Subchondral Trabecular Bone Microarchitecture Research Articles

Correlation between tibial and femoral bone and cartilage changes in end-stage knee osteoarthritis.

Knee osteoarthritis is a whole joint disease highlighting the coupling of cartilage and bone adaptations. However, the structural properties of the subchondral bone plate (SBP) and underlying subchondral trabecular bone (STB) in the femoral compartment have received less attention compared to the tibial side. Furthermore, how the properties in the femoral compartment relate to those in the corresponding tibial site is unknown. Therefore, this study aimed to quantify the structural bone and cartilage morphology in the femoral compartment and investigate its association with those of the tibial plateau. Specifically, tibial plateaus and femoral condyles were retrieved from 28 patients with end-stage knee-osteoarthritis (OA) and varus deformity. The medial condyle of tibial plateaus and the distal part of the medial femoral condyles were micro-CT scanned (20.1μm/voxel). Cartilage thickness (Cart.Th), SBP, and STB microarchitecture were quantified. Significant (P< <.001; 0.79 ≤r≤ 0.97) correlations with a relative difference within 10% were found between the medial side of the femoral and tibial compartments. The highest correlations were found for SBP porosity (r= 0.97, mean absolute difference of 0.50%, and mean relative difference of 9.41%) and Cart.Th (r= 0.96, mean absolute difference of 0.18mm, and relative difference of 7.08%). The lowest correlation was found for trabecular thickness (r= 0.79, mean absolute difference of 21.07μm, and mean relative difference of 5.17%) and trabecular number (r= 0.79, mean absolute difference of 0.18mm-1, and relative difference of 5.02%). These findings suggest that the distal femur is affected by OA in a similar way as the proximal tibia. Given that bone adaptation is a response to local mechanical forces, our results suggest that varus deformity similarly affects the stress distribution of the medial tibial plateau and the medial distal femur.

Microstructural adaptations of the subchondral bone are related to the mechanical axis deviation in end stage varus oa knees.

Recent studies highlighted the crucial contribution of subchondral bone to OA development. Yet, only limited data have been reported on the relation between alteration to cartilage morphology, structural properties of the subchondral bone plate (SBP) and underlying subchondral trabecular bone (STB). Furthermore, the relationship between the morphometry of the cartilage and bone in the tibial plateau and the OA-induced changes in the joint's mechanical axis remains unexplored. Therefore, a visualisation and quantification of cartilage and subchondral bone microstructure in the medial tibial plateau was performed. End stage knee-OA patients with varus alignment and scheduled for total knee arthroplasty (TKA) underwent preoperative fulllength radiography to measure the hip-knee-ankle angle (HKA) and the mechanical-axis deviation (MAD). 18 tibial plateaux were μ-CT scanned (20.1 μm/voxel). Cartilage thickness, SBP, and STB microarchitecture were quantified in 10 volumes of interest (VOIs) in each medial tibial plateau. Significant differences (p < 0.001) were found for cartilage thickness, SBP, and STB microarchitecture parameters among the VOIs. Closer to the mechanical axis, cartilage thickness was consistently smaller, while SBP thickness and STB bone volume fraction (BV/TV) were higher. Moreover, trabeculae were also more superior-inferiorly oriented, i.e. perpendicular to the transverse plane of the tibial plateau. As cartilage and subchondral bone changes reflect responses to local mechanical loading patterns in the joint, the results suggested that region-specific subchondral bone adaptations were related to the degree of varus deformity. More specifically, subchondral sclerosis appeared to be most pronounced closer to the mechanical axis of the knee.

Subchondral Bone Relative Area and Density in Human Osteoarthritic Femoral Heads Assessed with Micro-CT before and after Mechanical Embedding of the Innovative Multi-Spiked Connecting Scaffold for Resurfacing THA Endoprostheses: A Pilot Study.

The multi-spiked connecting scaffold (MSC-Scaffold) prototype is the essential innovation in the fixation of components of resurfacing total hip arthroplasty (THRA) endoprostheses in the subchondral trabecular bone. We conducted the computed micro-tomography (micro-CT) assessment of the subchondral trabecular bone microarchitecture before and after the MSC-Scaffold embedding in femoral heads removed during long-stem endoprosthesis total hip arthroplasty (THA) of different bone densities from 4 patients with hip osteoarthritis (OA). The embedding of the MSC-Scaffold in subchondral trabecular bone causes the change in its relative area (BA/TA, bone area/total area ratio) ranged from 18.2% to 24.7% (translating to the calculated density ρB relative change 11.1–14.4%, and the compressive strength S relative change 75.3–122.7%) regardless of its initial density (before the MSC-Scaffold embedding). The densification of the trabecular microarchitecture of subchondral trabecular bone due to the MSC-Scaffold initial embedding gradually decreases with the increasing distance from the apexes of the MSC-Scaffold’s spikes while the spatial extent of this subchondral trabecular bone densification ranged from 1.5 to 2.5 mm (which is about half the height of the MSC-Scaffold’s spikes). It may be suggested, despite the limited number of examined femoral heads, that: (1) the magnitude of the effect of the MSC-Scaffold embedding on subchondral trabecular bone densification may be a factor contributing to the maintenance of the MSC-Scaffold also for decreased initial bone density values, (2) the deeper this effect of the subchondral trabecular bone densification, the better strength of subchondral trabecular bone, and as consequence, the better post-operative embedding of the MSC-Scaffold in the bone should be expected.

Tibial cartilage, subchondral bone plate and trabecular bone microarchitecture in varus-and valgus-osteoarthritis versus controls.

This preliminary study quantified tibia cartilage thickness (Cart.Th), subchondral bone plate thickness (SBPl.Th)and subchondral trabecular bone (STB) microarchitecture 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.Thand 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.

Association between knee alignment, osteoarthritis disease severity, and subchondral trabecular bone microarchitecture in patients with knee osteoarthritis: a cross-sectional study

BackgroundKnee osteoarthritis (OA) is a common disabling disease involving the entire joint tissue, and its onset and progression are affected by many factors. However, the current number of studies investigating the relationship between subchondral trabecular bone (STB), knee alignment, and OA severity is limited. We aimed to investigate the variation in tibial plateau STB microarchitecture in end-stage knee OA patients and their association with knee alignment (hip-knee-ankle, HKA, angle) and OA severity.MethodsSeventy-one knee OA patients scheduled for total knee arthroplasty (TKA) underwent preoperative radiography to measure the HKA angle and Kellgren-Lawrence grade. Tibial plateaus collected from TKA were scanned using micro-computed tomography to analyze the STB microarchitecture. Histological sections were used to assess cartilage degeneration (OARSI score). Correlations between the HKA angle, OA severity (OARSI score, Kellgren-Lawrence grade), and STB microarchitecture were evaluated. Differences in STB microstructural parameters between varus and valgus alignment groups based on the HKA angle were examined.ResultsThe HKA angle was significantly correlated with all STB microarchitecture parameters (p < 0.01). The HKA angle was more correlated with the medial-to-lateral ratios of the microarchitecture parameters than with the medial or lateral tibia plateaus. The HKA angle and all STB microarchitecture parameters are significantly correlated with both the OARSI score and Kellgren-Lawrence grade (p < 0.01).ConclusionsThe STB microarchitecture is associated with the HKA angle and OA severity. With the increase of the knee alignment deviation and OA severity, the STB of the affected side tibial plateau increased in bone volume, trabecular number, and trabecular thickness and decreased in trabecular separation.

Pulsed Electromagnetic Field Versus Whole Body Vibration on Cartilage and Subchondral Trabecular Bone in Mice With Knee Osteoarthritis.

Pulsed electromagnetic field (PEMF) and whole body vibration (WBV) interventions are expected to be important strategies for management of osteoarthritis (OA). The aim of the study was to investigate the comparative effectiveness of PEMF versus WBV on cartilage and subchondral trabecular bone in mice with knee OA (KOA) induced by surgical destabilization of the medial meniscus (DMM). Forty 12-week-old male C57/BL mice were randomly divided into four groups (n = 10): Control, OA, PEMF, and WBV. OA was induced (OA, PEMF, and WBV groups) by surgical DMM of right knee joint. Mice in PEMF group received 1 h/day PEMF exposure with 75 Hz, 1.6 mT for 4 weeks, and the WBV group was exposed to WBV for 20 min/day with 5 Hz, 4 mm, 0.3 g peak acceleration for 4 weeks. Micro-computed tomography (micro-CT), histology, and immunohistochemistry analyses were performed to evaluate the changes in cartilage and microstructure of trabecular bone. The bone volume fraction (BV/TV), trabecular thickness (Tb.Th), and trabecular number (Tb.N) increased, and bone surface/bone volume (BS/BV) decreased by micro-CT analysis in PEMF and WBV groups. The Osteoarthritis Research Society International (OARSI) scores in PEMF and WBV groups were significantly lower than in the OA group. Immunohistochemical results showed that PEMF and WBV promoted expressions of Aggrecan, and inhibited expressions of IL-1β, ADAMTS4, and MMP13. Superior results are seen in PEMF group compared with WBV group. Both PEMF and WBV were effective, could delay cartilage degeneration and preserve subchondral trabecular bone microarchitecture, and PEMF was found to be superior to WBV. Bioelectromagnetics. 2020;41:298-307 © 2020 Bioelectromagnetics Society.

Relationships between in vivo dynamic knee joint loading, static alignment and tibial subchondral bone microarchitecture in end-stage knee osteoarthritis

To study, in end-stage knee osteoarthritis (OA) patients, relationships between indices of invivo dynamic knee joint loads obtained pre-operatively using gait analysis, static knee alignment, and the subchondral trabecular bone (STB) microarchitecture of their excised tibial plateau quantified with 3D micro-CT. Twenty-five knee OA patients scheduled for total knee arthroplasty underwent pre-operative gait analysis. Mechanical axis deviation (MAD) was determined radiographically. Following surgery, excised tibial plateaus were micro-CT-scanned and STB microarchitecture analysed in four subregions (anteromedial, posteromedial, anterolateral, posterolateral). Regional differences in STB microarchitecture and relationships between joint loading and microarchitecture were examined. STB microarchitecture differed among subregions (P<0.001), anteromedially exhibiting highest bone volume fraction (BV/TV) and lowest structure model index (SMI). Anteromedial BV/TV and SMI correlated strongest with the peak external rotation moment (ERM; r=-0.74, r=0.67, P<0.01), despite ERM being the lowest (by factor of 10) of the moments considered, with majority of ERM measures below accuracy thresholds; medial-to-lateral BV/TV ratios correlated with ERM, MAD, knee adduction moment (KAM) and internal rotation moment(|r|-range: 0.54-0.74). When controlling for walking speed, KAM and MAD, the ERM explained additional 11-30% of the variations in anteromedial BV/TV and medial-to-lateral BV/TV ratio (R2=0.59, R2=0.69, P<0.01). This preliminary study suggests significant associations between tibial plateau STB microarchitecture and knee joint loading indices in end-stage knee OA patients. Particularly, anteromedial BV/TV correlates strongest with ERM, whereas medial-to-lateral BV/TV ratio correlates strongest with indicators of medial-to-lateral joint loading (MAD, KAM) and rotational moments. However, associations with ERM should be interpreted with caution.

Joint loading and proximal tibia subchondral trabecular bone microarchitecture differ with walking gait patterns in end-stage knee osteoarthritis.

To (1) stratify patient subgroups according to their distinct walking gait patterns in end-stage knee osteoarthritis (OA); (2) compare measures of joint loading and proximal tibia subchondral trabecular bone (STB) microarchitecture among these gait subgroups. Twenty-five knee OA patients undergoing total knee arthroplasty (TKA) had pre-operative gait analysis. Following surgery, excised tibial plateaus were micro-CT-scanned and STB microarchitecture analysed in four tibial condylar regions of interest. Peak knee moments were input to k-means cluster analysis, to identify subgroups with homogeneous gait patterns. Joint loading and STB microarchitecture parameters were compared among gait subgroups (Kruskal-Wallis, Bonferroni-corrected Mann-Whitney U tests). Three gait subgroups were revealed: biphasics (n=7), flexors (n=9), counter-rotators (n=9). Peak knee adduction moment (KAM) and KAM impulse were significantly higher (P<0.05) in biphasics than in flexors and counter-rotators (KAM=-0.65, -0.40 and -0.21Nm/kg, respectively), suggesting a higher medial-to-lateral tibiofemoral load ratio in biphasics. Interestingly, STB medial-to-lateral bone volume fraction (BV/TV) ratio was also significantly higher (more than double) in biphasics and flexors than in counter-rotators (2.24, 2.00 and 1.00, respectively), whereas in biphasics it was only 10% higher than in flexors and not significantly so. Within the confines of the limited sample size, data suggests that different mechanisms between the biphasic and flexor gait subroups may generate comparable loads upon the tibial plateau and corresponding bony responses, despite significantly lower KAM indices in flexors. Hence, in flexor gait OA patients, conservative treatments designed to reduce KAM, may not be appropriate. Understanding joint loading among walking gait patterns and relationships to bone microarchitecture may aid at identifying/improving management of persons at risk for developing knee OA.

Effect of low-magnitude different-frequency whole-body vibration on subchondral trabecular bone microarchitecture, cartilage degradation, bone/cartilage turnover, and joint pain in rabbits with knee osteoarthritis

BackgroudWhole-body vibration(WBV) has been suggested for the prevention of subchondral bone loss of knee osteoarthritis (OA) . This study examined the effects of different frequency of whole-body vibration on subchondral trabecular bone microarchitecture, cartilage degradation and metabolism of the tibia and femoral condyle bone, and joint pain in an anterior cruciate ligament transection (ACLT)–induced knee osteoarthritisrabbit model.MethodNinety adult rabbits were divided into six groups: all groups received unilateral ACLT; Group 1, ACLT only; Group 2, 5 Hz WBV; Group 3, 10 Hz WBV; Group 4, 20 Hz WBV; Group 5, 30 Hz WBV; and Group 6, 40 Hz WBV. Pain was tested via weight-bearing asymmetry. Subchondral trabecular bone microarchitecture was examined using in vivo micro-computed tomography. Knee joint cartilage was evaluated by gross morphology, histology, and ECM gene expression level (aggrecan and type II collagen [CTX-II]). Serum bone-specific alkaline phosphatase, N-mid OC, cartilage oligometric protein, CPII, type I collagen, PIIANP, G1/G2 aggrecan levels, and urinary CTX-II were analyzed.ResultsAfter 8 weeks of low-magnitude WBV, the lower frequency (10 Hz and 20 Hz) WBV treatment decreased joint pain and cartilage resorption, accelerated cartilage formation, delayed cartilage degradation especially at the 20 Hz regimen. However, the higher frequencies (30 Hz and 40 Hz) had worse effects, with worse limb function and cartilage volume as well as higher histological scores and cartilage resorption. In contrast, both prevented loss of trabeculae and increased bone turnover. No significant change was observed in the 5 Hz WBV group.ConclusionOur data demonstrate that the lower frequencies (10 Hz and 20 Hz) of low-magnitude WBV increased bone turnover, delayed cartilage degeneration, and caused a significant functional change of the OA-affected limb in ACLT-induced OA rabbit model but did not reverse OA progression after 8 weeks of treatment.

Effect Of Low-magnitude Different-frequency Whole-body Vibration On Subchondral

PURPOSE: To investigate the effects of different vibration frequencies of low-magnitude whole-body vibration (WBV) on subchondral trabecular bone microarchitecture, cartilage degradation and metabolism of the tibia and femoral condyle bone, and jointpain in an anterior cruciate ligament transection (ACLT)-induced knee osteoarthritis(OA) rabbit model. METHODS: Ninety adult rabbits subjected to unilateral ACLT were divided into six groups:Group 1,ACLT control group;Group 2,WBV (5 Hz) + ACLT;Group 3,WBV (10 Hz) +ACLT;Group 4,WBV (20 Hz) + ACLT;Group 5,WBV (30 Hz);and Group 6,WBV (40Hz).Pain was tested via weight-bearing asymmetry.Subchondral trabecular bone microarchitecture was examined using in vivo micro-computed tomography. Knee joint cartilage was evaluated by gross morphology, histology, and ECM gene expression level (aggrecan and type II collagen [CTX-II]).Serum bone-specific alkaline phosphatase,N-mid OC,cartilage oligometric protein,CPII,type I collagen,PIIANP,G1/G2 aggrecan levels, and urinary CTX-II were analyzed. RESULTS: After 8 weeks of low-magnitude WBV, the lower frequency (10 Hz and 20 Hz) WBV treatment decreased joint pain and cartilage resorption, accelerated cartilage formation, delayed cartilage degradation especially at the 20 Hz regimen. However, the higher frequencies (30 Hz and 40 Hz) had worse effects, with worse limb function and cartilage volume as well as higher histological scores and cartilage resorption. In contrast, both prevented loss of trabeculae and increased bone turnover. No significant change was observed in the 5 Hz group. CONCLUSIONS: Our data demonstrate that the lower frequencies (10 Hz and 20 Hz) of low-magnitude WBV increased bone turnover, delayed cartilage degeneration, and caused a significant functional change of the OA-affected limb in ACLT-induced OA rabbit model but did not reverse OA progression after 8 weeks of treatment.

Pulsed electromagnetic field at different stages of knee osteoarthritis in rats induced by low-dose monosodium iodoacetate: Effect on subchondral trabecular bone microarchitecture and cartilage degradation.

The aim of the study was to investigate the efficacy of pre-emptive, early, and delayed pulsed electromagnetic field (PEMF) treatment on cartilage and subchondral trabecular bone in knee osteoarthritis (OA) rats induced by low-dose monosodium iodoacetate (MIA). Seventy-five 12-week-old male Sprague-Dawley rats were assigned to five groups: OA (n = 30), pre-emptive PEMF (n = 10), early PEMF (n = 10), delayed PEMF (n = 10), and control (n = 15). Osteoarthritis was induced by injecting 0.2 mg MIA in rat's right knee joint. Control rats received a single sterile saline injection in the right knee. Male rats received pre-emptive (n = 10, day 0-end of week 4), early (n = 10, end of week 4-end of week 8), or delayed (n = 10, end of week 8-end of week 12) PEMF treatment (75 Hz, 1.6 mT). After 4, 8, and 12 weeks, rats were sacrificed at each time point and right knees were harvested. After sacrifice, micro-computed tomography, histology, and biomarker analyses were performed. We found pre-emptive PEMF treatment preserved subchondral trabecular bone microarchitecture and prevented subchondral bone loss in MIA-induced OA rat model. Early and delayed PEMF treatment maintained subchondral trabeculae. PEMF treatment increased bone and cartilage formation, and decreased bone and cartilage resorption. Pre-emptive and early PEMF treatment had moderate effects on cartilage degradation. Time point of treatment initiation is crucial for treating OA. PEMF might become a potential biophysical treatment modality for osteoarthritis. Bioelectromagnetics. 38:227-238, 2017. © 2016 Wiley Periodicals, Inc.

Systematic mapping of the subchondral bone 3D microarchitecture in the human tibial plateau: Variations with joint alignment.

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 between these compartments, however, is limited. The aim of this study was to characterize the spatial distribution of SBP thickness, SBP porosity and STB microarchitecture, and relationships among them, in OA tibiae of varying joint alignment. Twenty-five tibial plateaus from end-stage knee-OA patients, with varus (n = 17) or non-varus (n = 8) alignment were micro-CT scanned (17 μm/voxel). SBP and STB microarchitecture was quantified via a systematic mapping in 22 volumes of interest per knee (11 medial, 11 lateral). Significant within-condylar and between-condylar (medial vs. lateral) differences (p < 0.05) were found. In varus, STB bone volume fraction (BV/TV) was consistently high throughout the medial condyle, whereas in non-varus, medially, it was more heterogeneously distributed. Regions of high SBP thickness were co-located with regions of high STB BV/TV underneath. In varus, BV/TV was significantly higher medially than laterally, however, not so in non-varus. Moreover, region-specific significant associations between the SBP thickness and SBP porosity and the underlying STB microarchitecture were detected, which in general were not captured when considering the values averaged for each condyle. As subchondral bone changes reflect responses to local mechanical and biochemical factors within the joint, our results suggest that joint alignment influences both the medial-to-lateral and the within-condyle distribution of force across the tibia, generating corresponding local bony responses (adaptation) of both the subchondral bone plate and underlying subchondral trabecular bone microarchitecture. © 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 35:1927-1941, 2017.

Pre-emptive, early, and delayed alendronate treatment in a rat model of knee osteoarthritis: effect on subchondral trabecular bone microarchitecture and cartilage degradation of the tibia, bone/cartilage turnover, and joint discomfort

Bisphosphonates are considered potential disease modifying osteoarthritis (OA) agents. The present study investigated the efficacy of pre-emptive, early, and delayed alendronate (ALN) treatment initiation on subchondral trabecular bone and cartilage in low-dose monosodium iodoacetate (MIA)-induced knee OAin rats. Male rats received pre-emptive (n=12, day 0-end of week 2), early (n=12, end of week 2-end of week 6), or delayed (n=12, end of week 6-end of week 10) ALN treatment (30μg/kg/week). Pre-emptive ALN-treated rats were scanned using invivo micro-computed tomography (micro-CT) after 2 weeks and then sacrificed, early ALN-treated rats were scanned after 2 and 6 weeks and sacrificed, and the delayed ALN-treated rats were scanned after 2, 6, and 10 weeks of OA induction and sacrificed. After sacrifice, bone histomorphometry and histology of the tibia and biomarker analyses were undertaken. Changes in hind limb weight-bearing were assessed from day-1 until day 14. MIA-induced pathological features similar to progressive human OA in the cartilage and subchondral bone. Pre-emptive ALN treatment preserved subchondral trabecular bone microarchitecture, prevented bone loss, decreased bone turnover and joint discomfort. Pre-emptive ALN treatment had moderate effects on cartilage degradation. Early and delayed ALN treatments prevented loss of trabeculae and decreased bone turnover, but had no significant effect on cartilage degradation. ALN prevented increased bone turnover and preserved the structural integrity of subchondral bone in experimental OA. The time point of treatment initiation is crucial for treating OA. Treating both the subchondral bone and cartilage in OA would be clinically more beneficial.