Peripheral quantitative computed tomography at the distal radius: cross-calibration between two scanners

Peripheral quantitative computed tomography (pQCT) is an important technique to study the interaction between the muscle and bone systems. We have recently established pQCT reference ranges for children, adolescents and young adults using a recent version (XCT 2000) of the Stratec scanners (Stratec Inc., Pforzheim, Germany). However, the previous version of this type of scanner (XCT 900) is still widely used and cross-calibration is needed to use these reference data. Therefore, both distal radii of 19 healthy subjects (age 21 to 59 years; 11 women) were analyzed at the "4% site" using both the XCT 900 and the XCT 2000. Cross-sectional area, total and trabecular bone mineral density (BMD), total bone mineral content (BMC) and polar Strength-Strain Index (SSI) results from the two scanners were compared using linear regression analysis. To achieve scanner calibration we used the intercept and slope of the correlations. The correlation coefficients between the two devices were 0.82 for the cross-sectional area, 0.81 for total BMD, 0.97 for trabecular BMD, 0.99 for total BMC and 0.86 for polar SSI. In conclusion, these data allow for the conversion of XCT 900 results at the distal radius to XCT 2000 values and vice versa.     

Densitometric and tomographic analyses of musculoskeletal interactions in humans

Previous studies with standard densitometry (DXA) have suggested that the bone mass is strongly dependent on the muscle mass in the species, following a similar relationship at any age and sex hormones or related factors potentiate that relationship. Studies with pQCT indicated that the surplus bone mass per unit of muscle mass previously observed in premenopausal women would be stored in skeletal regions with relatively little mechanical relevance, thus avoiding remotion through mechanically oriented remodelling by the bone mechanostat. Scanning the distal radius with pQCT has also showed a highly significant, linear relationship between SSI of the distal radius and the dynamometric maximal bending moment of the forearm in normal men and women. In order to investigate similar relationships in regions that are inaccessible to pQCT, we used spinal radiographs and axial QCT. This study affords additional evidence to the previous references concerning the direct, significant impact of the regional muscle strength on the determination of the tomographic indicators of bone mechanical quality and their indirect repercussion of the skeletal condition (curvature of the spine).     

Side-to-side differences in bone strength in master jumpers and sprinters

Introduction: This study evaluated side-to-side difference in tibial bone structure, calf muscle cross-sectional area (CSA) and hopping force in master athletes as a result of training for sports with different magnitudes of inter-leg loading difference. Methods: Tibial bone parameters (at 4%, 14%, 38% and 66% tibial length proximal to distal end), muscle CSA (at 66% tibial length) and hopping forces of both legs of 51 master athletes (conditioned jumpers, conditioned triple jumpers, unconditioned jumpers, hurdlers and sprinters) were examined using pQCT. In epiphyseal 4% slice bone CSA (Ar.tot), total BMC (vBMC.tot), trabecular BMC (vBMC.tb) cortical BMC (vBMC.ct), and trabecular BMD (vBMD.tb) were measured. In diaphyseal slices, Ar.tot, vBMC.ct, cortical density (vBMD.ct), cross-sectional moment of inertia (CSMI) and calf muscle CSA (MuscA) were examined. Results: In conditioned jumpers, side-to-side differences in favour of take-off leg were found in 4% slice in vBMC.tb (+4.1%) (P<0.05). A side-to-side difference was found in 66% slice vBMC.ct and CSMI (both P<0.05), with conditioned jumper (+2.8% and 6.6%) and triple jumper (+2.7% and 7.2%) values higher than other groups. Conclusion: The results suggest that regular training in high-impact sports with uneven lower limb loading results in side-to-side differences in skeletal adaptation independent of age and gender, suggesting that high-impact exercise is effective in maintaining bone strength throughout human lifespan.     

Radial bone mineral content of normal Japanese infants and prepubertal children: influence of age,sex and body size

The present study was performed to measure appendicular bone mass of Japanese infants and children, and to assess the influence of age, sex and body size on bone mass during the period of bone growth. The bone mineral content (BMC) and bone width (BW) at the distal third of the radius were measured by single photon absorptiometry (SPA) in 229 healthy Japanese infants and children aged 0–12 years, and the BMC/BW ratio was calculated to give the bone mineral density (BMD). BMC and BW increased with age until 2 years, while BMD did not obviously change until 2 years. After 2 years of age, the overall effect of aging appeared more prominent in BMC and BMD than in BW. There were no significant differences in BMC, BW and BMD between males and females aged 0–12 years. Age, body height, and body weight were strongly correlated with three parameters of bone mass (BMC, BW, and BMD). Among the three parameters of bone mass, BMC showed the highest Pearson coefficient of correlation with age (r = 0.955), body height (r = 0.957) and body weight (r = 0.966), as compared with BW and BMD. The present cross-sectional study provides normative data of the appendicular bone mass in healthy Japanese children, which may serve as a standard for assessment of bone mineralization in Japanese infants and children with medical problems.     

The muscle-bone unit in adulthood: influence of sex, height, age and gynecological history on the bone mineral content and muscle cross-sectional area

Bone and muscle development are both strongly influenced by sex hormones. The purpose of this study was to examine the changes in bone and muscle parameters (bone mineral content - BMC, muscle cross-sectional area - MA) in 130 men aged 31 -60 years, and in 180 pre-menopausal women aged 30-53 years with respect to age, body height and, with the women, their gynecological history (age-at-menarche, number of pregnancies, duration of lactation and use of oral contraception). The study was performed using peripheral quantitative computed tomography (pQCT) at a 65% site of the forearm length. Both BMC and MA were dependent on body height (p<0.0001), but not on age. The BMC/MA ratio was dependent neither on age nor on body height in both genders. MA as well as BMC were found significantly higher in males than in females (p<0.0001 for both variables). We observed a significantly higher BMC/MA ratio in females than in males (p<0.0001). We found no effect either of the analyzed variables of gynecological history on bone/muscle characteristics. The findings highlight the necessity of involving height-adjusted parameters and BMC/MA ratio into bone analysis in adults.     

Estimation of bone mineral density and architectural parameters of the distal radius in hemodialysis patients using peripheral quantitative computed tomography

We analyzed bone changes in a series of hemodialysis patients followed up for a maximum of 299 months by assessing bone mineral density (BMD) and architectural parameters of the distal radius using peripheral quantitative computed tomography (pQCT), and determined the predictors of skeletal changes in these patients. No significant differences in trabecular BMD (BMD(T)) were found compared with BMD(T) of the normal control. In contrast, cortical BMD (BMD(C)) was significantly decreased compared with BMD(C) of the normal controls. Hemodialysis patients had significantly lower values for cortical bone area, cortical thickness, moment of inertia, and polar moment of inertia than the age-matched controls. From single and multiple regression analysis, the most significant predictor of metabolic bone disease in these cases was found to be duration of hemodialysis. In addition, increases in serum alkaline phosphatase and intact parathyroid hormone in secondary hyperparathyroidism were found to correlate with a decrease in pQCT values in cortical bone; as such, these increases were also found to be a predictive. The present study confirms that the reduction in both BMD(C) and architectural parameters in hemodialysis patients occurs partly because of prolonged hemodialysis and secondary hyperparathyroidism. In addition, immobilization, dietary factors, daily intake of calcium or vitamin D, and so on must be taken into account when clarifying the causes of skeletal complications resulting from hemodialysis.     

Muscle mass during childhood--relationship to skeletal development

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). This functional approach to pediatric bone densitometric data should be adaptable to a variety of densitometric techniques.     

Case-control study of the muscular compartments and osseous strength in neurofibromatosis type 1 using peripheral quantitative computed tomography

Skeletal anomalies are observed in neurofibromatosis type 1 (NF1), but the pathogenesis is unknown. Given that muscle mass is important in the development of the strength of bone, peripheral quantitative computed tomography (pQCT) was utilized to compare measurements of muscle compartments between NF1 individuals and controls. Forty individuals with NF1 (age 5-18 years) were evaluated. Cross-sectional measurements, at the 66% tibial site, were obtained using pQCT (XCT-2000, Stratec) and variables were compared to controls without NF1 ((age 5-18 years, N=380) using analysis-of-covariance controlling for age, height, Tanner stage, and gender. The NF1 cohort showed decreased total cross-sectional area [p<0.001], decreased muscle plus bone cross-sectional area [p<0.001], decreased muscle cross-sectional area [p<0.001], and decreased Stress Strain Index [p=0.010]. These data indicate that NF1 individuals have decreased muscle cross-sectional area and decreased bone strength than individuals without NF1.     

Muscle-bone relationships in the lower leg of healthy pre-pubertal females and males

Muscle-bone relationships in healthy pre-pubertal children were investigated using four muscle measures as predictors of tibial strength: 66% tibia cross-sectional muscle area (CSMA) by pQCT; leg lean mass (LLM) by DXA; and muscle power (Power) and force (Force) measured during a two-footed jump. Polar strength strain index (pSSI), a calculated surrogate for bone strength at the 20% distal tibia, was obtained on 105 (54 male) self-assessed pre-pubertal children. The amount of muscle (CSMA, LLM) may influence bone strength more than muscle strength (Power, Force) during periods of rapid growth. Correlations and multiple regression partial-R values from models controlling for age, sex, height and weight were obtained for each muscle predictor. CSMA, LLM, Power and Force were positively correlated with pSSI (R=0.84, 0.92, 0.85; 0.66, respectively, all p<0.01). Partial-R values were highest for LLM (partial-R=0.21), similar for CSMA and Power (0.14, 0.15, respectively) and lowest for Force (0.04) in predicting pSSI. Muscle predictors were associated with total and cortical area (R=0.59 to 0.90; p<0.01 for all), but not cortical vBMD at the 20% distal tibia site. These data support relationships between muscle predictors and bone parameters measured by pQCT in healthy pre-pubertal children.     

Reduced trabecular bone mineral density and cortical thickness accompanied by increased outer bone circumference in metacarpal bone of rheumatoid arthritis patients: a cross-sectional study

Introduction

The objective of this study was to assess three-dimensional bone geometry and density at the epiphysis and shaft of the third meta-carpal bone of rheumatoid arthritis (RA) patients in comparison to healthy controls with the novel method of peripheral quantitative computed tomography (pQCT).

Methods

PQCT scans were performed in 50 female RA patients and 100 healthy female controls at the distal epiphyses and shafts of the third metacarpal bone, the radius and the tibia. Reproducibility was determined by coefficient of varia-tion. Bone densitometric and geometric parameters were compared between the two groups and correlated to disease characteristics.

Results

Reproducibility of different pQCT parameters was between 0.7% and 2.5%. RA patients had 12% to 19% lower trabecular bone mineral density (BMD) (P ≤ 0.001) at the distal epiphyses of radius, tibia and metacarpal bone. At the shafts of these bones RA patients had 7% to 16% thinner cortices (P ≤ 0.03). Total cross-sectional area (CSA) at the metacarpal bone shaft of pa-tients was larger (between 5% and 7%, P < 0.02), and relative cortical area was reduced by 13%. Erosiveness by Ratingen score correlated negatively with tra-becular and total BMD at the epiphyses and shaft cortical thickness of all measured bones (P < 0.04).

Conclusions

Reduced trabecular BMD and thinner cortices at peripheral bones, and a greater bone shaft diameter at the metacarpal bone suggest RA spe-cific bone alterations. The proposed pQCT protocol is reliable and allows measuring juxta-articular trabecular BMD and shaft geometry at the metacarpal bone.     

Analysis of the independent power of age-related,anthropometric and mechanical factors as determinants of the structure of radius and tibia in normal adults. A pQCT study

To compare the independent influence of mechanical and non-mechanical factors on bone features, multiple regression analyses were performed between pQCT indicators of radius and tibia bone mass, mineralization, design and strength as determined variables, and age or time since menopause (TMP), body mass, bone length and regional muscles’ areas as selected determinant factors, in Caucasian, physically active, untrained healthy men and pre- and post-menopausal women. In men and pre-menopausal women, the strongest influences were exerted by muscle area on radial features and by both muscle area and bone length on the tibia. Only for women, was body mass a significant factor for tibia traits. In men and pre-menopausal women, mass/design/strength indicators depended more strongly on the selected determinants than the cortical vBMD did (p<0.01-0.001 vs n.s.), regardless of age. However, TMP was an additional factor for both bones (p<0.01-0.001). The selected mechanical factors (muscle size, bone lengths) were more relevant than age/TMP or body weight to the development of allometrically-related bone properties (mass/design/strength), yet not to bone tissue “quality” (cortical vBMD), suggesting a determinant, rather than determined role for cortical stiffness. While the mechanical impacts of muscles and bone levers on bone structure were comparable in men and pre-menopausal women, TMP exerted a stronger impact than allometric or mechanical factors on bone properties, including cortical vBMD.     

Does Vitamin D affects changes in volumetric bone mineral density and architecture in postmenopausal women after conservatively treated distal radius fractures?

Objective:We examined the role of vitamin D on volumetric bone mineral density (vBMD) and architecture during the first week’s post-fracture in postmenopausal women (PMW) with distal radial fractures (DRF) treated conservatively using peripheral Quantitative Computed Tomography (pQCT).Methods:Patients were classified into 2 groups according to initial median 25(OH)D level; Group A (25(OH)D ≥15 ng/ml) and group B (25(OH)D <15 ng/ml). All patients were followed for 12 weeks at three visits: baseline, 6 weeks and 12 weeks post fracture. pQCT was performed at baseline in fractured and contralateral non-fractured radius and at 6^th and 12^th week on the fractured side.Results:39 patients completed the protocol. Mean 25(OH)D levels were 15.60±7.35 ng/ml (3.5-41.7). Trabecular (trab) bone mineral content (BMC) and trabvBMD increased at 6 wk. vs. baseline (p<0.001). Cortical BMC, cortvBMD and cross- sectional area (CSA) progressively decreased (p<0.001) during the 12 weeks. There was no interaction between baseline 25(OH)D levels and changes in trabecular and cortical BMC, vBMD and CSA. Advanced age and higher CTX and P1NP were associated with higher cortical bone loss.Conclusion:Vitamin D deficiency does not affect the early architectural changes after a DRF. Advanced age and higher bone remodeling were associated with higher cortical bone loss, probably related to immobilization and independent of vitamin D levels.     

Electromagnetic effects on forearm disuse osteopenia: a randomized, double-blind, sham-controlled study

A randomized, double‐blind, sham‐controlled, feasibility and dosing study was undertaken to determine if a common pulsing electromagnetic field (PEMF) treatment could moderate the substantial osteopenia that occurs after forearm disuse. Ninety‐nine subjects were randomized into four groups after a distal radius fracture, or carpal surgery requiring immobilization in a cast. Active or identical sham PEMF transducers were worn on the distal forearm for 1, 2, or 4 h/day for 8 weeks starting after cast removal (“baseline”) when bone density continues to decline. Bone mineral density (BMD) and bone geometry were measured in the distal forearm by dual energy X‐ray absorptiometry (DXA) and peripheral quantitative computed tomography (pQCT) at entry (“baseline”) and 8, 16, and 24 weeks later. Significant average BMD losses after baseline were observed in the affected forearm at all time points (5–7% distally and 3–4% for the radius/ulna shaft). However, after adjusting for age, gender, and baseline BMD there was no evidence of a positive effect of active versus sham PEMF treatment on bone loss by DXA or pQCT for subjects completing all visits (n = 82, ～20 per group) and for an intent‐to‐treat analysis (n = 99). Regardless of PEMF exposure, serum bone‐specific alkaline phosphatase (BSAP) was normal at baseline and 8 weeks, while serum c‐terminal collagen teleopeptide (CTX‐1) was markedly elevated at baseline and less so at 8 weeks. Although there was substantial variability in disuse osteopenia, these results suggested that the particular PEMF waveform and durations applied did not affect the continuing substantial disuse bone loss in these subjects. Bioelectromagnetics 32:273–282, 2011. © 2010 Wiley‐Liss, Inc.     

Peripheral quantitative computed tomography of the lower leg in children and adolescents: bone densities,cross-sectional sizes and muscle distribution reference data

Objectives:Peripheral quantitative computed tomography is utilised in increasing numbers of paediatric studies, however, very little is known about the reference limits for pQCT tibia measurements. The purpose of this study was to establish country-specific reference data for bone densities, cross-sectional sizes, strength and regional muscle distribution measured by pQCT in children and adolescents.Methods:Stratec XCT 2000L apparatus was used. The measurement sites were 4%, 14%, 38% and 66% of the tibia length. The study group consisted of 222 participants (103 girls) aged 4,3-19,4 yrs. ANCOVA was used to assess the main determinants of pQCT outcomes. The LMS method was used to fit the percentile curves for each outcomes.Results:Weight and age were the main determinants for most of the pQCT outcomes. Smoothed percentile curves were developed by age and by height for both sexes.Conclusion:In this study we present reference data for bone densities, cross-sectional size and strength as well as for regional muscle distribution measured by pQCT at certain sites of the lower leg to allow simple calculation of reliable Z scores.     

Cross sectional properties of the human radial tuberosity

This study examines the cross sectional shape and biomechanical properties of the radial bone shaft at mid-radial tuberosity (RT) musculoskeletal marker (MSM). This information will provide insight into factors affecting bone modelling at muscle insertions. Radial shaft cross-sectional properties at radial tuberosity area (RTA) have not been previously studied. The material consists of 54 male skeletons derived from autopsies performed during the 1920s and 1930s and housed at the Central Natural History Museum, University of Helsinki. The age, sex and occupation of these individuals are known. We applied a pQCT (peripheral quantitative computed tomography) scan on the mid-site of the radial tuberosity to investigate the cross-sectional shape, the bone mineral density (BMD) and biomechanical properties. Our results indicate that bone modelling does not produce increased wall thickness or BMD at the RT site. Additionally we noticed that aging and physical activity affect the biomechanics of the RT and that the bone distribution at mid-RT is adapted to accommodate the biceps brachii muscle pull. We also found a clear association between RTA and biomechanical properties of mid-RT cross section.     

Vitamin D Binding Protein Genotype Is Associated with Serum 25-Hydroxyvitamin D and PTH Concentrations,as Well as Bone Health in Children and Adolescents in Finland

Vitamin D binding protein (DBP)/group-specific component (Gc), correlates positively with serum vitamin D metabolites, and phenotype influences serum 25-hydroxyvitamin D (S-25(OH)D) concentration. The protein isoform has been associated with decreased bone mineral density (BMD) and increased fracture risk. We examined the role of GC genotypes in S-25(OH)D status and BMD in 231 Finnish children and adolescents aged 7−19 yr. BMD was measured with DXA from lumbar spine (LS), total hip, and whole body, and for 175 subjects, radial volumetric BMD was measured with pQCT. Background characteristic and total dietary intakes of vitamin D and calcium were collected. The concentrations of 25(OH)D, parathyroid hormone (PTH), calcium and other markers of calcium homeostasis were determined from blood and urine. Genotyping was based on single-nucleotide polymorphism (rs4588) in the GC gene. The genotype distribution was: GC 1/1 68%, GC 1/2 26% and GC 2/2 6%. A significant difference emerged in 25(OH)D and PTH concentrations between the genotypes, (p = 0.001 and 0.028 respectively, ANCOVA). There was also a linear trend in: Gc 2/2 had the lowest 25(OH)D and PTH concentrations (p = 0.025 and 0.012, respectively). Total hip bone mineral content was associated with GC genotype (BMC) (p = 0.05, ANCOVA) in boys. In regression analysis, after adjusting for relevant covariates, GC genotype was associated with LS BMC and strength and strain index (SSI) Z-score in both genders, and LS BMD in boys. In conclusion, the present study demonstrates the association between GC genotypes and S-25(OH)D and PTH concentrations. The results show the influence of DBP genetic variation on bone mass accrual in adolescence.     

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-3beta,17beta-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.     

Reduced bone mineral density and radial bone growth in young rabbits treated with dexamethasone eye drops

OBJECTIVE: To investigate the effect of dexamethasone eye drops on bone metabolism in newborn rabbits. METHODS: Thirty-four 3-week-old rabbits had unilateral clear lens extraction and were randomized into three groups. Postoperatively, group 1 received high-dose and group 2 low-dose dexamethasone eye drops (average doses 0.27 and 0.10 mg/kg body weight/day, respectively). These rabbits also received a postoperative subconjunctival injection of betamethasone. Group 3 (control) received vehicle eye drops only. After 8 weeks of treatment, all animals were killed and the left femurs were isolated and subjected to peripheral quantitative computerized tomography (pQCT) and dual X-ray absorptiometry (DXA) analyses. RESULTS: DXA showed that rabbits treated with either a high or low dose of dexamethasone eye drops had significantly reduced areal bone mineral density (BMD), area and total bone mineral content (BMC) of the femur. Measurements with pQCT demonstrated a dose-dependent reduction in cortical BMC, cortical volumetric BMD and cortical area. These effects were associated with an inhibition of radial femur growth, cortical thickness and periosteal and endosteal circumferences. CONCLUSION: Dexamethasone eye drops have systemic effects affecting several bone parameters in young rabbits. Any long-term systemic effects of ocular glucocorticoids need to be further studied.     

A cybernetic approach to osteoporosis in anorexia nervosa

A group of 25 female individuals, who had been admitted to the University Hospital with the diagnosis of anorexia nervosa (AN) 3 to 10 years before, was seen for a follow-up visit in the hospital. These women got a psychiatric exploration to detect a present eating disorder. Moreover, parameters of the muskuloskeletal interaction were determined on the non-dominant forearm. Bone mineral content (BMC) of the radius was measured by pQCT and maximal grip force was evaluated by the use of a dynamometer. Eating disorders were present in 12 females. The mean of BMC standard deviation (SD) score was significantly reduced in comparison with reference values. Furthermore, the mean of BMC SD score was also significantly lower than the mean of grip force in SD score. These results gave the suggestion that the adaptation of bone mass to biomechanical forces is disturbed in AN. The linear regression analyses between the parameters grip force and BMC were compared between the study and the reference group. The comparison delivered a significantly lower constant in the regression equation of the study group. This result can be interpreted on the background of the mechanostat theory. The affection with an eating disorder decreases the set point in the feedback loop of bone modeling. The results offer for the first time the possibility to analyse osteoporosis in anorexic females under the paradigm of muskuloskeletal interaction.