research grant program were presented at the GRAPPA 2025 annual meeting. Areas of study included hypoxia-inducible factor 1α (HIF1A) as a potential factor in psoriatic arthritis (PsA), plasma extracellular vesicle cytokines as potential biomarkers for predicting response to tumor necrosis factor inhibitors in PsA, bone properties and biomechanics in psoriatic disease (PsD), better understanding of differences in body composition in PsD, and the effect of sleep on PsD severity.

Background Psoriatic disease has a complex effect on bone metabolism, resulting in both pathological bone formation and bone resorption. However, microstructural changes in cortical and trabecular compartments remain poorly understood. The aim of this study was to investigate the prevalence and determinants of bone microarchitectural damage in patients with psoriatic disease.Methods We performed a cross-sectional study in patients with psoriasis (PsO), psoriatic arthritis (PsA) and age-matched healthy controls (HCs) recruited into the Department of Dermatology and Rheumatology of Verona centre. We conducted high-resolution peripheral quantitative CT of the radius and finger joints of the non-dominant hand. Bone microstructure parameters and finite element analysis (uFEA) were calculated.Results 51 patients with PsO and 39 patients with PsA were consecutively enrolled in the study. 24 age-matched HCs were enrolled. Distal radius total and cortical volumetric bone mineral density (Ct.BMD) levels were lower in patients with PsA and PsO compared with HC. On distal radius uFEA analysis, we found a significant reduction of stiffness in PsA compared with both HC and PsO. At the distal interphalangeal (DIP) joints, Ct.BMD and trabecular volumetric bone mineral density were lower in PsA and PsO compared with HC. Nail involvement in psoriatic disease was negatively associated with bone stiffness at the proximal and distal region of the DIPs.Conclusion Psoriatic disease negatively impacted bone integrity. Patients with psoriatic disease seemed to have lower bone density and more microarchitectural alteration that impacted on biomechanics properties. Nail involvement was associated with decreased bone stiffness in psoriatic disease.

We evaluated how romosozumab affects bone structure, density, and strength at the wrist over 12 months. Volumetric bone mineral density did not increase, but high-resolution quantitative computed tomography imaging showed modest improvements in bone strength. These findings suggest that romosozumab may improve bone quality even in areas where density changes are not seen with standard scans and highlight the importance of using more detailed imaging to fully understand how osteoporosis treatments work across different skeletal sites. Romosozumab (ROMO) is a monoclonal antibody that inhibits sclerostin, promoting bone formation and suppressing resorption. While ROMO leads to substantial BMD gains at the lumbar spine and the hip, its effects on distal radius volumetric BMD (vBMD) remain unclear. High-resolution peripheral quantitative computed tomography (HR-pQCT) allows for detailed assessment of bone microarchitecture and strength at peripheral regions. We aimed to evaluate the effects of 12 months of ROMO on vBMD, microarchitecture and biomechanical properties of the distal radius using HR-pQCT. We did a prospective study on 49 postmenopausal women with osteoporosis treated with ROMO for 12 months who underwent HR-pQCT with Cone Beam CT and microfinite element analysis (uFEA) assessments at baseline, 3, 6, and 12 months. We also performed DXA at lumbar spine, femoral neck, and total hip. HR-pQCT parameters trajectories were analyzed using mixed-effects modeling. No significant increases were observed in cortical or trabecular vBMD or microarchitectural parameters at the distal radius. On the other hand, uFEA showed early increases in cortical failure load and shear strength, suggesting potentially improved bone mechanical behavior. Lumbar spine, femoral neck, and total hip aBMD significantly increased by 11.6

In a peritoneal dialysis longitudinal cohort, REMS and DXA showed similar bone density, but only DXA detected significant cortical bone loss. REMS tended to give lower bone mineral density values and did not correlate with DXA changes. REMS may complement DXA when DXA findings are difficult to interpret or when closer longitudinal monitoring is needed, but larger studies are needed to define its role. Dual X-ray absorptiometry (DXA) is the gold standard for bone mineral density (BMD) assessment in chronic kidney disease patients, but it can have limited accuracy and radiofrequency echographic multi-spectrometry (REMS) may overcome some of its limitations. We aimed to evaluate and compare longitudinal BMD changes assessed by DXA and REMS in peritoneal dialysis (PD) patients. Prospective cohort study including 20 PD patients that underwent two separate DXA and REMS evaluations. Clinical, biochemical, and imaging data, including abdominal aorta calcification (AAC) scores and fracture history, were collected. Longitudinal BMD changes were analyzed using linear mixed-effects models. Over a median follow-up period of 19.8 months, DXA revealed significant BMD declines at the femoral neck (FN) (−3.2

Background: Rheumatoid arthritis (RA) is characterized by synovial inflammation leading to joint damage, periarticular bone loss, and systemic osteoporosis. While inflammation is a primary driver of structural damage, dysregulation of the Wnt signaling pathway, particularly through inhibitors such as Dickkopf-1 (Dkk1) and sclerostin, has been implicated in RA-associated bone loss. Objectives: Our study investigated factors associated with erosive RA, focusing on bone turnover markers and modulators of the Wnt system. Design: We performed a cross-sectional study of stable conventional synthetic disease-modifying anti-rheumatic drug (csDMARDs) in RA patients naïve to biologic DMARDs. Methods: Clinical, radiographic, and bone mineral density (BMD) data were collected. Serum markers of bone turnover, including Dkk1, sclerostin, C-terminal telopeptide of type I collagen (CTX), procollagen type 1 N-terminal propeptide (P1NP), parathyroid hormone, and vitamin D, were analyzed. Principal component analysis (PCA) and k -means clustering were applied to identify variable associations, and regression models were used to assess their cross-sectional associations with radiographic damage. Results: Sixty-two RA patients were included in the study. The Sharp van der Heijde score (SvdHS) was positively correlated with measures of disease activity, glucocorticoid use, anti-citrullinated protein antibodies (ACPA) titer, rheumatoid factor, C-reactive protein, Dkk1 levels, and CTX. P1NP was inversely associated with SvdHS. PCA identified three clusters related to disease activity measures, BMD, and markers of bone metabolism. Dkk1 was linked to ACPAs and osteoclastic activity, suggesting a role in bone loss. Conclusion: Our findings confirm the role of inflammation and autoantibodies in RA-related joint damage. We found that BMD and markers of bone metabolism were additional contributors. There is a complex interplay between inflammation, bone metabolism, and structural deterioration in RA.

OBJECTIVE:Transition from long-term denosumab (Dmab) to parathyroid hormone-analogs or romosozumab (Romo) might expose patients to the risk of the so-called rebound phenomenon. Adding Romo to Dmab might represent an option in patients experiencing a fracture while on Dmab. The aim of this study was to investigate the effects of the combination of Romo to Dmab in postmenopausal osteoporosis. METHODS:We did a 36-month combined retrospective and prospective study analyzed with prospective score matching. Postmenopausal women were divided into two groups: patients on Dmab who added Romo to Dmab (Dmab from baseline [M-24] to Romo initiation [M0] ➔ Dmab + Romo from M0 to M+12), and matched controls on Dmab continuing Dmab (Dmab from M-24 to M0 ➔ Dmab from M0 to M+12). Bone mineral density and bone turnover markers (CTX, P1nP) were assessed at follow-up time points. RESULTS:A total of 50 women were included in the study: 25 patients in the Dmab ➔ Dmab + Romo group and 25 matched controls in the Dmab ➔ Dmab group. The between-group difference at M+12 was 3.3% (95% confidence interval -5.2 to 11.8), indicating a nonsignificant trend toward greater improvement with combination therapy. Adding Romo to Dmab increased P1nP significantly between M0 and M+3 (+22.5 ng/mL, SE = 8.7; P = 0.028). CONCLUSION:Ongoing treatment with Dmab did not blunt the anabolic response of Romo, indicating sustained modeling-based bone formation activity. Adding Romo in patients failing Dmab might be a valuable option.

Brief rationale: Osteoporosis management in Italy shows regional inconsistencies. Main result: Expert surveys and meetings revealed limited access to anabolic treatments and fragmented care pathways. Significance of the paper: Findings support the need for updated national guidelines to promote equitable care and reduce the burden of osteoporotic fractures.PurposeOsteoporosis is a progressive bone disease characterized by reduced bone density and increased fracture risk, significantly affecting quality of life and imposing a substantial burden on healthcare systems. In Italy, managing osteoporosis is a national priority due to the rising incidence of fractures among the aging population. This study evaluates clinical practices in osteoporosis management across Northern, Central, and Southern Italy, focusing on diagnostics, therapies, and access to specialized care.MethodA detailed survey was distributed across multiple centers to evaluate diagnostic, therapeutic, and follow-up practices, along with specialists' perspectives on national guidelines and the challenges in accessing advanced treatments. Following the survey, three regional expert meetings were held to analyze the findings and gain further insight.ResultsFindings show widespread use of bone mineral density (BMD) testing and laboratory assessments, with regional differences in the use of fracture risk tools (FRAX, DeFRA) and markers such as CTX. Bisphosphonates, denosumab, and anabolic agents are commonly used; however, significant disparities persist in access to anabolic treatments. The patient journey remains uneven across regions, with challenges in accessing bone specialists, timely diagnosis, and appropriate treatment. In areas lacking structured care pathways, these gaps lead to delayed or suboptimal management.ConclusionThese findings highlight the need for updated, flexible guidelines to support a tailored and equitable approach to osteoporosis care in Italy. Improving access to specialized care and standardizing treatment pathways may enhance outcomes and reduce healthcare costs associated with osteoporosis-related fractures.

OBJECTIVES:Romosozumab (ROMO) is a monoclonal antibody targeting sclerostin (SOST), a key regulator of bone metabolism. It has been demonstrated that changes in SOST levels can affect distinct niches within the bone marrow that support haematopoiesis. This study investigated the effect of ROMO on complete blood count (CBC) parameters. METHODS:We conducted a 12-month prospective observational study in post-menopausal women with severe osteoporosis treated with ROMO 210 mg/monthly over one year between October 2023 and April 2025. CBC values were assessed at baseline, 6 and 12 months. Absolute changes in CBC were assessed with a mixed model for repeated measures. RESULTS:A total of 113 women (mean age of 73.4±9.7 years) were included. Neutrophils levels slightly decreased over time, with a significant decrease at 6 months (p=0.022), that was not sustained at 12 months (p=0.500). Haemoglobin and lymphocytes levels showed no significant differences over the period of the study. In the overall trend across time points, there was a statistically significant decrease in the neutrophil-to-lymphocyte ratio (NLR) over the 12 months (2.0 ± 1.1 at baseline, 1.8 ± 1.1 at month 6, and 1.8 ± 1.2 at month 12; p=0.034), with a small effect size (Cohen's δ = 0.22). CONCLUSIONS:In post-menopausal women with severe osteoporosis, 12 months of ROMO treatment was associated with a statistically significant reduction in NLR, reflecting a potential modulation of systemic inflammation, though the clinical relevance of this modest shift remains uncertain and warrants further investigation.

Objective To assess the effectiveness of belimumab (BEL) in improving anaemia, thrombocytopenia, lymphopenia and leucopenia in patients with SLE.Methods The BeRLiSS (Belimumab in Real Life Setting Study) 2.0 cohort included patients with SLE from 14 Italian referral centres treated with BEL for active joint or skin involvement, based on physician judgement, between June 2013 and May 2024. Clinical and laboratory parameters were recorded at baseline and every 6 months. Patients were eligible if they had baseline haematological abnormalities defined according to British Isles Lupus Assessment Group (BILAG) (grade C or higher): haemoglobin (Hb) ≤10.9 g/dL, platelets (Plts) ≤149×109/L, lymphocytes (Lym) ≤1.0×109/L or leucocytes (Leuc) ≤3.0×109/L. Follow-up data up to month 48 were available for 33 patients with anaemia, 20 with thrombocytopenia, 44 with lymphopenia and 18 with leucopenia.Results At baseline, 76 patients had anaemia, 44 thrombocytopenia, 107 lymphopenia and 53 leucopenia. Hb levels increased significantly from 9.9±0.6 g/dL to 11.7±1.4 g/dL at month 48 (p<0.001). Platelet counts rose from 110.2±38.1×109/L to 176.6±88.7×109/L (p=0.004), Lym counts from 0.72±0.21×109/L to 1.14±0.45×109/L (p<0.001) and leucocyte counts from 2.437±0.533×109/L to 4.732±1.897×109/L at 48 months (p<0.001). Improvement in Hb (p=0.97), Plts (p=0.12), Lym (p=0.86) and Leuc (p=0.73) was similar regardless of the use of concomitant immunosuppressants. Glucocorticoid (GC) doses decreased significantly across all manifestations, except for leucopenia: anaemia (12.9±12.1 to 3.6±4.9 mg/day, p=0.003), thrombocytopenia (10.8±9.6 to 4.4±5.5 mg/day, p=0.004), lymphopenia (10.6±8.6 to 3.1±3.2 mg/day, p<0.001). Proportion of GC users declined over 48 months: anaemia 96.1–60.7%, thrombocytopenia 93.1–80%, lymphopenia 96.3–70.3% and leucopenia 95.3–80%.Conclusion In this real-world cohort, BEL treatment was associated with improvement in anaemia, thrombocytopenia, lymphopenia and leucopenia with over half of patients achieving normalisation of blood counts. Haematological responses were similar regardless of concomitant immunosuppressive therapy, supporting the role of BEL as a therapeutic option for haematological abnormalities in SLE.

BackgroundThere is currently scarce data on the real-world effectiveness and safety of upadacitinib in patients with axial spondyloarthritis (axSpA). This study evaluated clinical outcomes and drug retention rate (DRR) at 6, 12, and 24 months in patients initiating upadacitinib for axSpA.MethodsThis prospective, observational study enrolled consecutive patients with radiographic axSpA (r-axSpA) or non-radiographic axSpA (nr-axSpA) initiating upadacitinib between December 2022 and January 2025 at 16 Italian centres. The primary endpoints were treatment effectiveness—evaluated using clinimetric indices, including the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) and Ankylosing Spondylitis Disease Activity Score (ASDAS) — safety and DRR at 6, 12, and 24 months.ResultsOverall, 203 patients were analysed (48% male; median age at diagnosis 44 years; 22.7% HLA-B27 positive; 71% with nr-axSpA). Sixty-three patients completed the 24-month follow-up. Upadacitinib demonstrated a statistically significant improvement in effectiveness outcomes at 6 months vs. baseline, which was sustained at 12 and 24 months, regardless of previous biologic therapy lines, axSpA subtype, or sex. Furthermore, DRR was 92%, 80%, and 55% at six, 12, and 24 months, respectively. Forty patients discontinued upadacitinib, including 22 for insufficient effectiveness and two for AEs. Twenty-two patients developed infections.ConclusionUpadacitinib demonstrated a favourable effectiveness profile in the evaluable axSpA population with sustained remission and high treatment retention over a two-year follow-up. Within the limitations inherent to this observational study, the tolerability profile of upadacitinib was generally consistent with that reported in randomized controlled trials, and no new safety signals were identified. Overall, these findings support the effectiveness of Janus kinase inhibitors in the treatment of patients with axSpA.

BACKGROUND:Anxiety is a frequent but often under-recognized comorbidity in patients with inflammatory rheumatic diseases. This study aimed to assess the prevalence of state and trait anxiety in patients with rheumatoid arthritis (RA), psoriatic arthritis (PsA), and axial spondyloarthritis (axSpA), and to identify their sociodemographic, clinical, and psychological correlates and independent determinants. METHODS:In this cross-sectional study, 807 consecutive outpatients were recruited. Anxiety was assessed using the State-Trait Anxiety Inventory (STAI-X1 and STAI-X2). Sociodemographic data, disease activity indices, functional disability, pain, pharmacological treatments, and radiographic progression were recorded. Depressive symptoms, perceived stress, fatigue, and coping strategies were evaluated using validated questionnaires. Univariate and multivariable logistic regression models were performed to identify independent determinants of anxiety. RESULTS:Moderate to high levels of state anxiety were observed in 19.8% of patients, while 22.3% exhibited moderate to high trait anxiety. Patients with higher anxiety levels showed greater disease activity, functional disability, pain intensity, radiographic progression, depressive symptoms, perceived stress, fatigue, and more frequent use of dysfunctional coping strategies (all p < 0.001). In multivariable analyses, state anxiety was independently associated with functional disability (OR = 2.11) and radiographic progression (OR = 1.72). Trait anxiety was independently associated with functional disability (OR = 1.58), female sex (OR = 2.13), glucocorticoid use (OR = 1.59), depression (OR = 1.46). CONCLUSION:Anxiety is highly prevalent and is closely linked to functional disability, disease severity, and maladaptive psychological factors. Distinct determinants characterize state and trait anxiety, supporting the need for routine psychological assessment and integrated, patient-centered care in rheumatology.

Data on the impact of vertebral fractures on lung function in interstitial lung diseases (ILDs) are limited. This study aimed to evaluate the association between vertebral fractures, quantified by the spinal deformity index (SDI), and pulmonary function parameters, independently of ILD pattern and thoracic morphometric indices. This cross-sectional study included adult patients diagnosed with ILD who underwent high-resolution computed tomography (HRCT) and pulmonary function tests (PFTs). PFTs included absolute and percent predicted values of forced vital capacity (ppFVC), absolute and percent predicted total lung capacity (ppTLC), forced expiratory volume in one second (FEV₁), and percent predicted diffusing capacity of carbon monoxide (ppDLCO). The SDI was calculated from T4 to T12 on sagittal HRCT reconstructions. A total of 200 patients were analyzed: 76 with idiopathic pulmonary fibrosis (IPF), 65 with systemic sclerosis–associated ILD (SSc-ILD), 31 with idiopathic inflammatory myopathy–associated ILD, and 28 with other ILDs. At least one mild thoracic vertebral fracture was detected in 46 subjects (23

Background The present study aimed to explore, in patients with rheumatoid arthritis, psoriatic arthritis, and axial spondyloarthritis, the direct effects of coping strategies on fatigue and the role of depression and anxiety as mediators. It also investigates how moderators, including diagnosis, disease activity, disease duration, and sex, affect the pathways. Methods This observational cross-sectional study examined a sample of 807 patients receiving outpatient care, who were assessed with the following self-report validated questionnaires: the Coping Orientation to the Problems Experienced, the Chalder Fatigue Questionnaire, the Quick Inventory of Depressive Symptomatology, and the State-Trait Anxiety Inventory. Results While the effect of problem-focused and emotion-focused coping did not seem to be related to fatigue, dysfunctional coping significantly was. Once depression and anxiety were considered as mediators, the direct effect of dysfunctional coping on fatigue lost its significance. When examining the diagnostic category as a moderator, dysfunctional coping has a more significant relationship with fatigue in axial spondyloarthritis compared to rheumatoid arthritis or psoriatic arthritis. When considering sex as a moderator, the association between dysfunctional coping and depression appeared stronger in females than in males. Disease activity and disease duration do not appear to moderate the paths. Conclusion Maladaptive coping in rheumatic diseases appears to contribute to higher fatigue levels, a relationship mediated by anxiety and depression symptoms, while diagnosis and sex moderate specific paths.

Osteoporosis weakens bones and increases the risk of fractures. Denosumab is a medication that reduces bone loss and increases bone mineral density (BMD). In this real-world study, we followed patients who received denosumab every 6 months for 10 years. We found that bone density continued to improve throughout treatment. People who had taken bisphosphonates before starting denosumab responded just as well in the long term. Blood tests showed stable reduction of bone turnover markers. Denosumab produces durable BMD gains and low fracture rates in clinical trials, but long-term real-world evidence is limited, especially on the effect of prior bisphosphonate exposure and characteristics of patients who fracture during therapy. We conducted a 10-year single-center real-world retrospective study including patients receiving continuous denosumab 60 mg every 6 months. Clinical, biochemical, and densitometric data were extracted from an institutional electronic database. Longitudinal changes in BMD at total hip, lumbar spine, and femoral neck were analyzed using linear mixed-effects models adjusted for baseline BMD, age, baseline severe vertebral fractures, and glucocorticoid exposure. Bone turnover markers (CTX, ALP, PTH) were analyzed with mixed-effects models adjusted for renal function. A total of 145 patients were included (mean age 70.9 years; 95.9