Substrain-specific differences in bone parameters, alpha-2-macroglobulin circulating levels, and osteonecrosis
Alberto V Carli1,2,3, Edward J Harvey1,2,3, Bouziane Azeddine1
1Vascular, Biology Research Lab, Research Institute, McGill University Health Centre, C9 Montreal General Hospital, 1650 Cedar Avenue, Montreal, QC H3G 1A4, Canada.
Summary
Wistar Kyoto rats are genetically susceptible to glucocorticoid-induced osteonecrosis of the femoral head (ONFH), showing early bone damage and collapse. Elevated alpha-2-macroglobulin (A2M) during treatment did not predict ONFH in this rodent model.
Area of Science:
- Orthopaedic Research
- Biomedical Science
- Pharmacology
Background:
- Chronic glucocorticoid (GC) therapy can cause osteonecrosis of the femoral head (ONFH), particularly in young adults.
- Wistar Kyoto (WK) rats, unlike Sasco Fischer (F344) rats, demonstrate genetic susceptibility to GC-induced ONFH.
- Previous studies established WK rats as a model for GC-induced ONFH.
Purpose of the Study:
- To investigate strain-specific differences in bone parameters, alpha-2-macroglobulin (A2M) levels, and ONFH incidence between WK and F344 rats under GC therapy.
- To evaluate the potential of A2M as a predictive biomarker for GC-induced ONFH.
Main Methods:
- WK and F344 rats received prednisone (1.5 mg/kg/day) or placebo for 6 months, with monthly blood collection.
- Femoral heads were analyzed histologically for ONFH and via micro-computed tomography (micro-CT).
Main Results:
- GC-treated WK rats showed histological signs of early ONFH (apoptosis, empty lacunae) and femoral head collapse via micro-CT.
- GC-treated F344 rats exhibited micro-CT changes with increased marrow fat but less articular involvement.
- Plasma A2M levels increased in GC-treated rats after 3 months but did not correlate with ONFH development.
Conclusions:
- Elevated serum A2M is not a reliable predictive biomarker for early GC-induced ONFH in this rodent model.
- WK rats are highly susceptible to GC-induced ONFH, presenting with early bone damage and collapse.
- A2M may play a role in the host's reparative response to GC-induced bone effects.
