Elsevier

Clinical Biomechanics

Volume 15, Issue 8, October 2000, Pages 624-631
Clinical Biomechanics

Early morphometric and anisotropic change in periarticular cancellous bone in a model of experimental knee osteoarthritis quantified using microcomputed tomography

https://doi.org/10.1016/S0268-0033(00)00023-1Get rights and content

Abstract

Objective. To quantify early stage microstructural changes of periarticular cancellous bone in a canine anterior cruciate ligament transection model for experimental osteoarthritis.

Design. Unilateral transection of the anterior cruciate ligament was performed in 10 animals. Bone structure changes were quantified in five animals at 3-week post-transection and five animals at 12-week post-transection. An additional two non-operated animals were used as controls.

Background. Changes in trabecular architecture of the periarticular cancellous bone in early stage post-traumatic osteoarthritis is not well understood. Previous studies have found alterations in bone mineral density in experimental osteoarthritis suggesting adaptation of the trabecular structure. Early change of the periarticular bone following a ligament injury may contribute to the long-term development of osteoarthritis.

Methods. Bone cores from the medial condyles of the femoral and tibial pairs were scanned with a three-dimensional microtomographic system. Structural indices were quantified including bone volume ratio, bone surface ratio, trabecular thickness, trabecular separation, trabecular number, as well as structural anisotropy determined by the mean-intercept-length method.

Results. Significant structural changes were observed at 3-week post-transection, and were more prominent at 12-week post-transection. These changes were accompanied by decreasing anisotropy.

Conclusions. Periarticular cancellous bone microstructure is significantly altered in experimental osteoarthritis. These changes occurred as early as 3-week post-transection, and were large at 12-week post-transection.
Relevance

The pathogenesis of post-traumatic osteoarthritis is poorly understood, but it is clear that this disease involves the entire organ system of the joint, including the cartilages, synovium, ligaments, and bones. This study focuses on the changes that occur in the bones during the early stages following a joint injury, and contributes to a better overall understanding of the disease aetiology.

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.

References (39)

  • K.D Brandt et al.

    Osteoarthritic changes in canine articular cartilage, subchondral bone, and synovium fifty-four months after transection of the anterior cruciate ligament

    Arthritis Rheum

    (1991)
  • Wolff J. The law of bone remodelling (Maquet P, Furlong R. Trans.). Berlin: Springer,...
  • D.M Daniel et al.

    Fate of the ACL-injured patient

    Am J Sport Med

    (1994)
  • P Kannus et al.

    A cruciate ligament injury produces considerable, permanent osteoporosis in the affected knee

    J Bone Miner Res

    (1992)
  • J Leppälä et al.

    Effect of anterior cruciate ligament injury on the knee on bone mineral density of the spine and affected lower extremity: a prospective one-year follow-up study

    Calcif Tissue Int

    (1999)
  • D.K Dedrick et al.

    A longitudinal study of subchondral plate and trabecular bone in cruciate-deficient dogs with osteoarthritis followed up for 54 months

    Arthritis Rheum

    (1993)
  • Boyd SK, Matyas JR, Wohl GR, Kantzas A, Zernicke RF. Early changes in periarticular bone mineral density after anterior...
  • S.A Goldstein et al.

    Measurement and significance of three-dimensional architecture to the mechanical integrity of trabecular bone

    Calcif Tissue Int

    (1993)
  • A Odgaard et al.

    A direct method for fast three-dimensional serial reconstruction

    J Microsc

    (1990)
  • Cited by (52)

    • Early zoledronate treatment inhibits subchondral bone microstructural changes in skeletally-mature, ACL-transected canine knees

      2023, Bone
      Citation Excerpt :

      The canine ACLT model, first developed by Pond & Nuki in 1973 [60], is a well-established preclinical model of PTOA that partially overcome the aforementioned limitations. As a pre-clinical model using large animals, it is particularly useful for studying subchondral bone changes in PTOA and investigating the effects of different therapeutic agents [61–70]. Several studies have examined adaptations in the subchondral bone in response to ACLT using the canine model.

    • Subchondral bone microarchitecture in ACL reconstructed knees of young women: A comparison with contralateral and uninjured control knees

      2018, Bone
      Citation Excerpt :

      While the contralateral knee is not an ideal control reference, at least from the perspective of bone microarchitecture it appears that it may be reasonable to use. Other studies investigating effects of ACL tears on the contralateral leg also found limited effect of the injury on bone parameters themselves [7–9,13,20,23,44]. Nevertheless, caution will need to be exercised before using the contralateral knee as a reference control, and this can be investigated further in the future through longitudinal studies (i.e. testing whether there are longitudinal changes to the contralateral knee).

    View all citing articles on Scopus
    View full text