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磁共振波谱评估唑来膦酸早期治疗兔糖皮质激素诱导性骨丢失后骨髓脂肪含量的恢复。

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

机构信息

Department of Radiology, Yueyang Hospital affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai 200437, China.

出版信息

Bone. 2013 Feb;52(2):668-75. doi: 10.1016/j.bone.2012.11.002. Epub 2012 Nov 9.

DOI:10.1016/j.bone.2012.11.002
PMID:23142803
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.

摘要

背景

尽管骨量与骨髓脂肪含量呈负相关,但唑来膦酸(ZOL)对增加的骨髓脂肪的逆转作用尚未得到研究。我们的研究目的是使用 3T 磁共振波谱(MRS)来描述兔糖皮质激素诱导性骨丢失模型中早期 ZOL 治疗对骨髓脂肪动态变化的影响。

方法

15 只 20 周龄雌性新西兰白兔随机分为对照组、甲泼尼龙(MPS)组和 MPS+ZOL 组。在第 0、4、8 和 12 周,通过双能 X 射线吸收仪和 MRS 测量 L3-L4 椎体和左侧股骨近端的骨矿物质密度(BMD)和骨髓脂肪分数(FF)。实验结束时处死动物,取出左侧股骨进行组织病理学检查。

结果

与对照组相比,MPS 组在第 4 和 8 周时 FF 显著增加,而 BMD 降低(均 P<0.05)。早期 ZOL 治疗可抑制骨退变,尽管骨量不会恢复到原来水平。MPS 组的 FF 随时间呈急剧增加趋势,与基线相比,第 4 周时 FF 变化增加(+31.6%,P=0.009),并持续至第 12 周(+75.2%,P<0.001)。在 MPS+ZOL 组中,ZOL 治疗后 FF 恢复到基线值。与对照组相比,MPS 组的骨髓脂肪细胞密度、脂肪细胞平均直径和脂肪细胞面积百分比较大(均 P<0.05),而 ZOL 治疗组与正常兔之间的骨髓脂肪细胞定量参数无显著差异。

结论

骨髓脂肪增多与 MPS 诱导的骨量恶化同步发生。单次早期 ZOL 治疗可完全逆转骨髓脂肪至原始水平。

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