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Bar graphs reporting average values and standard deviations (error bars) of subchondral trabecular bone volume fraction (BV/TV), subchondral bone plate thickness (Pl.Th) and plate porosity (Pl.Po) in the 11 subregions of interest within the medial and lateral tibial condyles of (left) varus and (right) non-varus knees. Ã Significant difference between corresponding medial and lateral region (paired t-test with Bonferroni adjustment, p < 0.05).  

Bar graphs reporting average values and standard deviations (error bars) of subchondral trabecular bone volume fraction (BV/TV), subchondral bone plate thickness (Pl.Th) and plate porosity (Pl.Po) in the 11 subregions of interest within the medial and lateral tibial condyles of (left) varus and (right) non-varus knees. Ã Significant difference between corresponding medial and lateral region (paired t-test with Bonferroni adjustment, p < 0.05).  

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Tibial subchondral bone plays an important role in knee osteoarthritis (OA). Microarchitectural characterization of subchondral bone plate (SBP), underlying subchondral trabecular bone (STB) and relationships in microarchitecture between these compartments, however, is limited. The aim of this study was to characterize the spatial distribution of S...

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... differences among regions, than in the medial condyle. Between-Condylar (Medial-to-Lateral) Differences in STB and SBP Morphometric Parameters In the varus subgroup, almost all ROIs exhibited consistently significantly higher BV/TV (up to 194% higher), Tb.Th and Tb.N and lower SMI and Tb.Sp in the medial condyle compared to lateral (Table 1, Fig. 7). Similarly, in the overlaying SBP, the Pl.Th was significantly higher in the medial compared to the lateral condyle, particularly in anterior and more external ROIs (up to þ145%, regions 1-6,8,9). The Pl.Po showed fewer significant differences (5 of 11 ROIs) between condyles and with signs depending on the region, being significantly ...
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... to þ145%, regions 1-6,8,9). The Pl.Po showed fewer significant differences (5 of 11 ROIs) between condyles and with signs depending on the region, being significantly lower anteriorexternally in the medial condyle compared to lateral and higher internal-anteriorly and posteriorly compared to lateral. Meanwhile, in the non-varus subgroup (Table 2, Fig. 7), the between-condylar differences in bone microarchitecture were of lower magnitude than in varus (e.g., BV/TV differences of up to þ96%, with BV/TV higher laterally than medially in the posterior regions), significant in much fewer regions and only for the parameters Tb. N (in most posterior region 11, medially lower than laterally), ...
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... regions, although significantly so only for varus. These results are in agreement with previous OA-reports that, however, used 2D histology on 3-4 subregions per condyle, although these did not consider variations in joint alignment. 7,8 Moreover, regions of higher STB BV/TV tended to be co-located with regions of higher overlaying Pl.Th (Figs. 7 and 8), supporting earlier reports that, however, were on normal subjects, using 2D techniques. 19,35 As bone adaptation occurs in response to the mechanical environment, 36 these regional variations in bone Statistically significant linear correlations (p < 0.05) are indicated: Ã p < 0.05, ÃÃ p < 0.01; the three strongest region-specific ...

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... Samples located in the medial part of the plateau were collected from two regions, representing the minimum (region Med1) and maximum (region Med2) levels of local BV/TV [3]. Our major finding is that the Lc.V, Lc.TV, and Lc.TV/BV are significantly (p < 0.001) changing across the medial compartment of tibial plateau, known as the more damaged compartment in varus cases [18]. The difference between Lc.N/BV in two regions of Med1 and Med2 in the medial compartment is also significant (p < 0.02). ...
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Subchondral bone remodeling, mediated by osteocytes within the lacuno-canalicular network, plays a crucial role in osteoarthritis (OA) progression. Following cell death, lacunae preserve integrity, offering insights into bone remodeling mechanisms. Limited and controversial data on osteocyte lacuna morphology in OA result from small sample sizes and two-dimensional (2D) techniques that have been used thus far. This study aimed to quantify three-dimensional (3D) osteocyte lacunar characteristics at well-defined tibial plateau locations, known to be differently affected by OA. Specifically, 11 tibial plateaus were obtained from end-stage knee-OA patients with varus deformity. Each plateau provided one sample from the less affected lateral compartment and two samples from the medial compartment, at minimum and maximum bone volume fraction (BV/TV) locations. High-resolution desktop micro-computed tomography (micro-CT) at 0.7 μm voxel resolution imaged the 33 samples. Lacuna number density (Lc.N/BV) and lacuna volume density (Lc.TV/BV) were significantly lower (p < 0.02) in samples from the medial side with maximum BV/TV compared to lateral side samples. In the medial compartment at maximum local BV/TV, mean lacuna volume (Lc.V), total lacuna volume (Lc.TV), and Lc.TV/BV were significantly (p < 0.001) lower than in the region with minimum BV/TV. Lc.N/BV was also significantly lower (p < 0.02) at the maximum local BV/TV location compared to the region with minimum BV/TV. Our findings suggest that subchondral bone lacunae adapt to the changing loads in end-stage OA.
... Although OA was previously considered a primary disorder of articular cartilage, recent studies suggest that OA influences the whole joint and highlight the crucial contribution of subchondral bone in OA development and its interaction with articular cartilage. 2,3 Knee OA involves both the proximal tibia and distal femur. In varus OA knees, the medial tibiofemoral compartment of the knee joint is more damaged than the lateral compartment. ...
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... Both quality and quantity must be preserved to maximize bone resistance in the area. The specific micro-architecture of the proximal medial tibial plateau has been described and combines a highly connected trabecular network of plate-like trabeculae and a high bone density [59]. The mechanical resistance of this structured cancellous bone is enhanced by the peripheral cortical bone ring. ...
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IntroductionOn rare occasions, fractures of the tibial plateau may occur after uni-compartmental knee arthroplasty (UKA) and account for 2% of total UKA failures. The purpose of this narrative review is to identify and discuss potential risk factors that might lead to prevention of this invalidating complication.Materials and methodsElectronic database of Pubmed, Scopus, Cochrane and Google Scholar were searched. A total of 457 articles related to the topic were found. Of those, 86 references were included in this narrative review.ResultsUKA implantation acts as a stress riser in the medial compartment. To avoid fractures, surgeons need to balance load and bone stock. Post-operative lower limb alignment, implant positioning, level of resection and sizing of the tibial tray have a strong influence on load distribution of the tibial bone. Pain on weight-bearing signals bone-load imbalance and acts as an indicator of bone remodeling and should be a trigger for unloading. The first three months after surgery are critical because of transient post-operative osteoporosis and local biomechanical changes. Acquired osteoporosis is a growing concern in the arthroplasty population. Split fractures require internal fixation, while subsidence fractures differ in their management depending of the amount of bone impaction. Loose implants require revision knee arthroplasty.Conclusion Peri-prosthetic fracture is a rare, but troublesome event, which can lead to implant failure and revision surgery. Better knowledge of the multifactorial risk factors in association with a thorough surgical technique is key for prevention.
... Micro-CT allows examination of bone segments without coring at spatial resolutions in the 10-20 µm range, enabling the quantification of bone microstructure [9][10][11][12]. Previous studies using this imaging modality enhanced clinical practice [9,13], whereas studying the greater tuberosity of the proximal humerus improved the surgical approach of trans-osseous equivalent rotator cuff repair for instance [14]. From a biomechanical point of view, it aids understanding the distribution of the bone microstructure and put it in relation with possible loads within the bone, leading to possible fractures [15]. ...
... The VOIs were selected on the axial image stack (green horizontal line, Fig. 3a inset and Fig. 3b), 3 mm distal from the most proximal axial image stack where the 12 cylindrical VOIs were fitting, without involving the cortex of the proximal side (blue horizontal line, Fig. 3a inset and Fig. 3b). The VOIs had a diameter of 3.5 mm and height of 3 mm (to satisfy the continuum condition for trabecular bone analysis) [9,13,23]. Analyses were performed in the following four regions (quadrants) (Figs. 1, 3a): the anterolateral (AL), posterolateral (PL), posteromedial (PM) and anteromedial (AM) quadrant (orange, pink, yellow and blue circles, respectively). Then, for each quadrant, the average of the values of the VOIs of the 3 sectors was taken. ...
... For the trabecular microstructure analysis, images were binarized separating bone from non-bone using uniform thresholding in all specimens [11,12]. The analysis included bone volume fraction (BV/TV in %; calculated as the voxels segmented as bone within the VOI, divided by the voxels constituting the examined VOI), trabecular thickness (Tb.Th. in mm; 3D measure of the average thickness of the trabeculae [24]), trabecular number (Tb.N in mm −1 ; the number of trabecular plates per unit length [25]), trabecular separation (Tb.Sp in mm; 3D measure of the mean distance between the trabeculae [26]) and structure model index (SMI) which describes the ratio of rod-to plate-like trabecular structures, ranging in value from 0 (ideal plate-like structure) to 3 (ideal rod-like structure), with intermediate values indicating a mixed structure [13,26,27]. ...
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Introduction A characterization of the internal bone microstructure of the radial head could provide a better understanding of commonly occurring fracture patterns frequently involving the (antero)lateral quadrant, for which a clear explanation is still lacking. The aim of this study is to describe the radial head bone microstructure using micro-computed tomography (micro-CT) and to relate it to gross morphology, function and possible fracture patterns. Materials and methods Dry cadaveric human radii were scanned by micro-CT (17 μm/pixel, isotropic). The trabecular bone microstructure was quantified on axial image stacks in four quadrants: the anterolateral (AL), posterolateral (PL), posteromedial (PM) and anteromedial (AM) quadrant. Results The AL and PL quadrants displayed the significantly lowest bone volume fraction and trabecular number (BV/TV range 12.3–25.1%, Tb.N range 0.73–1.16 mm⁻¹) and highest trabecular separation (Tb.Sp range 0.59–0.82 mm), compared to the PM and AM quadrants (BV/TV range 19.9–36.9%, Tb.N range 0.96–1.61 mm⁻¹, Tb.Sp range 0.45–0.74 mm) (p = 0.03). Conclusions Our microstructural results suggest that the lateral side is the “weaker side”, exhibiting lower bone volume faction, less trabeculae and higher trabecular separation, compared to the medial side. As the forearm is pronated during most falls, the underlying bone microstructure could explain commonly observed fracture patterns of the radial head, particularly more often involving the AL quadrant. If screw fixation in radial head fractures is considered, surgeons should take advantage of the “stronger” bone microstructure of the medial side of the radial head, should the fracture line allow this.
... Direct contact of the basal cartilage layer with deeper trabecular bone has been reported in adult non-pathological human femoral heads [14][15][16] as well as mature human knee joints [17][18][19], while components such as blood vessels, osteochondral tissues, parallel lamellar bone, woven bone fibers, fat, and other unidentified soft tissues were observed underneath such contacts [16]. Moreover, SB porosity has been detected in end-stage knee OA of patients with different joint alignments, showing region-specific associations with the subchondral bone plate thickness [20]. This raises the question of the physiological and pathophysiological significance of these microchannel connectors for the overlying cartilage. ...
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The interplay between articular cartilage (AC) and subchondral bone (SB) plays a pivotal role in cartilage homeostasis and functionality. As direct connective pathways between the two are poorly understood, we examined the location-dependent characteristics of the 3D microchannel network within the SB that connects the basal cartilage layer to the bone marrow (i.e. cartilage-bone marrow microchannel connectors; CMMC). 43 measuring points were defined on five human cadaveric femoral heads with no signs of osteoarthritis (OA) (age ≤ 60), and cartilage-bone cylinders with diameters of 2.00 mm were extracted for high-resolution scanning (n = 215). The micro-CT data were categorized into three groups (load-bearing region: LBR, n = 60; non-load-bearing region: NLBR, n = 60; and the peripheral rim: PR, n = 95) based on a gait analysis estimation of the joint reaction force (young, healthy cohort with no signs of OA). At the AC-SB interface, the number of CMMC in the LBR was 1.8 times and 2.2 times higher compared to the NLBR, and the PR, respectively. On the other hand, the median Feret size of the CMMC were smallest in the LBR (55.2 µm) and increased in the NLBR (73.5 µm; p = 0.043) and the PR (89.1 µm; p = 0.043). AC thickness was positively associated with SB thickness (Pearson's r = 0.48; p < 1e-13), CMMC number. (r = 0.46; p < 1e-11), and circularity index (r = 0.61; p < 1e-38). In conclusion, our data suggest that regional differences in the microchannel architecture of SB might reflect regional differences in loading.
... Several studies have been published in the scientific literature reporting on the bone microstructure [1][2][3][4][5][6]. A relatively recently introduced technique is micro-computed tomography (micro-CT), a non-destructive high-resolution imaging modality capable of 2D and 3D micro-architectural examination of excised bone segments [4,5], at a spatial resolution (10 µm) not achievable with conventional CT imaging scanners (500 µm [7]). ...
... Several studies have been published in the scientific literature reporting on the bone microstructure [1][2][3][4][5][6]. A relatively recently introduced technique is micro-computed tomography (micro-CT), a non-destructive high-resolution imaging modality capable of 2D and 3D micro-architectural examination of excised bone segments [4,5], at a spatial resolution (10 µm) not achievable with conventional CT imaging scanners (500 µm [7]). Nowadays, micro-CT systems allow the examination of entire excised human bones, rather than tiny excised bone portions. ...
... The trabecular bone microstructure was quantified by performing histomorphometry analysis (CT Analyzer) in cubic volumes of interest (VOI) of 5 mm side [4,31] in the following three regions (Fig. 1a): (1) the olecranon process in its medial and lateral part (squares in yellow color, Fig. 1a and 1c); (2) the bare area of the trochlear notch (square in blue color); and (3) the coronoid process (square in pink color). These VOIs were selected on the sagittal image stack which was centered around the "sagittal middle plane" as identified above, extending for 5 mm corresponding to 294 cross-sections from medial to lateral. ...
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Introduction The three-dimensional (3D) microstructure of the cortical and trabecular bone of the proximal ulna has not yet been described by means of high-resolution 3D imaging. An improved characterization can provide a better understanding of their relative contribution to resist impact load. The aim of this study is to describe the proximal ulna bone microstructure using micro-computed tomography (micro-CT) and relate it to gross morphology and function. Materials and methods Five dry cadaveric human ulnae were scanned by micro-CT (17 μm/voxel, isotropic). Both qualitative and quantitative assessments were performed on sagittal image stacks. The cortical thickness of the trochlear notch and the trabecular bone microstructure were measured in the olecranon, bare area and coronoid. Results Groups of trabecular struts starting in the bare area, spanning towards the anterior and posterior side of the proximal ulna, were observed; within the coronoid, the trabeculae were orthogonal to the joint surface. Consistently among the ulnae, the coronoid showed the highest cortical thickness (1.66 ± 0.59 mm, p = 0.04) and the olecranon the lowest (0.33 ± 0.06 mm, p = 0.04). The bare area exhibited the highest bone volume fraction (BV/TV = 43.7 ± 22.4%), trabecular thickness (Tb.Th = 0.40 ± 0.09 mm) and lowest structure model index (SMI = – 0.28 ± 2.20, indicating plate-like structure), compared to the other regions (p = 0.04). Conclusions Our microstructural results suggest that the bare area is the region where most of the loading of the proximal ulna is concentrated, whereas the coronoid, together with its anteromedial facet, is the most important bony stabilizer of the elbow joint. Studying the proximal ulna bone microstructure helps understanding its possible everyday mechanical loading conditions and potential fractures. Level of evidence N.A.
... The moments investigated in this study were the first peak KAM 34 The reconstructed cross-section images were then rotated in 3D, such that the anatomical superior-inferior axis of each plateau was aligned with the z-axis of the image stack. 34 ...
... The moments investigated in this study were the first peak KAM 34 The reconstructed cross-section images were then rotated in 3D, such that the anatomical superior-inferior axis of each plateau was aligned with the z-axis of the image stack. 34 ...
... This supports previous studies that have linked knee joint malalignment with altered medial-to-lateral distribution of loads upon the joint. 9,34,45 Positive correlations were found in the AM region between cartilage thickness and KAM1 and the peak KAM, but not so in the PM region. As a larger KAM magnitude could be indicative of higher medial joint loading compared with lateral, 46 this could suggest the thinning of cartilage medially to be due to higher medial habitual loads compared with lateral in knee OA, or to some areas of cartilage being exposed to loads they are unaccustomed to. ...
Article
Biomechanical factors (e.g. joint loading) have a significant role in the progression of osteoarthritis (OA). However, some relationships between in vivo joint loading indices and tibial cartilage thickness are conflicting. This study investigated relationships between pre-operative in vivo external knee joint moments, joint alignment and regional tibial cartilage thickness using micro-CT in subjects with end-stage knee OA. Tibial plateaus from 25 patients that underwent knee replacement for OA were micro-CT scanned (17µm/voxel). Prior to surgery, subjects underwent gait analysis to calculate external knee moments. The mechanical axis deviation (MAD) was obtained from pre-operative radiographs. Cartilage thickness (Cart.Th) was analyzed from micro-CT images, in anteromedial, anterolateral, posteromedial and posterolateral subregions of interest. Medial-to-lateral Cart.Th ratios were also explored. Relationships between Cart.Th and joint loading indices were examined using Pearson’s correlations. Significant correlations were found between Cart.Th and joint loading indices, positive anteromedially with the first peak knee adduction moment (r= 0.55, p<0.01) and external rotation moment (ERM; r= 0.52, p<0.01), and negative with MAD (r= -0.76, p<0.001). In the lateral regions, these correlations had opposite signs. The medial-to-lateral Cart.Th ratio correlated strongly with ERM (r= 0.63, p=0.001) and MAD (r= -0.75, p<0.001). Joint loading indices correlated with regional cartilage thickness values and their medial-to-lateral ratios in end-stage knee OA subjects, with higher regional loads corresponding to thinner cartilage. These relationships have the opposite sign compared to the subchondral bone microarchitecture found in our previous study on the same specimens, which may suggest a complementary bone-cartilage interplay in response to loading. This article is protected by copyright. All rights reserved.
... Knee joint malalignment has previously been linked to altered medial-to-lateral distribution of loads upon the joint 10,11 and has been associated with regional changes in either subchondral bone 10,[12][13][14][15][16] or cartilage 17,18 in OA. In our previous study, on mapping of the three-dimensional (3D) bone microarchitecture of end-stage knee OA tibial plateaus, 10 joint alignment was suggested to be related to medial-to-lateral and within-condylar bone microarchitecture differences in OA groups. ...
... Knee joint malalignment has previously been linked to altered medial-to-lateral distribution of loads upon the joint 10,11 and has been associated with regional changes in either subchondral bone 10,[12][13][14][15][16] or cartilage 17,18 in OA. In our previous study, on mapping of the three-dimensional (3D) bone microarchitecture of end-stage knee OA tibial plateaus, 10 joint alignment was suggested to be related to medial-to-lateral and within-condylar bone microarchitecture differences in OA groups. ...
... Knee joint malalignment has previously been linked to altered medial-to-lateral distribution of loads upon the joint 10,11 and has been associated with regional changes in either subchondral bone 10,[12][13][14][15][16] or cartilage 17,18 in OA. In our previous study, on mapping of the three-dimensional (3D) bone microarchitecture of end-stage knee OA tibial plateaus, 10 joint alignment was suggested to be related to medial-to-lateral and within-condylar bone microarchitecture differences in OA groups. However, it is unknown whether similar variations also exist in non-pathological joints. ...
Article
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This preliminary study quantified tibia cartilage thickness (Cart.Th), subchondral bone plate thickness (SBPl.Th) and subchondral trabecular bone (STB) micro-architecture in subjects with varus-or valgus-malaligned knees diagnosed with end-stage knee osteoarthritis (OA) and compared them to controls (non-OA). Tibial plateaus from 25 subjects with knee-OA (undergoing knee arthroplasty) and 15 cadavers (controls) were micro-CT scanned (17 µm/voxel). Joint alignment was classified radiographically for OA subjects (varus-aligned n = 18, valgus-aligned n = 7). Cart.Th, SBPl.Th, STB bone volume fraction (BV/TV) and their medial-to-lateral ratios were analyzed in anteromedial, anterolateral, posteromedial and posterolateral subregions. Varus-OA and valgus-OA were compared to controls. Compared to controls (1.19-1.54 mm), Cart.Th in varus-OA was significantly lower anteromedially (0.58 mm, −59%) and higher laterally (2.19-2.47 mm, +60-63%); in valgus-OA, Cart.Th was significantly higher posteromedially (1.86 mm, +56%). Control medial-to-lateral Cart.Th ratios were around unity (0.8-1.1), in varus-OA significantly below (0.2-0.6) and in valgus-OA slightly above (1.0-1.3) controls. SBPl.Th and BV/TV were significantly higher medially in varus-OA (0.58-0.72 mm and 37-44%, respectively) and laterally in valgus-OA (0.60-0.61 mm and 32-37%), compared to controls (0.26-0.47 mm and 18-37%). In varus-OA, the medial-to-lateral SBPl.Th and BV/TV ratios were above unity (1.4-2.4) and controls (0.8-2.1); in valgus-OA they were closer to unity (0.8-1.1) and below controls. Varus-and valgus-OA tibia differ significantly from controls in Cart.Th, SBPl.Th and STB microarchitecture depending on joint alignment, suggesting structural changes in OA may reflect differences in medial-to-lateral load distribution upon the tibial plateau. Here we identified an inverse relationship between cartilage thickness and underlying subchondral bone, suggesting a whole-joint response in OA to daily stimuli. Keywords: bone microarchitecture, cartilage, knee osteoarthritis, micro-CT, tibial plateau J Orthop Res. 2020;1-12. wileyonlinelibrary.com/journal/jor
... The pQCT cross-section images (each 805 × 805 pixels in size, corresponding to 161 × 161 mm) were converted into vBMD units (mg HA/cm 3 ) using a regression equation calculated from the phantom rods. For selection of the sub-regions for the vBMD analysis, images from each participant were manually processed according to a previously described technique by our group [13,19]. The tibial plateau was divided into a medial and lateral compartment following the posterior margins on the medial and lateral spines, respectively. ...
... Anterior and posterior circular sub-regions of 10 mm diameter were defined in each condyle, to produce anteromedial (AM), anterolateral (AL), posteromedial (PM) and posterolateral (PL) sub-regions within each participant (Fig. 2). These subregions, indicated as high-and low-load bearing in the literature and in which we found differences in bone volume fraction using ex-vivo μCT in OA previously [19][20][21], were defined as the midpoint between both the major and minor axes of the anterior and posterior compartments. These sub-regions were used to analyse apparent vBMD at the proximal tibia. ...
... Future work is essential to explore if the relationships reported here differ with age and pathology. pQCT has limited spatial resolution which is not sufficient to quantify micro-architectural parameters (e.g., trabecular thickness, trabecular separation) such as those commonly reported in μCT and HR-pQCT studies [19,33], but we must find a balance between dose, resolution and other practical issues, for example, gantry size in HR-pQCT. Although recent second-generation HR-pQCT (Xtreme CT II) systems can accommodate for larger knees, they still pose a physical limit to the cohorts to be studied (42 cm maximal knee circumference and a height of 52 cm to the center of the patella in upright stance [14,34]), whereas pQCT, having a bigger and ring-like gantry (as opposed to tube-like in HR-pQCT) with freely adjustable knee holder (Fig. 1), can offer a larger user base, accommodating for almost any human knee. ...
Article
The aim of this study was to investigate if the distribution of subchondral volumetric bone mineral density (vBMD) from peripheral quantitative computed tomography (pQCT) is related to estimates of knee joint loads calculated during walking gait in healthy young people. We recruited 19 young (age 18-40 years) healthy people with no self-reported knee pain or pathology. For all participants we collected two forms of data: (1) pQCT data at 2% of tibia length (from the proximal joint line) using a Stratec XCT3000 scanner at 0.2×0.2 mm in plane resolution; and (2) indices of joint loading, specifically external joint moment, at the indexed knee during walking gait. Joint moments were calculated from motion capture and ground reaction force data. pQCT scans were performed immediately prior to gait analysis. A sub-group of 9 participants attended a second scanning session to establish the reproducibility of the pQCT workflow. vBMD was extracted for four sub-regions (anteromedial, anterolateral, posteromedial and posterolateral). Reproducibility of the pQCT workflow was good to excellent (ICCs 0.832-0.985) with minimal detectable differences ranging from 2.3-39.5 mg HA/cm3. Significant independent correlations were identified between the external rotation moment and the medial-to-lateral (r=0.517), posteromedial-to-posterolateral (r=0.627) and posteromedial-to-anterolateral (r=0.518) vBMD ratios, and between the knee adduction moment and the medial-to-lateral (r=-0.476) and posteromedial-to-posterolateral (r=-0.497) vBMD ratios. There appear to be significant relationships between measures of vBMD from pQCT and indices of joint loading in healthy people. These data are the first to combine imaging at the resolution available with pQCT and indices of joint loading in the same cohort.
... We previously reported that a specific topographical pattern characterizes osteochondral damage in knee OA in sheep (5), emulating findings from clinical studies (6,7) that suggest a location-dependent development (8). Axial malalignment of the lower extremity alters the tibiofemoral load distribution and substantially accelerates knee OA progression (9). ...
... Axial malalignment of the lower extremity alters the tibiofemoral load distribution and substantially accelerates knee OA progression (9). Patients with OA and varus malalignment (bowleggedness), the most common deformity, chiefly suffer from a destruction of their overloaded medial compartment (7,10,11). Although longitudinal imaging studies suggest that the status of the osteochondral unit-the composite of articular cartilage, calcified cartilage, and subchondral bone (1)-differs between medial and lateral and may depend on malalignment (11)(12)(13)(14)(15), extended structural evidence for this essential relationship in OA is lacking. ...
... Obesity is another major contributing factor, increasing the risk of OA by more than three times (16) through mechanisms possibly exceeding overload (17). Despite their clinical importance and individual studies evaluating patterns of tibiofemoral cartilage (11,18), subchondral bone alterations (7,10), or both, without considering alignment (5,(19)(20)(21)(22) or obesity (5,(19)(20)(21)(22), the specific interplay between overload by malalignment or overweight and the resulting spatial alteration patterns within the entire osteochondral unit remains poorly understood (23). ...
Article
Osteoarthritis (OA) is considerably affected by joint alignment. Here, we investigate the patterns of spatial osteochondral heterogeneity in patients with advanced varus knee OA together with clinical data. We report strong correlations of osteochondral parameters within individual topographical patterns, highlighting their fundamental and location-dependent interactions in OA. We further identify site-specific effects of varus malalignment on the lesser loaded compartment and, conversely, an unresponsive overloaded compartment. Last, we trace compensatory mechanisms to the overloaded subarticular spongiosa in patients with additional high body weight. We therefore propose to consider and to determine axial alignment in clinical trials when selecting the location to assess structural changes in OA. Together, these findings broaden the scientific basis of therapeutic load redistribution and weight loss in varus knee OA.