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1,25-二羟基维生素D3对去卵巢大鼠股骨骨折愈合及骨重塑的影响

Effect of 1,25-dihydroxy vitamin D3 on fracture healing and bone remodeling in ovariectomized rat femora.

作者信息

Fu Lingjie, Tang Tingting, Miao Yanying, Hao Yongqiang, Dai Kerong

机构信息

Department of Orthopaedic Surgery, Ninth People's Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, PR China.

出版信息

Bone. 2009 May;44(5):893-8. doi: 10.1016/j.bone.2009.01.378. Epub 2009 Feb 5.

Abstract

Osteoporosis is a major health problem characterized by compromised bone strength that predisposes patients to an increased risk of fracture, more and more investigations are focusing on the treatment of osteoporotic fracture healing. However, there are few studies elucidating the efficacy of vitamin D, 1,25-dihydroxy vitamin D(3) (1,25(OH)(2)D(3)), on osteoporotic fracture healing. In the present study we have established an osteoporotic fracture rat model to evaluate the effects of 1,25(OH)(2)D(3) on fracture healing. Female SD rats of six-month-old (n=40) allocated randomly into two groups were given ovariectomy. Bilateral midshaft femoral osteotomy was performed 12 weeks post-ovariectomy. Then treatment was begun at the second day after osteotomy and continued until sacrifice at 6 and 16 weeks post-fracture with middle chain triglyceride (MCT) vehicle and 1,25(OH)(2)D(3) at 0.1 microg/kg/day by oral gavage. Fracture callus was evaluated by soft X-ray radiography, micro-computed tomography (micro-CT), biomechanical testing and histology. Soft X-ray radiography, at 6 weeks post-fracture, showed a less distinct fracture line in the 1,25(OH)(2)D(3) group compared with the MCT-vehicle group, however, the fracture line was invisible in both groups at 16 weeks post-fracture. Micro-CT based histomorphometric data, at 6 weeks post-fracture, showed that the total volume of callus (TV) was approximately 23% higher in the 1,25(OH)(2)D(3) group than that in the MCT-vehicle group (P<0.001), and the new bone volume (BV), BV/TV, the trabecular number (Tb.N), and density of TV also showed the same trend. At 16 weeks post-fracture, the increment still existed as shown by Tb.Th and density of TV (P<0.001, vs control). Biomechanical testing data, at 6 weeks post-fracture, showed that the ultimate load at failure and energy absorption of the 1,25(OH)(2)D(3) group were nearly one fold higher than that of the MCT-vehicle group (P<0.001). At 16 weeks post-fracture, the ultimate load and energy absorption were also higher with the treatment of 1,25(OH)(2)D(3) (P<0.01 vs control). Histology showed that the fracture callus in the 1,25(OH)(2)D(3) group was remodeled better compared to the control group. In conclusion, 1,25(OH)(2)D(3) could promote fracture healing by improving the histomorphometric parameters, mechanical strength and tendency to increase transformation of woven bone into lamellar bone in an ovariectomized rat model.

摘要

骨质疏松症是一个主要的健康问题,其特征是骨强度受损,使患者面临骨折风险增加的问题,越来越多的研究集中在骨质疏松性骨折愈合的治疗上。然而,很少有研究阐明维生素D、1,25 - 二羟基维生素D(3)(1,25(OH)₂D(3))对骨质疏松性骨折愈合的疗效。在本研究中,我们建立了骨质疏松性骨折大鼠模型,以评估1,25(OH)₂D(3)对骨折愈合的影响。将40只6月龄雌性SD大鼠随机分为两组并进行卵巢切除术。卵巢切除术后12周进行双侧股骨干中段截骨术。然后在截骨术后第二天开始治疗,持续至骨折后6周和16周处死,分别通过口服灌胃给予中链甘油三酯(MCT)载体和0.1μg/kg/天的1,25(OH)₂D(3)。通过软X线摄影、显微计算机断层扫描(micro-CT)、生物力学测试和组织学对骨折痂进行评估。骨折后6周的软X线摄影显示,与MCT载体组相比,1,25(OH)₂D(3)组的骨折线不太明显,然而,在骨折后16周两组的骨折线均不可见。基于micro-CT的组织形态计量学数据显示,骨折后6周,1,25(OH)₂D(3)组的骨痂总体积(TV)比MCT载体组高约23%(P<0.001),新骨体积(BV)、BV/TV、骨小梁数量(Tb.N)和TV密度也呈现相同趋势。骨折后16周,Tb.Th和TV密度显示仍存在增加(与对照组相比,P<0.001)。生物力学测试数据显示,骨折后6周,1,25(OH)₂D(3)组的破坏时极限载荷和能量吸收比MCT载体组高出近一倍(P<0.001)。骨折后16周,1,25(OH)₂D(3)治疗组的极限载荷和能量吸收也更高(与对照组相比,P<0.01)。组织学显示,与对照组相比,1,25(OH)₂D(3)组的骨折痂重塑更好。总之,在去卵巢大鼠模型中,1,25(OH)₂D(3)可通过改善组织形态计量学参数、机械强度以及增加编织骨向板层骨转化的趋势来促进骨折愈合。

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