Annelies Smit1, Kaiming Yue1, Marijke Koedam2, Bram van der Eerden2, Jan Kroon1, Sander Kooijman1, Patrick Rensen1, Onno Meijer1, Elizabeth Winter3
(1) Department of Medicine, Division of Endocrinology & Einthoven Laboratory, Leiden University Medical Center, Leiden, The Netherlands.
(2) Department of Internal Medicine, Erasmus Medical Center, Rotterdam, The Netherlands.
(3) Department of Medicine, Division of Endocrinology, Einthoven Laboratory & Center for Bone Quality, Leiden University Medical Center, Leiden, The Netherlands.
Background
Glucocorticoids prevent inflammation but cause osteoporosis with prolonged use. In the widely used collagen antibody-induced arthritis (CAIA) model, mice develop acute inflammation and trabecular bone loss. However, it is unknown how bone remodels after CAIA resolution and whether concurrent glucocorticoid treatment affects bone recovery.
Methods
CAIA was induced in 8-week-old male Balb/c mice via injecting Collagen-II antibodies on day 0 and LPS on day 4; healthy controls received saline. Daily injections of methylprednisolone or vehicle were given from day 7–49. Arthritis was scored from day 5–21 by paw redness and swelling. On day 49, plasma markers of bone formation (P1NP) and resorption (TRAP), femur microarchitecture (microCT), and femur bone formation rate (dynamic histomorphometry) were assessed.
Results
At day 7, all CAIA groups had elevated arthritis scores. By day 21, vehicle-treated CAIA mice sustained arthritis (+10% vs day 7), while methylprednisolone resolved it (-100%). P1NP and TRAP levels of vehicle-treated CAIA mice matched healthy controls (ns). Methylprednisolone reduced P1NP (-46% vs CAIA-vehicle, p<0.05) but not TRAP (ns). Cortical bone area and thickness were unchanged by CAIA (ns), while trabecular bone volume decreased (-23%, p<0.001). Methylprednisolone prevented trabecular bone loss (+24%, p<0.01) but reduced cortical thickness (-9.5%, p<0.001). Cortical bone formation rate was unchanged by CAIA (ns) but reduced by methylprednisolone (-41%, p<0.01); trabecular bone formation rate was similar across groups.
Conclusion
Bone remodeling recovers after CAIA, but trabecular loss persists. Because CAIA and glucocorticoids affect trabecular and cortical bone differently, this model can distinguish inflammation- from glucocorticoid-driven bone loss.