Children and adolescents with cystic fibrosis display moderate bone microarchitecture abnormalities: data from high-resolution peripheral quantitative computed tomography.

We investigated whether bone microstructure assessed by high-resolution peripheral quantitative tomography (HR-pQCT) could be altered in children and teenagers with cystic fibrosis (CF). In comparison to their healthy counterparts, bone microstructure was mildly affected at the tibial level only. INTRODUCTION: Cystic fibrosis-related bone disease (CFBD) may alter bone health, ultimately predisposing patients to bone fractures. Our aim was to assess bone microstructure using high-resolution peripheral quantitative tomography (HR-pQCT) in a cohort of children and teenagers with CF in comparison to age-, puberty-, and gender-matched healthy volunteers (HVs). METHODS: In this single-center, prospective, cross-sectional study, we evaluated the HR-pQCT bone parameters of CF patients and compared them to those of the healthy volunteers. RESULTS: At a median age of 15.4 [range, 10.5-17.9] years, 37 CF patients (21 boys) with 91% [range, 46-138%] median forced expiratory volume in 1 s were included. At the ultradistal tibia, CF patients had a smaller bone cross-sectional area (579 [range, 399-1087] mm2) than HVs (655 [range, 445-981] mm2) (p = 0.027), related to a decreased trabecular area, without any significant differences for height. No other differences were found (trabecular number, separation, thickness, or distribution) at the radial or tibial levels. Bone structure was different in patients receiving ursodeoxycholic acid and those bearing two F508del mutations. CONCLUSION: In our cohort of children and teenagers with good nutritional and lung function status, bone microstructure evaluated with HR-pQCT was not severely affected. Minimal microstructure abnormalities observed at the tibial level may be related to the cystic fibrosis transmembrane conductance regulator defect alone; the long-term consequences of such impairment will require further evaluation.

Induced membrane technique for reconstruction after bone tumor resection in children: a preliminary study.

AIM: Segmental long-bone defect due to tumor resection remains a challenge to treat. The induced membrane technique is a new alternative for biological reconstruction. During the first stage, a cement spacer is inserted after bone resection and stabilisation. The cement spacer is removed during a second stage procedure performed after chemotherapy, and cortico-cancellous bone autograft was placed in the biological induced chamber. The aim of this study was to assess preliminary results in eight children. PATIENTS AND METHODS: This prospective study included six girls and two boys, with a mean age of 12.1 years (range 9.5 to 18) and treated for a mean 15 cm defect (range 10 to 22 cms) due to resection of osteosarcoma (n=4), Ewing sarcoma (n=3) and low grade sarcoma. All patients except one, were given pre- and postoperative chemotherapy. Surgery was performed for three patients with a distal femur tumor, two patients with a proximal tibial tumor and three patients who had proximal humerus, shaft of humerus and fibular tumors. Fixation was mainly performed with locking compression plate (n=4) and locked nail (n=2). The mean operating times for first and second step procedures were 4.8 and 4h respectively. The healing process was radiologically assessed. RESULTS: After a mean follow-up of 21.6 months (15 to 30), all patients were free of disease and seven had bony union. For the lower limb reconstructions, full weight bearing was possible after a mean of 116 days (range 90 to 150) following the second stage. Mean time to bone union was 4.8 months (1.5 to 10). The early Musculoskeletal Tumor Society (MSTS) score was 25.2/30 (range 20-30). Complications were: non-union (n=1), paradoxical graft resorption (n=1) requiring graft revision. CONCLUSION: This two stage procedure reduces the operating time during the first stage and it also reduces early complications. Rapid bone union is objectively obtained despite major bone resection and the patients receiving chemotherapy. SIGNIFICANCE: The induced membrane technique could be an excellent alternative for biological reconstruction after tumor resection in children.

[Pain, osteopenia and body composition of 22 patients with Duchenne muscular dystrophy: a descriptive study]. / Douleur, ostéopénie et composition corporelle chez 22 patients atteints de dystrophie musculaire progressive de Duchenne. Etude descriptive.

OBJECTIVES: To study the link between pain, osteopenia and body composition in patients with Duchenne muscular dystrophy and to present a detailed questionnaire to evaluate their pain. MATERIALS AND METHODS: Twenty-two boys with Duchenne muscular dystrophy, mean age 11.4+/-4.0 years, were examined between February and March 2003. They were asked to complete a detailed questionnaire and undergo a global assessment of pain on a visual analog scale and muscular testing. They were also asked about a history of fractures. Their bone mineral content at the lumbar spine and femoral neck levels, as well as their body composition in fat and lean mass, were assessed by dual energy absorptiometry. RESULTS: The mean age for walking incapacity was 8.8+/-1.7 years. The youngest patients, who were still able to walk, had a higher level of pain than patients who depended on wheelchairs. No significant correlation was established between pain and osteopenia. One in 2 patients had spontaneous pain, and mobilization was painful for 21. The score obtained by detailed questioning about pain correlates with the average pain scores on visual analog scales. The bone mineral content was lower, especially in the lower limbs, had decreased before the inability to walk and was correlated with muscular weakness. Fractures were more frequent in mobile patients and usually occurred after a fall. CONCLUSION: Although pain in Duchenne muscular dystrophy has not been extensively studied, it is frequent and significant. Twenty-one patients had moderate to severe pain. The youngest patients had intense pain, especially during mobilisation. To evaluate this pain, we propose to use the mean results of 2 visual analog scales associated with a detailed questionnaire. However, in this study, Duchenne muscular dystrophy, pain and osteopenia were not correlated. Dual X-ray absorptiometry provides interesting information about bone mineral content, fat body mass and lean body mass. The fat body mass was higher than normal in our patients. The bone mineral content and lean body mass were lower than that for normal children, because the dystrophic process advances with age. The fracture prevalence was high, especially in young patients. Falling was the most common mechanism of fracture.

Annual changes in bone mineral content and body composition during growth.

OBJECTIVES: To compute the annual changes in total bone mineral content (BMCt), lean tissue mass and fat mass (LTM and FM) during growth. METHODS: Whole body DXA data were used to calculate the annual changes of the parameter P (P = BMCt, LTM or FM), as a percentage, as DeltaP% = 100 x (P(i+1) - P(i)) / P(i); with P(i) and P(i+1) the values for P at age i and age (i+1). Smoothed curves were then obtained from DeltaP% values plotted against age. RESULTS: Changes in FM were different in males and females. A peak velocity was marked for the three tissues at age 6.5 in boys, and at age 6.5-7.5 in girls; a pubertal peak spurt appeared at age 12 in girls and between age 13 and 14 in boys. This latter peak was followed by an exponential decrease, and no significant changes were found for the three components after age 20 in girls and age 21-22 in boys. CONCLUSION: Changes in tissue accretion during growth are easy to follow when expressed in percentages. Fat changes, especially, should be around 17% in girls and 15% in boys at the age of puberty.

Microarchitectural and physical changes during fetal growth in human vertebral bone.

The ossification process in human vertebra during the early stage of its formation was studied by X-ray diffraction (XRD) and X-ray microtomography (microCT) at the European Synchrotron Radiation Facility (ESRF), Grenoble, France. Twenty-two samples taken from vertebral ossification centers of human fetal bone (gestational age ranging between 16 and 26 weeks) were investigated. The analysis of three-dimensional images at high spatial resolution (approximately 10 and approximately 2 microm) allows a detailed quantitative description of bone microarchitecture. A denser trabecular network was found in fetal bone compared with that of adult bone. The images evidenced a global isotropic structure clearly composed of two regions: a central region (trabecular bone) and a peripheral region (immature bone). XRD experiments evidenced hydroxyapatite-like crystalline structure in the mineral phase at any fetal age after 16 weeks. Interestingly, the analysis of XRD patterns highlighted the evolution of crystalline structure of mineralized bone as a function of age involving the growth of the hydroxyapatite crystallites.

[Dual energy x-ray absorptiometry assessment of the bone mineral content and body composition during growth]. / Contenu minéral osseux et composition corporelle au cours de la croissance: quantification par absorptiométrie à rayons X.

PURPOSE: To propose a simple method of analysis of whole body DXA scan results, for the bone mineral content of the entire skeleton (BMCt) and the arms and legs (BMCa and BMCl), as well as the analysis of the body composition in lean (Lt, La and Ll) and fat (Ft, Fa and Fl) in children and adolescents with normal growth. Materials and methods. A whole body DXA scan (Norland XR36(TM) DXA system) was performed in 90 control females and 76 control males aged from 2.3 y to 21.0 y, and from 2.3 y to 20.1 y, respectively. BMC values, as well as L and F values were correlated with the body weight (BW) of the measured subjects. BMCt, Lt and Ft values corrected for the body surface area (BS), and the ratio BMCl/BMCa, were also calculated. RESULTS: High linear correlations (r>0.9) were found between BMCt, Lt or Ft values and BW, as well as between BMC (a & l) and BMCt, L (a & l) and Lt, F (a & l) and Ft. The ratios BMCt/BS(1.5), Lt/BS(1.5), and Ft/BS(1.5) had constant values of 1.2+/-0.1, 17.5+/-1.9, and 8.7+/-2.0, respectively, in females, and 1.2+/-0.1, 18.9+/-1.3, and 7.3+/-1.4, in males. The ratio BMCl/BMCa had a constant value of 2.8+/-0.4 in both sexes. CONCLUSION: The reference values obtained by DXA for the bone mineral content, lean and fat masses of the entire body and limbs are of interest, in our experience, to follow-up the growth in patients with long-term treatments, and to quantify orthopedic disorders and treatments.

Body composition in children after renal transplantation.

This study examines changes in body composition after renal transplantation (Tx) in 16 children who underwent dual-energy X-ray absorptiometry examination within 6 months preceding Tx; the examination was then repeated every 6 to 12 months after Tx. Body composition was analyzed with regard to whole-body bone mineral content (BMC), lean body mass (LBM), and fat body mass (FBM). Median BMC decreased from the initial value of +0.98 standard deviation scores (SDS) to -0.55 SDS during the first 3 months after Tx, and a further decrease was noted at the end of month 6 (M6; -1.34 SDS) and M12 after Tx (-1.32 SDS). Improvement was observed during the second year after Tx (P for global changes < 0.0001). LBM and FBM also changed significantly during the 2 years after Tx (P = 0.006 and P = 0.0001, respectively). LBM decreased during the first 3 months after Tx (median change, 0.71 SDS) and remained less than 0 SDS in all but 4 patients. Median LBM did not decrease to less than -1 SDS during the entire study period. Conversely, median FBM increased by a median of 3.73 SDS during the first 3 months and remained elevated during the first 12 months after Tx, with a subsequent decrease at 2 years after Tx. No significant correlation was found between cumulative doses of prednisone and BMC, FBM, or LBM at any interval if absolute values were considered. However, relative changes in FBM correlated significantly with relative changes in prednisone cumulative doses.

[Progressive limb lengthening with a centromedullary nail versus an external fixator: experimental study in sheep]. / L'allongement progressif des membres par clou mécanique centro-médullaire d'allongement: étude expérimentale chez le mouton.

PURPOSE OF THE STUDY: Progressive limb lengthening with an external fixator often leads to pin-related complications. A new technique allowing progressive lengthening with a centromedullary nail without external fixation has been developed. This original double-locked device consists of matching male and female components fitted with a continuous thread. Lengthening is achieved via a one-way ratchet system. Twelve back-and-forth movements produce 1.25 mm lengthening. MATERIAL AND METHODS: We tested this new device on 20 sheep and compared results with external fixation lengthening in 20 other sheep. The animals were divided into groups for sacrifice on days 5, 10, 20, 45 and 90. Serial x-ray were obtained for all animals. In the 45-day and 90-day groups, histomorphometric (trichrome goldner coloration and polarized light microscopy) and densitometric studies were also performed. Bone mineral density (BMD) was determined and bone trabecular density (BTD) and trabecular bone volume (TBV) were expressed in percent of bone trabecular surface area. RESULTS: Mean lengthening in the 45-day and 90-day groups was 39 mm for the nail and 20 mm for external fixation (1 mm/day). At 90 days, 3 sheep out of 4 had consolidated radiologically with external fixation and 2 out of 4 with the nail. BMD was slightly better for external fixation (0.811 vs 0.695/cm(2)). This difference could probably be attributed to the greater lengthening obtained with the nail. At 45 days, BMD was the same (0.6 g/cm(2)) for both devices. BTD was nearly two-fold higher for the nail compared with external fixation (59.65% vs 32.61% at 90 days), most probably due to primary bone formation. The histomorphometric study allowed an analysis of the osteoid border. Bone quality obtained in the bone regenerate with the nail was superior to that obtained with external fixation. Primary bone formation resulted from membrane ossification with direct transformation of fibroblasts into osteoblasts. CONCLUSION: This work demonstrated that progressive lengthening can be achieved with a specifically designed centromedullary nail without iterative opening of the operative site. Tolerance to this type of device and quality of the bone regenerate are altogether satisfactory.

Bone mineral density in subjects with mild asthma randomised to treatment with inhaled corticosteroids or non-corticosteroid treatment for two years.

BACKGROUND: Inhaled corticosteroids are clearly beneficial for patients with asthma of moderate severity, but the risks and benefits of using them in patients with milder asthma are less clear. We have compared the change in bone mineral density over 2 years in adults with mild asthma randomised to receive an inhaled corticosteroid or non-corticosteroid treatment. METHODS: Subjects with mild asthma (mean forced expiratory volume in one second (FEV(1)) 86% predicted, mean age 35 years, taking beta agonists only) were randomised to receive inhaled budesonide, inhaled beclomethasone dipropionate, or non-corticosteroid treatment for 2 years in a prospective randomised open study in 19 centres in France, New Zealand, Spain, and the UK. The corticosteroid dose was adjusted according to a written self-management plan. The main outcome measure-change in bone mineral density after 6, 12, and 24 months-was measured "blind". Secondary outcomes included lung function, the relation between change in bone density and inhaled steroid dose and change in biochemical markers of bone metabolism. RESULTS: Of 374 subjects randomised, 239 (64%) completed the study and were included in the analysis. The median daily doses of inhaled budesonide (n=87) and beclomethasone (n=74) were 389 microg and 499 microg, respectively. Subjects treated with an inhaled corticosteroid had better asthma control than those in the reference group (n=78). Change in bone mineral density did not differ between the three groups over the 2 years, nor did it correlate with changes in markers of bone metabolism. The mean change in bone mineral density over 2 years in the budesonide, beclomethasone dipropionate, and reference groups was 0.1%, -0.4%, and 0.4% for the lumbar spine and -0.9%, -0.9%, and -0.4% for neck of the femur. Mean daily dose of inhaled steroid was related to reduction in bone mineral density at the lumbar spine but not at the femoral neck. CONCLUSION: In subjects with mild asthma an inhaled corticosteroid provided better asthma control than alternative non-corticosteroid treatment with no difference in change in bone mineral density over 2 years. The relation between dose of inhaled corticosteroid and change in bone density at the lumbar spine may be due to a direct effect of inhaled corticosteroids on bone. Since inhaled steroid dose is also related inversely to lung function, an effect of asthma severity on bone density was also possible.

Bone mineral density in children after renal transplantation.

A successful kidney transplantation (Tx) offers good quality of life for children suffering from chronic renal failure. However, some metabolic abnormalities may not be corrected and may persist after Tx despite good graft function. Post-Tx bone disease seems to be a universal finding in adult Tx recipients, and is most probably related to steroids. Reports on bone mineral density (BMD) in children after renal Tx are not uniform. Recent studies suggest that BMD is normal when corrected for height. However, longitudinal studies show a transient decrease in BMD in the early post-Tx period. These controversial results raise the issue of the correct interpretation of dual-energy X-ray absorptiometry in children with stunted growth. Etiopathogenetic factors of the decreased BMD, preventive and therapeutic measures are discussed. In conclusion, the results of dual energy X-ray absorptiometry should be interpreted with caution, especially in children with disturbed growth.

Dual-energy X-ray absorptiometry in small subjects: influence of dual-energy X-ray equipment on assessment of mineralization and body composition in newborn piglets.

There is a growing body of literature that describes the use of dual-energy x-ray absorptiometry (DXA) for bone mineral content (BMC) and fat mass (FM) assessment in neonates, but the reproducibility and accuracy of the method are still controversial. Two different software programs have been developed for use on Hologic densitometers: the Pediatric Whole Body (PWB) and the Infant Whole Body (IWB) programs. They differ in scan time, radiation exposure, and in the algorithm used to assess BMC. We evaluated the reproducibility and accuracy of PWB and IWB in newborn piglets. Reproducibility of body mass (BM), FM, and BMC measurements from PWB and IWB were similar. BM agreed well with scale weight with both software programs; IWB was within +/- 0.5% and PWB was within +/- 0.3% of scale weight. FM was highly correlated with carcass fat (PWB: r = 0.962; IWB: r = 0.980). Errors in the DXA estimation of fat were similar with PWB and IWB. With both software programs, BMC was highly correlated with carcass calcium (PWB: r = 0.925, IWB: r = 0.987), but errors in the DXA estimation of calcium were about twice as high with PWB (+/- 16.9%) than with IWB (+/-9.2%). In four piglets, the addition of a layer of porcine lard was associated with an increase in BMC; this effect was more pronounced with PWB (+ 156%) than with IWB (+ 15%). The IWB software provided BMC measurements that were more precise, accurate, and stable in the presence of added fat than the measurements obtained with PWB, indicating that IWB is superior to PWB for in vivo determination of BMC and body composition.

Bone density reduction in various measurement sites in men and women with osteoporotic fractures of spine and hip: the European quantitation of osteoporosis study.

We have measured bone mineral density (BMD) using dual X-ray absorptiometry (DXA) of the spine and hip, spinal quantitative computed tomography (QCTspi), and peripheral radial quantitative computed tomography (pQCTrad) in 334 spine and 51 hip fracture patients. The standardized hip and spine BMD for each patient was calculated and compared with the combined reference ranges published previously, each densitometer having been cross-calibrated with the prototype European Spine Phantom (ESPp) or the European Forearm Phantom (EFP). Male and female fracture cases had similar BMD values after adjusting for body size, where appropriate. This suggests that the relationship between bone density (mass per unit volume) and fracture risk is similar between men and women. However, compared with age-matched controls, mean decreases in BMD ranged from 0.78 SD units (women with hip fracture, DXAspi) to 2.57 SD units (men with spine fractures, QCTspi). The proportion of spine and hip fracture patients falling below the cutoff for osteoporosis (T-score <-2.5 SD) proposed by the World Health Organization (WHO) study group varied according to different BMD measurement procedures (range 18-94%). This finding suggests that the WHO definition requires different thresholds when used with non-DXA BMD measurement techniques. Receiver operator characteristic (ROC) analysis was used to compare measurement techniques for their ability to discriminate between cases and controls. Among DXA sites, the proximal femur was preferred when evaluating generalized bone loss, particularly in elderly people. An additional spinal BMD measurement may add clinical value if spine fracture risk assessment has a high priority. Both axial and peripheral QCT techniques performed comparably to DXA in spinal osteoporosis, so investigators and clinicians may use any of the three technologies with similar degrees of confidence for the diagnosis of generalized or site-specific bone loss providing straightforward clinical guidelines are followed.

Periosteum and bone marrow in bone lengthening: a DEXA quantitative evaluation in rabbits.

We quantitatively studied the role of periosteum and bone marrow-endosteum during lengthening in 18 growing rabbits, comparing four surgical procedures: 1) periosteum and bone marrow preservation, 2) periosteum preservation, bone marrow destruction, 3) periosteum destruction, bone marrow preservation, 4) periosteum and bone marrow destruction. An external fixator was set on one femur, the other serving as a control. Distraction began on day 5 and stopped on day 25 (0.25 mm/12 hours). On day 30, femora were harvested with a layer of muscle. Area, bone mineral content and density were measured by dual-energy x-ray absorptiometry. Procedure 2 showed the highest increase in bone mineral content around the elongated callus (127%) compared to procedures: 1 (81%), 3 (25%) and 4 (-8%, i.e., resorption of bone ends). A statistically significant effect on bone formation was observed when preserving (vs. destroying): 1) periosteum, 2) bone marrow (effect observed only around the distraction gap), 3) periosteum and bone marrow in combination. Periosteum alone forms a larger callus, with more mineral content than bone marrow alone, and destruction of both results in the absence of bone formation around the distraction area. Careful preservation of periosteum is essential to bone healing. Formation of bone with a large mineral content does not require bone marrow preservation, but there is an interaction effect on healing between bone marrow and periosteum.

Dual energy X-ray absorptiometry of the hand and wrist--a possible technique to assess skeletal maturation: methodology and data in normal youths.

Ninety five normal Caucasian subjects (51F, 44M) aged from 2 to 25 y were measured at the hand and wrist level with a small DXA system (pDEXA) in order to obtain the normal values of the bone mineral content (BMC), density (BMD) and projected area (A) of carpal (c) and metacarpal (m) bones. BMDc ranged from 0.065 +/- 0.007 g/cm2 to 0.365 +/- 0.035 g/cm2 in females and 0.425 +/- 0.040 g/cm2 in males. It presented a sharp change of increase rate at 15.5 and 17 y of age in girls and boys, respectively. Ac presented the same kind of evolution as BMDc, but had a larger value dispersion. The second metacarpal bone had the highest BMCm value in 85% of females and 90% of males. The sum of BMCmi or Ami values (i = 1-5) and the projected mean density of the 5 metacarpal bones was well correlated with BMCc, Ac and BMDc, respectively (r > 0.90). A volumetric mineral density, dmi, calculated for each of these bones, approximated to a cylinder, was correlated with age (r > 0.85).

Body composition in children receiving recombinant human growth hormone after renal transplantation.

BACKGROUND: Recombinant human growth hormone (rhGH) is an anabolic hormone promoting protein synthesis in various tissues. Therefore, changes in body composition may be expected during rhGH treatment. METHODS: We studied changes in body composition during two years of rhGH treatment in 21 children after at least one year with a functioning renal transplant. The mean +/- SD age was 12.9+/-2.5 years at the start of rhGH therapy. A whole body, dual energy X-ray absorptiometry (DEXA) exam was performed before the initiation of rhGH therapy (T0), and was repeated at one and two year intervals after initiation of the therapy (T1 and T2, respectively). RESULTS: Lean body mass increased by a median of 0.48 SDS during the first year of treatment (P = 0.022), and the median increase during two years of therapy was 0.36 SDS (P = 0.061). On the contrary, the median fat body mass decreased by 2.17 SDS during the T0 to T1 period (P = 0.04) and by 1.99 SDS during the T0 to T2 period (P = 0.055). The index for fat body mass/lean body mass (FBM/LBM) decreased by a median of 5.3% during T0 to T1 (P < 0.001), however, a slower but still significant decrease by a median of 4.2% was noted at T2 (P < 0.05). Bone mass content did not change significantly during rhGH treatment. The medians in caloric and protein intakes were stable during rhGH treatment. CONCLUSION: A significant increase of lean body mass and a decrease of fat body mass was noted during rhGH therapy in children after renal transplantation.