Nitrate patch prevents steroid-related bone necrosis

J Orthop Res. 2011 Oct;29(10):1517-20. doi: 10.1002/jor.21420. Epub 2011 Apr 5.

Abstract

Avascular necrosis of the femoral head is a common complication with disabling effect for young patients after high-dose corticosteroid treatment. We could show that steroids have a vasoconstrictive effect on lateral epiphyseal arteries of the femoral head which could lead to ischemia and subsequent necrosis. In this study we investigated the preventive effect of a nitrate patch on steroid-related bone necrosis in a rabbit model. New Zealand White rabbits (male; 3-4.5 kg bodyweight) were injected with 20 mg/kg bodyweight methylprednisolone (GC group; n = 6). Control animals (n = 6) were treated with phosphate-buffered saline. A third group (GC + N; n = 6) additionally received a nitrate patch (0.675 mg/day). Four weeks after i.m. methylprednisolone injection the animals were sacrificed. For histology and immunohistochemistry, tissue samples were fixed in 3% paraformaldehyde, embedded in paraffin, sectioned, dewaxed, and stained with Ladewig. For quantification of empty lacunae, a histologic sign of FHN, histomorphometry was performed. Histomorphometry revealed a significant increase of empty lacunae in glucocorticoid-treated animals compared to controls and GC + N-treated animals. No significant difference in empty lacunae count was detected between the GC + N group and controls. HE staining revealed the different osteocyte amount in the GC versus GC and nitrate patch-treated groups. This study demonstrates an increased number of empty osteocyte lacunae representing a pathologic feature of osteonecrosis, in the GC group. Less empty lacunae were counted in the GC animals after additional treatment with a nitrate patch. This finding suggests that nitrate co-treatment has the potential to prevent steroid-associated FHN.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Endothelium-Dependent Relaxing Factors / administration & dosage*
  • Femur Head / pathology
  • Femur Head Necrosis / chemically induced
  • Femur Head Necrosis / pathology
  • Femur Head Necrosis / prevention & control*
  • Glucocorticoids / adverse effects*
  • Male
  • Methylprednisolone / adverse effects*
  • Nitric Oxide / administration & dosage*
  • Rabbits

Substances

  • Endothelium-Dependent Relaxing Factors
  • Glucocorticoids
  • Nitric Oxide
  • Methylprednisolone