The temporal characterization of marrow lipids and adipocytes in a rabbit model of glucocorticoid-induced osteoporosis

Abstract

To characterize the temporal changes in marrow lipids content and adipocytes in the development of glucocorticoid-induced osteoporosis (GIOP) in rabbits using MR spectroscopy. Twenty 20-week-old female rabbits were randomized to a control group and a GIOP group equally. Marrow lipids fraction and bone mineral density at the left proximal femur and L3-L4 vertebrae were measured by MR spectroscopy and dual-energy X-ray absorptiometry at week 0, 4, 8, and 12. Marrow adipocytes were quantitatively evaluated by histopathology. Marrow adiposity in the GIOP group showed a significant increase over time, with a variation of marrow lipids fraction (+35.9%) at week 4 from baseline and it was maintained until week 12 (+75.2%, p<0.001 for all). The GIOP group demonstrated continuous deterioration of bone with significant difference between the two groups at week 8, followed by increased marrow fat with significant difference at week 4 (p<0.05 for all). In comparison with the controls, marrow adipocyte density in the GIOP group increased by 57.1% at week 8 and 35.4% at week 12, respectively. A reduction (-13.3%) in adipocyte mean diameter at week 8 (but an increase (+22.7%) at week 12) were observed in the GIOP group compared with the control group (p<0.05 for all). There was significant difference between two periods (p=0.023) in adipocyte mean diameter in the GIOP group. The percentage area of marrow adipocytes in the GIOP group was 62.8±8.7% at week 8 and 79.2±7.7% at week 12, both of which were significantly higher than those of the controls (p<0.05 for all). Marrow adipogenesis is synchronized with bone loss in the development of GIOP, which was characterized by a significant increase in the number of small-sized marrow adipocytes in the relatively early stage and concomitant volume increase later on. MR spectroscopy appears to be the most powerful tool for detecting the sequential changes in marrow lipid content.