Aims: Transient ischemia of osteoporotic bones during elective orthopedic surgery or fracture repair carries risks for serious complications, and estrogen loss or replacement has a potential to influence ischemia-reperfusion-induced inflammatory activation. To clarify this, we investigated the periosteal inflammatory changes in a clinically relevant time frame in ovariectomized rats, an experimental model of postmenopausal bone loss. Furthermore, the effects of chronic estrogen supplementation on the postischemic local and systemic inflammatory reactions were assessed. Main methods: Bilateral ovariectomy or sham operation was performed in 3-month-old female Sprague-Dawley rats. Five months later, estrogen replacement therapy with 17β-estradiol (20 μg- 1 kg- 1 day- 1) or vehicle treatment was initiated. The microcirculatory inflammatory consequences of 60-min total hindlimb ischemia followed by 180-min reperfusion were examined 11 months after ovariectomy and were compared with those in 3-month-old animals. Key findings: The osteoporosis that developed 5 months after ovariectomy was significantly ameliorated by estrogen replacement therapy. Both in ovariectomized and in non-ovariectomized animals, ischemia-reperfusion elevated the neutrophil adherence ∼ 3-fold in the postcapillary venules of the periosteum (intravital microscopy), with an ∼ 50-60% increase in intravascular neutrophil activation (CD11b; FACS analysis), an enhanced TNF-α release (ELISA) and periosteal expression of ICAM-1 (the endothelial ligand of CD11b; immunohistochemistry). Exogenous 17β-estradiol considerably reduced TNF-α release and the number of neutrophil-endothelial interactions in the periosteum, without affecting the CD11b and ICAM-1 expression changes. Significance: Osteoporosis itself does not increase the magnitude of the limb ischemia-reperfusion-associated periosteal inflammatory reaction. Chronic estrogen supplementation, however, reverses osteoporosis and significantly ameliorates the microcirculatory consequences of transient ischemia.
- Intravital microscopy
ASJC Scopus subject areas
- Biochemistry, Genetics and Molecular Biology(all)
- Pharmacology, Toxicology and Pharmaceutics(all)