Bisphosphonates are potent inhibitors of
bone resorption. In previous studies, we have shown that
ovariectomy accelerates
bone resorption and 1-hydroxyethylidene-1, 1-bisphosphonate (HEBP) inhibits
ovariectomy-accelerated
bone resorption in female Wistar adult rats. As
interleukin 1 (IL-1) stimulates
bone resorption in vitro and in vivo, we have investigated the effects of
ovariectomy and HEBP administered in vivo on
IL-1 secretion from peritoneal macrophages in adult rats.
Ovariectomy or
sham surgery were performed in female Wistar rats at 40 weeks of age. Ovariectomized and
sham-operated rats were administered with HEBP (10 mg) or saline, 10 times in total, from 43 to 46 weeks of age.
Paraffin oil-induced peritoneal macrophages at 46 weeks of age were cultured for 24 hours.
Lipopolysaccharide (LPS)-stimulated peritoneal macrophages from ovariectomized rats secreted more
IL-1 than
sham-operated rats. HEBP decreased LPS-stimulated
IL-1 secretion from peritoneal macrophages in ovariectomized rats, but not in
sham-operated rats. In vivo administration of HEBP decreased
IL-1 secretion only in postovariectomy hyperresorptive states. These results suggest that alterations in LPS-stimulated
IL-1 secretion from oil-induced peritoneal macrophages may be responsible, at least in part, for the postovariectomy acceleration in
bone resorption and its inhibition by HEBP.