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

Biosci Rep. 2019 May 14;39(5):BSR20190024. doi: 10.1042/BSR20190024. Print 2019 May 31.

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.

Keywords: meta analysis; single nucleotide polymorphisms; steroids.

Publication types

  • Meta-Analysis

MeSH terms

  • ATP Binding Cassette Transporter, Subfamily B / genetics
  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Apolipoproteins B / genetics
  • Child
  • Femur Head Necrosis / chemically induced*
  • Femur Head Necrosis / genetics*
  • Genetic Predisposition to Disease
  • Humans
  • Incidence
  • Methylprednisolone / administration & dosage
  • Methylprednisolone / adverse effects
  • Middle Aged
  • Polymorphism, Single Nucleotide*
  • Prednisone / administration & dosage
  • Prednisone / adverse effects
  • Steroids / administration & dosage
  • Steroids / adverse effects*
  • Young Adult

Substances

  • ABCB1 protein, human
  • ATP Binding Cassette Transporter, Subfamily B
  • Apolipoproteins B
  • Steroids
  • Prednisone
  • Methylprednisolone