Strontium ranelate retards disc degradation and improves endplate and bone micro-architecture in ovariectomized rats with lumbar fusion induced – Adjacent segment disc degeneration

IF 2.1 Q3 ENDOCRINOLOGY & METABOLISM Bone Reports Pub Date : 2024-02-15 DOI:10.1016/j.bonr.2024.101744
Qi Sun , Fang Liu , Jiakang Fang , Qiangqiang Lian , Yunpeng Hu , Xinyu Nan , Fa-Ming Tian , Guochuan Zhang , Dianwen Qi , Liu Zhang , Jingwen Zhang , Yang Luo , Zuzhuo Zhang , Zhuang Zhou
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Abstract

Objectives

Adjacent segment disc degeneration (ASDD) is one of the long-term sequelae of spinal fusion, which is more susceptible with osteoporosis. As an anti-osteoporosis drug, strontium ranelate (SR) has been reported to not only regulate bone metabolism but also cartilage matrix formation. However, it is not yet clear whether SR has a reversal or delaying effect on fusion-induced ASDD in a model of osteoporosis.

Materials and methods

Fifth three-month-old female Sprague-Dawley rats that underwent L4-L5 posterolateral lumbar fusion (PLF) with spinous-process wire fixation 4 weeks after bilateral ovariectomy (OVX) surgery. Animals were administered vehicle (V) or SR (900 mg/kg/d) orally for 12 weeks post-PLF as follows: Sham+V, OVX + V, PLF + V, OVX + PLF + V, and OVX + PLF + SR. Manual palpation and X-ray were used to evaluate the state of lumbar fusion. Adjacent-segment disc was assessed by histological (VG staining and Scoring), histomorphometry (Disc Height, MVD, Calcification rate and Vascular Bud rate), immunohistochemical (Col-II, Aggrecan, MMP-13, ADAMTS-4 and Caspase-3), and mRNA analysis (ColI, Col-II, Aggrecan, MMP-13 and ADAMTS-4). Adjacent L6 vertebrae microstructures were evaluated by microcomputed tomography.

Results

Manual palpation and radiographs showed clear evidence of the fused segment's immobility. After 12 weeks of PLF surgery, a fusion-induced ASDD model was established. Low bone mass caused by ovariectomy can significantly exacerbate ASDD progression. SR exerted a protective effect on adjacent segment intervertebral disc with the underlying mechanism possibly being associated with preserving bone mass to prevent spinal instability, maintaining the functional integrity of endplate vascular microstructure, and regulating matrix metabolism in the nucleus pulposus and annulus fibrosus.

Discussion

Anti-osteoporosis medication SR treatments not only maintain bone mass and prevent fractures, but early intervention could also potentially delay degenerative conditions linked to osteoporosis. Taken together, our results suggested that SR might be a promising approach for the intervention of fusion-induced ASDD with osteoporosis.

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雷奈酸锶可延缓腰椎间盘退化,改善卵巢切除大鼠腰椎融合术诱发的邻节椎间盘退化的终板和骨微结构
目的邻节椎间盘退变(ASDD)是脊柱融合术的长期后遗症之一,骨质疏松症患者更易患上该病。据报道,作为一种抗骨质疏松症药物,雷奈酸锶(SR)不仅能调节骨代谢,还能调节软骨基质的形成。材料与方法五只三个月大的雌性 Sprague-Dawley 大鼠在双侧卵巢切除术(OVX)4 周后接受了 L4-L5 后外侧腰椎融合术(PLF),并用棘突钢丝固定。PLF术后给动物口服载体(V)或SR(900 mg/kg/d)12周,具体如下:Sham+V、OVX + V、PLF + V、OVX + PLF + V 和 OVX + PLF + SR。人工触诊和 X 光检查用于评估腰椎融合状况。通过组织学(VG 染色和评分)、组织形态学(椎间盘高度、MVD、钙化率和血管芽率)、免疫组化(Col-II、Aggrecan、MMP-13、ADAMTS-4 和 Caspase-3)和 mRNA 分析(ColI、Col-II、Aggrecan、MMP-13 和 ADAMTS-4)对相邻节段的椎间盘进行评估。通过微计算机断层扫描评估了相邻 L6 椎体的微结构。PLF手术12周后,融合诱导的ASDD模型得以建立。卵巢切除术导致的低骨量会明显加剧ASDD的发展。SR对邻近节段的椎间盘具有保护作用,其潜在机制可能与保护骨量以防止脊柱不稳定、维持终板血管微结构的功能完整性以及调节髓核和纤维环的基质代谢有关。讨论抗骨质疏松症药物SR治疗不仅能维持骨量和预防骨折,而且早期干预还可能延缓与骨质疏松症有关的退行性病变。综上所述,我们的研究结果表明,SR 可能是干预融合诱发的 ASDD 骨质疏松症的一种很有前景的方法。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Bone Reports
Bone Reports Medicine-Orthopedics and Sports Medicine
CiteScore
4.30
自引率
4.00%
发文量
444
审稿时长
57 days
期刊介绍: Bone Reports is an interdisciplinary forum for the rapid publication of Original Research Articles and Case Reports across basic, translational and clinical aspects of bone and mineral metabolism. The journal publishes papers that are scientifically sound, with the peer review process focused principally on verifying sound methodologies, and correct data analysis and interpretation. We welcome studies either replicating or failing to replicate a previous study, and null findings. We fulfil a critical and current need to enhance research by publishing reproducibility studies and null findings.
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