Systemic treatments with the low‐calcemic 1,25(OH)₂D₃ analogs JKF or QW increase both the morphological and biochemical responses to estradiol‐17β in rat tibiae

Abstract

We demonstrated previously that daily injection for 3 days of the less calcemic vitamin D analogs: JK 1624 F(2)-2 (JKF) and QW 1624F(2)-2 (QW) followed by estradiol-17beta (E(2)) in female rats upregulated creatine kinase-specific activity (CK) in skeletal tissues. In this study, we evaluated both histomorphological and biochemical changes due to a regime of 4 days treatment with JKF or QW, followed by injection of E(2) on day 5, repeated for 2.5 months. Ovariectomized female rats (Ovx) were injected 2 weeks after surgery, with JKF or QW at 0.2 ng/g BW followed by injections of E(2) (1 microg/rat) on day 5 of each week for 2.5 months. Rats were sacrificed 24 h after the last injection and bones were analyzed. JKF alone decreased growth plate width, increased % total bone volume (%TBV), with no change in cortical thickness. In contrast, QW restored growth plate width and %TBV with no change in cortical thickness. Combined with E(2), JKF restored %TBV and growth plate width but with no change in cortical thickness, while QW restored significantly all parameters including cortical thickness. Moreover, there was also an increase in the responsiveness of CK to E(2) in epiphyseal cartilage and diaphyseal bone but not in uterus. Thus, vitamin D less calcemic analogs increased responsiveness to E(2) morphologically as well as biochemically. We, therefore, conclude that combined treatment of less calcemic analogs vitamin D and E(2) might be superior for treatment of bone damage caused by ovariectomy in female rats and might be applied for post-menopausal osteoporosis.

Daidzein but not other phytoestrogens preserves bone architecture in ovariectomized female rats in vivo

“…In the present study, we compared the effects of long‐term daily treatment with E 2 , the SERM Ral or isolated phytoestrogens and their synthetic carboxy‐derivatives or vehicle on bone histology regarding their ability to prevent damage to bones caused by Ovx, leading to decreased trabecular mass and increased adipogenesis in bone marrow, as well as on a biochemical marker the CK specific activity in skeletal tissues of female rats. Ovariectomy caused almost a complete cessation of bone growth as demonstrated in the disruption of the growth plate cell organization, and the complete disappearance of thin bone spicules, as previously reported [Somjen et al, 2007]. The increased number of adipocytes in the bone marrow adjacent to the growth plate indicated that this treatment might affect the overall metabolism of bone marrow.…”