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Vitamin D deficiency is very common in patients with rheumatoid arthritis (RA). Aim of this study was to evaluate the prevalence of vitamin D deficiency among the different Italian regions and whether these variations are associated with different severity of the disease. The study includes 581 consecutive RA patients (464 women), not taking vitamin D supplements, from 22 Italian rheumatology centres uniformly distributed across Italy. Together with parameters of disease activity (disease activity score 28), functional impairment (activities of daily living and health assessment questionnaire disability index) and mean sun exposure time, all patients had serum 25-hydroxyvitamin D (25OHD) measured in a centralized laboratory. Vitamin D deficiency (25OHD level

Objective. Pharmacogenomics 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). Methods. We describe three motherdaughter 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. Results. All patients manifested improvements of all scores, but the daughters had a more prominent effect achieving faster complete disease remission. Conclusion. We 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.

BACKGROUND : Secukinumab is an anti-interleukin-17A monoclonal antibody that has been shown to control the symptoms of ankylosing spondylitis in a phase 2 trial. We conducted two phase 3 trials of secukinumab in patients with active ankylosing spondylitis. METHODS : In two double-blind trials, we randomly assigned patients to receive secukinumab or placebo. In MEASURE 1, a total of 371 patients received intravenous secukinumab (10 mg per kilogram of body weight) or matched placebo at weeks 0, 2, and 4, followed by subcutaneous secukinumab (150 mg or 75 mg) or matched placebo every 4 weeks starting at week 8. In MEASURE 2, a total of 219 patients received subcutaneous secukinumab (150 mg or 75 mg) or matched placebo at baseline; at weeks 1, 2, and 3; and every 4 weeks starting at week 4. At week 16, patients in the placebo group were randomly reassigned to subcutaneous secukinumab at a dose of 150 mg or 75 mg. The primary end point was the proportion of patients with at least 20% improvement in Assessment of Spondyloarthritis International Society (ASAS20) response criteria at week 16. RESULTS : In MEASURE 1, the ASAS20 response rates at week 16 were 61%, 60%, and 29% for subcutaneous secukinumab at doses of 150 mg and 75 mg and for placebo, respectively (P< 0.001 for both comparisons with placebo); in MEASURE 2, the rates were 61%, 41%, and 28% for subcutaneous secukinumab at doses of 150 mg and 75 mg and for placebo, respectively (P< 0.001 for the 150-mg dose and P = 0.10 for the 75-mg dose). The significant improvements were sustained through 52 weeks. Infections, including candidiasis, were more common with secukinumab than with placebo during the placebo-controlled period of MEASURE 1. During the entire treatment period, pooled exposure-adjusted incidence rates of grade 3 or 4 neutropenia, candida infections, and Crohn's disease were 0.7, 0.9, and 0.7 cases per 100 patient-years, respectively, in secukinumab-treated patients. CONCLUSIONS : Secukinumab at a subcutaneous dose of 150 mg, with either subcutaneous or intravenous loading, provided significant reductions in the signs and symptoms of ankylosing spondylitis at week 16. Secukinumab at a subcutaneous dose of 75 mg resulted in significant improvement only with a higher intravenous loading dose. (Funded by Novartis Pharma; ClinicalTrials.gov numbers, NCT01358175 and NCT01649375.)

This study aimed to compare two different classifications of the risk of fracture/osteoporosis (OP) based on quantitative ultrasound (QUS). Analyses were based on data from the Epidemiological Study on the Prevalence of Osteoporosis, a cross-sectional study conducted in 2000 aimed at assessing the risk of OP in a representative sample of the Italian population. Subjects were classified into 5 groups considering the cross-classification found in previous studies; logistic regression models were defined separately for women and men to study the fracture risk attributable to groups defined by the cross-classification, adjusting for traditional risk factors. Eight-thousand six-hundred eighty-one subjects were considered in the analyses. Logistic regression models revealed that the two classifications seem to be able to identify a common core of individuals at low and at high risk of fractures, and the importance of a multidimensional assessment in older patients to evaluate clinical risk factors together with a simple, inexpensive, radiation-free device such as QUS.

To analyze the influence of cyclosporine A (CYA) on bone using data from a large multicenter, cross-sectional study on bone mineral density (BMD) in rheumatoid arthritis (RA).We selected 558 female patients with RA and divided them into two groups on the basis of CYA use: those who had never used CYA (n = 467) and CYA users (n = 91; users for24 months n = 50; users for24 months n = 41). Demographic, disease and treatment-related variables were collected for each patient. BMD was measured at the lumbar spine and proximal femur using dual x-ray absorptiometry. Data was analyzed by means of a univariate and multivariate statistical procedure. Osteoporosis (OP) was defined as BMD-2.5 T score.The frequency of OP among non-CYA users and CYA users was 28.2% and 33.3% (p=NS) for the lumbar spine, and 34.2% and 31.3% (p=NS) for the femoral neck, respectively. The prevalence of fragility fractures was not significantly different between the two groups. Mean values for the T-score at either the lumbar spine or the femoral neck were comparable in the two groups, even after adjustment for age, menopausal status, body mass index (BMI), Health Assessment Questionnaire (HAQ) score and steroid use. The generalized linear model showed that age, BMI and the HAQ score were significant independent predictors of BMD at the lumbar and femoral levels, whereas CYA use was not. Logistic analysis showed that only age, the HAQ score and BMI were significantly associated with the risk of OP. However, the duration of CYA therapy24 months was associated with an adjusted decreased lumbar BMD and a significantly decreased femoral neck BMD (p = 0.01). The frequency of femoral neck OP in patients on CYA for24 months was significantly higher than in patients on CYA for24 months: 46.4% vs. 19.44% (p=0.03), while the prevalence of fragility fractures did not differ significantly: 23.1% vs. 16.6%, respectively (p=NS). Logistic analysis showed that CYA use was an independent predictor of osteoporosis at the femoral site.Long-term CYA therapy may have negative effects on BMD in female RA patients.

Tumour necrosis factor-receptor associated periodic syndrome (TRAPS) is a rare autosomal dominant autoinflammatory disorder characterised by recurrent episodes of long-lasting fever and inflammation in different regions of the body, as musculo-skeletal system, skin, gastrointestinal tube, serosal membranes and eye. Inflammatory attacks usually start in the pediatric age with initial corticosteroid-responsiveness. Most reported cases of TRAPS involve patients of European ancestry and diagnosis can be formulated by the combination of genetic analysis and a compatible phenotype. Its prognosis is strictly dependent on the appearance of amyloidosis, secondary to uncontrolled relapsing inflammation. Thanks to a better understanding of its pathogenesis, the disease is now managed with anti-interleukin (IL)-1 antagonists, rather than corticosteroids or tumour necrosis factor (TNF) inhibitors. The aim of this review is to describe the current understanding and advances of TRAPS genetic basis, pathogenesis and management options by integrating the most recent data in the medical literature.

Bisphosphonates are considered as a first-line therapy for the prevention and treatment of osteoporosis, showing in double-blind, randomized, controlled trials a significant reduction of incidence of new vertebral fractures compared to placebo. Recently also, Denosumab has been shown to reduce the appearance of new vertebral fractures by blocking RANK. There are not head to head comparative studies between the above mentioned drugs. Mixed treatment comparison, an extension of traditional meta-analysis, is able to compare simultaneously several drugs across a range producing a synthetic evidence of efficacy and a range of probability as to the best treatment.The aim of this study is to simultaneously compare alendronate, risedronate, ibandronate, zolendronate and denosumab in the prevention of OP vertebral fractures in a Bayesian meta-analysis for assessing indirect comparisons.A search for randomized controlled trials involving alendronate, risedronate, ibandronate, zolendronate and denosumab was conducted using several databases. Randomized controlled trials (RCTs) with a double blind treatment period of at least 3 years were included. Men and Glucorticoid Induced osteoporosis, RCTs having as primary or secondary endpoints continuous values as body mineral density (BMD) and studies comparing different dosing regimens of the same agent, which are not used in clinical practice, were excluded. Only fully published reports were considered.A total of 9 RCTs were identified providing data on 31,393 participants. Zolendronate had the highest probability (52%) of being the most effective treatment towards placebo, followed by denosumab (46% probability), ibandronate and then alendronate and risedronate against placebo.Although the mixed treatment comparisons among alendronate, risedronate, ibandronate, zolendronate and denosumab did not show a statistically significant difference, this analysis suggests that zolendronate, compared to placebo, is expected to provide the highest rate of reduction in vertebral fractures affecting osteoporosis affected patients.

Clodronate belongs to the first generation of the large biphosphonate family of drugs (the non-nitrogen ones), and from the earliest studies, conducted in the ’70s, it distinguished itself from etidronate, a powerful antiresorptive drug that acts at osteoclastic level but, however, causes an osteomalacic bone mineralisation deficit clearly evident on histomorphometry. Common experience and several clinical and biological studies have shown that clodronate exerts an antalgic effect not only in fracture patients but also in those affected by osteoarthrosis or athritis. The drug, therefore, can usefully be included in the treatment regimen of rheumatic patients, also on account of its symptomatic effects. Clodronate in small doses (2 mg) also appears to exert protective effects on cartilage (an intra-articular formulation is indeed to be introduced), while at doses 10–100 times higher it undoubtedly has anti-inflammatory effects and, more specifically, antimacrophage and anticytokine effects (IL-1, IL-6, TNF-alpha, PGE). These effects are amplified by the incorporation of clodronate into monolayer liposomes. The drug may therefore be considered a coadjuvant in the treatment of arthritis originating from strong osteoclast activation induced by increased levels of cytokines and by an increased RANKL/OPG ratio. It is clear that clodronate can act both upstream, on cytokines, and downstream, on the osteoclast effector function.

Ulnar neuropathy at the elbow (UNE) is the second most frequent focal neuropathy of the arm. The aim of our study was to establish the frequency of anatomical changes of the cubital tunnel capable of causing UNE.Ninety-one consecutive patients affected by UNE, as established by neurophysiological studies, were enrolled in the study. All patients underwent ultrasonographic examination of the elbow, paying particular attention to the cubital tunnel, which was studied with either static or dynamic scans.Fifty-four of the 91 patients (59.3%) had at least one anatomical alteration of the cubital tunnel. The changes observed in our patients were: subluxation of the ulnar nerve (18.7%), luxation of the ulnar nerve (9.9%), presence of osteophytes (6.6%), presence of accessory muscle (8.8%), articular ganglion (1.1%), post-traumatic lesions (3.3%), presence of osseous fragment (1.1%).A possible cause of ulnar nerve entrapment at the elbow was found in more than half of the patients. Joint ultrasonography is indispensable for the identification of such alterations as it allows for both static and dynamic evaluation of the ulnar nerve.

The guidelines for the osteoporosis management were first drafted by a working group and then critically evaluated by the board of SIOMMMS. The most relevant points are: Definition: Osteoporosis is defined as a quantitative and qualitative deterioration of bone tissue leading to increased risk of fracture. Postmenopausal and senile osteoporosis are defined as primitive. Diagnosis: The cornerstone for the diagnosis of osteoporosis is the measurement of bone mineral density (BMD) by DXA (dual-energy X-ray absortiometry) at the femoral neck with T-score values -2.5 is usually not justified. Pharmacological intervention: The use of drugs registered for the treatment of osteoporosis are recommended when the benefits overcome the risk. This is the case only when the risk of fracture is rather high. FRAX™ is recognized as a useful tool for easily estimate the long-term fracture risk. SIOMMMS with these guidelines is committed to validate and further develop this diagnostic tool.