Biomechanical properties of bone are impaired in patients with ACPA-positive rheumatoid arthritis and associated with the occurrence of fractures.

OBJECTIVES: Bone loss is a well-established consequence of rheumatoid arthritis (RA). To date, bone disease in RA is exclusively characterised by bone density measurements, while the functional properties of bone in RA are undefined. This study aimed to define the impact of RA on the functional properties of bone, such as failure load and stiffness. METHODS: Micro-finite element analysis (µFEA) was carried out to measure failure load and stiffness of bone based on high-resolution peripheral quantitative CT data from the distal radius of anti-citrullinated protein antibody (ACPA)-positive RA (RA+), ACPA-negative RA (RA-) and healthy controls (HC). In addition, total, trabecular and cortical bone densities as well as microstructural parameters of bone were recorded. Correlations and multivariate models were used to determine the role of demographic, disease-specific and structural data of bone strength as well as its relation to prevalent fractures. RESULTS: 276 individuals were analysed. Failure load and stiffness (both P<0.001) of bone were decreased in RA+, but not RA-, compared with HC. Lower bone strength affected both female and male patients with RA+, was related to longer disease duration and significantly (stiffness P=0.020; failure load P=0.012) associated with the occurrence of osteoporotic fractures. Impaired bone strength was correlated with altered bone density and microstructural parameters, which were all decreased in RA+. Multivariate models showed that ACPA status (P=0.007) and sex (P<0.001) were independently associated with reduced biomechanical properties of bone in RA. CONCLUSION: In summary, µFEA showed that bone strength is significantly decreased in RA+ and associated with fractures.

A potential mechanism for allometric trabecular bone scaling in terrestrial mammals.

Trabecular bone microstructural parameters, including trabecular thickness, spacing, and number, have been reported to scale with animal size with negative allometry, whereas bone volume fraction is animal size-invariant in terrestrial mammals. As for the majority of scaling patterns described in animals, its underlying mechanism is unknown. However, it has also been found that osteocyte density is inversely related to animal size, possibly adapted to metabolic rate, which shows a negative relationship as well. In addition, the signalling reach of osteocytes is limited by the extent of the lacuno-canalicular network, depending on trabecular dimensions and thus also on animal size. Here we propose animal size-dependent variations in osteocyte density and their signalling influence distance as a potential mechanism for negative allometric trabecular bone scaling in terrestrial mammals. Using an established and tested computational model of bone modelling and remodelling, we run simulations with different osteocyte densities and influence distances mimicking six terrestrial mammals covering a large range of body masses. Simulated trabecular structures revealed negative allometric scaling for trabecular thickness, spacing, and number, constant bone volume fraction, and bone turnover rates inversely related to animal size. These results are in agreement with previous observations supporting our proposal of osteocyte density and influence distance variation as a potential mechanism for negative allometric trabecular bone scaling in terrestrial mammals. The inverse relationship between bone turnover rates and animal size further indicates that trabecular bone scaling may be linked to metabolic rather than mechanical adaptations.

Bone remodeling and responsiveness to mechanical stimuli in individuals with type 1 diabetes mellitus.

Type 1 diabetes mellitus (T1DM) has been linked to increased osteocyte apoptosis, local accumulation of mineralized lacunar spaces, and microdamage suggesting an impairment of the mechanoregulation network in affected individuals. Diabetic neuropathy might exacerbate this dysfunction through direct effects on bone turnover, and indirect effects on balance, muscle strength, and gait. However, the in vivo effects of impaired bone mechanoregulation on bone remodeling in humans remain underexplored. This longitudinal cohort study assessed consenting participants with T1DM and varying degree of distal symmetric sensorimotor polyneuropathy (T1DM, n = 20, median age 46.5 yr, eight female) and controls (CTRL; n = 9, median age 59.0 yr, four female) at baseline and 4-yr follow-up. Nerve conduction in participants with T1DM was tested using DPNCheck and bone remodeling was quantified with longitudinal high-resolution peripheral quantitative-computed tomography (HR-pQCT, 82 µm) at the standard distal sites. Local trabecular bone formation (Tb.F) and resorption (Tb.R) sites were captured by implementing 3D rigid image registration of HR-pQCT images, and the mechanical environment across the bone microarchitecture at these sites was simulated using micro-finite element analysis. We calculated odds ratios to determine the likelihood of bone formation (ORF) and resorption (ORR) with increasing/decreasing strain in percent as markers for mechanoregulation. At the distal radius, Tb.F was 47% lower and Tb.R was 59% lower in T1DM participants compared with CTRL (P < .05). Tb.F correlated positively with nerve conduction amplitude (R = 0.69, P < .05) in participants with T1DM and negatively with glycated hemoglobin (HbA1c) (R = -0.45, P < .05). Additionally, ORF was 34% lower and ORR was 18% lower in T1DM compared with CTRL (P < .05). Our findings represent in vivo evidence suggesting that bone remodeling in individuals with T1DM is in a state of low responsiveness to mechanical stimuli, resulting in impaired bone formation and resorption rates; these correlate to the degree of neuropathy and level of diabetes control.

In a healthy adult, the body's skeleton self-repairs­or remodels­itself to maintain its strength. At the microscopic level, this process is orchestrated by cells, called osteocytes, which can sense and respond to local mechanical forces. Recent studies have suggested that type 1 diabetes mellitus (T1DM), a metabolic bone disease, may negatively impact this mechanically regulated process and reduce bone strength. To investigate this further, we utilized novel methods to monitor local changes in bone microstructure over time using high­resolution peripheral quantitative­computed tomography, allowing us to study the results of cellular behavior on bone remodeling in participants over time. Our study found that bone formation was 47% lower and bone resorption was 59% lower in participants with T1DM compared with controls (CTRL). Bone formation correlated positively with peripheral nerve function and negatively with glycaemic control in participants with T1DM. Furthermore, the links between mechanical forces acting on bone remodeling were 34% weaker for formation and 18% weaker for resorption compared with CTRL. Our findings show that bone remodeling in people with T1DM is in a state of low responsiveness to mechanical stimuli, resulting in impaired bone formation and resorption rates, and ultimately, impaired self-repair.

Elucidating the mechano-molecular dynamics of TRAP activity using CRISPR/Cas9 mediated fluorescent reporter mice.

Osteoclasts are essential for bone remodeling by adapting their resorptive activity in response to their mechanical in vivo environment. However, the molecular mechanisms underlying this process remain unclear. Here, we demonstrated the role of tartrate-resistant acid phosphatase (TRAP, Acp5), a key enzyme secreted by osteoclasts, in bone remodeling and mechanosensitivity. Using CRISPR/Cas9 reporter mice, we demonstrated bone cell reporter (BCRIbsp/Acp5) mice feature fluorescent TRAP-deficient osteoclasts and examined their activity during mechanically driven trabecular bone remodeling. Although BCRIbsp/Acp5 mice exhibited trabecular bone impairments and reduced resorption capacity in vitro, RNA sequencing revealed unchanged levels of key osteoclast-associated genes such as Ctsk, Mmp9, and Calcr. These findings, in conjunction with serum carboxy-terminal collagen crosslinks (CTX) and in vivo mechanical loading outcomes collectively indicated an unaltered bone resorption capacity of osteoclasts in vivo. Furthermore, we demonstrated similar mechanoregulation during trabecular bone remodeling in BCRIbsp/Acp5 and wild-type (WT) mice. Hence, this study provides valuable insights into the dynamics of TRAP activity in the context of bone remodeling and mechanosensation.

The contribution of lower-mineralized tissue to the healing of distal radius fractures assessed using HR-pQCT.

High-resolution peripheral quantitative CT (HR-pQCT) enables quantitative assessment of distal radius fracture healing. In previous studies, lower-mineralized tissue formation was observed on HR-pQCT scans, starting early during healing, but the contribution of this tissue to the stiffness of distal radius fractures is unknown. Therefore, the aim of this study was to investigate the contribution of lower-mineralized tissue to the stiffness of fractured distal radii during the first twelve weeks of healing. We did so by combining the results from two series of micro-finite element (µFE-) models obtained using different density thresholds for bone segmentation. Forty-five postmenopausal women with a conservatively-treated distal radius fracture had HR-pQCT scans of their fractured radius at baseline (BL; 1-2 weeks post-fracture), 3-4 weeks, 6-8 weeks, and 12 weeks post-fracture. Compression stiffness (S) was computed using two series of µFE-models from the scans: one series (Msingle) included only higher-mineralized tissue (>320 mg HA/cm3), and one series (Mdual) differentiated between lower-mineralized tissue (200-320 mg HA/cm3) and higher-mineralized tissue. µFE-elements were assigned a Young's Modulus of 10 GPa (higher-mineralized tissue) or 5 GPa (lower-mineralized tissue), and an axial compression test to 1 % strain was simulated. The contribution of the lower-mineralized tissue to S was quantified as the ratio Sdual/Ssingle. Changes during healing were quantified using linear mixed effects models and expressed as estimated marginal means (EMMs) with 95 %-confidence intervals (95 %-CI). Median time to cast removal was 5.0 (IQR: 1.1) weeks. Sdual and Ssingle gradually increased during healing to a significantly higher value than BL at 12 weeks post-fracture (both p < 0.0001). In contrast, Sdual/Ssingle was significantly higher than BL at 3-4 weeks post-fracture (p = 0.0010), remained significantly higher at 6-8 weeks post-fracture (p < 0.0001), and then decreased to BL-values at the 12-week visit. EMMs ranged between 1.05 (95 %-CI: 1.04-1.06) and 1.08 (95 %-CI: 1.07-1.10). To conclude, combining stiffness results from two series of µFE-models obtained using single- and dual-threshold segmentation enables quantification of the contribution of lower-mineralized tissue to the stiffness of distal radius fractures during healing. This contribution is minor but changes significantly around the time of cast removal. Its course and timing during healing may be clinically relevant. Quantification of the contribution of lower-mineralized tissue to stiffness gives a more complete impression of strength recovery post-fracture than the evaluation of stiffness using a single series of µFE-models.

Precision of bone mechanoregulation assessment in humans using longitudinal high-resolution peripheral quantitative computed tomography in vivo.

Local mechanical stimuli in the bone microenvironment are essential for the homeostasis and adaptation of the skeleton, with evidence suggesting that disruption of the mechanically-driven bone remodelling process may lead to bone loss. Longitudinal clinical studies have shown the combined use of high-resolution peripheral quantitative computed tomography (HR-pQCT) and micro-finite element analysis can be used to measure load-driven bone remodelling in vivo; however, quantitative markers of bone mechanoregulation and the precision of these analyses methods have not been validated in human subjects. Therefore, this study utilised participants from two cohorts. A same-day cohort (n = 33) was used to develop a filtering strategy to minimise false detections of bone remodelling sites caused by noise and motion artefacts present in HR-pQCT scans. A longitudinal cohort (n = 19) was used to develop bone imaging markers of trabecular bone mechanoregulation and characterise the precision for detecting longitudinal changes in subjects. Specifically, we described local load-driven formation and resorption sites independently using patient-specific odds ratios (OR) and 99 % confidence intervals. Conditional probability curves were computed to link the mechanical environment to the remodelling events detected on the bone surface. To quantify overall mechanoregulation, we calculated a correct classification rate measuring the fraction of remodelling events correctly identified by the mechanical signal. Precision was calculated as root-mean-squared averages of the coefficient of variation (RMS-SD) of repeated measurements using scan-rescan pairs at baseline combined with a one-year follow-up scan. We found no significant mean difference (p < 0.01) between scan-rescan conditional probabilities. RMS-SD was 10.5 % for resorption odds, 6.3 % for formation odds, and 1.3 % for correct classification rates. Bone was most likely to be formed in high-strain and resorbed in low-strain regions for all participants, indicating a consistent, regulated response to mechanical stimuli. For each percent increase in strain, the likelihood of bone resorption decreased by 2.0 ± 0.2 %, and the likelihood of bone formation increased by 1.9 ± 0.2 %, totalling 38.3 ± 1.1 % of strain-driven remodelling events across the entire trabecular compartment. This work provides novel robust bone mechanoregulation markers and their precision for designing future clinical studies.

Mechanostat parameters estimated from time-lapsed in vivo micro-computed tomography data of mechanically driven bone adaptation are logarithmically dependent on loading frequency.

Mechanical loading is a key factor governing bone adaptation. Both preclinical and clinical studies have demonstrated its effects on bone tissue, which were also notably predicted in the mechanostat theory. Indeed, existing methods to quantify bone mechanoregulation have successfully associated the frequency of (re)modeling events with local mechanical signals, combining time-lapsed in vivo micro-computed tomography (micro-CT) imaging and micro-finite element (micro-FE) analysis. However, a correlation between the local surface velocity of (re)modeling events and mechanical signals has not been shown. As many degenerative bone diseases have also been linked to impaired bone (re)modeling, this relationship could provide an advantage in detecting the effects of such conditions and advance our understanding of the underlying mechanisms. Therefore, in this study, we introduce a novel method to estimate (re)modeling velocity curves from time-lapsed in vivo mouse caudal vertebrae data under static and cyclic mechanical loading. These curves can be fitted with piecewise linear functions as proposed in the mechanostat theory. Accordingly, new (re)modeling parameters can be derived from such data, including formation saturation levels, resorption velocity moduli, and (re)modeling thresholds. Our results revealed that the norm of the gradient of strain energy density yielded the highest accuracy in quantifying mechanoregulation data using micro-finite element analysis with homogeneous material properties, while effective strain was the best predictor for micro-finite element analysis with heterogeneous material properties. Furthermore, (re)modeling velocity curves could be accurately described with piecewise linear and hyperbola functions (root mean square error below 0.2 µm/day for weekly analysis), and several (re)modeling parameters determined from these curves followed a logarithmic relationship with loading frequency. Crucially, (re)modeling velocity curves and derived parameters could detect differences in mechanically driven bone adaptation, which complemented previous results showing a logarithmic relationship between loading frequency and net change in bone volume fraction over 4 weeks. Together, we expect this data to support the calibration of in silico models of bone adaptation and the characterization of the effects of mechanical loading and pharmaceutical treatment interventions in vivo.

Characterization of mechanical stiffness using additive manufacturing and finite element analysis: potential tool for bone health assessment.

BACKGROUND: Bone health and fracture risk are known to be correlated with stiffness. Both micro-finite element analysis (µFEA) and mechanical testing of additive manufactured phantoms are useful approaches for estimating mechanical properties of trabecular bone-like structures. However, it is unclear if measurements from the two approaches are consistent. The purpose of this work is to evaluate the agreement between stiffness measurements obtained from mechanical testing of additive manufactured trabecular bone phantoms and µFEA modeling. Agreement between the two methods would suggest 3D printing is a viable method for validation of µFEA modeling. METHODS: A set of 20 lumbar vertebrae regions of interests were segmented and the corresponding trabecular bone phantoms were produced using selective laser sintering. The phantoms were mechanically tested in uniaxial compression to derive their stiffness values. The stiffness values were also derived from in silico simulation, where linear elastic µFEA was applied to simulate the same compression and boundary conditions. Bland-Altman analysis was used to evaluate agreement between the mechanical testing and µFEA simulation values. Additionally, we evaluated the fidelity of the 3D printed phantoms as well as the repeatability of the 3D printing and mechanical testing process. RESULTS: We observed good agreement between the mechanically tested stiffness and µFEA stiffness, with R2 of 0.84 and normalized root mean square deviation of 8.1%. We demonstrate that the overall trabecular bone structures are printed in high fidelity (Dice score of 0.97 (95% CI, [0.96,0.98]) and that mechanical testing is repeatable (coefficient of variation less than 5% for stiffness values from testing of duplicated phantoms). However, we noticed some defects in the resin microstructure of the 3D printed phantoms, which may account for the discrepancy between the stiffness values from simulation and mechanical testing. CONCLUSION: Overall, the level of agreement achieved between the mechanical stiffness and µFEA indicates that our µFEA methods may be acceptable for assessing bone mechanics of complex trabecular structures as part of an analysis of overall bone health.

MRI-based mechanical competence assessment of bone using micro finite element analysis (micro-FEA): Review.

Areal bone mineral density (aBMD) from dual-energy x-ray absorptiometry (DEXA) and volumetric bone mineral density (vBMD) have demonstrated limited capabilities in the evaluation of bone mechanical competence and prediction of bone fracture. Predicting the macroscopic mechanical behavior of the bone structure has been challenging because of the heterogeneous and anisotropic nature of bone, such as the dependencies on loading direction, anatomical location, and sample dimensions. Magnetic resonance imaging (MRI) has been introduced as a promising modality that can be coupled with finite element analysis (FEA) for the assessment of bone mechanical competence. This review article describes studies investigating MRI-based micro-FEA as a potential non-invasive method to predict bone mechanical competence and facilitate bone fracture risk estimation without exposure to ionizing radiation. Specifically, the steps, applications, and future potential of FEA using indirect and direct bone imaging are discussed.

Assessment of the healing of conservatively-treated scaphoid fractures using HR-pQCT.

Improving the clinical outcome of scaphoid fractures may benefit from adequate monitoring of their healing in order to for example identify complications such as scaphoid nonunion at an early stage and to adjust the treatment strategy accordingly. However, quantitative assessment of the healing process is limited with current imaging modalities. In this study, high-resolution peripheral quantitative computed tomography (HR-pQCT) was used for the first time to assess the changes in bone density, microarchitecture, and strength during the healing of conservatively-treated scaphoid fractures. Thirteen patients with a scaphoid fracture (all confirmed on HR-pQCT and eleven on CT) received an HR-pQCT scan at baseline and three, six, twelve, and 26 weeks after first presentation at the emergency department. Bone mineral density (BMD) and trabecular microarchitecture of the scaphoid bone were quantified, and failure load (FL) was estimated using micro-finite element analysis. Longitudinal changes were evaluated with linear mixed-effects models. Data of two patients were excluded due to surgical intervention after the twelve-week follow-up visit. In the eleven fully evaluable patients, the fracture line became more apparent at 3 weeks. At 6 weeks, individual trabeculae at the fracture region became more difficult to identify and distinguish from neighboring trabeculae, and this phenomenon concerned a larger region around the fracture line at 12 weeks. Quantitative assessment showed that BMD and FL were significantly lower than baseline at all follow-up visits with the largest change from baseline at 6 weeks (-13.6% and - 23.7%, respectively). BMD remained unchanged thereafter, while FL increased. Trabecular thickness decreased significantly from baseline at three (-3.9%), six (-6.7%), and twelve (-4.4%) weeks and trabecular number at six (-4.5%), twelve (-7.3%), and 26 (-7.9%) weeks. Trabecular separation was significantly higher than baseline at six (+13.3%), twelve (+19.7%), and 26 (+16.3%) weeks. To conclude, this explorative HR-pQCT study showed a substantial decrease in scaphoid BMD, Tb.Th, and FL during the first 6 weeks of healing of conservatively-treated scaphoid fractures, followed by stabilization or increase in these parameters. At 26 weeks, BMD, trabecular microarchitecture, and FL were not returned to baseline values.

Alterations in osteocyte lacunar morphology affect local bone tissue strains.

Osteocytes are capable of remodeling their perilacunar bone matrix, which causes considerable variations in the shape and size of their lacunae. If these variations in lacunar morphology cause changes in the mechanical environment of the osteocytes, in particular local strains, they would subsequently affect bone mechanotransduction, since osteocytes are likely able to directly sense these strains. The purpose of this study is to quantify the effect of alterations in osteocyte lacunar morphology on peri-lacunar bone tissue strains. To this end, we related the actual lacunar shape in fibulae of six young-adult (5-month) and six old (23-month) mice, quantified by high-resolution micro-computed tomography, to microscopic strains, analyzed by micro-finite element modeling. We showed that peak effective strain increased by 12.6% in osteocyte cell bodies (OCYs), 9.6% in pericellular matrix (PCM), and 5.3% in extra cellular matrix (ECM) as the lacunae volume increased from 100-200 µm3 to 500-600 µm3. Lacunae with a larger deviation (>8°) in orientation from the longitudinal axis of the bone are exposed to 8% higher strains in OCYs, 6.5% in PCM, 4.2% in ECM than lacunae with a deviation in orientation below 8°. Moreover, increased lacuna sphericity from 0 to 0.5 to 0.7-1 led to 25%, 23%, and 13% decrease in maximum effective strains in OCYs, PCM, and ECM, respectively. We further showed that due to the presence of smaller and more round lacunae in old mice, local bone tissue strains are on average 5% lower in the vicinity of lacunae and their osteocytes of old mice compared to young. Understanding how changes in lacunar morphology affect the micromechanical environment of osteocytes presents a first step in unraveling their potential role in impaired bone mechanoresponsiveness with e.g. aging.

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.

Mechano-Regulation of Trabecular Bone Adaptation Is Controlled by the Local in vivo Environment and Logarithmically Dependent on Loading Frequency.

It is well-established that cyclic, but not static, mechanical loading has anabolic effects on bone. However, the function describing the relationship between the loading frequency and the amount of bone adaptation remains unclear. Using a combined experimental and computational approach, this study aimed to investigate whether trabecular bone mechano-regulation is controlled by mechanical signals in the local in vivo environment and dependent on loading frequency. Specifically, by combining in vivo micro-computed tomography (micro-CT) imaging with micro-finite element (micro-FE) analysis, we monitored the changes in microstructural as well as the mechanical in vivo environment [strain energy density (SED) and SED gradient] of mouse caudal vertebrae over 4 weeks of either cyclic loading at varying frequencies of 2, 5, or 10 Hz, respectively, or static loading. Higher values of SED and SED gradient on the local tissue level led to an increased probability of trabecular bone formation and a decreased probability of trabecular bone resorption. In all loading groups, the SED gradient was superior in the determination of local bone formation and resorption events as compared to SED. Cyclic loading induced positive net (re)modeling rates when compared to sham and static loading, mainly due to an increase in mineralizing surface and a decrease in eroded surface. Consequently, bone volume fraction increased over time in 2, 5, and 10 Hz (+15%, +21% and +24%, p ≤ 0.0001), while static loading led to a decrease in bone volume fraction (-9%, p ≤ 0.001). Furthermore, regression analysis revealed a logarithmic relationship between loading frequency and the net change in bone volume fraction over the 4 week observation period (R 2 = 0.74). In conclusion, these results suggest that trabecular bone adaptation is regulated by mechanical signals in the local in vivo environment and furthermore, that mechano-regulation is logarithmically dependent on loading frequency with frequencies below a certain threshold having catabolic effects, and those above anabolic effects. This study thereby provides valuable insights toward a better understanding of the mechanical signals influencing trabecular bone formation and resorption in the local in vivo environment.

Micro-CT and micro-FE analysis of pedicle screw fixation under different loading conditions.

Anchorage of pedicle screw instrumentation in the elderly spine with poor bone quality remains challenging. In this study, micro finite element (µFE) models were used to assess the specific influence of screw design and the relative contribution of local bone density to fixation mechanics. These were created from micro computer tomography (µCT) scans of vertebras implanted with two types of pedicle screws, including a full region-or-interest of 10 mm radius around each screw, as well as submodels for the pedicle and inner trabecular bone of the vertebral body. The local bone volume fraction (BV/TV) calculated from the µCT scans around different regions of the screw (pedicle, inner trabecular region of the vertebral body) were then related to the predicted stiffness in simulated pull-out tests as well as to the experimental pull-out and torsional fixation properties mechanically measured on the corresponding specimens. Results show that predicted stiffness correlated excellently with experimental pull-out strength (R2 > 0.92, p < .043), better than regional BV/TV alone (R2 = 0.79, p = .003). They also show that correlations between fixation properties and BV/TV were increased when accounting only for the pedicle zone (R2 = 0.66-0.94, p ≤  .032), but with weaker correlations for torsional loads (R2 < 0.10). Our analyses highlight the role of local density in the pedicle zone on the fixation stiffness and strength of pedicle screws when pull-out loads are involved, but that local apparent bone density alone may not be sufficient to explain resistance in torsion.

Micro finite element analysis of dental implants under different loading conditions.

Osseointegration is paramount for the longevity of dental implants and is significantly influenced by biomechanical stimuli. The aim of the present study was to assess the micro-strain and displacement induced by loaded dental implants at different stages of osseointegration using finite element analysis (FEA). Computational models of two mandible segments with different trabecular densities were constructed using microCT data. Three different implant loading directions and two osseointegration stages were considered in the stress-strain analysis of the bone-implant assembly. The bony segments were analyzed using two approaches. The first approach was based on Mechanostat strain intervals and the second approach was based on tensile/compression yield strains. The results of this study revealed that bone surrounding dental implants is critically strained in cases when only a partial osseointegration is present and when an implant is loaded by buccolingual forces. In such cases, implants also encounter high stresses. Displacements of partially-osseointegrated implant are significantly larger than those of fully-osseointegrated implants. It can be concluded that the partial osseointegration is a potential risk in terms of implant longevity.

Micro-mechanical properties of different sites on woodpecker's skull.

The uneven distributed microstructure featured with plate-like spongy bone in woodpecker's skull has been found to further help reduce the impact during woodpecker's pecking behavior. Therefore, this work was to investigate the micro-mechanical properties and composition on different sites of Great Spotted woodpecker's (GSW) skull. Different sites were selected on forehead, tempus and occiput, which were also compared with those of Eurasian Hoopoe (EH) and Lark birds (LB). Micro structural parameters assessed from micro computed tomography (µCT) occurred significantly difference between GSW, EH and LB. The micro finite element (micro-FE) models were developed and the simulation was performed as a compression process. The maximal stresses of GSW's micro-FE models were all lower than those of EH and LB respectively and few concentrated stresses were noticed on GSW's trabecular bone. Fourier transform infrared mapping suggesting a greater organic content in the occiput of GSW's cranial bone compared with others. The nano-hardness of the GSW's occiput was decreasing from forehead to occiput. The mechanical properties, site-dependent hardness distribution and special material composition of GSW's skull bone are newly found in this study. These factors may lead to a new design of bulk material mimicking these characteristics.

Computational modeling of long-term effects of prophylactic vertebroplasty on bone adaptation.

Cement augmentation in vertebrae (vertebroplasty) is usually used to restore mechanical strength after spinal fracture but could also be used as a prophylactic treatment. So far, the mechanical competence has been determined immediately post-treatment, without considering long-term effects of bone adaptation. In this work, we investigated such long-term effects of vertebroplasty on the stiffness of the augmented bone by means of computational simulation of bone adaptation. Using micro-finite element analysis, we determined sites of increased mechanical stress (stress raisers) and stress shielding and, based on the simulations, regions with increased or decreased bone loss due to augmentation. Cement volumes connecting the end plates led to increased stress shielding and bone loss. The increased stiffness due to the augmentation, however, remained constant over the simulation time of 30 years. If the intervention was performed at an earlier time point, it did lead to more bone loss, but again, it did not affect long-term stability as this loss was compensated by bone gains in other areas. In particular, around the augmentation cement, bone structures were preserved, suggesting a long-term integration of the cement in the augmented bone. We conclude that, from a biomechanical perspective, the impact of vertebroplasty on the bone at the microstructural level is less detrimental than previously thought.

Bone density and anisotropy affect periprosthetic cement and bone stresses after anatomical glenoid replacement: A micro finite element analysis.

Glenoid loosening is still a main complication for shoulder arthroplasty. We hypothesize that cement and bone stresses potentially leading to fixation failure are related not only to glenohumeral conformity, fixation design or eccentric loading, but also to bone volume fraction, cortical thickness and degree of anisotropy in the glenoid. In this study, periprosthetic bone and cement stresses were computed with micro finite element models of the replaced glenoid depicting realistic bone microstructure. These models were used to quantify potential effects of bone microstructural parameters under loading conditions simulating different levels of glenohumeral conformity and eccentric loading simulating glenohumeral instability. Results show that peak cement stresses were achieved near the cement-bone interface in all loading schemes. Higher stresses within trabecular bone tissue and cement mantle were obtained within specimens of lower bone volume fraction and in regions of low anisotropy, increasing with decreasing glenohumeral conformity and reaching their maxima below the keeled design when the load is shifted superiorly. Our analyses confirm the combined influences of eccentric load shifts with reduced bone volume fraction and anisotropy on increasing periprosthetic stresses. They finally suggest that improving fixation of glenoid replacements must reduce internal cement and bone tissue stresses, in particular in glenoids of low bone density and heterogeneity.

Relationship between sample volumes and modulus of human vertebral trabecular bone in micro-finite element analysis.

Micro-finite element (µFE) models have been widely used to assess the biomechanical properties of trabecular bone. How to choose a proper sample volume of trabecular bone, which could predict the real bone biomechanical properties and reduce the calculation time, was an interesting problem. Therefore, the purpose of this study was to investigate the relationship between different sample volumes and apparent elastic modulus (E) calculated from µFE model. 5 Human lumbar vertebral bodies (L1-L5) were scanned by micro-CT. Cubic concentric samples of different lengths were constructed as the experimental groups and the largest possible volumes of interest (VOI) were constructed as the control group. A direct voxel-to-element approach was used to generate µFE models and steel layers were added to the superior and inferior surface to mimic axial compression tests. A 1% axial strain was prescribed to the top surface of the model to obtain the E values. ANOVA tests were performed to compare the E values from the different VOIs against that of the control group. Nonlinear function curve fitting was performed to study the relationship between volumes and E values. The larger cubic VOI included more nodes and elements, and more CPU times were needed for calculations. E values showed a descending tendency as the length of cubic VOI decreased. When the volume of VOI was smaller than (7.34mm(3)), E values were significantly different from the control group. The fit function showed that E values approached an asymptotic values with increasing length of VOI. Our study demonstrated that apparent elastic modulus calculated from µFE models were affected by the sample volumes. There was a descending tendency of E values as the length of cubic VOI decreased. Sample volume which was not smaller than (7.34mm(3)) was efficient enough and timesaving for the calculation of E.

Apparent- and Tissue-Level Yield Behaviors of L4 Vertebral Trabecular Bone and Their Associations with Microarchitectures.

The precise quantification of vertebral trabecular bone strength and the associations between the microarchitecture and nonlinear mechanics of trabecular bone under various loading conditions may provide insights into trabecular bone quality and trabecular strength prediction based on microarchitectures. In this research, 44 cubic L4 vertebral trabecular bone specimens (5 × 5 × 5 mm(3)) were selected from six male Chinese donors aged 62-70 years. For each vertebral trabecular cube, micro-computed tomography image-based nonlinear micro-finite element analyzes were conducted under compressive and tensile loadings along two orthogonal directions. A bilinear tissue constitutive model was used to describe the nonlinearity of bone tissue material. In each analysis, apparent Young's modulus and initial apparent yield point were determined; the average tissue von Mises stress at the apparent yield point was also calculated, and the amount of tissue elements yielded was obtained. Principal components (PCs) analysis revealed three independent components of the microarchitectural parameters of the vertebral trabecular bones; these three PCs can account for 80.744% of the total variability of trabecular microarchitectures; the first PC (PC1) included bone volume fraction, connectivity density and trabecular number; the second PC (PC2) comprised structure model index and degree of anisotropy; and the third PC (PC3) represented trabecular thickness and age. Multivariate linear regression analysis showed that the PCs were strongly predictive of the apparent- and tissue-level mechanical parameters of the vertebral trabecular bone. To gain further insights into the mechanical properties of trabecular bone, we divided the six vertebral bodies into two groups based on the microarchitectural parameters: high-quality group and low-quality group. We then compared the differences in the mechanical parameters between tension and compression, as well as along longitudinal and transverse loading directions. Results showed that the apparent Young's moduli of the high-quality group were significantly greater than those of the low-quality group in longitudinal and transverse directions. Only the apparent yield strains of the two groups under the longitudinal compressive loading condition were significantly different. The apparent yield stresses and the average tissue von Mises stresses of the trabeculae in the trabecular cubes of the high-quality group were significantly greater than those of the low-quality group under the four loading conditions. This study provided quantitative information regarding the nonlinear mechanical properties of vertebral trabecular bone. This study also described the associations of these mechanical properties with microarchitectures. Our findings may help estimate vertebral strength and the related fracture risk.