A comparative study of the trabecular bony architecture of the talus in humans, non-human primates, and Australopithecus

This study tested the hypothesis that talar trabecular microarchitecture reflects the loading patterns in the primate ankle joint, to determine whether talar trabecular morphology might be useful for inferring locomotor behavior in fossil hominins. Trabecular microarchitecture was quantified in the anteromedial, anterolateral, posteromedial, and posterolateral quadrants of the talar body in humans and non-human primates using micro-computed tomography. Trabecular bone parameters, including bone volume fraction, trabecular number and thickness, and degree of anisotropy differed between primates, but not in a manner entirely consistent with hypotheses derived from locomotor kinematics. Humans have highly organized trabecular struts across the entirety of the talus, consistent with the compressive loads incurred during bipedal walking. Chimpanzees possess a high bone volume fraction, consisting of plate-like trabecular struts. Orangutan tali are filled with a high number of thin, connected trabeculae, particularly in the anterior portion of the talus. Gorillas and baboons have strikingly similar internal architecture of the talus. Intraspecific analyses revealed no regional differences in trabecular architecture unique to bipedal humans. Of the 22 statistically significant regional differences in the human talus, all can also be found in other primates. Trabecular thickness, number, spacing, and connectivity density had the same regional relationship in the talus of humans, chimpanzees, gorillas, and baboons, suggesting a deeply conserved architecture in the primate talus. Australopithecus tali are human-like in most respects, differing most notably in having more oriented struts in the posteromedial quadrant of the body compared with the posterolateral quadrant. Though this result could mean that australopiths loaded their ankles in a unique manner during bipedal gait, the regional variation in degree of anisotropy was similar in humans, chimpanzees, and gorillas. These results collectively suggest that the microarchitecture of the talus does not simply reflect the loading environment, limiting its utility in reconstructing locomotion in fossil primates.     

A structural model for the mechanical behavior of trabecular bone

A quantitative model is developed for trabecular bone by approximating the trabecular geometry with a hypothetical network of compact bone. For the region immediately beneath the articular cartilage in the distal end of the femur, finite element analyses were performed with a high speed computer, assuming a physiological static load. The results indicate that bending and buckling of trabeculae are considerable in any elastic deformation of the bone; that fatigue fracture in some fraction of suitably oriented trabeculae is inevitable in normal ambulation; and that the stiffness varies considerably with lateral position across the subchondral plate. The latter depends totally on trabecular arrangement and may play a role in joint function and degeneration. The adjustments necessary to bring the gross stiffness into agreement with experiment imply that the intertrabecular soft tissues are of no consequence to the mechanical properties and that the compact bone of which trabeculae are made is probably not as stiff as cortical bone.     

Ultrasound indentation of bovine knee articular cartilage in situ

We have earlier developed a handheld ultrasound indentation instrument for the diagnosis of articular cartilage degeneration. In ultrasound indentation, cartilage is compressed with the ultrasound transducer. Tissue thickness and deformation are calculated from the A-mode ultrasound signal and the stress applied is registered with the strain gauges. In this study, the applicability of the ultrasound indentation instrument to quantify site-dependent variation in the mechano-acoustic properties of bovine knee cartilage was investigated. Osteochondral blocks (n=6 per site) were prepared from the femoral medial condyle (FMC), the lateral facet of the patello-femoral groove (LPG) and the medial tibial plateau (MTP). Cartilage stiffness (dynamic modulus, E(dyn)), as obtained with the ultrasound indentation instrument in situ, correlated highly linearly (r=0.913, p<0.01) with the values obtained using the reference material-testing device in vitro. Reproducibility (standardized coefficient of variation) of the ultrasound indentation measurements was 5.2%, 1.7% and 3.1% for E(dyn), ultrasound reflection coefficient of articular surface (R) and thickness, respectively. E(dyn) and R were site dependent (p<0.05, Kruskall-Wallis H test). E(dyn) was significantly higher (p<0.05, Kruskall-Wallis Post Hoc test) in LPG (mean+/-SD: 10.1+/-3.1MPa) than in MTP (2.9+/-1.4MPa). In FMC, E(dyn) was 4.6+/-1.3MPa. R was significantly (p<0.05) lower at MTP (2.0+/-0.7%) than at other sites (FMC: 4.2+/-0.9%; LPG: 4.4+/-0.8%). Cartilage glycosaminoglycan concentration, as quantified with the digital densitometry, correlated positively with E(dyn) (r=0.678, p<0.01) and especially with the equilibrium Young's modulus (reference device, r=0.874, p<0.01) but it was not associated with R (r=0.294, p=0.24). We conclude that manual measurements are reproducible and the instrument may be used for detection of cartilage quality in situ. Especially, combined measurement of thickness, E(dyn) and R provides valuable diagnostic information on cartilage status.     

Pathological change of articular cartilage in the mandibular head treated with immunosuppressant FK 506

While several reports have documented immunosuppressant-induced osteoporosis, the exact mechanism of the pathological change of the joint remains to be clarified. In the present study, we have demonstrated the pathological change of the articular cartilage in the mandibular head of five Sprague-Dawley rats administered with the immunosuppressant FK 506 for 28 days. Three-dimensional micro-computed tomography of the mandibular heads in treated rats showed a significant decrease in trabecular bone volume compared to control rats. Histological observation revealed atrophic change of the articular cartilage. Immunohistological observation using anti-proliferative cell nuclear antibody (PCNA), type I, II, and type X collagen antibodies showed significantly decreased proliferation and differentiation of chondrocytes in the articular cartilage compared with the control group (p<0.05). Tartrate-resistant acid phosphatase (TRAP) staining revealed no significant difference in the numbers of osteoclasts at the chondro-osseous junction. Thus, FK 506 administration inhibited chondrogenic cell proliferation and differentiation and might cause osteoporotic change of subcartilage trabecular bone that subsequently forms in the mandibular head.     

Age-related changes in human trabecular bone: Relationship between microstructural stress and strain and damage morphology

Accumulation of microdamage in aging and disease can cause skeletal fragility and is one of several factors contributing to osteoporotic fractures. To better understand the role of microdamage in fragility fracture, the mechanisms of bone failure must be elucidated on a tissue-level scale where interactions between bone matrix properties, the local biomechanical environment, and bone architecture are concurrently examined for their contributions to microdamage formation. A technique combining histological damage assessment of individual trabeculae with linear finite element solutions of trabecular von Mises and principal stress and strain was used to compare the damage initiation threshold between pre-menopausal (32-37 years, n=3 donors) and post-menopausal (71-80 years, n=3 donors) femoral cadaveric bone. Strong associations between damage morphology and stress and strain parameters were observed in both groups, and an age-related decrease in undamaged trabecular von Mises stress was detected. In trabeculae from younger donors, the 95% CI for von Mises stress on undamaged regions ranged from 50.7-67.9MPa, whereas in trabeculae from older donors, stresses were significantly lower (38.7-50.2, p<0.01). Local microarchitectural analysis indicated that thinner, rod-like trabeculae oriented along the loading axis are more susceptible to severe microdamage formation in older individuals, while only rod-like architecture was associated with severe damage in younger individuals. This study therefore provides insight into how damage initiation and morphology relate to local trabecular microstructure and the associated stresses and strains under loading. Furthermore, by comparison of samples from pre- and post-menopausal women, the results suggest that trabeculae from younger individuals can sustain higher stresses prior to microdamage initiation.     

Multipotential stromal cells in the talus and distal tibia in ankle osteoarthritis – Presence,potency and relationships to subchondral bone changes

A large proportion of ankle osteoarthritis (OA) has an early onset and is post-traumatic. Surgical interventions have low patient satisfaction and relatively poor clinical outcome, whereas joint-preserving treatments, which rely on endogenous multipotential stromal cells (MSCs), result in suboptimal repair. This study investigates MSC presence and potency in OA-affected talocrural osteochondral tissue. Bone volume fraction (BV/TV) changes for the loading region trabecular volume and subchondral bone plate (SBP) thickness in OA compared with healthy tissue were investigated using microcomputed tomography. CD271-positive MSC topography was related to bone and cartilage damage in OA tissue, and in vitro MSC potency was compared with control healthy iliac crest (IC) MSCs. A 1.3- to 2.5-fold SBP thickening was found in both OA talus and tibia, whereas BV/TV changes were depth-dependent. MSCs were abundant in OA talus and tibia, with similar colony characteristics. Tibial and talar MSCs were tripotential, but talar MSCs had 10-fold lower adipogenesis and twofold higher chondrogenesis than IC MSCs (P = .01 for both). Cartilage damage in both OA tibia and talus correlated with SBP thickening and CD271+ MSCs was 1.4- to twofold more concentrated near the SBP. This work shows multipotential MSCs are present in OA talocrural subchondral bone, with their topography suggesting ongoing involvement in SBP thickening. Potentially, biomechanical stimulation could augment the chondrogenic differentiation of MSCs for joint-preserving treatments.     

Effect of alendronate on post-traumatic osteoarthritis induced by anterior cruciate ligament rupture in mice

IntroductionPrevious studies in animal models of osteoarthritis suggest that alendronate (ALN) has antiresorptive and chondroprotective effects, and can reduce osteophyte formation. However, these studies used non-physiologic injury methods, and did not investigate early time points during which bone is rapidly remodeled prior to cartilage degeneration. The current study utilized a non-invasive model of knee injury in mice to investigate the effect of ALN treatment on subchondral bone changes, articular cartilage degeneration, and osteophyte formation following injury.MethodsNon-invasive knee injury via tibial compression overload or sham injury was performed on a total of 90 mice. Mice were treated with twice weekly subcutaneous injections of low-dose ALN (40 μg/kg/dose), high-dose ALN (1,000 μg/kg/dose), or vehicle, starting immediately after injury until sacrifice at 7, 14 or 56 days. Trabecular bone of the femoral epiphysis, subchondral cortical bone, and osteophyte volume were quantified using micro-computed tomography (μCT). Whole-joint histology was performed at all time points to analyze articular cartilage and joint degeneration. Blood was collected at sacrifice, and serum was analyzed for biomarkers of bone formation and resorption.ResultsμCT analysis revealed significant loss of trabecular bone from the femoral epiphysis 7 and 14 days post-injury, which was effectively prevented by high-dose ALN treatment. High-dose ALN treatment was also able to reduce subchondral bone thickening 56 days post-injury, and was able to partially preserve articular cartilage 14 days post-injury. However, ALN treatment was not able to reduce osteophyte formation at 56 days post-injury, nor was it able to prevent articular cartilage and joint degeneration at this time point. Analysis of serum biomarkers revealed an increase in bone resorption at 7 and 14 days post-injury, with no change in bone formation at any time points.ConclusionsHigh-dose ALN treatment was able to prevent early trabecular bone loss and cartilage degeneration following non-invasive knee injury, but was not able to mitigate long-term joint degeneration. These data contribute to understanding the effect of bisphosphonates on the development of osteoarthritis, and may support the use of anti-resorptive drugs to prevent joint degeneration following injury, although further investigation is warranted.     

Talar articular facets (facies articulares talares) in human calcanei

The variations of the talar articular facets in 176 calcanei were studied and classified. Three types were considered: type A = calcanei with two articular facets for the talar head, with four subtypes; type B = calcanei with one articular facet for the talar head, and two subtypes, and type C = unique articular facies in the superior surface of the calcaneus for the talus. We found 53% (94 cases) type B calcanei and 46% (82 cases) type A calcanei. No calcanei of type C were seen.     

Three-dimensional orientations of talar articular surfaces in humans and great apes

The morphology of the talus prescribes relative positions and movements of the calcaneus and navicular with respect to the tibia, hence determining the overall geometry, mobility and function of the foot that mechanically interacts with environments. Clarifying the variations of the articular surface orientations of the talus in humans and extant great apes is therefore of importance in understanding the evolution of bipedal locomotion in the human lineage. The aim of this study is to clarify the three-dimensional orientations of three articular surfaces of the talus (superior, posterior calcaneal and navicular articular surfaces) by means of the newly proposed surface approximation method. Thirty-two tali in humans, chimpanzees, gorillas and orangutans were scanned using a three-dimensional noncontact digitizer, and the articular surfaces were then approximated using a paraboloid or a plane to calculate the orientations of the surfaces with respect to the body of the talus. The results quantitatively demonstrated that the superior articular surfaces in humans were relatively more parallel with the horizontal plane of the talar body, while those in apes were more medially oriented. Furthermore, the cylindrical axis defined by the shape of the posterior calcaneal articular surface was directed less anteroposteriorly in humans than in apes, in contrast to the fact that the subtalar axis is more anteroposteriorly oriented in humans. It was also demonstrated that the navicular articular surface in humans was more plantarly oriented and axially twisted. These specialized features of the human talus seem to be functionally linked to obligate bipedal locomotion. The talar morphological differences among the great apes were prominent in the mediolateral and rotational orientations of the navicular articular surfaces, possibly reflecting the degree of arboreality among the great apes.     

Age-related changes in the tensile properties of human articular cartilage: a comparative study between the femoral head of the hip joint and the talus of the ankle joint

Specimens of articular cartilage from the superficial and mid-depth zones of the human femoral head and the talus of the ankle joint were tested in tension in planes parallel to the articular surface and parallel to the predominant orientation of the superficial collagen fibrils. The tensile fracture stress of cartilage from both the superficial and mid-depth zones of the femoral head decreased considerably with age. The superficial zone decreased from 33 MPa at 7 years to 10 MPa by the age of 90 years, while the mid-depth zone decreased from 32 MPa at 7 years to 2 MPa by the age of 85 years. In contrast the fracture stress of both levels of cartilage from the talus of the ankle did not decrease significantly with increasing age. The tensile stiffness at 10 MPa of both the superficial and mid-depth zones of the femoral head decreased with age. That of the superficial zone decreased from 150 MPa at 7 years to 80 MPa at 90 years, while the mid-depth zone decreased from 60 MPa at 7 years to 10 MPa at 60 years. The stiffness of talar cartilage from the superficial zone decreased by 20%, while that of the mid-depth zone showed a slight increase in stiffness at 10 MPa with increasing age. There was no significant decrease in the tensile stiffness at 1 MPa with age for either the femoral head or talar cartilage. Based on the results of previous studies it is possible to conclude that the decrease in tensile properties seen in the femoral head results from a deterioration in the tensile properties of the network of collagen fibrils. It is suggested that progressive fatigue failure, perhaps with associated changes in the structure of cartilage due to altered chondrocyte metabolism, causes the reduction in tensile properties with age. The results offer a potential explanation for the observation that osteoarthritis commonly occurs in the hip and knee joints at an increasing incidence as age increases, while the condition only rarely occurs in the ankle joint except as a secondary event to trauma.     

Jump exercise during remobilization restores integrity of the trabecular architecture after tail suspension in young rats.

Three-dimensional trabecular architecture was investigated in the femora of tail-suspended young growing rats, and the effects of jump exercise during remobilization were examined. Five-week-old male Wistar rats (n = 35) were randomly assigned to five body weight-matched groups: tail-suspended group (SUS; n = 7); sedentary control group for SUS (S(CON); n = 7); spontaneous recovery group after tail suspension (S+R(CON), n = 7); jump exercise group after tail suspension (S+R(JUM); n = 7); and age-matched control group for S+R(CON) and S+R(JUM) without tail suspension and exercise (S(CON)+R(CON); n = 7). Rats in SUS and S(CON) were killed immediately after tail suspension for 14 days. The jump exercise protocol consisted of 10 jumps/day, 5 days/wk, and jump height was 40 cm. Bone mineral density (BMD) of the femur and three-dimensional trabecular bone architecture at the distal femoral metaphysis were measured. Tail suspension induced a 13.6% decrease in total femoral BMD (P < 0.001) and marked deterioration of trabecular architecture. After 5 wk of free remobilization, femoral BMD, calf muscle weight, and body weight returned to age-matched control levels, but trabeculae remained thinner and less connected. On the other hand, S+R(JUM) rats showed significant increases in trabecular thickness, number, and connectivity compared with S+R(CON) rats (62.8, 31.6, and 24.7%, respectively; P < 0.05), and these parameters of trabecular architecture returned to the levels of S(CON)+R(CON). These results indicate that suspension-induced trabecular deterioration persists after remobilization, but jump exercise during remobilization can restore the integrity of trabecular architecture and bone mass in the femur in young growing rats.     

Localization of collagen X in human fetal and juvenile articular cartilage and bone.

The tissue localization was analysed of collagen X during human fetal and juvenile articular cartilage-bone metamorphosis. This unique collagen type was found in the hypertrophic cartilage zone peri- and extracellularly and in cartilage residues within bone trabeculae. In addition, occasionally a slight intracellular staining reaction was found in prehypertrophic proliferating chondrocytes and in chondrocytes surrounding vascular channels. A slight staining was also seen in the zone of periosteal ossification and occasionally at the transition zone of the perichondrium to resting cartilage. Our data provide evidence that the appearance of collagen X is mainly associated with cartilage hypertrophy, analogous to the reported tissue distribution of this collagen type in animals. In addition, we observed an increased and often "spotty" distribution of collagen X with increasing cartilage "degeneration" associated with the closure of the growth plate. In basal hypertrophic cartilage areas, a co-distribution of collagens II and X was found with very little and "spotty" collagen III. In juvenile cartilage areas around single hypertrophic chondrocytes, co-localization of collagens X and I was also detected.     

Knee joint kinematics during walking influences the spatial cartilage thickness distribution in the knee

The regional adaptation of knee cartilage morphology to the kinematics of walking has been suggested as an important factor in the evaluation of the consequences of alteration in normal gait leading to osteoarthritis. The purpose of this study was to investigate the association of spatial cartilage thickness distributions of the femur and tibia in the knee to the knee kinematics during walking. Gait data and knee MR images were obtained from 17 healthy volunteers (age 33.2 ± 9.8 years). Cartilage thickness maps were created for the femoral and tibial cartilage. Locations of thickest cartilage in the medial and lateral compartments in the femur and tibia were identified using a numerical method. The flexion-extension (FE) angle associated with the cartilage contact regions on the femur, and the anterior-posterior (AP) translation and internal-external (IE) rotation associated with the cartilage contact regions on the tibia at the heel strike of walking were tested for correlation with the locations of thickest cartilage. The locations of the thickest cartilage had relatively large variation (SD, 8.9°) and was significantly associated with the FE angle at heel strike only in the medial femoral condyle (R(2)=0.41, p<0.01). The natural knee kinematics and contact surface shapes seem to affect the functional adaptation of knee articular cartilage morphology. The sensitivity of cartilage morphology to kinematics at the knee during walking suggests that regional cartilage thickness variations are influenced by both loading and the number of loading cycles. Thus walking is an important consideration in the analysis of the morphological variations of articular cartilage, since it is the dominant cyclic activity of daily living. The sensitivity of cartilage morphology to gait kinematics is also important in understanding the etiology and pathomechanics of osteoarthritis.     

Overload arthrosis: strain patterns in the equine metacarpal condyle

An overload arthrosis occurs consistently in the palmar region of the metacarpal condyle of the equine fetlock (metacarpophalangeal) joint characterized by subchondral bone sclerosis, devitalization and mechanical failure leading to collapse of the overlying articular cartilage. Samples were selected of joints with mild, moderate, and severe subchondral sclerosis, in which cartilage collapse had not yet occurred. An additional group that had severe sclerosis with focal rarefaction suggesting impending collapse was also studied (n=5/group). Parasagittal slices were milled to 2.0 mm thickness and subjected to palmar forces 50 to 200% of those applied by the sesamoid bone at angles corresponding to early, mid and late stance support phases of the gait cycle. From contact radiographs in the loaded and unloaded samples, strains were determined by recognizing displacements in the trabecular patterns using texture correlation analysis. Failure did not occur in any of the samples. Strains were generally proportional to the forces applied and greatest at midstance. Strain patterns varied between samples and with the different loading positions. With increased subchondral bone sclerosis there was greater shear strain in overlying trabeculae. Strain patterns were not consistently different within the sclerotic bone at the site of failure. Focally higher strains at the surface were sometimes related to the edge of the platen which was molded to mimic the sesamoid bone in vivo. These results indicate that sclerotic thickening of subchondral bone transmits stresses to overlying trabeculae. No consistent strain pattern was recognized where devitalization and mechanical failure occurs. Focally higher strains related to the edge of the opposing sesamoid bone may play a role.     

Hip joint muscle forces during gait in patients with femoroacetabular impingement syndrome are associated with patient reported outcomes and cartilage composition

Femoroacetabular impingement syndrome (FAIS) consists of abnormal hip joint morphology and pain during activities of daily living. Abnormal gait mechanics and potentially abnormal muscle forces within FAI patients leads to articular cartilage damage. Therefore, there is a necessity to understand the effects of FAI on hip joint muscle forces during gait and the link between muscle forces, patient reported outcomes (PRO) and articular cartilage health. The purposes of this study were to assess: (1) hip muscle forces between FAI patients and healthy controls and (2) the associations between hip muscle forces with PRO and cartilage composition (T_1ρ/T₂ mapping) within FAI patients. Musculoskeletal simulations were used to estimate peak muscle forces during the stance phase of gait in 24 FAI patients and 24 healthy controls. Compared to controls, FAI patients ambulated with lower vasti (30% body-weight, p = 0.01) and higher sartorius (4.0% body-weight, p < 0.01) forces. Within FAI patients, lower peak gluteus medius, gluteus minimus, sartorius and iliopsoas forces were associated with worse hip joint pain and function (R = 0.43–0.70, p = 0–0.04), while lower muscle forces were associated with increased T_1ρ and T₂ values (i.e. altered cartilage composition) within the hip joint cartilage (R = −0.44 to −0.58, p = 0.006–0.05). Although FAI patients demonstrate abnormal muscle forces, it is unknown whether or not these altered muscle force patterns are associated with pain avoidance or weak musculature. Further investigation is required in order to better understand the effects of FAI on hip joint muscle forces and the associations with hip joint cartilage degeneration.     

Bone geometry of the hip is associated with obesity and early structural damage – a 3.0 T magnetic resonance imaging study of community-based adults

IntroductionThe mechanism by which obesity increases the risk of hip osteoarthritis is unclear. One possibility may be by mediating abnormalities in bony geometry, which may in turn be associated with early structural abnormalities, such as cartilage defects and bone marrow lesions.MethodsOne hundred and forty one older adults with no diagnosed hip osteoarthritis had weight and body mass index measured between 1990 and 1994 and again in 2009 to 2010. Acetabular depth and lateral centre edge angle, both measures of acetabular over-coverage, as well as femoral head cartilage volume, cartilage defects and bone marrow lesions were assessed with 3.0 T magnetic resonance imaging performed in 2009 to 2010.ResultsCurrent body mass index, weight and weight gain were associated with increased acetabular depth and lateral centre edge angle (all P ≤ 0.01). For every 1 mm increase in acetabular depth, femoral head cartilage volume reduced by 59 mm³ (95% confidence interval (CI) 20 mm³ to 98 mm³, P < 0.01). Greater acetabular depth was associated with an increased risk of cartilage defects (odds ratio (OR) 1.22, 95% CI 1.03 to 1.44, P = 0.02) and bone marrow lesions (OR 1.29, 95% CI 1.01 to 1.64, P = 0.04) in the central region of the femoral head. Lateral centre edge angle was not associated with hip structure.ConclusionsObesity is associated with acetabular over-coverage. Increased acetabular depth, but not the lateral centre edge angle, is associated with reduced femoral head cartilage volume and an increased risk of cartilage defects and bone marrow lesions. Minimising any deepening of the acetabulum (for example, through weight management) might help to reduce the incidence of hip osteoarthritis.     

Anatomically shaped osteochondral constructs for articular cartilage repair

Few successful treatment modalities exist for surface-wide, full-thickness lesions of articular cartilage. Functional tissue engineering offers a great potential for the clinical management of such lesions. Our long-term hypothesis is that anatomically shaped tissue constructs of entire articular layers can be engineered in vitro on a bony substrate, for subsequent implantation. To determine the feasibility, this study investigated the development of bilayered scaffolds of chondrocyte-seeded agarose on natural trabecular bone. In a series of three experiments, bovine chondrocytes were seeded in (1) cylindrical bilayered constructs of agarose and bovine trabecular bone, 0.53 cm² in surface area and 3.2 mm thick, and were cultured for up to 6 weeks; (2) chondrocyte-seeded anatomically shaped agarose constructs reproducing the human patellar articular layer (area=11.7 cm², mean THICKNESS=3.4 mm), cultured for up to 6 weeks; and (3) chondrocyte-seeded anatomically shaped agarose constructs of the patella (same as above) integrated into a corresponding anatomically shaped trabecular bone substrate, cultured for up to 2 weeks. Articular layer geometry, previously acquired from human cadaver joints, was used in conjunction with computer-aided design and manufacturing technology to create these anatomically accurate molds. In all experiments, chondrocytes remained viable over the entire culture period, with the agarose maintaining its shape while remaining firmly attached to the underlying bony substrate (when present). With culture time, the constructs exhibited positive type II collagen staining as well as increased matrix elaboration (Safranin O staining for glycosaminoglycans) and material properties (Young's modulus and aggregate modulus). Despite the use of relatively large agarose constructs partially integrated with trabecular bone, no adverse diffusion limitation effects were observed. Anatomically shaped constructs on a bony substrate may represent a new paradigm in the design of a functional articular cartilage tissue replacement.     

The effects of side-artifacts on the elastic modulus of trabecular bone

Determining accurate density-mechanical property relationships for trabecular bone is critical for correct characterization of this important structure-function relation. When testing any excised specimen of trabecular bone, an unavoidable experimental artifact originates from the sides of the specimen where peripheral trabeculae lose their vertical load-bearing capacity due to interruption of connectivity, a phenomenon denoted here as the 'side-artifact'. We sought in this study to quantify the magnitude of such side-artifact errors in modulus measurement and to do so as a function of the trabecular architecture and specimen size. Using parametric computational analysis of high-resolution micro-CT-based finite-element models of cores of elderly human vertebral trabecular bone, a specimen-specific correction factor for the side-artifact was quantified as the ratio of the side-artifact-free apparent modulus (Etrue) to the apparent modulus that would be measured in a typical experiment (Emeasured). We found that the width over which the peripheral trabeculae were mostly unloaded was between 0.19 and 0.58 mm. The side-artifact led to an underestimation error in Etrue of over 50% in some specimens, having a mean (+/-SD) of 27+/-11%. There was a trend for the correction factor to linearly increase as volume fraction decreased (p=0.001) and as mean trabecular separation increased (p<0.001). Further analysis indicated that the error increased substantially as specimen size decreased. Two methods used for correcting for the side-artifact were both successful in bringing Emeasured into statistical agreement with Etrue. These findings have important implications for the interpretation of almost all literature data on trabecular bone mechanical properties since they indicate that such properties need to be adjusted to eliminate the substantial effects of side-artifacts in order to provide more accurate estimates of in situ behavior.     

Pathways of load-induced cartilage damage causing cartilage degeneration in the knee after meniscectomy

Results of both clinical and animal studies show that meniscectomy often leads to osteoarthritic degenerative changes in articular cartilage. It is generally assumed that this process of cartilage degeneration is due to changes in mechanical loading after meniscectomy. It is, however, not known why and where this cartilage degeneration starts. Load induced cartilage damage is characterized as either type (1)--damage without disruption of the underlying bone or calcified cartilage layer--or type (2), subchondral fracture with or without damage to the overlying cartilage. We asked the question whether cartilage degeneration after meniscectomy is likely to be initiated by type (1) and/or type (2) cartilage damage. To investigate that we applied an axisymmetric biphasic finite element analysis model of the knee joint. In this model the articular cartilage layers of the tibial and the femoral condyles, the meniscus and the bone underlying the articular cartilage of the tibia plateau were included. The model was validated with data from clinical studies, in which the effects of meniscectomy on contact areas and pressures were measured. It was found that both the maximal values and the distributions of the shear stress in the articular cartilage changed after meniscectomy, and that these changes could lead to both type (1) and type (2) cartilage damage. Hence it likely that the cartilage degeneration seen after meniscectomy is initiated by both type (1) and type (2) cartilage damage.     

Distributional Variations in Trabecular Architecture of the Mandibular Bone: An In Vivo Micro-CT Analysis in Rats

Purpose

To evaluate the effect of trabecular thickness and trabecular separation on modulating the trabecular architecture of the mandibular bone in ovariectomized rats.

Materials and Methods

Fourteen 12-week-old adult female Wistar rats were divided into an ovariectomy group (OVX) and a sham-ovariectomy group (sham). Five months after the surgery, the mandibles from 14 rats (seven OVX and seven sham) were analyzed by micro-CT. Images of inter-radicular alveolar bone of the mandibular first molars underwent three-dimensional reconstruction and were analyzed.

Results

Compared to the sham group, trabecular thickness in OVX alveolar bone decreased by 27% (P = 0.012), but trabecular separation in OVX alveolar bone increased by 59% (P = 0.005). A thickness and separation map showed that trabeculae of less than 100μm increased by 46%, whereas trabeculae of more than 200μm decreased by more than 40% in the OVX group compared to those in the sham group. Furthermore, the OVX separation of those trabecular of more than 200μm was 65% higher compared to the sham group. Bone mineral density (P = 0.028) and bone volume fraction (p = 0.001) were also significantly decreased in the OVX group compared to the sham group.

Conclusions

Ovariectomy-induced bone loss in mandibular bone may be related to the distributional variations in trabecular thickness and separation which profoundly impact the modulation of the trabecular architecture.