Is pore size of subchondral plate an indicator for onset of osteoarthritis?

Abstract

Introduction: Osteoarthritis (OA) is the most common form of arthritic disease, and a major cause of joint pain, disability and also impairs quality of life specifically the elderly [1]. OA is not only a disease of articular cartilage, but subchondral bone. Yet it remains controversial that whether subchondral bone disturbance is primary or secondary to AC degeneration during OA development [2]. Subchondral plate is composed of calcified cartilage beneath the tidemark and bone plate under cement line, which links overlying articular cartilage and underlying trabecular bone biochemically and biomechanically [3]. We aimed to characterize subchondral plate structure in human tibial specimens with primary knee OA, and spatiotemporal changes in the porosity and pore size of subchondral plate in Dunkin Hartley (DH) guinea pigs with naturally occurring OA.

Methods: Human tibial plateau specimens were collected from 46 patients who underwent total knee replacement for advanced stage of OA, and 5 cadavers of healthy adults were used as control for comparison .The spatiotemporal changes of tibial plateau were also examined in DH strain guinea pigs with spontaneous occurring onset of OA at 3 month and progression at 7 months after birth. Bristol Strain 2 guinea pigs were used as control. Micro-CT was employed to evaluate the porosity and pore size distribution of subchondral bone and trabecular bone microstructure. Micro-CT findings were validated by routine histology.

Results: As compared with healthy specimens, the pore size of SP was significantly higher in OA at both medial (OA: 0.15±0.04mm; healthy: 0.10±0.01mm, p=0.023) and lateral tibial plateau (OA: 0.16±0.05mm; healthy: 0.11±0.01mm, p=0.020). The clustered cells, including osteoclasts, were observed in the enlarged pores. It was also found in DH guinea pigs of 3-month-old that the pore size was larger on medial tibial plateau (0.0823±0.0160mm) than BS2 strain (0.0701±0.0018mm, p=0.023), but not on the lateral (DH: 0.0836±0.0068mm; BS2: 0.0864±0.0080mm; p=0.479). The large pore size occurred with elevated level of RANKL expression and osteoclastogenesis in response to hypercellularity of articular cartilage and high serum level of active TGF-b1 in DH guinea pigs. It was followed by chondrocytes dropout in 7-month-old DH guinea pigs, and altered connectivity density of trabecular bone, which correlated inversely with the pore size (r*2=0.739; p=0.028).

Discussion: The enlarged pores in subchondral plate could allow invasion of cell cluster from subchondral bone to articular cartilage, and then trigger the onset of OA. The increased pore size in subchondral bone might signify primary OA initiation.

Significance: Our findings indicate the potential values of the pore enlargement of subchondral plate in early detection of OA.

Acknowledgements: The authors acknowledged University Seeding Fund program (Project No. HKU10400853 and 1111159186) for supporting this study.

References: 1. Hoaglund FT, Yau AC, Wong WL. Osteoarthritis of the hip and other joints in southern Chinese in Hong Kong. J Bone Joint Surg Am 1973;55:545-57. 2. Brandt KD, Dieppe P, Radin E. Etiopathogenesis of osteoarthritis. Med Clin North Am 2009;93:1-24, xv. 3. Suri S, Walsh DA. Osteochondral alterations in osteoarthritis. Bone 2012;51:204-11.