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

Sep 29, 2026

High-dose methylprednisolone (MP) is evaluated as a way to model glucocorticoid-induced osteoporosis (GIO) while simultaneously tracking skeletal muscle effects. Female mice from C57BL/6JRj and RjOrl:SWISS strains were assigned to control or MP doses of 15, 22.5, and 30 mg/kg/day. MP reduced muscle volume in both strains, but bone deterioration was not consistent, and sparse bone loss differed between strains, indicating that muscle atrophy induction is reliable while robust, reproducible bone outcomes require further refinement.

LanguageEnglish

CategoryHealthcare

FormatPDF

Pages12

Reading Time30 min

AccessFree to download

Background

Glucocorticoid use and adverse effects

Need for simultaneous muscle and bone assessment

Study aim and experimental design

Mouse strains and MP dose groups

Outcomes and findings

Muscle volume reduction

Bone deterioration inconsistency and strain differences

Comparison of SWISS vs C57 susceptibility

[www. nature.com/scientificreports](www. nature.com/scientificreports) OPEN High doses of methylprednisolone causes substantial muscle loss with minimal impact on bone mass and architecture in C57BL/6JRj and RjOrl:SWISS mice Oliver Lassen Slavensky1􀀍, Frederik Duch Bromer1,2,3, Jesper Skovhus Thomsen1,4 & Annemarie Brüel1,4 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 ofGIO 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, themusculoskeletal system of SWISS mice did not exhibit greater susceptibility to MP compared to that of C57 mice. Keywords Glucocorticoids, Glucocorticoid-induced osteoporosis, Osteoporosis, Sarcopenia, Muscle atrophy, Osteosarcopenia Glucocorticoids (GC) are widely used in the management of chronic autoimmune and inflammatory disorders1. Between 1989 and 2008 the annual prevalence of oral GC use was 0.85% in the adult UK population2. Unfortunately, systemic treatment with GCs is frequently accompanied by a rapid and profound bone loss. This adverse effect is termed glucocorticoid-induced osteoporosis (GIO), and it is characterized by a loss of bone mineral density (BMD) and a deterioration of the bone microarchitecture, increasing the risk of bone fractures3. As many as 30–50% of patients undergoing long-term systemic treatment with GCs will experience a bone fracture if preventive measures are not initiated at the onset of GC treatment4. Another common GCinduced adverse effect is skeletal muscle wasting, which can further exacerbate the risk of bone fractures5. The current pharmacological approach to prevent GIO involves the use of either anti-resorptive or osteoanabolic medications6. However, the latter is limited to a maximum of 24 months of treatment over a lifetime, after which preventive treatment of GIO is restricted to anti-resorptive medications only7. Importantly, the current preventive strategy focuses on minimizing the risk of bone fractures but does not address the accompanying muscle wasting. This limitation highlights the need for further research to develop new therapeutic interventions that simultaneously mitigate the detrimental effects of GCs on both skeletal muscle and bone tissue. To achieve this goal, a robust small animal model of skeletal muscle atrophy and GIO is essential. In medical research, small animals such as mice and rats are preferred over larger animals as the initial species for investigation due to ethical and cost considerations. In addition, small animal models of both postmenopausal 1Department of Biomedicine, Aarhus University, Wilhelm Meyers Allé 3, Aarhus, Denmark. 2Department of Clinical Medicine, Aarhus University Hospital, Aarhus, Denmark. 3Department of Endocrinology and Internal Medicine, Aarhus University Hospital, Aarhus, Denmark. 4These authors jointly supervised this work: Annemarie Brüel and Jesper Skovhus Thomsen. 􀀍 email: [OLS@biomed.au.dk](OLS@biomed.au.dk) [www. nature.com/scientific

FAQs

What was the study designed to evaluate about methylprednisolone?

The study aimed to develop a small-animal model that evaluates high-dose methylprednisolone effects on both skeletal muscle and bone tissue simultaneously.

How were the mice grouped and what MP doses were tested?

Female mice from C57BL/6JRj and RjOrl:SWISS were divided into four groups each: control, MP 15 mg/kg/day, MP 22.5 mg/kg/day, and MP 30 mg/kg/day.

Did high-dose MP produce consistent bone deterioration in both mouse strains?

No. MP caused muscle volume reduction in both strains, but it did not result in consistent bone deterioration, and the pattern of sparse bone loss differed between the strains.

Sep 29, 2026

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