Post-traumatic osteoarthritis of the ankle: A distinct clinical entity requiring new research approaches

Abstract

The diagnosis of ankle osteoarthritis (OA) is increasing as a result of advancements in non-invasive imaging modalities such as magnetic resonance imaging, improved arthroscopic surgical technology and heightened awareness among clinicians. Unlike OA of the knee, primary or age-related ankle OA is rare, with the majority of ankle OA classified as post-traumatic (PTOA). Ankle trauma, more specifically ankle sprain, is the single most common athletic injury, and no effective therapies are available to prevent or slow progression of PTOA. Despite the high incidence of ankle trauma and OA, ankle-related OA research is sparse, with the majority of clinical and basic studies pertaining to the knee joint. Fundamental differences exist between joints including their structure and molecular composition, response to trauma, susceptibility to OA, clinical manifestations of disease, and response to treatment. Considerable evidence suggests that research findings from knee should not be extrapolated to the ankle, however few ankle-specific preclinical models of PTOA are currently available. The objective of this article is to review the current state of ankle OA investigation, highlighting important differences between the ankle and knee that may limit the extent to which research findings from knee models are applicable to the ankle joint. Considerations for the development of new ankle-specific, clinically relevant animal models are discussed. © 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 35:440-453, 2017.

Keywords: PTOA; osteochondral injury; preclinical model; sprain; talocrural.

Figure 1

The proposed mechanism of posttraumatic osteoarthritis after a severe ankle sprain. (A) During a typical lateral ankle sprain (inversion) the medial aspect of the talus likely impacts the tibial plafond, which may result in (B) a talar osteochondral lesion (OCL). Direct trauma to the articular surface can initiate progressive, irreversible joint destruction culminating in (C) late-stage posttraumatic osteoarthritis (PTOA) years to decades after the original injury.

Figure 2

A comparison between the knee and ankle joints. The contact surface area of knee joint is approximately three times larger than the ankle. The ankle has more bony congruity than the knee, and is therefore less reliant on supporting soft tissues (pink-purple) to maintain stability. Ankle cartilage (blue) is approximately half the thickness of knee cartilage, although the superficial zone thickness is similar between joints. The extracellular matrix of ankle cartilage is more dense than that of the knee and has a higher dynamic stiffness and compressive modulus.

Figure 3

Comparative talus anatomy. Size comparison of left tali from species commonly used as animal models in osteoarthritis research; (A) horse, (B) pig, (C) sheep, (D) dog, (E) rat, (F) mouse, compared to the (G) human.