The effect of cement augmentation on pedicle screw fixation under various load cases : results from a combined experimental, micro-CT, and micro-finite element analysis.

AIMS: Anchorage of pedicle screw rod instrumentation in the elderly spine with poor bone quality remains challenging. Our study aims to evaluate how the screw bone anchorage is affected by screw design, bone quality, loading conditions, and cementing techniques. METHODS: Micro-finite element (µFE) models were created from micro-CT (µCT) scans of vertebrae implanted with two types of pedicle screws (L: Ennovate and R: S4). Simulations were conducted for a 10 mm radius region of interest (ROI) around each screw and for a full vertebra (FV) where different cementing scenarios were simulated around the screw tips. Stiffness was calculated in pull-out and anterior bending loads. RESULTS: Experimental pull-out strengths were excellently correlated to the µFE pull-out stiffness of the ROI (R2 > 0.87) and FV (R2 > 0.84) models. No significant difference due to screw design was observed. Cement augmentation increased pull-out stiffness by up to 94% and 48% for L and R screws, respectively, but only increased bending stiffness by up to 6.9% and 1.5%, respectively. Cementing involving only one screw tip resulted in lower stiffness increases in all tested screw designs and loading cases. The stiffening effect of cement augmentation on pull-out and bending stiffness was strongly and negatively correlated to local bone density around the screw (correlation coefficient (R) = -0.95). CONCLUSION: This combined experimental, µCT and µFE study showed that regional analyses may be sufficient to predict fixation strength in pull-out and that full analyses could show that cement augmentation around pedicle screws increased fixation stiffness in both pull-out and bending, especially for low-density bone. Cite this article: Bone Joint Res 2021;10(12):797-806.

The role of fabric in the quasi-static compressive mechanical properties of human trabecular bone from various anatomical locations.

Osteoporosis leads to an increased risk of bone fracture. While bone density and architecture can be assessed in vivo with increasing accuracy using CT and MRI, their relationship with the critical mechanical properties at various anatomical sites remain unclear. The objective of this study was to quantify the quasi-static compressive mechanical properties of human trabecular bone among different skeletal sites and compare their relationships with bone volume fraction and a measure of microstructural anisotropy called fabric. Over 600 trabecular bone samples from six skeletal sites were assessed by microCT and tested in uniaxial compression. Bone volume fraction correlated positively with elastic modulus, yield stress, ultimate stress, and the relationships depended strongly on skeletal site. The account of fabric improved these correlations substantially, especially when the data of all sites were pooled together, but the fabric-mechanical property relationships remained somewhat distinct among the anatomical sites. The study confirms that, beyond volume fraction, fabric plays an important role in determining the mechanical properties of trabecular bone and should be exploited in mechanical analysis of clinically relevant sites of the human skeleton.

Sex differences of human trabecular bone microstructure in aging are site-dependent.

UNLABELLED: In this study, we characterize bone microstructure, specifically sex differences, at multiple skeletal sites in 165 subjects >52 yr of age, using microCT technology in vitro. Significant sex differences are observed at the distal radius, femoral neck, and femoral trochanter, but not at the iliac crest, calcaneus, and lumbar vertebral body. Correlations in BV/TV between sites ranged from r = 0.13 to 0.56. INTRODUCTION: The goals of this study were (1) to assess potential sex differences of bone microstructure and their difference between skeletal sites and (2) to explore the relationship of trabecular microstructural properties between relevant skeletal sites. MATERIALS AND METHODS: Trabecular bone microstructural properties were measured in vitro in 165 subjects 52-99 yr of age using microCT. Defined volumes of interest (cylinders with 6 mm diameter and 6 mm length) were scanned at a resolution of 26 microm (isotropic) in six different anatomical sites: distal radius, femoral neck and trochanter, iliac crest, calcaneus, and second lumbar vertebral body. RESULTS: At the radius and femoral neck, trabecular bone displayed a more plate-like structure, thicker trabeculae, smaller separation/higher trabecular number, higher connectivity, and a higher degree of anisotropy in men than in women (p < 0.05). At the trochanter, men displayed more plate-like structure and thicker trabeculae (p < 0.05), but no differences in trabecular separation or other parameters compared with the women. At the calcaneus, iliac crest, and second lumbar vertebra none of the bone parameters displayed significant differences between sexes. The BV/TV at one site explained a range of only 2-32% of the variability at other sites. CONCLUSIONS: These results suggest that trabecular bone microstructural properties are remarkably heterogeneous throughout the skeleton. Significant differences between men and women are observed at some, but not at all, sites. The magnitude of sex differences in trabecular microstructure coincides with that of fracture incidence observed for some of the sites in epidemiological studies.

Non-invasive axial loading of mouse tibiae increases cortical bone formation and modifies trabecular organization: a new model to study cortical and cancellous compartments in a single loaded element.

Systematic study of bones' responses to loading requires simple non-invasive models in appropriate experimental animals where the applied load is controllable and the changes in bone quantifiable. Herein, we validate a model for applying axial loads, non-invasively to murine tibiae. This allows the effects of mechanical loading in both cancellous and cortical bone to be determined within a single bone in which genetic, neuronal and functional influences can also be readily manipulated. Using female C57Bl/J6 mice, peak strains at the tibial mid-shaft were measured during walking (<300 micro epsilon tension) and jumping (<600 micro epsilon compression) with single longitudinally oriented strain gauges attached to the bone's lateral and medial surfaces. Identically positioned gauges were also used to determine, for calibration, the strains engendered by external applied compressive tibial loading between the flexed knee and ankle ex vivo. Applied loads between 5 and 13 N produced strains of 1150-2000 micro epsilon on the lateral surface, and in vivo repetitions of these loads on alternate days for 2 weeks produced significant load magnitude-related increases in cortical bone formation that were similar in mice at 8, 12 and 20 weeks of age. Micro-CT scans showed that loading significantly increases trabecular bone volume in 8 week old mice, but modifies trabecular organization with decreases in trabecular bone volume in 12 and 20 week old mice. This model for loading the tibia has several advantages over other approaches, including scope to study the effects of loading in cancellous as well as cortical bone, against a background of either disuse or of treatment with osteotropic agents within a single bone in normal, mutant and transgenic mice.

Scaling relations between trabecular bone volume fraction and microstructure at different skeletal sites.

In this study, we investigated the scaling relations between trabecular bone volume fraction (BV/TV) and parameters of the trabecular microstructure at different skeletal sites. Cylindrical bone samples with a diameter of 8mm were harvested from different skeletal sites of 154 human donors in vitro: 87 from the distal radius, 59/69 from the thoracic/lumbar spine, 51 from the femoral neck, and 83 from the greater trochanter. µCT images were obtained with an isotropic spatial resolution of 26µm. BV/TV and trabecular microstructure parameters (TbN, TbTh, TbSp, scaling indices (< > and σ of α and αz), and Minkowski Functionals (Surface, Curvature, Euler)) were computed for each sample. The regression coefficient ß was determined for each skeletal site as the slope of a linear fit in the double-logarithmic representations of the correlations of BV/TV versus the respective microstructure parameter. Statistically significant correlation coefficients ranging from r=0.36 to r=0.97 were observed for BV/TV versus microstructure parameters, except for Curvature and Euler. The regression coefficients ß were 0.19 to 0.23 (TbN), 0.21 to 0.30 (TbTh), -0.28 to -0.24 (TbSp), 0.58 to 0.71 (Surface) and 0.12 to 0.16 (<α>), 0.07 to 0.11 (<αz>), -0.44 to -0.30 (σ(α)), and -0.39 to -0.14 (σ(αz)) at the different skeletal sites. The 95% confidence intervals of ß overlapped for almost all microstructure parameters at the different skeletal sites. The scaling relations were independent of vertebral fracture status and similar for subjects aged 60-69, 70-79, and >79years. In conclusion, the bone volume fraction-microstructure scaling relations showed a rather universal character.

The interrelation of trabecular microstructural parameters of the greater tubercle measured for different species.

In the present study the trabecular microstructural parameters (bone volume fraction, trabecular thickness, trabecular separation, trabecular number, connectivity density, degree of anisotropy, and structure model index) of the greater tubercle of the humeral head were measured for human healthy, human osteopenic, ovine, bovine, and porcine bones using micro-computed tomography. Except for trabecular thickness and degree of anisotropy the values of the trabecular microstructural parameters generally differed significantly between species. Thus, only the species for which the implant is designed should be used for in vitro mechanical tests on the stability of implants in trabecular bone. Multivariate regression analysis showed that the microstructural parameters have similar principal interrelations in all species. The most significant relations were found between trabecular thickness and bone volume fraction (median (over all species) p < 0.001), trabecular number and bone volume fraction (p = 0.001), the structural change from plates to rods and bone volume fraction (p < 0.001) as well as between connectivity density and trabecular number (p < 0.001). Trabecular thickness, trabecular number, and the structural change from plates to rods each contributed to the bone volume fraction approximately to the same extent. Based on the similar principal interrelations of the trabecular microstructural parameters found in all investigated species the design of trabecular microstructure in the greater tubercle follows similar phenomenological mechanisms in all species. Thus, in vivo experiments on trabecular bone healing and osteoporosis research for application in humans can be conducted in ovine, bovine, or porcine species.

Short-term exposure to low-carbohydrate, high-fat diets induces low bone mineral density and reduces bone formation in rats.

Low-carbohydrate, high-fat (LC-HF) diets are popular for inducing weight loss in adults and are also used as part of a treatment for children with epilepsy. However, potential risks and side effects remain controversial. We investigated effects of LC-HF diets on growth, bone mineral density (BMD), and turnover in growing rats fed for 4 weeks either normal chow (CH, 9% fat, 33% protein, and 58% carbohydrates), LC-HF-1 (66% fat, 33% protein, and 1% carbohydrates), or LC-HF-2 (94.5% fat, 4.2% protein, and 1.3% carbohydrates). Rats fed LC-HF diets accumulated significantly more visceral and bone marrow fat and showed increased leptin but decreased insulin-like growth-factor 1 (IGF-1). Both LC-HF diets significantly decreased body length (nose to rump), but lengths of humerus, tibia, and femur were significantly reduced with LC-HF-2 only. Peripheral quantitative computed tomography (pQCT) and micro-CT (microCT) independently revealed significant reductions in BMD of tibiae in both LC-HF groups, and tibial maximum load was impaired. Bone-formation marker N-terminal propeptide of type I procollagen was reduced in sera of LC-HF groups, whereas bone resorption marker CrossLaps remained unchanged. Real-time PCR analysis revealed significant reductions by 70% to 80% of transcription factors influencing osteoblastogenesis (Runx2, osterix, and C/EBPbeta) in bone marrow of rats fed LC-HF diets. In conclusion, both LC-HF diets impaired longitudinal growth, BMD, and mechanical properties, possibly mediated by reductions in circulating IGF-1. Serum bone-formation markers as well as expression of transcription factors influencing osteoblastogenesis were reduced. This might indicate a lower rate of mesenchymal stem cells differentiating into osteoblasts, thus explaining reduced bone formation with LC-HF diets.

Analysis of bone matrix composition and trabecular microarchitecture of the femoral metaphysis in patients with osteonecrosis of the femoral head.

Osteonecrosis of the femoral head (ONFH) usually affects young individuals. In advanced stages of ONFH, total hip replacement is the golden standard. However, survivorship after total hip replacement has been reported to be poorer in patients with ONFH compared to patients with primary osteoarthritis (OA). In radiological and histological studies, an impaired bone quality was found not only for the femoral head, but also for the intertrochanteric and metaphyseal region. We hypothesize that alterations of bone quality in the femoral metaphysis might contribute to early stem loosening. The objective of this study was to assess the gene expression levels of factors regulating bone formation and remodeling of the intertrochanteric regions and the proximal femoral canal in patients with ONFH and those with primary OA. The cellular and macromolecular composition of the bone matrix was assessed by osteocalcin immunohistochemistry, and the three-dimensional organization of trabecular bone was characterized by microCT analysis. Gene expression of BMP-2 is twofold higher in the proximal femur in the region of the greater trochanter of patients with ONFH compared to those with OA. The number of osteoblasts in the greater trochanter of patients with ONFH (253/mm(2)) is increased compared to patients with OA (156/mm(2)). Trabecular properties in ONFH bone are altered for bone volume (OA: 32 mm(3), ONFH: 51 mm(3)) and structure model index (OA: 2.2, ONFH: 1.6) in the proximal femoral canal, but not in the trochanteric regions. These alterations in bone metabolism and architecture might contribute to the higher rates of stem loosening after total hip replacement in patients with ONFH, however, further experimental and clinical studies are needed to support our findings.

Advances of 3T MR imaging in visualizing trabecular bone structure of the calcaneus are partially SNR-independent: analysis using simulated noise in relation to micro-CT, 1.5T MRI, and biomechanical strength.

PURPOSE: To investigate differences in magnetic resonance imaging (MRI) of trabecular bone at 1.5T and 3.0T and to specifically study noise effects on the visualization and quantification of trabecular architecture using conventional histomorphometric and nonlinear measures of bone structure. MATERIALS AND METHODS: Sagittal MR images of 43 calcaneus specimens (donor age: 81 +/- 10 years) were acquired at 1.5T and 3.0T using gradient echo sequences. Noise was added to obtain six sets of images with decreasing signal-to-noise ratios (SNRs). Micro-CT images were obtained from biopsies taken from 37 calcaneus samples and bone strength was determined. Morphometric and nonlinear structure parameters were calculated in all datasets. RESULTS: Originally, SNR was 1.5 times higher at 3.0T. In the simulated image sets, SNR was similar at both fields. Trabecular dimensions measured by microCT were adequately estimated by MRI, with residual errors (e(r)), ranging from 16% to 2.7% at 3.0T. Comparing e(r) at similar SNR, 3.0T consistently displayed lower errors than 1.5T (eg, bone fraction at SNR approximately 4: e(r)[3.0T] = 15%; e(r)[1.5T] = 21%, P < 0.05). CONCLUSION: The advances of 3.0T compared to 1.5T in visualizing trabecular bone structure are partially SNR-independent. The better performance at 3.0T may be explained by pronounced susceptibility, enhancing the visualization of thin trabecular structures.

The trabecular architecture of the superior articular process of the lumbar spine (L2-S1).

The role of the facet joint in low back pain has gained public attention lately. The objective of our study was to investigate whether there is any difference in the adaptation of the cancellous bone in the superior articular process depending on the specific stress condition in different levels of the spine. Therefore, the trabecular structure of the superior articular processes of L2 and S1 of 15 cadavers (aged 63-100 years) were studied using muCT (micro-computer tomography). Each sample was divided into five sections, each of which containing 20% of the slices. The following structure parameters were compared between L2 and S1 as well as within each process; bone-volume-fraction (BV/TV), trabecular number (Tb.N), trabecular thickness (Tb.Th), structure-model-index (SMI) and degree of anisotropy (DA). Statistically significant differences were observed between L2 and S1 for the BV/TV, SMI, Tb.Th and Tb.N in superior 2 sections. BV/TV, Tb.Th and Tb.N were higher in S1 than in L2. The SMI is lower, and even negative in S1 compared to L2, showing a more plate-like structure. Within the articular process all structure parameters show a similar distribution in L2 and S1. BV/TV, Tb.N and DA decreased from cranial to caudal while Tb.Th was highest in the most cranial and caudal sections, with the lowest value in the middle. The SMI, on the other hand, increased from cranial to caudal displaying more rod-like structures. These results can be explained by the different stress the processes of the different spinal levels are exposed to as well as the specific motion patterns of the facet joint. The processes of the os sacrum are exposed to a higher axial and ventral load due to their location and the lumbosacral flexion. In addition the upper sections of each process experience higher stress peaks than the lower ones. Therefore, this study shows the material distribution within the cancellous bone adapts to these specific stress conditions the facet joints are exposed to.

Influence of factors regulating bone formation and remodeling on bone quality in osteonecrosis of the femoral head.

Osteonecrosis of the femoral head (ONFH) usually affects young individuals and has a major impact on lifestyle. Notably, the pathogenetic mechanisms of osteonecrosis are unresolved and no effective treatment exists. The objective of this study was to assess the gene expression levels of factors regulating bone formation and remodeling (bone morphogenetic protein [BMP]-2, BMP-7, Runx2, osteocalcin, osteoprotegerin [OPG]) in patients with ONFH and to compare them to those of patients with primary osteoarthritis (OA). The cellular and macromolecular composition of the bone matrix was assessed by osteocalcin immunohistochemistry, and the three-dimensional organization of trabecular bone was characterized by micro-computed tomographic analysis. Our results demonstrate that gene expression of BMP-2, BMP-7, and Runx2 is elevated in patients with ONFH. We observed increased extracellular osteocalcin deposition, presumably caused by a higher number of osteoblasts in concordance with increased activity of Runx2. Constant gene expression level of OPG implies an unchanged osteoclast differentiation rate in ONFH bone. We found no significant change in bone volume, connectivity, and structural model index; further, no significant differences were detected for trabecular properties in ONFH bone. In conclusion, we have shown increased gene expression of factors regulating bone formation and remodeling in the femoral head and/or neck of patients with ONFH. Further, we observed an increase in osteocalcin immunoreactivity and osteoblast/osteocyte cell number, while no significant changes in trabecular microarchitecture were detected. This study increases our understanding of the pathophysiology and repair process following ONFH and might help in the development of new treatment strategies in the future.

Site-specific deterioration of trabecular bone architecture in men and women with advancing age.

We tested the hypothesis that the age dependence of trabecular bone microstructure differs between men and women and is specific to skeletal site. Furthermore, we aimed to investigate the microstructural pattern of bone loss in aging. Microstructural properties of trabecular bone were measured in vitro in 75 men and 75 age-matched women (age, 52-99 yr) using microCT. Trabecular bone samples were scanned at a 26-microm isotropic resolution at seven anatomical sites (i.e., distal radius, T(10) and L(2) vertebrae, iliac crest, femoral neck and trochanter, and calcaneus). DXA measurements were obtained at the distal radius and proximal femur and QCT was used at T(12). No significant decrease in bone density or structure with age was found in men using microCT, DXA, or QCT at any of the anatomical sites. In women, a significant age-dependent decrease in BV/TV was observed at most sites, which was strongest at the iliac crest and weakest at the distal radius. At most sites, the reduction in BV/TV was associated with an increase in structure model index, decrease in Tb.N, and an increase in Tb.Sp. Only in the calcaneus was it associated with a significant decrease in Tb.Th. In conclusion, a significant, site-specific correlation of trabecular bone microstructure with age was found in women but not in men of advanced age. The microstructural basis by which a loss of BV/TV occurs with age can vary between anatomical sites.

Fuzzy logic structure analysis of trabecular bone of the calcaneus to estimate proximal femur fracture load and discriminate subjects with and without vertebral fractures using high-resolution magnetic resonance imaging at 1.5 T and 3 T.

Newly developed fuzzy logic-derived structural parameters were used to characterize trabecular bone architecture in high-resolution magnetic resonance imaging (HR-MRI) of human cadaver calcaneus specimens. These parameters were compared to standard histomorphological structural measures and analyzed concerning performance in discriminating vertebral fracture status and estimating proximal femur fracture load. Sets of 60 sagittal 1.5 T and 3.0 T HR-MRI images of the calcaneus were obtained in 39 cadavers using a fast gradient recalled echo sequence. Structural parameters equivalent to bone histomorphometry and fuzzy logic-derived parameters were calculated using two chosen regions of interest. Calcaneal, spine, and hip bone mineral density (BMD) measurements were also obtained. Fracture status of the thoracic and lumbar spine was assessed on lateral radiographs. Finally, mechanical strength testing of the proximal femur was performed. Diagnostic performance in discriminating vertebral fracture status and estimating femoral fracture load was calculated using regression analyses, two-tailed t-tests of significance, and receiver operating characteristic (ROC) analyses. Significant correlations were obtained at both field strengths between all structural and fuzzy logic parameters (r up to 0.92). Correlations between histomorphological or fuzzy logic parameters and calcaneal BMD were mostly significant (r up to 0.78). ROC analyses demonstrated that standard structural parameters were able to differentiate persons with and without vertebral fractures (area under the curve [A(Z)] up to 0.73). However, none of the parameters obtained in the 1.5-T images and none of the fuzzy logic parameters discriminated persons with and without vertebral fractures. Significant correlations were found between fuzzy or structural parameters and femoral fracture load. Using multiple regression analysis, none of the structural or fuzzy parameters were found to add discriminative value to BMD alone. In summary significant correlations were obtained at both field strengths between all structural and fuzzy logic parameters. However, fuzzy logic-based calcaneal parameters were not well suited for vertebral fracture discrimination. Although significant correlations were found between fuzzy or structural parameters and femoral fracture load, multiple regression analysis showed limited improvement for estimating femoral failure load in addition to femoral BMD alone. Local femoral measurements are still needed to estimate femoral bone strength. Overall, parameters obtained at 3.0 T performed better than those at 1.5 T.

Trabecular bone structure of the calcaneus: comparison of MR imaging at 3.0 and 1.5 T with micro-CT as the standard of reference.

PURPOSE: To investigate in vitro the calcaneal trabecular bone structure in elderly human donors with high spatial resolution magnetic resonance (MR) imaging at 3.0 T and 1.5 T, to quantitatively compare MR measures of bone microarchitecture with those from micro-computed tomography (CT), and to compare the performance of 3.0-T MR imaging with that of 1.5-T MR imaging in differentiating donors with spinal fractures from those without spinal fractures. MATERIALS AND METHODS: The study was performed in line with institutional and legislative requirements; all donors had dedicated their body for educational and research purposes prior to death. Sagittal MR images of 49 human calcaneus cadaveric specimens were obtained (mean age of donors, 79.5 years +/- 11 [standard deviation]; 26 male donors, 23 female donors). After the spatial coregistering of images acquired at 3.0-T and 1.5-T MR imaging, the signal-to-noise-ratios and structural parameters obtained at each magnetic field strength were compared in corresponding sections. Micro-CT was performed on calcaneus cores obtained from corresponding regions in 40 cadaveric specimens. Vertebral deformities of the thoracic and lumbar spine were radiographically classified by using the spinal fracture index. Diagnostic performance of the structural parameters in differentiating donors with vertebral fractures from those without was assessed by using receiver operator characteristic (ROC) analysis, including area under the ROC curve (A(z)). RESULTS: Correlations between structural parameters at 3.0-T MR imaging and those at micro-CT were significantly higher (P < .05) than correlations between structural parameters at 1.5-T MR imaging and those at micro-CT (trabecular thickness, r = 0.76 at 3.0 T vs r = 0.57 at 1.5 T). Trabecular dimensions were amplified at 3.0 T because of increasing susceptibility artifacts. Also, higher ROC values were found for structural parameters at 3.0 T than at 1.5 T, but differences were not significant (trabecular thickness, A(z) = 0.75 at 3.0 T vs A(z) = 0.66 at 1.5 T, P > .05). CONCLUSION: MR imaging at 3.0 T provided a better measure of the trabecular bone structure than did MR imaging at 1.5 T. There was a trend for better differentiation of donors with from those without osteoporotic vertebral fractures at 3.0 T than at 1.5 T.

Assessment of external fixator reusability using load- and cycle-dependent tests.

No standard method has been established for investigating repeated use of an external fixator. The purpose of the current study was to establish a fatigue testing method for assessing fixator frame reuse. A unilateral DynaFix trade mark external fixator system was tested using high-load and low-cycle (900-150 N at 5 Hz) and low-load and high-cycle (450-100 N at 10 Hz) tests (assumed one use of 500,000 and 1 million cycles, respectively). These loading conditions were selected to simulate single clinical use and to satisfy Food and Drug Administration requirements. In the high-load low-cycle test, substantial failure of the serrated joint occurred before completion of the first simulated use. In the low-load high-cycle test, all fixators completed three simulated clinical uses without failure, although (1/4) of the serrated joint components had hairline cracks. The high-load low-cycle test identified the fixator components which should be examined and replaced if reuse of the fixator is to be considered. Wear and deformation of the set screw on the rotary joint and telescoping mechanisms were observed in the low-load high-cycle test but not in the high-load low-cycle test. Therefore, if the unilateral DynaFix trade mark fixators are being considered for reusability, the number of reuses should be limited as the whole structure of the device will experience fatigue damage as the loading cycle increases.