Francesca de Terlizzi

Bone quality assessment by quantitative ultrasound of proximal phalanxes of the hand in healthy subjects aged 3-21 years

Bone quality by quantitative ultrasound was assessed in 1083 (587 males) healthy white subjects aged 3–21 y. Amplitude-dependent speed of sound (AD-SoS) through the distal end of the first phalanx diaphysis of the last four fingers of the hand was measured by an ultrasound device (DBM Sonic 1200, IGEA, Carpi, Italy). Mean AD-SoS values increased progressively from 3 to 21 y (males, 1845.9–2119.1 m/s, p < 0.0001; females, 1842.3–2098.8 m/s, p < 0.0001). They did not differ (p = NS) between sexes up to age 11, but females showed higher (p < 0.05 –p < 0.0001) AD-SoS values than males in age groups 12, 13, and 14 y. There was no difference (p = NS) of AD-SoS values between sexes in pubertal stages 1, 2, and 5, but females had higher mean AD-SoS values than males in stages 3 (p < 0.01) and 4 (p < 0.001). Independent predictors of AD-SoS were weight, body mass index, pubertal stage, and mean width of fingers in males, and age, pubertal stage, and mean width of fingers in females (p < 0.01 –p < 0.0001). However, 7.8% in males and 3.6% in females of the increment of AD-SoS values can be related to the finger anatomy alone. AD-SoS values probably reflect the architectural organization of growing bone or changes in bone elasticity. Increased bone density and size may be additional factors influencing AD-SoS. Measurement of AD-SoS at the hand phalanxes may be a simple, noninvasive, and radiation-free technique to assess bone quality in children.

Assessment of bone quality by quantitative ultrasound of proximal phalanges of the hand and fracture rate in children and adolescents with bone and mineral disorders

Bone quality by quantitative ultrasound and fracture rate were assessed in 135 (64 males) children and adolescents aged 3-21 y with bone and mineral disorders such as chronic anticonvulsants or glucocorticoids treatment, juvenile rheumatoid arthritis, celiac disease, paucity of intrahepatic bile ducts, autoimmune hepatitis, genetic diseases, idiopathic juvenile osteoporosis, disuse osteoporosis, β-thalassemia major, survivors of acute lymphoblastic leukemia, liver transplantation, calcium deficiency, and nutritional or X-linked hypophosphatemic rickets. Amplitude-dependent speed of sound through the distal end of the first phalangeal diaphysis of the last four fingers of the hand was measured by an ultrasound device. In the majority of patients cortical area to total area ratio by metacarpal radiogrammetry (n=120) and lumbar bone mineral density (BMD) by dual-energy x-ray absorptiometry (n=99) were also assessed. In patients with X-linked hypophosphatemic rickets radial BMD by single-photon absorptiometry instead of lumbar BMD was measured. Mean values of amplitude-dependent speed of sound, cortical area to total area ratio, lumbar BMDarea, or lumbar BMD corrected for bone sizes estimated by a mathematical model (BMDvolume), as well as mean values of radial BMD in patients with X-linked hypophosphatemic rickets, expressed as z score, were significantly reduced (p < 0.0001) in comparison with their reference values (−1.7 ± 1.0, −2.0 ± 0.9, −3.0 ± 1.3, −1.9 ± 1.0, −2.7 ± 0.7, respectively). A positive relationship was found between amplitudedependent speed of sound and cortical area to total area ratio (r = 0.90, p < 0.0001), lumbar BMDarea (r = 0.62, p < 0.0001), or lumbar BMDvolume (r = 0.66, p < 0.0001). Fifty-two patients (38.5%) had suffered fractures in the 6 mo preceding the bone measurements, the radial distal metaphysis being the most frequent fracture site (28.8%). Mean values of amplitude-dependent speed of sound, cortical area to total area ratio, lumbar BMDarea, or lumbar BMDvolume, expressed as z score, of fractured patients were significantly lower (p < 0.0001) than those of fracture-free patients (−2.2 ± 1.0 and −1.4 ± 0.8, −2.6 ± 0.9 and −1.7 ± 0.7, −3.5 ± 1.2 and −2.5 ± 1.0, −2.5 ± 1.0 and −1.3 ± 0.7, respectively). Phalangeal quantitative ultrasound may be a useful method to assess bone quality and fracture risk in children and adolescents with bone and mineral disorders.

Influence of Bone Tissue Density and Elasticity on Ultrasound Propagation: An In Vitro Study

Ultrasound (US) waves are mechanical vibrations that are applied to a material—bone tissue—in order to study its properties, that is, density, elasticity, and structure. In this study we evaluated in which way density and elasticity of the spongy bone influenced the transmission of 1.25 MHz US pulses. Twelve cylindrical specimens (diameter, 8 mm; height, 5 mm) excised from phalanxes of pig were decalcified with 0.5 M EDTA for different times (0, 2, and 5 days). During these periods, the samples underwent the following investigations: US transmission, density, and elasticity measurements. To assess the homogeneity of decalcification, the cross‐sections of some samples were microradiographed. A detailed analysis of the US signal received was performed using velocity, Fourier analysis, and some parameters typical of signal processing technique. A good correlation was found between US velocity and density (r2 = 0.70); a lower correlation was found between velocity and elasticity (r2 = 0.59). If density and elasticity are considered simultaneously, the correlation with the US velocity improves significantly (r2 = 0.84). Fourier analysis enabled us to observe a shift of the main frequency toward lower values as the decalcification process advanced. We also observed that in the regressions weighted for density, US velocity correlated poorly with elasticity (r2 = 0.16), whereas signal processing parameters maintain a good correlation with elasticity (ultrasound peak amplitude [UPA], r2 = 0.48; slope, r2 = 0.62). In this study, it has been observed that when using a signal processing technique to analyze US pulses, it is possible to identify some parameters that are related in different ways to density and to elastic properties of bone. Our results show the potentiality of US technique to separate information on bone density and elasticity that X‐ray‐based densitometric methods do not provide.

Assessment of skeletal development in preterm and term infants by quantitative ultrasound

Assessment of skeletal development using a nonionizing method would be desirable in critically ill preterm infants. We investigated the second metacarpus by quantitative ultrasound (QUS). Cross-sectional data were collected in 132 preterm or term infants measured within 24 h from birth and in 142 term infants up to the age of 18 mo. Longitudinal data were collected in 150 preterm infants up to the age of 14 mo. Cross-sectional data were used to devise reference curves for metacarpal speed of sound (mcSOS) and metacarpal bone transmission time (mcBTT). Both parameters increase during the last trimester of gestation. After birth, mcSOS declines up to the 6 mo and then increases up to 18 mo of life. McBTT values remain stable after birth. At birth, QUS values of preterm infants are lower than those observed at birth in term infants. In the longitudinal study, mcSOS showed a trend similar to that observed among term infants, nevertheless, values are lower up to 4–6 mo of life. Among preterm infants, mcBTT increases until it reaches values observed in term infants. Preterm infants in their first months of life have lower QUS values compared with term infants of same weight or length. This study demonstrates that it is possible to follow skeletal development and maturation by QUS in preterm infants. More specifically, the mcBTT values may provide information on bone tissue that is independent of length and weight of the preterm infant. The method here described is safe, repeatable, and reliable.

Monitoring bone effect of transdermal hormone replacement therapy by ultrasound investigation at the phalanx: a four-year follow-up study.

ObjectiveA controlled 4-year follow-up study was conducted on a population composed of 112 healthy early postmenopausal women to evaluate the ability of ultrasound technology in detecting the effects of hormone replacement therapy (HRT) on bone. At the end of the study, 47 untreated and 25 treated women had been evaluated. Cyclic sequential estrogen/progestogen therapy, 50 &mgr;g/day of transdermal 17&bgr;-estradiol (Rotta Research Laboratorium) plus 5 mg/day of medrogestone (Wyeth-Ayerst) was used. DesignUltrasound transmission through the distal metaphysis of hand phalanxes was measured by DBM Sonic. Beside amplitude-dependent speed of sound (AD-SoS), three new parameters could be calculated: pure speed of sound (pSOS), bone transmission time (BTT), and ultrasound bone profile index (UBPI). Ultrasound measurements were taken at baseline and after 1, 2, and 4 years. ResultsAmong untreated women a significant decrease of all ultrasound parameters was observed at follow-up measurements. In the HRT-treated group we observed a significant increase of AD-SoS, pSoS, and BTT. We qualified as “responders” women in the treated group for whom AD-SoS, pSoS, and BTT increased by more than 2.77 times the coefficient of variation of the measurement, i.e., 95% variability. Women in the treated group were identified as responders at 4 years of follow-up by AD-SoS (56%), pSOS (56%), and BTT (60%). Ultrasound bone profile index declined in both groups, although to a lower extent among HRT-treated subjects. ConclusionsThe 4-year data confirm the results obtained at 1 and 2 years of follow-up. This study demonstrates that bone tissue investigation by ultrasound at the phalanx can be used to monitor the effect of HRT, and thus it should be considered a potential technology for the management of menopause by gynecologists.

Assessment of Bone Architecture with Ultrasonometry: Experimental and Clinical Experience

Over the last decade, ultrasound technology has been introduced as a method of analysing bone tissue in clinical practice, and several studies have compared various ultrasound devices with dual-energy X-ray absorptiometry (DXA). Unlike DXA, the ultrasound technique is not limited to the measurement of bone density – it also has the potential to provide information on the mechanical and architectural characteristics of bone. The first generation of ultrasound devices used the speed of sound and attenuation of the ultrasound signal to obtain information on bone mineral content. Second generation ultrasound devices, which analyse the ultrasound signal received, permit the study of bone structure and elasticity, in addition to its mineral content, in both experimental studies and clinical practice. This is accomplished by signal processing analysis, the study of backscattering and the application of Biot’s theory. This approach to the study of bone tissue represents the future for the development of ultrasound technology for use in clinical practice.

Treatment of keloids and hypertrophic scars with bleomycin and electroporation.

Background: Keloids and hypertrophic scars are the result of abnormal healing responses and dermal tissue proliferation; current surgical procedures can give rise to exuberant scarring and permanent functional loss or disfigurement. Considering the promising results reported when treating keloids and hypertrophic scars with intralesional bleomycin injection and the enhanced effect of bleomycin when combined with electroporation, the authors hypothesized that electrochemotherapy should be used to treat keloids and hypertrophic scars when other treatments have failed. Methods: Twenty patients with keloids or hypertrophic scars were treated with one or more sessions of electrochemotherapy and followed prospectively. Bleomycin was administered intravenously followed by application of electrical pulses to the lesion site. Treatment efficacy was determined either by clinical evaluation (e.g., volume, flattening, pliability, erythema) or by the patient’s self-reported symptomatology (e.g., pruritus, pain). Results: Treatment was well tolerated by patients, and no serious adverse events were observed. A median reduction of 87 percent (range, 41 to 100 percent) was observed in volume size, and 33 lesions (94 percent) showed a volume reduction of more than 50 percent. Scar pliability and erythema scores were also significantly reduced (p < 0.0001). A reduction in hitching was observed in 89 percent of patients (p < 0.0001), and a reduction in pain was observed in 94 percent (p < 0.0001). Only one recurrence was observed after 18 months. Conclusion: Electroporation in combination with bleomycin is an effective treatment for patients affected by large keloids or hypertrophic scars or patients who are nonresponders to other treatments. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, IV.

Analysis of quantitative ultrasound graphic trace and derived variables assessed at proximal phalanges of the hand in healthy subjects and in patients with cerebral palsy or juvenile idiopathic arthritis. A pilot study.

Amplitude-dependent speed of sound (AD-SoS) and bone transmission time (BTT) are the quantitative ultrasound (QUS) variables usually assessed at proximal phalanges of the hand to estimate bone mineral status. The aim of the study was to provide a reference database for some additional QUS variables reflecting morphology of the ultrasound graphic trace according to gender, age, height, weight, and body mass index (BMI), and to assess their clinical usefulness. Fifty-two patients (age 3.1-20.9 years) affected by cerebral palsy with spastic tetraplegia (CPST, n=38) or polyarticular active juvenile idiopathic arthritis (JIA, n=14) were examined. In addition to AD-SoS and BTT, two QUS variables derived from the morphological analysis of ultrasound graphic trace, such as energy, extrapolated from the area under the ultrasound signal received, and weighted-slope (W-slope), derived from the angular coefficient of the regression line fitting the top point of the peaks of the ultrasound signal, were measured by phalangeal QUS (DBM Sonic, IGEA). The values of all the QUS variables measured in the patients were compared with our own sex- and age-reference values (n=1083, 587 males and 496 females, aged 3-21 years). The mean values of AD-SoS, BTT, energy, and W-slope were reduced (P<0.0001) in patients as a whole compared with normative data (-2.4+/-1.2, -2.7+/-1.5, -2.5+/-1.1, -2.5+/-1.1 Z-score, respectively). Fractured patients showed lower (P<0.001-P<0.0001) values of the QUS variables than fracture-free patients (AD-SoS, -3.3+/-1.2 and -1.8+/-0.9; BTT, -3.9+/-1.7 and -1.8+/-1.1; energy, -3.2+/-1.2 and -2.2+/-0.7; W-slope, -3.4+/-1.4 and -2.2+/-0.9 Z-score, respectively). There was no difference (P=NS) between patients with CPST and those with JIA. Age and height were positively correlated with all the QUS variables (r=0.55-0.79, P<0.01-P<0.0001). QUS variables were positively correlated among them (r=0.74-0.94, P<0.0001). Age and number of fractures were independent predictors of the QUS variables (coefficients: AD-SoS, 11.466 and -17.642; BTT, 0.049 and -0.045; energy, 1.072 and -1.303; W-slope, 0.046 and -0.067; respectively). In conclusion, measurement of QUS variables derived from the morphological analysis of the ultrasound signal could give additional information in estimating bone mineral status in children and adolescents, probably reflecting some aspect related to bone structure.

Analysis of skeletal status by quantitative ultrasonometry in a cohort of postmenopausal women with high blood cholesterol without documented osteoporosis.

Osteoporosis and atherosclerosis are leading causes of mortality and morbidity in the Western world. A link between osteoporosis and atherosclerosis was proposed by epidemiologic and laboratory data. In the present study, we investigated skeletal status in postmenopausal women with hypercholesterolemia using quantitative ultrasonometry (QUS). Six hundred healthy postmenopausal subjects were enrolled within a 2-mo period by primary care physicians. Information on lifestyle and calcium intake was collected for each enrolled subject. Subjects (n = 256) were divided into two groups according to lipid profile: normal (n = 180) with serum cholesterol <200 mg/dL and hypercholesterolemic (n = 76) with serum cholesterol >or=200 mg/dL. Hypercholesterolemic subjects were further stratified into two groups, one receiving dietary treatment (n = 34) and the other receiving statin treatment (n = 42). We found a statistically significant reduction in amplitude dependent speed of sound (AD-SoS) in hypercholesterolemic subjects compared with subjects with normal cholesterol (p = 0.006). Calcium intake behaved similarly to AD-SoS (p = 0.0001). No statistical significant difference in AD-SoS were observed between the group on diet treatment versus the group on statin (p = 0.52). Calcium intake was lower in patients on statins treatment compared with subjects on diet treatment only (p < 0.0001). Our data suggest that hypercholesterolemia per se is a risk factor for impaired skeletal status. Our data also call attention to the risk of a poor calcium intake in patient receiving diet to lower plasma cholesterol. Moreover, our data suggest that statins per se may exert a protective effect on bone independently from calcium intake.

Performance of five phalangeal QUS parameters in the evaluation of gonadal-status, age and vertebral fracture risk compared with DXA.

The aim of this cross-sectional study was to study the value of five different quantified ultrasound (QUS) parameters-amplitude-dependent speed of sound (AD-SoS), Ultrasound Bone Profile Index (UBPI), fast-wave amplitude (FWA), bone transmission time (BTT) and signal dynamic (SDY)-measured at the phalanges of the hand in discriminating women with vertebral fracture and their relationship with some determinants of bone mass, in particular age and gonadal status compared with lumbar spine and hip dual-energy x-ray absorptiometry (DXA). We included 791 women aged 35-84 y, divided into pre-menopause, early menopause and late postmenopause groups on the basis of gonadal status and years since menopause (YSM). The presence of vertebral fracture was evaluated radiographically. All QUS parameters were very sensitive to changes in early postmenopause, with a doubled decrease in early postmenopausal with respect to late postmenopause. In particular AD-SoS and BTT decreases were markedly high in the early postmenopause group. In the late menopause group, similar decreases were observed for AD-SoS, UBPI and hip bone mineral density (BMD). In the multiple logistic model, DXA and QUS significantly discriminate women with and without fractures (p < 0.0001); odds ratio (OR) was higher at lumbar spine BMD (OR 4.01), FWA (OR 3.88), AD-SoS (OR 3.81) and total hip BMD (OR 3.77). Even adjusting the logistic model for age, height, weight, lumbar spine and total hip BMD, all QUS parameters remained significantly predictive of vertebral fracture. AD-SoS showed the best performances both in terms of OR and ROC analysis. QUS parameters show a different behavior in evaluating the effect on bone mass of the time since menopause; AD-SoS and BTT showed a high sensitivity to first changes in bone tissue after menopause. After correction for potential confounders, AD-SoS showed the same ability of lumbar spine BMD in discriminating women with or without vertebral fractures and in the prediction of fracture risk.