Relations Between Bone Quantity, Microarchitecture, and Collagen Cross-links on Mechanics Following In Vivo Irradiation in Mice.
Relations Between Bone Quantity, Microarchitecture, and Collagen Cross-links on Mechanics Following In Vivo Irradiation in Mice.
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DOI：
10.1002/jbm4.10545
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发表时间：
2021-11
期刊：
影响因子：
3.8
通讯作者：
Keaveny TM
中科院分区：
文献类型：
--
作者：
Pendleton MM;Emerzian SR;Sadoughi S;Li A;Liu JW;Tang SY;O'Connell GD;Sibonga JD;Alwood JS;Keaveny TM
人类通过航天或癌症放射治疗暴露于电离辐射，已知放射治疗暴露会增加骨骼骨折的风险。尽管辐照可减少骨小梁骨量、改变骨小梁微结构并增加胶原交联，但这些效应对机械完整性损失的相对贡献仍不清楚。为了提供见解，在解决单调强度和循环加载疲劳寿命的同时，我们对发育成熟（17周龄）的C57 BL/6 J雄性小鼠（n = 84）进行了全身、急性、伽马辐照实验。对小鼠给予0戈伊（假手术）、1戈伊（由火星使命累积暴露激发）或5戈伊（由临床治疗方案激发）剂量，并在暴露后短期（11天）或长期（12周）时间点取出腰椎。使用微型计算机断层扫描评估骨小梁和皮质的数量和结构，使用生化成分测定评估胶原质量，并进行机械测试以评价椎体压缩强度和疲劳寿命。在暴露后11天，5戈伊照射显著减少了小梁质量（p < 0.001），改变了微结构（例如，连接密度p < 0.001），并增加了胶原交联（p < 0.001）。尽管有这些变化，椎体强度（p = 0.745）和疲劳寿命（p = 0.332）保持不变。在5戈伊照射后12周，骨小梁的趋势持续存在;此外，无论是否照射，皮质厚度（p < 0.01）和疲劳寿命（p < 0.01）均降低。这些结果表明，5戈伊全身照射对骨小梁形态和胶原交联的高度显著影响未转化为对椎体力学的可检测影响。观察到的唯一机械缺陷与老化有关。总之，这些椎骨结果表明，对于航天飞行，单独辐照可能不会改变失效特性，对于放疗，需要进行更多的研究，包括暴露后时间作为阳性对照，并对两种失效模式进行测试，以确定骨折风险增加的原因。版权所有© 2021作者。JBMR Plus由Wiley Periodicals LLC代表美国骨与矿物质研究学会出版。本文由美国政府雇员贡献，他们的作品在美国属于公有领域。
Humans are exposed to ionizing radiation via spaceflight or cancer radiotherapy, and exposure from radiotherapy is known to increase risk of skeletal fractures. Although irradiation can reduce trabecular bone mass, alter trabecular microarchitecture, and increase collagen cross‐linking, the relative contributions of these effects to any loss of mechanical integrity remain unclear. To provide insight, while addressing both the monotonic strength and cyclic‐loading fatigue life, we conducted total‐body, acute, gamma‐irradiation experiments on skeletally mature (17‐week‐old) C57BL/6J male mice (n = 84). Mice were administered doses of either 0 Gy (sham), 1 Gy (motivated by cumulative exposures from a Mars mission), or 5 Gy (motivated by clinical therapy regimens) with retrieval of the lumbar vertebrae at either a short‐term (11‐day) or long‐term (12‐week) time point after exposure. Micro‐computed tomography was used to assess trabecular and cortical quantity and architecture, biochemical composition assays were used to assess collagen quality, and mechanical testing was performed to evaluate vertebral compressive strength and fatigue life. At 11 days post‐exposure, 5 Gy irradiation significantly reduced trabecular mass (p < 0.001), altered microarchitecture (eg, connectivity density p < 0.001), and increased collagen cross‐links (p < 0.001). Despite these changes, vertebral strength (p = 0.745) and fatigue life (p = 0.332) remained unaltered. At 12 weeks after 5 Gy exposure, the trends in trabecular bone persisted; in addition, regardless of irradiation, cortical thickness (p < 0.01) and fatigue life (p < 0.01) decreased. These results demonstrate that the highly significant effects of 5 Gy total‐body irradiation on the trabecular bone morphology and collagen cross‐links did not translate into detectable effects on vertebral mechanics. The only mechanical deficits observed were associated with aging. Together, these vertebral results suggest that for spaceflight, irradiation alone will likely not alter failure properties, and for radiotherapy, more investigations that include post‐exposure time as a positive control and testing of both failure modalities are needed to determine the cause of increased fracture risk. © 2021 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research. This article has been contributed to by US Government employees and their work is in the public domain in the USA.