Antonella Grimaldi

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.

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.

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

AB0780 The Influence of DXA Inaccuracies on The Evaluation of A New Ultrasound Method for Proximal Femur Densitometry

Background According to the operational definition provided by the World Health Organization, osteoporosis is diagnosed when bone mineral density (BMD) measured at lumbar spine or proximal femur is at least 2.5 standard deviations lower than the young adult mean. Currently, dual X-ray absorptiometry (DXA) is the most widely adopted method for osteoporosis diagnosis, since it is considered the gold standard for BMD measurements. Therefore, DXA outcomes are often used as the ground truth reference to assess the diagnostic performance of novel alternative approaches that are undergoing clinical validation. However, very recent literature [1] documented that high percentages of clinical routine DXA investigations are typically affected by specific errors altering the final measurement result. This may also have significant effects on the comparative evaluation of the effectiveness of the innovative diagnostic methods under validation. Objectives To assess the actual diagnostic performance of the Osteoporosis Score (OS), a recently introduced ultrasound (US) parameter for osteoporosis diagnosis on the femoral neck, through a retrospective analysis of the DXA reports of the enrolled patients. Methods In a previous study [2], we directly assumed the outcome of DXA investigations as the gold standard reference to assess the OS performance for osteoporosis diagnosis on the femoral neck in a population of 170 patients aged in 55–80 years, obtaining an overall accuracy of 84.7% in patient classification (osteoporotic, osteopenic, or healthy) coupled with a good correlation between DXA-measured BMD and corresponding OS-derived values (r =0.71, p<0.001). In the present work, we performed a retrospective check of the 170 DXA reports, excluding all those cases presenting a typical DXA error as identified by recent literature (e.g., incorrect patient positioning, presence of artefacts, improper image segmentation, etc.) [1] and re-assessing the actual diagnostic accuracy of our US approach by considering only those patients having a reliable DXA report. Results 57 patients out of the initial 170 (33.5%) were excluded because of clear DXA inaccuracies. The overall agreement between DXA and OS-based diagnoses on the remaining 113 patients was 93.8% (r =0.79, p<0.001), ranging from a minimum of 85.7% (r =0.79, p<0.001) to a maximum of 95.6% (r =0.82, p<0.001) when single 5-year age intervals were considered. Therefore, undetected DXA errors had resulted in a significant underestimation of OS accuracy in our previous study. Conclusions The actual potential of the OS-based approach for osteoporosis diagnosis on the femoral neck was previously underestimated. The adopted method for retrospective analysis of DXA reports could be also used to re-assess the performance of different US methods that assumed routine DXA investigations as the gold standard reference. References Messina et al, Eur Radiol 2015;25:1504–11. Muratore et al, Osteoporos Int 2015;26(Suppl 1):P530. Acknowledgement This work was partially funded by FESR PO Apulia Region 2007–2013 – Action 1.2.4 (grant n. 3Q5AX31: ECHOLIGHT Project). Disclosure of Interest 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. Muratore: None declared, A. Greco: None declared, P. Pisani: None declared, M. Peccarisi: None declared, M. Aventaggiato: None declared, M. Di Paola: None declared, D. Costanza: None declared, A. Grimaldi: 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