Tl Mueller

Non-invasive bone competence analysis by high-resolution pQCT: an in vitro reproducibility study on structural and mechanical properties at the human radius.

Osteoporosis is defined as a skeletal disorder characterized by compromised bone strength. Bone strength depends, among others, on bone density, bone geometry and its internal architecture. With the recent introduction of a new generation high-resolution 3D peripheral quantitative computed tomography (HR-pQCT) system, direct quantification of structural bone parameters has become feasible. Furthermore, it has recently been demonstrated that bone mechanical competence can be derived from HR-pQCT based micro-finite element modeling (microFE). However, reproducibility data for HR-pQCT-derived mechanical indices is not well-known. Therefore, the aim of this study was to quantify reproducibility of HR-pQCT-derived indices. We measured 14 distal formalin-fixed cadaveric forearms three times and analyzed three different regions for each measurement. For each region cortical and trabecular parameters were determined. Reproducibility was assessed with respect to precision error (PE) and intraclass correlation coefficient (ICC). Reproducibility values were found to be best in all three regions for the full bone compartment with an average PE of 0.79%, followed by the cortical compartment (PE=1.19%) and the trabecular compartment with an average PE of 2.31%. The mechanical parameters showed similar reproducibility (PE=0.48%-2.93% for bone strength and stiffness, respectively). ICC showed a very high reproducibility of subject-specific measurements, ranging from 0.982 to 1.000, allowing secure identification of individual donors ranging from healthy to severely osteoporotic subjects. From these in vitro results we conclude that HR-pQCT derived morphometric and mechanical parameters are highly reproducible such that differences in bone structure and strength can be detected with a reproducibility error smaller than 3%; hence, the technique has a high potential to become a tool for detecting bone quality and bone competence of individual subjects.

Computational finite element bone mechanics accurately predicts mechanical competence in the human radius of an elderly population

High-resolution peripheral quantitative computed tomography (HR-pQCT) is clinically available today and provides a non-invasive measure of 3D bone geometry and micro-architecture with unprecedented detail. In combination with microarchitectural finite element (μFE) models it can be used to determine bone strength using a strain-based failure criterion. Yet, images from only a relatively small part of the radius are acquired and it is not known whether the region recommended for clinical measurements does predict forearm fracture load best. Furthermore, it is questionable whether the currently used failure criterion is optimal because of improvements in image resolution, changes in the clinically measured volume of interest, and because the failure criterion depends on the amount of bone present. Hence, we hypothesized that bone strength estimates would improve by measuring a region closer to the subchondral plate, and by defining a failure criterion that would be independent of the measured volume of interest. To answer our hypotheses, 20% of the distal forearm length from 100 cadaveric but intact human forearms was measured using HR-pQCT. μFE bone strength was analyzed for different subvolumes, as well as for the entire 20% of the distal radius length. Specifically, failure criteria were developed that provided accurate estimates of bone strength as assessed experimentally. It was shown that distal volumes were better in predicting bone strength than more proximal ones. Clinically speaking, this would argue to move the volume of interest for the HR-pQCT measurements even more distally than currently recommended by the manufacturer. Furthermore, new parameter settings using the strain-based failure criterion are presented providing better accuracy for bone strength estimates.

Regional, age and gender differences in architectural measures of bone quality and their correlation to bone mechanical competence in the human radius of an elderly population ☆

An accurate prediction of bone strength in the human radius is of major interest because distal radius fractures are amongst the most common in humans. The objective of this study was to determine gender and age-related changes in bone morphometry at the radius and how these relate to bone strength. Specifically, our aims were to (i) analyze gender differences to get an insight into different bone quantities and qualities between women and men, (ii) to determine which microarchitectural bone parameters would best correlate with strength, (iii) to find the region of interest for the best assessment of bone strength, and (iv) to determine how loss of bone quality depends on age. Intact right forearms of 164 formalin-fixed cadavers from a high-risk elderly population were imaged with a new generation high-resolution pQCT scanner (HR-pQCT). Morphometric indices were derived for six different regions and were related to failure load as assessed by experimental uniaxial compression testing. Significant gender differences in bone quantity and quality were found that correlated well with measured failure load. The most relevant region to determine failure load based on morphometric indices assessed in this study was located just below the proximal end of the subchondral plate; this region differed from the one measured clinically today. Trends in bone changes with increasing age were found, even though for all morphometric indices the variation between subjects was large in comparison to the observed age-related changes. We conclude that HR-pQCT systems can determine how gender and age-related changes in morphometric parameters relate to bone strength, and that HR-pQCT is a promising tool for the assessment of bone quality in patient populations.

Endosseous implant anchorage is critically dependent on mechanostructural determinants of peri-implant bone trabeculae

Low bone mass is highly prevalent among patients receiving endosseous implants. In turn, the implantation prognosis in low‐density skeletal sites is poor. However, little is known about the mechanostructural determinants of implant anchorage. Using metabolic manipulations that lead to low bone density and to its rescue, we show here that anchorage is critically dependent on the peri‐implant bone (PIB). Titanium implants were inserted horizontally into the proximal tibial metaphysis of adult rats 6 weeks after orchiectomy (ORX) or sham ORX. Systemic intermittent administration of human parathyroid hormone (1–34) [iahPTH(1–34)] or vehicle commenced immediately thereafter for 6 weeks. The bone‐implant apparatus was then subjected to image‐guided failure assessment, which assesses biomechanical properties and microstructural deformation concomitantly. Anchorage failure occurred mainly in PIB trabeculae, 0.5 to 1.0 mm away from the implant. Mechanically, the anchorage performed poorly in ORX‐induced low‐density bone, attributable mainly to decreased trabecular number. iahPTH(1–34) rescued the PIB density and implant mechanical function by augmenting trabecular thickness (Tb.Th). However, implant biomechanical properties in low‐density bone were relatively insensitive to implant surface treatment that affected only the osseointegration (%bone‐implant contact). These results support a model wherein anchorage failure involves buckling of the weakest trabecular struts followed by sequential failure of the stronger trabeculae. Treatment with iahPTH(1–34) induced thicker struts, which were able to delay and even prevent failure of individual elements, thus implicating trabecular thickness as a prime target for enhancing implant anchorage by systemic bone anabolic therapy.

Hydroxyapatite particles maintain peri-implant bone mantle during osseointegration in osteoporotic bone

In osteoporotic bones, resorption exceeds formation during the remodelling phase of bone turnover. As a consequence, decreased bone volume and bone contact result in the peri-implant region. This may subsequently lead to loss of fixation. In this study we investigated whether the presence of nonresorbable, osteoconductive hydroxyapatite (HA) particles could help maintain a denser and more functional peri-implant bone structure. Titanium screws were implanted into the proximal tibial metaphysis of four months old, ovariectomized Wistar rats (n=60). In the right tibia, the drill hole was first filled with HA particles, while the left tibia served as a control without HA particles. Histological analysis demonstrated that during the remodelling phase the amount of newly formed bone was significantly higher on the HA over the control side. Micro-CT analysis corroborated the significant changes over time as well as differences in peri-implant bone volume density between treatment and control group. Mechanical tests demonstrated that the pull-out force was greater with HA particles. These results indicate that HA particles are able to induce and maintain for a longer time a denser peri-implant bone mantle in osteoporotic bone, which may have important implications in the prevention of implant migration and cut-outs.

Time-lapsed imaging of implant fixation failure in human femoral heads

The failure mechanisms of bone-implant constructs are still incompletely understood, because the role of the peri-implant bone in implant stability is unclear. We hypothesized that implant fixation failure is preceded by substantial peri-implant bone failure. A new device was developed that combines mechanical testing of large bone-implant constructs with high-resolution peripheral quantitative computed tomography, following the principles of image-guided failure assessment (IGFA). In this study, we investigated the push-in failure behavior of dynamic hip screws (DHS) implanted in human cadaveric femoral heads. For the first time the fixation failure of a clinically used implant in human trabecular bone could be experimentally visualized at the microstructural level. The ultimate force was highly correlated with the peri-implant bone volume fraction (R(2)=0.85). We demonstrated that primary fixation failure of DHS implants was accompanied by trabecular bone failure in the immediate peri-implant bone region only. Such experimental data are crucial to enhance the understanding on the quality of the bone-implant interface and of the trabecular bone in the process of implant fixation failure. We believe that this newly developed device will be beneficial for the development of new implant designs, especially for use in osteoporotic bone.

Quantification of Bone Structural Parameters and Mechanical Competence at the Distal Radius

For the clinician, predicting the fracture risk for individual patients is mainly restricted to the quantitative analysis of bone density. Several studies have shown that bone strength, an indicator for bone fracture risk, is only predicted moderately by bone density, indicating that there are other factors influencing bone competence. However, the relative importance of “bone quantity” and “bone quality” remains poorly understood. The objectives of this article are to describe some of the techniques used to measure the microarchitectural aspects of bone quality, how they can be quantified, and how these quantitative endpoints can be used in the assessment of bone competence. Special focus will be on the distal radius, a site with a high fracture incidence. With the introduction of high-resolution in vivo bone imaging systems, a new generation of imaging instruments has entered the arena allowing the reconstruction of the 3-dimensional microarchitecture of the bones at the wrist, thereby giving researchers and clinicians a powerful tool for the quantitative assessment of bone microstructure. In combination with large-scale finite element modeling, these methodologies have reached a level that it is now becoming possible to assess bone stiffness and strength in humans in a clinical setting. The procedure can help improve predictions of fracture risk, clarify the pathophysiology of skeletal diseases, and monitor the response to therapy.

Image interpolation allows accurate quantitative bone morphometry in registered micro-computed tomography scans.

Time-lapsed in vivo micro-computed tomography is a powerful tool to analyse longitudinal changes in the bone micro-architecture. Registration can overcome problems associated with spatial misalignment between scans; however, it requires image interpolation which might affect the outcome of a subsequent bone morphometric analysis. The impact of the interpolation error itself, though, has not been quantified to date. Therefore, the purpose of this ex vivo study was to elaborate the effect of different interpolator schemes [nearest neighbour, tri-linear and B-spline (BSP)] on bone morphometric indices. None of the interpolator schemes led to significant differences between interpolated and non-interpolated images, with the lowest interpolation error found for BSPs (1.4%). Furthermore, depending on the interpolator, the processing order of registration, Gaussian filtration and binarisation played a role. Independent from the interpolator, the present findings suggest that the evaluation of bone morphometry should be done with images registered using greyscale information.

Mechanical stability in a human radius fracture treated with a novel tissue-engineered bone substitute: a non-invasive, longitudinal assessment using high-resolution pQCT in combination with finite element analysis.

The clinical gold standard in orthopaedics for treating fractures with large bone defects is still the use of autologous, cancellous bone autografts. While this material provides a strong healing response, the use of autografts is often associated with additional morbidity. Therefore, there is a demand for off‐the‐shelf biomaterials that perform similar to autografts. Biomechanical assessment of such a biomaterial in vivo has so far been limited. Recently, the development of high‐resolution peripheral quantitative computed tomography (HR‐pQCT) has made it possible to measure bone structure in humans in great detail. Finite element analysis (FEA) has been used to accurately estimate bone mechanical function from three‐dimensional CT images. The aim of this study was therefore to determine the feasibility of these two methods in combination, to quantify bone healing in a clinical case with a fracture at the distal radius which was treated with a new bone graft substitute. Validation was sought through a conceptional ovine model. The bones were scanned using HR‐pQCT and subsequently biomechanically tested. FEA‐derived stiffness was validated relative to the experimental data. The developed processing methods were then adapted and applied to in vivo follow‐up data of the patient. Our analyses indicated an 18% increase of bone stiffness within 2 months. To our knowledge, this was the first time that microstructural finite element analyses have been performed on bone‐implant constructs in a clinical setting. From this clinical case study, we conclude that HR‐pQCT‐based micro‐finite element analyses show high potential to quantify bone healing in patients. Copyright

Towards validation of computational analyses of peri-implant displacements by means of experimentally obtained displacement maps

Micro-finite element (μFE) analysis has recently been introduced for the detailed quantification of the mechanical interaction between bone and implant. The technique has been validated at an apparent level. The aim of this study was to address the accuracy of μFE analysis at the trabecular level. Experimental displacement fields were obtained by deformable image registration, also known as strain mapping (SM), of dynamic hip screws implanted in three human femoral heads. In addition, displacement fields were calculated using μFE analysis. On a voxel-by-voxel basis, the coefficients of determination (R2) between experimental and μFE-calculated displacements ranged from 0.67 to 0.92. Linear regression of the mean displacements over nine volumes of interest yielded R2 between 0.81 and 0.84. The lowest R2 values were found in regions of very small displacements. In conclusion, we found that peri-implant bone displacements calculated with μFE analysis correlated well with displacements obtained from experimental SM.