BackgroundDigital ulcers (DUs) are a major clinical problem for patients with systemic sclerosis (SSc). Patients with DUs may suffer from severe pain and often undergo a limitation of daily life activities, thus resulting in a functional impairment with a significant impact on the patient9s health-related quality of life. Prevention of further complications and lesions is possible if the initial evaluation is performed early and correctly and if a treatment is started promptly.ObjectivesThe primary objective is to demonstrate the effect of Lecoxen cream (Ekuberg Pharma, Italy) in comparison with another cream (Fitostimoline cream, DAMOR SpA, Italy) on the reduction of the number and size of DUs in patients with systemic sclerosis evaluating in addiction the reduction of pain dealing with DUs and quality of life.MethodsIn this single-blind randomized progressive trial 39 women, with confirmed digital ulcers present for at least 4 weeks with a surface area greater than 0.5 cm2 but smaller than 2,5 cm2, that follow Iloprost therapy (0,05mg/2 times/month), afferent to the Operative Unit (O.U.) of Rheumatology of the Local Health Unit (LHU) of San Cesario di Lecce, were randomized to receive the topical application of Lecoxen cream (group I: 20 women) or Fitostimoline cream (group II: 19 women). We took digital photographs to measure ulcer surface area and to draw the periwound area before the first cream application and after 30 days. Then an evaluation of DUs diameter and number was carried out. A tailored questionnaire was administered as Visual Analogue Scale (VAS) during monitoring visits, to evaluate intensity of pain. Furthermore quality of life was monitored through Short Form (36) Health Survey.ResultsMean age was similar in the two study groups with values of 45.4±5.6 years and 46.1±4.1 respectively. In the patients treated with Lecoxen cream, the reduction of lesion size was significantly higher (70%–75%) (p<0,001) in comparison with those registered in group II (40–45%) (p<0,05); a significant improvement was observed in levels of pain in Group I (30 days: p<0,001), while in group II the results of reduction were not significant. The analysis of SF36 survey showed highly significant reduction (p<0,001) of indexes in group I. At last visit, 32 ulcers were healed: 17 in the group I (p<0,001), 11 in the Group II (p<0,01). Two-way analysis of variance (ANOVA) test was used to examine differences. Intragroup changes were evaluated with the paired Student t-test. A p-value of <0.05 was considered to be significant.ConclusionsLecoxen cream showed the greatest effect on the mean reduction of the lesion size and pain levels. In the patients treated with Lecoxen cream the reduction of lesion size was 70%–75%; the reduction was smaller in the group II. At last visit, 32 ulcers were healed: 17 in the group I, 11 in the Group II. Data collected from SF36 surveys are very interesting, because they show a clear improvement in quality of life of scleroderma patients, who underwent three different treatments. In particular, a better subjective perception of tactile sensation and minor discomfort in the pathological skin have been reported. On the basis of the results, it could be argued that the medical device Lecoxen cream may be useful in the treatment of DUs in patients suffering from systemic sclerosis.Disclosure of InterestNone declared

Background Osteoporotic fractures represents a huge socio-economic burden: almost 3 million fragility fractures occur each year in Europe, causing over 40,000 deaths and direct costs of about € 40 billion for national healthcare systems. Currently, osteoporosis diagnosis is based on bone mineral density (BMD) assessments carried out through dual X-ray absorptiometry (DXA). Unfortunately, DXA cannot be employed for population mass screenings because of the typical issues related to ionizing radiation employment. Moreover, in recent years the actual suitability of DXA investigations for osteoporosis diagnosis has been questioned, since BMD demonstrated a low sensitivity in the identification of patients at high fracture risk. Objectives Aim of this work was to evaluate the performance of a new ultrasound (US) parameter obtained from a spinal scan in the discrimination between “frail” and “non-frail” subjects. Methods 95 female patients [50-80 years; BMI (body mass index) ≤30 kg/m2] were enrolled, 46 with a recent non-vertebral osteoporotic fracture (“frail” subjects) and 49 controls without fracture history (“non-frail” subjects). All the patients underwent two examinations: a conventional spinal DXA (Hologic Discovery) and an abdominal US scan of lumbar spine. US data were analyzed by an innovative algorithm that processed both echographic images and “raw” radiofrequency (RF) signals providing as final output a new parameter named Fragility Score (F.S.), which quantifies skeletal fragility on the basis of statistical and spectral comparisons with previously-derived RF model spectra of “frail” and “non-frail” vertebrae. Analysis of receiver operating characteristic (ROC) curves was employed to assess the accuracy of both F.S. and DXA-measured BMD in the discrimination between fractured and non-fractured subjects. An unpaired two-sided Student t-test was also used to measure the statistical significance of the differences in F.S. and BMD values between the groups. Results BMD showed a good discrimination power in the identification of fractured women: as expected, BMD values of the “frail” group (0.836±0.122 g/cm2) were significantly lower than the corresponding values found in the “non-frail” group (0.958±0.137 g/cm2, p<0.001). An analogous discrimination power was also found for F.S., whose values in fractured patients (58.0±15.4) were significantly higher than the corresponding values found in controls (44.7±10.5, p<0.001). On the other hand, “frail” subjects could not be discriminated from “non-frail” ones on the basis of age (63.8±8.9 y vs. 64.4±7.4 y, p n.s.) nor on the basis of BMI (24.59±2.36 vs. 24.36±2.55, p n.s.). The effective and comparable performance of F.S. and BMD was confirmed by ROC curve analysis (AUC=0.76 for both). Conclusions The proposed US method demonstrated the same accuracy of DXA-measured BMD in discriminating between fractured and non-fractured patients. Therefore, this novel non-ionizing approach has the potential to become an innovative tool for the early identification of “frail” subjects through population mass screenings. Acknowledgements This work was partially funded by FESR P.O. Apulia Region 2007-2013 – Action 1.2.4, grant n. 3Q5AX31 (ECHOLIGHT Project). Disclosure of Interest None declared

Background A high percentage of fragility fractures occur in subjects showing low bone strength in presence of a normal bone mineral density (BMD). Consequently, the approach to bone health assessment and fracture prevention is gradually changing, moving the focus from the identification of osteoporotic patients (based on BMD thresholds) towards the detection of individuals at high risk of fracture. Currently, the only validated tool that provides a precise quantification of the osteoporotic fracture risk is FRAX®, which is based on age, sex, body mass index (BMI) and a series of clinical risk factors, taking into account epidemiological data that are specific for patient country. FRAX® calculation can also include femoral neck BMD measured by dual X-ray absorptiometry (DXA), since it has been shown that integration of BMD and clinical risk factors provides improved fracture predictions. Nevertheless, DXA availability is limited by the typical issues related to ionizing radiation employment (high costs, need of dedicated structures with certified operators, long-term safety risks). Objectives Aim of this work was to compare the performance of DXA-measured BMD and a novel ultrasound (US) parameter measured on lumbar spine in the estimation of osteoporotic fracture risk as calculated by FRAX®. Methods 80 female patients [40-80 years; BMI (body mass index) ≤30 kg/m2] were enrolled for the study. Each of them answered the FRAX® questionnaire and underwent the following diagnostic examinations: a conventional DXA investigation of lumbar spine and proximal femur (Hologic Discovery) and an abdominal US scan of lumbar spine. US data were analyzed by an innovative algorithm that processed both echographic images and “raw” radiofrequency (RF) signals, providing as final output a new parameter named Fragility Score (F.S.), which quantifies bone strength. For each patient, FRAX®10-year probability of a major osteoporotic fracture was calculated both with and without femoral neck BMD inclusion. Pearson coefficient (r) was used to compare the performance of F.S. and BMD values in the estimation of fracture risk provided by FRAX®. Results Fracture risk provided by FRAX® with femoral BMD included in the calculation showed a good correlation with F.S. (r =0.70, p<0.001) and, as expected, with femoral neck BMD (r = -0.72, p<0.001), while the correlation was weaker for lumbar BMD (r = -0.44, p<0.001). Furthermore, F.S. was the only considered diagnostic parameter that kept an appreciable correlation with FRAX® predictions even when their calculation did not include femoral BMD (r =0.52 for F.S., r = -0.21 for femoral BMD, r = -0.07 for lumbar BMD; p<0.001 for all). Conclusions The proposed US-based F.S. alone showed a good correlation with osteoporotic fracture risk calculated by FRAX® integrated with femoral neck BMD, which represents the most reliable value. The performance of F.S. in fracture risk estimation was significantly better than lumbar BMD and comparable with femoral BMD. Therefore, F.S. is a suitable candidate to be employed for fracture risk prediction in primary healthcare settings. Acknowledgements This work was partially funded by FESR P.O. Apulia Region 2007-2013 – Action 1.2.4, grant n. 3Q5AX31 (ECHOLIGHT Project) Disclosure of Interest None declared

Systemic sclerosis (scleroderma) is a disease of unknown cause, the hallmark of which is induration of the skin. This bad condition of the skin influences negatively the quality of life of patients with scleroderma. The aim of the study was to verify the efficacy of two formulations, specifically designed to wash, moisturize and soothe the scleroderma skin. An independent, randomized, double blind, controlled trial was conducted in the Department of Rheumatology of "A. Galateo" Hospital in San Cesario di Lecce. Forty-six women affected by scleroderma, and treated with Iloprost every month, were divided into two groups: group 1 followed a specific treatment with cleansing formulation only, group 2 followed a combined treatment with the cleansing solution and the moisturizing solution. In addition, a third group was evaluated: 14 women, who did not undergo intravenous Iloprost therapy, were treated simultaneously with the cleansing formulation and the moisturizing formulation. The three treatments lasted for 4 weeks. Reduction in trans epidermal water loss (TEWL), increase in moisturization of the stratum corneum, reduction in Skin Score and improvement in quality of life were assessed. Very significant improvement in quality of life occurred in each group. Group 2 obtained very significant improvement in hydration and reduction in skin score and TEWL. The study showed that the daily use of both formulations proved to be effective in washing, hydrating and soothing the skin of patients with scleroderma, especially in association with Iloprost therapy.

Introduction: The identification of therapeutic strategies aimed both at preventing and treating osteoporosis and osteoporotic fractures has become increasingly important; in particular, it is essential to promote adequate patient adherence to treatment. The primary aim of this study was to evaluate the effects on lumbar and femoral bone mass density (BMD) after two different intramuscular (IM) dosing regimens of clodronate (CLD), a bisphosphonate shown to be efficacious in reducing the incidence of both vertebral and nonvertebral fractures. Secondary aims were the assessments of bone resorption markers, safety, tolerability, pain, and patient compliance. Methods: Sixty women with postmenopausal osteoporosis were randomized to two groups: group A (CLD 100 mg IM weekly for 12 months), and group B (CLD 200 mg IM every 2 weeks for 12 months). All patients received 1 g of calcium supplemented with 800 IU vitamin D3, orally, once daily for 12 months Lumbar and femoral BMD, measured by DEXA Norland XR-36 (Norland Co., Fort Atkinson, WI), and bone turnover markers were assessed at baseline and at 12 months. Each patient was administered a visual analog scale of pain at baseline and after 6 and 12 months of treatment. Results: A significant increase of BMD in both groups and in both skeletal sites was observed at 12 months versus baseline. In group A (n=28), lumbar BMD increased by 3.5% and femoral BMD by 2.1%; in group B (n=32), lumbar and femoral BMD rose by 3.4% and 2.2%, respectively. No difference was observed between groups. Bone resorption markers significantly reduced from baseline. Pain significantly improved as early as after 6 months of therapy and even more after 12 months, although no significant difference between the two groups was observed. The most common side effect was pain at the injection site, particularly in group B. Six patients in group A discontinued treatment and failed adherence to the therapeutic protocol. Conversely, no patient from group B discontinued therapy. Conclusion: In agreement with published data, in our two groups of patients, therapy with IM CLD at the doses of 100 mg/week and 200 mg/2 weeks was shown to be effective in increasing BMD, without differences between the two dosing regimens in all assessed efficacy parameters. Therefore, the “twice-a-month” regimen with 200 mg IM CLD may well promote an improved adherence with the same clinical efficacy and safety profile.

Studies of the mechanisms of periprosthetic bone loss have led to the development of pharmacologic strategies intended to enhance bone mass recovery after surgery and consequently prevent aseptic loosening and prolong the implant survival. Bisphosphonates, potent anti-resorptive drugs widely used in the treatment of osteoporosis and other disorders of bone metabolism, were shown to be particularly effective in reducing periprosthetic bone resorption in the first year after hip and knee arthroplasty, both cemented and cementless. Based on these results, we investigated the inhibitory effects of ibandronate on periprosthetic bone loss in a 2-year study of postmenopausal women that underwent cementless total hip arthroplasty. In the first 6 months both groups (A, treated with ibandronate 3 mg i.v. within five days after surgery and then with oral ibandronate 150 mg/month, plus calcium and vitamin D supplementation; and B, treated with calcium and vitamin D supplementation only) experienced bone loss, though to a lesser extent in group A. After 12 months, group A showed a remarkable BMD recovery, that was statistically significant versus baseline values (about +1, 74% of global BMD) and most evident in region R1 (+3, 81%) and R2 (+4, 12%); in group B, on the contrary, BMD values were unchanged compared with those at 6 months post-surgery. Quality of life scores also showed a greater improvement in group A, both at 6 and 12 months after surgery, likely because of the pain-reducing effects of ibandronate treatment.

A total of 507,671 people ≥65 experienced hip fractures between 2000 and 2005. In 2005, 94,471 people ≥65 were hospitalized due to hip fractures, corresponding to a 28.5% increase over 6 years. Most fractures occurred in patients ≥75 (82.9%; n = 420,890; +16% across 6 years), particularly in women (78.2%; n = 396,967).

TG4010 is an immunotherapeutic vaccine based on Modified Vaccinia virus Ankara (MVA) encoding the human tumor-associated antigen MUC1 and human IL-2. In combination with first-line standard of care chemotherapy in advanced metastatic non-small-cell lung cancer (NSCLC), repeated subcutaneous injection of TG4010 improved progression-free survival in phase 2b clinical trials. In preclinical tumor models, MVATG9931, the research version of TG4010, conferred antigen-specific responses against the weak antigen human MUC1. The combination of a suboptimal dose of MVATG9931 and the type B TLR9 ligand Litenimod (Li28) markedly increased survival in a subcutaneous RMA-MUC1 tumor model compared to the treatment with MVATG9931 or Li28 alone. The requirements for this protection were (i) de novo synthesis of MUC1, (ii) Li28 delivered several hours after MVATG9931 at the same site, (iii) at least two vaccination cycles, and (iv) implantation of MUC1-positive tumor cells in the vicinity to the vaccination site. Subcutaneously injected MVATG9931 allowed transient local gene expression and induced the local accumulation of MCP-1, RANTES, M-CSF, IL-15/IL-15R and IP-10. After repeated injection, CD4+ and CD8+ T lymphocytes, B lymphocytes, NK cells, pDCs, neutrophils, and macrophages accumulated around the injection site, local RANTES levels remained high. Delayed injection of Li28 into this environment, led to further accumulation of macrophages, the secretion of IL-18 and IL-1 beta, and an increase of the percentage of activated CD69+ NK cell. Combination treatment augmented the number of activated CD86+ DCs in the draining lymph nodes and increased the percentage of KLRG1+ CD127−CD8+ T cells at the injection site. In vivo depletion of macrophages around the injection site by Clodronate liposomes reduced local IL-18 levels and diminished survival rates significantly. Thus, sequential administration of MVATG9931 and Li28 improves local innate and adaptive immune defense against tumors, arguing for intratumoral delivery of this peculiar sequential combination therapy.

The aim of the present study was to determine the safety and efficacy of combined therapy with raloxifene (RLX) and clodronate (CLD) in postmenopausal women. We enrolled 45 women with postmenopausal osteoporosis. The patients were randomly assigned to two different therapeutic groups: RLX 60 mg/day (n = 23) and RLX 60 mg/day plus CLD 100 mg intramuscularly (i.m.) once every 10 days (n = 22); 1 g of calcium and 800 IU of vitamin D3 were also given daily to both groups. Lumbar and femoral bone mineral density (BMD) were assessed at baseline and after 12 months of therapy using the dual X-ray absorptiometry technique (Norland XR36). We measured the bone turnover markers NTx and CTx, bone alkaline phosphatase (BAP) and osteocalcin at baseline and after 12 months of therapy. Our data demonstrate that 1 year of combined RLX+CLD therapy induced a higher increase in lumbar BMD than treatment with RLX alone as well as a major decrease in bone resorption markers, suggesting an additive effect of CLD on bone mass and inhibition of bone turnover. Furthermore, after 1 year of therapy levels of bone formation markers (osteocalcin and BAP) had increased in both groups, but the increase in osteocalcin and BAP was significantly higher in the RLX+CLD treated group, suggesting that, in addition to its inhibitory effects on resorption, CLD might also have stimulatory effects on mature osteoblast activity.

OBJECTIVE:To evaluate if parenteral gold-therapy with Sodium gold thiosulfate is effective and safe for the treatment of rheumatoid arthritis we began an open, multicenter trial.METHODS:126 rheumatoid arthritis patients were treated with Sodium gold thiosulfate for two years. Efficacy, quality of life, progression of joint damage, inflammatory parameters and side effects were evaluated.RESULTS:Gold salts reduced joint inflammation and improved subjective and objective symptoms, quality of life and activity of illness within 6 months. Side effects appeared in 13,8% of all cases and regressed, promptly, when gold therapy stopped. The poor efficacy caused the interruption and the change from the gold therapy to others disease-modifying anti-rheumatic drugs (DMRDs) in 17,8 % of the patients.CONCLUSIONS:The follow-up showed Sodium gold thiosulfate was effective in Rheumatoid Arthritis and the survival in therapy was of 77,8% to one year and of 68,4% to two years.

Steroid therapy is the third most common cause of osteoporosis, after loss of gonad function and senescence. The aim of the present study was to evaluate the protective action of clodronate on bone mass loss induced by steroid therapy. Sixty patients with bronchial asthma receiving either fluticasone (250 mg x 4/day) or beclomethasone (250 mg x 4/day) inhaled corticosteroid treatment were enrolled. Half the patients received combination treatment with clodronate (100 mg i.m./14 days), for a total period of 12 months. All patients were evaluated at baseline and at the end of treatment for bone mineral density (BMD) and calcium/phosphor metabolism parameters (kalemia, kaluria, phosphoremia, phosphaturia, alkaline phosphatase and hydroxyprolinuria over a 24-h period). The results of this preliminary study confirm the protective influence of clodronate on bone mass loss, as documented by the increment in mean values in BMD reported at the end of treatment compared with baseline values.