Dubrovsky Alanna M, Nyman Jeffrey S, Uppuganti Sasidhar, Chmiel Kenneth J, Kimmel Donald B, Lane Nancy E
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.
JBMR Plus. 2020 Dec 21;5(3):e10443. doi: 10.1002/jbm4.10443. eCollection 2021 Mar.
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.
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。