Initial Displacement of the Intra-Articular Surface after Articular Fracture Correlates with PTA in C57BL/6 mice but Not 'Superhealer' MRL/MpJ Mice

J Orthop Res. 2020 Nov 12. doi: 10.1002/jor.24912. Online ahead of print.

Abstract

Post-traumatic arthritis (PTA) occurs commonly after articular fracture and may arise, in part, from joint surface incongruity after injury. MRL/MpJ (MRL) "super-healer" mice are protected from PTA compared to C57BL/6 (B6) mice following articular fracture. However, the relationship between the initial displacement of the articular surface, biologic response, and susceptibility to PTA after fracture remains unclear. The objective of this study was to assess whether joint incongruity after articular fracture, as measured by in vivo microCT, could predict pathomechanisms of PTA in mice. B6 and MRL mice (n=12/strain) received a closed articular fracture (fx) of the left tibial plateau. Articular incongruity was quantified as Bone Surface Deviations (BSD) for each in vivo microCT scan obtained from pre-fx to 8 weeks post-fx, followed by histologic assessment of arthritis. Serum concentrations of bone formation (PINP) and bone resorption (CTX-I) biomarkers were quantified longitudinally. Both strains showed increases in surface incongruity over time, as measured by increases in BSD. In B6 mice, acute surface incongruity was significantly correlated to the severity of PTA (R2 =0.988; p=0.0006), but not in MRL mice (R2 =0.224; p=0.220). PINP concentrations significantly decreased immediately post-fx in B6 mice (p=0.023) but not in MRL mice, indicating higher bone synthesis in MRL mice. MRL/MpJ mice demonstrate a unique biologic response to articular fracture such that the observed articular bone surface displacement does not correlate with the severity of subsequent PTA. Clinical Relevance: Identifying therapies to enhance acute biologic repair following articular fracture may mitigate the risk of articular surface displacement for PTA. This article is protected by copyright. All rights reserved.