Association between genetic polymorphisms and osteonecrosis in steroid treatment populations: a detailed stratified and dose-response meta-analysis.

Jun Yang,Ming Jing,Xiaoge Yang

doi:10.1042/bsr20190024

Abstract

Steroid treatment has become recognized as an important risk factor for avascular osteonecrosis of the femoral head. However, not all patients who receive long-term, high-dose steroids develop osteonecrosis, indicating that there are individual differences in occurrence.We explored the relationship between polymorphisms and steroid-induced osteonecrosis of the femoral head (SONFH) incidence with variables. We used a multilevel mixed-effects logistic regression model, which is an expansion of logistic regression, for each type of steroid, primary disease, drug dose, applied duration, and single-nucleotide polymorphism (SNP). We also conducted a dose-response meta-analysis to analyze the cumulative dosage and SONFH risk in mutation carriers. There were significant correlations between the ABCB1 rs1045642 mutant and SONFH in the prednisone-use and methylprednisolone/prednisone-use populations. The ABCB1 rs2032582 mutant homozygote had a protective effect in the methylprednisolone/prednisolone renal transplant population. For ApoB rs693, mutation increased the incidence of SONFH in prednisone-use and methylprednisolone/prednisolone-use populations and renal transplant patients. For ApoB rs1042031, mutation increased the risk of SONFH in the prednisone-use population. The PAI-1 rs1799768 mutation had a protective effect on the SONFH risk prednisone-use and renal transplant populations. ABCB1 rs1045642 mutations have a protective effect against SONFH, and ApoB rs693 and rs1042031 increase the SONFH risk. Cumulative dosage and treatment duration had little effect on the results. In addition, there was a dose-effect correlation in ABCB1 rs1045642 and rs2032582 mutation carriers.

Highlights

Steroid-induced osteonecrosis of the femoral head (SONFH), which leads to collapse of the femoral head and articular dysfunction, has an incidence of 9–40% amongst patients receiving steroid treatment [1]
The full texts of 83 articles were assessed, amongst which studies were excluded for the following reasons: the control group did not receive steroid therapy (26); reviews (8);
ABCB1 rs1045642 mutations have a protective effect against SONFH, and mutations in ApoB rs693 and rs1042031 increase the SONFH risk

Summary

Introduction

Steroid-induced osteonecrosis of the femoral head (SONFH), which leads to collapse of the femoral head and articular dysfunction, has an incidence of 9–40% amongst patients receiving steroid treatment [1]. The exact pathology of SONFH is still unclear and might be related to lipid metabolism disorders, abnormal microcirculation, insufficient blood supply, inflammation, and bone marrow mesenchymal stem cell osteogenesis differentiation dysfunction. The abnormal blood supply leads to the apoptosis of osteocytes and osteoblasts, followed by bone loss and reduced bone mineral density [2]. Lipid metabolism dysfunction is an important pathology, and steroid application may lead to an increase in blood lipid levels and to the development of intravascular lipid embolism in the microvasculature [3]. Embolism accumulation might affect microcirculation and increase the pressure of the intramedullary cavity, eventually leading to the death of bone cells. Long-term or mass steroid application is the critical pathogenesis of SONFH [4]

Methods

Results

Conclusion