Oral Presentation 29th Australian and New Zealand Bone and Mineral Society Annual Scientific Meeting 2019

Severely Decreased Bone Formation in the Winnie Mouse Model of Inflammatory Bowel Disease (IBD) (#32)

Ahmed Al Saedi 1 2 , Shilpa Sharma 1 2 , Lulu Chen 2 3 , Ebrahim Hassan 1 2 , Kulmira Nurgali 2 4 , Gustavo Duque 1 2
  1. Department of Medicine – Western Health, The University of Melbourne, St Albans, VIC, Australia
  2. Australian Institute for Musculoskeletal Science (AIMSS), The University of Melbourne and Western Health, St Albans, VIC, Australia
  3. Department of Anatomy, Histology and Embryology, Nanjing Medical University, Najing, China
  4. Institute for Health and Sport, Victoria University, Melbourne , VIC, Australia

Although osteoporosis commonly afflicts patients with inflammatory bowel disease, the mechanisms of bone loss in these subjects remain poorly understood.  A major limitation to investigate those changes in bone mass has been the lack of an appropriate animal model for IBD. In this study, we characterized the bone phenotype of the Winnie mouse model, which carry a mutation in the Muc2 gene and closely replicate the symptoms and pathophysiology of IBD, and produce high levels of gut-derived serotonin (GDS); a potent inhibitor osteoblastogenesis. 6, 14 and 21-week-old Winnie mice were compared to age and sex-matched control C57BL/6 mice(WT). We assessed bone quality properties by static and dynamic bone-histomorphometry and microCT analyses. Despite similar body weight, bone formation in Winnie mice was severely decreased in trabecular surfaces at 14 and 21-weeks respectively compared to WT(bone formation rate/bone surface -20%,-28%,p<0.05), and mineral apposition rate MAR (44% at14 w, 46% at 21w,µm/day,p<0.05). Osteoblast number was significantly lower in Winnie mice compared to WT(-42%at 14w, -54% at 21w, p<0.001). Similarly, total-collagen (-17% at 14w, -19% at 21w) and collagen-I (-9% at 14w, -7% at 21 w) were significantly reduced in the Winnie group. In contrast, osteoclast number was significantly higher compared to WT mice (+59.9% at14w, +38% at21w,p<0.001). Osteoid volume/ Bone surface was significantly lower in Winnie mice compared to WT (28% at 14w,23.2% at21w,p<0.01). Furthermore, 3-point bending showed lower mean failure force in Winnie mice(-20% at 14w,-49% at 21w,p<0.05). No differences in these parameters were noticed in Winnie mice vs WT at 6W. Furthermore, microCT analysis of the distal femoral metaphysis showed that Winnie mice had significantly lower bone content (-23%). In summary, this is the first study performing a full bone phenotyping in a mouse model of IBD, which could open avenues for understanding the mechanisms involved in IBD-related bone loss.