Claus-Christian Glüer

Accuracy of bioelectrical impedance consumer devices for measurement of body composition in comparison to whole body magnetic resonance imaging and dual X-ray absorptiometry.

Objective: To compare body composition determined by bioelectrical impedance (BIA) consumer devices against criterion estimates determined by whole body magnetic resonance imaging (MRI) and dual energy X-ray absorptiometry (DXA) in healthy normal weight, overweight and obese adults. Methods: In 106 adults (54 females, 52 males, age 54.2 ± 16.1 years, BMI 25.8 ± 4.4 kg/m2) fat mass (FM), skeletal muscle mass (SM), total body bone-free lean mass (TBBLM), and level of visceral fat mass (VF) were estimated by 3 single-frequency bipedal (foot-to-foot) and one tretrapolar BIA device, and compared to body composition measured by MRI and DXA. Bland-Altman and simple linear regression analyses were used to determine agreement between methods. Results: %FMDXA, SMMRI or TBBLMDXA showed good relative and absolute agreement with two bipolar and one tetrapolar instrument (r2 = 0.92–0.96; all p < 0.001; mean bias <1.5 %FM and <1 kg SM or TBBLM) and less relative and absolute agreement for another bipolar device (r2 = 0.82 and 0.84, mean bias ∼3 %FM and ∼3 kg SM). The 95% limits of agreement (bias ± 2 SD) were narrowest for the tetrapolar device (–6.59 to 4.61 %FM and –4.62 to 4.74 kg SM) and widest for bipolar instruments (up to –14.54 to 8.58 %FM and –9.52 to 3.92 kg SM). Systematic biases for %FM were found for all bipedal devices, but not for the tetrapolar instrument. Conclusion: Because of the lower agreement between foot-to-foot BIA and DXA or MRI for the assessment of body composition in individuals, tetrapolar electrode arrangement should be preferred for individual or public use. Bipolar devices provide accurate results for field studies with group estimation.

Mechanical strength of the thoracolumbar spine in the elderly: prediction from in situ dual-energy X-ray absorptiometry, quantitative computed tomography (QCT), upper and lower limb peripheral QCT, and quantitative ultrasound.

The objective of this study was to compare the ability of clinically available densitometric measurement techniques for evaluating vertebral strength in elderly individuals. Measurements were related to experimentally determined failure strength in the thoracic and lumbar spine. In 127 specimens (82 women and 45 men, age 80 +/- 10 years), dual-energy X-ray absorptiometry (DXA) was performed at the lumbar spine, femur, radius, and total body, and peripheral-quantitative computed tomography (pQCT) at the distal radius, tibia, and femur under in situ conditions with intact soft tissues. Spinal QCT and calcaneal ultrasound parameters were performed ex situ in degassed specimens. Mechanical failure loads of thoracic vertebrae 6 and 10 (T-6 and -10), and lumbar vertebra 3 (L-3) were determined in axial compression on functional three-segment units. In situ anteroposterior DXA and QCT of the lumbar spine explained approximately 65% of the variability of thoracolumbar failure. A combination of cortical and trabecular density (QCT) provided the best prediction in the lumbar spine. However, this was not the case in the thoracic spine, for which lumbar cortical density (QCT) and DXA provided significantly better estimates than trabecular density (QCT). pQCT was significantly less correlated with the strength of lumbar and thoracic vertebrae (r(2) = 40%), but was equivalent to femoral or radial DXA. pQCT measurements in the lower limb showed no advantage over those at the distal radius. Ultrasound explained approximately 25% of the variability of vertebral failure strength and added independent information to spinal QCT, but not to spinal DXA. These experimental results advocate site-specific assessment of vertebral strength by either spinal DXA or QCT.

Contribution of individual organ mass loss to weight loss–associated decline in resting energy expenditure

BACKGROUND Weight loss leads to reduced resting energy expenditure (REE) independent of fat-free mass (FFM) and fat mass (FM) loss, but the effect of changes in FFM composition is unclear. OBJECTIVE We hypothesized that a decrease in REE adjusted for FFM with weight loss would be partly explained by a disproportionate loss in the high metabolic activity component of FFM. DESIGN Forty-five overweight and obese women [body mass index (in kg/m(2)): 28.7-46.8] aged 22-46 y followed a low-calorie diet for 12.7 +/- 2.2 wk. Body composition was measured by magnetic resonance imaging, dual-energy X-ray absorptiometry, and a 4-compartment model. REE measured by indirect calorimetry (REEm) was compared with REE calculated from detailed body-composition analysis (REEc) by using specific organ metabolic rates (ie, organ REE/mass). RESULTS Weight loss was 9.5 +/- 3.4 kg (8.0 +/- 2.9 kg FM and 1.5 +/- 3.1 kg FFM). Decreases in REE (-8%), free triiodothyronine concentrations (-8%), muscle (-3%), heart (-5%), liver (-4%), and kidney mass (-6%) were observed (all P < 0.05). Relative loss in organ mass was significantly higher (P < 0.01) than was the change in low metabolically active FFM components (muscle, bone, and residual mass). After weight loss, REEm - REEc decreased from 0.24 +/- 0.58 to 0.01 +/- 0.44 MJ/d (P = 0.01) and correlated with the decrease in free triiodothyronine concentrations (r = 0.33, P < 0.05). Women with high adaptive thermogenesis (defined as REEm - REEc < -0.17 MJ/d) had less weight loss and conserved FFM, liver, and kidney mass. CONCLUSIONS After weight loss, almost 50% of the decrease in REEm was explained by losses in FFM and FM. The variability in REEm explained by body composition increased to 60% by also considering the weight of individual organs.

High resolution quantitative computed tomography-based assessment of trabecular microstructure and strength estimates by finite-element analysis of the spine, but not DXA, reflects vertebral fracture status in men with glucocorticoid-induced osteoporosis

High-resolution quantitative computed tomography (HRQCT)-based analysis of spinal bone density and microstructure, finite element analysis (FEA), and DXA were used to investigate the vertebral bone status of men with glucocorticoid-induced osteoporosis (GIO). DXA of L1-L3 and total hip, QCT of L1-L3, and HRQCT of T12 were available for 73 men (54.6±14.0years) with GIO. Prevalent vertebral fracture status was evaluated on radiographs using a semi-quantitative (SQ) score (normal=0 to severe fracture=3), and the spinal deformity index (SDI) score (sum of SQ scores of T4 to L4 vertebrae). Thirty-one (42.4%) subjects had prevalent vertebral fractures. Cortical BMD (Ct.BMD) and thickness (Ct.Th), trabecular BMD (Tb.BMD), apparent trabecular bone volume fraction (app.BV/TV), and apparent trabecular separation (app.Tb.Sp) were analyzed by HRQCT. Stiffness and strength of T12 were computed by HRQCT-based nonlinear FEA for axial compression, anterior bending and axial torsion. In logistic regressions adjusted for age, glucocorticoid dose and osteoporosis treatment, Tb.BMD was most closely associated with vertebral fracture status (standardized odds ratio [sOR]: Tb.BMD T12: 4.05 [95% CI: 1.8-9.0], Tb.BMD L1-L3: 3.95 [1.8-8.9]). Strength divided by cross-sectional area for axial compression showed the most significant association with spine fracture status among FEA variables (2.56 [1.29-5.07]). SDI was best predicted by a microstructural model using Ct.Th and app.Tb.Sp (r(2)=0.57, p<0.001). Spinal or hip DXA measurements did not show significant associations with fracture status or severity. In this cross-sectional study of males with GIO, QCT, HRQCT-based measurements and FEA variables were superior to DXA in discriminating between patients of differing prevalent vertebral fracture status. A microstructural model combining aspects of cortical and trabecular bone reflected fracture severity most accurately.

What is the best reference site for a single MRI slice to assess whole-body skeletal muscle and adipose tissue volumes in healthy adults?

BACKGROUND Whole-body magnetic resonance imaging (MRI) is the gold standard for the assessment of skeletal muscle (SM) and adipose tissue volumes. It is unclear whether single-slice estimates can replace whole-body data. OBJECTIVE We evaluated the accuracy of the best single lumbar and midthigh MRI slice to assess whole-body SM, visceral adipose tissue (VAT), and subcutaneous adipose tissue (SAT). DESIGN Whole-body MRI was performed in 142 healthy adults aged 19-65 y [mean ± SD age: 37.0 ± 11.8 y; BMI (in kg/m(2)): 25.3 ± 5.9]. Single slices were taken at lumbar vertebrae L1-L5 plus intervertebral discs and the thigh (midthigh, 10 cm distally from the midthigh, and 10 cm proximally from the midthigh). The value of single-slice areas was also tested in a longitudinal study on 48 healthy volunteers during weight loss (8.2 ± 5.2 kg). RESULTS Cross-sectionally, all SM and adipose tissue single-slice areas correlated with total tissue volumes (P < 0.01). Because of the close associations between L3 areas and corresponding tissue volumes (r = 0.832-0.986, P < 0.01), this location was identified as the reference to estimate SM and adipose tissue in both sexes. SM, SAT, and VAT areas at L3 explained most of the variance of total tissue volumes (69-97%, with SEs of estimation of 1.96 and 2.03 L for SM, 0.23 and 0.61 L for VAT, and 4.44 and 2.47 L for SAT for men and women, respectively. There was no major effect on the explained variance compared with that for optimal slices. For SM, the optimal slice area was shown at midthigh. With weight-loss changes in total SM, VAT, and SAT, volumes were significantly different from those at baseline (SM changes: -2.8 ± 2.9 L; VAT changes: -0.7 ± 1.0 L; SAT changes: -5.1 ± 6.0 L). The area at L3 reflected changes in total VAT and SAT. To assess changes in total SM volumes, areas at midthigh showed the best evidence. CONCLUSION In both sexes, a single MRI scan at the level of L3 is the best compromise site to assess total tissue volumes of SM, VAT, and SAT. By contrast, L3 does not predict changes in tissue components. This trial was registered at clinicaltrials.gov as NCT01737034.

Administration of romosozumab improves vertebral trabecular and cortical bone as assessed with quantitative computed tomography and finite element analysis

Romosozumab inhibits sclerostin, thereby increasing bone formation and decreasing bone resorption. This dual effect of romosozumab leads to rapid and substantial increases in areal bone mineral density (aBMD) as measured by dual-energy X-ray absorptiometry (DXA). In a phase 1b, randomized, double-blind, placebo-controlled study, romosozumab or placebo was administered to 32 women and 16 men with low aBMD for 3 months, with a further 3-month follow-up: women received six doses of 1 or 2mg/kg every 2 weeks (Q2W) or three doses of 2 or 3mg/kg every 4 weeks (Q4W); men received 1mg/kg Q2W or 3mg/kg Q4W. Quantitative computed tomography (QCT) scans at lumbar (L1-2) vertebrae and high-resolution QCT (HR-QCT) scans at thoracic vertebra (T12) were analyzed in a subset of subjects at baseline, month 3, and month 6. The QCT subset included 24 romosozumab and 9 placebo subjects and the HR-QCT subset included 11 romosozumab and 3 placebo subjects. The analyses pooled the romosozumab doses. Linear finite element modeling of bone stiffness was performed. Compared with placebo, the romosozumab group showed improvements at month 3 for trabecular BMD by QCT and HR-QCT, HR-QCT trabecular bone volume fraction (BV/TV) and separation, density-weighted cortical thickness, and QCT stiffness (all p<0.05). At month 6, improvements from baseline were observed in QCT trabecular BMD and stiffness, and in HR-QCT BMD, trabecular BV/TV and separation, density-weighted cortical thickness, and stiffness in the romosozumab group (all p<0.05 compared with placebo). The mean (SE) increase in HR-QCT stiffness with romosozumab from baseline was 26.9% ± 6.8% and 35.0% ±6.8% at months 3 and 6, respectively; subjects administered placebo had changes of -2.7% ± 13.4% and -6.4% ± 13.4%, respectively. In conclusion, romosozumab administered for 3 months resulted in rapid and large improvements in trabecular and cortical bone mass and structure as well as whole bone stiffness, which continued 3 months after the last romosozumab dose.

Bone defect regeneration and cortical bone parameters of type 2 diabetic rats are improved by insulin therapy.

Zucker Diabetic Fatty (ZDF) rats represent an established model of type 2 diabetes mellitus (T2DM) and display several features of human diabetic bone disease, including impaired osteoblast function, decreased bone strength, and delayed bone healing. Here, we determined whether glycemic control by insulin treatment prevents skeletal complications associated with diabetes. Subcritical femur defects were created in diabetic (fa/fa) and non-diabetic (+/+) ZDF rats. Diabetic rats were treated once daily with long-lasting insulin glargin for 12weeks for glycemic control. Insulin treatment successfully maintained serum levels of glycated hemoglobin, while untreated diabetic rats showed a 2-fold increase. Trabecular and cortical bone mass measured by μCT were decreased in diabetic rats. Insulin treatment increased bone mass of the cortical, but not of the trabecular bone compartment. Dynamic histomorphometry revealed a lower bone formation rate at the trabecular and periosteal cortical bone in diabetic animals and decreased serum procollagen type 1 N-terminal propeptide (P1NP, -49%) levels. Insulin treatment partially improved these parameters. In T2DM, serum levels of tartrate-resistant acid phosphatase (TRAP, +32%) and C-terminal telopeptide (CTX, +49%) were increased. Insulin treatment further elevated TRAP levels, but did not affect CTX levels. While diabetes impaired bone defect healing, glycemic control with insulin fully reversed these negative effects. In conclusion, insulin treatment reversed the adverse effects of T2DM on bone defect regeneration in rats mainly by improving osteoblast function and bone formation. This article is part of a Special Issue entitled Bone and diabetes.

Apolipoprotein E (APOE) genotype regulates body weight and fatty acid utilization-Studies in gene-targeted replacement mice

SCOPE Of the three human apolipoprotein E (APOE) alleles, the ε3 allele is most common, which may be a result of adaptive evolution. In this study, we investigated whether the APOE genotype affects body weight and energy metabolism through regulation of fatty acid utilization. METHODS AND RESULTS Targeted replacement mice expressing the human APOE3 were significantly heavier on low- and high-fat diets compared to APOE4 mice. Particularly on high-fat feeding, food intake and dietary energy yields as well as fat mass were increased in APOE3 mice. Fatty acid mobilization determined as activation of adipose tissue lipase and fasting plasma nonesterified fatty acid levels were significantly lower in APOE3 than APOE4 mice. APOE4 mice, in contrast, exhibited higher expression of proteins involved in fatty acid oxidation in skeletal muscle. CONCLUSION Our data suggest that APOE3 is associated with the potential to more efficiently harvest dietary energy and to deposit fat in adipose tissue, while APOE4 carriers tend to increase fatty acid mobilization and utilization as fuel substrates especially under high-fat intake. The different handling of dietary energy may have contributed to the evolution and worldwide distribution of the ε3 allele.

Quantitativer Ultraschall Status 1999

ZusammenfassungQuantitative Ultraschall(QUS)-Verfahren haben in den vergangenen Jahren zunehmende Verbreitung in der Osteoporosediagnostik gefunden. Die Entwicklung der Technologie hat sich weiterhin beschleunigt, so daß nun eine Vielzahl unterschiedlicher Geräte auf dem Markt ist. Eine ausgewogene Bewertung der Verfahren muß 2 Aspekten Rechnung tragen: Es gibt unterschiedliche Einsatzbereiche und unterschiedliche QUS-Verfahren und -Geräte. Bezüglich der Einsatzbereiche ist die Frakturrisikoabschätzung bei Osteoporose das primäre Anwendungsgebiet, während für Verlaufskontrollen und Diagnose weitere Fortschritte bzw. Studien erforderlich sind. Bezüglich der Verfahren müssen die Unterschiede zwischen den Meßparametern Schallgeschwindigkeit (SOS) und Breitband Ultraschall Abschwächung (BUA), den verschiedenen Meßorten und den verschiedenen Technologien in Rechnung gestellt werden. Zudem sind einige Geräte sehr gut validiert, während neuere Geräte naturgemäß zwar eine modernere Technologie aufweisen, die sich aber gegenüber den älteren, bewährten Geräten erst noch bewähren muß. Gleich wie die Wahl des Geräts ausfällt, es müssen regelmäßig adäquate Qualitätssicherungsmaßnahmen durchgeführt werden, und der Nutzer muß um die allgemeinen und gerätespezifischen Grenzen des Verfahrens wissen. Richtig eingesetzt, können QUS-Geräte für die Einschätzung der Osteoporose eine wesentliche Rolle spielen.SummaryIn recent years Quantitative Ultrasound (QUS) approaches have increasingly been used for the assessment of osteoporosis. The development of new technologies has accelerated, and today a number of different devices are commercially available. For a balanced evaluation of the approaches one needs to recognise two issues: There are different applications for QUS, and there are different QUS approaches and devices. Regarding the applications, today the main area for use of QUS approaches is the assessment of a fracture risk. For use in monitoring and diagnosis, further advances and studies are required. Regarding the various approaches, one needs to recognise the differences between the measurement parameters Speed Of Sound (SOS) and Broadband Ultrasound Attenuation (BUA), the different measurement sites and the different technologies employed. Moreover, some of the earlier devices are very well validated whereas newer machines may feature more advanced technology – which, however, needs to be tested and validated. Whatever the choice of a device will be, adequate and regularly performed measures for quality assurance and in-depth knowledge on the general and device specific limitations of the approach are of substantial importance. When used appropriately, QUS devices can play an important role in the assessment of osteoporosis.

Gender-Specific Associations in Age-Related Changes in Resting Energy Expenditure (REE) and MRI Measured Body Composition in Healthy Caucasians

BACKGROUND The effect of gender as well as gender-specific changes of fat free mass (FFM) and its metabolic active components (muscle mass and organ masses [OMs]) and fat mass (FM) on age-related changes in resting energy expenditure (REE) are not well defined. We hypothesized that there are gender differences in (1) the age-specific onset of changes in detailed body composition (2); the onset of changes in body composition-REE associations with age. METHODS Using a cross-sectional magnetic resonance imaging database of 448 Caucasian participants (females and males) with comprehensive data on skeletal muscle (SM) mass, adipose tissue (AT), OMs, and REE. RESULTS We observed gender-specific differences in the onset of age-related changes in metabolic active components and REE. Declines in body composition and REE started earlier in females than in males for SM (29.4 vs 39.6 years), AT (38.2 vs 49.9 years), OM (34.7 vs 45.7 years), and REE (31.9 vs 36.8 years). The age-related decrease of AT was significantly higher in females than in males (-5.69kg/decade vs -0.59kg/decade). In females adjusted REEmFFM&FM (resting energy expenditure measured adjusted for FFM and FM) and REEmSM/OM/AT (resting energy expenditure measured adjusted for skeletal muscle and organ mass and adipose tissue) decreased by -145 kJ/d/decade and -604.8 kJ/d/ decade after the age of 35.2 respectively 34.3 years. SM was main determinant of REEm in females (R (2) = .67) and males (R (2) = .66) with remaining variance mainly explained by kidney mass (R (2) = .07) in females and liver mass (R (2) = .09) in males. CONCLUSION We concluded that gender affects the age-related changes in body composition as well as changes in body composition-REE relationship. This trial was registered at linicaltrials.gov as NCT01737034.