Steroid therapy and the risk of osteonecrosis in SARS patients: a dose-response meta-analysis

Osteoporos Int. 2017 Mar;28(3):1027-1034. doi: 10.1007/s00198-016-3824-z. Epub 2016 Nov 14.


This meta-analysis synthesized current evidence from 10 trials to evaluate the association between steroid therapy and osteonecrosis incidence in patients with severe acute respiratory syndrome (SARS). Our results suggest that higher cumulative doses and longer treatment durations of steroids are more likely to lead to the development of osteonecrosis in SARS patients.

Introduction: The link between steroid treatment and the risk of osteonecrosis in SARS patients remains unknown. The present meta-analysis aimed to examine the dose-response association between steroid therapy and osteonecrosis incidence in SARS patients. The sex differences in the development of steroid-induced osteonecrosis were also examined.

Methods: We searched PubMed, Web of Science, CNKI, and WANFANG for studies that involved steroid therapy and reported osteonecrosis data in SARS patients. Two authors independently extracted the data from the individual studies, and the rate ratio (RR) of osteonecrosis was calculated using random-effect models.

Results: Ten studies with 1137 recovered SARS patients met the inclusion criteria. Close relationships between osteonecrosis incidence and both the cumulative dose and treatment duration of steroids were observed. The summary RR of osteonecrosis was 1.57 (95% confidence interval (CI) 1.30-1.89, p < 0.001) per 5.0 g increase in the cumulative dose of steroids and was 1.29 (95% CI 1.09-1.53, p = 0.003) for each 10-day increment of increase in treatment duration. The relationship was non-linear (p non-linear < 0.001 and p non-linear = 0.022). There were no significant differences in the risk of developing osteonecrosis between the male and female patients (RR 0.01, 95% CI -0.03 to 0.06, p = 0.582).

Conclusions: SARS patients who received higher cumulative doses and longer treatment durations of steroids were more likely to develop osteonecrosis, and there were no sex differences in this dose-dependent side effect. Our findings suggest that it is important to reduce osteonecrosis risk by modifying the cumulative dose and the treatment duration of steroids in SARS patients.

Keywords: Dose-response; Osteonecrosis; SARS; Sex difference; Steroid therapy.

Publication types

  • Meta-Analysis
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Dose-Response Relationship, Drug
  • Drug Administration Schedule
  • Glucocorticoids / administration & dosage
  • Glucocorticoids / adverse effects*
  • Glucocorticoids / therapeutic use
  • Humans
  • Osteonecrosis / chemically induced*
  • Risk Factors
  • Sensitivity and Specificity
  • Severe Acute Respiratory Syndrome / drug therapy*
  • Sex Factors


  • Glucocorticoids