High doses of methylprednisolone causes substantial muscle loss with minimal impact on bone mass and architecture in C57BL/6JRj and RjOrl:SWISS mice

Glucocorticoids are widely used to treat chronic autoimmune and inflammatory disorders. Unfortunately, glucocorticoid treatment frequently results in severe adverse effects, such as skeletal muscle atrophy and glucocorticoid-induced osteoporosis (GIO). Developing a reliable small animal model of GIO has been challenging, especially in achieving consistent bone loss, microstructural deterioration, and reduced bone strength. The study aimed to develop a robust small animal model to evaluate the effects of high doses of methylprednisolone (MP) on muscle and bone tissue simultaneously. Two strains of female mice, C57BL/6JRj (C57) and RjOrl: SWISS (SWISS), were divided into four groups each: (1) Control, (2) MP 15 mg/kg/day, (3) MP 22.5 mg/kg/day, and (4) MP 30 mg/kg/day. While MP caused a reduction in muscle volume in both strains, it did not result in consistent bone deterioration in either strain. Furthermore, the sparse bone loss manifested differently in the two strains. Therefore, although high-dose MP effectively induced muscle atrophy, further refinement is needed in order to achieve consistent bone deterioration. Moreover, unlike previous studies, the musculoskeletal system of SWISS mice did not exhibit greater susceptibility to MP compared to that of C57 mice.