The sacroiliac joint: An original and highly sensitive tool to highlight altered bone phenotype in murine models of skeletal disorders

Bone disorders may affect the skeleton in different ways, some bones being very impaired and others less severely. In translational studies using murine models of human skeletal diseases, the bone phenotype is mainly evaluated at the distal femur or proximal tibia. The sacroiliac joint (SIJ), which connects the spine to the pelvis, is involved in the balanced transfer of mechanical energy from the lumbar spine to the lower extremities. Because of its role in biomechanical stress, the SIJ is a region of particular interest in various bone diseases. Here we aimed to characterize the SIJ in several murine models to develop a highly reliable tool for studying skeletal disorders. We performed a 12-month in vivo micro-computed tomography (micro-CT) follow-up to characterize the SIJ in wild-type (WT) C57BL/J6 mice and compared the bone microarchitecture of the SIJ and the distal femur at 3 months by micro-CT and histology. To test the sensitivity of our methodology, the SIJ and distal femur were evaluated at 3 and 6 months, in 2 murine models of skeletal disorder, X-linked hypophosphatemia (Hyp mice) and HLA-B27 transgenic mice and compared to WT mice. A multimodal analysis was performed, using a com-bination of microCT and histological analysis. With the Hyp model, the SIJ displayed more bone microarchitecture alterations than the distal femur. Hyp mice showed a significant reduction in trabecular bone at both the distal femur and sacral slope as compared with WT mice, with a significant positive correlation between trabecular bone parameters of the distal femur and sacral side of the SIJ. Furthermore, trabecular bone parameters (Bone Volume/Total Volume (BV/TV), trabecular thickness (Tb.Th), trabecular separation (Tb.Sp), trabecular number (Tb.N), trabecular pattern factor (Tb.Pf)) were significantly increased compared to femoral parameters at the SIJ. The sacral articular cortical bone, which is indicative of osteoarticular lesions, was altered in Hyp mice. Interestingly, in accordance to previous studies, HLA-B27 transgenic mice did not show any osteoarticular lesions as compared with WT mice. Cortical bone parameters (thickness, porosity), as well as scoring performed with double blinding, did not show difference between the 2 genotypes. The characterization and evaluation of the SIJ surface appears very sensitive to emphasize alterations of bone and joint. The SIJ may represent a valuable tool to investigate both bone and local osteoarticular alterations in murine models of skeletal disorders and might be a relevant site for assessing the response to treatment of chronic bone diseases.