Abstract

Osteoarthritis is traditionally associated with cartilage degeneration although is now widely accepted as a whole-joint disease affecting the entire osteochondral unit; however site-specific cartilage and bone material properties during healthy ageing and disease are absent limiting our understanding. Cadaveric specimens (n = 12; 31–88 years) with grades 0–4 osteoarthritis, were dissected and spatially correlated cartilage, subchondral and trabecular bone samples (n = 8 per cadaver) were harvested from femoral and tibial localities. Nanoindentation was utilised to obtain cartilage shear modulus (G′) and bone elastic modulus (E). Cartilage G′ is strongly correlated to age (p = 0.003) and osteoarthritis grade (p = 0.007). Subchondral bone E is moderately correlated to age (p = 0.072) and strongly correlated to osteoarthritis grade (p = 0.013). Trabecular bone E showed no correlation to age (p = 0.372) or osteoarthritis grade (p = 0.778). Changes to cartilage G′ was significantly correlated to changes in subchondral bone E (p = 0.007). Results showed preferential medial osteoarthritis development and moderate correlations between cartilage G′ and sample location (p = 0.083). Also demonstrated for the first time was significant correlations between site-matched cartilage and subchondral bone material property changes during progressive ageing and osteoarthritis, supporting the role of bone in disease initiation and progression. This clinically relevant data indicates a causative link with osteoarthritis and medial habitual loading.

Introduction

Osteoarthritis (OA) is one of the most prevalent musculoskeletal conditions amongst the adult population with the most common diagnosis at the knee joint1. Individuals with OA have increased variability in gait spatial-temporal parameters2, which in turn can lead to a decline in locomotor stability and increase the risk of falls through reduced functionality3. Ageing is a high risk factor for the development and progression of knee OA and is known to influence mechanical and biochemical changes within tissue structure, even in the absence of OA and other disease or injury status4,5.

OA is traditionally associated with degeneration of the articular cartilage; however it is now more widely accepted that OA is a whole-joint disease that alters the integrity of multiple tissues of the osteochondral unit6. A recent review suggests tissue-level adaptations of the subchondral bone are thought to occur in OA prior to degeneration of the overlying articular cartilage;7 however this has been rarely explored in the human knee joint. Abnormal remodeling of the subchondral bone has been identified, including high proliferation of volume at the bone-cartilage interface, with observations of changes to density, separation and quantity of the trabecular bone8,9. These structural modifications of bone and cartilage occur in synergy further suggesting subchondral bone plays an important but mostly unexplored role in the initiation and progression of the disease10.

These structural adaptations may logically influence the mechanical strength of such tissues. Research shows that cartilage elastic modulus (E) declines with progressive grades of OA11,12. However, there is minimal research on the effect of OA on subchondral bone material properties. Indeed there has been no comparison of the material properties of site matched cartilage and bone from the same donor in the presence of OA when compared to healthy controls. Knowledge of material properties of all tissues involved would enhance the development of treatment and clinical outcomes by advancing our understanding of disease mechanisms13.

Subsequently the aim of this research is to systematically quantify age and OA related trends in the material properties of multiple tissues from the human knee joint. Articular cartilage, subchondral bone and trabecular bone samples from a cohort of donors spanning a large age range are tested using nanoindentation techniques. This study includes samples with varying grades of OA in order to understand how ageing and disease status affects multiple tissues of the knee joint simultaneously. Extraction of multiple, spatially distributed samples of all tissues from the same donors allows us to explicitly test for localised changes within tissues and furthermore for correlated changes between tissues during ageing and OA progression for the first time.

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