Background: Adjuvant endocrine therapy is the treatment for estrogen-receptor (ER)-positive breast cancer (BC). Aromatase inhibitors (AIs) significantly reduce recurrence risk but cause significant bone loss and increased fracture risk. Denosumab (DmAb), an anti-osteoporotic treatment, shows promise in mitigating these effects. Aims: To assess the short-term effects of DmAb and AIs on bone health in ER-positive BC patients using Radiofrequency Echographic Multi-Spectrometry (REMS) compared with DXA. Methods: Post-menopausal BC patients.receiving AIs who were referred for osteoporosis assessment were retrospectively identified and classified into two groups according to routine clinical management: patients receiving 60mg DmAb every 6 months (Group A) and not receiving any anti-osteoporotic treatment (Group B). Bone health was evaluated at baseline (T0), 6- (T1), 12- (T2), and 18-months (T3). DXA and REMS were performed at T0 and T2, while REMS alone was performed at T1 and T3. Results: Group B showed a decline in spine and femoral BMD at all time points by REMS and at T2 by DXA. Group A, receiving DmAb, exhibited significant BMD improvements at both sites, observed at all time points by REMS and at T2 by DXA. Conclusions: Routine bone monitoring during AI therapy is essential for primary osteoporosis prevention. This study, for the first time, quantifies the short-, medium- and long-term effects of AIs on bone loss and the positive impact of DmAb on bone density recovery in BC patients without the use of radiation. REMS proved to be a reliable tool for longitudinal monitoring of treatment response in patients receiving anti-osteoporosis therapy.

Adjuvant endocrine therapy is the treatment for estrogen-receptor (ER)-positive breast cancer (BC). Aromatase inhibitors (AIs) reduce recurrence risk but accelerate bone loss and fracture risk. Denosumab (DmAb), an antiresorptive agent, shows promise in mitigating these effects. To assess the short-term effects of DmAb and AIs on bone health in ER-positive BC patients using Radiofrequency Echographic Multi-Spectrometry (REMS) compared with DXA. Post-menopausal BC patients receiving AIs who were referred for osteoporosis assessment were retrospectively identified and classified into 2 groups according to routine clinical management: patients receiving DmAb (Group A) or any anti-osteoporotic treatment (Group B). Bone health was evaluated at baseline (T0) and after 6 (T1), 12 (T2), and 18 months (T3). DXA was performed at T0 and T2, while REMS was also performed at T1 and T3. 364 patients were included in the study. Group B showed a progressive decline in spine and femoral BMD, detected at all time points. Conversely, Group A exhibited significant BMD improvements at both skeletal sites, observed at all time points. Over 18 months, lumbar spine REMS-BMD decreased of -3.92

Disclosure: E. Luna: None. F. Conversano*: None. F. Lombardi*: None. M. Muratore*: None. P. Pisani*: None. C. Stomaci*: None. S. Casciaro*: None. Background: Type 2 Diabetes Mellitus (T2DM) is a metabolic disease characterized by high blood glucose levels due to insulin resistance. Globally, approximately 462 million people are affected by T2DM, with significant socio-economic implications. Numerous studies have already established a link between T2DM and bone health, highlighting a markedly increased risk of fractures (up to 5 times higher than in healthy individuals). However, despite the elevated fracture risk, bone mass and strength in individuals with T2DM often remain within the normal range or even show increases. This phenomenon, known as the “diabetic paradox”, emphasizes the need to assess both bone quality and quantity. The mechanisms underlying bone involvement seem to involve the glycosylation of collagen by excess of glucose, which disrupts bone structure and increases fragility. Additionally, obesity, a common condition in T2DM, plays a crucial role by inducing inflammatory responses that further contribute to bone degradation. Objectives: The objective of this study is to assess the impact of T2DM on bone quality by using the Radiofrequency Echographic Multi Spectrometry (REMS)-based parameter Fragility Score (FS). REMS is an advanced ultrasound technology that assesses both bone quantity and quality through a simple scan of reference sites such as lumbar spine and femoral neck. The FS, which ranges from 0 to 100, reflects skeletal fragility independently of Bone Mineral Density (BMD), with a score of 100 indicating maximum similarity to a fractured bone model and 0 representing a healthy model. Methods: A total of 45T2DM patients (both genders) were evaluated and compared to a matched group of healthy controls (HC), for gender, ethnicity, age, and Body Mass Index (BMI). All patients underwent lumbar spine measurements (L1-L4), and differences in FS between the groups were analyzed using a t-test. Results: The mean age and BMI of the T2DM group and HC group were as follows: 69.7±10.7 y and 26.6±4.1 kg/m² for the T2DM group, and 69.5±10.8 y and 26.8±3.9 kg/m² for the HC group. The average FS at the lumbar spine was significantly higher in T2DM patients (53.6±17.0) compared to HC (49.8±16.7), with a mean difference of -3.8 ± 16.7. Conclusion: This study highlights the impaired bone quality in T2DM patients compared to healthy controls. The FS parameter provided by REMS offers a reliable method for assessing bone quality in this population, making it a valuable tool for bone health monitoring in clinical routine. Presentation: Saturday, July 12, 2025

BACKGROUND: Multiple mechanisms underlie the connection between osteoporosis and vertebral pain, beyond the established correlation from the occurrence of fragility fractures, both clinical and morphometric. Among these mechanisms are alterations in certain bone quality parameters, which result in the deterioration of vertebral trabecular architecture and have been correlated with the genesis of vertebral microfractures. Identifying these mechanisms necessitates a reinterpretation of spinal pain in osteoporotic patients without any evidence of fracture, often attributed to degenerative arthritic changes. This has important therapeutic implications, allowing for the possibility of effective pain treatments specific to the type of pain involved. Similarly to vertebral fractures, microfractures may also play a role in causing postural deviations and gait alterations through an antalgic mechanism, as detected by baropodometric examination. These, in turn, can contribute to the risk of falls and new vertebral fractures. Based on these premises, it was decided to combine these observations by evaluating the use of clodronate in the treatment of dorso-lumbar pain secondary to the deterioration of trabecular microarchitecture and in the prevention of trabecular microfractures. This was done using baropodometry as a tool for detecting vertebral pain and radiofrequency echographic multi spectrometry (REMS) technology for determining bone mineral density (BMD) and bone quality characteristics. METHODS: Thirty-six female patients with dorso-lumbar pain and densitometric T-scores between-2 and-2.5 were enrolled. All patients were prescribed clodronate 200 mg every 2 weeks, calcium carbonate 500 mg daily, and cholecalciferol 25,000 IU twice a month. All patients underwent REMS densitometry at T0 and T2 (8 months) and baropodometric examination at T0, T1 (4 months), and T2. The primary outcome was the number of patients achieving a 20% reduction in the WOMAC pain index (Western Ontario McMaster Universities Osteoarthritis Index), and the secondary outcome was the reduction in analgesic consumption in terms of days of use per month. Statistical significance of results was determined using Student's t-test. RESULTS: All patients included in the study showed alterations in foot support in both static and dynamic conditions at baseline. At T2, there was a statistically significant reduction (P<0.001) in the average differences in these alterations compared to T0 and T1; all patients showed a significant reduction in the Womac pain score (P<0.03 vs. baseline) and average paracetamol consumption (P<0.02 vs. baseline). In REMS, there was a slight improvement in the average BMD value over the 8-month study period, while the average Fragility Score values (a dimensionless indicator independent of BMD and directly correlated with bone microarchitecture) at T0 remained constant at T2, showing slight improvement in some cases. CONCLUSIONS: The results of this study highlight the analgesic efficacy of clodronate, supporting the possibility that, in osteoporotic patients, even minimal structural alterations in vertebral trabecular bone, in the absence of clinical or morphometric fractures, can cause pain. This suggests reconsidering the often purely mechanical, arthritic genesis attribution of the pain. The analgesic action of clodronate may thus also be expressed through the improvement of bone quality aspects.

Background Osteoporosis in males is largely under-diagnosed and under-treated, with most of the diagnosis confirmed only after an osteoporotic fracture. Therefore, there is an urgent need for highly accurate and precise technologies capable of identifying osteoporosis earlier, thereby avoiding complications from fragility fractures. Aims This study aimed to evaluate the diagnostic accuracy and precision of the non-ionizing technology Radiofrequency Echographic Multi Spectrometry (REMS) for the diagnosis of osteoporosis in a male population in comparison with conventional Dual-energy X-ray Absorptiometry (DXA). Methods A cohort of 603 Caucasian males aged between 30 and 90 years were involved in the study. All the enrolled patients underwent lumbar and femoral scans with both DXA and REMS. The diagnostic agreement between REMS and DXA-measured BMD was expressed by Pearson correlation coefficient and Bland-Altman method. The accuracy of the diagnostic classification was evaluated by the assessment of sensitivity and specificity considering DXA as reference. Results A significant correlation between REMS- and DXA-measured T-score values ( r = 0.91, p < 0.0001) for lumbar spine and for femoral neck (r = 0.90, p < 0.0001) documented the substantial equivalence of the two measurement techniques. Bland-Altman outcomes showed that the average difference in T-score measurement is very close to zero (−0.06 ± 0.60 g/cm 2 for lumbar spine and − 0.07 ± 0.44 g/cm 2 for femoral neck) confirming the agreement between the two techniques. Furthermore, REMS resulted an effective technique to discriminate osteoporotic patients from the non-osteoporotic ones on both lumbar spine (sensitivity = 90.1%, specificity = 93.6%) and femoral neck (sensitivity = 90.9%, specificity = 94.6%). Precision yielded RMS-CV = 0.40% for spine and RMS-CV = 0.34% for femur. Conclusion REMS, is a reliable technology for the diagnosis of osteoporosis also in men. This evidence corroborates its high diagnostic performance already observed in previous studies involving female populations.

Objective: Due to the limitations of available methods for muscle strength evaluation, there is a need to develop more effective ways to quantify muscle function and performance in individuals suffering from musculoskeletal diseases. This study investigated the relationship between handgrip strength and a novel parameter derived from ultrasound scans of the forearm obtained using Radiofrequency Echographic Multi Spectrometry (REMS) technology. Estimations of muscle strength were performed in two study groups: healthy subjects and individuals affected by sarcopenia. Methods: A total of 58 Caucasian volunteers (30 healthy individuals and 28 subjects affected by sarcopenia) were recruited. A handgrip strength test was used to measure the Maximum Voluntary Contraction (MVC) of each subject’s dominant arm. Transversal echographic scans of the forearm were performed using an EchoStation device (Echolight S.p.a., Lecce, Italy) equipped with a 40 mm linear probe. A dedicated segmentation algorithm was designed and optimized for automatic identification of the ulnar and radius muscle profiles. The correlation between MVC values and REMS-based estimations of MVC (MVCREMS) was established using a linear regression approach. Results: MVCREMS showed excellent correlation with the MVC taken as ground truth. A high correlation value (r=0.95) was found in the overall population, and the corresponding values in the healthy and pathological subgroups were r=0.90 and r=0.83, respectively (p<0.0001). Conclusion: This technique allows reliable estimation of muscle strength in both pathological and healthy subjects, and is a valid alternative to conventional handgrip tests for use in primary care. In the future, this technique might help to enhance the assessment, screening and prevention of musculoskeletal diseases.

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. 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. 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. 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. FS displayed a superior performance in fracture prediction, representing a valuable diagnostic tool to accurately detect a short-term fracture risk.

Abstract Disclosure: F.A. Lombardi: None. P. Pisani*: None. A.P. Quezada*: None. M. Muratore*: None. M. Di Paola*: None. E. Casciaro*: None. F. Conversano*: None. S. Casciaro: None. *Equal contributors in alphabetical order Thyroid hormones play a crucial role in skeletal development, adult bone turnover, and bone maintenance, but they can also have detrimental effects on bone formation when there is thyroid dysfunction. Thyrotoxicosis (hyperthyroidism), including subclinical illness, can affect bone metabolism, resulting in decreased Bone Mineral Density (BMD) and increased fractures risk, and is a significant contributor to secondary osteoporosis, especially in postmenopausal women. On the other hand, little is known about the impact of overt or subclinical hypothyroidism on bone metabolism. However, hypothyroidism lessens bone turnover, reducing both osteoclastic bone resorption and osteoblastic activity. Such alterations in bone metabolism could potentially result in an increase in bone mineralization, although data on BMD and the risk of fracture in hypothyroidism are lacking and conflicting. Radiofrequency Echographic Multi-spectrometry (REMS) is a novel radiation-free technology for assessing BMD and fracture risk. In this context, the goal of this study was to assess BMD using REMS in patients with and without hypothyroidism, in order to look a possible correlation between the disease, BMD loss and fracture risk. Methods: A sample of 51 Caucasian females with hypothyroidism was compared to a reference group of healthy women who were matched for gender, ethnicity, age, and body mass index (BMI). Using REMS technology, the BMD was measurement at the lumbar spine in all participants at the study. To determine whether the two groups’ lumbar spine BMD value varied, a t-test was run. Results: Patients with and without hypothyroidism were matched in order to get similar anthropometric parameters. In patient with and without hypothyroidism mean ± standard deviation (SD) for age and BMI are (64.8 ± 10.2, 65.2 ± 9.8) and (25.1 ± 3.6, 25.0 ± 3.7), respectively. Patients with hypothyroidism were shown to have a significative lumbar spine BMD difference (0.801 g/cm2 ± 0.063 vs 0.831 g/cm2 ± 0.071, p=0.03) respect to the healthy subjects. Conclusions: Although just a small number of hypothyroidism patients are included in this investigation, without any indication of the drug therapy and its effect, it has been shown that, as compared to controls, women with hypothyroidism have a net decline in REMS-measured BMD values. Based on this thought, REMS technology, thanks to its precision and diagnostic accuracy, might improve the efficient care and follow-up programmes of these patients. Presentation: Friday, June 16, 2023

Purpose: 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. Methods: 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. Results: 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-value < 0.001). 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). Conclusions: 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: 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.

Objective To describe the baseline characteristics of the patients enrolled in the QUality of life in patients with Axial Spondylo ARthritis (QUASAR) study in terms of quality of life (QoL), disease activity, therapy adherence, and work ability in a real-world setting. Methods QUASAR is an Italian multicentre, prospective 12-month observational study, including consecutive adult patients classified as axial spondyloarthritis (axSpA) according to the Assessment of Spondylo Arthritis international Society criteria for axSpA. Results Of 512 patients enrolled in 23 rheumatology centres, 80.7% had ankylosing spondylitis (AS) and 19.3% had non-radiographic axSpA (nr-axSpA). Mean ages were 34.1 +/- 13.3 years at axSpA symptoms onset and 39.5 +/- 13.0 years at diagnosis. Of the patients, 51.4% presented with >= 1 extra articular manifestation (EAM); the most common were psoriasis (17.8%) and uveitis (16.4%). Patients with nr-axSpA and AS had similar EAM rates, disease activity, and QoL. Biologic disease-modifying anti-rheumatic drugs (bDMARDs; 83.2%) were the most commonly received medication, followed by conventional synthetic DMARDs (22.9%) and non-steroidal anti-inflammatory drugs (NSAIDs; 16.6%). At baseline, higher treatment satisfaction was reported with bDMARDs which, together with NSAIDs, were associated with the best overall scores for disease activity, function, and QoL in the overall population and AS subgroup. Conclusion QUASAR is the first Italian prospective study that comprehensively evaluated a large axSpA patient sample in a real-world setting. This interim analysis at baseline confirmed that i) patients with AS and nr-axSpA have similar QoL and disease burden, ii) nearly all axSpA patients receive treatment, and iii) bDMARDs and NSAIDs, overall, yield better disease activity and QoL.