Effects of methylprednisolone on bone mineral density and microarchitecture of trabecular bones in rats with administration time and assessed by micro-computed tomography

Abstract

Little research exists on the dynamic effects of glucocorticoids on bone mineral density (BMD) and microarchitecture of trabecular bones of rats assessed by micro-computed tomography (micro-CT). To investigate time-related changes in the BMD and microarchitecture of trabeculae in rats exposed to glucocorticoid. Female Sprague-Dawley rats were recruited into a baseline group, glucocorticoid-treated groups, or control groups. Glucocorticoid-treated rats were given daily subcutaneous injections of methylprednisolone at a dosage of 3.5 mg/kg for 1 or 9 weeks. A high-resolution micro-CT was used to identify the densitometric and microarchitectural properties of trabeculae in both the proximal metaphysis of tibiae and the sixth lumbar vertebrae (L6). Compared with baseline rats, volumetric BMD, tissue BMD, bone volume fraction, trabecular number, and degree of anisotropy of trabeculae from tibiae or L6 increased in control rats and glucocorticoid-treated rats with time; however, changes in the latter group were smaller. Compared with control rats at each time point, a decrease occurred in volumetric BMD, tissue BMD, bone volume fraction, trabecular number, degree of anisotropy, and trabecular connectivity density in trabecular bones from tibiae or L6 in glucocorticoid-treated rats. The decrease was greater in week 9 compared to week 1. Contrarily, an increase was noted in trabecular thickness, trabecular separation, and structure model index in glucocorticoid-treated rats. A time-related analysis within glucocorticoid-treated groups in both skeletal regions showed a decline in bone volume fraction, trabecular connectivity density, trabecular number, and degree of anisotropy with time, but trabecular thickness and trabecular separation were elevated. Methylprednisolone can inhibit bone mineralization and bone mass gain with growth in rats. It can also deteriorate microarchitecture of trabeculae in a time-dependent or an accumulative dose-dependent manner. Further, the remaining trabeculae appear to thicken in order to adapt to altered stress.