Laura Quarta

A novel ultrasound methodology for estimating spine mineral density.

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.

Canakinumab efficacy and long-term tocilizumab administration in tumor necrosis factor receptor-associated periodic syndrome (TRAPS).

Abstract 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.

Clinical utility of clodronate in the prevention and management of osteoporosis in patients intolerant of oral bisphosphonates.

Bisphosphonates have a long history in the treatment of osteoporosis and bone-related disease. This review focuses on the use of a specific nonaminobisphosphonate, clodronate, which appears to be much better tolerated than other bisphosphonates and free of high-risk contraindications. Specifically, this paper reviews its use in the prevention of osteoporosis in postmenopausal women, taking into account its tolerability profile and recent safety issues arising regarding the use of bisphosphonates.

FRI0568 Echosound approach for short-term follow-up of the denosumab effect on bmd recovery against aromatase inhibitor impact in breast cancer patients

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<0.01) according to DXA and to -2.22%±0.89% (p<0.01) according to EchoSound; Group B showed a BMD increase of 4.06%±1.49% (p<0.01) and 4.31% ±0.62% (p<0.01) as measured by DXA and EchoSound scans, respectively. At time T2, Group A showed a further BMD decrement, resulting in a total decrease of -3.95%±1.09% (p<0.01) with respect to T0 values; on the contrary, in Group B Denosumab treatment produced an additional BMD increment, resulting in a total BMD increase of 4.98%±1.03% (p<0.01) in the same 18-month period. Similar results were obtained for femoral neck BMD: a total BMD decrease of -2.37%±0.97% (p<0. 01) during the whole treatment period was observed in Group A, whereas a total BMD increment of 3.53%±0.43% (p<0.01) was measured in the same period in Group B. 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. Forcignanò: 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

THU0743-HPR A new and alternative treatment in sclerodermic digital ulcers

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 patients 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<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. 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

AB0847 Accurate assessment of femoral echosound approach performance through dxa error analysis

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<0.001) was obtained for the EchoSound approach when all the DXA reports were included in the analysis. In the second part of the study, 61 out of the initial 202 (30.4%) patients were excluded from the analysis because their DXA reports were affected by specific errors. An actual diagnostic accuracy of 94.2% was then obtained on the remaining 141 patients, together with a high correlation between DXA-measured BMDs and OS-derived BMD values (r =0.88, p<0.001). Intra- and inter-operator repeatability of OS-derived BMD values, expressed in terms of the root mean square coefficient of variation (RMS-CV), resulted equal to 0.29% and 0.34% for intra- and inter-operator variability, respectively, therefore documenting a very good measurement repeatability. 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

THU0485 An Advanced Echosound Approach for Femoral Neck Densitometry

Background Dual X-ray absorptiometry (DXA) currently represents the most common method for osteoporosis diagnosis and it is considered the gold standard for bone mineral density (BMD) measurements. However, DXA has also some important limitations that prevent its use for population screenings and this has led to the investigation of alternative ultrasound (US) approaches. In this context, we have recently introduced a new US methodology for osteoporosis diagnosis, which is based on a closely integrated processing of echographic images and corresponding “raw” radiofrequency (RF) signals (“echosound approach” [1]). The basic idea underlying this approach is that the RF signals acquired during an echographic scan of the investigated bone district can be employed to assess the bone health status through comparisons with previously derived reference spectral models. The implemented RF signal analysis method is also integrated with echographic imaging, which provides both the identification of the regions of interest and the simultaneous acquisition of a statistically significant number of US signals for each frame. Objectives To assess the accuracy of an advanced echosound approach, which was specifically tailored and optimized for femoral neck densitometry. Methods A total of 289 female patients (55–80 y) underwent both a femoral DXA and an echographic scan of proximal femur. Specific attention was paid to ensure adherence to correctness criteria for DXA scanning and data analysis as reported in the guidelines of the International Society for Clinical Densitometry [2]. The algorithm adopted for US data analysis was based on the echosound approach and included an additional dedicated signal compensation, which was specifically implemented to better account for the physiological variability in soft tissue thickness and corresponding US attenuation. The diagnostic agreement between DXA and US was assessed by accuracy calculation, Cohens k, Pearson correlation coefficient (r), root mean square error (RMSE), and Bland-Altman analysis, whereas the method precision was assessed by the root mean square (RMS) average of the SD (RMS-SD) of repeated measurements, the root mean square coefficient of variation (RMS-CV), and the least significant change for a 95% confidence level (LSC95). Results By assuming DXA output as the gold standard reference, the overall US accuracy in patient classification was 93.1% (k =0.882, p<0.0001). A strong correlation was also found between US-estimated BMD values and DXA-measured ones (r =0.86, p<0.001), with a low residual error (RMSE =0.044 g/cm2). The average difference between paired BMD measurements was -0.002 ± 0.089 g/cm2 (bias ± 2 SDs). US method precision, expressed as RMS-SD, resulted to be 0.003 g/cm2 (RMS-CV =0.29%; LSC95 =0.008 g/cm2). Conclusions The proposed echosound approach for femoral neck densitometry showed an excellent agreement with corresponding DXA diagnoses and an optimal measurement reproducibility, indicating a potential for an effective clinical routine adoption. References Casciaro et al, Clin Cases Min Bone Metab 2015;12:142–150 http://www.iscd.org/official-positions/2013-iscd-official-positions-adult/ Acknowledgement Work partially funded by FESR PO Apulia Region 2007–2013 – Action 1.2.4 (grant 3Q5AX31: ECHOLIGHT Project) Disclosure of Interest M. Muratore: None declared, F. Conversano Shareholder of: Echolight srl, a National Research Council spin-off that may or may not benefit from the results of this study, M. Peccarisi: None declared, P. Pisani: None declared, T. De Marco: None declared, R. Franchini: None declared, E. Casciaro Shareholder of: Echolight srl, a National Research Council spin-off that may or may not benefit from the results of this study, E. Quarta: None declared, L. Quarta: None declared, O. E. Casilli: None declared, S. Casciaro Shareholder of: Echolight srl, a National Research Council spin-off that may or may not benefit from the results of this study

SAT0292 An Innovative Echographic Parameter Reporting About Bone Fragility Measured on Lumbar Vertebrae

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

A new ultrasonic method for diagnosis of osteoporosis on hip and spine

INTRODUCTION: Currently, the only available method to reliably predict osteoporotic fractures is represented by bone mineral density (BMD) measurements on proximal femur or spine, which require the use of X-rays. Aim of this study is to illustrate working principles and feasibility of a new ultrasound (US) method for bone densitometry and osteoporosis diagnosis applicable on both proximal femur and spine.