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Biomedical subjects

Felix Eckstein

Publications and source records attributed to Felix Eckstein.

At least 19 recordsLinked to original sources
PubMed2004

Longitudinal in vivo effects of growth hormone overexpression on bone in transgenic mice.

UNLABELLED: In this study we examined the effect of systemic overexpression of GH on bone in transgenic mice longitudinally in vivo over a period of 9 months. We observed substantially increased BMC in GH transgenic mice and a significant reduction in serum osteocalcin. GH effects on bone were strongly dependent on gender and developmental stage. INTRODUCTION: State-of-the-art bone marker and microimaging technology was applied in this longitudinal study to examine bone metabolism, BMC, bone density, and cortical bone structure over the life span of growth hormone (GH) transgenic (tg) mice. MATERIALS AND METHODS: Thirty-eight mice from four genetic groups (male, female, tg, and controls) were examined with DXA, and their femur and tibia were examined with peripheral QCT (pQCT). Osteocalcin (formation) and collagen cross-links (resorption) from serum and urine were also measured at postnatal weeks 3, 6, 9, 12, 18, 26, and 38. RESULTS: GH tg mice displayed a significant increase in body weight (up to 50%) and BMC (up to 90%), but serum osteocalcin was significantly reduced compared with controls. GH tg females (but not males) displayed increased trabecular density over controls up to week 12. In contrast, male (but not female) GH tg mice displayed a higher cortical cross-sectional area than controls. Cortical density was significantly lower in both male and female GH tg mice compared with control mice. CONCLUSIONS: The increase in BMC in GH tg mice is associated with reduced serum osteocalcin levels, indicating that bone turnover may be lower than in the control mice. On a structural level, bone responds to GH excess in a gender-specific manner, with alterations varying substantially between different developmental stages.

Amino Acids↗
PubMed2004

Quantitative assessment of cartilage status in osteoarthritis by quantitative magnetic resonance imaging: technical validation for use in analysis of cartilage volume and further morphologic parameters.

OBJECTIVE: Quantitative diagnostic tools for osteoarthritis (OA) are important for evaluating the treatment response to structure-modifying drugs. This study was undertaken to test the technical validity (accuracy) of quantitative magnetic resonance imaging (qMRI) for reliable determination of the total bone interface area, percentage of cartilaginous (denuded) joint surface area, and cartilage thickness in OA. METHODS: High-resolution MRIs of femorotibial and patellar cartilage were acquired in 21 patients prior to total knee arthroplasty, using a T1-weighted gradient-echo sequence with water excitation. After segmentation of original bone interface areas (before disease onset) and the actual cartilage layer, the percentages of cartilaginous joint surface area, cartilage thickness, and cartilage volume were determined using proprietary software. During surgery, the patella and the medial and lateral tibia were resected. Results obtained with qMRI were compared with those obtained by direct image analysis of surface area, cartilage thickness, and cartilage volume of the surgically removed tissue. RESULTS: Pairwise differences between results obtained with qMRI and morphologic analysis were +/-4.6% for percentage of cartilaginous surface area, +/-8.9% for cartilage thickness, and +/-9.1% for cartilage volume. Correlation coefficients ranged from 0.92 (thickness) to 0.98 (volume). CONCLUSION: Quantitative MRI permits technically accurate and differential assessment of increases in eroded joint surface area and reductions in cartilage thickness in OA. The surrogate validity of these parameters requires testing in longitudinal studies. These parameters may be advantageous over determination of cartilage volume alone when diagnosing OA, exploring its progression, or testing responsiveness to new therapies.

Aged↗
PubMed2004

Determinants and heterogeneity of mechanical competence throughout the thoracolumbar spine of elderly women and men.

Vertebral fractures represent the hallmark of osteoporosis. Here, we test the hypotheses that (sub)cortical bone strength and density predict failure better than trabecular core strength and density, and that elderly women display lower failure stress of thoracic vertebrae than men. We examined the vertebral bodies T3 to L5 in 39 spines from elderly donors (23 women; 16 men; age 79 +/- 11 years). Peripheral quantitative computed tomography was used to measure total, trabecular, and (sub)cortical bone density. Mechanical tests were performed in functional spinal units, planoparallel sections of vertebrae, trabecular cores, and (sub)cortical ring specimens. The failure stress decreased with descending vertebral level. Failure stress was highest for the (sub)cortical rings and planoparallel sections and lowest for the trabecular core. The failure stress did not differ significantly between men and women. Mechanical strength of the functional unit was more strongly correlated with the strength of the (sub)cortical ring (r = 0.78) than with that of the trabecular core (r = 0.62). However, total density was more highly correlated with mechanical strength of the same and remote vertebrae (r = 0.63) than trabecular (r = 0.50) or (sub)cortical density (r = 0.36), respectively. The results show that vertebral strength is similar in elderly women and men. Strength of (sub)cortical bone provides significantly better prediction of strength of functional spinal units than that of the trabecular core. However, total density predicts functional segment failure stress with higher accuracy than (sub)cortical or trabecular density and is thus recommended for predicting fracture strength clinically.

Aged↗
PubMed2004

Strength prediction of the distal radius by bone densitometry--evaluation using biomechanical tests.

Osteoporotic fractures represent an important medical problem as they are often early predictors of future fractures at other skeletal sites. The distal radius is one such fracture site. To determine the individual's risk of fracture, different measurement techniques have been developed. These methods differ in physical background, measurement site, output parameters, and cost. If correctly applied, biomechanical testing can be an efficient tool for the preclinical evaluation of these techniques. With biomechanical testing it is possible to determine the structural strength of bone which can then be correlated with various densitometric parameters. Here we will review experimental work performed in this context. Biomechanical testing conditions vary considerably from study to study with 3-point bending (shaft), axial compression (metaphysis), and fall simulations being some of the techniques used. Experimental evidence suggests that site-specific osteodensitometric measurements can predict the mechanical strength of the distal radius with moderate to high accuracy, but that measurements at remote sites display considerably lower predictive value. Geometry-based parameters of cortical bone are also good predictors, but have not been shown to offer significant advantage over measurement of bone mass. Some (but not all) studies have found that quantitative ultrasound and microstructural parameters contribute significant additional information to bone mass measurement. The most accurate prediction of distal radius fractures, however, appears to be (patient-specific) microstructural finite element modeling.

Animals↗
PubMed2004

Measuring cartilage morphology with quantitative magnetic resonance imaging.

Magnetic resonance imaging (MRI) is a three-dimensional imaging technique with unparalleled ability to delineate articular cartilage morphology in health and disease. In this article we will review work on the assessment of cartilage morphology with quantitative magnetic resonance imaging and its relevance to the study of cartilage anatomy, physiology, deformation, disease status, disease progression, and response to treatment. The review outlines available pulse sequences and techniques for segmentation and morphological analysis of cartilage morphology. It addresses the accuracy (validity) and precision (reproducibility) of these techniques and summarizes studies on cartilage deformation in intact joints. This article will also review work on determinants and functional adaptation of cartilage morphology and describe changes seen in osteoarthritis. We conclude that fat-suppressed or water excitation gradient-echo magnetic resonance sequences and state-of-the-art digital image analysis techniques display high accuracy and adequate precision for quantitative assessment of cartilage morphology. This renders these techniques powerful and promising tools for cartilage and osteoarthritis research.

Cartilage, Articular↗
PubMed2004

Toward imaging biomarkers for osteoarthritis.

Many new therapeutic strategies have been and are being developed to correct, prevent, or slow the progression of osteoarthritis. Our ability to evaluate the efficacy of these techniques, or to determine the situations for which they might provide the most benefit, critically depends on diagnostic measures that can serve as proxies for the present or predicted state of the cartilage. Many of the magnetic resonance imaging techniques that have been emerging over the past decades appear promising in that they have shown technical validity in measuring the morphologic and molecular state of cartilage. With continued development and added insight from pilot clinical studies, these or related methods may soon be in customary use. These techniques are part of a paradigm shift where therapeutic strategies are developed hand-in-hand with diagnostic approaches-a shift that offers the promise of speeding development of effective therapies, and focusing their use in areas where they can be most successful.

Biomarkers↗
PubMed2004

Trabecular bone structure of the distal radius, the calcaneus, and the spine: which site predicts fracture status of the spine best?

RATIONALE AND OBJECTIVES: To compare trabecular bone structure measures obtained in magnetic resonance images of the distal radius and the calcaneus as well as computed tomographic images of the spine versus bone mineral density (BMD) of the spine and the calcaneus in the prediction of osteoporotic spine fracture status. MATERIAL AND METHODS: High-resolution magnetic resonance images of the calcaneus and the distal radius and thin-section computed tomographic images of thoracic and lumbar vertebrae were obtained from 74 cadavers. Structure analysis was performed using parameters analogous to standard histomorphometry. BMD of the spine was determined by using quantitative computed tomography and of the calcaneus by using dual x-ray absorptiometry. Spine radiographs of these cadavers were assessed concerning vertebral deformities. RESULTS: The diagnostic performance in differentiating fracture and nonfracture subjects was highest for structure parameters in the spine and slightly lower for these parameters in the distal radius and for BMD of the spine. CONCLUSION: In this study structure parameters in the spine were best suited to predict the osteoporotic fracture status of the spine.

Absorptiometry, Photon↗
PubMed2004

Noninvasive study of human cartilage structure by MRI.

Magnetic resonance (MR) imaging is a 3D imaging technique that has recently begun to permit direct delineation of cartilage structure. This chapter summarizes current methodology for the morphological (e.g., volume, thickness) and compositional imaging of cartilage using quantitative MR as well as for semiquantitative scoring of cartilage disease. The chapter explains the relevance of MR in identifying disease status, in monitoring disease progression, and in identifying risk factors of osteoarthritis, as well as in evaluating treatment response to so-called structure-modifying osteoarthritis drugs. The practical methodological procedures presented involve the description of how to acquire MR images for structural analysis and the semiquantitative scoring of articular cartilage. We also present a description of image-analysis techniques for cartilage segmentation and characterization of cartilage structure (quantitative outcome parameters, such as volume and thickness) and guidelines for how to test the validity (accuracy), precision (reproducibility), and sensitivity to change of such methodologies inosteoarthritis.

Antirheumatic Agents↗
PubMed2004

Multislice computed tomography of the distal radius metaphysis: relationship of cortical bone structure with gender, age, osteoporotic status, and mechanical competence.

We explore the relationship of region-specific densitometric and geometry-based (cortical) parameters at the distal radial metaphysis with gender, age, and osteoporotic status, using multislice computed tomography (CT). We specifically test the hypothesis that these parameters can improve the prediction of mechanical strength of the distal radius vs bone mass (bone mineral content [BMC]). The BMC was determined in 56 forearm specimens with peripheral dual-energy X-ray absorptiometry (DXA). Trabecular and cortical density and geometric properties of the metaphyseal cortex were determined using multislice CT and proprietary image analysis software. Specimens were tested to failure in a fall simulation, maintaining the integrity of the elbow joint and hand. Women displayed significantly lower failure strength (-34%), BMC (-35%), trabecular density (-26%), and cortical area (-12%) than men. The reduction of trabecular density with age and osteoporotic status was stronger than that of cortical density or thickness. DXA explained approx 50% (r2) of the variability in bone failure loads. This proportion was slightly increased (55%) when adding geometry-based parameters. The study suggests that high-resolution tomographic measurements with current clinical imaging methodology can marginally improve the prediction of mechanical failure strength. Further efforts are required to improve spatial resolution for determining metaphyseal cortical properties clinically.

Aged↗
PubMed2003

Reproducibility and side differences of mechanical tests for determining the structural strength of the proximal femur.

UNLABELLED: In this experimental study, we evaluated the reproducibility error of mechanical strength tests of the proximal femur when simulating a fall on the trochanter. Based on side differences in femoral failure loads in 55 pairs of femora, we estimated the upper limit of the precision error to be 15% for the side impact test, whereas the intersubject variability was >40%. INTRODUCTION: Mechanical tests are commonly used as the gold standard for determining one of the main functions of bones, that is, to provide mechanical strength. However, it is unknown what magnitude of error is associated with these tests. Here we investigate the precision error and side difference of a side impact test of the proximal femur. MATERIALS AND METHODS: BMC was measured using DXA in 54 pairs of femora from donors 79.0 +/- 10.6 years of age. Bones were tested to failure, simulating a fall on the greater trochanter. RESULTS: Failure loads were 3951 +/- 1659N (CV% = 42%) on the right and 3900 +/- 1652N (CV% = 42%) on the left (no significant side difference). The average random difference of femoral BMC was 7 +/- 7% and that of femoral failure loads was 17 +/- 12%. The correlation between BMC and failure load was 79% (r2), but the association between side differences in failure load with those in BMC was only 4%. When confining the analysis to pairs with less than 5% differences in BMC (n = 31), side differences in failure loads were 15 +/- 13%. When correcting failure loads for side differences of BMC, the difference was 16 +/- 15% CONCLUSIONS: These results suggest that the upper limit of the precision error for femoral strength tests is approximately 15% in a side impact configuration. Given the large intersubject variability of failure loads, this test provides an efficient tool for determining the structural strength of the proximal femur in a fall.

Biomechanical Phenomena↗
PubMed2003

Correlation of knee-joint cartilage morphology with muscle cross-sectional areas vs. anthropometric variables.

We tested the hypothesis that muscle cross-sectional areas (MCSAs) are more highly (and independently) correlated with cartilage morphology than are body height and weight, and that the physiological reduction of cartilage thickness with aging is associated with a proportional, age-dependent decrease in MCSAs. In 59 asymptomatic individuals (23-75 years old), morphological parameters of the knee cartilages (volume, thickness, and bone-cartilage interface area), and MCSAs were determined from magnetic resonance imaging (MRI) data. Multiple regression models were used to calculate which proportion of the variability of the normal cartilage morphology can be predicted based on independent variables. MCSAs and body height and weight showed correlation coefficients of +0.66, +0.60, and +0.25, respectively, with knee-joint cartilage volume. The correlation coefficients with cartilage thickness were +0.44, +0.35, and +0.24, respectively. Age accounted for a significant (P<0.01) reduction in cartilage thickness, but there was no proportional change of MCSAs. Approximately 76% of the variability of the knee cartilage volume could be predicted from independent variables in a multiple regression model with MCSAs contributing significant, independent information. In conclusion, we find that MCSAs are more highly correlated with cartilage morphology than are body height and weight. The significant decrease in cartilage volume and thickness with age is not associated with a proportional decrease in MCSAs.

Adult↗
PubMed2003

Femoro-tibial cartilage metrics from coronal MR image data: Technique, test-retest reproducibility, and findings in osteoarthritis.

MRI-based measures of cartilage morphology are being increasingly used as surrogate markers in osteoarthritis. In contrast to other knee joint surfaces, quantitative analysis of the femoral condyles from sagittal MRI suffers from limited precision. The objective, therefore, was to develop a technique for reproducible assessment of femoral cartilage morphology from coronal image data. Coronal MR images (3D T(1)-w FLASHwe) of the knee were obtained in 16 healthy volunteers and in 7 patients with severe osteoarthritis (OA, prior to knee arthroplasty), with repositioning between repeated scans. After segmentation the cartilage volume, thickness, and joint surface areas were quantified in the tibia and in an anatomically defined region of the femoral condyle. Immediate test-retest interscan precision errors (CV%) for femoral cartilage volume were 3.0% (SD = 26 microl) and 3.2% (29 microl) medially and laterally in volunteers, and 3.0% (34 microl) and 7.0% (37 microl) in OA patients. The estimated loss, from cross sectional data, in the patients in the medial femoral condyle (-61%/-4.4 SD) was higher than that in the medial tibia (-45%/-3.1 SD) and compared favorably with precision errors (ratio > 16:1). The technique proposed overcomes some of the problems associated with sagittal scans and thus shows high promise for reliable assessment of femoro-tibial cartilage loss in OA.

Adult↗
PubMed2003

Inhomogeneous cartilage properties enhance superficial interstitial fluid support and frictional properties, but do not provide a homogeneous state of stress.

It has been well established that articular cartilage is compositionally and mechanically inhomogenous through its depth. To what extent this structural inhomogeneity is a prerequisite for appropriate cartilage function and integrity is not well understood. The first hypothesis to be tested in this study was that the depth-dependent inhomogeneity of the cartilage acts to maximize the interstitial fluid load support at the articular surface, to provide efficient frictional and wear properties. The second hypothesis was that the inhomogeneity produces a more homogeneous state of elastic stress in the matrix than would be achieved with uniform properties. We have, for the first time, simultaneously determined depth-dependent tensile and compressive properties of human patellofemoral cartilage from unconfined compression stress relaxation tests. The results show that the tensile modulus increases significantly from 4.1 +/- 1.9 MPa in the deep zone to 8.3 +/- 3.7 MPa at the superficial zone, while the compressive modulus decreases from 0.73 +/- 0.26 MPa to 0.28 +/- 0.16 MPa. The experimental measurements were then implemented with the finite-element method to compute the response of an inhomogeneous and homogeneous cartilage layer to loading. The finite-element models demonstrate that structural inhomogeneity acts to increase the interstitial fluid load support at the articular surface. However, the state of stress, strain, or strain energy density in the solid matrix remained inhomogeneous through the depth of the articular layer, whether or not inhomogeneous material properties were employed. We suggest that increased fluid load support at the articular surface enhances the frictional and wear properties of articular cartilage, but that the tissue is not functionally adapted to produce homogeneous stress, strain, or strain energy density distributions. Interstitial fluid pressurization, but not a homogeneous elastic stress distribution, appears thus to be a prerequisite for the functional and morphological integrity of the cartilage.

Anisotropy↗
PubMed2003

Influence of adducting and abducting muscle forces on the subacromial space width.

PURPOSE: Strengthening of the shoulder depressors is an important component in the treatment of impingement syndrome. However, the quantitative effect of various muscle forces on the width of the subacromial space has never been demonstrated in vivo. Therefore, the purpose of this study was to analyze the influence of adducting and abducting muscle forces on the subacromial space width in healthy volunteers in various arm positions. METHODS: The shoulders of 12 healthy volunteers were imaged with an open MR system at 30 degrees, 60 degrees, 90 degrees, 120 degrees, and 150 degrees of arm elevation under both isometric adducting and abducting muscle activity (15 N). After segmentation and three-dimensional reconstruction of anatomically relevant structures, the minimal spatial acromiohumeral and claviculohumeral distances were quantified. RESULTS: Adducting muscle forces led to a significant increase of the acromiohumeral distance in all arm positions (P < 0.01), varying from 32% (30 degrees ) to 138% (90 degrees ) relative to abducting muscle forces. The claviculohumeral distance showed an increase of 9% (30 degrees ) to 24% (90 degrees ), this increase being also statistically significant at all positions (P < 0.05). During elevation of the arm (30-120 degrees ), the absolute subacromial space width was reduced significantly (P = 0.001) by 30% under isometric contraction of the adductors compared with 53% (P = 0.001) under activation of the abductors. CONCLUSION: This in vivo study shows for the first time that adducting muscle forces lead to a significant increase of the subacromial space width compared with abducting muscle activity. In the future, this technique and data can be used to objectively quantify the effect of physical therapy protocols focused on increasing the depressor effect of adducting muscles in the postoperative and conservative treatment of impingement syndrome of the shoulder.

Acromion↗
PubMed2003

Can novel clinical densitometric techniques replace or improve DXA in predicting bone strength in osteoporosis at the hip and other skeletal sites?

New peripheral techniques are now available for the diagnosis of osteoporosis, but their value in the clinical management of the disease remains controversial. This study tests the hypothesis that peripheral quantitative computed tomography (pQCT) at the distal radius and/or quantitative ultrasound (QUS) at the calcaneus can serve as replacement or improvement of current methodology (QCT and DXA) for predicting bone strength at the hip and other sites. In 126 human cadavers (age, 80.2 +/- 10.4 years), DXA of the femur, spine, and radius and pQCT of the radius were acquired with intact soft tissues. QCT (spine) and QUS (calcaneus) were performed ex situ in degassed specimens. Femoral failure loads were assessed in side impact and vertical loading. Failure loads of the thoracolumbar spine were determined at three levels in compression and those of the radius by simulating a fall. Site-specific DXA explained approximately 55% of the variability in femoral strength, whereas pQCT and QUS displayed a lower association (15-40%). QUS did not provide additional information on mechanical strength of the femur, spine, or radius. All techniques displayed similar capability in predicting a combined index of failure strength at these three sites, with only QUS exhibiting significantly lower associations than other methods. These experimental results suggest that clinical assessment of femoral fracture risk should preferably rely on femoral DXA, whereas DXA, QCT, and pQCT display similar capability of predicting a combined index of mechanical strength at the hip, spine, and radius.

Absorptiometry, Photon↗
PubMed2003

Precision and accuracy of peripheral quantitative computed tomography (pQCT) in the mouse skeleton compared with histology and microcomputed tomography (microCT).

UNLABELLED: pQCT was evaluated for accuracy of phenotypic characterization of mouse bone in vivo. Bones (tibia, femur, spine) of 27 animals were measured ex vivo with pQCT, microCT, and histomorphometry and of 23 mice in vivo (pQCT). pQCT yielded satisfactory in vivo precision and accuracy in skeletal characterization. INTRODUCTION: Important aspects of modern skeletal research depend on the phenotypic characterization of genetically manipulated mice, with some approaches requiring in vivo measurement. Peripheral quantitative computed tomography (pQCT) is applicable in vivo and provides opportunities to determine a large variety of bone parameters. Here we test the ex vivo and in vivo reproducibility of pQCT, and its accuracy in comparison with histomorphometry and microcomputed tomography (microCT). MATERIALS AND METHODS: We examined the tibia, femur, and lumbar spine of 27 mice ex vivo with high-resolution pQCT, using two mouse models (wild-type and ob/ob) with known differences in bone density. Measurements were repeated three times at different days in nine animals. In a second experiment, 23 animals (10 wild-type and 13 bGH transgenic mice) were repeatedly measured in vivo at 12 and 13 weeks of age, respectively. RESULTS: Among metaphyseal sites, the ex vivo precision was highest at the distal femur (RMS CV < 1% for density and < 2% for area). The correlation between density (pQCT) and bone volume fraction (histomorphometry) was r2 = 0.79 (tibia, femur, and spine), and that with microCT was r2 = 0.94 (femur). At the diaphysis, the precision was highest at the femur (< 2% for total and cortical area), and the correlation with microCT was r2 > 0.77. The in vivo precision for bone density (distal femur) was 2.3-5.1%, and that for absolute and relative cortical area (tibia) was 3.1% and 2.2%. CONCLUSIONS: The results show that pQCT can yield satisfactory precision and accuracy in skeletal characterization of mouse bones, if properly applied. The potential advantage of pQCT is that it provides a large set of parameters on bone properties and that it can be used in vivo, extending the available methodological repertoire for genetic studies.

Animals↗
PubMed2002

Insulin-like growth factor-binding protein-2 (IGFBP-2) overexpression negatively regulates bone size and mass, but not density, in the absence and presence of growth hormone/IGF-I excess in transgenic mice.

Insulin-like growth factor-binding protein-2 (IGFBP-2) has been suggested to be a negative regulator of bone growth and maintenance. The objective of this study was to characterize the effect of elevated IGFBP-2 on the skeletal phenotype of adult transgenic mice, in the absence and presence of growth hormone (GH) excess. 43 male mice were examined at an age of 4 months (7 IGFBP-2 transgenic mice, 12 GH transgenic mice, 10 mice carrying both transgenes, and 14 controls). The bone mineral content of the total skeleton and of isolated bones was quantified by dual energy X-ray absorptiometry (DXA), after validation versus ash analysis. Cortical and trabecular bone was quantified by peripheral quantitative computed tomography (pQCT), after validation versus microCT. A strong linear relationship was found between DXA and ash weight, and between pQCT and micro CT ( r>0.95). Bone size and bone mineral content were significantly reduced in IGFBP-2 transgenic mice, the magnitude of the effect varying between skeletal sites and between bone compartments. Elevated IGFBP-2 negatively modulated the GH-stimulated increase in bone size and mineral content, and completely blocked GH-effects at cortical sites. Notably, bone density was not decreased in IGFBP-2 transgenic animals compared with controls. In conclusion, IGFBP-2 is identified as a potent negative regulator of normal and GH-stimulated bone growth in vivo. Interestingly, elevated IGFBP-2 levels did not lead to a decrease in bone density, suggesting that IGFBP-2 negatively affects bone size and mineral content, but not bone maintenance in adult mice.

Absorptiometry, Photon↗