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Background Accurate estimation of the imminent fragility fracture risk currently represents a challenging task. The novel Fragility Score (FS) parameter, obtained during a Radiofrequency Echographic Multi Spectrometry (REMS) scan of lumbar or femoral regions, has been developed for the non-ionizing estimation of skeletal fragility. Aims The aim of this study was to assess the performance of FS in the early identification of patients at risk for incident fragility fractures with respect to bone mineral density (BMD) measurements. Methods Data from 1989 Caucasians of both genders were analysed and the incidence of fractures was assessed during a follow-up period up to 5 years. The diagnostic performance of FS to discriminate between patients with and without incident fragility fracture in comparison to that of the BMD T-scores measured by both Dual X-ray Absorptiometry (DXA) and REMS was assessed through ROC analysis. Results Concerning the prediction of generic osteoporotic fractures, FS provided AUC = 0.811 for women and AUC = 0.780 for men, which resulted in AUC = 0.715 and AUC = 0.758, respectively, when adjusted for age and body mass index (BMI). For the prediction of hip fractures, the corresponding values were AUC = 0.780 for women and AUC = 0.809 for men, which became AUC = 0.735 and AUC = 0.758, respectively, after age- and BMI-adjustment. Overall, FS showed the highest prediction ability for any considered fracture type in both genders, resulting always being significantly higher than either T-scores, whose AUC values were in the range 0.472–0.709. Conclusion FS displayed a superior performance in fracture prediction, representing a valuable diagnostic tool to accurately detect a short-term fracture risk.

Identification of predictors of clinical response to certolizumab-pegol (certolizumab) may aid the decision-making process for treating patients with rheumatoid arthritis (RA), spondyloarthritis (SpA), and psoriatic arthritis (PsA). The aim of our study was to evaluate the effectiveness of certolizumab and identify any predictors of favorable outcome in patients with RA, PsA, or SpA. We studied 355 RA, SpA, and PsA patients starting treatment with certolizumab. Endpoints of the study were drug survival and identification of predictors of clinical outcome. Drug retention was analyzed via the Kaplan–Meier method, and hazard ratios (HRs) were estimated using Cox regression models. Of 355 certolizumab initiators, 178 had RA, 94 had PsA, and 83 had SpA. Biologic-naive RA patients had significantly higher survival rates (73.3%) than switchers taking certolizumab as a second-line (49.0%) or third- or next-line biologic agent (51.2%; p = 0.0001). Instead, PsA and SpA patients showed similar drug retention rates regardless of the line of treatment. A significant clinical improvement from baseline was seen at 3 months for RA (28 joint-Disease Activity Score [DAS28]; p = 0.001), PsA (Disease Activity Index for PsA [DAPSA]; p = 0.001), and SpA (Bath Ankylosing Disease Index; p = 0.01). Biologic-naive patients had the lowest HR (0.31; p = 0.001) of discontinuing certolizumab for RA, and the highest HR (7.94; p = 0.01) of achieving minimal disease activity (MDA) for PsA. For PsA, a predictor of late MDA was the achievement of low/remission DAPSA at 3 months, and 3-month low/remission DAS28 predicted late remission for RA. Our study revealed that the best predictor of certolizumab effectiveness in unselected patients with RA, PsA, or SpA was a biologic-naive status and achievement of an early response within 3 months.

To investigate the effectiveness of the T-score values provided by Radiofrequency Echographic Multi Spectrometry (REMS) in the identification of patients at risk for incident osteoporotic fractures.A population of Caucasian women (30-90 years), enrolled from 2013 to 2016, underwent dual X-ray absorptiometry (DXA) and REMS scans at axial sites. The incidence of fragility fractures was assessed during a follow-up period up to 5 years. Afterwards, patients with and without incident fractures were stratified in two age-matched groups with a 1: 2 proportion (Group F' and Group NF', respectively). The performance of REMS T-score in discriminating between the two groups was quantitatively assessed and compared with DXA.1516 patients were enrolled and 1370 completed the follow-up (mean ± SD: 3.7 ± 0.8 years; range: 1.9-5.0 years). Fracture incidence was 14.0%. Age-matched groups included 175 fractured patients and 350 non-fractured ones, respectively (median age 70.2 [interquartile range: 61.0-73.3] and 67.3 [65.4-69.8] years, p-value ns). The groups resulted also balanced for height, weight and BMI (p-values ns). As expected, the differences in REMS T-score (for vertebral site, -2.9 [-3.6 to -1.9] in Group F', -2.2 [-2.9 to -1.2] in Group NF') and DXA T-score (-2.8 [-3.3 to -1.9] in Group F', -2.2 [-2.9 to -1.4] in Group NF') were statistically significant (p-value0.001). Analogous results were obtained for femoral neck. Considering the T-score cut-off of -2.5, REMS identified Group F' patients with a sensitivity of 65.1% and specificity of 57.7% of (OR = 2.6, 95%CI: 1.77-3.76, p 0.001), whereas DXA showed a sensitivity of 57.1% and a specificity of 56.3% (OR = 1.7, 95%CI: 1.20-2.51, p-value = 0.0032). For femoral neck, REMS sensitivity and specificity were 40.2% and 79.9%, respectively, with an OR of 2.81 (95%CI: 1.80-4.39, p 0.001). DXA, instead, showed a sensitivity and specificity of 42.3% and 79.3%, respectively, with an OR of 2.68 (95%CI: 1.71-4.21, p 0.001).REMS T-score resulted an effective predictor for the risk of incident fragility fractures in a population-based sample of female subjects, representing a promising parameter to enhance osteoporosis diagnosis in the clinical routine.

Background Controversial experimental and clinical evidences have raised questions regarding the role of B12 and insulin-like growth factor 1 (IGF-1) on osteoblast function and bone health. In this study, we aimed to determine if the serum levels of B12, IGF-1 and procollagen type 1 N-terminal propeptide (P1NP) are associated with different degrees of bone mineral density (BMD). Methods A total of 287 subjects (190 women and 97 men; mean age 53 years) volunteered for evaluation of BMD and serum levels of B12, IGF-1 and P1NP; BMD at lumbar spine and proximal femur was evaluated by means of dual-energy X-ray absorption (DEXA) and expressed as T-score; serum concentrations of vitamin B12 and IGF1 were measured with a chemiluminescent immunoassay on Access II Beckman Coulter and DiaSorin Liaison XL analyzers, respectively; P1NP was assessed in 61 women and 35 men with reduced T-score on Roche Modular platform. Results A total of 101 subjects (66 women and 35 men) had a reduced BMD (T-score < -1) or osteoporosis with a T-score < -2.5, while 186 (124 women and 62 men) had a normal BMD. No significant difference in the B12 levels was observed between the subjects with reduced BMD (mean 265.15 pg/mL, 95% CI: 236 - 294.25) and those with normal BMD (mean 243.91, 95% CI: 225.78 - 262.03) (P = 0.1990); lower levels of IGF-1 were observed in the group with reduced BMD (mean 138.7 pg/mL, 95% CI: 126.75 - 150.83) than in that with normal BMD (mean 167.34, 95% CI: 136.49 - 198.18) (P< 0.001); serum levels of P1NP were significantly lower in 22 subjects younger than 50 years (mean 44.8 ng/mL, 95% CI: 36.4 - 53.1) vs. 74 subjects > 50 years old (mean 53.3, 95% CI: 34.3 - 72.3) (P < 0.001), and in women (mean 45.3, 95% CI: 37.6 - 52.9) vs. men (mean 62, 95% CI: 23 - 101) (P < 0.001). Conclusion We found no significant association between B12 levels and BMD, but significant associations of lower levels of IGF1 with reduced BMD and lower levels of P1NP with younger age and female sex were found; additional studies to further investigate the association of serum levels of B12, growth factors and biochemical turnover markers with human bone health are needed.

In the last decade, we have seen how Moore's law has lost its validity because it has reached the physical limit of miniaturization of components and the problem of thermal dissipation increasing with the chip’s clock frequency. For this reason, multi-core architectures were born, and quantum computing is being looked at as a possible solution for more computing power. The aim of this article is to demonstrate the possibility to realize computer architectures using multi-value logic. The objective is reached when we are able to translate any MVL function into the corresponding MVL circuit. The method proposed is completely independent of the basis adopted in the MVL domain and the physical quantity used to represent or transfer the domain values. Thus, this approach provides a new theoretical and practical context for applying new technologies or polymorphic materials, which can represent multiple values. In order to give concreteness to the analyzed theoretical aspects, we will represent a case study based on a classical combinational circuit, the summing circuit using LTspice® XVII (© Analog Device Corporation) as simulation environment has been carried out. The results show that it is possible to build MVL combinatorial circuits, although there are limitations because the proposed solution is just a proof of concept. The method can also be successfully applied to sequential MVL circuits, which are not the subject of the present article.

Objectives To assess the drug survival of golimumab, and predictors thereof, in patients affected with rheumatoid arthritis (RA), spondyloarthritis (SpA), and psoriatic arthritis (PsA) in a prospective observational cohort. Methods This is a non-interventional, longitudinal study on RA, SpA, and PsA patients starting treatment with golimumab. Endpoints were the 2 years persistence rate of golimumab and predictors of therapy discontinuation. Drug retention was analyzed using Kaplan–Meier and Cox models. Hazard ratios (HR) of golimumab discontinuation were estimated by Cox-regression hazard models. Results Of 416 patients starting golimumab, 171 biologic-naive and 245 inadequate responders to prior biologic drugs, 88 had RA, 147 SpA, and 181 PsA. Global 2 years drug retention was 70.2%, with no different hazard of discontinuation among diseases or line of biologic treatment. The strongest predictor of golimumab discontinuation was female gender (HR = 1.95). Golimumab monotherapy was associated with higher risk drug interruption (HR = 1.67). Within SpA, predictors of golimumab discontinuation were female sex (HR = 4.19), and absence of extra-articular manifestations (HR = 4.60). In PsA, duration of disease was negatively associated to drug interruption (HR = 0.93), whereas golimumab monotherapy was positively (HR = 2.21) associated. Interestingly, failing to achieve a good EULAR response at 3 months was the only predictor of golimumab discontinuation for RA patients (HR = 3.03). Conclusions This study provided evidence that golimumab has high retention rate in real-life settings. SpA male patients with extra-articular manifestations, PsA patients on co-therapy with DMARDs, and RA patients attaining an early clinical response had the highest probability to continue golimumab over 2 years.

Aim of this paper was to assess the discrimination power of a novel ultrasound (US) parameter, called the Fragility Score (F.S.), in the early identification of subjects prone to osteoporotic fractures. A total of 102 female patients were recruited: 49 with a recent osteoporotic fracture (“frail” subjects), 53 were controls without fracture history (“non-frail” subjects). All the patients underwent a spinal DXA (dual X-ray absorptiometry) and an abdominal US scan of lumbar vertebrae. Acquired US data were analyzed by a novel algorithm, which calculated the F.S. through spectral and statistical analyses involving both echographic images and corresponding “raw” signals. F.S. showed a good performance in discriminating “frail” from “non-frail” subjects (sensitivity = 76%, specificity = 68%), resulting even slightly more effective than DXA-measured BMD (sensitivity = 73%, specificity = 66%). This methodology has a potential to become an effective tool for the early identification, and timely treatment, of “frail” subjects.

Aim of this paper was to assess the clinical effectiveness of a novel ultrasound (US) approach for the estimation of bone fragility. A total of 85 female patients (40–80 years) were recruited and underwent conventional DXA investigations of both lumbar spine and proximal femur, an abdominal US scan of the lumbar spine and the FRAX® questionnaire for the calculation of osteoporotic fracture probabilities. Acquired US data were analyzed through an automatic algorithm that calculated the Fragility Score (F.S.), a parameter that estimates skeletal fragility from dedicated spectral and statistical analyses. F.S. showed a good correlation with the most reliable fracture risk predictions obtained by FRAX® (r = 0.71, p

Background To date numerous quantitative methods to diagnose osteoporosis at peripheral sites have been developed. REMS (Radiofrequency Echographic Multi Spectrometry) is a non-ionizing instrument used to quantitatively evaluate bone mineral density at lumbar spine and femoral neck sites [1]. Objectives To assess the accuracy of REMS in osteoporosis diagnosis at axial sites (lumbar spine and hip) compared with the gold standard, Dual-energy X-ray absorptiometry (DXA). Methods We enrolled patients aged from 50 to 75 years and perfomed a total of 1,699 and 1,794 lumbar spine and proximal femur scans with REMS and DXA. A quality checks on DXA and REMS acquired data were performed through direct examination of scans by experienced operators. We investigated the agreement between the two techniques calculating: Pearson`s correlation coefficient (r), Standard Error of the Estimate (SEE) and efficiency (sensitivity and specificity) in identifying osteoporotic individuals (i.e. T-score ≤ -2.5). Results We found a good linear correlation between REMS and DXA BMD estimation, Pearson coefficient r=0.938 for lumbar spine and r=0.933 for proximal femur (p Conclusion REMS exhibited a high sensitivity and specificity in identifying osteoporotic patients at lumbar spine or proximal femur sites compared with gold-standard DXA. REMS accurately diagnosed osteoporotic patients in clinical routine, at both lumbar spine and proximal femur sites, without using ionizing radiation. References [1] Di Paola M, Gatti D, Viapiana O, et al. Osteoporos Int, 2018 Disclosure of Interests Giovanni Adami: None declared, Giovanni Arioli: None declared, Gerolamo Bianchi: None declared, Maria Luisa Brandi: None declared, Carla Caffarelli: None declared, Loredana Cavalli: None declared, Marco Matucci-Cerinic Grant/research support from: Actelion, MSD, Pfizer, BMS, Chemomab, Sanipedia, Speakers bureau: Actelion, BMS; MSD, Janssen, Luisella Cianferotti Speakers bureau: Abiogen Pharma, Bruno Farmaceutici, Shire, Francesco Conversano Shareholder of: Francesco Conversano own stocks of Echolight Spa, Marco Di Paola: None declared, Davide Gatti Speakers bureau: Abiogen, Amgen, Janssen-Cilag, Mundipharma, Pfeizer, Giuseppe Girasole: None declared, Andrea Giusti: None declared, Stefano Gonnelli: None declared, Monica Manfedini: None declared, Maurizio Muratore: None declared, Ranuccio Nuti: None declared, Paola Pisani: None declared, Laura Quarta: None declared, Ombretta Viapiana Speakers bureau: Novartis, Abbvie, Eli-Lilly, Sanofi Genzyme

The MARI study investigated the prescription patterns of methotrexate (MTX) in patients presenting with rheumatoid arthritis (RA) in Italy. The primary aims of this cross-sectional analysis from the MARI study were to investigate the effect of gender on the prescription patterns and safety of MTX therapy.The study enrolled 1336 patients with RA. Retrospective data included patients' clinical history, previous treatment with MTX and other DMARDs, and MTX modifications in the previous 12-month period. Cross-sectional data included information about current treatment with MTX (dose and route of administration, and adverse events), concomitant medications, disease activity, and modifications of MTX treatment at study entry. The prescription patterns of MTX, rates and causes of MTX modifications were analysed according to gender.There were no significant differences related to gender in the prescription patterns of MTX, either at 6 months after starting MTX or at the time of study entry. In the 12 months prior to study entry, women (4%) were more likely to undergo MTX modifications (dose or route of administration) compared to men (2%, p=0.032), due to subjective intolerance, but this difference was no longer significant after controlling for confounders. At study entry, a higher proportion of women (27%) reported tolerability issues (nausea and weakness) related to MTX compared to men (14%, p=0.001). Although a similar percentage of males and females changed dose or route of administration of MTX at the time of study entry, the reasons for such modifications were dissimilar between genders. Particularly, a higher proportion of women underwent MTX modification due to intolerance (women 6% vs. men 1%, p=0.002).In Italy, prescription patterns of MTX do not differ between genders. However, women seem to be at higher risk of adverse events leading to MTX modifications.

Background:In recent years, the technology based on the analysis of raw ultrasound signals, Radiofrequency Echographic Multi Spectrometry (REMS), has been validated against Dual-energy X-ray Absorptiometry (DXA) for the diagnosis of osteoporosis and risk fracture prediction.Objectives:The aim of this multicenter observational study was to evaluate the diagnostic performance of REMS with respect to DXA in patients with different body mass index (BMI) categories.Methods:The inclusion criteria were: Caucasian women; age between 30 and 90 years; referral by their clinician for spinal DXA assessment; absence of significant walking impairment; signed informed consent.Patients underwent DXA and REMS scans at the lumbar spine, according to the procedures described in Di Paola et al. [1], including an a-posteriori quality check of the examinations in order to guarantee the maximum reliability of the diagnostic outputs.Three groups of patients were considered according to BMI:: underweight (BMI2), normal weight (BMI≥18.5 kg/m2 and 2), and overweight/obese (BMI≥25 kg/m2). DXA and REMS BMD values were also stratified in 3 diagnostic categories: osteoporotic, osteopenic, or healthy.The degree of correlation between DXA and REMS BMD values was quantified by calculating Pearson’s correlation coefficient (r). The diagnostic concordance between REMS and DXA was assessed by Cohen’s K considering the 3 diagnostic categories. REMS´s sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) for discriminating patients with and without osteoporosis were also calculated using DXA outcomes as reference. The same statistics were calculated accepting a 0.3 T-score tolerance on T-score values of borderline cases [1].Results:Overall, 4282 patients were enrolled and, after the quality check, 3501 couples of scans were included in the analyses. Of these patients, 122 (3.5%) were underweight, 1964 (56.1%) were normal weight, and 1415 (40.4%) were overweight. The results of the diagnostic performance in patients after BMI stratification are reported in Table 1.Conclusion:We observed an excellent correlation between REMS-based diagnosis with respect to the osteoporosis diagnosis performed by DXA in patients from each BMI category. These results indicate that lumbar spine REMS analysis is a suitable and accurate diagnostic tool for patients with different BMI.References:[1]Di Paola M et al. Osteoporos Int. 2019 Feb;30(2):391-402.Table 1.Diagnostic performance of REMS with respect to DXA considered as reference for patients of different body size.BMIcategoriesrNo tolerance0.3 T-score toleranceSens.Spec.PPVNPVKSens.Spec.PPVNPVKUnderweight0.94697.591.586.898.40.8998.293.289.299.30.91Normal weight0.94692.694.487.096.90.8597.596.792.399.00.93Overweight0.93086.795.884.896.40.8296.397.892.199.00.93Abbreviations: BMI = body mass index; r = Pearson correlation coefficient; Sens. = sensitivity; Spec. = specificity; PPV = positive predictive value; NPV = negative predictive value; K = Cohen’s K.The authors BC, ED, ADP, ML, MM, XN, DOC are equal contributors listed in alphabetical order.Disclosure of Interests:None declared.

Background: Radiofrequency Echographic Multi Spectrometry (REMS) is a non-ionizing technology for the densitometric assessment of osteoporosis. It has already been validated in Italian women with respect to the current clinical reference technology, Dual-energy X-ray Absorptiometry (DXA). Purpose: Aim of the current study was to assess the diagnostic accuracy of REMS technology with respect to DXA in a wider European clinical context. Methods: A total of 4307 female Caucasian patients aged between 30 and 90 years underwent DXA and REMS scans at femoral neck and/or lumbar spine (the site depending on the medical prescription). The acquired data underwent a rigorous quality check in order to exclude the erroneous DXA and REMS reports. The diagnostic agreement between the two technologies was assessed, also stratifying for patients' age groups. The ability to recognise previously fractured patients was also investigated. Results: Overall, 4245 lumbar spine scans and 4271 femoral neck scans were performed. The ability to discriminate patients with and without osteoporosis by femoral neck investigation resulted in sensitivity and specificity of 90.4% and 95.5%, respectively. For lumbar spine scans, a sensitivity of 90.9% and a specificity of 95.1% were obtained. The areas under the curve (AUCs) of the Receiver Operating Characteristic (ROC) curve evaluating the ability to discriminate groups of patients with previous osteoporotic fracture using DXA and REMS T-score values were 0.631 and 0.683 (p < 0.0001), respectively, for femoral neck scans, whereas 0.603 and 0.640 (p = 0.0002), respectively, for lumbar spine scans. Conclusion: The diagnostic effectiveness of REMS technology at reference anatomical sites for the assessment of osteoporosis has been confirmed in a large series of female patients, spanning from younger and pre-menopausal to elderly women up to 90 years, in a multicenter European clinical context.

Aim of this study was to perform a detailed clinical validation of a novel fully automatic method for vertebral morphometry. About 80 spine lateral radiographs were evaluated both automatically, by the proposed algorithm, and manually, by an experienced radiologist. The following metrics were used for algorithm performance assessment: sensitivity and specificity in vertebra detection; errors in the localisation of characteristic points of vertebral border; errors in the measurement of six diagnostic parameters; level of agreement and correlation between manual and automatic morphometric measurements; overall accuracy of automatic diagnoses with respect to manual ones. Obtained results showed a very good performance in vertebra detection (sensitivity = 89.1% and specificity = 100.0%). Average errors in the localisation of vertebral characteristic points were always smaller than 3 mm (range 0.85–2.79 mm), causing relative errors in diagnostic parameter values ranging from −5.01 to +6.10%. Bland–Altman analysis documented a mean error in automatic measurements of diagnostic ratios of 0.01 ± 0.18 (bias ± 2 SDs), while Pearson's correlation coefficient resulted r = 0.71 (p < 0.001). Finally, an optimal diagnostic coincidence (92.8%) was found between automatic and manual diagnoses. Therefore, the adopted method has a potential for an effective employment in clinical routine for reliable diagnosis of vertebral fractures.

Aim of this study was to perform a detailed clinical validation of a new fully automatic algorithm for vertebral interface segmentation in echographic images. Abdominal echographic scans of lumbar vertebrae L1–L4 were carried out on 150 female subjects with variable age and body mass index (BMI). Acquired datasets were automatically processed by the algorithm and the accuracy of the obtained segmentations was then evaluated by three independent experienced operators. Obtained results showed a very good specificity in vertebra detection (93.3%), coupled with a reasonable sensitivity (68.1%), representing a suitable compromise between the detection of a sufficient number of vertebrae for reliable diagnoses and the limitation of the corresponding computation time. Importantly, there was only a minimum presence of ‘false vertebrae’ detected (2.8%), resulting in a very low influence on subsequent diagnostic analyses. Furthermore, the algorithm was specifically tuned to provide an improved sensitivity (up to 73.1%) with increasing patient BMI, to keep a suitable number of correctly detected vertebrae even when the acquisition was intrinsically more difficult because of the augmented thickness of abdominal soft tissues. The proposed algorithm will represent an essential added value for developing echographic methods for the diagnosis of osteoporosis on lumbar vertebrae.

The aim of this study is to assess the accuracy of a novel ultrasound (US) approach for lumbar spine densitometry on overweight and obese women of variable age through a clinical validation study. The US method was originally developed in women with body mass index (BMI) 25 kg/m2) and underwent dual X-ray absorptiometry (DXA) of lumbar spine (L1–L4) and an US scan of the same vertebrae L1–L4, performed with a dedicated device providing both echographic images and ‘raw’ radiofrequency signals. Acquired US data were analysed through a novel automatic algorithm that performed a series of spectral and statistical analyses to calculate bone mineral density employing an innovative method. Diagnostic accuracy of US investigations was quantitatively assessed through a direct comparison with DXA results. The average agreement between US and DXA diagnoses was acceptable for patients aged 45–65 years (81.5%), while a slight decrement was observed for older patients (69.6%), which can be partially due to a decrease in DXA accuracy because of age-related degenerations. The adopted method has a potential for early osteoporosis diagnosis in people younger than 65 years, independent of their BMI.

Background:Aromatase inhibitor (AI) therapy in women with estrogen receptor-positive (ER+) breast cancer (BC) causes accelerated bone loss and increased risk of osteoporosis and fractures as side effects. Denosumab (i.e. 60 mg twice a year) is a viable therapy against bone resorption, but the short-term monitoring of bone mineral density (BMD) change with time is still an unmet clinical need, since the current techniques (including dual-energy X-ray absorptiometry, DXA) require 1-2 years between two consecutive measurements [1]. Radiofrequency Echographic Multi Spectrometry (REMS), with high performance in terms of precision and repeatability [2], might be used in this setting of patients for short-term monitoring of bone health-related parameters.Objectives:The objective is the short-term monitoring of the effect of AIs with/without denosumab on bone health in BC patients using REMS and DXA scans at lumbar spine.Methods:Post-menopausal ER+ BC patients treated with adjuvant AIs were recruited. Two subgroups were identified, whether receiving also 60 mg of denosumab therapy every 6 months or not (named Group A and Group B, respectively). All patients underwent baseline DXA and REMS lumbar spine scans at time T0, previous to the first AI therapy, and after 12 months (time T1). REMS scan only was repeated also at 18 months (T2), since a 6-month interval between two consecutive scans is not recommended for DXA. The bone mineral density (BMD) was measured with both techniques.Results:Overall, 254 ER+ BC patients were enrolled (127 per group). The effect of denosumab on BMD is reported in Table. The BMD values obtained by DXA and REMS were not significantly different at T0 and T1, whereas the difference between Group A and B at T1 was statistically significant (pConclusion:Several studies have shown the effect of denosumab on BMD over a period not less than 2 years from the start of treatment. This study showed the feasibility of short-term follow-up using REMS lumbar spine scans at 6-month time steps.References:[1]Diez-Perez A et al, Aging Clin Exp Res 2019;31(10):1375–89[2]Di Paola M et al, Osteoporos Int 2018;30:391–402Table 1.BMD values, expressed as g/cm2, measured by DXA and REMS for Group A (patients receiving AIs only) and Group B (patients receiving AIs and denosumab) at baseline (T0), 12 months (T1) and 18 months (T2) from the start of therapy. Results are presented as median values with 25thand 75thpercentiles. P-values are obtained with a Mann-Whitney test.DXAREMSScan timeGroup AGroup BpGroup AGroup BpT00.840 (0.719-0.959)0.867 (0.723-0.958)0.990.833 (0.708-0.949)0.855 (0.714-0.973)0.77T10.823 (0.702-0.944)0.889 (0.749-0.990)0.0030.819 (0.691-0.927)0.887 (0.740-1.018)T2---0.801 (0.679-0.909)0.899 (0.754-1.020)Note:The authorsD. Ciardo, M. Ciccarese, F. Conversano, M. Di Paola, R. Forcignanò, A. Grimaldi, F.A. Lombardi, M. Muratore and P. Pisaniare listed in alphabetical orderDisclosure of Interests:None declared

Background:The monitoring of bone mineral density (BMD) is a key aspect for patients undergoing pharmacological treatments that might cause BMD changes at non-physiological rates. At present, the short-term follow-up of patients under treatment in terms of BMD change with time remains an unmet clinical need, since the current techniques, including the gold standard dual X-ray absorptiometry (DXA), require at least 1 year between two consecutive measurements [1]. Therefore, an effective strategy for the assessment of BMD should guarantee high accuracy, precision and repeatability of the measurements.Objectives:The aim is to assess the influence of the variation 1) in patient position, 2) operator (both intra- and inter-) and 3) device on the REMS performance at lumbar spine and femoral neck.Methods:210 women were enrolled, divided in 7 groups of 30-patient each for the assessment of the parameters of interest, i.e. inter-device, intra- and inter-operator repeatability for lumbar spine scans and inter-patient position, inter-device, intra- and inter-operator repeatability for femoral neck scans.All patients underwent 2 REMS scans at lumbar spine or femoral neck, performed by the same operator or by 2 different operators or by the same operator using 2 different devices or in different patient position (i.e. supine without constraints or with a constrained 25°-rotation of the leg). The percentage coefficient of variation (CV%) with 95% confidence interval and least significant change for a 95% confidence level (LSC) have been calculated.Results:For lumbar spine, intra-operator repeatability resulted in CV%=0.37% (95%CI: 0.26%-0.48%), with LSC=1.02%, inter-operator repeatability resulted in CV%=0.55% (95% CI: 0.42%-0.68%), with LSC=1.52%, inter-device repeatability resulted in CV%=0.53% (95% CI: 0.40%-0.66%), with LSC=1.47%.For femoral neck, intra-operator repeatability resulted in CV%=0.33% (95%CI: 0.23%-0.43%), with LSC=0.91%, inter-operator repeatability resulted in CV%=0.47% (95% CI: 0.35%-0.59%), with LSC=1.30%, inter-device repeatability resulted in CV%=0.42% (95% CI: 0.30%-0.51%), with LSC=1.16%, inter-patient position repeatability resulted in CV%=0.24% (95% CI: 0.18%-0.30%), with LSC=0.66%.Conclusion:REMS densitometry is highly precise for both anatomical sites, showing high performance in repeatability. These results suggest that REMS might be a suitable technology for short-term monitoring. Moreover, thanks to its ionizing radiation-free approach, it might be applied for population mass investigations and prevention programs also in paediatric patients and pregnant women.References:Note:Carla Caffarelli, Giovanni Adami§, Giovanni Arioli§, Gerolamo Bianchi§, Maria Luisa Brandi§, Sergio Casciaro§, Luisella Cianferotti§, Delia Ciardo§, Francesco Conversano§, Davide Gatti§, Giuseppe Girasole§, Monica Manfredini§, Maurizio Muratore§, Paola Pisani§, Eugenio Quarta§, Laura Quarta§, Stefano Gonnelli§Equal contributors listed in alphabetical orderDisclosure of Interests:Carla Caffarelli: None declared, Giovanni Adami: None declared, Giovanni Arioli *: None declared, Gerolamo Bianchi Grant/research support from: Celgene, Consultant of: Amgen, Janssen, Merck Sharp & Dohme, Novartis, UCB, Speakers bureau: Abbvie, Abiogen, Alfa-Sigma, Amgen, BMS, Celgene, Chiesi, Eli Lilly, GSK, Janssen, Medac, Merck Sharp & Dohme, Novartis, Pfizer, Roche, Sanofi Genzyme, Servier, UCB, Maria Luisa Brandi: None declared, Sergio Casciaro: None declared, Luisella Cianferotti: None declared, Delia Ciardo: None declared, Francesco Conversano: None declared, Davide Gatti Speakers bureau: Davide Gatti reports personal fees from Abiogen, Amgen, Janssen-Cilag, Mundipharma, outside the submitted work., Giuseppe Girasole: None declared, Monica Manfedini: None declared, Maurizio Muratore: None declared, Paola Pisani: None declared, Eugenio Quarta: None declared, Laura Quarta: None declared, Stefano Gonnelli: None declared

Background:Radiofrequency Echographic Multi Spectrometry (REMS) is the first clinically available approach for direct non-ionizing measurement of bone mineral density (BMD) at lumbar spine (LS) and femoral neck (FN). Available scientific evidences describe BMD estimated by REMS as an accurate parameter for the diagnosis of osteoporosis [1].Objectives:To investigate the effectiveness of the T-score values provided by REMS scans at FN and LS in the identification of frail patients at risk for osteoporotic fractures and to compare the performance of REMS with the dual-energy X-ray absorptiometry (DXA) one.Methods:The patients underwent DXA and REMS scans at FN and at LS. Five clusters of fractures occurred during a median 3.5-year follow-up were identified whether involving the upper limb (forearm, elbow, humerus, wrist, hand), lower limb (tibia, ankle, metatarsus), thorax (shoulder blade, shoulder, rib), hip (femur or pelvis bones), or vertebrae. The ability of REMS and DXA T-score values to assess the incidence and site of fractures was evaluated through an analysis of covariance.Results:Seven hundred twenty-one Caucasian women were enrolled. Ninety-five fractures occurred, in particular 41 at upper limb, 16 at hip, 15 at thorax, 14 at lower limb, 9 at vertebrae. Patients characteristics are reported in table. Considering subcategories of fractured patients, there were not statistically significant differences for age, height, weight and BMI.In the analysis of covariance including age and BMI as covariates, the difference of T-score values between fractured and non-fractured patients is statistically significant for REMS and DXA at both sites.Lower FN T-score values were found for patients with fractures at hip or vertebra with respect to non-fractured patients both for REMS and DXA (pConclusion:REMS T-score measured at axial sites is an effective parameter for identification of patients at the risk of incident fragility fractures, in particular occurring at hip, vertebra or upper limb in a population-based sample of female subjects.References:[1]Diez-Perez, Aging Clin Exp Res 2019;31(10):1375–89Table 1.Baseline patient characteristics, expressed as median (25th– 75thpercentiles).Patients with incident fragility fracturePatients without incident fragility fracturep-value*Age [years]70 (60-73)59 (54-64)Height [cm]159 (155-164)160 (156-165)0.08Weight [kg]63 (58-70)62 (57-69)0.42BMI [kg/m2]24.97 (23.13-26.86)24.24 (22.22-26.59)0.04FN REMS T-score-2.3 (-2.8 – -1.7)-1.8 (-2.3 – -1.1)FN DXA T-score-2.2 (-2.8 – -1.6)-1.7 (-2.3 – -1.1)LS REMS T-score-3.0 (-3.5 – -2.0)-2.0 (-2.8 – -1.0)LS DXA T-score-2.8 (-3.4 – -1.8)-1.9 (-2.7 – -1.0)* Wilcoxon ranksum testFigure.Boxplot of the distribution of T-score values estimated REMS and DXA at FN and LS among patients without incident fragility fracture and patients with incident fragility fractures at different sites.Note:G. Adami, G. Arioli§, G. Bianchi§, M.L. Brandi§, C. Caffarelli§, L. Cianferotti§, G. Girasole§, S. Gonnelli§, M. Manfredini§, M. Muratore§, E. Quarta§, L. Quarta§, D. Gatti§ equal contributors listed in alphabetical order.Disclosure of Interests:Giovanni Adami: None declared, Giovanni Arioli *: None declared, Gerolamo Bianchi Grant/research support from: Celgene, Consultant of: Amgen, Janssen, Merck Sharp & Dohme, Novartis, UCB, Speakers bureau: Abbvie, Abiogen, Alfa-Sigma, Amgen, BMS, Celgene, Chiesi, Eli Lilly, GSK, Janssen, Medac, Merck Sharp & Dohme, Novartis, Pfizer, Roche, Sanofi Genzyme, Servier, UCB, Maria Luisa Brandi: None declared, Carla Caffarelli: None declared, Luisella Cianferotti: None declared, Giuseppe Girasole: None declared, Stefano Gonnelli: None declared, Monica Manfedini: None declared, Maurizio Muratore: None declared, Eugenio Quarta: None declared, Laura Quarta: None declared, Davide Gatti Speakers bureau: Davide Gatti reports personal fees from Abiogen, Amgen, Janssen-Cilag, Mundipharma, outside the submitted work.

Background Radiofrequency Echographic Multi Spectrometry (REMS) is an innovative densitometric technique able to automatically provide BMD values, which it has been shown to highly correlate with BMD obtained by DXA.1 Objectives To evaluate the accuracy of REMS measurements in postmenopausal women’s femoral neck health assessment versus DXA results in a multicenter clinical study. Methods In seven Italian referral centres for osteoporosis management, 1659 postmenopausal women (51–70 years old) were enrolled. Both DXA and REMS examinations were performed on each patient at femoral neck, in the strictest adherence to the corresponding guidelines. After excluding the scans affecting by errors, the REMS diagnostic accuracy was evaluated by assessing sensibility and specificity in the discrimination between “osteoporotic” and “healthy” patients; the degree of correlation between DXA-BMD and REMS-BMD was quantified through Pearson’s correlation coefficient (r) evaluation. In addition, the agreement between DXA-BMD and REMS-BMD was measured calculating the root mean square error (RMSE). Results A strong correlation (r=0.94, p Conclusions Thanks to its high capability to identify osteoporotic patients, and the strong correlation with DXA parameters, REMS has been shown to be an accurate non-ionising approach to detect osteoporosis at femoral neck. Reference [1] Casciaro S, et al. UMB2016;42:1337–56. Disclosure of Interest None declared

Background Chronic pain conditions, such as fibromyalgia(FM), are among the most common health problems managed by general practitioners, rheumatologists, clinical psychologists.FM is characterised by multifocal pain, fatigue, non-restorative sleep, cognitive complaints high levels of distress, associated with greater affect intensity. There’s evidence from randomised controlled trials that some treatments like pharmacotherapy, patient education,behavioural therapy and physiotherapy are effective in reducing symptoms;however the majority of the patients aren’t satisfied with the current treatments.HBOT showed some clinical effects that may induce a significant improvement of the FM symptoms. Objectives The goal of this work was to evaluate the effect of HBOT on FM symptoms. Methods 33 female patients aged 29–63 y, with FM were included in this work. Patients initially pharmacologically treated(Pregabalin 150 mg/die, Duloxetine 60 mg/die) with unsatisfactory clinical improvement, were enrolled at the Rheumatology Unit San Cesario-Italy. The HBOT protocol comprised 20 sessions,3d/w,90 min,100% oxygen at 2.5ATA. Patients were randomly assigned to treated and control groups and evaluated every month for the next 4 months:patients in group A were treated with 20 sessions of HOBT in the first 2 months and evaluated for the following 2 months;patients in group B used the pharmacological treatment for the first 2 months and then were treated with 20 session of HOBT in the last 2 months. During HOBT no pharmacological treatment was allowed. The treated group patients were evaluated at baseline and after 10 and 20 HBOT sessions. Evaluations consisted of physical examination, including tender point count, and socio-demographic and clinimetric questionnaires:Fibromyalgia Impact Questionnaire(FIQ), Functional Assessment of Chronic IllnessTherapy, Pittsburgh Sleep Quality Index, Quality of life, Beck Depression Inventory, State Trait Anxiety Inventory, Pain Catastrophizing Scale. Results 5 patients withdrew from the HBOT treatment for claustrophobia.HBOT led to significant amelioration of all FM symptoms, with significant improvement in life quality.HOBT leads to a reduction in the number of tender points in the 2 groups. This reduction occurs in the group A without changing during the following 2 months of osservation. In the group B the improvement is more related to the HOBT than to the therapy. The FIQ score improves in group A. No improvement was observed in the control group. Conclusions The analgesic effects of HBOT have been studied in nociceptive, in inflammatory and neuropathic pain models, and may be useful for the treatment of various chronic pain syndromes. Excessive pain in FM may be due to hyperexcitability of the pain processing pathways and under-activity of the pain inhibiting pathways in the brain. It has been shown that HBOT increases cell metabolism, reduces apoptosis, alleviates oxidative stress, increases neurotrophin and nitric oxide levels by enhancing mitochondrial function in neurons and glial cells, it may even promote the neurogenesis of endogenous neural stem cells.HBOT-induced neuroplasticity also leads to the repair of chronically impaired brain functions. Our data confirm the effecicy of HBOT in treating FM. Further studies are required to evaluate the protocol and to understand the duration of the clinical effect. Disclosure of Interest None declared

Background Osteoporosis is a systemic skeletal disease characterised by a compromised bone resistance that predisposes a subject to an increased risk of fracture. In particular, vertebral fractures are the most common of all osteoporotic fractures. A common clinically-used method for vertebral fracture detection is vertebral morphometry, which is based on measurements of front (Ha), middle (Hm), and rear (Hp) heights of vertebral bodies in radiographic images. This method is quantitative and does not require specific operator skills, but its actual accuracy is affected by errors made during the time-consuming manual measurements. Objectives In this work we propose a fully automatic algorithm for morphometric measurement, whose final goal is to reduce errors due to manual and semi-automatic processes. Our automatic method identifies the vertebrae and their edges. Then, the algorithm measures the characteristic vertebra heights (Ha, Hm, Hp) and determines possible vertebral deformities. Methods The vertebral morphometry uses lateral X-ray images and it is based on height measurements of vertebral bodies: Hp=||P1–P2||2, Ha = ||A1–A2||2, Hm = ||M1–M2||2. Where Pi: rear vertebral corners; Mi: middle vertebral points; Ai: front vertebral corners. The vertebral deformities can be determined as follows: biconcave deformity: Hm/Hp The main problem in implementing our fully automatic algorithm was the correct placement of the six reference points for each detected vertebra. Our approach first combined literature-reported methods for the identification of vertebrae in X-Ray images, subsequent emphasise the vertebral borders. The four corners of the vertebra (Pi and Ai) were localised on the borders detected vertebra.While, the middle points Mi were positioned at equal distance from Pi and Ai. Results The performance tests were based on the comparison between the results coming from our automatic approach and those obtained from the manual measurements by an experienced radiologist. We analysed 100 conventional lateral radiographs. The following metrics were used: sensitivity and specificity in vertebra detection; errors in the localization of characteristic points and in the measurement of diagnostic parameters; correlation between manual and automatic measurements. The results of our method showed a sensitivity of 90.8% and a specificity of 99.0%. Average errors in the localisation of vertebral characteristic points were always smaller than 3 mm. Bland-Altman analysis documented a mean error in automatic measurements of diagnostic ratios of 0.01±0.15 (bias ±2 SDs), while Pearson’s correlation coefficient resulted r=0.71 (p Conclusions Obtained results of our method compared to the results obtained by a trained radiologist showed an acceptable low error rate, a very good performance in vertebra detection and the same diagnosis (normal, biconcave deformity, crushing deformity, and wedge deformity). Overall, the adopted method has a strong potential for an effective employment in clinical routine for fast and accurate diagnosis of vertebral fractures. Reference [1] Melton LJ, et al. ”Epidemiology of vertebral fractures in women”. in Am J Epidemiol1989May;129(5):1000–1011. Disclosure of Interest None declared

Background Lower serum vitamin D levels have been associated with various autoimmune disorders. Especially in patients affected by Rheumatoid Arthritis (RA), has been observed an inverse correlation between serum levels of 25-hydroxyvitamin D (25OHD), pain and disease activity, but the cause-effect relationship is not clear. Objectives The aim of this exploratory study is to investigate the effects of supplementation with cholecalciferol (vitD3) in improving pain and disease activity in RA patients with or without vitamin D deficiency (25OHD Methods In this prospective open-label intervention study, patients fulfilling the EULAR/ACR 2010 criteria for diagnosis of RA, in non-remission (DAS28-CRP>2,6), on stable disease-modifying antirheumatic drugs, and whose treatment was not expected to be changed over a 3 month period following inclusion, were recruited. DAS28-CRP, VAS pain and serum levels of 25OHD, were evaluated at the baseline and after 3 months of supplementation with oral 100,000 IU/monthly of vitD3. Results A sample composed by 61 patients (47 females), with an average age (SD) of 5812 years within 26–86 years range were included. At baseline the mean (SD) 25OHD levels were 2210 ng/mL. 57% of the patients were found to have vitamin D deficiency ( Conclusions VitD3 supplementation appears to be associated with significant and different effects on pain and disease activity in RA patients dependent on 25OHD serum levels. Vitamin D deficiency ( Disclosure of Interest None declared

Background In BIO.PU.RE. Registry are collected data from patients being treated with Biologics from rheumatologic centres in Apulia (Southern Italy). Methods We analysed longitudinal data of consecutive patients, affected with RA, PsA or axial-SpA starting a treatment with certolizumab (CTZ) in the time frame from 1st January 2011 to 30th June 2017. Demographic and disease related characteristics were collected at baseline and at last observation visit. Primary endpoint was the persistence on CTZ, and secondary endpoint was the search of baseline predictors of drug survival and clinical outcomes. Drug survival was evaluated by Kaplan-Meier life table analysis. Estimates hazard ratios (HRs, 95% confidence intervals (CI)) of drug discontinuation or achievement of low-disease/remission in RA, and minimal disease activity (MDA) in PsA at last visit, adjusted for patient’s demographics, disease characteristics and prior biologic treatments were computed by Cox-regression stepwise backward models. Results 345 patients were included in this analysis (table 1). Global median survival time (95% CI) was 30 [23–36] months. Drug survival rate was significantly higher in SpA (63.9%, p=0.009) than in RA (54.0%) or PsA (54.5%). Within each disease, naive-CTZ patients showed higher survival rates than biologic-experienced patients in RA (63.4% vs 45.7%, p=0.0001), but not in PsA (59.1% vs 52.3%, p=0.60), or SpA (62.5% vs 64.4%, p=0.94). In the whole cohort, the only negative predictor of drug discontinuation was the CTZ-naive status (HR 0.62, 95 CI 0.40–0.96, p=0.03). This association was even stronger for RA (HR 0.45, 95 CI 0.26–0.77, p=0.004). In SpA, patient’s age at baseline was weakly correlated to CTZ stopping (HR 0.96, 95 CI 0.93–0.99, p=0.02), but no predictor of CTZ discontinuation was detected in PsA. No factor did correlate to the achievement of low disease/remission in RA, while co-medication with MTX was significantly associated to the achievement of MDA (HR 3.82, 95 CI 1.26–11.54, p=0.01) in PsA. Globally, the causes of discontinuation were: ineffectiveness (nr 94, 27.2%), adverse event (nr. 40, 11.6%), pregnancy (nr.1, 0.3%), remission (nr. 3, 0.9%), others (nr.13, 3.8%). Conclusions In our real-life experience CTZ seems to have better drug survival in PsA rather in RA and SpA; in all these polyarthritis was observed CTZ-naive status as negative predictor of drug discontinuation. Disclosure of Interest None declared

We performed a retrospective analysis to evaluate the survival on first line biologic drug of rheumatoid arthritis (RA) patients with potential occult HBV infection (pOBI). We analysed longitudinal data of 486 consecutive RA patients starting a first biological drug in a time frame from 1st January 2008 to 31st December 2014. Demographic and disease related characteristics were collected at baseline and at the last observation visit. Baseline serological markers of HBV infection and causes of treatment discontinuation were also recorded. Primary endpoint was the influence of pOBI on drug survival, estimated by Kaplan-Meier life table analysis. Estimates hazard ratios (HRs) of drug discontinuation, adjusted for disease characteristics, biological drug class and HBcAb status were computed by Cox-regression models. The retention rate was significantly lower in pOBI positive patients (58.2%) when compared to pOBI negative ones (67.8%) and this data was confirmed also when only discontinuation due to ineffectiveness was considered (pOBI positive 66.4% vs pOBI negative 75.3%, long rank 7.93, p=0.005). Cox regression models showed a significant association between HBcAb-neg (HR 0.58, 0.41-0.84), higher ESR-DAS28 at baseline (HR 1.07, 1.03-1.11) or RF/ACPA-neg (HR 1.46, 1.04-2.06) and drug discontinuation. Occult HBV infection seems to influence negatively the effectiveness of biological therapies in RA patients.

ObjectiveTo define the role of ultrasound (US) for the assessment of patients with rheumatoid arthritis (RA) in clinical remission, including joint and tendon evaluation.MethodsA multicentre longitudinal study has been promoted by the US Study Group of the Italian Society for Rheumatology. 25 Italian centres participated, enrolling consecutive patients with RA in clinical remission. All patients underwent complete clinical assessment (demographic data, disease characteristics, laboratory exams, clinical assessment of 28 joints and patient/physician-reported outcomes) and Power Doppler (PD) US evaluation of wrist, metacarpalphalangeal joints, proximal interphalangeal joints and synovial tendons of the hands and wrists at enrolment, 6 and 12 months. The association between clinical and US variables with flare, disability and radiographic progression was evaluated by univariable and adjusted logistic regression models.Results361 patients were enrolled, the mean age was 56.20 (±13.31) years and 261 were women, with a mean disease duration of 9.75 (±8.07) years. In the 12 months follow-up, 98/326 (30.1%) patients presented a disease flare. The concurrent presence of PD positive tenosynovitis and joint synovitis predicted disease flare, with an OR (95% CI) of 2.75 (1.45 to 5.20) in crude analyses and 2.09 (1.06 to 4.13) in adjusted analyses. US variables did not predict the worsening of function or radiographic progression. US was able to predict flare at 12 months but not at 6 months.ConclusionsPD positivity in tendons and joints is an independent risk factor of flare in patients with RA in clinical remission. Musculoskeletal ultrasound evaluation is a valuable tool to monitor and help decision making in patients with RA in clinical remission.

This study aims to evaluate the drug survival and effectiveness of ustekinumab in psoriatic arthritis (PsA) patients naïve to biologics or inadequate responders to tumor necrosis factor (TNF-IR) inhibitors in real life. PsA patients starting ustekinumab were enrolled from 2014 to 2016. Joint involvement, peripheral or axial, Psoriatic Area Severity Index, Disease Activity Psoriatic Arthritis (DAPSA), Lee Enthesitis Index, Health Assessment Questionnaire, body mass index, comorbidities, co-therapies, mechanism of action, and causes of discontinuation of prior TNFi were collected at baseline, and 6 and 12 months. Twelve-month drug survival was evaluated by Kaplan-Meier curves. Hazard ratios (HRs) of drug discontinuation adjusted for baseline factors were estimated by multiple Cox regression analysis. Percentages of DAPSA-based remission, as crude value and adjusted for drug retention (LUNDEX index), were compared by χ

Background Currently, the accepted “gold standard” method for bone mineral density (BMD) measurement and osteoporosis diagnosis related to the reference axial anatomical sites is dual-energy X-ray absorptiometry (DXA). However, actual DXA effectiveness is limited by several factors, including intrinsic accuracy uncertainties and specific errors in patient positioning, image segmentation, and post-acquisition data analysis, as documented by very recent literature [1]. This may affect the comparative evaluation of the effectiveness of novel diagnostic methods whose validation studies adopt DXA outcomes as standard reference to assess diagnostic performance. Objectives To assess the impact of DXA errors on the performance of an innovative ultrasound parameter for osteoporosis diagnosis on the femoral site, known as Osteoporosis Score (OS). Methods 202 patients aged in 46–75 years underwent two diagnostic investigations on the femoral neck: a conventional femoral DXA and an echographic scan performed by employing the innovative EchoSound technology [2]. Initially, the performance of the OS parameter was evaluated considering all the available DXA reports as reference in the data analysis, and calculating the corresponding accuracy in patient classification (osteoporotic, osteopenic, or healthy) and the correlation coefficient between the DXA-measured BMDs and the OS-derived BMD values. At a later stage, the DXA errors were taken into account by performing a strict quality control on DXA reports: all those cases affected by a typical inaccuracy [1] were excluded from the analysis and the actual diagnostic accuracy of the EchoSound technology was re-assessed by analysing only the reliable DXA reports. Intra- and inter-operator repeatability of OS-derived BMD values were also measured in a group of patients. Results A diagnostic accuracy of 84.4% (r =0.78, p Conclusions Undetected DXA errors had an impact on the accuracy evaluation of EchoSound femoral neck densitometry, causing an underestimation of OS performance in osteoporosis diagnosis. The quality control analysis on DXA reports can be useful to study the actual performance of different ultrasonic methods that considered routine DXA reports as the gold standard reference. References Eur Radiol 2015;25:1504. UMB 2015;41:281. Acknowledgements Work partially funded by FESR PO Apulia Region 2007–13 – Action 1.2.4 (grant n. 3Q5AX31: ECHOLIGHT Project). Disclosure of Interest M. Muratore: None declared, F. Conversano Shareholder of: Echolight spa, a National Research Council spin-off that may or may not benefit from results of this study, P. Pisani: None declared, M. Peccarisi Employee of: Echolight Spa, A. Greco Employee of: Echolight Spa, T. De Marco Employee of: Echolight Spa, E. Quarta: None declared, L. Quarta: None declared, A. Grimaldi: None declared, S. Casciaro Shareholder of: Echolight spa, a National Research Council spin-off that may or may not benefit from results of this study

Background The use of teriparatide in fracture management by high-energy trauma with loss of bone substance and muscle and skin with possible nerve/vascular lesions is poorly documented. The aim of our study is to evaluate how the intermittent administration of teriparatide may affect the bone consolidation newly generated and compression in patients with bone loss and my-skin during treatment reconstruction with the technique of resection Ilizarov-lengthening. Objectives In large trauma or in the outcomes of these,in which there is loss of bone substance and muscle and skin the technique of reconstruction of Ilizarov (1 mm/day) is used; the main problem is the long time required to reach complete healing with optimal bone consolidation newly generated and the compression outbreak of ensuring the mechanical strength necessary to be able to remove the external fixator (1). The rationale of this study, therefore, was to evaluate the influence of treatment with teriparatide, administered subcutaneously 1 dose 1 time/day from a pre-filled syringe of 20mcg and for a period of three months, the evolution radiographic, on the healing time and the external fixator removal and on the functional recovery quality in multiple trauma patient. Methods In our prospective study, we evaluated two groups of patients: Group 1: 9 patients treated with PTH during bone transport; Control Group 2: 10 patients treated with bone transport. Results The group 1 compared to the 2 (control group) showed a bone radiographic progression slower newly-generated in the first month of administration of teriparatide; subsequently it was observed an acceleration of bone maturation but not uniform; after about 3 months, the bone maturation accelerates further also at the level of the compression outbreak if already in compression, allowing the removal of the fixator about 1.5 months earlier than the estimated time. This is due to the reduction of the time allowed for “elongation stage” bone that physiologically is around 1mm/day, thus ensuring an optimal functional recovery. Conclusions The action of teriparatide (2) on bone healing is derived from increased differentiation of cells responsible for bone callus formation, chondrocytes and osteoblasts, mediated in part by increased activation of genes that produce the Wnt, Osterix and Runx2, all fundamental elements in the osteoblastogenesis. Although the sample examined is small for the specificity of the described treatment, the data reported showed that the intermittent administration of teriparatide is able to accelerate the timing for the “elongation stage” bone and therefore the bone healing and reconstructive treatment times in serious loss of substance. References Treatment of complex nonunion of the shaft of the tibia using Ilizarov technique and its functional outcome. Sahu RL, Ranjan R. Niger Med J. 2016 Mar-Apr;57(2):129–33. Stimulation of fracture-healing with systemic intermittent parathyroid hormone treatment. Barnes GL, Kakar S, Vora S, Morgan EF, Gerstenfeld LC, Einhorn TA. J Bone Joint Surg Am. 2008;90(Suppl 1):120–127. Disclosure of Interest None declared

Background The Aromatase Inhibitors (AIs)-based therapy used in breast cancer patients to profoundly lower estrogen levels seems to enhance the loss of bone mineral density (BMD) and to increase the fragility fracture rate [1]. Several clinical studies demonstrated that, in breast cancer patients that received the adjuvant AIs, the subcutaneous administration of Denosumab-based therapy significantly increased BMD values and reduced the rate of clinical fractures. Objectives To monitor the short-term Denosumab and AIs therapeutic effects on BMD in breast cancer patients through an innovative echographic approach, the EchoSound technology [2]. Methods 154 breast cancer patients selected for receiving the adiuvant AIs therapy were recruited. All the patients underwent spinal and femoral dual X-ray absorptiometry (DXA) examinations before AIs therapy administration starting (time T0). After AIs treatment starting, enrolled patients were divided into 2 groups: 105 patients received only the AIs treatment (Group A), whereas the remaining 49 patients (Group B) received also an additional Denosumab treatment, in order to contrast the BMD reduction induced by AIs administration. Follow-up measurements were conducted at two different time points: 12 (T1) and 18 (T2) months from AIs treatment starting. At time T1, patients underwent both DXA examinations and EchoSound echographic scans, whereas at time T2 only the echographic scans were performed, since DXA cannot be used for short-term follow-ups. Results At time T1, the following results were obtained on lumbar spine: Group A showed a BMD decrement, which was equal to -2.07%±1.66% (p Conclusions By using the EchoSound technology the short-term follow-up of the positive Denosumab effects on BMD reduction in patients treated with adjuvant AIs was feasible and accurate. This approach can be also useful to monitor the therapy effectiveness in patients undergoing specific anti-osteoporotic treatments. References J Clin Endocrinol Metab.2011;96:308. Clin Cases Min Bone Metab 2015;12:142. Acknowledgements Work partially funded by FESR PO Apulia Region 2007–13; Action 1.2.4 (grant n. 3Q5AX31: ECHOLIGHT Project). Disclosure of Interest P. Pisani: None declared, M. Muratore: None declared, F. Conversano Shareholder of: Echolight spa, a National Research Council spin-off that may or may not benefit from results of this study, E. Casciaro Shareholder of: Echolight spa, a National Research Council spin-off that may or may not benefit from results of this study, M. Di Paola: None declared, R. Forcignano: None declared, M. Ciccarese: None declared, G. Surico: None declared, L. Quarta: None declared, E. Quarta: None declared, D. Costanza: None declared, R. Franchini: None declared, R. Tarparelli Employee of: Echolight Spa, S. Casciaro Shareholder of: Echolight spa, a National Research Council spin-off that may or may not benefit from results of this study

Background Digital 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. Objectives The 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. Methods In 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. Results Mean 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 Conclusions Lecoxen 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 Interest None declared

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

Osteoporosis is the most common disorder of bone metabolism. The main consequence of this disease is the increased risk of fracture. Osteoporotic fractures represent a serious problem in terms of social and economic costs. Then, there is a strong need for the assessment of the best practices in prevention and treatment of osteoporosis. Dual X-ray absorptiometry (DXA) represents the current “gold standard” method for osteoporosis diagnosis. However, DXA cannot be employed for population mass screenings, because of required exposition to ionizing radiation and high management costs. The aim of this paper was to review the currently available techniques for osteoporosis diagnosis and also to illustrate the feasibility of an innovative quick, cheap and non-invasive ultrasound-based methodology. The results recently published by the authors' research group suggest that the proposed approach has the potential for routine application in early diagnosis, which is the key to resize the impact of osteoporosis on healthcare systems.

In Fig. 1 - paned D, incorrect image was published. This is now presented correctly in this article.

Osteoporosis is a silent disease without any evidence of disease until a fracture occurs. Approximately 200 million people in the world are affected by osteoporosis and 8.9 million fractures occur each year worldwide. Fractures of the hip are a major public health burden, by means of both social cost and health condition of the elderly because these fractures are one of the main causes of morbidity, impairment, decreased quality of life and mortality in women and men. The aim of this review is to analyze the most important factors related to the enormous impact of osteoporotic fractures on population. Among the most common risk factors, low body mass index; history of fragility fracture, environmental risk, early menopause, smoking, lack of vitamin D, endocrine disorders (for example insulin-dependent diabetes mellitus), use of glucocorticoids, excessive alcohol intake, immobility and others represented the main clinical risk factors associated with augmented risk of fragility fracture. The increasing trend of osteoporosis is accompanied by an underutilization of the available preventive strategies and only a small number of patients at high fracture risk are recognized and successively referred for therapy. This report provides analytic evidences to assess the best practices in osteoporosis management and indications for the adoption of a correct healthcare strategy to significantly reduce the osteoporosis burden. Early diagnosis is the key to resize the impact of osteoporosis on healthcare system. In this context, attention must be focused on the identification of high fracture risk among osteoporotic patients. It is necessary to increase national awareness campaigns across countries in order to reduce the osteoporotic fractures incidence.

Aim of this paper was to assess the diagnostic accuracy of a novel ultrasound (US) approach for femoral neck densitometry. A total of 173 female patients (56–75 years) were recruited and all of them underwent a dual X-ray absorptiometry (DXA) of the proximal femur and an US scan of the same anatomical district. Acquired US data were analysed through a novel algorithm that performed a series of spectral and statistical analyses in order to calculate bone mineral density employing an innovative method. Diagnostic accuracy of US investigations was quantitatively assessed through a direct comparison with DXA results. The average diagnostic agreement resulted pretty good (85.55%), with a maximum (88.00%) in correspondence of the youngest investigated patients (56–60 y). Overall, diagnostic accuracy showed only minimal variations with patient age, indicating that the proposed approach has the potential to be effectively employable for osteoporosis diagnosis in the whole considered age interval.

Background Subclinical synovial inflammation detected by ultrasonography (US) in patients with rheumatoid arthritis (RA) in clinical remission relates to disease flare. The impact of tenosynovitis in this context is not known. Objectives To evaluate the association between US-detected tenosynovitis and synovitis in RA patients in clinical remission and flare over 12-months. Methods STARTER is a multicentre cohort study of the US Study Group of the Italian Society for Rheumatology. Participants were selected on the basis of a reliability exercise and the availability of high-end equipment. Patients with RA in clinical remission underwent clinical evaluation and US synovitis (-S) and tenosynovitis (-T) were assessed categorically for Grey Scale (GS) and power Doppler (PD) at 11 joints, extensor and flexor tendons in both hands and wrists. Patients were seen at 6 and 12 months. Flare within 12 months was defined as increase of >1.2 or >0.6 if final DAS28>3.2. The relationship between the presence of GS-T/-S, PD-T/-S was evaluated by logistic models, presented as odds ratios (OR) and 95% confidence interval (CI), adjusted for pre-specified confounders. Results 361 patients (72.3% f, mean age (sd) 56.1 (13.3), median disease duration (IQR) 7.1 years (3.6–13.5)) were included. 98/326 (30.6%) patients had a flare within 12 months. Considering US variables separately, only PD-S significantly predicted flare (OR 1.87 (1.12,3.14)). When the model included both –T and –S, only the concurrent presence of –T and –S predicted flare (PD-T+-S: OR 2.06 (1.04, 4.07); GS-T+-S: OR 2.27, (1.01,5.10)), while isolated –S and –T did not. Conclusions In patients with RA in clinical remission, US-detected synovial and tenosynovial inflammation identifies patients at risk of flare. US might help decisions on management in this population. Disclosure of Interest None declared

Background The use of cyclooxygenase-2 inhibitors, a new class of analgesic drugs, is suggested in patients with hypersensitivity to nonsteroidal anti-inflammatory drugs (NSAIDs). Objective To evaluate tolerance to etoricoxib, a new cyclooxygenase-2 inhibitor, in NSAID-sensitive patients with urticaria-type adverse reactions. Patients Thirty-seven patients with adverse reactions to NSAIDs. Methods Single-blind, placebo-controlled oral challenge with increasing doses of etoricoxib. Results Thirty-four patients tolerated etoricoxib treatment without adverse reactions, but a generalized urticarial rash developed in 3 patients (8%). Conclusions Etoricoxib, like other cyclooxygenase-2 inhibitors, is a well-tolerated drug in most NSAID-sensitive patients. However, according to our experience, a previous challenge test in a safe environment may be necessary before prescribing the drug to such patients.

The patients’ adherence to osteoporosis treatments is low. In our study population a history of osteoporotic fractures was associated to better compliance and persistence; however, a 12-month randomized study carried out on 816 osteoporotic women showed that providing the patients with their individual fracture risk information did not prove effective. Several drugs are currently available for the treatment of osteoporosis, but the patients’ compliance and persistence with these treatments are low. This study aimed to both analyze the adherence to oral osteoporosis medications among Italian osteoporotic patients (cross-sectional study) and evaluate if providing patients with their individual fracture risk information may improve compliance and persistence (prospective study). A total of 3379 osteoporotic patients referred as outpatients for a visit 1 year after receiving a prescription of oral osteoporosis medications for the first time, were enrolled for the retrospective study. Moreover, 816 postmenopausal women receiving an oral prescription for osteoporosis for the first time, were randomized into two groups: group 1 (managed according to standard clinical practice) and group 2 (managed with greater patient involvement and information on the individual risk of major osteoporotic fractures calculated by DeFRA algorithm). In the retrospective study, a history of osteoporotic fractures, the frequency of drug administration and a condition of being overweight/obese had a significant influence on both compliance and persistence. Of the 816 patients enrolled in the longitudinal study, 731 (374 of group 1 and 357 of group 2) attended the 1 year follow-up visit. The percentage of women with high compliance or persistence was greater in group 2 (64.2 vs. 58.1 % and 66.8 vs. 62.6 %, respectively), but without reaching any statistical significance. Although providing the patients with their individual fracture risk information was not statistically effective, further studies on additional interventions able to improve the patients’ perceived risk of fracture are warranted.

Aim of this work was to evaluate the effectiveness of a recently introduced ultrasound (US) parameter for the estimation of bone mineral density (BMD) of the lumbar spine, when extensively used in a clinical context to investigate adult women of variable body mass index (BMI). A total of 414 female patients (aged 51–60 years) underwent a spinal dual X-ray absorptiometry (DXA) and an abdominal echographic scan of the lumbar spine. US images and corresponding unfiltered radiofrequency signals were analyzed through a new fully automatic algorithm, which performed a series of spectral and statistical analyses to calculate the novel diagnostic parameter, called the Osteoporosis Score (O.S.). Effectiveness of O.S. in BMD estimation and subsequent osteoporosis diagnosis was assessed through a direct comparison with DXA measurements (assumed as the gold standard reference), by quantifying the agreement between the two methods through accuracy calculation and Pearson correlation coefficient (r). A very good and significant correlation was found between O.S.-estimated BMDs and corresponding DXA values over the whole considered study population (r=0.81, p

Tumor necrosis factor receptor-associated periodic syndrome (TRAPS) is an autosomal dominantly inherited autoinflammatory disease caused by mutations in the TNFRSF1A gene. Treatment is aimed at preventing acute disease attacks, improving quality of life, and preventing long-term complications such as systemic reactive amyloidosis. Biologic agents have significantly improved TRAPS management. In particular, interleukin 1 (IL-1) inhibition either with the recombinant IL-1 receptor antagonist anakinra or with the human IgG1 anti-IL-1β monoclonal antibody canakinumab has recently shown to induce a prompt and stable disease remission. Conversely, the successful experience with IL-6 inhibition is nowadays limited to a single patient. Anyway, introduction of new treatment options for patients requiring a lifelong therapy is desirable. We describe two TRAPS patients (son and father) successfully treated with canakinumab and tocilizumab, respectively. In particular, we highlight the clinical and laboratory efficacy as well as the good safety profile of tocilizumab during a 42-month follow-up period.

Currently, the accepted “gold standard” method for bone mineral density (BMD) measurement and osteoporosis diagnosis is dual-energy X-ray absorptiometry (DXA). However, actual DXA effectiveness is limited by several factors, including intrinsic accuracy uncertainties and possible errors in patient positioning and/or post-acquisition data analysis. DXA employment is also restricted by the typical issues related to ionizing radiation employment (high costs, need of dedicated structures and certified operators, unsuitability for population screenings). The only commercially-available alternative to DXA is represented by “quantitative ultrasound” (QUS) approaches, which are radiation-free, cheaper and portable, but they cannot be applied on the reference anatomical sites (lumbar spine and proximal femur). Therefore, their documented clinical usefulness is restricted to calcaneal applications on elderly patients (aged over 65 y), in combination with clinical risk factors and only for the identification of healthy subjects at low fracture risk. Literature-reported studies performed some QUS measurements on proximal femur, but their clinical translation is mostly hindered by intrinsic factors (e.g., device bulkiness). An innovative ultrasound methodology has been recently introduced, which performs a combined analysis of B-mode images and corresponding “raw” radiofrequency signals acquired during an echographic scan of the target reference anatomical site, providing two novel parameters: Osteoporosis Score and Fragility Score, indicative of BMD level and bone strength, respectively. This article will provide a brief review of the available systems for osteoporosis diagnosis in clinical routine contexts, followed by a synthesis of the most promising research results on the latest ultrasound developments for early osteoporosis diagnosis and fracture prevention.

The paper reports the results from the observational retrospective-prospective RUBINO study conducted in Italy to assess the safety of rituximab in the treatment of rheumatoid arthritis (RA) in routine clinical practice. The percentage of patients who manifested at least one grade 3 or 4 adverse event (AE) assessed by the Common Terminology Criteria for Adverse Events version 3.0 (CTCAE v.3) during the observation period (primary objective) was evaluated. The percentage of patients manifesting a severe AE (SAE), clinical response to rituximab treatment, clinical remission according to disease activity score for 28 joints (DAS28) criteria, markers of disease and quality of life were also assessed. Fifty-three Italian rheumatology centers took part in the study. Patients with a diagnosis of RA and inadequate response to anti-tumor necrosis factor b (anti-TNFa) drugs were enrolled. Participating patients had previously received at least one cycle of rituximab, and treatment was still ongoing at the time of recruitment. Out of 205 patients enrolled, 60% manifested no form of AE, 14.2% had at least one grade 3 or 4 AE, and 11.2% patients reported an SAE. The overall percentage of patients manifesting AEs (40%) was lower compared to the DANCER (81% and 85%), REFLEX (85%) and RESET (85% and 69%) studies, but higher than that observed in the CERERRA registry (from 10.2% to 13.9%). This difference may be due to the shorter observation period applied in the CERERRA registry (only 12 months) compared to the RUBINO study (up to 3 years). All parameters of RA activity (erythrocyte sedimentation rate, C-reactive protein, health assessment questionnaire score, DAS28) improved significantly during the study.

We investigated the possible clinical feasibility and accuracy of an innovative ultrasound (US) method for diagnosis of osteoporosis of the spine. A total of 342 female patients (aged 51-60 y) underwent spinal dual X-ray absorptiometry and abdominal echographic scanning of the lumbar spine. Recruited patients were subdivided into a reference database used for US spectral model construction and a study population for repeatability and accuracy evaluation. US images and radiofrequency signals were analyzed via a new fully automatic algorithm that performed a series of spectral and statistical analyses, providing a novel diagnostic parameter called the osteoporosis score (O.S.). If dual X-ray absorptiometry is assumed to be the gold standard reference, the accuracy of O.S.-based diagnoses was 91.1%, with k = 0.859 (p < 0.0001). Significant correlations were also found between O.S.-estimated bone mineral densities and corresponding dual X-ray absorptiometry values, with r(2) values up to 0.73 and a root mean square error of 6.3%-9.3%. The results obtained suggest that the proposed method has the potential for future routine application in US-based diagnosis of osteoporosis.

Osteoporosis affects about 200 million subjects in the world and is responsible for 8.9 million fractures each year. The frequency of osteoporotic fractures is rising in many countries, due to the increased longevity of the population. In Europe, the annual cost of all osteoporotic fractures has been estimated to be 30 billion of Euros. In this paper, after an overview of the socioeconomic impact of osteoporosis in the world and in Italy, with particular focus on Apulia region, the most important techniques used to assess the fracture risk are briefly described. Moreover, the most commonly used pharmacological agents for the treatment of osteoporosis are reported. The aim of this review is to analyze the main factors causing the huge impact of osteoporosis on healthcare system, in terms of diagnosis and therapies, and to illustrate recent advances for treatment and prevention of this “silent disease”.

Aim of this work was to carry out a first clinical validation of a new ultrasound (US)-based approach to bone densitometry of lumbar spine. A total of 290 female patients were enrolled for this study (45-75 years of age, body mass index (BMI)

Effective prevention and management of osteoporosis would require suitable methods for population screenings and early diagnosis. Current clinically-available diagnostic methods are mainly based on the use of either X-rays or ultrasound (US). All X-ray based methods provide a measure of bone mineral density (BMD), but it has been demonstrated that other structural aspects of the bone are important in determining fracture risk, such as mechanical features and elastic properties, which cannot be assessed using densitometric techniques. Among the most commonly used techniques, dual X-ray absorptiometry (DXA) is considered the current "gold standard" for osteoporosis diagnosis and fracture risk prediction. Unfortunately, as other X-ray based techniques, DXA has specific limitations (e.g., use of ionizing radiation, large size of the equipment, high costs, limited availability) that hinder its application for population screenings and primary care diagnosis. This has resulted in an increasing interest in developing reliable pre-screening tools for osteoporosis such as quantitative ultrasound (QUS) scanners, which do not involve ionizing radiation exposure and represent a cheaper solution exploiting portable and widely available devices. Furthermore, the usefulness of QUS techniques in fracture risk prediction has been proven and, with the last developments, they are also becoming a more and more reliable approach for assessing bone quality. However, the US assessment of osteoporosis is currently used only as a pre-screening tool, requiring a subsequent diagnosis confirmation by means of a DXA evaluation. Here we illustrate the state of art in the early diagnosis of this "silent disease" and show up recent advances for its prevention and improved management through early diagnosis.