Early morphometric and anisotropic change in periarticular cancellous bone in a model of experimental knee osteoarthritis quantified using microcomputed tomography
Introduction
Post-traumatic osteoarthritis (OA) is characterized by changes throughout a joint, including the articular cartilage and periarticular bone. Considerable research has been aimed at the changes that occur in the joint cartilages [1], [2], [3], however, the contribution of subchondral bone [4], [5] in the pathogenesis of OA is less well understood. Subchondral bone, i.e., the thin subchondral plate and the underlying cancellous bone, is reportedly sensitive to changes in its physiological [6] and mechanical environment [7], with changes in the cancellous bone being particularly conspicuous.
The natural history of post-traumatic OA involves progressive changes in the joint beginning at the time of injury, and continuing until the late stages of the disease, which are characterized by joint space narrowing, full thickness cartilage erosion, osteophyte development, and subchondral sclerosis [8]. While late-stage subchondral bone changes have been described for ACL injured patients with developed symptoms of OA [9], little is known about changes that occur shortly after joint trauma. However, one study showed that areal bone mineral density (BMD) decreased up to 21% during one year after anterior cruciate ligament (ACL) rupture [10], though these patients were treated surgically. Nonetheless, the bone seems sensitive to injury.
In a longitudinal study with the ACL transected (ACLX) dog model for post-traumatic OA, Brandt and colleagues [4] reported degenerative changes in the knee joint 54-month post-ACLX that had similar characteristics to late-stage OA development in humans. Specifically investigating bone changes, Dedrick and colleagues [11] reported a significant increase in subchondral bone plate thickness at 54 months, but not at 3 and 18 months. This result is consistent with increased subchondral sclerosis found in late-stage human patients [8], [10]. Notably, in this animal model, changes in the subchondral cancellous bone were evident at all three time points investigated (3, 18, 54 months). This suggests that the periarticular cancellous bone is more sensitive to the effects of joint injury than the subchondral plate, however, the temporal evolution of these changes, and the nature of the changes in the cancellous bone microarchitecture have not been described. Decreases in volumetric BMD have been reported as early as 3 weeks after injury in this model [12], suggesting that structural adaptations may be occurring.
The cancellous architecture is related to the mechanical properties of cancellous bone [13], and its measurement provides not only important information about the structural changes that occur in cancellous bone, but also provides clearer information about the significance of these changes in bone morphology and bone strength. If the changes in bone morphology are irreversible, i.e., exceed the physiological capacity to adapt, then understanding when these changes occur may influence the decision to apply preventative measures early in the progression of the disease. Morphometric properties of the microarchitecture of cancellous bone can be calculated from three-dimensional (3D) imaging techniques such as serial sectioning [14] or microcomputed tomography (μCT) [15], [16]. Some established morphometric parameters [17] include bone volume ratio (BV/TV), bone surface ratio (BS/BV), trabecular thickness (Tb.Th), trabecular number (Tb.N), and trabecular separation (Tb.Sp).
Anisotropy of the bone fabric, or the trabecular orientation, is closely related to the bone mechanical anisotropy [18]. The development and maintenance of the fabric anisotropy is influenced by the loading environment of the bone, and the change in anisotropy may indicate alterations in the loading conditions that occur in the post-traumatic knee joint. Although several methods for characterizing anisotropy are available [19], mean intercept length (MIL) [20] is a well-established method to quantify the degree of anisotropy (DA) and trabecular orientation.
The pathogenesis of post-traumatic OA is poorly understood, however, it is clear that this disease involves the entire organ system of the joint, including the cartilages, synovium, ligaments, and bones. Previously, significant changes in articular cartilage were reported, particularly in the medial aspect of the joint, as early as four weeks after surgery [21]. The present study focuses on the changes that occur in the subchondral bone architecture during the early stages following a cruciate ligament transection. It is hypothesized that a decrease in BMD after this post-traumatic knee injury is the result of morphological and anisotropic changes to the cancellous architecture. Thus, the objective of this study is to quantify these early morphometric and anisotropic changes to cancellous bone architecture in this canine model of experimental OA.
Section snippets
Methods
Skeletally mature, mixed-breed dogs (n=10) were randomly assigned to one of two experimental groups: 3-week (n=5) and 12-week (n=5) post-unilateral ACLX. Two non-operated animals were used as a baseline comparison with the contralateral limbs. Animal body masses ranged from 16 to 34 kg (mean 23.5 kg), and ages ranged from 1.5 to 3 yr (mean 2.5 yr). All procedures were approved by the University of Calgary Animal Care Committee. After unilateral ACLX by lateral arthrotomy as described previously
Results
The tibia and femur exhibited architectural changes in the subchondral bone at both 3- and 12-week post-ACLX. These changes can be observed visually, for example, in rendered 3D images of typical bone samples (based on having median morphological measures) from both the ACLX and contralateral medial femoral condyle (Fig. 1). Similar visual changes in trabecular bone architecture occur in the tibia.
At 3-week post-ACLX significant changes were found in the tibia, but not the femur, although the
Discussion
The trabecular structure of knee joint periarticular cancellous bone in this model of post-traumatic early OA was detectable as early as 3-week post-ACLX and was prominent at 12-week post-ACLX. Fig. 1 illustrates that architectural changes in the subchondral trabecular bone occur at both time points, and are particularly obvious at 12-week post-ACLX. These bone changes precede cartilage degeneration which typically are absent at 10–12 weeks, but are present by 32-week post-ACLX [21].
A
Acknowledgements
Funded by The Arthritis Society, Alberta Heritage Foundation for Medical Research, Medical Research Council of Canada, Natural Science and Engineering Research Council of Canada, Pfizer, Killam Memorial Scholarship, and International Society of Biomechanics Student Grant.
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