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Journal of Orthopaedic Surgery and Research

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Open Access 01-12-2021 | Ovariectomy | Research article

Raloxifene retards the progression of adjacent segmental intervertebral disc degeneration by inhibiting apoptosis of nucleus pulposus in ovariectomized rats

Authors: Qi Sun, Xin-Yu Nan, Fa-Ming Tian, Fang Liu, Shao-Hua Ping, Zhuang Zhou, Liu Zhang

Published in: Journal of Orthopaedic Surgery and Research | Issue 1/2021

Abstract

Background

Adjacent segmental intervertebral disk degeneration (ASDD) is a major complication secondary to lumbar fusion. Although ASSD pathogenesis remains unclear, the primary cause of intervertebral disk degeneration (IVDD) development is apoptosis of nucleus pulposus (NP). Raloxifene (RAL) could delay ASDD by inhibiting NP apoptosis.

Methods

An ASDD rat model was established by ovariectomy (OVX) and posterolateral spinal fusion (PLF) on levels 4–5 of the lumbar vertebrae. Rats in the treatment groups were administered 1 mg/kg/d RAL by gavage for 12 weeks, following which, all animals were euthanized. Lumbar fusion, apoptosis, ASDD, and vertebrae micro-architecture were evaluated.

Results

RAL maintained intervertebral disk height (DHI), delayed vertebral osteoporosis, reduced histological score, and inhibited apoptosis. The OVX+PLF+RAL group revealed upregulated expression of aggrecan and B-cell lymphoma-2 (bcl2), as well as significantly downregulated expression of a disintegrin and metalloproteinase with thrombospondin motifs 4 (ADAMTS-4), metalloproteinase-13 (MMP-13), caspase-3, BCL2-associated X (bax), and transferase dUTP nick end labeling (TUNEL) staining. Micro-computed tomography (Micro-CT) analysis revealed higher bone volume fraction (BV/TV), bone mineral density (BMD), and trabecular number (Tb.N), and lower trabecular separation (Tb.Sp) in OVX+PLF+RAL group than in the OVX+PLF group.

Conclusions

RAL can postpone ASDD development in OVX rats through inhibiting extracellular matrix metabolic imbalance, NP cell apoptosis, and vertebral osteoporosis. These findings showed RAL as a potential therapeutic target for ASDD.

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Title: Raloxifene retards the progression of adjacent segmental intervertebral disc degeneration by inhibiting apoptosis of nucleus pulposus in ovariectomized rats
Authors: Qi Sun
Xin-Yu Nan
Fa-Ming Tian
Fang Liu
Shao-Hua Ping
Zhuang Zhou
Liu Zhang
Publication date: 01-12-2021
Publisher: BioMed Central
Keywords: Ovariectomy
Osteoporosis
Osteoporosis
Raloxifene
Estrogens
Published in: Journal of Orthopaedic Surgery and Research / Issue 1/2021
Electronic ISSN: 1749-799X
DOI: https://doi.org/10.1186/s13018-021-02504-4

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Raloxifene retards the progression of adjacent segmental intervertebral disc degeneration by inhibiting apoptosis of nucleus pulposus in ovariectomized rats

Abstract

Background

Methods

Results

Conclusions

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Background

Methods

Results

Conclusions

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