Effects of glucocorticoid treatment on bone strength

Area of Science:

• Biomedical Science
• Orthopedics
• Pharmacology

Background:

• Glucocorticoids (GCs) are widely used medications with known side effects, including osteoporosis.
• GCs are suspected to suppress the Wnt/beta-catenin pathway, impacting bone protein expression.
• Understanding GC effects on different bone genotypes is crucial for managing treatment side effects.

Purpose of the Study:

• To investigate the impact of glucocorticoid (GC) treatment on bone structure and strength in high bone mass (HBM) mice and low density lipoprotein receptor-related protein 5 (LRP5) knockout (KO+/-) mice.
• To compare GC-induced bone changes in HBM and LRP5+/- mice against wild-type (WT) controls.
• To determine if GC effects are specific to trabecular or cortical bone compartments.

Main Methods:

• Mice (HBM, LRP5+/-, WT) were treated with prednisone or a placebo.
• Femurs and L4 vertebral bodies were analyzed using micro-computed tomography (micro-CT) for structural assessment.
• Mechanical testing was performed to evaluate bone strength and apparent material properties.
• Two-way ANOVA was used to analyze differences related to GC treatment and genotype.

Main Results:

• GC treatment significantly decreased structural strength, apparent material properties, and bone structure in HBM mice.
• HBM mice, despite GC-induced losses, maintained higher trabecular bone structure and strength compared to LRP5+/- and WT mice.
• GCs negatively affected both cortical and trabecular bone structure in HBM femurs, and both structural and strength parameters in HBM vertebral bodies.

Conclusions:

• High bone mass (HBM) mice exhibit unique susceptibility to glucocorticoid-induced bone degradation.
• Glucocorticoid treatment impairs bone structure and strength, with varying effects across different bone compartments and genotypes.
• Despite negative impacts, HBM mice demonstrate resilience in trabecular bone parameters post-glucocorticoid treatment.