Diagnosis of Recurrent Fracture in a Pediatric Cohort.

Significant fracture history in children is defined as having at least one vertebral fracture, at least 2 fractures by age 10, or at least 3 fractures by age 19. Between September 2011 and December 2014, clinical data were collected on children with a significant fracture history that attended a major Australian children's hospital. Fifty-six patients were identified as having 305 fractures in total, including 44 vertebral fractures. 18% of patients (10/56) were diagnosed with osteogenesis imperfecta (OI) by a bone health expert, molecular testing or both, and they sustained 23% of all fractures (71/305). Analysis of serum bone biochemistry showed all median values to be within a normal range and no clinically significant differences between patients with and without OI. The DXA and pQCT derived bone mineral density (BMD) and bone mineral content (BMC) Z scores were reduced overall. DXA derived total body and lumbar spine areal BMD-for-age and BMC-for-age Z scores were significantly lower in children who had vertebral fractures or who were later diagnosed with OI. Similarly, pQCT performed on radii and tibiae showed Z scores significantly less than zero. pQCT-derived limb muscle cross sectional area Z scores were significantly lower in the OI subgroup. In conclusion, this study describes the bone phenotype of children referred to a tertiary hospital clinic for recurrent fractures and highlights a subset of children with previously undiagnosed OI, but a larger cohort without classic OI. Thus it can be clinically challenging to differentiate between children with OI type 1 (mild phenotype) and non-OI children without bone densitometry and genetic testing. We conclude that recurrent fractures in children should prompt a comprehensive bone and systemic health assessment to eliminate an underlying pathology.

Intravenous pamidronate treatment in children with moderate-to-severe osteogenesis imperfecta started under three years of age.

OBJECTIVE: Evaluate clinical outcome of early cyclic intravenous pamidronate treatment in children with moderate-to-severe osteogenesis imperfecta (OI), commenced before three years of age. METHODS: A retrospective review of 17 patients with moderate-to-severe OI. Development, anthropometry, fracture history, bone mineral density (BMD) and biochemistry were collected at baseline, 12 and 24 months. RESULTS: Four had OI type I, eleven had type III, one OI-FKBP10 type and one OI type V. Mean age at start of pamidronate was 14 ± 11 months. Pamidronate ranged from 6 to 12 mg/kg/year. No adverse reaction apart from fever and vomiting was noted. Long bone fracture decreased from a mean of 10.4/year to 1.2/year after 12 months and 1.4/year after 24 months (p = 0.02). Lumbar spine age- and height-matched BMD Z-scores increased (p < 0.005). Sixteen with vertebral compression fractures at baseline all showed improved vertebral shape (p < 0.001). Concavity index, likewise, improved (p < 0.005). Motor milestones compared to historical data show earlier attainment in rolling over, crawling, pulling to stand and walking independently but not sitting. CONCLUSION: Cyclic intravenous pamidronate, started under 3 years of age in children with moderate-to-severe OI, was well tolerated and associated with an increase in lumbar spine BMD, reduced fracture frequency, vertebral remodelling and attainment of motor milestones at an earlier age.

SPECT/CT scans allow precise anatomical location of sentinel lymph nodes in breast cancer and redefine lymphatic drainage from the breast to the axilla.

BACKGROUND: Historical studies of lymphatic drainage of the breast have suggested that the lymphatic drainage of the breast was to lymph nodes lying in the antero-pectoral group of nodes in the axilla just lateral to the pectoral muscles. The purpose of this study was to confirm this is not correct. METHODS: The hybrid imaging method of SPECT/CT allows the exact anatomical position of the sentinel lymph node (SLN) in the axilla to be documented during pre-operative lymphoscintigraphy (LS) in patients with breast cancer. We have done this in a series of 741 patients. The Level I axillary nodes were defined as anterior, mid or posterior. This was related to the anatomical location of the primary cancer in the breast. RESULTS: A SLN was found in the axilla in 97.8% of our patients. Just under 50% of SLNs located in the axilla were not in the anterior group and lay in the mid or posterior group of Level I axillary nodes. There was a SLN in a single node field in 460 patients (63%), two node fields in 261(36%), three node fields in 6 and four node fields in 1 patient. CONCLUSION: Axillary lymphatic drainage from the breast is not exclusively to the anterior (or antero-pectoral) group of Level I nodes. SYNOPSIS: SPECT/CT lymphoscintigraphy shows that the breast does not always drain to the anterior group of Level I lymph nodes in the axilla but may drain to the mid axilla and/or posterior group in about 50% of patients with breast cancer regardless of the location of the cancer in the breast. These data redefine lymph drainage from the breast to axillary lymph nodes.

The successful use of pamidronate in an 11-year-old girl with complex regional pain syndrome: response to treatment demonstrated by serial peripheral quantitative computerised tomographic scans.

Complex regional pain syndrome (CRPS) is a disorder that can cause significant functional morbidity. While it usually presents in adulthood, it has also been reported in children. Multiple treatment modalities have been reported with mixed success. Bisphosphonate therapy has been shown to be effective in adult patients, but there are limited data in children. We report the successful use of intravenous pamidronate therapy in diminishing pain, improving function, and restoring bone mass in an 11-year-old girl with CRPS of her left lower limb following a tibial fracture. Previous treatment with intense physiotherapy and regional sympathetic blockade had not improved her symptoms. Pain improved within weeks of the first pamidronate infusion, with subsequent improvement in function. The benefit in pain reduction and function was sustained during the 2-year treatment regime. Improvement in bone mass and density was demonstrated by dual-energy X-ray absorptiometry (DXA) and peripheral quantitative computerised tomography (pQCT). pQCT scans showed marked improvement in bone size and geometry and muscle bulk on the affected side. No adverse affects were reported. We conclude that intravenous pamidronate was associated with reduced pain, a return of function, and recovery of bone and muscle parameters in a child with CRPS. Before definitive conclusions can be drawn, a randomised controlled trial similar to those undertaken in adults previously is required to fully validate this approach.

Assessment of bone strength at differentially-loaded skeletal regions in adolescent middle-distance runners.

Bone adaptations to loading extend beyond mineral accrual to geometric markers of bone strength. Available technology and regional differences in cortical bone dictate how bone strength is reported. Examination of bone strength at two differentially-loaded skeletal sites using hip structure analysis (HSA) and bone strength index (BSI) is under-explored in adolescent sporting populations. The purpose of this study was to compare HSA at the femoral neck and BSI at the distal tibia in adolescent middle-distance runners and age- and gender-matched controls. Four groups of 20 adolescents aged 14-18 years were composed of male and female middle-distance runners, and male and female controls. Distal tibial BSI was calculated using data from dual energy X-ray absorptiometry (DXA) and magnetic resonance imaging (MRI). Calculations for femoral neck strength were acquired from DXA-derived HSA software. Female athletes displayed greater distal tibial BSI than controls t(38)=3.4, p=0.002, but femoral neck bone measures did not differ. In males, no group differences were found at either the distal tibia or femoral neck. In conclusion, exposure to similar high training loads may advantage female adolescent athletes more than male adolescent athletes compared with less active peers in bone strength at the distal tibia.

Bone strength index in adolescent girls: does physical activity make a difference?

BACKGROUND: Bone strength index (BSI) combines bone mineral and bone biomechanical properties to measure resistance to bending. This index may have greater clinical significance than the more often described markers of bone mineral content (BMC), areal density, or geometry alone and, in turn, may show a stronger relation to fracture risk. The BSI is the product of volumetric cortical bone mineral density (BMD) and cross sectional moment of inertia within a region of interest. Calculations combine dual energy x ray absorptiometry and magnetic resonance imaging technologies and provide a useful, non-invasive measure of in vivo bone strength. OBJECTIVES: (a) To compare BSI in adolescent female middle distance runners and age matched controls; (b) to examine factors predictive of BSI in adolescent girls. METHODS: Twenty adolescent female middle distance runners (mean (SD) age 16 (1.7) years, physical activity 8.9 (2.1) hours a week) and 20 female controls (age 16 (1.8) years, physical activity 2.0 (0.07) hours a week) were recruited. To calculate BSI, a region of interest representing 10% of the mid-distal tibia was analysed for dual energy x ray absorptiometry derived BMC and was combined with bone geometry and biomechanical properties obtained by magnetic resonance imaging assessments. Potential predictors of BSI were also examined. RESULTS: Independent t tests showed that BMC (p = 0.028), cortical bone volume (p = 0.002), volumetric cortical BMD (p = 0.004), cross sectional moments of inertia (p = 0.005), and BSI (p = 0.002) were higher in the distal tibia of athletes than of controls. The strongest predictor of BSI was hours of physical activity a week (R2 = 0.46). CONCLUSIONS: Athletes habitually exposed to high training loads displayed greater BSI at the distal tibia than controls. The results further confirm BSI as a significant and discerning marker in musculoskeletal health in adolescent girls engaged in high and low mechanical loading.

Cyclic bisphosphonate therapy in osteogenesis imperfecta type V.

The clinical and radiographic features and management of a young person with recently delineated Osteogenesis Imperfecta Type V is described. A female aged 9 years presented with a history of multiple fractures since 3 years of age and bilateral dislocation of the elbows from infancy. She was commenced on a low dose frequent regimen of cyclic intravenous pamidronate, which resulted in progressive improvement in bone density, reduced fracture frequency and remission of symptoms of osteoporosis.

Musculoskeletal health in elite male adolescent middle-distance runners.

The impact of high training volumes on musculoskeletal adaptations of male adolescents is poorly understood. We compared bone mineral content (BMC) of total body, lumbar spine and proximal femur using Dual X-ray Absorptiometry (Lunar Prodigy, GE Medical Systems, Madison WI) in elite level (n=20), male adolescent middle distance runners (mean 16.8 yrs, range 14-18 yrs) and age-matched (n=20) controls. Athletes averaged 14 hrs of physical activity per week and controls reported participating in physical activity an average of two hrs per week. Total body mass was 10.97 kg less in athletes than controls (p=0.005). Within the total body mass difference, fat tissue mass of athletes was 10.93 kg less in athletes than controls (p= 0.001). Multiple regression analysis identified total body lean mass and total body fat mass as the strongest predictors of total body BMC (R2 0.71). After adjusting for lean tissue mass per kg of body weight (p=0.07), no difference in BMC was detected. Lower limb muscle strength and macronutrient intakes were also measured but no between group differences were found. The number of weeks of training and/or competition missed through injury was not associated with total body BMC (R2=0.19) among athletes. Our results imply high training volumes in middle distance running are not detrimental to musculoskeletal health and are associated with positive body composition profiles in elite adolescent male athletes.

Features of the metabolic syndrome after childhood craniopharyngioma.

Obesity and multiple pituitary hormone deficiency are common complications after surgery for childhood craniopharyngioma. We hypothesized that post craniopharyngioma surgery, children are at high risk for the metabolic syndrome, including insulin resistance due to excess weight gain and GH deficiency. This study characterized body composition (anthropometry and dual energy x-ray absorptiometry) and metabolic outcomes in 15 children (10 males and 5 females; age, 12.2 yr; range, 7.2-18.5 yr) after surgical removal of craniopharyngioma. In 9 subjects, outcomes were compared with those of healthy age-, sex-, body mass index-, and pubertal stage-matched controls. Insulin sensitivity was measured by 40-min iv glucose tolerance test. Seventy-three percent of subjects were overweight or obese. Sixty-six percent had normal growth velocity without GH treatment. Subjects had increased abdominal adiposity (P = 0.008) compared with controls. However, there was no significant difference in total body fat. Subjects had higher fasting triglycerides (P = 0.02) and lower high density lipoprotein cholesterol to total cholesterol ratio (P = 0.015). Insulin sensitivity was equally reduced for subjects and controls (P = 0.86). After craniopharyngioma removal, patients had more features of the metabolic syndrome compared with controls. This could be a result of hypothalamic damage causing obesity and GH deficiency. Further studies exploring predictors of the metabolic syndrome after craniopharyngioma surgery are required.

A comparison of bone geometry and cortical density at the mid-femur between prepuberty and young adulthood using magnetic resonance imaging.

In upper extremity bones, a sexual dimorphism exists in the development of periosteal and endocortical bone surfaces during growth. Little is known about developmental patterns of bone geometry at weight-bearing bones like the femur. Using MRI and dual energy X-ray absorptiometry (DXA), this study assessed the differences in mid-femoral total (TA), cortical (CA) and medullary areas (MA), cortical thickness, and cortical density (BMD(compartment)) between prepuberty and young adulthood in 145 healthy subjects (94 females) 6 to 25 years old. Additionally, agreement between mid-femoral total bone volume (TV) measurements by DXA and MRI were investigated. In both sexes, TA, CA, MA, and cortical thickness were significantly larger in adults compared to prepubertal subjects (P < 0.001), and males had greater values than females. This sex difference persisted for TA, CA, and cortical thickness (P < 0.05), but not MA, after adjusting for femur length and weight. Mean (SD) cortical BMD increased from 1.05 (0.07) and 1.09 (0.10) g/cm(3) in prepubertal children to 1.46 (0.14) and 1.42 (0.1) g/cm(3) in young adults, females and males, respectively (P < 0.001). TV measurements by DXA were significantly greater than by MRI (P < 0.001) in young adults. In conclusion, periosteal and endocortical expansion and increasing cortical BMD are the growth processes found at the mid-femur in both sexes. Our findings contrast to that in upper extremity bones, where MA is constant in females during growth. The difference in femoral bone development may be due to higher strains caused by weight bearing and genetic factors. DXA, in contrast to MRI, is inaccurate in the determination of mid-femoral TV measures.

Importance of lean mass in the interpretation of total body densitometry in children and adolescents.

OBJECTIVE: Most studies that use total body dual energy x-ray absorptiometry (DEXA) in children rely on areal bone mineral density (BMD=bone mineral content [BMC]/bone area [BA]) and compare the output with age- and sex-specific normative data. Because this approach is prone to size-related misinterpretation, this study focuses on the interrelations among BMC, body size (height), and lean tissue mass (LTM). STUDY DESIGN: This cross-sectional study presents normative total body LTM data in relation to height and BMC for 459 healthy white subjects (249 female), 3 to 30 years of age. Guidelines for DEXA interpretation in children are provided and illustrated for patients with growth hormone deficiency (n=5) and anorexia nervosa (n=5). RESULTS: LTM/height tended to be greater in male than in girls. The BMC/LTM ratio was greater in female than in boys (P<.001), even after adjustment for age and height. Sex-specific reference curves were created for LTM/height, the BMC/LTM ratio, BA/height, and BMC/BA. CONCLUSIONS: We recommend that total body DEXA in children should be interpreted in 4 steps: (1) BMD or BMC/age, (2) height/age, (3) LTM/height, and (4) BMC/LTM ratio for height. This allows differentiation of the origin of a low BMD or BMC/age, for example, short stature and primary, secondary, and mixed bone defects.

Zoledronic acid improves the mechanical properties of normal and healing bone.

OBJECTIVE: To determine the effects of the bisphosphonate zoledronic acid on the mechanical properties of normal and regenerating bone in a rabbit model of distraction osteogenesis. BACKGROUND: Bisphosphonate therapy is used for treating osteoporosis and, more recently, to enhance bone healing and reduce stress-shielding osteoporosis in distraction osteogenesis. METHODS: Thirty eight rabbits underwent 14 days of distraction osteogenesis on the right rear limb. They received either zero, one or two doses of intravenous zoledronic acid. Four point bending tests were performed to collect mechanical data. RESULTS: The peak load capacity of the regenerating bone was significantly increased by bisphosphonate therapy, but a similar trend in normal bone was not significant. The energy absorbed to failure did not vary significantly in either group. CONCLUSIONS: These data suggest that bisphosphonate therapy has a beneficial effect on the load capacity of regenerating bone, without increasing the brittleness of either new or existing bone. RELEVANCE: Zoledronic acid administration may be a potentially valuable adjunct to distraction osteogenesis treatment, to enhance bone strength, thus reducing refracture complications.

Intravenous pamidronate reduces osteoporosis and improves formation of the regenerate during distraction osteogenesis. A study in immature rabbits.

We examined the effect on bone mineral density (BMD) of a single dose of 3 mg/kg of the bisphosphonate, pamidronate (Novartis) in distraction osteogenesis in immature rabbits. Seventeen rabbits (9 control, 8 given pamidronate) were examined by dual-energy x-ray absorptiometry. There was a significant increase in the BMD in the pamidronate group compared with the control animals. The mean areal BMD (g/cm2) in the bone proximal and distal to the regenerate was increased by 40% and 39%, respectively, compared with the control group (p < 0.05). The BMD of the regenerate bone was increased by a mean of 43% (p < 0.05). There was an increase of 22% in the mean area of regenerate formed in the pamidronate group (p < 0.05). Histological examination of bone in nine rabbits (5 control, 4 pamidronate) showed an increase in osteoblastic rimming and mineralisation of the regenerate, increased formation of bone around the pin sites and an increase in the cortical width of the bone adjacent to the regenerate in the rabbits given pamidronate. Pamidronate had a markedly positive effect. It reduced the disuse osteoporosis normally associated with lengthening using an external fixator and increased the amount and density of the regenerate bone. Further study is required to examine the mechanical properties of the regenerate after the administration of pamidronate.

Osteoporosis: A possible aetiological factor in the development of Scheuermann's disease.

The aim of this study was to test the hypothesis that spinal osteoporosis is an aetiological factor in the development of Scheuermann's disease in adolescents. Clinical and radiological data was collected on 12 individuals with Scheuermann's disease (SD). Lumbar spine bone mineral density (L2-4) was measured using dual energy X-ray absorptiometry. Age and sex-matched adolescents were used as controls. The number of standard deviations from the mean of age and sex-matched controls were calculated. In regards to results, SD patients demonstrated high bone densities of between 1 and 1.5 standard deviations above the mean of age-matched controls. These results suggest that osteoporosis is not an aetiological factor in Scheuermann's disease and that bone density measurements may indeed be higher than aged-matched controls in the general population.

Effect of pamidronate on distraction osteogenesis and fixator-related osteoporosis.

We examined the effect on bone mineral density (BMD), bone mineral content (BMC) and mechanical properties of a single 1.0 mg/kg dose of the bisphosphonate pamidronate (Novartis), in a distraction osteogenesis model in immature rabbits. Twenty rabbits underwent a tibial osteotomy. Ten rabbits received pamidronate 1.0 mg/kg via ear vein intra-operatively while 10 received saline infusions only. After a 24 h latency, all underwent distraction of 0.375 mm twice daily for 15 days. The animals were culled at 42 days. After culling, the distracted and non-distracted tibiae were examined by quantitative computer tomography (QCT). The volumetric bone mineral density (vBMD, mg/cm(3)) in the bone proximal and distal to the regenerate in the operated limb was increased by a mean of 11 and 14%, respectively, compared to controls (P<0.05). The vBMD of the regenerate bone was increased by a mean of 8% over controls (NS, P=0.17). The bone mineral content (BMC, mg) was increased by 23% (proximal and distal) (P<0.05) in the bone surrounding the lengthening and there was a 17% trend towards an increase in the regenerate (NS, P=0.3). Four-point bending analysis documented that the load to failure was increased by 32% from 436 to 574 N (P<0.01) in the pamidronate group. The modulus of elasticity was not different between the control and pamidronate groups (P=0.3), and in both groups was only approximately one-third of the intact tibiae (P<0.001). The administration of a single dose of pamidronate can improve the bone mineral density, content and mechanical properties of a bone undergoing distraction osteogenesis.

Measurement of midfemoral shaft geometry: repeatability and accuracy using magnetic resonance imaging and dual-energy X-ray absorptiometry.

Although macroscopic geometric architecture is an important determinant of bone strength, there is limited published information relating to the validation of the techniques used in its measurement. This study describes new techniques for assessing geometry at the midfemur using magnetic resonance imaging (MRI) and dual-energy X-ray absorptiometry (DXA) and examines both the repeatability and the accuracy of these and previously described DXA methods. Contiguous transverse MRI (Philips 1.5T) scans of the middle one-third femur were made in 13 subjects, 3 subjects with osteoporosis. Midpoint values for total width (TW), cortical width (CW), total cross-sectional area (TCSA), cortical cross-sectional area (CCSA), and volumes from reconstructed three-dimensional (3D) images (total volume [TV] and cortical volume [CVol]) were derived. Midpoint TW and CW also were determined using DXA (Lunar V3.6, lumbar software) by visual and automated edge detection analysis. Repeatability was assessed on scans made on two occasions and then analyzed twice by two independent observers (blinded), with intra- and interobserver repeatability expressed as the CV (CV +/- SD). Accuracy was examined by comparing MRI and DXA measurements of venison bone (and Perspex phantom for MRI), against "gold standard" measures made by vernier caliper (width), photographic image digitization (area) and water displacement (volume). Agreement between methods was analyzed using mean differences (MD +/- SD%). MRI CVs ranged from 0.5 +/- 0.5% (TV) to 3.1 +/- 3.1% (CW) for intraobserver and 0.55 +/- 0.5% (TV) to 3.6 +/- 3.6% (CW) for interobserver repeatability. DXA results ranged from 1.6 +/- 1.5% (TW) to 4.4 +/- 4.5% (CW) for intraobserver and 3.8 +/- 3.8% (TW) to 8.3 +/- 8.1% (CW) for interobserver variation. MRI accuracy was excellent for TV (3.3 +/- 6.4%), CVol (3.5 +/- 4.0%), TCSA (1.8 +/- 2.6%), and CCSA (1.6 +/- 4.2%) but not TW (4.1 +/- 1.4%) or CW (16.4 +/14.9%). DXA results were TW (6.8 +/- 2.7%) and CW (16.4 +/- 17.0%). MRI measures of geometric parameters of the midfemur are highly accurate and repeatable, even in osteoporosis. Both MRI and DXA techniques have limited value in determining cortical width. MRI may prove valuable in the assessment of surface-specific bone accrual and resorption responses to disease, therapy, and variations in mechanical loading.

Effects of delaying puberty on bone mineralization in female rats.

The effect of delaying puberty on bone mineralization was studied using female rats as a model. Repeated injections of gonadotrophin-releasing hormone antagonist (GnRHa) were used to suppress the onset of puberty from the age of 6-10 weeks. A group of control female rats was given aqueous solution injections at the same age and for the same duration. The effect of delaying puberty on bone mineralization was examined using dual energy X-ray absorptiometry (DXA) and peripheral quantitative computerized tomography (QCT), both methods being adapted for small animals. Bone mineral parameters were measured at baseline and at the ages of 10, 17 and 24 weeks in total body, femur and spine. Compared to controls, bone mineral content (BMC) and bone mineral density (BMD), as measured by DXA, were significantly decreased in GnRHa-treated rats in total body and femur at 10 and 24 weeks of age (P < 0.05). The results were even more significant after adjusting for weight. After this adjustment, spine BMC and BMD at 10, 17 and 24 weeks were significantly lower in the treatment group (P < 0.05). Trabecular BMD at the distal femur in the GnRHa treated group as measured by peripheral QCT was significantly lower (P < 0.05). However, cortical bone in the mid-femur had higher BMD, concurrent with lower cortical thickness in the treatment group. In conclusion, a delay in the onset of sexual maturation may cause prolonged, possibly irreversible defect in bone mineralization.

Vitamin D receptor alleles predict growth and bone density in girls.

OBJECTIVES: Polymorphism of the vitamin D receptor (VDR), collagen alpha I type I (Col I alpha I), and oestrogen receptor (ER) genes have been shown to account for some of the heritability of bone mineral density (BMD) in adults. This study examined this relation in prepubertal children. METHODS AND SUBJECTS: The relation between genotypes of VDR gene (Taq I, Bsm I, Fok I), Col I alpha I gene (Msc I), and ER gene (Pvu II) with areal BMD, volumetric BMD, and growth were examined in 114 (68 girls) healthy 7 year old, white children. RESULTS: The genotype of the VDR gene (Taq I) correlated with lumbar spine (L1-4) volumetric BMD in girls only, but at no other bone sites. In girls, VDR genotype affected areal BMD at all sites. After adjusting for height and weight, however, this effect was explained completely by the independent effect of the VDR genotype on growth. Girls with genotype TT, were 3.9 kg heavier and 4.1 cm taller than those with tt, but this relation was not present at birth. No relation was found between genotypes of the VDR gene (Fok I), Col I alpha I gene (Msc I), or ER gene (Pvu II) and BMD or growth variables. CONCLUSIONS: In prepubertal girls, VDR alleles contribute to lumbar spine volumetric BMD variance, but the areal BMD effect reflects the relation between areal BMD and growth. VDR alleles might affect postnatal growth regulation.

Fat distribution in children and adolescents--the influence of sex and hormones.

A significant proportion of the morbidity related to obesity is now recognized to be related to the regional distribution of fat. The advent of dual energy X-ray absorptiometry has facilitated the assessment of body composition in a number of investigations on body fat. From current data, including the authors' own study of trunk and leg fat in 335 children and young adults, it is evident that gender differences for total body fat, percentage of body fat and distribution of fat occur after the pubertal years. Males develop a distribution of fat which favours central deposition of fat irrespective of their total body fat--a distribution that is, unfortunately, associated with a number of adverse implications on health. Furthermore, this tendency to increasing abdominal fat is independent of adipose tissue mass. Hormonal regulators of adipose tissue, including growth hormone which is already known to increase free fatty acids and decrease fat cell mass, need to be studied to account for these gender differences.

Volumetric bone mineral density in normal subjects, aged 5-27 years.

Concerns have been raised regarding the validity of using areal bone mineral density (aBMD) as a substitute for the true volumetric bone mineral density (vBMD) in the pediatric population. We studied 209 normal subjects (109 males), aged 5-27 yr, to examine the influence of age, gender and growth on vBMD. The femoral neck, midthird of the femoral shaft, and the four lumbar vertebral bodies (L1-L4) were studied. Using data on bone width and height obtained by dual energy x-ray absorptiometry, bone volume was calculated with the assumption that all three sites are cylinders. In contrast to aBMD, vBMD of the femoral neck bore no relationship to age or weight in both sexes, but was significantly related to height in females (r2 = 0.07; P = 0.01). Similarly, vBMD of the femoral shaft (vFBMD) did not change with age or height in either sex. In females, a significant inverse relationship was seen between vFBMD and weight (r2 = 0.14; P = 0.001). Male subjects had higher vFBMD than females (mean +/- SD, 0.73 +/- 0.11 vs. 0.70 +/- 0.12; P = 0.047), but no sex difference was seen in vBMD of the femoral neck. Conversely, vBMD of L1-L4 remained age and growth dependent, although the strength of the relationship was weaker than that for aBMD (data not shown). In conclusion, the vBMD of the femoral neck and shaft is independent of age and is less dependent on growth variables in children and young adults than is aBMD. These observations offer a different perspective from our previous concepts of aBMD.