K.A. Ward

Low Magnitude Mechanical Loading Is Osteogenic in Children With Disabling Conditions

The osteogenic potential of short durations of low‐level mechanical stimuli was examined in children with disabling conditions. The mean change in tibia vTBMD was +6.3% in the intervention group compared with −11.9% in the control group. This pilot randomized controlled trial provides preliminary evidence that low‐level mechanical stimuli represent a noninvasive, non‐pharmacological treatment of low BMD in children with disabling conditions.

Vitamin D status and muscle function in post-menarchal adolescent girls

CONTEXT There has been a resurgence of vitamin D deficiency among infants, toddlers, and adolescents in the United Kingdom. Myopathy is an important clinical symptom of vitamin D deficiency, yet it has not been widely studied. OBJECTIVE Our objective was to investigate the relationship of baseline serum 25 hydroxyvitamin D [25(OH)D] concentration and PTH with muscle power and force. DESIGN This was a cross-sectional study. SETTING The study was community based in a secondary school. PARTICIPANTS A total of 99 post-menarchal 12- to 14-yr-old females was included in the study. MAIN OUTCOME MEASURES Jumping mechanography to measure muscle power, velocity, jump height, and Esslinger Fitness Index from a two-legged counter movement jump and force from multiple one-legged hops was performed. Body height, weight, and serum concentrations of 25(OH)D, PTH, and calcium were measured. RESULTS Median serum 25(OH)D concentration was 21.3 nmol/liter (range 2.5-88.5) and PTH 3.7 pmol/liter (range 0.47-26.2). After correction for weight using a quadratic function, there was a positive relationship between 25(OH)D and jump velocity (P = 0.002), jump height (P = 0.005), power (P = 0.003), Esslinger Fitness Index (P = 0.003), and force (P = 0.05). There was a negative effect of PTH upon jump velocity (P = 0.04). CONCLUSION From these data we conclude that vitamin D was significantly associated with muscle power and force in adolescent girls.

A randomised controlled trial of standing programme on bone mineral density in non-ambulant children with cerebral palsy

Background: Severely disabled children with cerebral palsy (CP) are prone to low trauma fractures, which are associated with reduced bone mineral density. Aims: To determine whether participation in 50% longer periods of standing (in either upright or semi-prone standing frames) would lead to an increase in the vertebral and proximal tibial volumetric trabecular bone mineral density (vTBMD) of non-ambulant children with CP. Methods: A heterogeneous group of 26 pre-pubertal children with CP (14 boys, 12 girls; age 4.3–10.8 years) participated in this randomised controlled trial. Subjects were matched into pairs using baseline vertebral vTBMD standard deviation scores. Children within the pairs were randomly allocated to either intervention (50% increase in the regular standing duration) or control (no increase in the regular standing duration) groups. Pre- and post-trial vertebral and proximal tibial vTBMD was measured by quantitative computed tomography (QCT). Results: The median standing duration was 80.5% (9.5–102%) and 140.6% (108.7–152.2%) of the baseline standing duration in the control group and intervention group respectively. The mean vertebral vTBMD in the intervention group showed an increase of 8.16 mg/cm3 representing a 6% mean increase in vertebral vTBMD. No change was observed in the mean proximal tibial vTBMD. Conclusion: A longer period of standing in non-ambulant children with CP improves vertebral but not proximal tibial vTBMD. Such an intervention might reduce the risk of vertebral fractures but is unlikely to reduce the risk of lower limb fractures in children with CP.

Increased Estrogen Rather Than Decreased Androgen Action Is Associated with Longer Androgen Receptor CAG Repeats.

CONTEXT The individual variability in the waning androgenic-anabolic functions of aging men may be influenced by the CAG repeat polymorphism in exon 1 of the androgen receptor (AR), affecting androgen sensitivity. However, findings on its phenotypic effects are inconclusive. OBJECTIVE The aim was to investigate the relationships between health status, various reproductive hormones, and the AR CAG repeat length. DESIGN We conducted a multinational prospective cohort observational study with cross-sectional baseline data. SETTING This was a population survey of community-dwelling men. PARTICIPANTS Men (40-79 yr old; n = 3369) were randomly recruited from centers in eight European countries; CAG repeat analysis was performed in 2878 men. MAIN OUTCOME MEASURES We measured the correlations of the CAG repeat length with selected endocrine, metabolic, and phenotypic parameters related to aging and sex hormone action. RESULTS Only minor differences were found in CAG repeat lengths between the eight European countries. They showed significant positive association with total, free, and bioavailable levels of testosterone (T) and estradiol. FSH but not LH correlated inversely with CAG repeat length. Significant associations were found with bone ultrasound parameters at the calcaneus. Negative correlation was found with triglycerides, but not with other blood lipids or with anthropometry, blood pressure, hemoglobin, insulin sensitivity, or sexual and prostatic functions. CONCLUSIONS The AR CAG repeat length correlates significantly with serum T and estradiol of aging men. Weaker transcriptional activity of the AR with longer CAG-encoded polyglutamine repeats appears to be totally or nearly totally compensated for by higher T levels. The residual phenotypic correlations may reflect differences in estrogen levels/actions after aromatization of the higher T levels.

A randomized, controlled trial of vitamin D supplementation upon musculoskeletal health in postmenarchal females

CONTEXT There has been a resurgence of vitamin D deficiency rickets throughout the developed world, with infants and adolescents being primarily affected. Adolescence is a crucial period for muscle and bone mineral accumulation. OBJECTIVE The aim was to determine the effect of vitamin D supplementation on the adolescent musculoskeletal system. DESIGN AND SETTING We conducted a community-based, double-blind, randomized controlled trial in a secondary school. PARTICIPANTS Postmenarchal 12- to 14-yr-old females participated in the trial. Ninety-nine were screened, 73 were included in randomized controlled trial, and 69 completed the trial. There were no adverse events. INTERVENTION Four doses of 150,000 IU vitamin D(2) (ergocalciferol) were given over 1 yr. MAIN OUTCOME MEASURES Dual-energy x-ray absorptiometry, peripheral quantitative computed tomography, and jumping mechanography were used. RESULTS At follow-up, 25-hydroxyvitamin D [25(OH)D] status was 56.0 ± 8.9 nmol/liter in the intervention group and 15.8 ± 6.6 nmol/liter in controls. There were no effects of supplementation on bone; however, for muscle function, efficiency of movement improved in the vitamin D-treated group. There was an interaction between baseline 25(OH)D concentration and response to vitamin D supplementation for muscle jump velocity. CONCLUSIONS Despite improvements in 25(OH)D status, treatment with vitamin D(2) was not shown to increase mineral accretion, bone geometry or strength, muscle force, or power. There were greater increases in jump velocity in girls with the lowest baseline 25(OH)D concentrations. Lack of effect of intervention after the period of peak mineral and muscle mass accretion suggests that earlier action is required.

Dual-Energy X-ray Aborptiometry Assessment in Children and Adolescents with Diseases that May Affect the Skeleton: The 2007 ISCD Pediatric Official Positions

The Task Force focusing on the use of dual energy X-ray absorptiometry (DXA) in children and adolescents with diseases that may affect the skeleton reviewed over 300 articles to establish the basis for the Official Positions. A significant number of studies used DXA-based outcome measures to assess the effects of specific interventions and charted the natural history of incremental changes in bone size and mass in specific disease states in children. However, the utility of DXA in clinical practice has not been evaluated systematically, in large part due to the lack of a workable definition for childhood osteoporosis. Thus, in combination with the Official Positions addressing the diagnosis of osteoporosis in children, and the reporting of DXA results in children, this document presents clear guidelines from which clinicians and researchers alike can work. This report delineates a set of disorders in which it is appropriate to use DXA as part of the comprehensive assessment of skeletal health in children and adolescents, and provides guidance concerning the initiation of assessment and the frequency of monitoring. Importantly, this document also highlights significant gaps in our knowledge, emphasizing areas for future research.

Mobility status and bone density in cerebral palsy.

The spinal bone mineral density (SBMD) and calcaneal broadband ultrasound attenuation (BUA) was measured in 27 children with cerebral palsy. They were categorised into four mobility groups: mobile with an abnormal gait, mobile with assistance, non-mobile but weight bearing, non-mobile or weight bearing. Mean SD scores for BUA and SBMD differed among mobility groups (analysis of variance, p < 0.001 and p = 0.078, respectively).

Peripheral quantitative computed tomography in children and adolescents: the 2007 ISCD Pediatric Official Positions.

Peripheral quantitative computed tomography (pQCT) has mainly been used as a research tool in children. To evaluate the clinical utility of pQCT and formulate recommendations for its use in children, the International Society of Clinical Densitometry (ISCD) convened a task force to review the literature and propose areas of consensus and future research. The types of pQCT technology available, the clinical application of pQCT for bone health assessment in children, the important elements to be included in a pQCT report, and quality control monitoring techniques were evaluated. The review revealed a lack of standardization of pQCT techniques, and a paucity of data regarding differences between pQCT manufacturers, models and software versions and their impact in pediatric assessment. Measurement sites varied across studies. Adequate reference data, a critical element for interpretation of pQCT results, were entirely lacking, although some comparative data on healthy children were available. The elements of the pQCT clinical report and quality control procedures are similar to those recommended for dual-energy X-ray absorptiometry. Future research is needed to establish evidence-based criteria for the selection of the measurement site, scan acquisition and analysis parameters, and outcome measures. Reference data that sufficiently characterize the normal range of variability in the population also need to be established.

Recommendations for Thresholds for Cortical Bone Geometry and Density Measurement by Peripheral Quantitative Computed Tomography

Peripheral quantitative computed tomography (pQCT) is widely used for clinical and research purposes. For accurate determination of bone geometry (bone cross-sectional area, cortical thickness, and cortical area), volumetric bone mineral density (vBMD) and cortical bone mineral content (BMC), it is important to select the appropriate thresholds. A Stratec XCT-2000 scanner was used to compare current standard practice with new optimized thresholds. Currently, a single threshold of 710 mg/mL for the measurement of cortical vBMD and geometry is used. We hypothesised that this threshold may not be optimal and used the European Forearm Phantom (EFP) and patient data to test more appropriate thresholds. A single slice (1.2 mm width, 0.4 mm pixel size) was made at section 4 of the EFP (representing the diaphyseal portion of a long bone). The EFP has a known cortical thickness of 2.5 mm and, therefore, the correct threshold for geometry would be that which measures cortical thickness as 2.5 mm. Thresholds were altered at approximately the 50% value between soft tissue (60 mg/mL) and peak density (879 mg/mL), and cortical thickness versus threshold was plotted; the correct threshold for geometry was 460 mg/mL. By expressing this threshold as a percentage of the range of density values in the EFP ([460–60]/[879–60] = 49%) and then applying this percentage to in vivo data, the optimum threshold for geometry can be determined: ([1240−79] × 0.49) + 79 = 648 mg/mL. For cortical vBMD of in vivo bone measurements at the midshaft site of the radius, thresholds were varied around the peak value (1240 mg/mL), and the threshold was set to that which gave a cortical density of 1240 mg/mL; the threshold for cortical density was, therefore, 1200 mg/mL. A subset of radius scans from a population of young healthy females was analyzed using the new thresholds (648 mg/mL for bone geometry, 1200 mg/mL for cortical vBMD) versus the current threshold (710 mg/mL). For bone geometry, the mean difference between the analysis based on the new threshold and that based on the manufacturer-recommended threshold ranged between 2.1% and 14% (total area = 2.1%, cortical thickness = 14%, cortical area = 3.7%). Although there was a 10% difference between the analysis based on the new threshold and that based on the manufacturer-recommended threshold, this difference was not systematic. Thresholds will significantly affect results obtained from pQCT. The current threshold of 710 mg/mL is inadequate for accurate determination of bone geometry and cortical vBMD. New thresholds of 648 mg/mL for geometry and 1,200 mg/mL for cortical vBMD should be used.

ASSESSMENT OF BONE STATUS USING THE CONTACT ULTRASOUND BONE ANALYSER

Broadband ultrasound attenuation (BUA) was measured at the calcaneum in 367 healthy white schoolchildren (193 girls and 174 boys) aged 6–15 years. The mean calcaneal (BUA) increased with age and was significantly related to age, height, and weight. Measurement of calcaneal (BUA) may be helpful in the radiation free assessment of childhood disorders associated with increased fracture risk.