Christina Neu

Bone Mineral Content per Muscle Cross‐Sectional Area as an Index of the Functional Muscle‐Bone Unit

Bone densitometric data often are difficult to interpret in children and adolescents because of large inter‐ and intraindividual variations in bone size. Here, we propose a functional approach to bone densitometry that addresses two questions: Is bone strength normally adapted to the largest physiological loads, that is, muscle force? Is muscle force adequate for body size? To implement this approach, forearm muscle cross‐sectional area (CSA) and bone mineral content (BMC) of the radial diaphysis were measured in 349 healthy subjects from 6 to 19 years of age (183 girls), using peripheral quantitative computed tomography (pQCT). Reference data were established for height‐dependent muscle CSA and for the variation with age in the BMC/muscle CSA ratio. These reference data were used to evaluate results from three pediatric patient groups: children who had sustained multiple fractures without adequate trauma (n = 11), children with preterminal chronic renal failure (n = 11), and renal transplant recipients (n = 15). In all three groups mean height, muscle CSA, and BMC were low for age, but muscle CSA was normal for height. In the multiple fracture group and in renal transplant recipients the BMC/muscle CSA ratio was decreased (p < 0.05), suggesting that bone strength was not adapted adequately to muscle force. In contrast, chronic renal failure patients had a normal BMC/muscle CSA ratio, suggesting that their musculoskeletal system was adapted normally to their (decreased) body size. This functional approach to pediatric bone densitometric data should be adaptable to a variety of densitometric techniques.

Modeling of Cross-sectional Bone Size, Mass and Geometry at the Proximal Radius: A Study of Normal Bone Development Using Peripheral Quantitative Computed Tomography

Abstract: It is becoming increasingly accepted that bone size is an important determinant of bone mass. Studies on the development of bone size may therefore promote a better understanding of the basis of diseases which are due to low bone mass. Here, we characterize the temporal changes in cross-sectional bone size, geometry and mass at the radial diaphysis in healthy subjects from 6 to 40 years of age (n= 469; 273 females). Peripheral quantitative computed tomography was used to measure total and cortical cross-sectional area, bone mineral content (BMC) and volumetric bone mineral density (BMD) at the site of the forearm whose distance from the ulnar styloid process corresponded to 65% of forearm length. Over the age range of the study, total cross-sectional area increased by 39 mm2 (50%) in females and by 85 mm2 (116%) in males. Cortical area increased to a similar extent in both sexes. Between 6–7 years and adulthood, BMC increased by 52 mg/mm (111%) in females and by 73 mg/mm (140%) in males and was significantly higher in males after the age of 15 years. Volumetric BMD increased by 246 mg/cm3 (48%) in females but by only 132 mg/cm3 (23%) in males and was significantly higher in women than in men. In summary, these data show that BMC in men is higher than in women, because periosteal modeling continues longer in boys than in girls. Volumetric BMD is higher in women, partly because the size of the marrow cavity does not increase in girls as it does in boys.

The Development of Metaphyseal Cortex—Implications for Distal Radius Fractures During Growth

Fractures of the distal radial metaphysis are very common in otherwise healthy children. The reasons for this high fracture incidence are not entirely clear. To address this problem, we undertook a detailed analysis of distal radius development using peripheral quantitative computed tomography (pQCT) at a site 4% proximal to the radial articular surface. The study population comprised 337 healthy children and adolescents (aged 6‐18 years; 171 girls) and 107 adults (aged 29‐40 years; 88 women). Total volumetric bone mineral density (vBMD) remained stable at about 70% of the adult value between the ages of 6‐7 years and 14‐15 years in both genders. Cortical thickness increased little between 6‐7 years and 12‐13 years in girls and 14‐15 years in boys. Strength‐Strain Index (SSI; a parameter combining geometry and density) was still at only 20% of the adult value in girls aged 10‐11 years and at 21% of the adult level in boys aged 12‐13 years. At these ages, factors that contribute to the mechanical challenge to the distal radius in case of a fall (forearm length and body weight) had already reached 49% and 36% of the adult value in girls and boys, respectively. The shaping of the distal radius cortex (metaphyseal inwaisting) was assessed by analyzing the decrease in cross‐sectional bone size between adjacent bone slices in a separate population of 44 children (aged 8‐19 years; 26 girls). The rates of periosteal resorption and endocortical apposition were estimated to average 8 μm/day and 10 μm/day, respectively, during the growth period. In conclusion, during growth the increase in distal radius strength lags behind the increase in mechanical challenges caused by a fall, because metaphyseal cortical thickness does not increase sufficiently. The endocortical apposition rate is already very high at that site and apparently cannot be further increased to levels that would be necessary to keep bone strength adapted to the mechanical requirements.

Gender-specific pubertal changes in volumetric cortical bone mineral density at the proximal radius

It is well established that puberty affects the geometry of cortical bone differently in females and males. In the present study we investigated whether there are also gender differences in the volumetric bone mineral density of the cortical compartment (BMDcort). BMDcort was determined at the proximal radial diaphysis in 362 healthy children and adolescents (age 6-23 years; 185 females, 177 males) and in 107 adults (age 29-40 years; 88 women, 19 men) using peripheral quantitative computed tomography (pQCT). The densitometric result for BMDcort was similar in prepubertal girls and boys, but was significantly higher in females after pubertal stage 3. pQCT results for BMDcort are influenced by cortical thickness due to the partial volume effect. Therefore, these gender differences were reanalyzed in groups of subjects of the same developmental stage who were matched for cortical thickness. Thus calculated, no gender difference in BMDcort was detected in prepubertal children. However, adolescent females after pubertal stage 3 and adult women had a 3%-4% higher BMDcort than males at the same developmental stage. BMDcort is an integrated measure of both cortical porosity and mean material density of cortical bone. The metabolic activity of cortical bone (intracortical remodeling) increases cortical porosity and decreases the mean material density of cortical bone. Our results therefore suggest that intracortical remodeling is lower in postpubertal females than in males.

Muscle Analysis by Measurement of Maximal Isometric Grip Force: New Reference Data and Clinical Applications in Pediatrics

Skeletal muscle development is one of the key features of childhood and adolescence. Determining maximal isometric grip force (MIGF) using a hand-held Jamar dynamometer is a simple method to quantify one aspect of muscle function. Presently available reference data present MIGF as a function of chronological age. However, muscle force is largely determined by body size, and many children undergoing muscle performance tests in the clinical setting suffer from growth retardation secondary to a chronic disorder. Reference data were established from simple regressions between age or log height and log MIGF in a population of 315 healthy children and adolescents aged 6 to 19 y (157 girls). These data were used to calculate age- or height-dependent SD scores (SDS) for MIGF in three pediatric patient groups. In renal graft recipients (n = 14), the age-dependent MIGF SDS was markedly decreased (−2.5 ± 1.9; mean ± SD). However, these patients had short stature (height SDS, −2.5 ± 1.2), and the height-dependent MIGF SDS was close to normal (−0.4 ± 1.5). Similarly, in cystic fibrosis patients (n = 13) age-dependent MIGF SDS was −1.6 ± 1.6, but height-dependent MIGF SDS was −0.5 ± 1.1. Children with epilepsy who were taking anticonvulsant therapy (n = 34) had normal stature, and consequently age- and height-dependent MIGF SDS were similar (0.4 ± 1.0 and 0.4 ± 0.8, respectively). In conclusion, MIGF determination provides information on an important aspect of physical development. Height should be taken into account to avoid misinterpretation.

From Bone Biology to Bone Analysis

Bone development is one of the key processes characterizing childhood and adolescence. Understanding this process is not only important for physicians treating pediatric bone disorders, but also for clinicians and researchers dealing with postmenopausal and senile osteoporosis. Bone densitometry has great potential to enhance our understanding of bone development. The usefulness of densitometry in children and adolescents would be increased if the physiological mechanisms and structural features of bone were given more consideration in the design and interpretation of densitometric studies. This review gives an overview on the most relevant techniques of quantitative noninvasive bone analysis. Furthermore it describes the relationship between bone biology, selected surrogates describing the biological processes and the possibilities of measuring these surrogates specifically and precisely by the different devices. The overall recommendation for researchers in this field is to describe firstly the biological process to be analyzed (bone growth in length, remodeling or modeling, or all together), secondly the bone parameter which describes this process, and thirdly the reason for selecting a special device.

Adrenarche and Bone Modeling and Remodeling at the Proximal Radius: Weak Androgens Make Stronger Cortical Bone in Healthy Children†

Adrenarche, the physiological increase in adrenal androgen secretion, may contribute to better bone status. Proximal radial bone and 24‐h urinary steroid hormones were analyzed cross‐sectionally in 205 healthy children and adolescents. Positive adrenarchal effects on radial diaphyseal bone were observed. Obviously, adrenarche is one determinant of bone mineral status in children.

Analysis of Cancellous Bone Turnover by Multiple Slice Analysis at Distal Radius: A Study Using Peripheral Quantitative Computed Tomography

We compared the results of peripheral quantitative computed tomography (pQCT) measurements (XCT-900; Stratec) at the 4% site of the distal radius (section 1; slice thickness of 2 mm) and in two proximally adjacent sections (sections 2 and 3). The study population consisted of 138 ambulatory patients (age 16.4 +/- 5.6 yr; mean +/- SD; 71 female) who were referred to a pediatric densitometry unit. Total volumetric bone mineral density (BMD) increased, whereas the area of the radial cross-section decreased in a proximal direction. There was a decrease in bone mineral content between sections 1 and 3, which was more pronounced in subjects under age 16. Cancellous BMD significantly decreased from section 1 to 3 only under the age of 16. In 12 patients under age 17 who suffered from increased bone fragility, cancellous BMD decreased about 2.5 times more between sections 1 and 3 than in age-matched patients who received anticonvulsant therapy but had a normal neurologic and musculoskeletal status (-21.4% +/- 16.9 vs -8.1% +/- 6.3; p = 0.02). This suggests that in the bone fragility group, trabeculae were removed faster during longitudinal growth of the radius. In conclusion, multiple slice analysis may provide information on the dynamic turnover of metaphyseal trabeculae during growth.

Adrenal Steroid Hormones and Metaphyseal Bone in Children

Background/Objectives: The responses of metaphyseal bone tissue to physiological variations of endogenous adrenal steroid hormones during childhood are unclear. Therefore, we studied potential hormonal influences in children before the appearance of pubic hair (onset of pubarche). Methods: Excretions of major glucocorticoid metabolites (C21), cortisol, sum of adrenarchal dehydroepiandrosterone and its immediate 16-hydroxylated metabolites (DHEA&M), and 5-androstene-3β,17β-diol (hermaphrodiol) were analyzed in a cross-sectional study in 24-hour urine samples of 109 healthy boys and girls, aged 6–13 years, using steroid profiling by gas chromatography-mass spectrometry. Total and trabecular volumetric bone mineral densities, bone mineral content (BMC) and bone strength strain index were determined with peripheral quantitative computed tomography at the distal forearm. Results: In multiple regression analyses significant associations with the metaphyseal radius were seen for grip force, age, or BMI depending on gender and bone variable analyzed. DHEA&M did not contribute to the explanation of the variance of any bone variable. However, hermaphrodiol positively explained a significant part of variation of bone mineral densities, and BMC (p < 0.01) in girls. Significantly negative associations with all bone variables were seen in boys for cortisol. Conclusions: The steroid hormones, cortisol and hermaphrodiol, in their physiological ranges, but not the adrenarche marker DHEA&M, appear to associate with metaphyseal bone in a sex-dependent manner during childhood.