Zenon Halaba

The assessment of development of bone mass in children by quantitative ultrasound through the proximal phalanxes of the hand.

The purpose of this study was to determine the relationship between quantitative ultrasound and age and body size, and to establish reference ranges for speed of sound (Ad-SoS) in the phalanxes of children. Healthy children (433), aged from 9 to 15 y were studied (226 girls and 207 boys). Ultrasound device (DBM Sonic 1200, IGEA, Italy) measuring the Ad-SoS through the phalanxes was used. Up to 11 y, the mean values for boys and girls were not significantly different. The increase of values was observed in the girls at 11 y, in the boys 2 y later. Stepwise multiple linear-regression analysis has shown that, in girls, the main factor influencing Ad-SoS was age and, in boys, height and weight. In the study, the ability of measurements of proximal phalanxes to reveal skeletal changes in healthy Polish children was shown. The study enabled us to establish the reference curves for healthy Polish children.

Skeletal Status in Children, Adolescents and Young Adults with End-Stage Renal Failure Treated with Hemo- or Peritoneal Dialysis

Abstract: The skeletal status in 30 children, adolescents and young adults (18 females, 12 males) with end-stage renal failure (ESRF) aged 9-23 years (mean 15.8 ± 3.6 years) was evaluated using measurements of bone mineral density (BMD, g/cm2) at the spine and total body (TB) (Lunar DPX-L, USA), quantitative ultrasound (QUS) of the hand phalanges (DBM Sonic 1200, IGEA, Italy) and laboratory investigations (parathyroid hormone, serum total and ionized calcium, serum phosphate). Eleven subjects were treated with hemodialysis and 19 with peritoneal dialysis. The mean value of the amplitude-dependent speed of sound (Ad-SoS, m/s) measured by QUS was significantly decreased in comparison with the value obtained in a group of 686 age-matched controls (1942 ± 74 m/s vs 2050 ± 77 m/s, p<0.0001). BMD measurements were also decreased in comparison with mean values for the healthy population (Z-scores for spine −1.47, and for TB −1.53). Duration of dialysis correlated significantly with spine-BMD, TB-BMD and Ad-SoS (r=−0.37, r = −0.45, r=−0.55, respectively, p<0.05), while duration of ESRF did not have such an influence. Laboratory investigations did not correlate with skeletal parameters. Ad-SoS correlated significantly with spine-BMD (r= 0.45, p<0.05) and TB-BMD (r= 0.56, p<0.01). Both QUS and BMD values correlated significantly with Tanner stages (r ranged from 0.59 to 0.69, p<0.001) and did not increase with age except for correlation between age and TB-BMD. In conclusion, skeletal status in the population studied is strongly affected by ESRF. Both QUS and BMD measurements show an ability to express skeletal changes in a similar manner, though the QUS parameter seems to be more sensitive at revealing changes due to renal failure.

Skeletal status in adolescents with end-stage renal failure: a longitudinal study

In a longitudinal study, bone status was assessed in adolescents and young adults aged 15.3±3.4 years at the onset of the study with end-stage renal failure (ESRF). The group consisted of 18 subjects (11 females and seven males), of whom nine patients were on hemodialysis and nine patients on peritoneal dialysis. Six patients were previous or current glucocorticoid (GCS) users. Renal failure was recognized before 6.1±4.1 years, and dialysis was performed for 3.0±2.0 years. Follow-up took placed 8.6±0.8 and 21.7±2.5 months later, and the following data were collected: bone mineral density (BMD) at the spine (s-BMD) and total body (TB-BMD) using DPX-L (Lunar, USA); quantitative ultrasound by DBM 1200 (IGEA, Italy) at the hand phalanges (Amplitude-dependent Speed of Sound, Ad-SoS), serum concentration of i-PTH, total calcium, ionized calcium and phosphate. Tanner stages were also evaluated. The mean values of BMD measurements and Ad-SoS were stable during a period of observation, and a mean Z-score for TB-BMD was significantly lower at the third versus baseline value (−1.87±1.75 versus −1.49±1.53, P<0.05). Z-scores for s-BMD and Ad-SoS decreased non-significantly. Changes in s-BMD and TB-BMD Z-scores were influenced by changes in body size and changes in biochemical parameters, and a change in Ad-SoS Z-score was not dependent on these factors. The values of second (P<0.05) and third (P<0.01) s-BMD Z-score were significantly lower in GCS treated subjects, and longitudinal change in spine Z-score was greater in GCS treated patients versus others (P<0.05). Duration of ESRF, duration and type of dialysis and gender did not influence skeletal variables. Skeletal measurements correlated significantly with Tanner stages (besides the correlation with Ad-SoS in the first measurement, r ranged from 0.5 to 0.72, P<0.05), and changes in Tanner stages observed over a period of observation did not correlate with changes in skeletal variables. Among laboratory variables, the following non-significant tendencies to change were observed: serum concentration of i-PTH and phosphate increased, and total and ionized calcium decreased. In conclusion, adolescent subjects with ESRF treated with dialysis showed stable mean values of skeletal measurements, and these were expressed as Z-scores, a tendency to drop was observed. The lack of an increase observed in normal healthy subjects of the same age, and low values in Z-scores, indicates that skeletal status is seriously affected in subjects with ESRF.

Quantitative Ultrasound at the Hand Phalanges in 2850 Females Aged 7 to 77 Yr: A Cross-Sectional Study

In the study, skeletal status was evaluated in 2850 females aged 7 to 77 yr using quantitative ultrasound (QUS amplitude-dependent speed of sound [Ad-SoS]). Ad-SoS ranged from 1923 +/- 30 to 1876 +/- 81 m/s, and the peak value (2121 m/s) was achieved in 19-yr-old females. Ad-SoS increased significantly between subgroups aged 11 and 12 yr, 12 and 13 yr, 13 and 14 yr, 14 and 15 yr, and 15 and 16 yr. After the age of 19 yr the only significant drop was noted between age groups 47 and 48 yr. Ad-SoS was regressed on age, weight, and height for age ranges 7 to 11 yr.(before an increase in Ad-SoS), 12 to 19 yr (from the onset of the increase to the peak value), and older than 19 yr to menopause. In females after menopause, years since menopause (YSM) were taken into consideration. In the two youngest groups Ad-SoS was affected positively by age, and in the two next groups, age had a negative influence on Ad-SoS, whereas weight had a negative and height a positive influence in all groups. YSM did not influence the Ad-SoS value. It was concluded that QUS measurements at the hand phalanges are a useful tool in assessment of skeletal status in the female population.

Quantitative Ultrasound Measurements at Hand Phalanges in Children and Adolescents: A Longitudinal Study

The purpose of this longitudinal study was to characterize changes in quantitative ultrasound (QUS) values over a 1-y period in healthy boys and girls aged 7 to 12 y at baseline and assess the relation between the increase in anthropometric parameters and amplitude dependent speed of sound (Ad-SoS). A total of 269 children completed the study (139 girls and 130 boys). Ultrasound measurements were performed with a DBM Sonic 1200 device (IGEA, Carpi, Italy), which measures the Ad-SoS, m/s. Girls had significantly higher QUS values than boys at first and second measurements (p < 0.01 and p < 0.00001, respectively). Both girls and boys experienced statistically significant increases in Ad-SoS and all anthropometric parameters over a 1-y period. When the studied group was divided into age groups by year, the differences in QUS values between genders were significant only for 11 and 12 y groups at baseline (p < 0.02 and p < 0.01, respectively) and second visit (p < 0.00001 and p < 0.001, respectively). Stepwise regression analyses models with Ad-SoS at baseline and after 1 y as dependent variables showed a strong correlation between Ad-SoS and Tanner stage in girls but not in boys. In the entire survey group, only 21.5% of the boys and 41% of the girls experienced increases in Ad-SoS more than least significant change. This article suggests that QUS measurements allow the investigation of longitudinal changes and give reliable information about skeletal status in a manner similar to other methods.

Skeletal status in survivors of childhood acute lymphoblastic leukemia assessed by quantitative ultrasound: a pilot cross-sectional study.

Intensive treatment in acute lymphoblastic leukemia (ALL) with the use of multimodality therapies, including radiotherapy, corticosteroids and cytotoxic agents, may lead to disturbances in bone metabolism. The aim of this study was to determine the degree of possible changes in bone status in survivors of ALL. The studied population consisted of 54 subjects aged 13.0 +/- 3.3 years (31 girls and 23 boys). The mean age at diagnosis was 5.5 +/- 3.5 years, age at the completion of therapy was 8.4 +/- 3.5 years, and the period of follow-up was 4.6 +/- 3.4 years. Patients were divided into three subgroups (low-, moderate- and high-risk) according to the presence of risk factors of ALL and compared with 1020 healthy subjects (508 girls and 512 boys). Patients and controls did not differ significantly in regard to age, height, or weight. Bone status was assessed by quantitative ultrasound (US) at right (dominant) hand phalanges using DBM Sonic 1200 (IGEA, Carpi, Italy) that measures amplitude-dependent speed of sound (Ad-SoS, m/s). Root mean square (RMS)_CV% was 0.43%. Mean Ad-SoS values were 2018 +/- 73 m/s in patients and 2003 +/- 80 m/s in controls and did not differ significantly. Ad-SoS tended to be lower in moderate- and high-risk patients, but differences were not significant. Ad-SoS correlated significantly with age in patients (r value ranged from 0.63 to 0.77, p < 0.01) and controls (r value ranged from 0.79 to 0.84, p < 0.0001). In multiple forward regression analysis, the following equation was obtained: Ad-SoS (m/s) = 1878 (m/s) + 11.4 x age at the study (y) + 4.0 x period after therapy completion (y) - 9.5 x duration of the therapy (y). It can be concluded that bone status assessed by quantitative US at the hand phalanges in survivors of acute lymphoblastic leukemia 4.6 years after completion of the therapy is not affected in comparison to healthy controls.

Quantitative Ultrasound Bone Measurements in Pre-Pubertal Children with Type 1 Diabetes

This case-control study aimed to assess bone status in children with type 1 diabetes mellitus (T1DM). Fifty-seven pre-pubertal patients (37 boys, aged 7.9 ± 2.5 years, T1DM duration 3.1 ± 1.6 years) and 171 age-matched healthy controls (111 boys) were studied. Quantitative ultrasound (QUS) was used to measure amplitude dependent speed of sound (Ad-SoS) at hand phalanges (expressed as standard deviation score [SDS]). Anthropometric and disease-related data (including mean HbA(1c) from whole T1DM duration [T], last year [Y], examination day [D]) were collected. Mean Ad-SoS SDS in patients -0.13 ± 1.32 (95% confidence interval [CI] -0.48, 0.22) was similar to that of controls. Subgroups discriminated according to HbA(1c) D, Y and T (cut-off 7.0%) did not differ regarding analyzed parameters. In patients, Ad-SoS SDS was comparable for both genders. Multivariable stepwise regression analysis showed significant negative influence of diabetes duration on Ad-SoS SDS. QUS findings in pre-pubertal children with T1DM do not differ from those in healthy children. Disease duration seems to affect negatively Ad-SoS SDS. However, independent prospective studies are needed to elucidate the true associations.

ASSESSMENT OF SKELETAL STATUS BY QUANTITATIVE ULTRASOUND AT THE HAND PHALANGES IN CHILDREN WITH BRONCHIAL ASTHMA—A PILOT STUDY

The aim of the study was to assess the skeletal status by quantitative ultrasound measurement at hand phalanges in asthmatic children treated with inhaled corticosteroids. Sixty-nine (69) children with a mean age of 10.9 ± 2.6 y and 251 controls matched for age and body size were enrolled into the study. The mean value of amplitude-dependent speed of sound in asthmatic children was 1953.8 ± 60.2 m/s and the mean Z-score was -0.05 ± 1.02; the corresponding values in the controls were 1951.0 ± 53.9 m/s and -0.26 ± 1.05, respectively. The results did not differ between the asthmatic and the healthy (control) children. A cumulative dose of inhaled steroids was identified in a stepwise regression analysis as a factor with potentially negative influence on bone status. In conclusion, the skeletal status in asthmatic children, assessed by quantitative ultrasound, shows no difference in comparison with healthy children. Nonetheless, special caution is necessary in case of long-term corticosteroid therapy, in which a slightly negative influence of treatment on the skeleton cannot be excluded.

Quantitative Ultrasound Measurement at the Hand Phalanges Does Not Reveal Skeletal Disturbances in Children With Bronchial Asthma: A Longitudinal Observation

To assess the skeletal status in asthmatic children treated with inhaled corticosteroids in a longitudinal observation by quantitative ultrasound (US) measurement at the hand phalanges.

Pediatric reference curves for multi-site quantitative ultrasound and its modulators—reply

Recently in Osteoporosis International, an interesting study on skeletal status in children population was published by Zadik et al. [1]. The measurements were performed in 1085 healthy subjects using quantitative ultrasound (QUS) at tibia and distal third of radius. The purpose of the study was to establish pediatric reference curves for bone properties, expressed as speed of sound (SOS). The authors stated that SOS showed a steep increase during the first 5 years of life, and during the pubertal period was observed the second growth burst, starting at the age of 11 years in girls and 14 years in boys. The study also estimated the influence of pubertal stages expressed in Tanner stages, physical activity and diet calcium intake. We consider that study provides some new, interesting data on the clinical utility of QUS in children population, but some results need to be clarified. Firstly, in order to establish reference values a number of subjects in age subgroups for both genders ought to be given, and Table 1 lacks these data. More importantly, the authors did not provide the exact results of comparisons between values in 1-year subgroups. The increase in years 0–5 seems to be reliable, but we doubt if increases during puberty really begin at the age indicated in the study. For example, in girls aged 11 and 12 years, tibial SOS had the same value of 3674 m/s and in the same age subgroups SOS at the radius was 3805 and 3800 m/s. It means that the increase did not start at the age of 11 years. Similarly, in boys at the radius SOS was 3789 and 3798 m/s at 14 and 15 years, respectively. Did these values differ significantly? Secondly, we have some comments on the analysis of calcium intake and level of physical activity on measured parameters. Despite physical activity shown to be related to current tibial and radial QUS parameters and calcium intake, we do not recommend analysis of the influence of these factors separately before and after the pubertal period. It is well known that the potential of calcium intake and physical activity to interfere with skeletal growth is present mainly before pubertal period [2, 3], and analysis performed in adequate age subgroups would probably show more precise data. During puberty, other factors are more potent than calcium. This is especially true of estrogen, which can easily overwhelm any calcium effect. We consider that providing by the authors requested information might give additional, clinically important data on skeletal status in children and help to explain the results of the study.