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糖皮质激素治疗成年小鼠的骨强度/骨量差异

Bone Strength/Bone Mass Discrepancy in Glucocorticoid-Treated Adult Mice.

作者信息

Dubrovsky Alanna M, Nyman Jeffrey S, Uppuganti Sasidhar, Chmiel Kenneth J, Kimmel Donald B, Lane Nancy E

机构信息

Center for Musculoskeletal Health University of California at Davis Medical Center Sacramento CA USA.

Department of Orthopaedic Surgery Vanderbilt University Medical Center Nashville TN USA.

出版信息

JBMR Plus. 2020 Dec 21;5(3):e10443. doi: 10.1002/jbm4.10443. eCollection 2021 Mar.

Abstract

Glucocorticoids increase bone fragility in patients in a manner that is underestimated by bone mass measurement. This study aimed to determine if the adult mouse could model this bone strength/bone mass discrepancy. Forty-two 13-week-old BALB/cJ mice were randomized into vehicle and glucocorticoid groups, implanted with vehicle or 6-methylprednisolone pellets, and necropsied after 60 and 120 days. Bone strength and bone mass/microarchitecture were assessed at the right central femur (CF; cortical-bone-rich) and sixth lumbar vertebral body (LVB6; trabecular-bone-rich). Bound water (BW) of the whole right femur was analyzed by proton-nuclear magnetic resonance (H-NMR) relaxometry. Data were analyzed by two-factor ANOVA with time (day 60 and day 120) and treatment (vehicle and glucocorticoid) as main effects for all data. Significant interactions were further analyzed with a Tukey's post hoc test. Most bone strength measures in the CF were lower in the glucocorticoid group, regardless of the duration of treatment, with no time × treatment interaction. However, bone mass measures in the CF showed a significant time × treatment interaction ( = 0.0001). Bone strength measures in LVB6 showed a time × treatment interaction ( < 0.02) such that LVB6 strength was lower after 120 days of glucocorticoids compared with 120 days of vehicle treatment. Whole-femur-BW was lower with both glucocorticoid treatment ( = 0.0001) and time ( < 0.02), with a significant time × treatment interaction ( = 0.005). Glucocorticoid treatment of male BALB/cJ mice resulted in the lowering of bone strength in both cortical and trabecular bone that either appeared earlier or was greater than the treatment-related changes in bone mass/microarchitecture. The adult mouse may be a good model for investigating the bone strength/mass discrepancy observed in glucocorticoid-treated patients. © 2020 The Authors. published by Wiley Periodicals LLC. on behalf of American Society for Bone and Mineral Research.

摘要

糖皮质激素会增加患者的骨脆性,其方式未被骨量测量充分评估。本研究旨在确定成年小鼠是否能模拟这种骨强度/骨量差异。42只13周龄的BALB/cJ小鼠被随机分为溶剂对照组和糖皮质激素组,分别植入溶剂或6-甲基泼尼松龙微丸,并在60天和120天后进行尸检。在右侧股骨中段(CF;富含皮质骨)和第六腰椎椎体(LVB6;富含小梁骨)评估骨强度和骨量/微结构。通过质子核磁共振(H-NMR)弛豫测量法分析整个右侧股骨的结合水(BW)。对所有数据,以时间(60天和120天)和处理(溶剂对照组和糖皮质激素组)作为主要效应进行双因素方差分析。显著的交互作用进一步用Tukey事后检验进行分析。无论治疗持续时间如何,糖皮质激素组CF的大多数骨强度指标均较低,不存在时间×处理交互作用。然而,CF的骨量指标显示出显著的时间×处理交互作用(P = 0.0001)。LVB6的骨强度指标显示出时间×处理交互作用(P < 0.02),即与溶剂处理120天相比,糖皮质激素处理120天后LVB6的强度更低。糖皮质激素处理组的全股骨BW在处理(P = 0.0001)和时间(P < 0.02)上均较低,且存在显著的时间×处理交互作用(P = 0.005)。对雄性BALB/cJ小鼠进行糖皮质激素处理会导致皮质骨和小梁骨的骨强度降低,这种降低要么出现得更早,要么大于与骨量/微结构相关的治疗变化。成年小鼠可能是研究糖皮质激素治疗患者中观察到的骨强度/骨量差异的良好模型。© 2020作者。由Wiley Periodicals LLC代表美国骨与矿物质研究学会出版。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7708/7990143/a17ec91c3e2f/JBM4-5-e10443-g001.jpg

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