title: Nitrate patch prevents steroid-related bone necrosis.
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.
authors.affiliation: Department of Orthopedic and Trauma Surgery, RWTH Aachen University, Pauwelsstrasse 30, D-52074 Aachen, Germany. wolfdrescher@hotmail.com
authors.forename: Wolf
authors.initials: W
authors.lastname: Drescher
authors.forename: Rainer
authors.initials: R
authors.lastname: Beckmann
authors.forename: Richard
authors.initials: R
authors.lastname: Kasch
authors.forename: Melanie
authors.initials: M
authors.lastname: Pufe
authors.forename: Matthias
authors.initials: M
authors.lastname: Knobe
authors.forename: Nisreen
authors.initials: N
authors.lastname: Kweider
authors.forename: Joachim
authors.initials: J
authors.lastname: Hassenpflug
authors.forename: Markus
authors.initials: M
authors.lastname: Tingart
authors.forename: Thomas
authors.initials: T
authors.lastname: Pufe
authors.forename: Mahmed
authors.initials: M
authors.lastname: Kadyrov
mesh_terms: D000818:Animals; D045462:Endothelium-Dependent Relaxing Factors / Q000008:administration & dosage*; D005270:Femur Head / Q000473:pathology; D005271:Femur Head Necrosis / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control*; D005938:Glucocorticoids / Q000009:adverse effects*; D008297:Male; D008775:Methylprednisolone / Q000009:adverse effects*; D009569:Nitric Oxide / Q000008:administration & dosage*; D011817:Rabbits
chemical_list: D045462:Endothelium-Dependent Relaxing Factors; D005938:Glucocorticoids; D009569:Nitric Oxide; D008775:Methylprednisolone