Early diagnosis to enable early treatment of pre-osteoarthritis

Abstract

Osteoarthritis is a prevalent and disabling disease affecting an increasingly large swathe of the world population. While clinical osteoarthritis is a late-stage condition for which disease-modifying opportunities are limited, osteoarthritis typically develops over decades, offering a long window of time to potentially alter its course. The etiology of osteoarthritis is multifactorial, showing strong associations with highly modifiable risk factors of mechanical overload, obesity and joint injury. As such, characterization of pre-osteoarthritic disease states will be critical to support a paradigm shift from palliation of late disease towards prevention, through early diagnosis and early treatment of joint injury and degeneration to reduce osteoarthritis risk. Joint trauma accelerates development of osteoarthritis from a known point in time. Human joint injury cohorts therefore provide a unique opportunity for evaluation of pre-osteoarthritic conditions and potential interventions from the earliest stages of degeneration. This review focuses on recent advances in imaging and biochemical biomarkers suitable for characterization of the pre-osteoarthritic joint as well as implications for development of effective early treatment strategies.

Figure 1

Chondropathy and the modified Outerbridge system. Sample arthroscopic images demonstrating different grades of the modified Outerbridge scoring system. (a) Grade 0: smooth, firm articular cartilage. (b) Grade 1: articular cartilage is surface-intact, but softened. (c) Grade 2: articular cartilage with a damaged surface <50% of tissue depth. (d) Grade 3: articular cartilage with a damaged surface >50% of tissue depth. (e) Grade 4: articular cartilage with full-thickness tissue disruption extending to the subchondral bone.

Figure 2

Optical coherence tomography. Optical coherence tomography (OCT) permits cross-sectional imaging of articular cartilage at resolutions comparable with low-power histology. (a) Arthroscopically firm and surface-intact cartilage shows OCT form birefringence. (b) Loss of birefringent banding on OCT correlates to softened cartilage. (c) Subsurface voids and fissures can be visualized with OCT.

Figure 3

Ultrashort echo-time enhanced T2 * maps of cartilage and meniscus show changes after knee injury. Ultrashort echo-time enhanced T2* (UTE-T2*) maps of articular cartilage and meniscus tissue show quantitative differences between (a) an uninjured asymptomatic subject and (b) an anterior cruciate ligament-injured subject with concomitant posterolateral meniscus pathology.