Marrow adiposity recovery after early zoledronic acid treatment of glucocorticoid-induced bone loss in rabbits assessed by magnetic resonance spectroscopy

Abstract

Background: Although there is an inverse relationship between bone mass and marrow adiposity, the reversal function of zoledronic acid (ZOL) on increased marrow fat has not been studied. The aim of our study is to use the 3T magnetic resonance spectroscopy (MRS) to characterize the dynamical change process of the marrow fat responding to early ZOL treatment in the rabbit model with glucocorticoid-induced bone loss.

Methods: Fifteen 20-week-old female New Zealand White rabbits were randomized to control group, methylprednisolone (MPS) group, and MPS+ZOL group equally. Bone mineral density (BMD) and marrow fat fraction (FF) at L3-L4 vertebrae and left proximal femur were measured by Dual-energy X-ray absorptiometry and MRS at week 0, 4, 8, and 12. The animals were euthanized at the end of our experiment and their left femurs were dissected out for the histopathological examination.

Results: The MPS group demonstrated a remarkable increase in FF but a reduction in BMD compared with the controls at week 4 and 8, respectively (P<0.05 for all). Early treatment of ZOL can inhibit bone degeneration, although the bone mass would not recover to its original level. FF in MPS group exhibited a dramatic increase over time, with an increased FF variation (+31.6%, P=0.009) at week 4 from baseline and it was maintained until week 12 (+75.2%, P<0.001). In MPS+ZOL group, the FF returned to baseline value after the ZOL treatment. Comparing with the controls, larger marrow adipocyte density, the mean of the adipocyte diameter, and the percentage area of the adipocyte were observed in the MPS group (P<0.05 for all), whereas there were no significant differences in quantitative parameters of marrow adipocytes between the ZOL-treated group and the normal rabbits.

Conclusion: An increase of the marrow adiposity is synchronized with the deterioration of the MPS-induced bone mass. A single dose of early ZOL can reverse the marrow adiposity to its original level completely.