Bone Transmission Time Z-scores Research Articles

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.

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.

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.

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.

Bone Mineral Status in Children and Adolescents with Klinefelter Syndrome

Objective. Klinefelter syndrome (KS) has long-term consequences on bone health. However, studies regarding bone status and metabolism during childhood and adolescence are very rare. Patients. This cross-sectional study involved 40 (mean age: 13.7 ± 3.8 years) KS children and adolescents and 80 age-matched healthy subjects. For both patient and control groups, we evaluated serum levels of ionised and total calcium, phosphate, total testosterone, luteinising hormone, follicle stimulating hormone, parathyroid hormone (PTH), 25-hydroxyvitamin D (25(OH)D), 1,25-dihydroxyvitamin D, osteocalcin, bone alkaline phosphatase, and urinary deoxypyridinoline concentrations. We also calculated the z-scores of the phalangeal amplitude-dependent speed of sound (AD-SoS) and the bone transmission time (BTT). Results. KS children and adolescents showed significantly reduced AD-SoS (p < 0.005) and BTT (p < 0.0005) z-scores compared to the controls. However, KS patients presented significantly higher PTH (p < 0.0001) and significantly lower 25(OH)D (p < 0.0001), osteocalcin (p < 0.05), and bone alkaline phosphatase levels (p < 0.005). Interestingly, these metabolic bone disorders were already present in the prepubertal subjects. Conclusions. KS children and adolescents exhibited impaired bone mineral status and metabolism with higher PTH levels and a significant reduction of 25-OH-D and bone formation markers. Interestingly, this impairment was already evident in prepubertal KS patients. Follow-ups should be scheduled with KS patients to investigate and ameliorate bone mineral status and metabolism until the prepubertal ages.

Pamidronate treatment stimulates the onset of recovery phase reducing fracture rate and skeletal deformities in patients with idiopathic juvenile osteoporosis: comparison with untreated patients

Although spontaneous remission occurs in patients with idiopathic juvenile osteoporosis (IJO), permanent bone deformities may occur. The effects of long-term pamidronate treatment on clinical findings, bone mineral status, and fracture rate were evaluated. Nine patients (age 9.8±1.1years, 7 males) with IJO were randomized to intravenous pamidronate (0.8±0.1mg/kg per day for 3days; cycles per year 2.0±0.1; duration 7.3±1.1years; n=5) or no treatment (n=4). Fracture rate, phalangeal quantitative ultrasound, and lumbar bone mineral density (BMD) by dual energy X-ray absorptiometry at entry and during follow-up (range 6.3-9.4years) were assessed. Bone pain improved in treated patients. Difficulty walking continued for 3-5years in untreated patients, and vertebral collapses occurred in three of them. During follow-up, phalangeal amplitude-dependent speed of sound (AD-SoS), bone transmission time (BTT), and lumbar BMDarea and BMDvolume progressively increased in treated patients (P<0.05-P<0.0001). In untreated patients AD-SoS and BTT decreased during the first 2-4years of follow-up (P<0.05-P<0.01); lumbar BMDarea increased after 6years (P<0.001) whereas BTT and lumbar BMDvolume increased after 7years of follow-up (P<0.05 and P<0.001, respectively). At the end of follow-up, AD-SoS, BTT, lumbar BMDarea, and BMDvolume Z-scores were lower in untreated patients than in treated patients (-2.2±0.3 and -0.5±0.2; -1.9±0.2 and -0.6±0.2; -2.3±0.3 and -0.7±0.3; -2.4±0.2 and -0.7±0.3, P<0.0001, respectively). Fracture rate was higher in untreated patients than in treated patients during the first 3years of follow-up (P<0.02). Our study showed that spontaneous recovery of bone mineral status is unsatisfactory in patients with IJO. Pamidronate treatment stimulated the onset of recovery phase reducing fracture rate and permanent disabilities without evidence of side-effects.

Bone health in children with long–term idiopathic subclinical hypothyroidism

BackgroundSubclinical hypothyroidism (SH) is a relatively common condition characterized by a mild persistent thyroid failure. The management of children with SH is still a controversial issue and the decision to treat with L-thyroxine represents a clinical dilemma. Thyroid hormone and TSH play an important role in skeletal growth and bone mineral homeostasis.AimTo evaluate whether untreated idiopathic SH may affect bone health in childhood and to compare two different diagnostic tools such as dual-energy X-ray densitometry (DXA) and quantitative ultrasound (QUS).Patients and MethodsTwenty-five children and adolescents (11 males) aged 9.8 ± 3.5 years (range 4.2-18.7) with untreated idiopathic SH were enrolled in the study. SH was diagnosed on the basis of normal FT4 levels with TSH concentrations between 4.2 and 10 mU/l. Children have been followed for 3.3 ± 0.3 years from the time of SH diagnosis. Twenty-five healthy children, age- and sex-matched, were enrolled as controls. Patients and controls underwent DXA to evaluate lumbar spine bone mineral density (BMD) and QUS at proximal phalanges of the non-dominant hand to assess bone quality, measured as amplitude-dependent speed of sound (Ad-SoS) and bone transmission time (BTT).ResultsMean BMD Z-score was −0.4 ± 1.36 in patients and −0.2 ± 1.2 in controls. Mean Ad-SoS Z-score was 0.01 ± 1.0 in patients and 0.1 ± 1.2 in controls and mean BTT Z-score was −0.03 ± 0.8 and 0.04 ± 1.1 respectively. All values were within the normal range, both in patients and in controls. There were no statistically significant differences between the two groups.ConclusionBone health, evaluated by lumbar spine DXA and phalangeal QUS, is not impaired in our children, despite long-term duration of idiopathic SH. Data about bone status provided by QUS are comparable to those provided by DXA. Therefore, QUS may represent a good, cheaper and safe screening test for bone evaluation in children with SH.

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

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. 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. 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). 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.

Quantitative ultrasound detects bone impairment after bone marrow transplantation in children and adolescents affected by hematological diseases

PurposeBone marrow transplantation (BMT) recipients are at risk of bone mass impairment and skeletal morbidity. We investigated bone status with quantitative ultrasound (QUS) technique in children and adolescents with hematological diseases before and after BMT. MethodsPhalangeal QUS measures for amplitude-dependent speed of sound (AD-SoS) and bone transmission time (BTT) were obtained in 144 hematological patients (81M, 63F; 11.6±5.2 years); forty two were evaluated before BMT and 102 after allogeneic or autologous BMT. Bone parameters were expressed as Z-scores based on age–sex-matched normal controls. ResultsMean BTT Z-score was reduced in subjects after BMT compared to patients before BMT (M, −0.35±1.04 vs. 0.70±1.11, P<0.001; F, −0.60±1.23 vs. 0.23±1.17, P<0.05). Females and males with hormone deficiencies showed reduced BTT Z-scores when compared with subjects without hormone defects (M, −0.52±1.0 vs. 0.05±1.17, P<0.05; F, −0.50±1.27 vs. −0.19±1.26; P=0.06). AD-SoS and BTT Z-scores were reduced in 15 subjects with fractures and/or avascular osteonecrosis compared to patients without bone events (−1.52±1.7 vs. −0.41±1.32 and −0.85±1.19 vs. −0.10±1.18; both Ps<0.05). Bone event cumulative incidence was 4 times greater in subjects who suffered from chronic GVHD. ConclusionsAssessment of phalangeal QUS in young BMT survivors points towards impairment of bone status and endocrine dysfunction and chronic GVHD as risk factors of adverse bone events.

Phalangeal Quantitative Ultrasound in Children with Phenylketonuria: A Pilot Study

Bone alterations in phenylketonuria (PKU) have been detected, especially with increasing age, in several studies by using different radiologic techniques. Quantitative ultrasound (QUS) assesses skeletal status by measuring the amplitude-dependent speed of sound (AD-SoS) and the bone transmission time (BTT), mainly dependent on mineral density and cortical thickness. Bone condition in 30 children and adolescents (mean age 15.1 ± 6.4 y) affected by PKU was evaluated by phalangeal QUS, considering its relationship with their clinical, biochemical and therapeutic features. Measured AD-SoS Z-Score and BTT Z-Score were 0.27 ± 1.42 and –0.26 ± 1.21, respectively. In patients with previous fractures, the two QUS parameters were lower than in patients without history of fracture ( p < 0.001 and p = 0.006, respectively). AD-SoS Z-Score and BTT Z-Score were negatively correlated with plasma phenylalanine (Phe) concentration in the year before QUS ( p = 0.005 and p < 0.001, respectively) and with age ( p < 0.001 for both parameters). These results parallel the previous findings obtained by different radiologic tools and suggest phalangeal QUS as an attractive option for the regular evaluation and longitudinal monitoring of bone condition in children and adolescents affected by PKU. (E-mail: porta.franc@gmail.com)