The development of bone strength at the proximal radius during childhood and adolescence.

Current investigations of bone development mostly focus on bone mass, but bone strength may be functionally more important than mass. Therefore, we compared the developmental changes in cortical bone mass (BMCcort) and parameters of cortical bone strength [polar moment of inertia, section modulus, and strength strain index (SSI)]. Analyses were performed at the 65% site of the proximal radius using peripheral quantitative computed tomography. The study population comprised 469 healthy subjects, 6-40 yr of age (273 females). Both in prepubertal children (pubertal stage 1) and after puberty (pubertal stage 5 and adults) all studied parameters were significantly higher in males. During puberty (pubertal stages 2-4) the gender-specific differences were generally somewhat smaller. All of the measured parameters increased significantly with age and pubertal stage. However, although the percent increase in BMCcort between the youngest children and adults was similar between the genders, the increases in polar moment of inertia, section modulus, and SSI were higher in males. The ratio between section modulus and BMCcort was consistently higher in males after the age of 11 yr and after pubertal stage 2. Similar results were found for ratios between polar moment of inertia or SSI and BMCcort. These results show that for a given bone mass, males have stronger bones than females after pubertal stage 2. This reflects the fact that in puberty males add bone mostly on the periosteal surface, where the effect on bone strength is highest, whereas females add bone on the endocortical surface, which has a small effect on bone stability. The purpose of the mechanically inefficient endocortical apposition in female puberty might be to create a reservoir of calcium for future pregnancy and lactation.

Influence of puberty on muscle area and cortical bone area of the forearm in boys and girls.

The aim of the current study is to analyze the interaction of the muscle and bone system (muscle-bone unit) during puberty in males and females by computed tomography of the nondominant forearm. The data presented here are the first results from 318 healthy children (159 boys and 159 girls), aged 6-22 yr, and 336 adults (parents) participating in the DONALD Study (Dortmund Nutritional and Anthropometric Longitudinally Designed Study). Cortical area (CA) of the radius representing bone strength and muscle area (MA) representing muscle strength were measured with peripheral quantitative computed tomography (XCT 2000; Stratec, Pforzheim, Germany). A single slice measurement at a site corresponding to 65% of the ulnar length proximal to the radial endplate was used. MA and CA of the radius have been determined by a built-in software algorithm using density differences. There was a strong correlation between MA (x) and CA (y) in all children, adolescents, and adults (y = 0.019x + 10.93; r2 = 0.77). Before puberty, boys and girls displayed a similar relation between MA and CA. CA in relation to MA was greater in girls than in boys during puberty. Analysis of covariance was performed investigating the dependency of CA on MA, five pubertal stages, sex, and interaction of sex and pubertal stages. MA representing muscle strength was the strongest predictor of CA (P < 0.001) representing bone mass. Pubertal stage (P < 0.001) and interaction of pubertal stage*sex (P = 0.002) also had a significant influence on CA. r2 of the model was 0.85. These data suggest that in pubertal girls and women rather than in pubertal boys and men an additional factor shifts the relationship between MA and CA to higher values of cortical area. The present data confirm previous studies of the influence of puberty and estrogens or related factors on the muscle-bone interaction.

Musculoskeletal analyses of the forearm in young women with Turner syndrome: a study using peripheral quantitative computed tomography.

Turner syndrome (TS) is associated with multiple skeletal abnormalities. Fracture incidence appears to be increased, but the reasons for this are not entirely clear. In the present study, we used peripheral quantitative computed tomography to evaluate bone mass, density, geometry, and strength of the radial metaphysis and diaphysis as well as maximum forearm muscle cross-sectional area (CSA) in a group of 21 TS patients. These individuals were 19.5 +/- 2.3 yr of age (mean +/- SD; range, 16.2-25.4 yr) and had completed growth after having received GH therapy; all but one were receiving estrogen supplementation. Despite short stature, cross-sectional bone size was normal compared with age-matched healthy controls. However, bone mineral content was decreased, resulting in a low total volumetric bone mineral density. This was due to decreased cortical thickness at both sites of measurement, whereas trabecular volumetric bone mineral density of the metaphysis was normal. Muscular CSA was normal. The relationship between muscle CSA and external bone size was similar between TS patients and healthy young women. However, TS patients had less bone mineral content and cortical CSA relative to muscle CSA than healthy young women, but similar muscle-bone relationships as healthy prepubertal girls. These findings are compatible with a normal adaptation of external bone size to the mechanical loads imposed by the muscle system and a lack of pubertal effect on the endocortical bone surface, despite estrogen supplementation. Bone strength may not be adequate for the relatively high body weight of TS patients (+0.8 SD score), which could contribute to an increased propensity for fractures.

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.

Bone densities and bone size at the distal radius in healthy children and adolescents: a study using peripheral quantitative computed tomography.

Peripheral quantitative computed tomography (pQCT) has the ability to improve the diagnostic utility of densitometry in children and adolescents, because bone size and volumetric bone mineral density (vBMD) can be measured independently. Nevertheless, detailed reference data are lacking. We therefore performed pQCT (XCT-2000 scanner, Stratec, Inc., Pforzheim, Germany) at the distal radius in 371 healthy children, adolescents, and young adults (185 males and 186 females, ages 6-23 years) and in 107 of their parents (19 men and 88 women, ages 29-40 years). Total vBMD, trabecular, and "cortical + subcortical" vBMD as well as cross-sectional area (CSA) were determined at the "4% site" of the distal radius. This location was defined as the site whose distance to the most distal portion of the growth plate or to the radial articular surface corresponded to 4% of the forearm length. In both genders, total vBMD remained stable between 6 and 15 years of age and then increased by 30% in girls and by 46% in boys. Regarding pubertal development, total vBMD remained almost constant throughout pubertal stages 1-4 and thereafter increased in both genders. Trabecular vBMD did not change with age in girls, whereas in boys an increase with age of about 10% was noted after 15 years of age. Males had higher trabecular vBMD than females. This gender difference increased from 6% in prepubertal children to 23% in adults. The variation with age and pubertal stage in "cortical + subcortical" vBMD-cort was similar to that of total vBMD. CSA roughly doubled between 6 and 15 years of age in both genders. In conclusion, the availability of this reference material will provide a basis for the use of pQCT in the assessment of pediatric bone diseases.

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.

Modeling of cross-sectional bone size, mass and geometry at the proximal radius: a study of normal bone development using peripheral quantitative computed tomography.

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.

Influence of puberty on muscle development at the forearm.

Despite its fundamental importance for physical development, the growth of the muscle system has received relatively little consideration. In this study, we analyzed the relationship between cross-sectional area (CSA) of forearm muscles and maximal isometric grip force with age and pubertal stage. The study population comprised 366 children, adolescents, and young adults from 6 to 23 yr of age (185 female) and 107 adults (88 female) aged 29 to 40 yr. By use of peripheral quantitative computed tomography, muscle CSA was determined at the site of the forearm, whose distance to the ulnar styloid process corresponded to 65% of forearm length. Both muscle CSA and grip force were higher in prepubertal boys than in girls. The gender differences decreased until pubertal stage 3 and reincreased thereafter. In girls at pubertal stage 5, muscle CSA no longer increased with age (P > 0.4), whereas there was still some age-related increase in grip force (P = 0.02). In boys at pubertal stage 5, both muscle CSA and grip force continued to increase significantly with age (P < 0.005 each). Specific grip force (grip force per muscle CSA) adjusted for forearm length increased by almost one-half between 6 and 20 yr of age, with no difference between the genders. In conclusion, forearm muscle growth takes a gender-specific course during puberty, indicating that it is influenced by hormonal changes. However, the increase in specific grip force is similar in both genders and thus appears to be independent of sex hormones.

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.