Lipid Transporter Activity-Related Genetic Polymorphisms Are Associated With Steroid-Induced Osteonecrosis of the Femoral Head: An Updated Meta-Analysis Based on the GRADE Guidelines

Xiantao Chen,Leilei Zhang,Dawei Liang,Hongxia Ma,Fenzhi Liu,Jing Li

doi:10.3389/fphys.2018.01684

Abstract

Aims: The purpose of this study was to assess the relationship between genetic variants and steroid-induced osteonecrosis of the femoral head (SONFH) in steroid use populations.Methods: We searched the public databases up to April 15, 2018. This study analyzed only the single-nucleotide polymorphisms (SNPs) that have appeared in more than three studies and assessed the level of evidence by classifying the outcomes according to the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach.Results: The ABCB1 rs1045642 C>T mutation had a protective effect against SONFH in the allelic model (I2 = 50.2%; OR: 0.74; 95% CI: 0.55–1.00; p = 0.046). The rs2032582 mutation in the ABCB1 gene showed no relationship to SONFH (allelic model: I2 = 63.4%; OR: 0.85; 95% CI: 0.58–1.23; p = 0.382). In ApoB rs693, four models showed that mutations can increase SONFH risk, but the allelic model did not. The ApoB rs1042031 mutation increased SONFH risk in the dominant model (I2 = 50.3%; OR: 2.90; 95% CI: 1.49–5.66; p = 0.002).Conclusion: An allelic model of ABCB1 rs1045642 showed that mutations have a protective effect against SONFH at a very low level of evidence. The mutations in ApoB rs693 and rs1042031 increase the SONFH risk with moderate levels of evidence.

Highlights

Osteonecrosis of the femoral head (ONFH) is caused by the obstruction or interruption of local blood supply, resulting in tissue ischemia, necrosis, and bone collapse (Kim et al, 2011)
The full texts of 81 articles were assessed, among which the control group did not receive steroid therapy (25); the article was a review (7); the study was non-single-nucleotide polymorphisms (SNPs)-related (5); the research was basic (3); the study did not report frequencies or effect size results (2); the study did not include steroid-related ONFH (2); the study was a case report (2); the research was microRNA related (2); the report was a duplicate (2); and the research was of heredity steroid-induced ONFH (SONFH) (1)
The results showed that there was no significant relationship between this mutation and SONFH in the allelic model (I2 = 58%; odds ratio (OR): 2.63; 95% confidence intervals (CIs): 0.92–7.54; p = 0.072)

Summary

Introduction

Osteonecrosis of the femoral head (ONFH) is caused by the obstruction or interruption of local blood supply, resulting in tissue ischemia, necrosis, and bone collapse (Kim et al, 2011). The core decompression method only relieved the pressure of the pulp cavity and delayed the progression of necrosis (Yu et al, 2018). The pathogenesis of steroid-induced ONFH (SONFH) is not yet clear and may be related to an imbalance in lipid metabolism and abnormal microcirculation (Johnson et al, 2004). The abnormal blood supply leads to apoptosis of osteocytes and osteoblasts, which causes bone loss and reduces bone mineral density (Luo et al, 2018). Disordered lipid metabolism is another crucial pathogenesis that leads to increases in circulating lipid levels, microvascular fat embolisms, and lipid accumulation in the pulp cavity and causes osteocyte death

Methods

Results

Discussion

Conclusion