Abstract：
Osteoporosis easily causes delayed fracture union, even non-union. It has been demonstrated that dehydroepiandrosterone (DHEA) supplementation can increase estrogen levels and improve bone mineral density (BMD) in the elderly, while the role of DHEA on fracture healing remains unknown. This study aimed to elucidate the impact of DHEA supplementation on osteoporotic fracture healing. Seventy-two female Sprague-Dawley rats were used. Forty-eight rats received ovariectomy (OVX), and the remaining rats received a sham OVX operation (sham group). A right transverse femoral osteotomy was performed in all rats at 12 weeks post-OVX. OVX rats were randomly allocated into 2 groups (n = 24 in each group): (i) ovariectomized rats (control group) and (ii) ovariectomized rats treated with DHEA (DHEA group, 5 mg/kg/day). The DHEA supplementation was initiated on the first day post-fracture for 3, 6, and 12 weeks. Fracture healing was evaluated by radiography, histology, biomechanical analysis, and dual-energy X-ray absorptiometry (DEXA). Serum biomarkers were analyzed using enzyme-linked immunosorbent assay (ELISA). At 3 and 6 weeks, radiographs revealed reduced calluses formation and lower radiographic scores in the control group than in other groups. The sham and DHEA groups showed higher BMD and bone mineral content (BMC) at the fracture site than the control group after fracture. Histological analysis revealed the fracture callus was remodeled better in the sham and DHEA groups than in the control group. At the early phase of healing, DHEA supplementation increased osteoblast number, callus area, and cartilage area than the control group. An increased bone area was observed in the DHEA group than in the control group at the late phase of healing. Additionally, improved biomechanical characteristics were observed in both the sham and DHEA groups than those in the control group post-fracture. ELISA showed higher levels of insulin-like growth factor-1 (IGF-1) and 17β-estradiol (E2) in the DHEA group than in the control group post-fracture. Furthermore, the DHEA group exhibited significantly elevated alkaline phosphatase (ALP) and osteocalcin (OC) levels compared to the control group at 6 and 12 weeks. The DHEA group and the control group did not exhibit a notable difference in TRAP-5b levels. The present study demonstrated that the DHEA treatment has a favorable impact on osteoporotic fracture healing by enhancing callus formation, consolidation, and strength in the OVX rats.
摘要：
骨质疏松易导致骨折延迟愈合，甚至是非工会。已经证明，补充脱氢表雄酮（DHEA）可以增加雌激素水平并改善老年人的骨密度（BMD），而DHEA对骨折愈合的作用尚不清楚。本研究旨在阐明补充DHEA对骨质疏松性骨折愈合的影响。使用72只雌性Sprague-Dawley大鼠。48只大鼠接受卵巢切除术（OVX），其余大鼠接受假OVX手术(假手术组)。在OVX后12周对所有大鼠进行右股骨横向截骨术。将OVX大鼠随机分为2组（每组n=24）：（i）去卵巢大鼠（对照组）和（ii）接受DHEA治疗的去卵巢大鼠（DHEA组，5mg/kg/天)。在骨折后的第一天开始补充DHEA,持续3、6和12周。骨折愈合通过射线照相术评估，组织学,生物力学分析,和双能X射线吸收法（DEXA）。使用酶联免疫吸附测定(ELISA)分析血清生物标志物。在3周和6周，X线照片显示，对照组的老茧形成减少，放射学评分低于其他组。假手术组和DHEA组骨折后BMD和骨矿物质含量（BMC）高于对照组。组织学分析显示，假手术和DHEA组比对照组的骨折骨痂重塑更好。在愈合的早期阶段，补充DHEA可增加成骨细胞数量，愈伤组织面积,软骨面积优于对照组。在愈合后期，DHEA组的骨面积比对照组增加。此外,假手术组和DHEA组骨折后生物力学特性均优于对照组。ELISA显示DHEA组骨折后胰岛素样生长因子-1（IGF-1）和17β-雌二醇（E2）的水平高于对照组。此外，与对照组相比,DHEA组在第6周和第12周表现出显著升高的碱性磷酸酶(ALP)和骨钙蛋白(OC)水平.DHEA组和对照组的TRAP-5b水平没有显着差异。本研究表明，DHEA治疗对骨质疏松性骨折愈合有良好的影响，通过促进骨痂的形成，合并，OVX大鼠的力量。
