Objective. Fragility fractures (FF) resulting from osteoporosis pose a significant public health challenge in Italy, with considerable socio-health and economic implications. Despite the availability of safe and effective drugs, osteoporosis remains underdiagnosed and undertreated, leaving over 2 million high-risk Italian women without treatment. This paper aims to identify and propose key improvements in the management of osteoporosis, focusing particularly on the critical issues related to the use of anabolic drugs in secondary prevention, according to the current Italian Medicines Agency (AIFA) Note 79. Methods. The Expert Panel, composed of nine recognized Italian experts in rheumatology, analyzed current practices, prescribing criteria, and the most recent literature. Three main reasons for revising the indications on pharmacological treatment of osteoporosis were identified: inadequate treatment of osteoporosis, new evidence regarding frontline placement of anabolics in high-risk conditions, and emerging sequential or combined strategies. Results. The proposed improvements include the adoption of the Derived Fracture Risk Assessment algorithm for accurate fracture risk assessment, revision of AIFA Note 79 to reflect current evidence, improved prescribing appropriateness, broader access to anabolic agents, and the provision of sequential therapies with antiresorptives for teriparatide. These changes aim to enhance patient outcomes, streamline healthcare processes, and address the high percentage of undertreated individuals. Conclusions. This expert opinion emphasizes the importance of the appropriate use of anabolic drugs to reduce FF and associated costs while ensuring the sustainability of the National Health Service. The proposed recommendations are in line with the latest scientific evidence, providing a comprehensive strategy to optimize the management of osteoporosis in Italy. On behalf of the Study Group on Osteoporosis and Skeletal Metabolic Diseases of the Italian Society of Rheumatology.

The primary objectives of the study were to evaluate the efficacy and safety of tofacitinib and baricitinib up to 24 months of follow-up in patients with rheumatoid arthritis (RA) treated in Southern Italy. Patients' data, activity index, and clinimetric scores were collected at baseline (T0), six (T6), twelve (T12), and twenty-four (T24) months following treatment initiation. At six, twelve, and twenty-four months, adverse events and treatment cessation were also recorded. Sixty-eight patients (mean age: 62.2±10.9 years; mean RA duration: 15±9.6 years) were enrolled over a period of 12 weeks. At baseline, twenty-four patients (35.3%) were treated with tofacitinib, and forty-four patients (64.7%) were treated with baricitinib. The baseline mean disease activity was moderate as measured by DAS28- ESR (5.0±1.0), DAS 28 CRP (4.69±0.94), and SDAI (26.87±10.73) score. Before beginning JAKinhibs therapy, thirty-two patients (61.8%) were taking bDMARDs, while the remaining thirty-six (38.2%) were bDMARDs-naïve. The 24-month retention rate for JAKinhibs was 91.1%. Six months after beginning treatment with JAKinhibs, a statistically significant improvement was observed in all evaluated activity indices and clinimetric scores. Improvement was confirmed during the 12- and 24-month follow-up evaluations. The positive correlation between baseline-T6 SDAI delta and discontinuation of JAKinhibs (p=0.02) suggests that RA worsening in the first six months may be a predictor of therapy withdrawal. Patients with RA responded favorably to tofacitinib and baricitinib in this prospective, real-world study from a single center in Southern Italy. Efficacy was observed despite an underlying persistent and treatment-resistant disease.

OBJECTIVESDactylitis has long been recognised as one of the significant features of spondyloarthropathies. In the literature, the prevalence of dactylitis in enteropathic spondyloarthritis (EASpA) ranges between 2% and 4%. The aim of this study was to identify the prevalence of dactylitis in EASpA patients and to investigate its association with clinical subset and with articular and bowel disease activity.METHODS78 EASpA patients and 78 controls were enrolled for this study. All patients and controls underwent a rheumatological and a gastroenterological clinical examination. Demographic and clinical features were recorded. Diagnosis of dactylitis was made by physical examination and was evaluated using the Leeds Dactylitis Instrument (LDI).RESULTSIn our study the prevalence of dactylitis in EASpA was 15.38%, mainly in patients with Crohn's disease (CD) and peripheral arthritis. A significantly higher articular and bowel disease activity was found in patients with dactylitis compared to those without it. The family history of psoriasis represented a predictor of occurrence of dactylitis. Finally, a significant correlation between disease activity and LDI score was found in EASpA.CONCLUSIONSThe results of our study showed a high prevalence of dactylitis in EASpA. It was more frequent in patients with CD and peripheral involvement with a higher articular disease activity, confirming that dactylitis may be a severity marker and a prognostic factor for EASpA. The significant correlation between disease activity and LDI score could address LDI as a potential tool of assessment of dactylitis.

OBJECTIVE:Rheumatoid Arthritis (RA) is an autoimmune inflammatory disease that leads to local and systemic arthritis and bone loss. Exploring genetic markers of candidate genes in osteoporosis and inflammatory cytokine genes could be a useful tool for the early identification of bone loss and fracture risk in RA patients. The target of this study is the evaluation and correlation between of Single Nucleotide Polymorphisms (SNPs) of Vitamin D Receptor (VDR) and possible effects on bone loss in RA.PATIENTS AND METHODS:40 Caucasian patients with RA (26 of them with a severe bone loss) and 40 healthy donors as control samples were genotyped for the VDR SNPs (called BsmI, ApaI, TaqI and FokI). The detection method is based on Restriction Fragment Length Polymorphism (RFLP).RESULTS:Genotyping profile shown no difference between RA patients and controls. Only VDR-TaqI genotype (TT vs. tt) seem to influence the bone density in females, but not in males. The mean differences of Bone Mass Density (BMD) at the lumbar spine in RA women with the tt allele were 4.7% compared to 0.1% in women with the TT allele (p < 0.05).CONCLUSIONS:The results of these studies support an association between specific VDR alleles and bone loss in RA. The TaqI t and BsmI B alleles were associated with an accelerated bone loss in RA, but not with a focal bone loss. These effects of VDR genotypes and vitamin D supplementation are not unexpected, given that the central pathological feature in RA is bone and joint destruction. The VDR SNPs genotyping should be a useful tool to screen early women RA patients with the bone loss.

ObjectiveTo evaluate the efficacy and safety of combined treatment of mud-bath therapy and glucosamine crystalline sulfate (GIcN-S) in patients with knee osteoarthritis (OA).MethodsThis study was a randomised, controlled, crossover investigation. Patients were randomly assigned ( I :1) by the investigators to two groups, named group 1 and 2. Group 1 included twenty-three patients receiving oral GlcN-S treatment from the beginning of the study (TO) to the end of the 3rd month of treatment (T3) and a combined treatment of both mud-bath therapy and GIcN-S from T3 to the end of the study at six months (T6). Group 2 included twenty-two patients receiving a combined treatment of both mud-bath therapy and GIcN-S from TO to T3 and that discontinued mud-bath therapy, receiving GIcN-S treatment alone, from T3 to T6. Primary endpoints of the study consisted of evaluating OA severity and activity at baseline and at follow-up visits.ResultsAll 45 patients, eligible for the study, completed the period of the crossover. In group I, no significant difference was shown in the comparison from TO to T3, while from T3 to T6 most variables were significantly improved. In group 2, instead, the comparison between TO and T3 showed a significant difference in different parameters. When comparing T3 and T6, despite an improvement of all the variables, no significant difference was shown.ConclusionThe association of GlcN-S and mud-bath therapy has a positive and safe role in improving pain, function and quality of life in knee OA patients.

Immobilization osteoporosis represents a severe complication in hemiplegic patients (HPs), causing fragility fractures, which may occur during rehabilitation reducing functional recovery and survival. The aim of the study was to investigate determinants of bone loss, independent from length of immobilization, which may be useful in early identification of HPs at higher risk of demineralization. Forty-eight HPs of both sexes underwent anthropometric measurements, evaluation of scores of spasticity and of lower limb motory capacity. Laboratory tests were performed. On serum: calcium; phosphorus; creatinine; ALP; iPTH; 25(OH) vitamin-D; sex hormones; Δ4-androstenedione; DHEA-S; insulin; IGF-1; FT3; FT4; TSH; c-AMP. On urine: c-AMP and calcium/creatinine ratio. Two bone turnover markers were measured: serum osteocalcin (BGP) and urinary deoxypyridinoline (DPD). Bone mineral density was determined at both femoral necks, defining a percentage difference in bone loss between paretic and non-paretic limb, thus controlling for the complex cofactors involved. Only bone turnover markers significantly and directly correlated with the entity of demineralization, controlling for age, sex and length of immobilization in the multivariate analysis (BGP coefficient estimate=0.008; SE=0.003; p=0.020; DPD coefficient estimate=0.005; SE=0.002; p=0.036). BGP and DPD are not dependent on anthropometric and endocrine-metabolic parameters, disability patterns and duration of immobilization, thus represent independent determinants of the degree of demineralization. A cutoff was defined for BGP and DPD above which subjects show significantly greater risk of demineralization. The immobilization event generates more severe bone loss when it occurs in subjects with higher bone turnover. BGP and DPD measurements may be of primary importance for early identification of HPs at risk, with relevant preventive implications.

ObjectiveTo evaluate the effects on disease activity of seasonal influenza vaccination with adjuvant in psoriatic arthritis (PsA) patients in stable disease activity on anti-TNF-alpha drugs as compared to not vaccinated PsA patients adequately matched.MethodsAn observational study was conducted on a cohort of PsA patients in stable disease activity who underwent administration of an adjuvanted vaccine for seasonal influenza. Cases (Group 1) were matched for age, sex, disease activity and therapy with not vaccinated PsA patients (Group 2). Analysis included patients data before vaccination (T0), and one month (T1) and three months (T3) after administration of the vaccination for Group 1 and at correspondent intervals for Group 2. Assessment of disease activity parameters was performed at each visit.ResultsTwenty-five vaccinated and 25 not vaccinated patients were included in the study. As a first approach, we analysed the data within groups. At T1, as compared to baseline, the group of vaccinated patients had a statistically significant increase in TJC (tender joint count) and ESR (erythrocyte sedimentation rate). At T3, a statistically significant difference from baseline characteristics was found only for the TJC. In Group 2, all the observed variables showed no significant differences when comparing baseline to T1 and T3. Analysis of the data between groups at T1, Group 1, as compared to Group 2, showed a significant increase of TJC, ESR, HAQ (Health Assessment Questionnaire), PtGA (patient global assessment) and PhGA (physician global assessment). These findings were also confirmed when comparing the two groups at T3 for ESR and PtGA, while they were not confirmed for TJC, HAQ and PhGA.ConclusionInfluenza vaccination is clinically efficacious in PsA patients under anti-TNF-alpha therapy, but it could trigger a short-lasting exacerbation of the disease.

OBJECTIVESPharmacogenomics is considered as the new frontier to predict the response to treatments and it can also be based on the comparison of family members being treated for the same condition. No data are available on the impact of anti-tumour necrosis factor (TNF)-α therapies in members of the same family with ankylosing spondylitis (AS).METHODSWe describe three mother-daughter couples concordant for AS and HLA-B27, both treated with TNF-α inhibitors, for whom the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), Bath Ankylosing Spondylitis Functional Index (BASFI), and Ankylosing Spondylitis Disease Activity Score (ASDAS)-CRP were evaluated during a follow-up of 24 months.RESULTSAll patients manifested improvements of all scores, but the daughters had a more prominent effect achieving faster complete disease remission.CONCLUSIONSWe hypothesise that longer standing chronic inflammation and older age may cause a less prompt and effective response to treatment in SA when compared with their genetically related controls.

Osteoporosis represents a relevant health issue, being the first cause of bone fractures in the elderly with subsequent implications in terms of survival and social costs. The improved knowledge about the physiopathology of this disease has led to a new definition of Osteoporosis, which shifts the attention from the “"decrease in bone mass"” to several elements related to what has globally been defined as bone quality. In fact, it has been shown that clinical risk factors affecting bone homeostasis coincide with osteoporosis risk factors. The evaluation of such clinical risk factors is an important element in the assessment of the global fracture risk. The availability of instruments for the assessment of the global fracture risk also suggests a change in the clinical perspective and raises new questions as yet unanswered.

Background: Glycogen storage disease type 1 (GSD1) is a rare and genetically heterogeneous metabolic defect of gluconeogenesis due to mutations of either the G6PC gene (GSD1a) or the SLC37A4 gene (GSD1b). Osteopenia is a known complication of GSD1. Objectives: The aim of this study was to investigate the effects of poor metabolic control and/or use of GSD1-specific treatments on bone mineral density (BMD) and metabolism in GSD1 patients. Methods: In a multicenter, cross-sectional case-control study, we studied 38 GSD1 (29 GSD1a and 9 GSD1b) patients. Clinical, biochemical and instrumental parameters indicative of bone metabolism were analyzed; BMD was evaluated by dual-emission X-ray absorptiometry and quantitative ultrasound. Results: Both GSD1a and GSD1b patients showed reduced BMD compared with age-matched controls. In GSD1a patients, these abnormalities correlated with compliance to diet and biochemical indicators of metabolic control. In GSD1b patients, BMD correlated with the age at first administration and the duration of granulocyte colony-stimulating factor (G-CSF) therapy. Conclusions: Our data indicate that good metabolic control and compliance with diet are highly recommended to improve bone metabolism in GSD1a patients. GSD1b patients on G-CSF treatment should be carefully monitored for the risk of osteopenia/osteoporosis.

Osteoporosis and fractures are common and invalidating consequences of chronic glucorticoid (GC) treatment. Reliable information regarding the epidemiology of GC induced osteoporosis (GIOP) comes exclusively from the placebo group of randomized clinical trials while observational studies are generally lacking data on the real prevalence of vertebral fractures, GC dosage and primary diagnosis. The objective of this study was to evaluate the prevalence and incidence of osteoporotic fractures and to identify their major determinants (primary disease, GC dosage, bone mineral density, risk factors, specific treatment for GIOP) in a large cohort of consecutive patients aged >21 years, on chronic treatment with GC (≥5 mg prednisone - PN - equivalent) and attending rheumatology centers located all over Italy. Glucocorticoid Induced OsTeoporosis TOol (GIOTTO) is a national multicenter cross-sectional and longitudinal observational study. 553 patients suffering from Rheumatoid Arthritis (RA), Polymyalgia Rheumatica (PMR) and Connective Tissue Diseases (CTDs) and in chronic treatment with GCs were enrolled. Osteoporotic BMD values (T score <-2.5) were observed in 28%, 38% and 35% of patients with CTDs, PMR or RA at the lumbar spine, and in 18%, 29% and 26% at the femoral neck, respectively. Before GC treatment, prevalent clinical fractures were reported by 12%, 37% and 17% of patients with CTDs, PMR, or RA, respectively. New clinical fragility fractures during GC treatment were reported by 12%, 10% and 23% of CTDs, PMR and RA patients, respectively. Vertebral fractures were the prevailing type of fragility fracture. More than 30% of patients had recurrence of fracture. An average of 80% of patients were in supplementation with calcium and/or vitamin D during treatment with GCs. Respectively, 64%, 80%, and 72% of the CTDs, PMR and RA patients were on pharmacological treatment for GIOP, almost exclusively with bisphosphonates. The GIOTTO study might provide relevant contributions to clinical practice, in particular by highlighting and quantifying in real life the prevalence of GIOP and relative fractures, the frequency of the main risk factors, and the currently sub-optimal prevention. Moreover, these results emphasize the importance of the underlying rheumatic disease on the risk of GIOP associated fractures.

OBJECTIVES Osteoporosis (OP) and increased risk of fracture are relevant features in patients with rheumatoid arthritis (RA). Low levels of serum vitamin D are frequently reported and correlate with a higher RA activity. This study evaluated factors related with the prescription of vitamin D supplements in RA patients and variables influencing the achievement of adequate vitamin D levels. METHODS Study population was made up by 1168 consecutive RA patients from 22 Italian rheumatology centers. Demographic and clinical variables data were collected and 25OH serum vitamin D was measured in all patients. Insufficient serum 25OH vitamin D levels were defined as values lower than 20 ng/mL. RESULTS The majority of patients (56.0%) was not taking vitamin D supplements. Among the 514 supplemented patients, 196 (38.1%) were taking insufficient dosages (≤440 IU/day). Variables related with the prescription of supplements were older age, female sex, previous bone density assessment and OP diagnosis. Among the 318 patients using daily supplements ≥800 IU, 88 patients (27.7%) did not reach adequate levels of vitamin D. In these patients a higher HAQ score (OR for 1 point=1.62, 95% CI: 1.06-2.49; p=0.03) and poor sun exposure (OR=2.38, 95% CI: 1.05-5.55; p=0.04) were predictors of vitamin D insufficiency. CONCLUSIONS Vitamin D deficiency is common in patients with RA, even in patients who are regularly using supplements. Vitamin D supplementation is often ineffective even at the recommended dose of 800 IU/day in more disabled patients.