Health-related quality of life trajectories in melanoma patients after electrochemotherapy: real-world insights from the InspECT register.

BACKGROUND: Electrochemotherapy (ECT) effectively controls skin metastases from cutaneous melanoma. OBJECTIVES: This study aimed to evaluate health-related quality of life (HRQoL) in melanoma patients pre-/post-ECT and its effect on treatment outcome. METHODS: The analysis included prospective data from the International Network for Sharing Practices of ECT register. Following the Standard Operating Procedures, patients received intravenous or intratumoural bleomycin (15,000 IU/m2 ; 1000 IU mL/cm3 ) followed by 100-microsecond, 1000-V/cm electric pulses. Endpoints included response (RECIST v3.0), local progression-free survival (LPFS), toxicity (CTCAE v5.0), and patient-reported HRQoL at baseline, one, two, four and ten months (EuroQol [EQ-5D-3L], including 5-item utility score [EQ-5D] and visual analogue scale for self-reported health state [EQ-VAS]). Comparisons within/between subgroups were made for statistical and minimal important differences (MID). HRQoL scores and clinical covariates were analysed to identify predictors of response in multivariate analysis. RESULTS: Median tumour size was 2 cm. Complete response rate, G3 toxicity and one-year LPFS in 378 patients (76% of the melanoma cohort) were 47%, 5%, and 78%. At baseline, age-paired HRQoL did not differ from the general European population. Following ECT, both EQ-5D and EQ-VAS scores remained within MID boundaries, particularly among complete responders. A subanalysis of the EQ-5D items revealed a statistically significant deterioration in pain/discomfort and mobility (restored within four months), and self-care and usual activities (throughout the follow-up) domains. Concomitant checkpoint inhibition correlated with better EQ-5D and EQ-VAS trajectories. Baseline EQ-5D was the exclusive independent predictor for complete response (RR 14.76, p=0.001). CONCLUSIONS: HRQoL of ECT melanoma patients parallels the general population and is preserved in complete responders. Transient deterioration in pain/discomfort and mobility and persistent decline in self-care and usual activities may warrant targeted support interventions. Combination with checkpoint inhibitors is associated with better QoL outcomes. Baseline HRQoL provides predictive information which can help identify patients most likely to respond.

Electrochemotherapy in the treatment of cutaneous malignancy: Outcomes and subgroup analysis from the cumulative results from the pan-European International Network for Sharing Practice in Electrochemotherapy database for 2482 lesions in 987 patients (2008-2019).

BACKGROUND: Electrochemotherapy (ECT) is a treatment for both primary and secondary cutaneous tumours. The international Network for sharing practices on ECT group investigates treatment outcomes after ECT using a common database with defined parameters. METHODS: Twenty-eight centres across Europe prospectively uploaded data over an 11-year period. Response rates were investigated in relation to primary diagnosis, tumour size, choice of electrode type, route of bleomycin administration, electrical parameters recorded and previous irradiation in the treated field. RESULTS: Nine hundred eighty-seven patients, with 2482 tumour lesions were included in analysis. The overall response (OR) rate was 85% (complete response [CR]: 70%, partial response rate: 15%, stable disease: 11%, and progressive disease: 2%). For different histologies, OR and CR rates for metastases of malignant melanoma were 82% and 64%, basal cell carcinoma were 96% and 85%, breast cancer metastases were 77% and 62%, squamous cell carcinoma were 80% and 63% as well as Kaposi's sarcoma were 98% and 91%, respectively. Variance was demonstrated across histotypes (p < 0.0001) and in accordance with size of lesion treated (dichotomised at diameter of 3 cm (p < 0.0001). Hexagonal electrodes were generally used for larger tumours, but for tumours up to 3 cm, linear array electrodes provided better tumour control than hexagonal electrodes (80%:74%, p < 0.003). For tumours more than 2 cm, intravenous administration was superior to intratumoural (IT) administration (p < 0.05). Current recorded varied across tumour histologies and size but did not influence response rate. In previously irradiated areas, responses were selectively lower for IT administration. CONCLUSIONS: These cumulative data endorse efficiency of ECT across a broad range of histotypes. Analysis of 2482 lesions details subgroup analysis on treatment response informing future treatment choices.

Electrochemotherapy of unresectable cutaneous tumours with reduced dosages of intravenous bleomycin: analysis of 57 patients from the International Network for Sharing Practices of Electrochemotherapy registry.

BACKGROUND: Electrochemotherapy (ECT) is currently used to treat unresectable superficial tumours of different histotypes through the combination of cytotoxic chemotherapy and local application of electric pulses. In 2006, a collaborative project defined the ESOPE (European Standard Operating Procedures of Electrochemotherapy) guidelines to standardize the procedure. The International Network for Sharing Practices of Electrochemotherapy (InspECT) aims to refine the ESOPE and improve clinical practice. Limiting patient exposure to systemic chemotherapy would be advisable to ameliorate ECT safety profile. OBJECTIVE: The aim of this study was to evaluate the efficacy and toxicity of ECT with reduced chemotherapy dosages. METHODS: In a retrospective analysis of a prospectively maintained database (InspECT registry), we evaluated the outcome of patients who received ECT with reduced dosages of bleomycin (7500, 10 000 or 13 500 IU/m2 , instead of the standard dose of 15 000 IU/m2 ). Tumour response in melanoma patients was compared with melanoma patients of the InspECT registry who received the standard dose of bleomycin. RESULTS: We identified 57 patients with 147 tumours (melanoma, 38.6%; squamous cell carcinoma, 22.8%; basal cell carcinoma, 17.5%; breast cancer 7%; Kaposi sarcoma 7%; other histotypes, 7.1%). Per-tumour complete response (CR) rate at 60 days was 70.1% (partial, 16.3%); per-patient CR was 57.9% (partial, 21.1%). Local pain was the most frequently reported side-effect (n = 22 patients [39%]), mostly mild; two patients experienced flu-like symptoms, one patient nausea. We observed the same CR rate (55%) in patients with melanoma treated by reduced or conventional bleomycin dosages (P = 1.00). CONCLUSIONS: Electrochemotherapy performed with reduced bleomycin dosages could be as effective as with currently recommended dose. Patients with impaired renal function or candidate to multiple ECT cycles could benefit from a reduced dose protocol. Our findings need prospective confirmation before being adopted in clinical practice.

Electrochemotherapy in the treatment of metastatic malignant melanoma: a prospective cohort study by InspECT.

BACKGROUND: (ECT) is an effective local treatment for cutaneous metastasis. Treatment involves the administration of chemotherapeutic drugs followed by delivery of electrical pulses to the tumour. OBJECTIVES: To investigate the effectiveness of ECT in cutaneous metastases of melanoma and to identify factors that affect (beneficially or adversely) the outcome. METHODS: Thirteen cancer centres in the International Network for Sharing Practices on Electrochemotherapy consecutively and prospectively uploaded data to a common database. ECT consisted of intratumoral or intravenous injection of bleomycin, followed by application of electric pulses under local or general anaesthesia. RESULTS: In total, 151 patients with metastatic melanoma were identified from the database, 114 of whom had follow-up data of 60 days or more. Eighty-four of these patients (74%) experienced an overall response (OR = complete response + partial response). Overall, 394 lesions were treated, of which 306 (78%) showed OR, with 229 showing complete response (58%). In multivariate analysis, factors positively associated with overall response were coverage of deep margins, absence of visceral metastases, presence of lymphoedema and treatment of nonirradiated areas. Factors significantly associated with complete response to ECT treatment were coverage of deep margins, previous irradiation of the treated area and tumour size (< 3 cm). One-year overall survival in this cohort of patients was 67% (95% confidence interval 57-77%), while melanoma-specific survival was 74% (95% confidence interval 64-84%). No serious adverse events were reported, and the treatment was in general very well tolerated. CONCLUSIONS: ECT is a highly effective local treatment for melanoma metastases in the skin, with no severe adverse effects noted in this study. In the presence of certain clinical factors, ECT may be considered for local tumour control as an alternative to established local treatments, or as an adjunct to systemic treatments.

Bone status in preterm infant: influences of different nutritional regimens and possible markers of bone disease.

OBJECTIVE: The objective of this study was to evaluate possible influences of parenteral nutrition on growth and bone development in preterms and to search for markers of bone status. STUDY DESIGN: Metacarpus bone transmission time (mc-BTT) was performed at birth, 21 days and 36 weeks of gestational age (GA) in preterms, receiving two different nutritional regimens, together with biochemical analysis. RESULT: A total of 234 patients were studied. Newborns with aggressive nutrition had significantly better growth rate and higher values of mc-BTT until discharge. Mc-BTT at day 21 correlates positively with nutritional intakes and phosphatemia; lower limb length positively correlated with mc-BTT (P<0.01). Newborns with low energy intake in the first week of life (<70 kcal kg(-1) per day) and low serum phosphate level (<1.4 mmol l(-1)) at 21 days had lower mc-BTT at 36 weeks of GA (P<0.01). CONCLUSION: Aggressive parenteral intakes in preterms improve growth and bone status in the short-medium term, suggesting that early nutrition could influence bone development.

Parenteral amino acid intakes: possible influences of higher intakes on growth and bone status in preterm infants.

OBJECTIVE: To study the possible influences of amino acid (AA) intakes on growth and bone status in preterms. STUDY DESIGN: Newborns, weighing <1250 g, received standard (S) or higher (H) parenteral AA intakes (3 or 4 g kg(-1) per day). Anthropometry, biochemistry and quantitative ultrasound (metacarpus bone transmission time (mcBTT), in µs) were measured prospectively. RESULT: A total of 55 patients in group S and 60 in group H were studied. Significantly better growth rate was found in the H group during the study without signs of intolerance. We found a significant decrease in mcBTT from birth to 21 days in the H group; nonetheless, mcBTT at 36 weeks of gestational age significantly positively correlated with early AA and energy intakes. A significant positive correlation between mcBTT and lower limb length (LLL) at 21 days was found. CONCLUSION: Early higher AA intakes improved growth without short-term AA intolerance. Nutritional parameters could influence bone growth. LLL was the anthropometric parameter that best correlated to bone status.

Phalangeal quantitative ultrasound in 1,719 children and adolescents with bone disorders.

SUMMARY: We measured bone properties by phalangeal quantitative ultrasound in 1,719 pediatric patients with bone disorders, classifying them according to fracture status. Quantitative ultrasound discriminated fractured and nonfractured pediatric patients and enabled us to stratify fractured patients into classes according to the severity of the causative trauma (spontaneous, minimal trauma, appropriate trauma fractures). INTRODUCTION: The correlation between quantitative bone measurements and fractures is poorly established in pediatric patients with bone disorders. We correlated phalangeal quantitative ultrasound (QUS) and fracture history in children and adolescents with bone disorders and evaluated the ability of QUS to recognize fractured patients. METHODS: Amplitude-dependent speed of sound (AD-SoS) and bone transmission time (BTT) were measured in 1,719 pediatric patients with bone disorders and related to fracture history. The patients were classified as (1) spontaneously (77), (2) minimal trauma (101), or (3) appropriate trauma fractured (206), and (4) nonfractured (1,335). The likelihood of fracture according to QUS was calculated as odds ratio per SD decrease (OR/SD), and the effectiveness in discriminating fractured patients was evaluated by receiver operating characteristic (ROC) analysis. The influence of age, sex, puberty, height, and BMI was explored by respective adjustments and multiple logistic regression. RESULTS: Fractured patients showed significantly reduced AD-SoS and BTT standard deviation score (-0.32 ± 1.54 and -0.78 ± 1.49) compared to nonfractured subjects (0.43 ± 1.63 and -0.11 ± 1.34). QUS measurements paralleled the causative trauma severity, ranging from the lowest values in spontaneously fractured patients to normal values in appropriate trauma fractured subjects. The OR/SD were increasingly higher in appropriate trauma fractured, minimal trauma fractured, and spontaneously fractured patients. At ROC analysis, both parameters proved to have significant discrimination power in recognizing spontaneously and minimal trauma-fractured patients. CONCLUSIONS: QUS identifies fractured pediatric patients with bone disorders, reflecting the severity of the causative trauma with a high discrimination power for fragility fractures.

Identification of in vitro electropermeabilization equivalent pulse protocols.

Exposure of cells to an external sufficiently strong electric field results in the formation of pores across the membrane. This phenomenon, termed electropermeabilization, permits the transport of poorly permeant molecules into cytosol. In clinical practice, cell membrane permeabilization for drug electrotransfer is achieved using the ESOPE pulse protocol (1000 V/cm, 8 pulses, 100 µs, 5 kHz). The aim of this study was to investigate several combinations of electric field amplitude and pulse number able to induce electropermeabilization as the one observed when the ESOPE protocol was applied. Decreasing electric field amplitudes (1000 to 300 V/cm) in combination with increasing number of pulses (8 to 320) were applied to in vitro MG63 cells. Propidium iodide and Calcein blue AM uptake were used to evaluate cell electropermeabilization and viability. Results showed that the threshold of local electric field needed to obtain electropermeabilization decreased exponentially with increasing the number of pulses delivered (r2 5 0.92, p<0.0001). The absorbed dose threshold was dependent on the number of pulses for each voltage applied (r2 5 0.96, p<0.0001). In conclusion, the possibility of applying an increased number of pulses rather than increasing the electric field amplitude to perform electropermeabilization, may become an important tool for electropermeabilization-related clinical applications.

Quantitative ultrasound of the phalanges and DXA of the lumbar spine and proximal femur in evaluating the risk of osteoporotic vertebral fracture in postmenopausal women.

PURPOSE: This study was undertaken to compare the quantitative ultrasound (QUS) parameters of amplitude-dependent speed of sound (AD-SoS) and ultrasound bone profile index (UBPI) of the phalanges with bone mineral density (BMD) of the lumbar spine and proximal hip using dual-energy X-ray absorptiometry (DXA) in discriminating women with vertebral fracture. MATERIALS AND METHODS: A total of 692 postmenopausal Caucasian women were included in the study. The presence of vertebral fracture was evaluated by radiography. AD-SoS and UBPI were measured at the phalangeal metaphysis using a DBM Sonic device. Multiple logistic regression analysis was performed to estimate the odds ratio (OR) for vertebral fractures. The ORs were also adjusted for the significant anthropometric variables of age, weight and height. Furthermore, for QUS parameters, the ORs were also adjusted for lumbar spine and total hip BMD. RESULTS: All measurements obtained with DXA and QUS significantly discriminated between women with and without fractures (p<0.0001). However, the OR was higher for lumbar spine BMD (OR 4.01), AD-SoS (OR 3.81), total hip (OR 3.7) and femoral neck BMD (OR 3.62). CONCLUSIONS: The QUS parameter AD-SoS showed diagnostic sensitivity equal to that of lumbar DXA in discriminating between women with and without osteoporotic vertebral fractures.

Quantitative ultrasound detects bone changes following bone marrow transplantation in pediatric subjects with hematological diseases: a longitudinal study.

BACKGROUND: Bone marrow transplantation (BMT) is associated with bone morbidity. We investigated bone status with quantitative ultrasound (QUS) in pediatric patients with hematological diseases prior to and up to 3 yr following BMT. METHODS: Phalangeal QUS measures for amplitude- dependent speed of sound (Ad-SoS) and bone transmission time (BTT) were obtained in 40 hematological patients (25 with malignant, 15 with non-malignant disease; 9.7+/-4.9 yr) before BMT and 6, 12, 24, and 36 months after BMT. Bone parameters were expressed as Z-scores based on age-sex-matched normal controls. RESULTS: Mean Ad-SoS and BTT Z-scores were normal before BMT and reduced at 36 months (analysis of variance: p=0.0542 and p=0.0233). Ad-SoS and BTT Z-scores remained relatively stable in the first 6 months after BMT and then progressively decreased reaching a plateau at 12-36 months. In non-malignant patients, BTT Z-score decreased at 6-12 months (p=0.029) and subsequently increased, while in malignant patients BTT Z-score showed a decrease at 12-24 months. Pre-pubertal subjects displayed a drop of BTT Z-Score values at both 12 (p=0.023) and 36 months after BMT (p=0.049), while BTT Z-score remained relatively unchanged in pubertal subjects. Early impairment of BTT Z-score was found in patients who suffered acute graft versus host disease (GVHD) compared to patients without this clinical condition; BTT Z-score was lower at 36 months (p=0.045). CONCLUSIONS: Longitudinal assessment by QUS of pediatric BMT survivors evidenced that bone status is mildly affected up to 36 months after BMT, mainly in malignant patients, in pre-pubertal subjects at BMT and in patients who suffered acute GVHD.

Influence of density, elasticity, and structure on ultrasound transmission through trabecular bone cylinders.

The aim of this in vitro study is to evaluate the potentiality of quantitative ultrasound (QUS) to separate information on density, elasticity, and structure on specimens of trabecular bone. Fifteen cylinders of spongy bone extracted from equine vertebrae were progressively demineralized and subjected to QUS, micro computed tomography (muCT), Dual energy X-ray absorptiometry (DXA) at various mineralization levels. Eventually all cylinders underwent a compression test to calculate the Young's modulus. Correlation analysis shows that speed of sound (SOS) is strictly associated to bone mineral density (BMD), Young's modulus, and all muCT parameters except for degree of anisotropy (DA). Fast wave amplitude (FWA) is directly correlated with bone surface and total volume ratio (BS/TV) and trabecular separation (Tb Sp), and inversely correlated with trabecular number (Tb N). Because muCT parameters were strictly correlated to BMD and Young's modulus data, partial correlation analysis was performed between SOS, FWA, and structural and elastic data in order to eliminate the effect of density. SOS was significantly correlated to bone volume and total volume ratio (BV/TV), BS/TV, and Young's modulus, and FWA was significantly correlated to Tb Sp only. These results show that SOS is strongly influenced by volumetric mineral bone density and elastic modulus of the specimen, and FWA is mainly affected by trabecular separation independently on density. Therefore, SOS and FWA are able to provide different and complementary information, at least on trabecular bone samples.

Bone quality assessed by phalangeal quantitative ultrasonography in children and adolescents with isolated idiopathic growth hormone deficiency.

OBJECTIVE: Some observations indicate that GH deficiency (GHD) may have little impact on bone mineralization in contrast to its effects on bone growth and maturation. The aim of the present study was to evaluate the effects of isolated GHD and GH-replacement therapy on bone quality assessed by a quantitative ultrasound (QUS) technique at the proximal phalanges of the hand. DESIGN: Growth and QUS data of 68 subjects (50 males and 18 females) aged 5-18 yr with isolated GHD were retrospectively examined. A cross-sectional series of 120 observations was collected and compared with data obtained from a control population (1227 healthy children, 641 males and 586 females, aged 3-16 yr). METHODS: QUS variables amplitude- dependent speed of sound (AD-SoS) and bone transmission time (BTT) were assessed by the sonographic device DBM Sonic BP IGEA. Height and weight measurements were performed according to standard techniques. In patients, skeletal age (SA) was determined by Tanner-Whitehouse method (3rd version). RESULTS: Before treatment height, SA, ADSoS and BTT were reduced in patients. Height SD score (SDS), SA SDS, AD-SoS SDS, and BTT SDS improved during treatment. Significant associations of both AD-SoS and BTT with age, SA, height, and therapy duration were observed. Using multivariate regression models the disease state, SA, and height proved to be significant variables in predicting BTT and AD-SoS. CONCLUSIONS: QUS measurements adjusted for body size and skeletal maturity in GHD patients seem to be only slightly reduced. A body size and skeletal maturity adjustment should be incorporated in studies on bone mass in GHD children and adolescents. A non-invasive technique such as QUS technology opens new perspectives.

QUS in monitoring raloxifene and estrogen-progestogens: a 4-year longitudinal study.

The aim of the study is to evaluate the effectiveness of phalangeal quantitative ultrasound (QUS) in monitoring the treatment with raloxifene or estrogen-progestogens in postmenopausal women attending an Italian Menopause Centre. Caucasian women (n = 268) were enrolled in the study and underwent annual check-ups between October 1998 and October 2004. All were measured with the IGEA DBM Sonic Bone Profiler (BP) at the startup of treatment and in the following years. Three groups were identified: subjects not receiving treatment (n = 144), subjects treated with raloxifene (n = 53) and subjects treated with estrogen-progestogens (n = 71). The three analyzed groups were similar for age, weight and menopausal age. A significant decrease in amplitude-dependent speed of sound (AD-SoS) and Ultrasound Bone Profile Index (UBPI; p < 0.05) was observed in the nontreated group, whereas a positive effect in treated groups could be evidenced in the follow-up. In particular, a significant positive effect (p < 0.05) on AD-SoS corrected for age in the group treated with raloxifene has been observed, whereas in the group treated with estrogen-progestogens a nonsignificant positive effect on AD-SoS corrected for age was observed. The absolute AD-SoS value was maintained over the years of follow-up. The UBPI data show a slowing down of the bone loss in the treated groups, especially in the raloxifene group, in contrast with the significant decrease in the nontreated group. The result of this study shows the DBM Sonic Bone Profiler is an efficient device to monitor the effects of treatment, not only in the strict control settings of clinical trials, but also in clinical practice.

Quantitative ultrasound in adults with cystic fibrosis: correlation with bone mineral density and risk of vertebral fractures.

In several conditions, including cystic fibrosis (CF) and corticosteroid-induced osteoporosis, bone mineral density (BMD) measurements provide a modest prediction of fracture risk. We investigated in adult CF patients whether quantitative ultrasound (QUS) parameters were able to discriminate between patients with and without prevalent vertebral fractures. One hundred seventy-two adults with CF, 91 men and 81 women, often on chronic oral or inhaled corticosteroid therapy, were studied. BMD at the lumbar spine, proximal femur, and total body were measured by dual-energy X-ray absorptiometry (DXA). QUS parameters were assessed by Achilles Express at the calcaneus and by the DBM Sonic 1200 at the phalanges. All bone measurements by DXA and QUS were significantly correlated with each other, with the exception of phalangeal amplitude-dependent speed of sound versus spine BMD. The mean T-score values in CF patients with and without prevalent vertebral fractures were similar for all DXA measurements and for stiffness index. A significant difference between the two groups was observed only for phalangeal ultrasound bone profile index (UBPI) values (relative risk = 1.25, 95% confidence interval 1.05-1.49 for each decrease in T score), and this difference was maintained after adjusting the values for age, body weight, forced expiratory volume in 1 second, gender, and corticosteroid use. In conclusion, only a phalangeal QUS parameter (UBPI), in contrast with calcaneus QUS or DXA measurements, was able to discriminate CF patients with from those without vertebral fractures, possibly as a result of qualitative alterations of bone tissue independent of BMD.

Longitudinal assessment of bone quality by quantitative ultrasonography in children and adolescents.

Among the techniques available to assess bone quality, quantitative ultrasonography of the proximal phalanges of the hand (QUS) has emerged as particularly attractive. In this study, amplitude-dependent speed of sound (AD-SoS) and bone transmission time (BTT) were obtained by the sonographic device DBM Sonic BP IGEA in two sessions at two years' interval, in a school-age population (589 subjects, 290 mol/L and 299F, aged 3 to 16 y) with the aim to determine accuracy of QUS measurements, evaluate QUS variable changes during growth, relate these values with age and growth variables. Mean AD-SoS and BTT at age classes from 5 to 12 y as determined at the first and second measurement sessions were not significantly different. A significant increment (p < 0.0001) between the first and the second measurement was observed for both QUS variables. AD-SoS and BTT showed significantly different variations in the various age groups (ANOVA). Correlations were found of AD-SoS and BTT increments with age, height, weight, pubertal stage and with height growth velocity (p < 0.05). AD-SoS and BTT increment curves presented a very similar trend decreasing from 4 to 7 y of age. Thereafter a plateau was reached up to the age of 10 to 11 y in girls and 11 to 12 y in boys, when an increase was observed corresponding to pubertal growth rate acceleration. In conclusion, the present study would confirm that QUS measurements are accurate. Ad-SoS and BTT increment models are similar to most growth velocity curves and follow a strongly age- and growth-dependent pattern.

Quantitative ultrasound technique at the phalanges in discriminating between uremic and osteoporotic patients.

This study was conducted to test the ability of quantitative ultrasound technique (QUS) at the phalanges to discriminate between uremic and osteoporotic patients. Three groups of subjects (38 dialytic women, 16 osteoporotic women with vertebral fractures, 19 non-dialytic and non-fractured women) were recruited at the Department of Radiology at "Casa Sollievo della Sofferenza" Hospital, San Giovanni Rotondo, Italy. The groups were matched for age and body mass index (BMI). On all subjects the following measurements were performed: spinal BMD by QCT and by DXA, Femoral BMD by DXA, phalangeal QUS. For QUS measurements, the DBM Sonic (IGEA, Carpi, Italy) was applied to the metaphysis of the proximal phalanges of the last four fingers of the hand. Osteoporotic women with vertebral fractures showed significantly lower values of spinal BMD by QCT and DXA and Ward's Triangle BMD with respect to hemodialytic patients (p<0.005). All QUS values, except for BTT and SoS, showed lower values in osteoporotic women with respect to hemodialytic patients (p<0.05). Control group showed higher values of AD-SoS, BTT and SoS than hemodialytic patients (p<0.005) while the two groups did not differ for BMD values measured with both QCT and DXA. UBPI and FWA data showed a similar behaviour to DXA and QCT results, whereas BTT and SoS showed a completely different behaviour. AD-SoS was the only parameter that could effectively discriminate among the three groups (ANOVA, p<0.0001). We conclude that phalangeal QUS can discriminate between hemodialysed patients and controls with similar bone mineral density, and can also discriminate between hemodialysed and osteoporotic subjects with vertebral fractures. Different characteristics of ultrasound signal can be ascribed to each bone tissue condition, enabling a clear differentiation of bone tissue changes occurring in menopause, osteoporosis and renal osteodystrophy.

Usefulness of quantitative ultrasound in evaluating structural and mechanical properties of bone: comparison of ultrasound, dual-energy X-ray absorptiometry, micro-computed tomography, and mechanical testing of human phalanges in vitro.

INTRODUCTION: Ultrasound studies evaluating bone tissue generally concentrate on two parameters--velocity and attenuation. This study aimed to determine whether ultrasound signal analysis techniques could provide additional information on the structural and mechanical characteristics of bone. MATERIALS AND METHODS: In vitro measurements were made on 26 left index fingers from human cadavers. Ultrasound measurements at the distal metaphysis and epiphysis; dual-energy X-ray absorptiometry of the whole phalanx; micro-computed tomography at the distal quarter of the phalanx (that is, the distal epiphysis and metaphysis), and mechanical three-point bending tests were performed. Univariate and multivariate linear regression techniques were used to analyze the results. RESULTS: The ultrasound parameters, speed of sound and ultrasound peak amplitude correlated significantly with the three micro-computed tomography measures used to describe the characteristics of mineralized material (r=0.69-0.79, p<0.05). Low frequency ultrasound correlated significantly with micro-computed tomography parameters describing inter-trabecular or marrow spaces (r=0.68-0.78, p<0.05). Comparison of ultrasound parameters with geometric characteristics showed that while speed of sound and ultrasound peak amplitude were related to the cortical area, moment of inertia, and mechanical load (r=0.57-0.83, p< 0.05), the amplitude of the fastest part of the ultrasound signal and full width at 80% maximum of the low frequency peak were related to the relative area of the medullary canal (r=0.40-0.43, p<0.05). DISCUSSION: Quantitative ultrasound may provide information on structural, material and mechanical characteristics of bone to the same extent and even better than DXA Bone Mineral Density. These results have been obtained by a complete and exhaustive use of QUS technology in situ but under clinical conditions. The ultrasound parameters, correctly used and combined, seem to be effective tools for investigating bone tissue.

Quantitative ultrasound of the hand phalanges in a cohort of monozygotic twins: influence of genetic and environmental factors.

OBJECTIVE: Our objective was to evaluate the similarities and differences in bone mass and structure between pairs of monozygotic twins as measured by means of the quantitative ultrasound (QUS) technique. DESIGN: A cohort of monozygotic twins was measured by QUS of the hand phalanges using the DBM sonic bone profiler (IGEA, Carpi, Italy). The parameters studied were amplitude-dependent speed of sound (AD-SoS), ultrasound bone profile index (UBPI), signal dynamics (SDy) and bone transmission time (BTT). Linear correlation coefficients, multivariate linear analysis and the ANOVA test were used to assess intrapair associations between variables and to determine which factors influence the intrapair differences in QUS variables. PATIENTS: One hundred and six pairs of monozygotic twins were enrolled in the study, 68 females and 38 males in the age range 5 to 71 years. RESULTS: Significant intrapair correlations were obtained in the whole population and separately for males and females, regarding height ( r =0.98-0.99, p <0.0001), weight ( r =0.95-0.96, p <0.0001), AD-SoS ( r =0.90-0.92, p <0.0001), BTT ( r =0.94-0.95, p <0.0001) and other QUS parameters ( r >0.74, p <0.0001). Multivariate analysis revealed that intrapair differences between AD-SoS, SDy, UBPI and BTT are significantly influenced by age in the whole population and in the female population. Furthermore, the ANOVA test showed, for the female group, a significant increase in the intrapair differences in SDy and UBPI above 40 years. CONCLUSIONS: A relative contribution of genetic factors to skeletal status could be observed by phalangeal QUS measurement in monozygotic twins. A significant increase in the intrapair difference in QUS parameters with increasing age and onset of menopause also suggests the importance of environmental factors in the female twin population.

Ten-year probabilities of clinical vertebral fractures according to phalangeal quantitative ultrasonography.

The objectives of the present study were to estimate 10-year probabilities of clinical vertebral fractures in women, according to age and bone mineral assessment using phalangeal quantitative ultrasound (QUS). Risks were computed from UK derived data on the incidence of a first symptomatic vertebral fracture and mortality rates for each year of age using Poisson models. The 10-year probability of vertebral fracture was determined as the proportion of individuals fracture-free at that site from the age of 45 years. We assumed that the risk of fracture increased with decreasing QUS as assessed by an independent re-analysis of a previously published, multicenter cross-sectional study. For amplitude-dependent speed of sound (AD-SoS) information was available from 8,502 women, and vertebral fracture risk increased 1.7-fold for each SD decrease in measurement. For fast wave amplitude (FWA), available in 6,573 women, the risk gradient was 2.4/SD. In a subset of the population ( n =1,572) in whom bone mineral density was measured at the lumbar spine, the gradient of risk was 2.3/SD, with similar gradients of risk noted for AD-SoS (1.8/SD) and FWA (2.6/SD). Ten-year probabilities increased with age and decreasing Z -score. The use of absolute risk permits information from different types of bone mineral measurements to be applied for the assessment of patients, either alone or in combination with other independent risk factors.