Abstract：
Glucocorticoid-induced osteoporosis (GIOP) changes the microarchitecture of bones and often leads to the reduction of bone-mineral density (BMD) and increased fracture rates. Zebrafish has been used as an alternative model for GIOP, however, the interaction of GIOP, and its treatment, with zebrafish bone morphometrics and mechanical properties, remains a challenge. Thus, this study aimed to evaluate the effects of prednisolone and alendronate on the properties of zebrafish vertebrae. Adult 7-month-old zebrafish were distributed into four groups: control (CTRL), prednisolone-only (PN), alendronate-only (ALN), and the sequential use of both medicines (PN + ALN). Fish skeletons were scanned via micro-tomography (n = 3) to obtain vertebra morphometrics (e.g., BMD). Bone morphology was assessed using scanning electron microscopy (n = 4) and the biomechanical behaviour with nanoindentation technique (n = 3). The BMD decreased in PN (426.08 ± 18.58 mg/cm3) and ALN (398.23 ± 10.20 mg/cm3) groups compared to the CTRL (490.43 ± 41.96 mg/cm3) (p < 0.001); however, administering the medicines in sequence recovered the values to healthy levels (495.43 ± 22.06 mg/cm3) (p > 0.05). The bone layered structures remain preserved in all groups. The vertebrae of the groups that received ALN and PN + ALN, displayed higher modulus of elasticity (27.27 ± 1.59 GPa and 25.68 ± 2.07 GPa, respectively) than the CTRL (22.74 ± 1.60 GP) (p < 0.001). ALN alone increased the hardness of zebrafish vertebrae to the highest value among the treatments (1.32 ± 0.13 GPa) (p < 0.001). Conversely, PN + ALN (1.25 ± 0.11 GPa) showed unaltered hardness from the CTRL (1.18 ± 0.13 GPa), but significantly higher than the PN group (1.08 ± 0.12 GPa) (p < 0.001). ALN administered after GIOP development, rescued osteoporotic condition by recovering the BMD and bone hardness in zebrafish vertebrae.
摘要：
糖皮质激素诱导的骨质疏松症（GIOP）会改变骨骼的微观结构，并经常导致骨矿物质密度（BMD）降低和骨折率增加。斑马鱼已被用作GIOP的替代模型，然而,GIOP的相互作用，和它的治疗,具有斑马鱼骨形态计量学和力学性质，仍然是一个挑战。因此，本研究旨在评价泼尼松龙和阿仑膦酸钠对斑马鱼椎骨特性的影响。成年7个月大的斑马鱼分为四组：对照组（CTRL），仅泼尼松龙（PN），仅阿仑膦酸盐（ALN），以及两种药物的顺序使用（PN+ALN）。通过显微断层扫描（n=3）扫描鱼类骨骼以获得椎骨形态计量学（例如，BMD）。使用扫描电子显微镜（n=4）和纳米压痕技术（n=3）评估骨形态。与CTRL（490.43±41.96mg/cm3）相比，PN（426.08±18.58mg/cm3）和ALN（398.23±10.20mg/cm3）组的BMD降低（p<0.001）；然而，依次给药，使其恢复到健康水平（495.43±22.06mg/cm3）（p>0.05）。骨层结构在所有组中保持保留。接受ALN和PN+ALN的组的椎骨，显示较高的弹性模量(27.27±1.59GPa和25.68±2.07GPa，分别）高于CTRL（22.74±1.60GP）（p<0.001）。单独的ALN将斑马鱼椎骨的硬度提高到处理中的最高值（1.32±0.13GPa）（p<0.001）。相反，PN+ALN(1.25±0.11GPa)显示与CTRL(1.18±0.13GPa)相比硬度不变,但显著高于PN组(1.08±0.12GPa)(p<0.001)。在GIOP发展后给予ALN，通过恢复斑马鱼椎骨的BMD和骨硬度来挽救骨质疏松状况。
