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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.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.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.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.

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.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.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 (P0.01). 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 (P0.01).Aggressive parenteral intakes in preterms improve growth and bone status in the short-medium term, suggesting that early nutrition could influence bone development.

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.

Background Electrochemotherapy (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. The aim of this study was to investigate the effectiveness of ECT in cutaneous metastases of melanoma and to identify factors which affect (beneficially or adversely) the outcome. Methods 13 cancer centres in the International Network for Sharing Practices on Electrochemotherapy (INSPECT) consecutively and prospectively uploaded data to a common database. ECT consisted of intratumoural or intravenous injection of bleomycin, followed by application of electric pulses under local or general anaesthesia. Results 151 patients with metastatic melanoma were identified from the database, 114 of which had follow-up data of 60 days or more. 80 of these patients (73%) experienced an overall response (complete response + partial response = OR). 394 lesions were treated, of which 306 (77%) revealed an OR, 229 a complete response (58%). In multivariate analysis, factors positively associated with overall response were coverage of deep margins, absence of visceral metastases, presence of lymphoedema, treatment of non-irradiated areas were factors significantly influencing treatment efficacy. Factors significant associated to a complete response to ECT treatment were: coverage of deep margins, previous irradiation of treated area, and tumour size (

To study the possible influences of amino acid (AA) intakes on growth and bone status in preterms.Newborns, weighing1250 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.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.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.

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.

Background: Quantitative ultrasonography of the proximal phalanges of the hand (QUS) has emerged as an attractive technical choice to assess bone quality features both in terms of bone mass and structure. Strong associations were found between QUS measures, chronological age and growth variables, such height, weight and pubertal stages. Aim: To evaluate the relationship between skeletal age and QUS variables and the influence of skeletal age on QUS variables after allowing for chronological age, height, weight and pubertal stage. Subjects and Methods: 235 healthy children and adolescents (85 boys and 150 girls) aged 3 - 18 years were examined. Height, weight, body mass index (BMI) were collected. Skeletal age was assessed by the third version of Tanner-Whitehouse method (TW3). QUS variables amplitude dependent speed of sound (AD-SoS, m/s) and bone transmission time (BTT, ∝sec) were measured by DBM Sonic BP IGEA sonograph. Results: Statistically significant positive correlations were found between AD-SoS and BTT and skeletal age (R2 = 0.76 in boys and 0.83 in girls for AD-SoS and 0.96 in boys and 0.93 in girls for BTT). A very close correlation was observed between skeletal age and BTT even after adjusting for chronological age, height, weight, and pubertal stage. In both sexes, chronological age, height and BTT resulted significant predictors of skeletal age. Conclusion: Skeletal age has emerged as an important determinant of phalangeal QUS measurements, mainly BTT. Skeletal maturity should be taken into account when QUS technology is used to evaluate bone mass and structure in children.

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 (p0.005). All QUS values, except for BTT and SoS, showed lower values in osteoporotic women with respect to hemodialytic patients (p0.05). Control group showed higher values of AD-SoS, BTT and SoS than hemodialytic patients (p0.005) 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, p0.0001). 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.

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.

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.

The aim of this study was to assess the capability of ultrasonography and densitometry to predict the mechanical competence of cortical bone in healthy and osteopenic rats, respectively. Thirty 10-month-old Sprague-Dawley retired breeder female rats were used and randomized into three groups of 10 animals each. A group underwent bilateral ovariectomy by dorsal approach (Ovx), another group underwent a simulated ovariectomy (Sham-Ovx), and the last group served as a sham-aged control group (Control). Sixteen weeks after surgery, the animals were euthanized and the femurs of each rat excised for ultrasonographic and densitometric measurements, and mechanical analyses. The Ovx Group had a significantly decreased amplitude dependent speed of sound (AD-SoS-about 7-8%) when compared to the other groups (p0.0005). For Ovx animals compared with Sham-Ovx and Control rats, significant decreases in densitometric data were observed (6-13%), as well as significant decreases in femoral Max. Load (about 18%) and flexural rigidity (about 30%). The best correlation (R2=0.55, p0.0005) found was between SoS and femoral shaft bone mineral density (SBMD). The regression coefficient R2 increased when power-law fits were used, particularly from 0.34 (p0.001) to 0.36 (p0.0005) in the correlation between SoS and Max. Load and from 0.21 (p0.05) to 0.25 (p0.01) in the correlation between SBMD and Max. Load. The ability of QUS or DXA to accurately predict the actual mechanical characteristics of bone, and in particular bone elasticity, remained relatively poor and the improvement of the power-law model did not describe exhaustively the relationships between the variables tested. The DXA and QUS capability to discriminate between ovariectomized and non-ovariectomized rats did not improve when tested together.

The aim of this study was to evaluate the association among phalangeal morphometric parameters, amplitude-dependent speed of sound (AD-SOS), ultrasound bone profile index (UBPI), and spinal bone mineral density (BMD) and fracture status. One hundred women (controls, mean age 53 ± 12 years) and 40 osteoporotic women (mean age 59 ± 7 years) with atraumatic fractures, diagnosed by spinal radiographs, were investigated. Quantitative ultrasound (QUS) assessment was performed using the DBM Sonic 1200. Morphological properties of the phalanges were measured from a digitized X-ray image of the hand acquired using industrial film. Spinal BMD was assessed by dual X-ray absorptiometry (DXA) and quantitative computed tomography (QCT). An increase in medullary canal width and a decrease in cortical thickness with aging were observed from the morphometric analysis of the hand radiographs. This phenomenon can be attributed mainly to endosteal resorption. QUS measurements at the phalanges were not significantly related to finger thickness (r

Quantitative ultrasound (QUS) of the finger phalanges is a useful tool in the assessment of disease- or age-related deterioration of bone. For studying the impact of juvenile diseases or growth disorders affecting the skeleton, a reference database for QUS parameters is needed. The aim of this study was to establish a calibrated reference database of parameters of transverse ultrasound transmission through juvenile finger phalanges. A total of 1328 children (650 females, 678 males; ages 3-17 years) were measured in Heidelberg and Kiel in order to establish a German reference database. Highly significant gender-specific correlations (p0.0001) were found between the QUS parameters amplitude-dependent speed of sound (AD-SoS) and bone transmission time (BTT) versus age, body height and body mass index (BMI). For AD-SoS the correlation coefficients were R2 = 0.64 against age in males and R2 = 0.73 in females, R2 = 0.60 against body height in males and R2 = 0.68 in females, and R2 = 0.19 against BMI in males and R2 = 0.23 in females. For BTT the correlation coefficients were R2 = 0.74 against age in males and R2 = 0.79 in females, R2 = 0.75 against body height in males and R2 = 0.77 in females, and R2 = 0.32 against BMI in males and R2 = 0.35 in females. Age and height were the strongest determinants of QUS results. Gender-specific differences were observed in AD-SoS (significant for ages 11-14 years and for 150-170 cm body height) and in BTT (significant for ages 7 and 11-17 years and for 160-170 cm body height). Tables of QUS parameters versus age and height can serve as a basis for the evaluation of the impact of skeletal diseases or growth disorders on phalangeal QUS. Depending on the type of disease or growth disorder, measurement results can be compared with age- or height- specific reference data. In this way a simple and radiation-free assessment of juvenile skeletal disorders using quantitative ultrasound might be possible in the future.

Phalangeal osteosonogrammetry was introduced as a method for bone tissue investigation in 1992. It is based on the measure of the velocity of ultrasound (amplitude-dependent speed of sound [AD-SoS]) and on the interpretation of the characteristics of the ultrasound signal. In this study we have collected a database of 10,115 subjects to evaluate the performance of AD-SoS and to develop a parameter that is able to quantify the signal characteristics: ultrasound bone profile index (UBPI). The database only includes females of which 4.5% had documented vertebral osteoporotic fractures, 16% lumbar spine dual X-ray absorptiometry (DXA), and 6% hip DXA. The analysis of the ultrasound signal has shown that with aging the UBPI, first wave amplitude (FWA), and signal dynamics (SDy) follow a trend that is different from the one observed for AD-SoS; that is, there is no increase during childhood. In the whole population, the risk of fracture per SD decrease for AD-SOS was odds ratio (OR) 1.71 (CI, 1.58-1.84). The AD-SoS in fractured subjects was significantly lower than in a group of age-matched nonfractured subjects (p < 0.0001). In a small cohort of hip-fractured patients UBPI proved to be lower than in a control age-matched group (p < 0.0001). When the World Health Organization (WHO) working group criteria were applied to this population to identify the T score value for osteoporosis, for AD-SoS we found a T score of -3.2 and for UBPI we found a T score of -3.14. Sixty-six percent of vertebral fractures were below the AD-SoS -3.2 T score and 62% were below UBPI -3.14. We observed the highest incidence of fractures (63.6%) among subjects with AD-SoS who had both DXA T score values below the threshold. We conclude from this study that ultrasound investigation at the hand phalanges is a valid methodology for osteoporosis assessment. It has been possible to quantify signal changes by means of UBPI, a parameter that will improve the possibility of investigating bone structure.

The aim of this work was to use ultrasonographic technology to differentiate osteoporosis from osteomalacia on the basis of different patterns of the graphic trace. Three patients with osteomalacia and three with osteoporosis, all with the same lumbar spine bone mineral density, were studied. The velocity of the ultrasound beam in bone was measured by a DBM Sonic 1,200/I densitometer at the proximal phalanges of the hands in all the patients. The ultrasound beam velocity was measured when the first peak of the waveform reached a predetermined minimum amplitude value (amplitude-dependent speed of sound) as well as at the lowest point prior to the first and second peaks, before they reached the predetermined minimum amplitude value (first and second minimum speeds of sound). The graphic traces were further analyzed by Fourier analysis, and both the main frequency (f0) and the width of the peak centered in the f0 (full width at half maximum) were measured. The first and second minimum speeds of sound were significantly lower in the patients with osteomalacia than in the osteoporosis group. The first minimum speed of sound was 2,169 +/- 73 m/s in osteoporosis and 1,983 +/- 61 m/s in osteomalacia (P < 0.0001); the second minimum peak speed of sound was 1,895 +/-59 m/s in osteoporosis and 1,748 +/- 38 m/s in osteomalacia (P < 0.0001). The f0 was similar in the two groups (osteoporosis, 0.85 +/- 0.14 MHz; osteomalacia, 0.9 +/- 0.22 MHz; P = 0.72), and the full width at half maximum was significantly higher in the osteomalacia patients (0.52 +/- 0.14 MHz) than in the osteoporosis patients (0.37 +/- 0.15 MHz) (P = 0.022). This study confirms that ultrasonography is a promising, noninvasive method that could be used to differentiate osteoporosis from osteomalacia, but further studies should be carried out before this method can be introduced into clinical practice.

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). 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. 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. 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. QUS identifies fractured pediatric patients with bone disorders, reflecting the severity of the causative trauma with a high discrimination power for fragility fractures.

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.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.All measurements obtained with DXA and QUS significantly discriminated between women with and without fractures (p0.0001). 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).The QUS parameter AD-SoS showed diagnostic sensitivity equal to that of lumbar DXA in discriminating between women with and without osteoporotic vertebral fractures.

Electrical pulses were applied to the distal femur of rabbits by inserting four electrodes in order to evaluate if and to what extent cell electroporation could be achieved in such a non-homogenous tissue. Dose response effect of number of pulses delivered was observed. 120 pulses at 1750V/cm successfully removed all osteogenetic activity among the electrodes, as evidenced by tetracyclin staining. These preclinical results lay the foundation for use of electroporation in the treatment of bone metastases.

As part of the Ogliastra project, which focuses on the study of genealogical, genetic and clinical features of isolated populations of this area of Sardinia, we conducted a cross-sectional epidemiological study to estimate the prevalence, the environmental determinants and heritability of osteoporosis in ten villages. Ogliastra area is one of the most isolated and anciently populated region of Sardinia; its population has grown slowly and uniformly during the time with no relevant immigration and it is characterized by a great deal of homogeneity in life style and eating habits and a high rate of endogamy and consanguinity. The sample cohort consists of 6056 individuals (4166 women and 1890 men), aged 30-103. The voluntary participants gave a blood sample, underwent anthropometric measurements, bioelectrical impedance, Quantitative Ultrasonography (QUS) and a standardized interview collecting socio-demographic, lifestyle, medical and pharmacological history data and family history of osteoporosis. The T-score threshold for AD-SoS (Amplitude Dependent Speed of Sound) of -3.2 SD, was used to estimate the osteoporosis prevalence. Both AD-SoS and UBPI (Ultrasound Bone Profile Index) parameters were investigated because they provide different information on bone structure properties: AD-SoS being related mostly to density and UBPI to bone fragility. Overall osteoporosis prevalence is 11.4%, 17.0% in females and 5.2% in males. We checked for dissimilarities in prevalence of main risk factors for osteoporosis in the ten villages, but none substantial discrepancy was found. Notably, differences in osteoporosis prevalence were found among villages, especially between the two closest ones: Talana (10.5% in men and 24.6% in women) and Urzulei (2.7% in men and 6.9% in women). This may reflect the presence of different founders and genetic background. Both QUS parameters resulted significantly correlated to anthropometric and bioimpedance measures: the negative impact of weight, BMI and fat mass can be ascribed to the effect of soft tissue, even if it has been observed only for AD-SoS. This result suggests a possible influence of local adiposity on AD-SoS, as UBPI is not influenced by soft tissue. High fractions of lean, muscular and body cell masses and high phase angles seem to be protective factors, whereas fat mass and extra cellular water appear as risk factors for osteoporosis. Among blood serum parameters Alkp showed a weak significant inverse relationship with QUS measurements while calcium, phosphorus, SGOT and GPT resulted to have negligible correlations. In women age at menarche, number of pregnancies and months since menopause are inversely correlated to AD-SoS and UBPI, even if, when age-adjusted, age at menarche becomes directly related to QUS measures as in our sample mean age at menarche is higher in older age classes. Then we constructed multiple models for both AD-SoS and UBPI putting all the significant variables. Covariates, all significant at the 0.05 level, explain 58% of AD-SoS variability and 60% of UBPI variability. Heritability estimates were obtained using SOLAR software: we run variance component models on 45 extended pedigrees, each up to 4 generations deep, adjusting for the associated covariates. Global heritability was 35.3% for Ad-SoS and 43.5% for UBPI. Some conclusions can be safely drawn: risk factors usually associated to DXA-BMD and calcaneal QUS are also associated to phalangeal QUS parameters; prevalence of osteoporosis in Ogliastra population is comparable to that of Italy and Europe; a large part of variances of AD-SoS and UBPI were found to be attributable to genetic factors. Furthermore, the advantageous features of these genetic isolates and the differences found among the ten villages encourage us to deepen the study looking for genetic variants predisposing to osteoporosis.

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.

As part of the Ogliastra project, which focuses on the study of the genealogy, genetics and clinical features of isolated populations in this area of Sardinia, we conducted a transversal epidemiological study to estimate the prevalence, the environmental determinants and heredibility of osteoporosis in Baunei (n=3800). This village has historically been geographically isolated, and this is seen by its limited number of founders, high rate of endogamous marriages (82.04%), and low number of immigrants (3.97% before 1950). Beyond this, the population is generally attached to the traditional ways, retaining many old features of lifestyle, eating habits and behaviour. This genetic and environmental homogeneity facilitates the study of complex diseases. Participation study was voluntary: 917 women, ranging in age from 33 to 98 years old and previously informed that the study was conformed with international ethical guidelines, furnished a blood sample used for hematological and serological parameters, anthropometrical measurements, bioimpedance, Quantitative Ultrasonography (QUS) using a DBM Sonic Bone Profiler (IGEA Srl) and the structured interview to collected socio-economic, lifestyle, medical and pharmacological history and family history of osteoporosis. The main determinants of bone mass were modelled using General Linear Models. The T-score threshold for AD-SoS (Amplitude Dependent Speed of Sound) of -3.2 SD, was used to estimate the osteoporosis prevalence. The prevalence estimate was age adjusted using the general Italian population for 2005 (ISTAT). The 10 years probability of clinical vertebral fractures was calculated according to guidelines reported for diagnosis, prevention and therapy of osteoporosis (EDIMES - Pavia 2005). Using the genealogical data referred to the last 400 years and PedNavigator, a useful software able to reconstruct multigenerational pedigrres, we created 6 big families including all participants to the study; heritability estimate of QUS parameters was obtained by the variance component method implemented in the SOLAR software. The ultrasonic parameters AD-SoS and Ultrasound Bone Profile Index (UBPI) are strictly related to age and months since menopause. Multiple regression analysis detected significant association with height and alkaline phosphatase. UBPI resulted to be significantly correlated with weight, fat mass and menarche. Besides, AD-SoS and UBPI corrected for age and months since menopause, were found to be significantly associated with: hormone replacement therapy, sport activity (only AD-SoS), current or past diet (only AD-SoS), chronic use of steroids drugs, present or past chemotherapy, endocrine and gastrointestinal disorders. The prevalence of osteoporosis in baunei was 19.4 %. (95% CI: 17.0%-21.7%). The percentage of subjects with high 10 years risk of vertebrate fracture (>4%) was 4.1%. Using PedNavigator, we observed that individuals with reduced mineral bone density clustered in big families, showing that familiarity is an important risk factor for this disease. Heritability estimates of AD-SoS and UBPI, after adjusting for the associated covariates explaining more than 60% of the variability of trait variability, were found to be 30% and 64% respectively. (p

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.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.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.Significant intrapair correlations were obtained in the whole population and separately for males and females, regarding height ( r =0.98-0.99, p0.0001), weight ( r =0.95-0.96, p0.0001), AD-SoS ( r =0.90-0.92, p0.0001), BTT ( r =0.94-0.95, p0.0001) and other QUS parameters ( r0.74, p0.0001). 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.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.

Quantitative Ultrasound (QUS) is a relatively new method of bone assessment that measures the velocity of sound and the broadband ultrasound attenuation at different skeletal sites: heel and phalanges. This is a mobile, inexpensive, easy to perform and radiation-free technique, capable of assessing not only bone density, commonly measured by means of Single Energy X-ray Absorptiometry, SXA, Dual Energy X-ray Absorptiometry, DXA and Quantitative Computed Tomography, QCT, but also its elasticity and structure. QUS has been validated for diagnosis of osteoporosis and prevention of hip fractures. Very recently, QUS was also been applied to the study of uremic osteodistrophy, of female premenopausal osteoporosis, male osteoporosis and in paediatric population. Moreover, many studies in the dialysis population has also shown the effectiveness of QUS at the phalanges site in evaluating bone turn-over and bone osteopenia. QUS may be an useful tool for the nephrologist in the day by day monitoring of uremic osteodistrophy and secondary hyperparathyroidism.

Over the last decade, the use of ultrasounds has been developed into an effective tool for investigating bone tissue and predicting the risk of fracture in osteoporosis. Studies have focused on hip and vertebral fractures while no information is available on the use of phalangeal ultrasonography to identify patients with forearm fractures. Thus, the current authors decided to compare 50 postmenopausal women with low energy forearm fractures (Fractured Group) with a control age-matched group of 94 women (Control Group). Measurements were taken at the distal metaphysis of the proximal phalanxes of the hand of the non-fractured arm using the DBM Sonic Bone Profiler. The reproducibility of the method was assessed by amplitude-dependent speed of sound (AD-SoS) CV% = 0.64 and by Ultrasound Bone Profiler Index (UBPI) CV% = 2.38. In the Control Group, the AD-SoS and UBPI mean values and standard deviations were significantly higher compared to the group with fractures (P0.0005). The receiver operating characteristic (ROC) curves were calculated and the areas under the curve (AUC) were 0.78 +/- 0.04 for AD-SoS and 0.77 +/- 0.05 for UBPI, respectively. Logistic regression analysis adjusted to age revealed that both AD-SoS (78.2%, ORAD-SoS = 12.03, P0.0005) and UBPI (76.0%, ORAD-SoS = 7.39, P0.0005) parameters discriminated correctly between fractured and non-fractured control women whereas the association of both parameters could not allow better discrimination. The present results showed that ultrasound investigation at the phalanxes is reproducible and efficiently discriminates between subjects with forearm fractures and those in the control subjects.

To investigate in detail the mechanical and structural characteristics of cancellous bone from the femoral distal epiphysis of normal and ovariectomized rats, and to provide reference values in order to improve experimental research on osteoporosis by characterising an alternative and complementary anatomic site.40 female Sprague-Dawley rats (10 months old) were randomly divided into 4 groups of 10 each: baseline, ovariectomized (Ovx), sham-operated (Sham-Ovx) and sham-aged (Sham-Aged). Baseline animals were sacrificed at the beginning of the study. Ovx and Sham-Ovx animals were sacrificed 16 weeks after surgery, whereas Shamaged rats were killed when aged 14 months. Femurs were excised and densitometric, ultrasonographic, mechanical and histomorphometric analyses were performed.When comparing the Ovx group with the others, ultrasonographic and densitometric measurements showed significant decreases (p0.0005) amounting to 3-5% in the amplitude dependent speed of sound (AD-SOS) and 13-20% in the BMD, respectively. Significant decreases were also seen in the femoral condyle Max. Load (28-31%; p0.0005) and Elastic Modulus (19-25%; p0.005) in the Ovx group in comparison with the Sham-Ovx and Sham-Aged groups. Histomorphometric analysis showed a significant cancellous bone loss (p0.0005). Densitometric (p0.01), histomorphometric (p0.01) and mechanical (p0.05) parameters were correlated with AD-SOS. Among the histomorphometric parameters, stepwise regression analysis showed that the trabecular bone volume (BV/TV) and Max. Load correctly predicted AD-SOS (p0.0005) and BMD (p0.0005).The data from this study characterize osteopenia occurring in the rat distalfemur 16 weeks after ovariectomy and provide methodology and reference values forfurther investigations on osteoporosis and bone-implant osteointegration in osteopenic bone.

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, AD-SoS 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.

5 years after a previous study, we followed up a group of thalassemic patients, determining DHEA-S levels in peripubertal age, with the aim of evaluating whether adrenarche maturation occurred in boys and advanced in girls. Furthermore, we evaluated the degree of bone mineral density (BMD SDS(BA)) and analyzed growth parameters calculating standard deviation score with respect to bone age (BA) of height (Ht SDS(BA)), sitting height (SH SDSBA), and subischial leg length (SLL SDSBA), body mass index (BMI) and the difference between the values of the previous and the present study (deltaBMI), thyroid function and serum markers of bone metabolism. Our results showed persistent lack of adrenarche (DHEA-S 25+/-9.5 microg/dl) in all 6 boys and the absence of pubertal signs at chronological age (CA) of 12.4+/-1.4 yr and BA of 11.1+/-1.1 yr. Only one boy, 6 months later, showed a testicular volume of 4 ml (Tanner stage G2) with an increase of DHEA-S value (181 microg/dl) at BA 12.8 yr. Body disproportion and severe degree of osteopenia (BMD SDSBA -2.41+/-0.5) were observed in all boys, even though Ht SDSBA (0.14+/-0.8) and markers of bone metabolism were within the normal range. No change in nutritional status was observed (deltaBMI 0.09+/-0.4 kg/m2). In contrast, all the thalassemic girls had DHEA-S values (172.7+/-97.7 microg/dl) within the normal range at BA 12.7 +/-0.6 yr that was similar to CA. Furthermore, the appearance of Tanner stage B2 occurred in each of them at BA, near to CA, of 10.4+/-0.9 yr, and menarche was observed in three of them at mean BA, near to CA, of 11.4+/-0.9 yr. Ht SDSBA was below normal range (-1.11+/-0.8), but SLL SDSBA and SH SDS(BA) values were reduced homogeneously, so that proportional body growth was observed. A significant change in nutritional status was observed (deltaBMI 2.69+/-0.9 kg/m2). Bone density value (BMD SDS(BA) -0.25+/-0.4) was in the normal range. There were no statistically significant differences between boys and girls for ferritin serum levels, blood consumption and desferrioxamine dosage. In conclusion, lack of change in nutritional status, measurable in the form of deltaBMI, but not BMI alone, considered an important physiological regulator of adrenarche, regardless of individual adrenal androgen secretion, could have a key role in the lack of adrenarche persisting in thalassemic boys during peripubertal age. Further follow up is necessary, in particular when boys reach puberty, because delayed adrenarche represents the most intriguing aspect in these patients.

The capacity of dual x-ray absorptiometry and quantitative ultrasound to discriminate bone loss and to predict the mechanical and microarchitectural properties of cancellous bone in an animal model of osteopenia was evaluated. Thirty-five female Sprague-Dawley rats (10 months old) were randomized into three groups: baseline group, 10 rats killed at the beginning of the study; ovx group, 15 rats ovariectomized; and sham group, 10 rats sham operated. At the beginning and end of the study, all the animals underwent osteosonography to record the proximal tail (C3 vertebra) bone speed of sound. Sixteen weeks after surgery, the animals were euthanized and the L5–6 lumbar vertebrae of each rat were excised for densitometric, biomechanical (compression test), and histomorphometric studies. Significant differences were found among the groups for final speed of sound ( p = 0.01). The L5 bone mineral density of the ovx group decreased by 12.1% ( p = 0.049) and 12.6% ( p = 0.035) compared, respectively, with baseline and sham groups. The biomechanical parameters of the ovx group decreased by 15–47% compared with the other groups, showing significant differences between the ovx and sham groups both for maximal stress ( p = 0.026) and elastic modulus ( p = 0.013). Histomorphometric parameters of the ovx group showed significant decreases in comparison with other groups. Logistic regression analysis showed that dual X-ray absorptiometry and quantitative ultrasound discriminate ovariectomized and healthy rats with a similar capacity, classifying correctly all rats used in the model in a range of 61–70%. This similar capacity seems to derive from two different capacities to detect bone changes. Dual X-ray absorptiometry, depending on bone mineralization and density, is able to detect modifications in bone stiffness and strength, confirmed also by the correlation with biomechanical data. On the contrary, quantitative ultrasound seems to depend more on cancellous bone microarchitecural changes because it is correlated to histomorphometric parameters.

This study was performed to investigate the ability of ultrasonographic technique to distinguish osteomalacia from normal bone with the same mineral content. Ten rats with experimentally induced osteomalacia (group A) and 12 control rats having similar body size and weight (group B) were studied. Histomorphometric analysis confirmed the presence of osteomalacia in two rats from group A and showed normally mineralized bone in two rats from group B. Whole body bone mineral density, measured by dual-energy x-ray absorptiometry, was similar in the two groups (86 +/- 6 mg/cm2 in group A and 89 +/- 4 mg/cm2 in group B). The velocity of the ultrasound beam in bone was measured by densitometer at the first caudal vertebra of each rat. The velocity was measured when the first peak of the waveform reached a predetermined minimum amplitude value (amplitude-dependent speed of sound) as well as at the lowest point of this curve before it reaches the predetermined minimum amplitude (first minimum speed of sound). Although the amplitude-dependent speed of sound was similar in the two groups (1381.9 +/- 11.8 m/s in group A and 1390.9 +/- 17.8 m/s in group B), the first minimum speed of sound was clearly different (1446.1 +/- 8.9 m/s in group A and 1503.3 +/- 10.9 m/s in group B; P < 0.001). This study shows that ultrasonography could be used to identify alterations in bone quality, such as osteomalacia, but further studies need to be carried out before this method can be introduced into clinical practice.

Purpose of the study Tenofovir disoproxil fumarate (TDF) is not approved for use in HIV-infected children (

Objective To investigate both the biochemical and the potential morphological changes in bovine cartilage explants following treatment with glucosamine HCl, and to evaluate the capability of glucosamine to counteract the degradation of cartilage induced by catabolic agents such as interleukin-1β (IL-1β) and the bacterial lipopolysaccharide (LPS). Design Bovine articular cartilage explants were treated with increasing doses of glucosamine HCl (0.25–25mg/ml) in the absence or in the presence of IL-1β or LPS. The release of matrix proteoglycans in the medium, as well as variations in nitric oxide and lactate production were evaluated by standard assays. Proteoglycan synthesis was determined by incorporation of Na 2 - 35 SO 4 . Ultrastructural analysis was performed by transmission electron microscopy. Results Increasing doses of glucosamine (2.5, 6.5, 25mg/ml) induced a dose-dependent decrease in proteoglycan synthesis and in lactate production after 24h treatment. The biochemical changes induced by IL1-β or LPS appeared to be inhibited by 6.5 and 25mg/ml glucosamine. At these concentrations a decrease in cell viability was observed, which reached over 90% at 25mg/ml. Conclusions This study shows that pharmacological doses of glucosamine induce a broad impairment in the metabolic activity of bovine chondrocytes, leading to cell death. The inhibition of the catabolic effects induced by IL1-β and LPS appears related to glucosamine toxicity. In other experimental models, the same or similar doses of glucosamine have previously been used, without showing any adverse effect. We conclude that, in studying the effects of glucosamine, particular attention should be addressed to the experimental model, the doses and the length of treatment. Copyright 2002 OsteoArthritis Research Society International. Published by Elsevier Science Ltd. All rights reserved .

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 50.92, p < 0.0001). The absorbed dose threshold was dependent on the number of pulses for each voltage applied (r2 50.96, 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.

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.

BACKGROUND: A multicenter retrospective analysis of patients treated for leg fractures was conducted to develop a score that correlates with fracture healing time and to identify the risk gradient for delayed healing. METHODS: Fifty-three patients were analyzed and considered healed when full weight bearing was possible. Patients were divided into those who healed within 180 days and those who took longer to heal. Risk factors associated with delayed healing, fracture morphology, and orthopedic treatments were recorded. The available literature was used to weight the relative risk associated with each factor; values were combined into a score evaluating the risk of delayed healing: L-ARRCO (a literature-based score where the risk of delayed bone healing is calculated using a specific algorithm). Other risk factors associated with delayed healing were then considered in order to calculate a new score, ARRCO. Continuous variables were compared between groups using Student's heteroschedastic two-tail t test. Receiver operating characteristic (ROC) curves and the areas under the curves were calculated to determine the ability of this score to discriminate subjects with delayed healing. RESULTS: The mean L-ARRCO scores of the patients who healed within and after 180 days were significantly different (5.78 ± 1.59 and 7.05 ± 2.46, respectively). The mean ARRCO scores of the patients who healed within and after 180 days were also significantly different (5.92 ± 1.78 and 9.03 ± 2.79, respectively). However, the area under the ROC curve was significantly smaller for L-ARRCO than for ARRCO (0.62 ± 0.09 versus 0.82 ± 0.07). CONCLUSIONS: The ARRCO score is significantly associated with fracture healing time and could be used to identify "fractures at risk," allowing early intervention to stimulate osteogenesis.