J Orthop Res. 2014 Oct;32(10):1371-80.

A new measure of tibiofemoral subchondral bone interactions that correlates with early cartilage damage in injured sheep.

Beveridge JE, Heard BJ, Brown JJ, Shrive NG, Frank CB.

Department of Mechanical and Manufacturing Engineering, McCaig Institute for Bone and Joint Health, University of Calgary, Calgary, Alberta, Canada.

 

Abstract

We have demonstrated previously that chondral damage is associated with increased knee surface velocities following ligament and meniscus injuries in sheep. We tested the hypothesis that cartilage damage scores would correlate with a new bone surface interaction measure that captures complex changes in tibiofemoral alignment, “proximity disturbance” (PD). Six sheep underwent combined anterior cruciate and medial collateral ligament transection (ACL/MCLx), five complete lateral meniscectomy (Mx), and four sham arthrotomy (Sham). Tibiofemoral subchondral bone surfaces were modeled, and the post-operative changes in relative separation of the surfaces (i.e., “proximity”) were derived from subject-specific in vivo 3D stifle kinematics. Surface areas of regions of near contact were determined, and PD was calculated as the range of change in tibiofemoral proximity, divided by normalized overlapping proximity surface areas between baseline and post-operative time points. Cartilage morphology was graded at dissection. ACL/MCLx PD was significantly elevated relative to Mx and Shams, and correlated with cartilage damage (r(2)  = 0.88-0.98). Although not statistically significant, Mx PD values tended to be higher than those of Shams, and correlated with cartilage damage. Results from both injury models suggest that increasing change in tibiofemoral surface alignment may be increasingly deleterious to long-term cartilage health in sheep. © 2014 Orthopaedic Research Society.

KEYWORDS: ACL; kinematics; meniscectomy; osteoarthritis; surface interaction

PMID: 25042631

 

Supplement:

Osteoarthritis (OA) is the most common form of arthritis, and is characterized by cartilage loss, bony deformity, joint pain and dysfunction. There is no known cure or disease-modifying therapy for OA. The reasons why OA develops in some individuals, but not others, are poorly understood. One of the major barriers to developing effective therapies for OA has been our inability to study the early pathologic processes associated with OA onset; we do not yet know who will get OA, and when. Post-traumatic OA (PTOA) is OA that arises following some form of trauma to the joint, and is used widely to study biological and mechanical changes we think are important in PTOA onset. Anterior cruciate ligament (ACL) and/or meniscus tear are two knee injuries that occur clinically, and most individuals will develop signs of PTOA within just 5-10 years (1). The occurrence of an ACL or meniscus injury points to “who” will potentially develop OA, and gives us an indication of “when” PTOA is likely to develop. Knowing who might get PTOA, and when, gives us a window of opportunity to investigate the mechanisms that contribute to “why” it happens.

The ACL functions to constrain knee joint motion. When the ACL is torn, we know that dynamic knee motions and alignment are affected. Exactly how these functional abnormalities relate to PTOA is of critical importance if we are to understand the linkages between injury and cartilage damage in particular, as cartilage loss is irreversible and is a hallmark of OA onset. The study featured on this site is one of a larger body of work aimed at characterizing abnormal contact mechanics between the articulating surfaces of the knee that underpin progressive cartilage and joint damage using sheep models of knee injury. The sheep model was chosen because of its size, trainability, and popularity in orthopaedic research. The methodology used to measure in vivo joint motion longitudinally at the time of the study is accurate to within 0.4 ± 0.4 mm. This level of accuracy allows us to detect even subtle changes in three-dimensional (3D) joint motion, which appear to have a significant impact on cartilage integrity and long-term joint health. We are able to investigate how injury alters dynamic joint alignment on an individual basis by quantifying abnormal joint motion as the change from the uninjured intact state. This capability allows us to treat each subject as its own control, and is a central strength of our approach as joint geometry and motion are unique individually.

In this featured study, we observed that combined ACL and medial collateral ligament transection (ACL/MCLx) changed the inter-surface distance, or “proximity”, between the articulating surfaces of the sheeps’ injured knees. Notably, some sheep had a large change in proximity, whereas others did not, even though all sheep received identical injuries. When the extent of cartilage damage was compared between those sheep with the greatest change in dynamic alignment versus those with minimal change, sheep with the greatest range of changed proximity values also had the most cartilage damage (Figure 1). Visually, there appeared to be an association between sheep with “disturbed” proximity, and those without. We hypothesized that the inherent joint geometry and abnormal dynamic alignment must be contributing to the variation in cartilage damage severity we were observing in these animals.

 

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Figure 1. Examples of how ACL/MCL transection affects inter-surface proximity and cartilage damage severity in two sheep that were given identical injuries. The change in proximity is mapped for each of the four surfaces within the knee, with the change (in mm) corresponding to the colour bar just to the right of the colour-coded surface maps. Negative values (red) mean that the surfaces became closer as a result of injury, whereas positive values (blue) indicate that surfaces became further apart. The four-bar legend with the capital letters F, B, I, O to the left of the surface maps indicates the right knee surface orientation: Front, Back, Inside, Outside. The cartoon with blue shading immediately to the right of the surface maps is where cartilage damage occurred for that particular sheep. The severity of cartilage damage is expressed as the composite cartilage score. One sheep had minimal cartilage damage and little change in proximity (A), whereas another had widespread cartilage damage and proximity changes (B).

 

Based on our previous work (2), we knew that combined ligament transection resulted in the shin bone being positioned more forward relative to the thigh bone when the animal was fully weight-bearing while walking. In this altered alignment, the less congruent new regions of near cartilage-cartilage contact would occur over a smaller region, and more abrupt changes in inter-surface proximity would result (Figure 2). Although the forward shift in shinbone position is a hallmark of ACL/MCL-deficient motion in sheep, it is not the only way dynamic alignment is altered. Smaller 3D alignment changes also occur, which we have also reported previously in this animal model (2). Building on these observations, we developed a new metric to encompass both the individual changes in joint function, as well as the subject-specific joint surface geometry. “Proximity disturbance” describes alterations in dynamic 3D surface alignment using a single value, with larger values indicative of greater change from the original alignment.

 

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Figure 2. Proximity disturbance quantifies the abnormal alignment between the sheep knee joint surfaces that results because of injury. (A) Surface alignment in a healthy uninjured knee. (B) Abnormal alignment after combined ACL/MCL transection.

 

Advantage of using the proximity disturbance metric: Proximity disturbance reduces complex alignment to a single value that correlates with cartilage damage. Quantifying 3D joint motion is complex, and is described traditionally as one segment rotating and translating relative to the other. So while the standard of describing motion in six degrees of freedom (6-DOF) is used clinically, proximity disturbance may relate better to the actual mechanisms that modulate the risk of developing progressive long-term joint damage because it quantifies interactions between the structures that become damaged.

Importance of the study: The results of our featured study suggest that proximity disturbance is a sensitive measure that may have clinical value as a measureable risk factor for cartilage damage progression, and is complementary to existing metrics of abnormal joint motion.

Next steps: From a mechanistic standpoint, it remains to be seen how proximity disturbance relates to changes in contact stress, particularly in the presence of the menisci. To understand the extent proximity disturbance could be used as a surrogate measure of abnormal contact stress, experimental measures of contact stress during in vivo joint motion are needed. Clinically, accurate measures of human ACL-deficient dynamic joint motion, joint surface geometry and cartilage damage are likewise needed to confirm that proximity disturbance is also relevant in the human condition.

 

References:

  1. Lohmander, L.S., et al., The long-term consequence of anterior cruciate ligament and meniscus injuries. The American Journal of Sports Medicine, 2007. 35(10): p. 1756-69.
  2. Tapper, J., et al., Dynamic in vivo three-dimensional (3D) kinematics of the anterior cruciate ligament/medial collateral ligament transected ovine stifle joint. J. Orthop. Res., 2008. 26(5): p. 660-72.

 

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