Contribution of joint tissue properties to load-induced osteoarthritis

Abstract

Objective: Clinical evidence suggests that abnormal mechanical forces play a major role in the initiation and progression of osteoarthritis (OA). However, few studies have examined the mechanical environment that leads to disease. Thus, using a mouse tibial loading model, we quantified the cartilage contact stresses and examined the effects of altering tissue material properties on joint stresses during loading.

Design: Using a discrete element model (DEA) in conjunction with joint kinematics data from a murine knee joint compression model, the magnitude and distribution of contact stresses in the tibial cartilage during joint loading were quantified at levels ranging from 0 to 9 N in 1 N increments. In addition, a simplified finite element (FEA) contact model was developed to simulate the knee joint, and parametric analyses were conducted to investigate the effects of altering bone and cartilage material properties on joint stresses during compressive loading.

Results: As loading increased, the peak contact pressures were sufficient to induce fibrillations on the cartilage surfaces. The computed areas of peak contact pressures correlated with experimentally defined areas of highest cartilage damage. Only alterations in cartilage properties and geometry caused large changes in cartilage contact pressures. However, changes in both bone and cartilage material properties resulted in significant changes in stresses induced in the bone during compressive loading.

Conclusions: The level of mechanical stress induced by compressive tibial loading directly correlated with areas of biological change observed in the mouse knee joint. These results, taken together with the parametric analyses, are the first to demonstrate both experimentally and computationally that the tibial loading model is a useful preclinical platform with which to predict and study the effects of modulating bone and/or cartilage properties on attenuating OA progression. Given the direct correlation between computational modeling and experimental results, the effects of tissue-modifying treatments may be predicted prior to in vivo experimentation, allowing for novel therapeutics to be developed.

Keywords: Bone; Cartilage; Contact mechanics; Discrete element analysis; Finite element analysis.

Fig. 1

A) Schematic of the mouse tibial loading device, and B) the loading protocol for each stepped loading trial applied to the joint. C) Knee joint kinematics were analyzed using roentgen stereophotogrammetric analysis (RSA) (Adebayo et al., 2016). Arrows denote bead locations on the tibia and femur. Reference frame beads evident along perimeter of image. Scale bar = 5.0 mm. D) One sample was scanned by microCT, manually contoured, and E) bead locations from RSA and microCT were aligned to produce F) point clouds of each bone geometry with cartilage (red) inserted between the two surfaces to calculate the contact forces at each joint position by discrete element analysis.

Fig. 2

A) Tibial (yellow) and femoral (red) radii of curvature were measured on the medial aspect of the joint by fitting of spheres. The radius of curvature and depth of the tibial concavity (yellow arrow) was also measured. C) Simplified geometric contact model with the noted boundary conditions for finite element analysis based on the geometry measurements made of the contacting surfaces. B) Mesh convergence analysis concluded that approximately 15,000 cartilage elements (red arrow) were required for accurate contact pressure results.

Fig. 3

Geometric property values for the parametric analysis conducted on the simple contact finite element model. Cartilage layer in purple; subchondral cortical plate in green; epiphyseal geometry in yellow.

Fig. 4

Side and top views of a trial exhibiting compressive behavior and a trial exhibiting rolling behavior as seen by comparing the 0 N and 9 N positions. The compressive behavior maintained contact between the tibia and femur.

Fig. 5

In trials exhibiting compressive behavior, A) mean and B) peak contact stresses increased with load magnitude (mean ± SD). C) Mean and D) peak contact strains also increased with load magnitude. E) Contact forces increased in magnitude with load, and F) peak contact stresses translated posteriorly on the tibial plateau as loading increased.

Fig. 6

A) Peak contact pressures calculated using finite element analysis validated contact stress values determined by discrete element analysis (mean ± SD). B) A 0.5 N compressive load resulted in a peak contact stress of 6.37 MPa in the middle of the tibial cartilage surface.