Zdenek Hlavka

Bone geometry and volumetric bone mineral density in girls with Turner syndrome of different pubertal stages

Objective  An increased rate of fractures has been reported in patients with Turner syndrome (TS). We aimed to assess bone geometry and volumetric bone mineral density (vBMD) at the radius in girls with TS and to evaluate the relationships between bone parameters and fracture history.

Prepubertal Girls With Turner Syndrome and Children With Isolated SHOX Deficiency Have Similar Bone Geometry at the Radius

CONTEXT The low bone mineral density (BMD) and alterations in bone geometry observed in patients with Turner syndrome (TS) are likely caused by hypergonadotropic hypogonadism and/or by haploinsufficiency of the SHOX gene. OBJECTIVE Our objective was to compare BMD, bone geometry, and strength at the radius between prepubertal girls with TS and children with isolated SHOX deficiency (SHOX-D) to test the hypothesis that the TS radial bone phenotype may be caused by SHOX-D. DESIGN AND SETTING This comparative cross-sectional study was performed between March 2008 and May 2011 in 5 large centers for pediatric endocrinology. PATIENTS Twenty-two girls with TS (mean age 10.3 years) and 10 children with SHOX-D (mean age 10.3 years) were assessed using peripheral quantitative computed tomography of the forearm. MAIN OUTCOMES BMD, bone geometry, and strength at 4% and 65% sites of the radius were evaluated. RESULTS Trabecular BMD was normal in TS (mean Z-score = -0.2 ± 1.1, P = .5) as well as SHOX-D patients (mean Z-score = 0.5 ± 1.5, P = .3). At the proximal radius, we observed increased total bone area (Z-scores = 0.9 ± 1.5, P = .013, and 1.5 ± 1.4, P = .001, for TS and SHOX-D patients, respectively) and thin cortex (Z-scores = -0.7 ± 1.2, P = 0.013, and -2.0 ± 1.2, P < .001, respectively) in both groups. Bone strength index was normal in TS as well as SHOX-D patients (Z-scores = 0.3 ± 1.0, P = .2, and 0.1 ± 1.3, P = .8, respectively). CONCLUSIONS The similar bone geometry changes of the radius in TS and SHOX-D patients support the hypothesis that loss of 1 copy of SHOX is responsible for the radial bone phenotype associated with TS.

Boys with haemophilia have low trabecular bone mineral density and sarcopenia, but normal bone strength at the radius

Summary.  Although a decreased areal bone mineral density (BMD) has been reported in patients with haemophilia, data are lacking that would reflect the three‐dimensional structure of the bone and the muscle‐bone relationship. We aimed to assess volumetric BMD, bone geometry and muscle‐bone phenotype in boys with haemophilia, and to describe the association between clinical characteristics of haemophilia and bone quality and structure. A cross‐sectional study was conducted in 41 boys with haemophilia (mean age 12.4, range 6.6–19.8 years) using peripheral quantitative CT (pQCT) at the nondominant forearm. Results were transformed into Z‐scores using previously published reference data. Significant differences were tested by one‐sample t‐test or sign test. Two‐sample t‐test and anova were used to compare results between subgroups of patients divided according to the severity of the disease, the fracture history and the number of joint and muscle bleedings. Boys with haemophilia had a decreased trabecular volumetric BMD (mean Z‐score −0.5, P < 0.01), while their cortical volumetric BMD was increased (mean Z‐score 0.4, P < 0.05). The volumetric bone mineral content and the bone geometry at the radial diaphysis were normal when adjusted for patients’ shorter body height. Muscle area was decreased (mean Z‐score −1.0, P < 0.001), irrespective of age. No association was observed of bone quality parameters and bone geometry with the disease severity, fracture history or number of bleedings. Bone strength measured at the diaphysis of the radius is not impaired in boys with haemophilia. The finding of the decreased trabecular bone density can be most likely attributed to their sarcopenia.

Tests for independence in non-parametric heteroscedastic regression models

Consistent procedures are constructed for testing independence between the regressor and the error in non-parametric regression models. The tests are based on the Fourier formulation of independence, and utilize the joint and the marginal empirical characteristic functions of the regressor and of estimated residuals. The asymptotic null distribution as well as the behavior of the test statistic under alternatives is investigated. A simulation study compares bootstrap versions of the proposed tests to corresponding procedures utilizing the empirical distribution function.

Muscle function in Turner syndrome: normal force but decreased power.

Although hypogonadism and SHOX gene haploinsufficiency likely cause the decreased bone mineral density and increased fracture rate associated with Turner syndrome (TS), the exact mechanism remains unclear. We tested the hypothesis that muscle dysfunction in patients with TS contributes to increased fracture risk. The secondary aim was to determine whether menarche, hormone therapy duration, positive fracture history and genotype influence muscle function parameters in patients with TS.

Bootstrap Procedures for Online Monitoring of Changes in Autoregressive Models

We compare the behavior of several bootstrap procedures for monitoring changes in the error distribution of autoregressive time series. The proposed procedures are designed to control the overall significance level and include classical tests based on the empirical distribution function as well as Fourier-type methods that utilize the empirical characteristic function, both functions being computed on the basis of properly estimated residuals. The Monte Carlo study incorporates different estimators and a variety of sampling situations with and without outliers.

The muscle-bone interaction in Turner syndrome

OBJECTIVES Turner syndrome (TS) is associated with an increased fracture rate due to reduced bone strength, which is mainly determined by skeletal muscle force. This study aimed to assess the muscle force-bone strength relationship in TS and to compare it with that of healthy controls. METHODS This study included 39 girls with TS and 67 healthy control girls. Maximum muscle force (Fmax) was assessed through multiple one-legged hopping with jumping mechanography. Peripheral quantitative computerized tomography assessed the bone strength index at the tibial metaphysis (BSI 4) and the polar strength-strain index at the diaphysis (SSI polar 66). The effect of TS on the muscle-bone unit was tested using multiple linear regression. RESULTS TS had no impact on Fmax (p=0.14); however, a negative effect on bone strength (p<0.001 for BSI 4 and p<0.01 for SSI polar 66) was observed compared with healthy controls. Bone strength was lower in the TS group (by 18%, p<0.01, for BSI 4 and by 7%, p=0.027, for SSI polar 66), even after correcting for Fmax. CONCLUSIONS Similar muscle force induces lower bone strength in TS compared with healthy controls, which suggests altered bone-loading sensitivity in TS.

Muscle functions and bone strength are impaired in adolescents with type 1 diabetes

BACKGROUND Sarcopenia and osteoporosis are among the late complications of type 1 diabetes (T1D) in adults. Whether and to what extent musculoskeletal impairment is present in childhood and adolescence has yet to be determined. The aim of this study was to assess volumetric bone mineral density (BMD) and dynamic muscle function in adolescents with T1D and to assess the clinical and biochemical predictors of their musculoskeletal system. METHODS Ninety-five children and adolescents (59 boys and 36 girls, mean age 16.2±1.2years) with T1D were included in this cross-sectional study. Study participants were divided into two groups according to the duration of the disease (<6years and >9years, respectively). Volumetric BMD of the non-dominant tibia was assessed using peripheral quantitative computed tomography (pQCT). Dynamic muscle function was evaluated using jumping mechanography. Gender- and height-specific Z-scores were calculated using published reference data. HbA1c was evaluated retrospectively as an average over the past 5years. RESULTS Relative muscle power (Pmax/mass) and force (Fmax/body weight) were significantly decreased in T1D subjects (mean Z-scores -0.4±1.0; p<0.001, and -0.3±1.1; p<0.01, respectively). The duration of T1D negatively affected Pmax/mass (p<0.01) but not Fmax/body weight (p=0.54). Patients with T1D had also decreased trabecular BMD, the Strength-Strain Index and cortical thickness (mean Z-scores -0.8±1.3; -0.5±0.8 and -1.1±0.8, respectively, p<0.001 for all) whereas cortical BMD was increased when compared to controls (Z-score 1.2±0.90, p<0.001). No association was observed between the HbA1c and 25-hydroxyvitamin D levels and bone or muscle parameters. CONCLUSION T1D influences the musculoskeletal system in adolescence. Decreased muscle function could contribute to the osteoporosis reported in adult diabetic patients.

A 6-Year Follow-Up of Fracture Incidence and Volumetric Bone Mineral Density Development in Girls With Turner Syndrome

Context Patients with Turner syndrome (TS) are at risk for osteoporotic fractures. Objective The aims of this study were to assess the incidence of clinically important fractures in girls with TS and prospectively describe the development of volumetric bone mineral density (BMD). Design Peripheral quantitative computerized tomography (pQCT) of the radius every other year over the 6 years of observation. Setting Government-funded university referral center. Participants Thirty-two girls with TS, aged 6 to 16 years, were included in the analyses. Fracture incidence was compared with the data in the general population. Bone density and strength were compared with data from 185 healthy girls. Outcomes The main clinical outcome was the fracture occurrence. The secondary outcomes were the changes in Z-scores of the bone parameters. Results Three girls with TS sustained four fractures during 6 years of observation. The fracture rate in TS was not substantially higher than the downward-biased fracture-rate estimate from age-matched, healthy controls (P = 0.48). Whereas the trabecular BMD Z-score decreased with age (β estimate -0.21 ± 0.04, P < 0.001), total bone cross-sectional area correspondingly increased (+0.16 ± 0.04, P < 0.001), which led to normal bone strength. A positive history of incident fractures was not significantly associated with any of the pQCT-derived bone parameters. Conclusions Current pediatric TS patients that are treated with growth hormone and estrogens are not at risk for osteoporotic fractures. Low BMD in TS may be counterweighted by enlarged bone radius, which leads to normal bone strength at the appendicular skeleton.

Cerebellar Symptoms Are Associated With Omission Errors and Variability of Response Time in Children With ADHD.

Objective: We examined the presence of cerebellar symptoms in ADHD and their association with behavioral markers of this disorder. Method: Sixty-two children with ADHD and 62 typically developing (TD) children were examined for cerebellar symptoms using the ataxia rating scale and tested using Conners’ Continuous Performance Test. Results: Children with ADHD had significantly more cerebellar symptoms compared with the TD children. Cerebellar symptom scores decreased with age in the ADHD group; in the TD group remained stable. In both groups, cerebellar symptoms were associated with parent-rated hyperactive/impulsive symptoms, variability of response time standard error (RT-SE) and increase of RT-SE as the test progresses. More variables were associated with cerebellar symptoms in the ADHD group including omission errors, overall RT-SE and its increase for prolonged interstimulus intervals. Conclusion: Our results highlight the importance of research into motor functions in children with ADHD and indicate a role for cerebellar impairment in this disorder.