Sexually dimorphic tibia shape is linked to natural osteoarthritis in STR/Ort mice

Abstract

Objectives:Human osteoarthritis (OA) is detected only at late stages. Male STR/Ort mice develop knee OAspontaneously with known longitudinal trajectory, offering scope to identify OA predisposing factors. Weexploit the lack of overt OA in female STR/Ort and in both sexes of parental, control CBA mice to explorewhether early divergence in tibial bone mass or shape are linked to emergent OA.Method:We undertook detailed micro-CT comparisons of trabecular and cortical bone, multiple struc-tural/architectural parameters andfinite element modelling (FEM) of the tibia from male and female STR/Ort and CBA mice at 8e10 (pre-OA), 18e20 (OA onset) and 40þweeks (advanced OA) of age.Results:We found higher trabecular bone mass in female STR/Ort than in either OA-prone male STR/Ortor non-prone CBA mice. Cortical bone, as expected, showed greater cross-sectional area in male thanfemale CBA, which surprisingly was reversed in STR/Ort mice. STR/Ort also exhibited higher cortical bonemass than CBA mice. Our analyses revealed similar tibial ellipticity, yet greater predicted resistance totorsion in male than female CBA mice. In contrast, male STR/Ort exhibited greater ellipticity than bothfemale STR/Ort and CBA mice at specific cortical sites. Longitudinal analysis revealed greater tibia cur-vature and shape deviations in male STR/Ort mice that coincided with onset and were more pronouncedin late OA.Conclusion:Generalised higher bone mass in STR/Ort mice is more marked in non OA-prone females, butpre-OA divergence in bone shape is restricted to male STR/Ort mice in which OA develops spontaneously.