A.J. Wirth

Implant stability is affected by local bone microstructural quality

It is known that low bone quality, caused for instance by osteoporosis, not only increases the risk of fractures, but also decreases the performance of fracture implants; yet the specific mechanisms behind this phenomenon are still largely unknown. We hypothesized that especially peri-implant bone microstructure affects implant stability in trabecular bone, to a greater degree than more distant bone. To test this hypothesis we performed a computational study on implant stability in trabecular bone. Twelve humeral heads were measured using micro-computed tomography. Screws were inserted digitally into these heads at 25 positions. In addition, at each screw location, a virtual biopsy was taken. Bone structural quality was quantified by morphometric parameters. The stiffness of the 300 screw-bone constructs was quantified as a measure of implant stability. Global bone density correlated moderately with screw-bone stiffness (r2=0.52), whereas local bone density was a very good predictor (r2=0.91). The best correlation with screw-bone stiffness was found for local bone apparent Youngs modulus (r2=0.97), revealing that not only bone mass but also its arrangement in the trabecular microarchitecture are important for implant stability. In conclusion, we confirmed our hypothesis that implant stability is affected by the microstructural bone quality of the trabecular bone in the direct vicinity of the implant. Local bone density was the best single morphometric predictor of implant stability. The best predictability was provided by the mechanical competence of the peri-implant bone. A clinical implication of this work is that apparently good bone stock, such as assessed by DXA, does not guarantee good local bone quality, and hence does not guarantee good implant stability. New tools that could quantify the structural or mechanical quality of the peri-implant bone may help improve the surgical intervention in reaching better clinical outcomes for screw fixation.

Abnormal Bone Microarchitecture and Evidence of Osteoblast Dysfunction in Premenopausal Women with Idiopathic Osteoporosis

CONTEXT Idiopathic osteoporosis (IOP) in premenopausal women is an uncommon disorder of uncertain pathogenesis in which fragility fractures occur in otherwise healthy women with intact gonadal function. It is unclear whether women with idiopathic low bone mineral density and no history of fragility fractures have osteoporosis. OBJECTIVE The objective of the study was to elucidate the microarchitectural and remodeling features of premenopausal women with IOP. DESIGN We performed transiliac biopsies after tetracycline labeling in 104 women: 45 with fragility fractures (IOP), 19 with idiopathic low bone mineral density (Z score ≤-2.0) and 40 controls. Biopsies were analyzed by two-dimensional quantitative histomorphometry and three-dimensional microcomputed tomography. Bone stiffness was estimated using finite element analysis. RESULTS Compared with controls, affected women had thinner cortices; fewer, thinner, more widely separated, and heterogeneously distributed trabeculae; reduced stiffness; and lower osteoid width and mean wall width. All parameters were indistinguishable between women with IOP and idiopathic low bone mineral density. Although there were no group differences in dynamic histomorphometric remodeling parameters, serum calciotropic hormones, bone turnover markers, or IGF-I, subjects in the lowest tertile of bone formation rate had significantly lower osteoid and wall width, more severely disrupted microarchitecture, lower stiffness, and higher serum IGF-I than those in the upper two tertiles, suggesting that women with low turnover IOP have osteoblast dysfunction with resistance to IGF-I. Subjects with high bone turnover had significantly higher serum 1,25 dihydroxyvitamin D levels and a nonsignificant trend toward higher serum PTH and urinary calcium excretion. CONCLUSIONS These results suggest that the diagnosis of IOP should not require a history of fracture. Women with IOP may have high, normal or low bone turnover; those with low bone turnover have the most marked deficits in microarchitecture and stiffness. These results also suggest that the pathogenesis of idiopathic osteoporosis is heterogeneous and may differ according to remodeling activity.

The discrete nature of trabecular bone microarchitecture affects implant stability

Small endosseous implants, such as screws, are important components of modern orthopedics and dentistry. Hence they have to reliably fulfill a variety of requirements, which makes the development of such implants challenging. Finite element analysis is a widely used computational tool used to analyze and optimize implant stability in bone. For these purposes, bone is generally modeled as a continuum material. However, bone failure and bone adaptation processes are occurring at the discrete level of individual trabeculae; hence the assessment of stresses and strains at this level is relevant. Therefore, the aim of the present study was to investigate how peri-implant strain distribution and load transfer between implant and bone are affected by the continuum assumption. We performed a computational study in which cancellous screws were inserted in continuum and discrete models of trabecular bone; axial loading was simulated. We found strong differences in bone-implant stiffness between the discrete and continuum bone model. They depended on bone density and applied boundary conditions. Furthermore, load transfer from the screw to the surrounding bone differed strongly between the continuum and discrete models, especially for low-density bone. Based on our findings we conclude that continuum bone models are of limited use for finite element analysis of peri-implant mechanical loading in trabecular bone when a precise quantification of peri-implant stresses and strains is required. Therefore, for the assessment and improvement of trabecular bone implants, finite element models which accurately represent trabecular microarchitecture should be used.

The different contributions of cortical and trabecular bone to implant anchorage in a human vertebra.

The quality of the peri-implant bone and the strength of the bone-implant interface are important factors for implant anchorage. With regard to peri-implant bone, cortical and trabecular compartments both contribute to the load transfer from the implant to the surrounding bone but their relative roles have yet to be investigated in detail. However, this knowledge is crucial for the better understanding of implant failure and for the development of new implants. This is especially true for osteoporotic bone, which is characterized by a deterioration of the trabecular architecture and a thinning of the cortical shell, leading to a higher probability of implant loosening. The aim of this study was to investigate the relative biomechanical roles of cortical and trabecular bone on implant pull-out stiffness in human vertebrae. The starting point of our investigation was a micro-computed tomography scan of an adult human vertebra. The cortical shell was identified and an implant was digitally inserted into the vertebral body. Pull-out tests were simulated with micro-finite element analysis and the apparent stiffness of the system with various degrees of shell thickness and bone volume fraction was computed. Our computational models demonstrated that cortical bone, although being very thin, plays a major role in the mechanical competence of the bone-implant construct.

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.

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

High-throughput quantification of the mechanical competence of murine femora — A highly automated approach for large-scale genetic studies

Animal models are widely used to gain insight into the role of genetics on bone structure and function. One of the main strategies to map the genes regulating specific traits is called quantitative trait loci (QTL) analysis, which generally requires a very large number of animals (often more than 1000) to reach statistical significance. QTL analysis for mechanical traits has been mainly based on experimental mechanical testing, which, in view of the large number of animals, is time consuming. Hence, the goal of the present work was to introduce an automated method for large-scale high-throughput quantification of the mechanical properties of murine femora. Specifically, our aims were, first, to develop and validate an automated method to quantify murine femoral bone stiffness. Second, to test its high-throughput capabilities on murine femora from a large genetic study, more specifically, femora from two growth hormone (GH) deficient inbred strains of mice (B6-lit/lit and C3.B6-lit/lit) and their first (F1) and second (F2) filial offsprings. Automated routines were developed to convert micro-computed tomography (micro-CT) images of femora into micro-finite element (micro-FE) models. The method was experimentally validated on femora from C57BL/6J and C3H/HeJ mice: for both inbred strains the micro-FE models closely matched the experimentally measured bone stiffness when using a single tissue modulus of 13.06 GPa. The mechanical analysis of the entire dataset (n=1990) took approximately 44 CPU hours on a supercomputer. In conclusion, our approach, in combination with QTL analysis could help to locate genes directly involved in controlling bone mechanical competence.

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.

Augmentation of peri‐implant bone improves implant stability: Quantification using simulated bone loss

Low bone quality, such as induced by osteoporosis, is considered a main factor leading to failure of fracture fixations. Peri‐implant bone augmentation has been proposed as a means of reducing failure rates in osteoporotic bone by improving implant stability. The beneficial effects of pharmacological augmentation of bone in the immediate vicinity of the implant have been demonstrated. Yet, a quantitative understanding of the role of peri‐implant bone in implant stability is lacking. Therefore, the aim of our study was to quantify the effects of bone loss and peri‐implant bone augmentation on implant stability using image‐based finite element analyses. Using a validated model, we simulated how osteoporotic bone loss would affect implant stability in human humeral heads. We also quantified how augmentation of peri‐implant bone can enhance implant stability. Our simulations revealed that a 30% reduction in bone mass led to a 50% decrease in implant stability. We also found that peri‐implant bone augmentation increased implant stability and that the efficiency of bone augmentation decreased with increasing peri‐implant distance. These findings highlight the strong effect that bone loss has on implant fixation and the potential of peri‐implant bone augmentation for improving implant anchorage in low quality bone.

Quantification of trabecular spatial orientation from low-resolution images

No accepted methodology exists to assess trabecular bone orientation from clinical CT scans. The aim of this study was to test the hypothesis that the distribution of grey values in clinical CT images is related to the underlying trabecular architecture and that this distribution can be used to identify the principal directions and local anisotropy of trabecular bone. Fourteen trabecular bone samples were extracted from high-resolution (30 μm) micro-CT scans of seven human femoral heads. Trabecular orientations and local anisotropy were calculated using grey-level deviation (GLD), a novel method providing a measure of the three-dimensional distribution of image grey values. This was repeated for different image resolutions down to 300 μm and for volumes of interest (VOIs) ranging from 1 to 7 mm. Outcomes were compared with the principal mechanical directions and with mean intercept length (MIL) as calculated for the segmented 30-μm images. For the 30-μm images, GLD predicted the mechanical principal directions equally well as MIL. For the 300-μm images, which are resolutions that can be obtained in vivo using clinical CT, only a small increase (3°–6°) in the deviation from the mechanical orientations was found. VOIs of 5 mm resulted in a robust quantification of the orientation. We conclude that GLD can quantify structural bone parameters from low-resolution CT images.