Biomechanical Changes of Repair Tissue after Autologous Chondrocyte Implantation at Long-Term Follow-Up.

Objective. This study aims to describe biomechanical maturation process of repair tissue after cartilage repair with autologous chondrocyte implantation (ACI) at long-term follow-up. Design. After ACI, 40 patients underwent altogether 60 arthroscopic biomechanical measurements of the repair tissue at various time points during an up to 11-year follow-up period. Of these patients, 30 patients had full-thickness cartilage lesions and 10 had an osteochondritis dissecans (OCD) defect. The mean lesion area was 6.5 cm2 (SD 3.2). A relative indentation stiffness value for each individually measured lesion was calculated as a ratio of repair tissue and surrounding cartilage indentation value to enable interindividual comparison. Results. Repair tissue stiffness improved during approximately 5 years after surgery. Most of the increase in stiffness occurred during the first 2 years. The curvilinear correlation between relative stiffness values and the follow-up time was 0.31 (95% CI 0.07-0.52), P = 0.017. The interindividual variation of the stiffness was high. Lesion properties or demographic factors showed no significant correlation to biomechanical outcome. The overall postoperative average relative stiffness was 0.75 (SD 0.47). Conclusions. Our clinical study describes a biomechanical maturation process of cartilage repair that may continue even longer than expected. A substantial increase in tissue stiffness proceeds for the first two years postoperatively. Minor progression proceeds for even longer. In some repairs, the biomechanical result was equal to native cartilage, suggesting hyaline-type repair. The variation in biomechanical results suggests substantial inconsistency in the structural outcome following ACI.

Dual contrast in computed tomography allows earlier characterization of articular cartilage over single contrast.

Cationic computed tomography contrast agents are more sensitive for detecting cartilage degeneration than anionic or non-ionic agents. However, osteoarthritis-related loss of proteoglycans and increase in water content contrarily affect the diffusion of cationic contrast agents, limiting their sensitivity. The quantitative dual-energy computed tomography technique allows the simultaneous determination of the partitions of iodine-based cationic (CA4+) and gadolinium-based non-ionic (gadoteridol) agents in cartilage at diffusion equilibrium. Normalizing the cationic agent partition at diffusion equilibrium with that of the non-ionic agent improves diagnostic sensitivity. We hypothesize that this sensitivity improvement is also prominent during early diffusion time points and that the technique is applicable during contrast agent diffusion. To investigate the validity of this hypothesis, osteochondral plugs (d = 8 mm, N = 33), extracted from human cadaver (n = 4) knee joints, were immersed in a contrast agent bath (a mixture of CA4+ and gadoteridol) and imaged using the technique at multiple time points until diffusion equilibrium. Biomechanical testing and histological analysis were conducted for reference. Quantitative dual-energy computed tomography technique enabled earlier determination of cartilage proteoglycan content over single contrast. The correlation coefficient between human articular cartilage proteoglycan content and CA4+ partition increased with the contrast agent diffusion time. Gadoteridol normalized CA4+ partition correlated significantly (P < .05) with Mankin score at all time points and with proteoglycan content after 4 hours. The technique is applicable during diffusion, and normalization with gadoteridol partition improves the sensitivity of the CA4+ contrast agent.

Elucidating failure mechanisms in human femurs during a fall to the side using bilateral digital image correlation.

An improved understanding of the mechanical properties of human femurs is a milestone towards a more accurate assessment of fracture risk. Digital image correlation (DIC) has recently been adopted to provide full-field strain measurements during mechanical testing of femurs. However, it has typically been used to measure strains on the anterior side of the femur, whereas in both single-leg-stance and sideways fall loading conditions, the highest deformations result on the medial and lateral sides of the femoral neck. The goal of this study was to measure full-field deformations simultaneously on the medial and lateral side of the femoral neck in a configuration resembling a fall to the side. Twelve female cadaver femurs were prepared for DIC measurements and tested in sideways fall at 5 mm/s displacement rate. Two pairs of cameras recorded the medial and lateral side of the femoral neck, and deformations were calculated using DIC. The samples exhibited a two-stage failure: first, a compressive collapse on the superolateral side of the femoral neck in conjunction with peak force, followed by complete femoral neck fracture at the force drop following the post-elastic phase. DIC measurements corroborated this observation by reporting no tensile strains above yield limit for the medial side of the neck up to peak force. DIC measurements registered onto the bone micro-architecture showed strain localizations in proximity of cortical pores due to, for instance, blood vessels. This could explain previously reported discrepancies between simulations and experiments in regions rich with large pores, like the superolateral femoral neck.

Clinical Contrast-Enhanced Computed Tomography With Semi-Automatic Segmentation Provides Feasible Input for Computational Models of the Knee Joint.

Computational models can provide information on joint function and risk of tissue failure related to progression of osteoarthritis (OA). Currently, the joint geometries utilized in modeling are primarily obtained via manual segmentation, which is time-consuming and hence impractical for direct clinical application. The aim of this study was to evaluate the applicability of a previously developed semi-automatic method for segmenting tibial and femoral cartilage to serve as input geometry for finite element (FE) models. Knee joints from seven volunteers were first imaged using a clinical computed tomography (CT) with contrast enhancement and then segmented with semi-automatic and manual methods. In both segmentations, knee joint models with fibril-reinforced poroviscoelastic (FRPVE) properties were generated and the mechanical responses of articular cartilage were computed during physiologically relevant loading. The mean differences in the absolute values of maximum principal stress, maximum principal strain, and fibril strain between the models generated from semi-automatic and manual segmentations were <1 MPa, <0.72% and <0.40%, respectively. Furthermore, contact areas, contact forces, average pore pressures, and average maximum principal strains were not statistically different between the models (p >0.05). This semi-automatic method speeded up the segmentation process by over 90% and there were only negligible differences in the results provided by the models utilizing either manual or semi-automatic segmentations. Thus, the presented CT imaging-based segmentation method represents a novel tool for application in FE modeling in the clinic when a physician needs to evaluate knee joint function.

Automated segmentation of cortical and trabecular bone to generate finite element models for femoral bone mechanics.

Finite element (FE) models based on quantitative computed tomography (CT) images are better predictors of bone strength than conventional areal bone mineral density measurements. However, FE models require manual segmentation of the femur, which is not clinically applicable. This study developed a method for automated FE analyses from clinical CT images. Clinical in-vivo CT images of 13 elderly female subjects were collected to evaluate the method. Secondly, proximal cadaver femurs were harvested and imaged with clinical CT (N = 17). Of these femurs, 14 were imaged with µCT and three had earlier been tested experimentally in stance-loading, while collecting surface deformations with digital image correlation. Femurs were segmented from clinical CT images using an automated method, based on the segmentation tool Stradwin. The method automatically distinguishes trabecular and cortical bone, corrects partial volume effect and generates input for FE analysis. The manual and automatic segmentations agreed within about one voxel for in-vivo subjects (0.99 ±â€¯0.23 mm) and cadaver femurs (0.21 ±â€¯0.07 mm). The strains from the FE predictions closely matched with the experimentally measured strains (R2 = 0.89). The method can automatically generate meshes suitable for FE analysis. The method may bring us one step closer to enable clinical usage of patient-specific FE analyses.

Correction to: Prediction of femoral strength using 3D finite element models reconstructed from DXA images: validation against experiments.

In the original publication of the article, Fig. 3 and Tables 2, 4 and 5 were published with errors. The issue was caused by an error in the code used to predict femoral strength in the finite element (FE) models.

Simultaneous Quantitation of Cationic and Non-ionic Contrast Agents in Articular Cartilage Using Synchrotron MicroCT Imaging.

Early diagnosis of acute cartilage injuries enables monitoring of disease progression and improved treatment option planning to prevent post-traumatic osteoarthritis. In contrast-enhanced computed tomography (CECT), the changes in cationic agent diffusion within the tissue reflect cartilage degeneration. The diffusion in degenerated cartilage depends on proteoglycan (PG) content and water content, but each having an opposite effect on diffusion, thus compromising the diagnostic sensitivity. To overcome this limitation, we propose the simultaneous imaging of cationic (sensitive to PG and water contents) and non-ionic (sensitive to water content) agents. In this study, quantitative dual-energy CT (QDECT) imaging of two agents is reported for the first time at clinically feasible imaging time points. Furthermore, this is the first time synchrotron microCT with monochromatic X-rays is employed in cartilage CECT. Imaging was conducted at 1 and 2 h post contrast agent immersion. Intact, PG-depleted, and mechanically injured + PG-depleted cartilage samples (n = 33) were imaged in a mixture of cationic (iodine-based CA4+) and non-ionic (gadolinium-based gadoteridol) agents. Concurrent evaluation of CA4+ and gadoteridol partitions in cartilage is accomplished using QDECT. Subsequent normalization of the CA4+ partition with that of the gadoteridol affords CA4+ attenuations that significantly correlate with PG content - a key marker of OA.

Publisher Correction: Quantitative Evaluation of the Mechanical Risks Caused by Focal Cartilage Defects in the Knee.

A correction has been published and is appended to both the HTML and PDF versions of this paper. The error has not been fixed in the paper.

Computational evaluation of altered biomechanics related to articular cartilage lesions observed in vivo.

Chondral lesions provide a potential risk factor for development of osteoarthritis. Despite the variety of in vitro studies on lesion degeneration, in vivo studies that evaluate relation between lesion characteristics and the risk for the possible progression of OA are lacking. Here, we aimed to characterize different lesions and quantify biomechanical responses experienced by surrounding cartilage tissue. We generated computational knee joint models with nine chondral injuries based on clinical in vivo arthrographic computed tomography images. Finite element models with fibril-reinforced poro(visco)elastic cartilage and menisci were constructed to simulate physiological loading. Systematically, the lesions experienced increased peak values of maximum principal strain, maximum shear strain, and minimum principal strain in the surrounding chondral tissue (p < 0.01) compared with intact tissue. Depth, volume, and area of the lesion correlated with the maximum shear strain (p < 0.05, Spearman rank correlation coefficient ρ = 0.733-0.917). Depth and volume of the lesion correlated also with the maximum principal strain (p < 0.05, ρ = 0.767, and ρ = 0.717, respectively). However, the lesion area had non-significant correlation with this strain parameter (p = 0.06, ρ = 0.65). Potentially, the introduced approach could be developed for clinical evaluation of biomechanical risks of a chondral lesion and planning an intervention. Statement of Clinical Relevance: In this study, we computationally characterized different in vivo chondral lesions and evaluated their risk of cartilage degeneration. This information is vital in decision-making for intervention in order to prevent post-traumatic osteoarthritis. © 2019 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res.

Imaging of proteoglycan and water contents in human articular cartilage with full-body CT using dual contrast technique.

Assessment of cartilage composition via tomographic imaging is critical after cartilage injury to prevent post-traumatic osteoarthritis. Diffusion of cationic contrast agents in cartilage is affected by proteoglycan loss and elevated water content. These changes have opposite effects on diffusion and, thereby, reduce the diagnostic accuracy of cationic agents. Here, we apply, for the first time, a clinical full-body CT for dual contrast imaging of articular cartilage. We hypothesize that full-body CT can simultaneously determine the diffusion and partitioning of cationic and non-ionic contrast agents and that normalization of the cationic agent partition with that of the non-ionic agent minimizes the effect of water content and tissue permeability, especially at early diffusion time points. Cylindrical (d = 8 mm) human osteochondral samples (n = 45; four cadavers) of a variable degenerative state were immersed in a mixture of cationic iodinated CA4+ and non-charged gadoteridol contrast agents and imaged with a full-body CT scanner at various time points. Determination of contrast agents' distributions within cartilage was possible at all phases of diffusion. At early time points, gadoteridol, and CA4+ distributed throughout cartilage with lower concentrations in the deep cartilage. At ≥24 h, the gadoteridol concentration remained nearly constant, while the CA4+ concentration increased toward deep cartilage. Normalization of the CA4+ partition with that of gadoteridol significantly (p < 0.05) enhanced correlation with proteoglycan content and Mankin score at the early time points. To conclude, the dual contrast technique was found advantageous over single contrast imaging enabling more sensitive diagnosis of cartilage degeneration. © 2019 The Authors. Journal of Orthopaedic Research Published by Wiley Periodicals, Inc. J Orthop Res 9999:1-12, 2019.

Comparison between kinetic and kinetic-kinematic driven knee joint finite element models.

Use of knee joint finite element models for diagnostic purposes is challenging due to their complexity. Therefore, simpler models are needed for studies where a high number of patients need to be analyzed, without compromising the results of the model. In this study, more complex, kinetic (forces and moments) and simpler, kinetic-kinematic (forces and angles) driven finite element models were compared during the stance phase of gait. Patella and tendons were included in the most complex model, while they were absent in the simplest model. The greatest difference between the most complex and simplest models was observed in the internal-external rotation and axial joint reaction force, while all other rotations, translations and joint reaction forces were similar to one another. In terms of cartilage stresses and strains, the simpler models behaved similarly with the more complex models in the lateral joint compartment, while minor differences were observed in the medial compartment at the beginning of the stance phase. We suggest that it is feasible to use kinetic-kinematic driven knee joint models with a simpler geometry in studies with a large cohort size, particularly when analyzing cartilage responses and failures related to potential overloads.

Method for Segmentation of Knee Articular Cartilages Based on Contrast-Enhanced CT Images.

Segmentation of contrast-enhanced computed tomography (CECT) images enables quantitative evaluation of morphology of articular cartilage as well as the significance of the lesions. Unfortunately, automatic segmentation methods for CECT images are currently lacking. Here, we introduce a semiautomated technique to segment articular cartilage from in vivo CECT images of human knee. The segmented cartilage geometries of nine knee joints, imaged using a clinical CT-scanner with an intra-articular contrast agent, were compared with manual segmentations from CT and magnetic resonance (MR) images. The Dice similarity coefficients (DSCs) between semiautomatic and manual CT segmentations were 0.79-0.83 and sensitivity and specificity values were also high (0.76-0.86). When comparing semiautomatic and manual CT segmentations, mean cartilage thicknesses agreed well (intraclass correlation coefficient = 0.85-0.93); the difference in thickness (mean ± SD) was 0.27 ± 0.03 mm. Differences in DSC, when MR segmentations were compared with manual and semiautomated CT segmentations, were statistically insignificant. Similarly, differences in volume were not statistically significant between manual and semiautomatic CT segmentations. Semiautomation decreased the segmentation time from 450 ± 190 to 42 ± 10 min per joint. The results reveal that the proposed technique is fast and reliable for segmentation of cartilage. Importantly, this is the first study presenting semiautomated segmentation of cartilage from CECT images of human knee joint with minimal user interaction.

Multi-scale imaging techniques to investigate solute transport across articular cartilage.

As articular cartilage is an avascular tissue, the transport of nutrients and cytokines through the tissue is essential for the health of cells, i.e. chondrocytes. Transport of specific contrast agents through cartilage has been investigated to elucidate cartilage quality. In laboratory, pre-clinical and clinical studies, imaging techniques such as magnetic imaging resonance (MRI), computed tomography (CT) and fluorescent microscopy have been widely employed to visualize and quantify solute transport in cartilage. Many parameters related to the physico-chemical properties of the solute, such as molecular weight, net charge and chemical structure, have a profound effect on the transport characteristics. Information on the interplay of the solute parameters with the imaging-dependent parameters (e.g. resolution, scan and acquisition time) could assist in selecting the most optimal imaging systems and data analysis tools in a specific experimental set up. Here, we provide a comprehensive review of various imaging systems to investigate solute transport properties in articular cartilage, by discussing their potentials and limitations. The presented information can serve as a guideline for applications in cartilage imaging and therapeutics delivery and to improve understanding of the set-up of solute transport experiments in articular cartilage.

Quantitative Dual Contrast CT Technique for Evaluation of Articular Cartilage Properties.

Impact injuries of cartilage may initiate post-traumatic degeneration, making early detection of injury imperative for timely surgical or pharmaceutical interventions. Cationic (positively-charged) CT contrast agents detect loss of cartilage proteoglycans (PGs) more sensitively than anionic (negatively-charged) or non-ionic (non-charged, i.e., electrically neutral) agents. However, degeneration related loss of PGs and increase in water content have opposite effects on the diffusion of the cationic agent, lowering its sensitivity. In contrast to cationic agents, diffusion of non-ionic agents is governed only by steric hindrance and water content of cartilage. We hypothesize that sensitivity of an iodine(I)-based cationic agent may be enhanced by simultaneous use of a non-ionic gadolinium(Gd)-based agent. We introduce a quantitative dual energy CT technique (QDECT) for simultaneous quantification of two contrast agents in cartilage. We employ this technique to improve the sensitivity of cationic CA4+ (q =+4) by normalizing its partition in cartilage with that of non-ionic gadoteridol. The technique was evaluated with measurements of contrast agent mixtures of known composition and human osteochondral samples (n = 57) after immersion (72 h) in mixture of CA4+ and gadoteridol. Samples were arthroscopically graded and biomechanically tested prior to QDECT (50/100 kV). QDECT determined contrast agent mixture compositions correlated with the true compositions (R2= 0.99, average error = 2.27%). Normalizing CA4+ partition in cartilage with that of gadoteridol improved correlation with equilibrium modulus (from ρ = 0.701 to 0.795). To conclude, QDECT enables simultaneous quantification of I and Gd contrast agents improving diagnosis of cartilage integrity and biomechanical status.

Dual Contrast CT Method Enables Diagnostics of Cartilage Injuries and Degeneration Using a Single CT Image.

Cartilage injuries may be detected using contrast-enhanced computed tomography (CECT) by observing variations in distribution of anionic contrast agent within cartilage. Currently, clinical CECT enables detection of injuries and related post-traumatic degeneration based on two subsequent CT scans. The first scan allows segmentation of articular surfaces and lesions while the latter scan allows evaluation of tissue properties. Segmentation of articular surfaces from the latter scan is difficult since the contrast agent diffusion diminishes the image contrast at surfaces. We hypothesize that this can be overcome by mixing anionic contrast agent (ioxaglate) with bismuth oxide nanoparticles (BINPs) too large to diffuse into cartilage, inducing a high contrast at the surfaces. Here, a dual contrast method employing this mixture is evaluated by determining the depth-wise X-ray attenuation profiles in intact, enzymatically degraded, and mechanically injured osteochondral samples (n = 3 × 10) using a microCT immediately and at 45 min after immersion in contrast agent. BiNPs were unable to diffuse into cartilage, producing high contrast at articular surfaces. Ioxaglate enabled the detection of enzymatic and mechanical degeneration. In conclusion, the dual contrast method allowed detection of injuries and degeneration simultaneously with accurate cartilage segmentation using a single scan conducted at 45 min after contrast agent administration.

Contrast-Enhanced Computed Tomography Enables Quantitative Evaluation of Tissue Properties at Intrajoint Regions in Cadaveric Knee Cartilage.

Objective The aim of this study was to investigate whether the concentration of the anionic contrast agent ioxaglate, as quantitated by contrast-enhanced computed tomography (CECT) using a clinical cone-beam CT (CBCT) instrument, reflects biochemical, histological, and biomechanical characteristics of articular cartilage imaged in an ex vivo, intact human knee joint. Design An osteoarthritic human cadaveric knee joint (91 years old) was injected with ioxaglate (36 mg I/mL) and imaged using CBCT over 61 hours of ioxaglate diffusion into cartilage. Following imaging, the joint surfaces were excised, rinsed to remove contrast agent, and compressive stiffness (equilibrium and instantaneous compressive moduli) was measured via indentation testing ( n = 17 sites). Each site was sectioned for histology and assessed for glycosaminoglycan content using digital densitometry of Safranin-O stained sections, Fourier transform infrared spectroscopy for collagen content, and morphology using both the Mankin and OARSI semiquantitative scoring systems. Water content was determined using mass change after lyophilization. Results CECT attenuation at all imaging time points, including those <1 hour of ioxaglate exposure, correlated significantly ( P < 0.05) with cartilage water and glycosaminoglycan contents, Mankin score, and both equilibrium and instantaneous compressive moduli. Early time points (<30 minutes) also correlated ( P < 0.05) with collagen content and OARSI score. Differences in cartilage quality between intrajoint regions were distinguishable at diffusion equilibrium and after brief ioxaglate exposure. Conclusions CECT with ioxaglate affords biochemical and biomechanical measurements of cartilage health and performance even after short, clinically relevant exposure times, and may be useful in the clinic as a means for detecting early signs of cartilage pathology.

Histomorphometric and osteocytic characteristics of cortical bone in male subtrochanteric femoral shaft.

The histomorphometric properties of the subtrochanteric femoral region have rarely been investigated. The aim of this study was to investigate the age-associated variations and regional differences of histomorphometric and osteocytic properties in the cortical bone of the subtrochanteric femoral shaft, and the association between osteocytic and histological cortical bone parameters. Undecalcified histological sections of the subtrochanteric femoral shaft were obtained from cadavers (n = 20, aged 18-82 years, males). They were cut and stained using modified Masson-Goldner stain. Histomorphometric parameters of cortical bone were analysed with ×50 and ×100 magnification after identifying cortical bone boundaries using our previously validated method. Within cortical bone areas, only complete osteons with typical concentric lamellae and cement line were selected and measured. Osteocytic parameters of cortical bone were analyzed under phase contrast microscopy and epifluorescence within microscopic fields (0.55 mm2 for each). The cortical widths of the medial and lateral quadrants were significantly higher than other quadrants (P < 0.01). Osteonal area per cortical bone area was lower and cortical porosities were higher in the posterior quadrant than in the other quadrants (P < 0.05). Osteocyte lacunar number per cortical bone area was found higher in the young subjects (≤ 50 years) than in the older ones (> 50 years) both before and after adjustments for body height and weight (P < 0.05). Moreover, significant but low correlations were found between the cortical bone and osteocytic parameters (0.20 ≤ R2  ≤ 0.35, P < 0.05). It can be concluded that in healthy males, the cortical histomorphometric parameters differ between the anatomical regions of the subtrochanteric femoral shaft, and are correlated with the osteocytic parameters from the same site. These findings may be of use when discussing mechanisms that predispose patients to decreasing bone strength.

Iliac crest histomorphometry and skeletal heterogeneity in men.

PURPOSE: The cortical characteristics of the iliac crest in male have rarely been investigated with quantitative histomorphometry. Also it is still unknown how cortical microarchitecture may vary between the iliac crest and fractures related sites at the proximal femur. We studied the microarchitecture of both external and internal cortices within the iliac crest, and compared the results with femoral neck and subtrochanteric femoral shaft sites. METHODS: Undecalcified histological sections of the iliac crest were obtained bicortically from cadavers (n = 20, aged 18-82 years, males). They were cut (7 µm) and stained using modified Masson-Goldner stain. Histomorphometric parameters of cortical bone were analysed with low (× 50) and high (× 100) magnification, after identifying cortical bone boundaries using our previously validated method. Within cortical bone area, only complete osteons with typical concentric lamellae and cement line were selected and measured. RESULTS: At the iliac crest, the mean cortical width of external cortex was higher than at the internal cortex (p < 0.001). Also, osteon structural parameters, e.g. mean osteonal perimeter, were higher in the external cortex (p < 0.05). In both external and internal cortices, pore number per cortical bone area was higher in young subjects (≤ 50 years) (p < 0.05) while mean pore perimeter was higher in the old subjects (> 50 years) (p < 0.05). Several cortical parameters (e.g. osteon area per cortical bone area, pore number per cortical area) were the lowest in the femoral neck (p < 0.05). The maximal osteonal diameter and mean wall width were the highest in the external cortex of the iliac crest (p < 0.05), and the mean cortical width, osteon number per cortical area were the highest in the subtrochanteric femoral shaft (p < 0.05). Some osteonal structural parameters (e.g. min osteonal diameter) were significantly positively correlated (0.29 ≤ R2 ≤ 0.45, p < 0.05) between the external iliac crest and the femoral neck. CONCLUSIONS: This study reveals heterogeneity in cortical microarchitecture between the external and internal iliac crest cortices, as well as between the iliac crest, the femoral neck and the subtrochanteric femoral shaft. Standard iliac crest biopsy does not reflect accurately cortical microarchitecture of other skeletal sites.

Porosity predicted from ultrasound backscatter using multivariate analysis can improve accuracy of cortical bone thickness assessment.

A rapidly growing area of interest in quantitative ultrasound assessment of bone is to determine cortical bone porosity from ultrasound backscatter. Current backscatter analyses are based on numerical simulations, while there are no published reports of successful experimental measurements. In this study, multivariate analysis is applied to ultrasound reflections and backscatter to predict cortical bone porosity. The porosity is then applied to estimate cortical bone radial speed of sound (SOS) and thickness using ultrasound backscatter signals obtained at 2.25 and 5 MHz center frequencies from cortical bone samples (n = 43) extracted from femoral diaphyses. The study shows that the partial least squares regression technique could be employed to successfully predict (R2 = 0.71-0.73) cortical porosity. It is found that this multivariate approach can reduce uncertainty in pulse-echo assessment of cortical bone thickness from 0.220 to 0.045 mm when porosity based radial SOS was applied, instead of a constant value from literature. Upon further validation, accurate estimation of cortical bone porosity and thickness may be applied as a financially viable option for fracture risk assessment of individuals.