Background:Skeletal disorders affect the skeleton in different ways with some bones being very impaired while others less severely. In translational studies using murine models of human disorders, the bone phenotype is mainly evaluated at 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. Its role in biomechanical stress makes it of particular interest in various bone diseases. For instance, patients with X-linked hypophosphatemia (XLH), who mainly display osteomalacia, are frequently affected with early osteoarthritis of the SIJ. Interestingly, we recently showed that the Hyp mouse, a murine model of XLH that greatly mimics the human disorder, displayed early and severe osteoarticular alterations of the SIJ [1].Objectives:Here, using the Hyp mouse as a model, we show that the SIJ constitutes a highly reliable joint to investigate in murine models of skeletal disorders.Methods:SIJ and distal femur were evaluated in 3-month-old Hyp mice compared to wild-type (WT) mice (n=10 per group). using high-resolution microCT. Measurements of trabecular and cortical bone parameters at sacral and iliac sides and trabecular bone parameters at distal femur were performed with the CTanalyzer software.Results:Hyp mice displayed a significant reduction in parameters of trabecular bone at distal femur, compared to WT mice (Figure 1A). Similarly, a reduction in trabecular bone was shown in Hyp SIJ compared to WT at sacral side (Figure 1B). There was a significant positive correlation between trabecular bone parameters of distal femur and sacral side of SIJ in Hyp mice (e.g. bone volume to total volume [BV/TV]: r = 0,763 p: 0,01). Bone parameters such as sacral BV/TV were higher in comparison to femoral parameters (Figure 1C). No difference was observed on trabecular bone parameters at iliac side of Hyp and WT mice. However, regarding the cortical bone of SIJ, significant alterations were noticed especially at iliac side of SIJ in Hyp mice compared to WT mice. An increase in open cortical porosity, and a decrease in cortical area fraction, as well as in average cortical thickness at iliac side of SIJ in Hyp mice were suggestive of osteo-articular lesions, characteristic for XLH.Conclusion:Trabecular bone parameters at the SIJ, in comparison to the femur, appear to be a relevant alternative to evaluate bone alterations in Hyp mice. Our study suggests that the SIJ represents a valuable tool to investigate both bone and local osteo-articular alterations for murine models of skeletal disorders.Figure 1.A) Bone to total volume ratio in the trabecular bone of distal femur, expressed in percent. B) Bone to total volume ratio in the trabecular bone of sacral slope of the SIJ, expressed in percent. C) Bone to total volume ratio in the trabecular bone of distal femur and sacral slope of the SIJ of Hyp mice, expressed in percent. *: p < 0,05; **: p < 0,01; ***: p< 0,001; ****: p< 0,0001.References:[1]Cauliez, Zhukouskaya et al. Impact of Early Conventional Treatment on Adult Bone and Joints in a Murine Model of X-Linked Hypophosphatemia. Front Cell Dev Biol.:doi: 10.3389/fcell.2020.591417Disclosure of Interests:None declared.
The Effect of the Supplementation of a Diet Low in Calcium and Phosphorus with Either Sheep Milk or Cow Milk on the Physical and Mechanical Characteristics of Bone using A Rat Model