Animal Models of Corticosteroid-Associated Bone Diseases

Osteonecrosis (ON) is a disease that is characterized by lesions of dead bone, most frequently detected in the subchondral bone of the convex side of the major diarthrodial joints (hips, knees, shoulders, and talus). High-dose corticosteroid therapy is one major risk factor for ON. The pathological appearance of ON of the femoral head, however, is fairly consistent regardless of the etiology. Depending on the stage of the disease, this includes evidence of bone marrow edema, lipocyte and bone cell necrosis, fibrosis, creeping substitution (new bone lying on dead bone), and the presence of osteoporosis (Chernetsky SG et al., Clin Orthop Relat Res. 368:149–61, 1999). Hemorrhage within the bone marrow compartment has also been observed in patient specimens from corticosteroid-associated ON (Saito S et al., Clin Orthop Relat Res. 277:98–110, 1992). Previous investigators have suggested that corticosteroid-associated ON has more rapid progression than other etiologies (Chernetsky SG et al., Clin Orthop Relat Res. 368:149–61, 1999; Hastings and Macnab, Can J Surg. 8:68–83, 1965). The mechanisms involved in the development of ON are difficult to explore from clinical samples as they provide a single snapshot at one timepoint subsequent to the onset of the disease, usually months after the onset of the disease when the symptoms first appear. While some investigators have used corticosteroid-associated animal models to evaluate different potential treatments (Li X et al., Bone. 33(4):652–9, 2003; Zhang KJ et al., Rheumatol Int. 32(11):3405–11, 2012; Erken HY et al., Int Orthop. 36(7):1523–8, 2012), it is not clear whether the results can be extrapolated to the human condition. A better understanding of the pathophysiological mechanisms is needed.