Effect of raloxifene-analog (LY 117018-Hcl) on the bone marrow of ovariectomized mice

The effects of LY117018-Hcl (Ralox-A) on body metabolism and differentiatio n of bone marrow cells were studied in ovariectomized (OVX) mice. We used a mouse model in which estrogen depletion was established for a period of th ree months before treatment. After that period the animals were divided int o three experimental groups consisting of sham-operated, OVX, and OVX-Ralox -A-treated mice. The OVX animals received daily treatment of Ralox-A during two time periods (35 and 65 days). After the treatment we measured the ser um levels of protein, ion(s), lipid content, liver, and kidney functions. O ur findings indicated that a change in hormonal stale did not affect basic body metabolism except for causing an increase in triglycerides (TC) in the OVX mice, which was lowered by the Ralox-A. A higher alkaline phosphatase (ALK-P) level was observed in serum of the OVX-Ralox-A-treated mice than in serum of the OVX mice. We investigated the effects of estrogen depletion o n the differentiation of hematopoietic and stromal cells that directly affe ct bone resorption and formation. OVX and OVX-treated mice were compared wi th the sham group and assessed for the alteration of these cells' different iation. The proliferation of stromal stem cells was measured by CFU-F assay in vitro. A decrease in CFU-F colonies derived from OVX mice was observed and after the Ralox-A treatment the number of CFU-F reached sham levels. On the contrary, an upregulation of myeloid cells was observed when analyzed by FAGS and by granulocyte/macrophage-colony forming unit (G/M-CFU) assay i n selective culture conditions. The G/M-CFUs were increased in the OVX mice and were reduced to sham levels after Ralox-A treatment. In this study, we demonstrated cellular changes of stromal and hemopoietic cells in OVX mice and a beneficial Ralox-A effect that protected such cellular changes. (C) 2000 Wiley-Liss, Inc.