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口服脱氢表雄酮补充剂可增强去卵巢大鼠骨质疏松性骨折的愈合。

Oral dehydroepiandrosterone supplementation enhances osteoporotic fracture healing in the OVX rats.

机构信息

Department of Orthopaedic Surgery, The Second Affiliated Hospital of Fujian Medical University, Quanzhou 362000, Fujian, PR China.

Department of Radiology, The Second Affiliated Hospital of Fujian Medical University, Quanzhou 362000, Fujian, PR China.

出版信息

Bone. 2024 Oct;187:117201. doi: 10.1016/j.bone.2024.117201. Epub 2024 Jul 10.

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

骨质疏松症容易导致延迟骨折愈合,甚至不愈合。已经证明,脱氢表雄酮(DHEA)补充剂可以增加老年人的雌激素水平并改善骨密度(BMD),而 DHEA 对骨折愈合的作用尚不清楚。本研究旨在阐明 DHEA 补充剂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),其余大鼠接受假卵巢切除术(假手术组)。所有大鼠在 OVX 后 12 周进行右侧股骨横断骨折。OVX 大鼠随机分为 2 组(每组 24 只):(i)卵巢切除大鼠(对照组)和(ii)卵巢切除大鼠用 DHEA 治疗(DHEA 组,5mg/kg/天)。骨折后第 1 天开始 DHEA 补充治疗,持续 3、6 和 12 周。通过影像学、组织学、生物力学分析和双能 X 射线吸收法(DEXA)评估骨折愈合。使用酶联免疫吸附测定法(ELISA)分析血清生物标志物。在 3 和 6 周时,对照组的 X 光片显示骨痂形成减少,放射评分低于其他组。假手术组和 DHEA 组在骨折后显示出比对照组更高的骨折部位骨密度和骨矿物质含量(BMC)。组织学分析显示,在假手术组和 DHEA 组中,骨折骨痂的重塑优于对照组。在愈合的早期阶段,DHEA 补充剂增加了成骨细胞数量、骨痂面积和软骨面积,高于对照组。在愈合的晚期阶段,DHEA 组的骨面积高于对照组。此外,与对照组相比,骨折后 sham 组和 DHEA 组的生物力学特性得到了改善。ELISA 显示,与对照组相比,骨折后 DHEA 组的胰岛素样生长因子 1(IGF-1)和 17β-雌二醇(E2)水平更高。此外,与对照组相比,DHEA 组在 6 周和 12 周时碱性磷酸酶(ALP)和骨钙素(OC)水平显著升高。DHEA 组和对照组在 TRAP-5b 水平上没有显著差异。本研究表明,DHEA 治疗通过增强 OVX 大鼠的骨痂形成、骨痂整合和强度,对骨质疏松性骨折愈合有积极影响。

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