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Osteoporosis International, 16 (7), ISSN:0937-941X, ISSN:1433-2965, ISSN:0936-6555

This study intended to compare bone density and architecture in three groups of women: young women with anorexia nervosa (AN), an age-matched control group of young women, and healthy late postmenopausal women. Three-dimensional peripheral quantitative high resolution computed-tomography (HR-pQCT) at the ultradistal radius, a technology providing measures of cortical and trabecular bone density and microarchitecture, was performed in the three cohorts. Thirty-six women with AN aged 18–30 years (mean duration of AN: 5.8 years), 83 healthy late postmenopausal women aged 70–81 as well as 30 age-matched healthy young women were assessed. The overall cortical and trabecular bone density (D100), the absolute thickness of the cortical bone (CTh), and the absolute number of trabecules per area (TbN) were significantly lower in AN patients compared with healthy young women. The absolute number of trabecules per area (TbN) in AN and postmenopausal women was similar, but significantly lower than in healthy young women. The comparison between AN patients and post-menopausal women is of interest because the latter reach bone peak mass around the middle of the fertile age span whereas the former usually lose bone before reaching optimal bone density and structure. This study shows that bone mineral density and bone compacta thickness in AN are lower than those in controls but still higher than those in postmenopause. Bone compacta density in AN is similar as in controls. However, bone inner structure in AN is degraded to a similar extent as in postmenopause. This last finding is particularly troubling.

A semi-anthropomorphic 'distal radius like' phantom, developed by Kalender and Ruegsegger for use in peripheral bone densitometry using single photon (DPA) dual X-ray (DXA) and quantitative computed tomography (QCT) machines, has been studied with a view to cross-calibrating different types and brands of densitometers in current use. In the context of an EU 'Concerted Action' (second Framework Programme) the phantom was repeatedly measured on six SPA machines, three DXA machines and nine QCT machines (545 measurements). Linear regression equations were derived, individual to each machine, which allowed the derivation of 'standardized densities'. In this way we converted measurements made by machines of the same modality to a common scale of measurements. Two machines (one DXA, one SPA) showed statistically significant instability over time emphasising the need for rigorous quality control in the application of densitometry. In other respects these results provide an encouraging basis for the derivation of standardized normative ranges and the more effective use of peripheral densitometry in future clinical and epidemiological studies.

We assessed the effects of tail-suspension in two skeletal genetic backgrounds, the high C3H/HeJ (C3H) and low C57BL/6J (B6) bone masses inbred mice (male, 4-months old). Cancellous bone mass and structural parameters were evaluated in distal femoral metaphysis by three dimensional microcomputed tomography. Bone cellular activities were evaluated by histomorphometry and measurements of alkaline phosphatase activity (ALP) and osteocalcin in blood and deoxypyridinoline (D-pyr) in urine. In C3H mice, 2- and 3-week unloading experiments were performed. After an early and transient decrease in body weight, a 2-week suspension period resulted in stimulation of both bone formation rate by 45% and active osteoclastic surfaces by 19%. D-pyr did not change, but ALP and osteocalcin levels increased by 18% and 72%, respectively, in 2-week suspended mice, and osteocalcin remained elevated by 30% in the 3-week suspended mice. Such cellular modifications allowed the C3H mice to maintain their initial bone mass and trabecular structural parameters even after a 3-week suspension period. In B6 mice, 1- and 2-week unloading experiments were performed. Tail suspension resulted in decreased body weight during the first days followed by an incomplete recovery during the second week of unloading. The resorption activity was unaffected by any suspension time period, whereas a decrease of 42.5% in bone formation rate and of 21.5% in ALP were seen by the end of the first week of suspension, both values being restored after a 2-week suspension period. At this latter time, trabeculae were thinner, leading to a 24.5% cancellous bone loss. Trabecular number and connectivity, rod-plate index, and degree of anisotropy were not modified. We concluded that C3H mice constituted a unique model in which genetic background overwhelmed the usual effects of reduced biomechanical usage in bone, whereas B6 mice, compared with the standardized rat model, offered an alternative model of bone loss in a mature skeleton.

Quantitative information about bone tissue-level loading is essential for understanding bone mechanical behavior. We made microfinite element models of a healthy and osteoporotic human femur and found that tissue-level strains in the osteoporotic femoral head were 70% higher on average and less uniformly distributed than those in the healthy one. INTRODUCTION: Bone tissue stresses and strains in healthy load-adapted trabecular architectures should be distributed rather evenly, because no bone tissue is expected to be overloaded or unused. In this study, we evaluate this paradigm with the use of microfinite element (microFE) analyses to calculate tissue-level stresses and strains for the human femur. Our objectives were to quantify the strain distribution in the healthy femur, to investigate to what extent this distribution is affected by osteoporosis, to determine if osteoporotic bone is simply bone adapted to lower load levels, and to determine the "safety factor" for trabecular bone. MATERIALS AND METHODS: microFE models of a healthy and osteoporotic proximal femur were made from microcomputed tomography images. The models consisted of over 96 and 71 million elements for the healthy and osteoporotic femur, respectively, and represented their internal and external morphology in detail. Stresses and strains were calculated for each element and their distributions were calculated for a volume of interest (VOI) of trabecular bone in the femoral head. RESULTS: The average tissue-level principal strain magnitude in the healthy VOI was 304 +/- 185 microstrains and that in the osteoporotic VOI was 520 +/- 355 microstrains. Calculated safety factors were 8.6 for the healthy and 4.9 for the osteoporotic femurs. After reducing the force applied to the osteoporotic model to 59%, the average strain compared with that of the healthy femur, but the SD was larger (208 microstrains). CONCLUSIONS: Strain magnitudes in the osteoporotic bone were much higher and less uniformly distributed than those in the healthy one. After simulated joint-load reduction, strain magnitudes in the osteoporotic femur were very similar to those in the healthy one, but their distribution is still wider and thus less favorable.

X-ray computer microtomography is a powerful tool for nondestructive examinations in medicine, biology, and material sciences. The resolution of the presently used detector systems is restricted by scintillator properties, optical light transfer, and charge-coupled-device granularity, which impose a practical limit of about 1 μm spatial resolution at detector efficiencies of a few percent. A recently developed detector, called the Bragg magnifier, achieves a breakthrough in this respect, satisfying the research requirements that ask for an efficient advance towards the submicron range. The Bragg magnifier uses the properties of asymmetric Bragg reflections to increase the cross section of the diffracted x-ray beam. Magnifications of up to 100×100 can be achieved even at hard x-rays energies (>20 keV). In this way, the influence of the detector resolution can be scaled down accordingly and the efficiency increased. Such a device has been developed and successfully integrated into the Microtomography Statio...

Synchrotron-based microtomographic devices are powerful, non-destructive, high-resolution research tools. Highly brilliant and coherent X-rays extend the traditional absorption imaging techniques and enable edge-enhanced and phase-sensitive measurements. At the Materials Science Beamline MS of the Swiss Light Source (SLS), the X-ray microtomographic device is now operative. A high performance detector based on a scintillating screen optically coupled to a CCD camera has been developed and tested. Different configurations are available, covering a field of view ranging from 715×715 μm 2 to 7.15×7.15 mm 2 with magnifications from 4× to 40×. With the highest magnification 480 lp/mm had been achieved at 10% modulation transfer function which corresponds to a spatial resolution of 1.04 μm. A low-noise fast-readout CCD camera transfers 2048×2048 pixels within 100–250 ms at a dynamic range of 12–14 bit to the file server. A user-friendly graphical interface gives access to the main parameters needed for running a complete tomographic scan. This novel device will be used to study the physical structure and chemical composition of biological and technical materials, e.g. enabling pseudo-dynamic testing of bone samples to establish structure–function relationships in simulated osteoporosis or enabling non-destructive testing during the development of modern composite materials.

This study was designed to investigate whether the administration of dietary essential amino acid supplements in adult rats made osteoporotic by estrogen deficiency and reduced protein intake could reverse the deleterious effects caused by these maneuvers. This animal model was selected to mimic the situation observed in elderly women in whom estrogen deficiency and/or low-protein intake (but also calcium and vitamin D deficiency) are known to contribute to the pathogenesis of osteoporosis. Six-month-old rats were ovariectomized (OVX) and fed an isocaloric 2.5% casein diet for 10 weeks or sham-operated (SHAM) and fed an isocaloric 15% casein diet. The animals fed the 2.5% casein diet were given isocaloric supplements of essential amino acids in similar relative proportion to that of casein at doses of 2.5% or 5% of total diet for an additional 16 weeks. Vertebrae, femur, and tibia bone mineral density (BMD); ultimate strength; and microtomographic histomorphometry were evaluated before and after dietary essential amino acid supplements. Essential amino acid supplements increased vertebrae, femur, and tibia bone strength in OVX rats fed a low-protein diet. The mechanical changes induced by this dietary isocaloric supplement were associated with the prevention of a further BMD decrease or even with some increases and changes in microarchitecture such as from a rod to a plate trabecular spacial configuration and increased cortical thickness. Higher insulin-like growth factor (IGF) I levels, as well as greater bone formation and reduced bone resorption as assessed by biochemical markers of bone remodeling, were found in rats receiving essential amino acid supplements. In conclusion, dietary essential amino acid supplements increased bone strength through modifications of BMD, trabecular architecture, and cortical thickness possibly by an IGF-I-mediated process.

26 European centres participated in a concerted research action Biomedical Engineering: Quantitative Assessment of Osteoporosis. With a newly designed European spine and forearm phantom, the stability, accuracy, precision of dual energy absorption (DXA) and quantitative computer tomography (QCT) densitometry machines have been evaluated. Marked and clinically significant differences were found between brands and between techniques. Cross-calibration formulae have been made and normative data evaluated for different regions (spine, femoral neck, femoral trochanteric and forearm). A general fit for all data obtained from different machines was established.The cross-calibration formulae will allow a sensitivity analysis to assist the choice of equipment for clinical management of different categories of patients with bone disease. The present results obtained with an internationally accepted European spine and forearm phantom can now serve to stimulate the manufacturers to improve the comparability of bone measurements between machines.

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

Tomographic techniques are attractive for the investigation of trabecular bone architecture. Using either conventional X-ray sources or synchrotron sources currently allows the acquisition of 3D images in a wide range of spatial resolution that may be as small as a few micrometers. Since it is technically possible to examine trabecular architecture at different scales, a question is to know what type of information it is possible to get at each scale. For this purpose, a series of ten vertebrae samples from healthy females of different ages (33 to 90) was imaged at various resolutions on three different micro-CT systems (cubic voxel size respectively 14, 6.7 and 1.4 \mum). The comparison of morphometric parameters extracted from the different images is in agreement with simulation results on the influence of spatial resolution on structure parameters. The conclusion is that a 14 \mum voxel size gives a reasonably good parameterisation of trabecular architecture. Besides the synchrotron radiation 2 \mum level images reveal interesting features on the irregularities and rupture of trabecular surface, and on remodeling zones.

The mechanical properties of cancellous bone have been shown to depend on bone density and on the anisotropy of the trabecular bone structure. By means of high-resolution quantitative computed tomography (QCT), providing a nominal resolution of 0.17 mm, it became possible to assess both apparent density and trabecular microstructure of intact bones. In order to study the influence of age- and disease-related bone loss on the mechanical properties of cancellous bone, a more phenomenological approach was used to develop a novel bone resorption algorithm, called simulated bone atrophy. The algorithm, which is principlally based on constrained Gauss filtration of segmented data volumes, was applied to create derived microstructural models. The mechanical behavior of the cancellous bone can be expressed as a function of the anisotropic bone properties of the microstructural model on the continuum level. To study the influence of bone atrophy on bone strength we compared three models: the originally noninvasively measured bone biopsy and two derived models simulating moderate and pronounced atrophy. For the comparison of the three models, the apparent Young's moduli in the three orthogonal directions were predicted for each model with the help of three-dimensional finite-element analysis. Realistic results for the apparent Young's moduli were found for the tissue moduli chosen. The results siggest that the prediction of anisotropic material properties of cancellous bone based on noninvasive measurements of trabecular microstructures and the application of simulated bone atrophy may be helpful to understand the influence of age- and disease-related bone loss on bone strength.

The three-dimensional microstructure of cancellous bone seems to be one of the key factors in the prediction of mechanical bone properties like bone strength or bone stiffness. In this paper trabecular bone structure was assessed nondestructively by means of high-resolution computed tomography (CT) with a spatial resolution of 250 μm. Mineralized bone was separated from bone marrow and muscle tissue with the help of a three-dimensional segmentation algorithm based on the analysis of directional derivatives. From the three-dimensional stack of CT slices a subvolume comparable in size (3.6 × 3.4 × 3.4 mm 3 ) to standard histologic bone sections was selected. We refer to this subvolume as non-invasive bone biopsy. A new automated mesh generator was developed to create a three-dimensional finite element model of the non-invasive bone biopsy. Four-noded tetrahedron solid elements were used to guarantee a smooth surface representation. The aim of the presented work was to demonstrate the potential of high-resolution CT imaging in the prediction of the anisotropic material properties of cancellous bone. Preliminary results of the 3D finite element stress analysis are very promising. The predicted value of the apparent Young's modulus (564 MPa) is within the range reported for uniaxial compression testings of cancellous bone specimens.

Nondestructive investigations at ultrahigh spatial resolution can be carried out with synchrotron-based x-ray computer tomography. The performance of presently used detectors is restricted by scintillation properties, optical light transfer and charge coupled device granularity to a limit of 1 μm spatial resolution and efficiency of a few percent. A recently developed detector, called Bragg magnifier, exploits double asymmetrical Bragg diffraction to efficiently produce hard x-ray images with magnification factors up to 100×100 and pixel size of less than 200×200 nm2. Combining it with tomography, we obtained full volumetric information of a sample with spatial resolution well below 1 μm in less than 40 min.

A phantom consisting of water- and bone-equivalent solid materials was devised to test peripheral bone densitometry systems. A circular cross section with a diameter of 60 mm was chosen, with the sides flattened by 1 cm to model the forearm. Three inserts with precisely 50, 100 and 200 mg cm-3 hydroxyapatite simulate trabecular bone and provide the basis for the linearity check of PQCT systems. Density and thickness of the simulated compact bone is selected such that the phantom can also be used to calibrate DXA and SPA machines. Quality control with CT showed a homogeneously distributed trabecular bone with an average density that deviates less than 1 mg cm-3 from linearity. The phantom is presently used in the multicentre study of the COMAC-BME project 'quantitative assessment of osteoporosis' as a reference relative to which all peripheral bone mineral work is reported. Furthermore, trabecular bone density of peripheral and axial measurements can now be compared since the inserts used in the forearm phantom are identical to those used in the previously reported spine phantom.

Osteoarthritis is a common disease that constitutes a considerable socioeconomic burden. So far no radiological procedure was available that allowed the disease to be detected in an early stage. Monitoring disease progression and efficacy of therapeutic procedures was also not possible.We present a measuring procedure and describe evaluation tools that are based on 3D computed tomography. The procedure provides quantitative data on pathological features known to be associated with osteoarthritis such as subchondral sclerosis, osteophytes, joint space narrowing, and bone lesions. It is fully three dimensional, the results are operator independent and describe global as well as local parameters. Changes in these parameters are evaluated from differential images. For that purpose a 3D matching procedure based on translation and rotation-specific correlation techniques is used that allows a repositioning of the bone objects with a mismatch of less than 0.3 mm with regard to translations and 0.250 with regard to rotations.The use of the new tools for measurement, repositioning and evaluation is illustrated with the results from a clinical study. Patients with mild osteoarthritis of the knee joint, healthy controls and osteoporotic patients, all in the same age range of 60 to 75 years, were examined during three years. The cortical to trabecular bone ratio describing subchondral sclerosis proved to be especially helpful to distinguish early osteoarthritic cases from age matched controls. Disease progression is best shown by the increase in the number of detected bone lesions, a reduction of the mean distance between femur and tibia and an increase in the cortical to trabecular bone ratio. Hence the presented procedure appears to have a great potential in diagnosis and treatment monitoring of osteoarthritis.

The modulation transfer function (MTF) of an imaging system may be used as a figure of merit to assess its geometrical resolution. As such it is often derived from the point spread function (PSF) through a Fourier transformation, or through a FFT in case of digital images. Using the special features of the convolution-backprojection algorithm and making some simplifying assumptions about the number of rays, it is shown that the desired MTF is also obtainable without a Fourier transformation of the PSF, different shapes and sizes of the beam-profile are then analyzed, and finally it is shown that calculated and measured MTF functions are in good agreement. The effects of aliasing on the cutoff frequency are also discussed.

The precise site of bone loss was evaluated in early postmenopausal women using high resolution computed tomographic (CT) images of forearm measurements. A procedure was devised to quantitate trabecular and subcortical bone density of the distal radius, cortical bone density of the diaphyseal radius, and cortical wall thickness at both measuring sites. Twenty women (mean age 52 years, time since menopause 1 to 4 years) were examined twice at one-year intervals to determine the yearly change of the above mentioned bone parameters. Trabecular bone and subcortical bone showed the same density reduction of 7 mg/cm3 per year. Cortical bone density remains unchanged and no increase in porosity can be seen. For early postmenopausal women the reduction of bone mass (BMC) in the diaphysis of the radius is, therefore, due to a thinning of the cortical wall. This is in accordance with the observed average loss of wall thickness of 0.04 mm per year. The non-invasive determination of the precise localization of bone changes in individual patients should be of value in the assessment of the severity of osteoporosis. Furthermore it has potential in the evaluation of the efficacy of therapeutic procedures in the various disease states.

Quantitative computed tomography is extensively used to assess bone density; its potential to quantify bone structure, however, remains to be explored. In this work we present the modifications of the run-length method necessary to enable an analysis of the trabecular bone structure at the distal radius and the distal tibia. Furthermore, the close relationship between histomorphometric values and the run-length parameters is shown. The procedure may be regarded as a noninvasive, reproducible biopsy. For an adequate analysis, high resolution CT images are required. To obtain such images, we modified a special purpose CT system and achieved a high contrast resolution of 0.25 mm. The procedure was applied to groups of normal volunteers and osteoporotic patients, and the results are interpreted with the help of simple two- and three-dimensional models of the trabecular architecture.

We constructed a special purpose CT system to get a spatial resolution of 0.2 mm and developed a procedure for the precise determination of trabecular and compact bone density (TBD and CBD) in the radius. Seven groups of healthy females and patients were measured to explore differential effects on compact and trabecular bone. In healthy females CBD remains constant within 0.2% from age 20 to 70. TBD measured in the same individuals is reduced by 50%. The scatter of the individual CBD values is 1.5% only, that of TBD 20%. Longitudinal examinations of corticosteroid treated asthmatics during one year showed a loss of TBD of 4.8%. During the same period CBD remained completely stable. In other diseases such as hyperparathyroidism CBD is reduced as well. This study showed the feasibility of a noninvasive determination of the density of compact bone and demonstrated that density loss of compact and trabecular bone is considerably different.

Osteoporosis is a serious side effect of systemic treatment with steroids. Cloprednol, a synthetic glucocorticoid with an anti-inflammatory potency twice that of prednisone, causes less calcium and nitrogen excretion than does prednisone in equipotent doses. Therefore a double-blind study was undertaken comparing the effects of alternate-day cloprednol and prednisone therapy on bone mineral density in 39 patients (cloprendol: 13 men and 8 women aged 48.5 ± 2.8 years; prednisone: 9 men and 9 women aged 49.7 ±1.7 years) with lung diseases. Ten patients with asthma (9 men and 1 woman aged 37.8 ± 3.7 years) inhaling daily beclomethasone served as control subjects. Trabecular and total bone density of the distal tibia and radius was determined quarterly during 1 year with a special-purpose computed tomographic system. Initial mean trabecular bone density of the patients receiving cloprednol and prednisone was 17% below normal. After a treatment period of 1 year, we found a loss of radial trabecular bone density (mean ± SEM) of 1.33% ± 0.49% in the cloprednol group and 2.38% ± 0.69% in the prednisone group. In postmenopausal women, prednisone but not cloprednol therapy caused significant (p < 0.01) trabecular bone loss (5.29% ± 0.99% versus 0.70% ± 0.65%). The control group lost 0.91% ± 0.79%. Loss of cortical bone was insignificant in all three groups. In postmenopausal women, 1 year of alternate-day cloprednol therapy was associated with significantly less bone loss than was prednisone therapy in equipotent dosages. Clinical Pharmacology and Therapeutics (1990) 48, 455–466; doi:10.1038/clpt.1990.175

In the early s, Prof. Ruegsegger, Institute forMedical Technology andMedical Informatics, Eidg. Technische Hochschule (ETH) and University in Zurich, was asked by the NASA to develop a device cable of quantifying bone loss in astronauts and people working or training under conditions of weightlessness (micro-gravity). The result was the Isotom, a small tomograph for peripheral quantitative computed tomography (pQCT), which allowed us in these early days to perform measurements of the trabecular compartment of the bone only, as the cortical part of the bone was not yet accessible (Fig. ; Ruegsegger et al. , ). Our first step was to perform “bed-rest studies” in male volunteers in . After  weeks of immobilization, trabecular bone loss exceeded 15% in the radius, a tremendously high bone loss as compared with the approximately 1% of yearly trabecular bone loss in perimenopausal women. Having completed these studies, the device was transferred back to Zurich and we decided to adapt it in order to match the specific needs of our patients with osteoporosis.This laid the basis forGeneration , i. e. theDensiscan ,manufactured by

X‐ray computer microtomography using synchrotron light (SRμCT) has proven to be a highly powerful method in many fields of modern research as medicine, biology and material science. Presently used instruments, however, are limited to about 1μm resolution at a total efficiency of a few percent, due to the properties of the scintillator, the optical light transfer, and the CCD granularity. To overcome these limitations we have realized a novel approach based on extremely asymmetrical Bragg reflection. Our instrument, the “Bragg Magnifier” combines two asymmetrically cut Si crystals, mounted close to each other on two rotation and adjustment units. It is installed at the Materials Science Beamline of the Swiss Light Source (SLS). It operates at favorably high energies between 21 keV and 23 keV. In a first experiment using a human bone trabecula a two‐dimensional magnification factor of 100×100 was achieved yielding a spatial resolution of 140nm.

At the Material Science Beamline 4S of the Swiss Light Source (SLS), the X-ray Tomographic Microscopy (XTM) facility is entering its final construction phase. A high performance detector based on a scintillating screen optically coupled to a CCD camera has been developed and tested. MTF-responses of the detector system show spatial resolution down to the micrometer level. A second detector, which will provide a quantum jump in term of spatial resolution and efficiency, has been successfully simulated and will be integrated in the current device soon. A user- friendly graphical interface gives access to the main measurements parameters needed for a complete tomographic scan in absorption as well as in phase-contrast mode. The new instrumentation shall be used for the analysis of the physical structure and chemical composition of technical materials and biological samples, e.g. enabling non- destructive testing during the development of modern composite materials, or enabling pseudo-dynamic testing of bone samples to establish structure-function relationships in simulated osteoporosis.

The diagnosis of osteoporosis is challenging. Usually, the disease progresses slowly, and it is therefore difficult to detect osteoporosis early, or to document the progression of the disease and the effect of a treatment. Several researchers have observed that bone quality cannot be assessed reliably with bone density alone, and that bone microarchitecture has to be considered as well.1-4In spite of these findings, clinical diagnosis still relies almost exclusively on the measurement of bone density. Three-dimensional computed tomography offers a way out of this dilemma. Laib, Ruegsegger, et al. showed with a three-dimensionalin vivoCT scanner that bone structure provides valuable additional information on the skeleton.5,6In recent years, microtomography became an increasingly popular method to image complex structures with features in the micrometer range. A microtomographic system typically assesses a sample in 3D at high spatial resolution, and thus allows unobstructed visual access to the sample’s inner structure. Regardless of whetherin vivoorin vitromeasurements are to be performed, high spatial resolution is the prime factor guiding today’s CT scanner developments. Dose and scanning speed become important issues forin vivomeasurements. Since patient or subject movement have an adverse effect on image quality, the scanning speed ofin vivoCT systems has to be as short as possible.

As a part of the European Union BIOMED I study "Assessment of Bone Quality in Osteoporosis," the trabecular structure of transiliac bone biopsies was assessed by conventional histomorphometry and by three-dimensional microcomputed tomography (microCT). Sixty-three cylindrical human transiliac bone specimens were obtained post mortem from 27 women and 36 men (age 23-92 years) and evaluated morphometrically in this study. For the conventional histomorphometric analysis, a pair of four undecalcified sections were prepared from two regions in the mediolateral plane of the bone cores. The sections were stained with the von Kossa technique to obtain high-contrast two-dimensional images. Prior to the histologic sectioning the samples were measured with a desktop microCT, providing a 14 microm nominal resolution. The morphometric parameters computed by both methods in two or three dimensions, respectively, were bone volume density (BV/TV), bone surface density (BS/TV), trabecular thickness (Tb.Th), and trabecular separation (Tb.Sp). Results showed highly significant (p < 0.0001) correlations between conventional histology and microCT for BV/TV (r = 0.93), BS/TV (r = 0.91), Tb.Th (r = 0.84), and Tb.Sp (r = 0.91). The mean percentage differences between histology and microCT ranged from 2.5% (BV/TV) to 6.1% (Tb.Th). The high correlations and the low differences in terms of absolute numbers between conventional histomorphometric and microtomographic analysis are very promising for the use of micro-tomographic imaging. MicroCT is a nondestructive, fast, and very precise procedure that allows the measurement of cancellous and compact bone in unprocessed biopsies or small bones, as well as a fully automatic determination of three-dimensional morphometric indices.

The architecture of trabecular bone is thought to be controlled by mechanosensitive bone cells, where hormones provide a background for their responses to mechanical signals. It has been suggested that, in osteoporosis, this response is hampered by changed hormonal levels, thereby increasing the mechanical set point of the cells, which would lead to bone loss. We have investigated if a temporary increase of the mechanical set point causes deterioration of trabecular bone architecture, such as seen in osteoporosis. Furthermore, the effects of a changed loading pattern were investigated for the same reason. For this purpose, we used a computer simulation model, which was based on the regulation of bone architecture by mechanosensitive osteocytes. It was found that a temporary shift of the mechanical set point causes no lasting changes in architecture. Although an increase of the mechanical set point induces bone loss, the mechanism of bone loss (trabecular thinning) differs from what is observed in osteoporosis (loss of whole trabeculae). Hence, a change of the mechanical set point alone cannot explain bone loss as seen in osteoporosis. On the other hand, the removal of load components in a particular direction resulted in irreversible loss of whole trabeculae. These results indicate that such temporary changes in loading patterns could be important risk factors for osteoporosis. [Journal Article; In English; United States]

An advanced analysis of the mechanical properties of bone should include information about the microarchitecture of cancellous bone in addition to its density. It has recently been shown that high-resolution quantitative computed tomography and magnetic resonance imaging have the potential to assess such information in a noninvasive way in patients. Both techniques, however, lack sufficient spatial resolution to image the individual trabeculae with true precision. In this work, a new parameter, Ridge number density (RND), is introduced. RND is a measure for the trabecular number, which can be extracted directly from high-resolution three-dimensional (3D) images of patients. We applied the RND technique to a test group of nine healthy, postmenopausal women measured repetitively with a high-resolution 3D peripheral quantitative computed tomography (3D-pQCT) system with 165 x 165 x 165 microm3 voxel size. Simultaneously with the RND determination, the trabecular bone density (TBD) was also assessed in the same volume of interest. The examination site was the distal radius. The intersubject variability of the measured test group was 10.5% for RND and 26.3% for TBD. The root mean square error between first and second examinations (midterm reproducibility) was 1.6% and 1.1%, respectively. RND is determined independently from TBD and pertains to the structure of the cancellous bone. As such, it might add crucial information in cases where bone mass or bone density measurements alone give ambiguous results.

We previously showed that it is possible to cross-calibrate peripheral bone densitometers using the European Spine Phantom (ESP). We have now performed a multinational study of cross-calibrated radius bone density based on normal subjects of both sexes in eight European centers. Six centers were equipped with machines made by Scanco or Stratec for determining distal radial trabecular bone density by quantitative computed tomography (QCT) and two were equipped with Lunar SP2 single photon absorptiometry (SPA) equipment for measuring midshaft cortical bone density. Subjects recruited ranged from 20 to over 80 years of age. Over one hundred and fifteen men were studied by QCT and a different cohort of 104 men were studied with SPA; the equivalent figures for women were 235 and 123. Reference ranges were derived for bone density against age for each of the four groups, and their applicability is discussed in relation to between-center differences in the results obtained. There were insignificant differences (P > 0.05 with Bonferroni correction) between centers in the values obtained by QCT in the different populations. However, there were considerably larger and highly statistically significant differences between midshaft cortical bone density values of about 10% of overall means between subjects from eastern Finland and central Belgium (P < 0.001), with higher Finnish values. Women had considerably lower radial trabecular bone density values than men at all ages, a result that differentiates the radius from the spine. This sex difference widened after menopause. These results have important implications for understanding the contribution of bone density to the differential risk of Colles' fracture in the two sexes and suggest that further work is needed to establish young normal reference ranges for radial bone density in Europe.

Bone density measurements by dual X-ray absorptiometry (DXA) of the spine can now be made precisely, but there is no uniformity in reporting results and in presenting reference data. A European Union Concerted Action therefore devised a uniform procedure for cross-calibrating and standardizing instruments, using the European spine phantom (ESP) prototype. This phantom differs in a number of respects from the final version of the ESP. Eighteen centers in nine countries obtained 1619 records (1035 women) from Caucasian subjects, aged 20–80 years, drawn from normal populations. The DXA machines used were made by the Hologic, Lunar, and Norland companies. Highly statistically significant differences were evident between populations, both in apparent rates of bone loss with age and in the spread of values about the age-adjusted means. There were small residual differences in the results obtained with the three machine brands which could have been due to the relatively large between-center population differences we observed. The alternative or additional explanation that they were attributable, in part, to the design differences between the ESP prototype and the definitive ESP, which became available after this study was completed, was shown to be a valid possibility. Results from postmenopausal women reported in relation to the years that have elapsed since menopause showed reduced population variance when compared with conventional reporting in relation to age. After cross-calibration, the center with the highest age-adjusted normal density value averaged 23% more than the center with the lowest. It is therefore crucially important to select appropriate reference data in clinical and epidemiological studies. These results provide a basis for designing protocols for multicenter studies using currently installed densitometers. ( Bone 17:247–254; 1995 )

Up to now it has not been possible to reliably cross-calibrate dual-energy X-ray absorptiometry (DXA) densitometry equipment made by different manufacturers so that a measurement made on an individual subject can be expressed in the units used with a different type of machine. Manufacturers have adopted various procedures for edge detection and calibration, producing various normal ranges which are specific to each individual manufacturer's brand of machine. In this study we have used the recently described European Spine Phantom (ESP, prototype version), which contains three semi-anthropomorphic "vertebrae" of different densities made of stimulated cortical and trabecular bone, to calibrate a range of DXA densitometers and quantitative computed tomography (QCT) equipment used in the measurement of trabecular bone density of the lumbar vertebrae. Three brands of QCT equipment and three brands of DXA equipment were assessed. Repeat measurements were made to assess machine stability. With the large majority of machines which proved stable, mean values were obtained for the measured low, medium and high density vertebrae respectively. In the case of the QCT equipment these means were for the trabecular bone density, and in the case of the DXA equipment for vertebral body bone density in the posteroanterior projection. All DXA machines overestimated the projected area of the vertebral bodies by incorporating variable amounts of transverse process. In general, the QCT equipment gave measured values which were close to the specified values for trabecular density, but there were substantial differences from the specified values in the results provided by the three DXA brands. For the QCT and Norland DXA machines (posteroanterior view), the relationships between specified densities and observed densities were found to be linear, whereas for the other DXA equipment (posteroanterior view), slightly curvilinear, exponential fits were found to be necessary to fit the plots of observed versus specified densities. From these plots, individual calibration equations were derived for each machine studied. For optimal cross-calibration, it was found to be necessary to use an individual calibration equation for each machine. This study has shown that it is possible to cross-calibrate DXA as well as QCT equipment for the measurement of axial bone density. This will be of considerable benefit for large-scale epidemiological studies as well as for multi-site clinical studies depending on bone densitometry.

Measurements of the proximal femur by dual X-ray absorptiometry (DXA) are assuming increasing importance in clinical and epidemiological studies. However, different DXA manufacturers have adopted varying approaches to measuring the femoral neck and trochanter regions with the result that there is ns yet no agreement on normal ranges and how to cross-calibrate between different machines. In tits Concerted Action (of the EU's 2nd Framework Programme), 12 clinical centers in eight countries recruited a total of 855 female and 517 male Caucasian subjects who were judged to be free of conditions known to cause secondary osteoporosis and who had not been treated with drugs known to affect bone mass. The DXA machines used were made by Hologic, Lunar, and Norland. Each machine was cross-calibrated with the European Spine Phantom prototype designed by Kalender. All femoral neck and trochanter results were expressed as standardized values and were first examined for possible bins due to between-brand differences in choice of areas for measurement. On average, trochanter areas were similar between brands but Norland chose a narrower neck region for analysis. Bone mineral density (BMA or BMD g/cm 2 ) was log-normally distributed for all groups at the femoral neck but normally distributed at the trochanter in men and postmenopausal women. There were substantial between-center differences after cross-calibration in age-adjusted mean walues at both sites and also in the rates of apparent bone loss with age and the amounts of scatter within populations about mean age-adjusted values. With the proviso that locally derived normal ranges would allow more accurate comparisons for clinical purposes, European normal ranges were derived for both neck and trochanter. Data obtained with the three individual brands of machine fitted these overall ranges well. Bone loss was apparent in premenopausal women at the femoral neck but not the trochanter. Postmenopausal women's data was somewhat better fitted by reference to years since menopause than to chronological age. This work provides a basis for conducting future epidemiological and clinical studies with more than one brand of machine as long as each individual subject, if measured consecutively, is measured on the same machine throughout

Heute ist die quantitative Computertomographie eine weit verbreitete und akzeptierte Methode, um die Dichte von Knochen sicher bestimmen zu konnen. Periphere quantitative Computertomographie (pQCT) wird vor allem dort eingesetzt, wo es darum geht, den Grad einer Osteoporose quantifizieren oder aber die Effektivitat der medikamentosen Therapie kontrollieren zu konnen [1, 2].

Three-dimensional structure is one of the main factors influencing the mechanical behaviour of cancellous bone. To analyse the trabecular bone structure non-destructively we used a peripheral QCT system and applied a special thin-slice technique to create high-resolution volumetric data sets serving as a basis for something we would like to call non-invasive bone biopsy. In order to obtain binary data sets, the mineralized bone in the CT volume was separated from bone marrow and muscle tissue with the help of a sophisticated three-dimensional segmentation algorithm based on the analysis of directional derivatives, which are computed from a locally approximated fit function of the original CT volume. Binary volumes including either a solid representation of trabecular plates and rods or a topological representation of the cancellous bone architecture were acquired. Such volumes can be processed non-destructively and, even more important, repetitively. By using a surface reconstruction algorithm based on interpolating triangulation it was possible to visualize the three-dimensional surface of the trabecular bone structure. The results showed that surface representation and visualization in combination with a multiple thin-slice measuring technique are valuable tools in studying three-dimensional bone architecture. In the future, the non-invasive bone biopsies will be evaluated by means of three-dimensional mechanical analysis incorporating finite element modelling and direct morphological investigations of the cancellous bone architecture for a better prediction of bone strength as an index for fracture risk or osteoporosis.

Nachdem die starren Osteoporoseprophylaxe- und -therapieschemata ebensowenig befriedigen konnen wie die Abschatzung der sogenannten „Risikofaktoren“ und die biochemischen Parameter (z.B. alkalische Phosphatase, Osteocalcin, Kollagenmetaboliten, Urinhydroxyprolin und Urincalcium) vorlaufig nicht treffsicher genug sind, um routinemasig individuelle Therapieentscheidungen fur den einzelnen Patienten zu erlauben, bedienen wir uns hierfur seit Jahren hoch-reproduzierbarer (0,1 bis 0,3%) densitometrischer Methoden. Das periphere quantitative Computertomogramm („pQCT“) stellt als etablierte Methode ein risikoarmes, quantitatives Knochendichtemesverfahren am peripheren Skelett dar, das zwischen „total bone“, Spongiosa und Kompakta an Radius und Tibia zu unterscheiden vermag. Die Gerate der IV. Generation (Densican 1000) verfugen nicht nur uber die erwahnte sehr hohe Langzeitreproduzierbarkeit, sondern sind auch in der Lage, routinemasig hochauflosende Bilder aus den quantitatiy erfasten Volumina zur zusatzlichen qualitativen Auswertung zu liefern. Nur so konnen die erhaltenen Daten (mg/cm3) richtig interpretiert werden (Fischer et al. 1992, Muller et al. 1989) (Tab. 1).

Traditionally, diseases of the knee joint are evaluated by grading radiographs, i.e. x-rays are visually inspected and assessed for joint narrowing, spurs, lesions and. sclerosis. Our concept for the quantification of bone changes in diseased knee joints is based on slice-wise measured volumetric CT-data (Computed Tomography). 61 slices, with an interslice distance of one millimeter, are measured with a high resolution low dose CT-system. Considering its three-dimensional context, each slice is separated into objects (femur, patella, tibia, fibula). The contour sets are then used as input for an automatic triangulation procedure. Finally, the surface of the objects and the underlying bone structure is analyzed with regard to localize density loss, lesions, surface roughness, width of joint gap, and so on. It is expected, that the quantitative parameters extracted from 3D CT-data will help to understand the gradual development of joint diseases and help to evaluate new therapeutic procedures.

A technique is presented for measuring surface motions ranging in amplitude from 1 to 60 A, with the aid of a phase-stabilized linear Michelson interferometer. Finite trains of sinusoidal stress waves with amplitudes in this range and frequencies between 0.5 kHz and 0.5 MHz are generated by means of a piezoelectric transducer attached to one end of a bar. It is shown how the displacement recordings may be used to visualize the wave, measure its phase velocity and discriminate between flexural and axial wave motions. The dispersion curves obtained for both flexural and axial waves in a Plexiglas bar and in a beam-like bone sample from a human femur agree with theoretical predictions based on classical beam theory.