Bone Transmission Time Research Articles

Thalassaemia Patients with Polymorphism of COL1A1 Sp1 are at Greater Risk of Spine Degenerative Changes.

To explore the association of the COL1A1 Sp1 polymorphism with decreased bone density and spinal changes in β-thalassaemia patients. Cross-sectional, comparative study. Place and Duration of the Study: University of Health Sciences, Lahore, from May 2020 to June 2021. A total of 110 participants (55patients and 55 controls) of either gender, with ages ranging from 18-40 years were enrolled in the study. Bone density parameters including T-score, Z-score, bone-transmission time (BTT), and amplitude-dependent speed of sound (ADSOS) were assessed by ultrasound bone profiler. Lumbar spine radiographs were collected from patients and assessed for spine changes. Genotype analysis was done by HRM-PCR. Data were analysed using SPSS version 23. All bone density parameters were significantly lower in β-thalassaemai patients (p<0.001). Spine degenerative changes were more obvious in patients with age <25 years (p=0.04). Loss of lumbar lordosis was seen in 74.5% of the patients. The frequency of mutant allele (ss) was 7.3% while heterozygous (Ss) frequency was found to be 33.6%. The polymorphism showed significant association with T-scores (p=0.03) and ADSOS (p=0.02) in patients. Radiographic grades were higher in osteopenic and osteoporotic patients (p=0.04). The association of polymorphism with decreased bone density in β-thalassaemia patients revealed the potential role of genetics in bone changes and related disorders. Bone Density, COL1A1 Polymorphism, Osteoporosis, Thalassaemia.

Bone Status and Early Nutrition in Preterm Newborns with and without Intrauterine Growth Restriction.

Intrauterine growth restriction (IUGR) together with preterm birth could be harmful to bone health. The aim of the study was to examine bone status in IUGR versus non-IUGR preterms and to analyze the nutritional management best correlated with its improvement. Newborns < 34 weeks of gestational age (wGA), 75 IUGR and 75 non-IUGR, admitted to the Neonatal Intensive Care Unit of the University Hospital of Padova were enrolled and monitored from birth until 36 wGA through anthropometry (weight, length, head circumference, lower limb length (LLL)), biochemistry, bone quantitative ultrasound assessment of bone status (metacarpus bone transmission time, mc-BTT, us) and nutritional intakes monitoring during parenteral nutrition. IUGR compared to non-IUGR showed lower mean mc-BTT (0.45 vs. 0.51, p = 0.0005) and plasmatic phosphate (1.45 vs. 1.79, p < 0.001) at birth. Mc-BTT at 36 wGA, though equal between groups, correlated in IUGR newborns with basal phosphate, mean total energy of the first week and month (positively) and days to reach full enteral feeding (negatively). Lower i.v. vitamin D intake, LLL and prolonged total parenteral nutrition predicted worse mc-BTT at 36 wGA in the enrolled infants. These results suggest that preterms and in particular IUGR newborns need special nutritional care to promote bone development.

Trabecular bone score and phalangeal quantitative ultrasound are associated with muscle strength and fracture risk in hemodialysis patients.

There is growing interest in the relationship between chronic kidney disease (CKD) and fragility fracture risk. Bone mineral density (BMD) is a major determinant of bone strength, although its role as a predictor of fracture in advanced CKD and hemodialysis is still under debate. We aimed to further investigate surrogates of bone quality and their associations with muscle strength and fracture risk in hemodialysis. Multiple clinical risk factors for fracture and an estimated 10-year probability of fracture, BMD at lumbar spine and femur, trabecular bone score (TBS), X-ray vertebral morphometry, phalangeal bone quantitative ultrasonography (QUS), tibial pulse-echo ultrasonography (PEUS), and handgrip strength were evaluated in a setting of hemodialysis patients in treatment with acetate-free biofiltration (AFB) or bicarbonate hemodialysis. The bone ultrasound measurements, both at phalangeal and tibial sites, were significantly associated with lumbar and femoral DXA values. Handgrip strength was significantly associated with the 10-year probability of fracture (r = −0.57, p < 0.001 for major fractures and r = −0.53, p < 0.001 for hip fracture, respectively), with femur neck, total femur, and L1–L4 BMD values (r = 0.47, p = 0.04; r = 0.48, p = 0.02; r = 0.58, p = 0.007, respectively), with TBS at the lumbar spine (r = 0.71, p < 0.001) and with the phalangeal QUS measure of AD-SoS (r = 0.369, p = 0.023). In the hemodialysis group, 10 participants (24.3%) reported at least one morphometric vertebral fracture (Vfx); conversely, only six participants (15%) showed Vfx in the control group. In the hemodialysis group, participants with Vfx compared with participants without Vfx reported significantly different TBS, bone transmission time (BTT), cortical thickness, and handgrip strength (p < 0.05). At multiple regression analysis, by identifying as dependent variable the 10-year fracture risk for major fracture, after correcting for age, BMI, time since dialysis, AD-SoS, cortical bone thickness, and handgrip strength, only BTT (β = −15.21, SE = 5.91, p = 0.02) and TBS (β = −54.69, SE = 21.88, p = 0.02) turned out as independently associated with fracture risk. In conclusion, hemodialysis patients showed a higher fracture risk and lower surrogate indices of bone strength as TBS and QUS parameters. In this cohort of patients, handgrip strength measurements appeared to be a useful instrument to identify high-fracture-risk subjects.

Skeletal status in children and adolescents with new-onset type 1 diabetes: a preliminary study based on bone densitometry and quantitative ultrasound.

Type 1 diabetes (T1D) represents a risk factor for bone loss and impaired bone quality. We conducted an exploratory retrospective cross-sectional study involving youths with new-onset T1D, to investigate the relationship between lumbar spine dual-energy X-ray absorptiometry (DXA) and phalangeal quantitative ultrasound (QUS) measurements, along with their correlation with markers of bone turnover, glucose homeostasis, and residual β-cell function. 17 children and adolescents (8 females) with recent-onset T1D were enrolled into this study. Lumbar spine areal bone mineral density (aBMD) and age-adjusted amplitude-dependent speed of sound (AD-SoS) Z-scores were indicative of low BMD status (≤ -2.0 SD) in 11.7% and 17.6% of participants, respectively. Spearman's correlation analysis revealed significant inverse correlations between AD-SoS values and circulating levels of β-CrossLaps, alkaline phosphatase, and osteocalcin, along with a significant positive correlation between bone transmission time (BTT) values and fasting plasma C-peptide (FCP) levels. There was no statistically significant correlation between DXA-QUS parameters, fasting plasma glucose (FPG), and glycated haemoglobin (HbA1c). Finally, there was a significant positive correlation between lumbar spine aBMD and BTT values. Our study suggests that DXA and/or QUS parameters may be altered in a small proportion of T1D children and adolescents at the disease onset. Additionally, residual β-cell function may represent a protective factor against T1D-related detrimental skeletal changes. Large and long-term prospective studies are needed to confirm these preliminary findings since the present study is limited by the retrospective cross-sectional design and by its small sample size.

Is quantitative ultrasound a measure for metabolic bone disease in preterm-born infants? A prospective subcohort study

In this study, we aimed to (a) evaluate postnatal changes in bone development in relation to growth and (b) to determine factors associated with bone development, from birth to 24 months of corrected age. The metacarpal speed of sound (mcSOS) and metacarpal bone transmission time (mcBTT) were used to evaluate bone development in 98 preterm infants, during hospitalization and follow-up. The mcSOS and mcBTT values not only declined in the first 6 weeks of hospitalization but also during follow-up. The mcSOS reached its lowest point at 12 months (β=-34.64), while the mcBTT reached a plateau between 12 and 24 months (β=0.06). Univariable analysis showed that gender (p=0.28), time (p<0.001), and growth parameters (p<0.001) were significant negative associated factors with mcSOS, whereas with mcBTT, time (p=0.009), length (p=0.063), length standard deviation scores (SDS) (p=0.027), head circumference (p=0.005), and head circumference SDS (p=0.007) were significant positive. The multivariable model revealed that time (β= -3.364, p=<0.001), weight (β=-0.007, p<0.001) and length (β=1.163, p<0.001) for mcSOS and length (β=-0.021, p<0.001), and length SDS (β= 0.066, p<0.001) and head circumference (β=0.049, p<0.001) for mcBTT remained highly significant associated factors.Conclusion: The most important finding is that mcSOS decreased and the mcBTT reached a plateau to 24 months. In both mcSOS and mcBTT, the growth parameters were significant factors.Clinical Trial Registration: N/AWhat is known:• Metabolic bone disease is one of the possible long term adverse outcomes after preterm birth.• Metacarpal speed of sound (mcSOS) and metacarpal bone transmission time (mcBTT) decline in the early postnatal period.What is new:• During follow-up, mcSOS further decreased and reached its lowest point at 12 months, while the mcBTT reached a plateau up to 24 months.• Postnatal nutrition in relation to comorbidity does not meet the optimal mineralization rate of the developing preterm bone.

Shedding "LIGHT" on the Link between Bone and Fat in Obese Children and Adolescents.

Obesity may affect bone health, but literature reports are contradictory about the correlation of body mass index (BMI) and bone markers. LIGHT, one of the immunostimulatory cytokines regulating the homeostasis of bone and adipose tissue, could be involved in obesity. The study involved 111 obese subjects (12.21 ± 3.71 years) and 45 controls. Patients underwent the evaluation of bone status by quantitative ultrasonography (QUS). LIGHT amounts were evaluated in sera by ELISA, whereas its expression on peripheral blood cells was evaluated by flow cytometry. Osteoclastogenesis was performed by culturing peripheral blood mononuclear cells (PBMCs) with or without anti-LIGHT antibodies. Obese patients showed significant high BMI-standard deviation score (SDS), weight-SDS, and Homeostatic model assessment for insulin resistance (HOMA-IR) that negatively correlated with the reduced Amplitude Dependent Speed of Sound (AD-SoS)-Z-score and Bone Transmission Time (BTT-Z)-score. They displayed significantly higher serum levels of LIGHT compared with controls (497.30 ± 363.45 pg/mL vs. 186.06 ± 101.41 pg/mL, p < 0.001). LIGHT expression on monocytes, CD3+-T-cells, and neutrophils was also higher in obese patients than in the controls. Finally, in PBMC cultures, the addition of anti-LIGHT antibodies induced a significant osteoclastogenesis inhibition. Our study highlighted the high serum levels of LIGHT in obese children and adolescents, and its relationship with both the grade of obesity and bone impairment.

Methyl-CpG-binding protein 2 (MECP2) mutation type is associated with bone disease severity in Rett syndrome

BackgroundMore than 95% of individuals with RTT have mutations in methyl-CpG-binding protein 2 (MECP2), whose protein product modulates gene transcription. The disorder is caused by mutations in a single gene and the disease severity in affected individuals can be quite variable. Specific MECP2 mutations may lead phenotypic variability and different degrees of disease severity. It is known that low bone mass is a frequent and early complication of subjects with Rett syndrome. As a consequence of the low bone mass Rett girls are at an increased risk of fragility fractures. This study aimed to investigate if specific MECP2 mutations may affects the degree of involvement of the bone status in Rett subjects.MethodsIn 232 women with Rett syndrome (mean age 13.8 ± 8.3 yrs) we measured bone mineral density at whole body and at femur (BMD-FN and BMD-TH) by using a DXA machine (Hologic QDR 4500). QUS parameters were assessed at phalanxes by Bone Profiler-IGEA (amplitude dependent speed of sound: AD-SoS and bone transmission time: BTT). Moreover, ambulation capacity (independent or assisted), fracture history and presence of scoliosis were assessed. We divided the subjects with the most common point mutations in two group based on genotype-phenotype severity; in particular, there has been consensus in recognising that the mutations R106T, R168X, R255X, R270X are considered more severe.ResultsAs aspect, BMD-WB, BMD-FN and BMD-TH were lower in subjects with Rett syndrome that present the most severe mutations with respect to subjects with Rett syndrome with less severe mutations, but the difference was statistically significant only for BMD-FN and BMD-TH (p < 0.05). Also both AD-SoS and BTT values were lower in subjects that present the most severe mutations with respect to less severe mutations but the difference was not statistically significant. Moreover, subjects with Rett syndrome with more severe mutations present a higher prevalence of scoliosis (p < 0.05) and of inability to walk (p < 0.05).ConclusionThis study confirms that MECP2 mutation type is a strong predictor of disease severity in subjects with Rett syndrome. In particular, the subjects with more severe mutation present a greater deterioration of bone status, and a higher prevalence of scoliosis and inability to walk.

Trabecular bone score and quantitative ultrasound measurements in the assessment of bone health in breast cancer survivors assuming aromatase inhibitors.

Aromatase inhibitors (AIs) represent the first-line adjuvant therapy for hormone receptor-positive breast cancer (BC) women. AIs have been associated with an increased rate of fractures. The aim of our study was to investigate trabecular bone score (TBS) and bone quantitative ultrasound (QUS) measurements as bone quality surrogates in AIs users. Sixty postmenopausal BC women starting AIs and forty-two controls (mean age 61.64 ± 8.33years) were considered. Bone mineral density (BMD) at lumbar spine and femoral neck and TBS were measured by DXA; QUS-derived Amplitude-Dependent Speed of Sound (AD-SoS), Bone Transmission Time (BTT), and Ultrasound Bone Profile Index (UBPI) were assessed at phalangeal site; morphometric vertebral fractures (Vfx) by X-ray, serum bone-specific alkaline phosphatase (BSAP), and C-telopeptide of type 1 collagen (CTX) were also evaluated. After 18months, changes of TBS vs baseline were significantly different between AIs group and controls [Δ TBS - 2.2% vs - 0.4%, respectively, p = 0.001]. AD-SoS, BTT and UBPI values decreased only in AIs' group (- 3.7%, - 6.45%, -8.5%, vs baseline, respectively, pall < 0.001). 3 Vfx occurred in AIs users and were associated with the greater TBS and AD-SoS modifications. In the AIs' group, ΔTBS was associated with ΔAD-SoS (r = 0.58, p < 0.001) and ΔUBPI (r = 0.415, p = 0.001), but not with ΔBMD. Moreover, ΔTBS was independently predicted by ΔAD-SoS, after correcting for BMD, CTX and BSAP level changes (β = 0.37, SE = 2.44, p < 0.001). TBS and phalangeal QUS provide useful information related to bone quality in AI-treated BC survivors and could be considered for fracture risk evaluation.

Irisin serum levels are positively correlated with bone mineral status in a population of healthy children.

Irisin is a myokine secreted by skeletal muscle during physical activity. Irisin treatment increased cortical bone mineral density (BMD) in young healthy mice and restored bone and muscle mass loss in a mouse model of disuse-induced osteoporosis and muscular atrophy. In humans, Irisin was positively correlated with BMD in young athletes. Considering that the bone mass reached during childhood is one of the most important determinants of lifelong skeletal health, we sought to determine if Irisin levels were correlated with bone mineral status in children. Irisin and bone metabolic markers were quantified in sera and bone mineral status was evaluated by quantitative ultrasound in a population of 34 healthy children (9.82 ± 3.2 years). We found that Irisin levels were positively correlated with the amplitude-dependent speed of sound Z-score (r = 0.305; p < 0.001), bone transmission time Z-score (r = 0.375; p < 0.001) and osteocalcin (r = 0.370; p < 0.001), and negatively with Dickkopf WNT Signaling Pathway Inhibitor 1 (r = -0.274; p < 0.001). In a regression analysis model, Irisin was one of the determinants of bone mineral status to a greater extent than bone alkaline phosphatase and parathyroid hormone, indicating that Irisin might be considered as one of the bone formation markers during childhood.

Bone status in relation to ambulatory performance in girls with Rett syndrome: a 10-year longitudinal study.

Low bone mass is a frequent and early complication of girls with Rett syndrome. As a consequence of the low bone mass, Rett patients are at an increased risk of fragility fractures. This study aimed to investigate the long-term influences of mobility on bone status in girls with Rett syndrome. In 58 girls with Rett syndrome, biochemical parameters and quantitative ultrasound parameters at phalanges (amplitude-dependent speed of sound: AD-SoS and bone transmission time: BTT) were measured at baseline and after 5 and 10 years. The subjects were divided into two groups: nonambulatory (n = 28) and ambulatory (n = 30). In nonambulatory Rett subjects, the values of AD-SoS and BTT were significantly lower than in ambulatory Rett subjects at each time point. However, during the 10-year follow-up both ambulatory and nonambulatory Rett patients showed a similar worsening in their bone status. This longitudinal study suggests that both ambulatory and nonambulatory Rett subjects present a progressive deterioration of bone status as assessed by quantitative ultrasound parameters, and the ambulatory impairment and the nutritional status seem to play a key role in the deterioration of bone status.

Incidence of metabolic bone disease in preterm infants of birth weight

Preterm infants are exposed to a higher risk of developing Metabolic Bone Disease (MBD) with an increased bone fragility, a higher fracture risk and a long-term reduced linear growth and childhood height. Monitoring bone growth has become mandatory in neonatology. Several risk factors have been identified among the population of extremely low birth weight infants, but we still do not know which is the real incidence of MBD since its evaluation is not routinely performed worldwide. The aim of this study was to evaluate the incidence of MBD in preterm infants and in those suffering from bronchopulmonary dysplasia (BPD). Prospective evaluation of patients who developed BPD (BPD group) versus infants who did not develop it (no-BPD group). We examined, in preterms <1.250g, the metacarpus bone transmission time (mc-BTT) at birth, 21 days and 36 weeks of gestational age (GA) together with biochemical markers of bone status. We included 135 patients, 55 with BPD. BPD patients received less total proteins in the first two weeks and less energy in the first month of life (p=0.007 and p<0.001 respectively). BPD patients had a worse growth velocity at two weeks of age (12.36±7.86 vs 16.59±7.05g/kg/day, p=0.001). At 21 days, BPD patients had lower phosphatemia (1.65±0.031mmol/L vs 1.85±0.034mmol/L, p=0.007) and higher alkaline phosphatase levels (411.62±135.31IU/l vs 338.98±102.20IU/l, p=0.005). BPD patients had significantly worse mc-BTT at 36weeks GA (0.45±0.06 vs 0.50±0.08μsec, p<0.001) and a higher incidence of MBD (60% vs 34%; p=0.012). BPD infants are a special subset of patients among preterms who receive, in the first month of life, a lower energy intake than patients without BPD. BPD patients have a suboptimal bone growth and a higher incidence of MBD. Monitoring growth, bone status and optimizing nutritional intakes need to be further improved in preterm infants with BPD.

Assessing bone development in preterm infants using quantitative ultrasonography showed a decline in the early postnatal period.

Preterm infants have an insufficient bone mineral store at birth and this study explored their bone development during the early postnatal period. The metacarpal speed of sound (mcSOS) and metacarpal bone transmission time (mcBTT) were used to assess bone development in 277 preterm infants, admitted to the neonatal intensive care unit of the VU University Medical Center, Amsterdam, the Netherlands from 2007-2012. During the first nine postnatal weeks, the mcSOS declined from 10 to 38m per second per week and the mcBTT declined from 20 to 71 nanoseconds per week. The pattern of change in both of these measurements showed a significant difference between infants born before 32weeks of gestation (p=0.048) and those born between 28 and 32weeks of gestation (p=0.008). There was a borderline significant difference in the pattern of change of the mcBTT in infants with a protein intake below 2g/kg per day versus a higher intake (p=0.050). The mcSOS and mcBTT of preterm infants showed a small to moderate decline during the early postnatal period. Future studies should explore the clinical relevance of this decline and develop interventions to halt it.

Metabolic Outcomes, Bone Health, and Risk of Polycystic Ovary Syndrome in Girls with Idiopathic Central Precocious Puberty Treated with Gonadotropin-Releasing Hormone Analogues

Background/Aims: Gonadotropin-releasing hormone analogues (GnRHa) represent the gold standard treatment for central precocious puberty (CPP). We aimed to assess the effects of GnRHa treatment on metabolic outcomes, bone status, and polycystic ovary syndrome (PCOS) prevalence in young girls with idiopathic CPP (ICPP). Methods: We enrolled 94 ICPP girls who were at least 2 years after menarche and had already attained adult height at the time of the study: 56 previously treated with depot triptorelin (3.4 ± 0.6 years) and 38 untreated. Auxological parameters, lipid profile, homeostatic model assessment of insulin resistance (HOMA-IR), bone state, and prevalence of PCOS were assessed. Results: The 2 groups were similar for body mass index (BMI) and waist circumference. HOMA-IR, dehydroepi­androsterone sulfate, and Δ4-androstenedione were higher in the treated than in the untreated subjects (p < 0.001). Significant differences were found for amplitude-dependent speed of sound (p < 0.03) and bone transmission time z-scores (p < 0.01). The prevalence of PCOS was higher in the treated than in the untreated subjects (p < 0.04). Conclusion: GnRHa therapy is associated with hyperandrogenism and an increase in insulin resistance and PCOS prevalence, but not with increased BMI or lipid profile alterations. Long-term evaluations at the time of expected peak bone mass achievement are needed to understand the persistent or transient nature of subtle bone abnormalities.

Quantitative ultrasound and DXA measurements in aromatase inhibitor-treated breast cancer women receiving denosumab.

Denosumab has been proven to reduce fracture risk in breast cancer (BC) women under aromatase inhibitors (AIs). Quantitative ultrasound (QUS) provides information on the structure and elastic properties of bone. Our aim was to assess bone health by phalangeal QUS and by dual-energy X-ray absorptiometry (DXA), and to evaluate bone turnover in AIs-treated BC women receiving denosumab. 35 Postmenopausal BC women on AIs were recruited (mean age 61.2 ± 4.5years) and treated with denosumab 60mg administered subcutaneously every 6 months. Phalangeal QUS parameters [Amplitude Dependent Speed of Sound (AD-SoS), Ultrasound Bone Profile Index (UBPI), Bone Transmission Time (BTT)] and DXA at lumbar spine and femoral neck were performed. Serum C-telopeptide of type 1 collagen (CTX) and bone-specific alkaline phosphatase (BSAP) were also measured. The main outcomes were compared with a control group not receiving denosumab (n = 39). In patients treated with denosumab, differently from controls, QUS and DXA measurements improved after 24 months, and a reduction of CTX and BSAP was detected at 12 and 24 months in comparison to baseline (P < 0.05). The percent changes (Δ) of QUS measurements were significantly associated with ΔBMD at femoral neck, and ΔCTX and ΔBSAP were associated with ΔBMD at lumbar spine (r = -0.39, P = 0.02; r = -0.49, P = 0.01, respectively). Denosumab preserves bone health as assessed by phalangeal QUS and DXA. Since inexpensive and radiation-free, phalangeal QUS may be considered in the follow-up of AIs-treated BC women receiving denosumab.

Cross‐sectional study shows that impaired bone mineral status and metabolism are found in nonmosaic triple X syndrome

The effect of a supernumerary X chromosome on bones has not been reported, and this study evaluated bone mineral status and metabolism in nonmosaic triple X syndrome. This cross-sectional study comprised 19 girls, with a median age of 10.9years, with nonmosaic triple X syndrome and a control group matched for age and body size. We studied ionised and total calcium, phosphate, parathyroid hormone (PTH), 25-hydroxyvitamin D (25(OH)D), 1,25-dihydroxyvitamin D, osteocalcin, bone alkaline phosphatase levels and urinary deoxypyridinoline concentrations. We also measured the phalangeal amplitude-dependent speed of sound (AD-SoS) and the bone transmission time (BTT) Z-scores. Patients with nonmosaic triple X syndrome showed significantly reduced AD-SoS (p<0.005) and BTT Z-scores (p<0.0001) compared to the control group, and these results persisted when we divided the sample into prepubertal and pubertal patients (p<0.05). These patients also had significantly reduced ionised calcium (p<0.005) and 25(OH)D levels (p<0.005) and higher phosphate (p<0.0001) and PTH (p<0.0001) levels. Subjects with nonmosaic triple X syndrome exhibited a significant impairment in bone mineral status and metabolism similar to other X polisomy, such as Klinefelter's syndrome. This suggests the presence of a primary bone deficit and the need for regular and close monitoring of these subjects.

Constitutional bone impairment in Noonan syndrome.

Noonan syndrome (NS) is an autosomal dominant trait characterized by genotypic and phenotypic variability. It belongs to the Ras/MAPK pathway disorders collectively named Rasopathies or neurocardiofaciocutaneous syndromes. Phenotype is characterized by short stature, congenital heart defects, facial dysmorphisms, skeletal and ectodermal anomalies, cryptorchidism, mild to moderate developmental delay/learning disability, and tumor predisposition. Short stature and skeletal dysmorphisms are almost constant and several studies hypothesized a role for the RAS pathway in regulating bone metabolism. In this study, we investigated the bone quality assessed by phalangeal quantitative ultrasound (QUS) and the metabolic bone profiling in a group of patients with NS, to determine whether low bone mineralization is primary or secondary to NS characteristics. Thirty-five patients were enrolled, including 20 males (55.6%) and 15 females (44.5%) aged 1.0-17.8 years (mean 6.4 ± 4.5, median 4.9 years). Each patients was submitted to clinical examination, estimation of the bone age, laboratory assays, and QUS assessment. Twenty-five percent of the cohort shows reduced QUS values for their age based on bone transmission time. Bone measurement were adjusted for multiple factors frequently observed in NS patients, such as growth retardation, delayed bone age, retarded puberty, and reduced body mass index, potentially affecting bone quality or its appraisal. In spite of the correction attempts, QUS measurement indicates that bone impairment persists in nearly 15% of the cohort studied. Our results indicate that bone impairment in NS is likely primary and not secondary to any of the phenotypic traits of NS, nor consistent with metabolic disturbances. © 2017 Wiley Periodicals, Inc.

BONE MASS BY QUANTITATIVE ULTRASOUND OF FINGER PHALANGES IN YOUNG KARATE PRACTITIONERS.

ABSTRACTObjective: To evaluate bone mass by quantitative ultrasound of the phalanges in young karate practitioners compared to a control group. Methods: Sample composed of 162 karate practitioners (52 females) and 326 healthy controls (110 females) aged 6 to 16 years old, in Western Paraná (Southern Brazil). Weight, height, BMI, amplitude-dependent speed of sound (AD-SoS) and bone transmission time (BTT) were evaluated. BMI, AD-SoS and BTT values were converted to Z scores. Mann-Whitney, chi-square or Fisher Exact tests and multiple linear regression were applied, with significance level set at p≤0.05.Results: Both genders showed higher values of BTT as Z scores when compared to control group. Females from the control group had higher AD-SoS values (m/s and Z score) compared to female karate practitioners. When relative and absolute frequencies were assessed according to BTT Z score in both groups, male karate practitioners’ bone mass was shown to be adequate more frequently. In female practitioners, age and weight were independent predictors of AD-SoS (R2=0.42) and BTT (R2=0.45), respectively. Among male karate practitioners, age was related to 26% of AD-SoS variances and height was responsible for 36% of BTT variances.Conclusions: Children and adolescents who practice karate were shown to have more bone mass in comparison to the control group, regardless of gender. BTT was more sensitive for this evaluation.

Bone health assessment by quantitative ultrasound and dual-energy x-ray absorptiometry in postmenopausal women with breast cancer receiving aromatase inhibitors.

Phalangeal quantitative ultrasound (QUS) measurements provide surrogate information on bone quality. The aim of the present study was to assess bone status by phalangeal QUS and by dual-energy x-ray absorptiometry (DXA), and to evaluate bone turnover in breast cancer (BC) women receiving aromatase inhibitors (AIs). Sixty postmenopausal BC women and 42 matched controls were recruited (mean age 61.64 ± 8.33 y). Amplitude-dependent speed of sound (AD-SoS), bone transmission time (BTT), Ultrasound Bone Profile Index, as QUS parameters, L1-L4 and femoral neck BMD by DXA were assessed at baseline and after 18 months; serum bone-specific alkaline phosphatase (BSAP) and C-telopeptide of type 1 collagen were measured at baseline, 9 and 18 months. FRAX (without BMD) derived 10-years probability of major fractures and hip fractures were significantly associated with AD-SoS (r = -0.381, P = < 0.001 and r = -0.370, P < 0.001, respectively), Ultrasound Bone Profile Index (r = -0.434, P ≤ 0.001 and r = -0.409, P = < 0.001, respectively), BTT (r = -0.309, P = 0.002 and r = -0.340, P = 0.001, respectively). The median percent changes of AD-SoS (-3.71 [-5.38 to 0.11] vs -0.7 [-4.15 to 0.83], P = 0.02 respectively), BTT (-8.4 [-14.91 to -3.53] vs -1 [-5.72 to 3.75], P < 0.001 respectively) were significantly different between AIs users and controls. The same trend was observed for DXA measurements. BSAP and C-telopeptide of type 1 collagen significantly changed in AIs users. AD-SoS was associated with change of BMD at lumbar spine (β, 0.16; SE, 0.08; P = 0.04) and change of BSAP (β, -0.04; SE, 0.02; P = 0.04). Phalangeal QUS appeared a useful tool to evaluate bone quality in BC women on AIs.

High Sclerostin and Dickkopf-1 (DKK-1) Serum Levels in Children and Adolescents With Type 1 Diabetes Mellitus.

Childhood type 1 diabetes mellitus (T1DM) is associated with decreased bone mass. Sclerostin and dickkopf-1 (DKK-1) are Wnt inhibitors that regulate bone formation. To evaluate sclerostin and DKK-1 levels in T1DM children and to analyze the influence of glycemic control on bone health. Cross-sectional study conducted at a clinical research center. One hundred and six T1DM subjects (12.2 ± 4 years), 66 on multiple daily injections (MDIs) and 40 on continuous subcutaneous infusion of insulin (CSII), and 80 controls. The average bone transmission time (BTT) and amplitude-dependent speed of sound (AD-SoS) z scores were lower in patients with diabetes than in controls. Significantly increased DKK-1 (3593 ± 1172 vs 2652 ± 689 pg/mL; P < 0.006) and sclerostin (29.45 ± 12.32 vs 22.53 ± 8.29; P < 0.001) levels were found in patients with diabetes with respect to controls, particularly in patients on MDI compared with ones on CSII. Glycemic control was improved in CSII patients compared with MDI ones (P < 0.001) and was also associated with significantly higher BMI-SDS (P < 0.002) and BTT z scores (P < 0.02). With adjustment for age, multiple linear regression analysis of DKK-1 and sclerostin as dependent variables showed that levels of glycated hemoglobin, glucose, 25(OH) vitamin D, osteocalcin, and parathyroid hormone; years of diabetes; and BMI-SDS and AD-SoS z score were the most important predictors (P < 0.0001). Our study highlighted (1) the high serum levels of DKK-1 and sclerostin in T1DM children and their relationship with altered glycemic control and (2) the effect of CSII on improvement of glycemic control and bone health in T1DM children.

Bone mineral status and metabolism in patients with Williams-Beuren syndrome.

To evaluate bone mineral status and metabolism in a cohort of patients with Williams-Beuren syndrome (WBS). Thirty-one children (15 females, 16 males; mean age 9.6±2.74 years) and 10 young adults (6 females, 4 males; mean age 21.4±5.11 years) with WBS were cross-sectionally evaluated and compared with two age-, sex-, and body-size-matched paediatric (155 subjects, 75 females and 80 males; mean age 9.7±2.93 years) and adult (50 subjects, 30 females and 20 males; mean age 22.3±5.42 years) healthy controls. We evaluated ionised and total calcium, phosphate, parathyroid hormone (PTH), 25-hydroxyvitamin D, 1,25-dihydroxyvitamin D, osteocalcin, bone alkaline phosphatase levels, and urinary deoxypyridinoline concentrations. We also calculated the phalangeal amplitude-dependent speed of sound (AD-SoS) and the bone transmission time (BTT) z-scores. WBS patients showed a significantly reduced AD-SoS z-score (p <0.001) and BTT z-score (p <0.001) compared with the controls. This finding persisted when we divided the sample into paediatric and adult patients. WBS patients also had significantly higher ionised (p <0.001) and total calcium (p <0.001) levels as well as higher PTH levels (p <0.001) compared with the controls. Furthermore, WBS children and adolescents had significantly lower serum osteocalcin levels (p <0.001) and urinary deoxypyridinoline concentrations (p <0.001) than controls. WBS subjects exhibit a significant reduction in bone mineral status and impaired bone metabolism. These findings point to the need for close monitoring of WBS patients.