Systemic treatments with the low-calcemic 1,25(OH)(2)D(3) analogs JKF or QW increase both the morphological and biochemical responses to estradiol-17beta in rat tibiae.
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.
Somjen
D
D
Institute of Endocrinology, Hypertension and Metabolism, Tel-Aviv Sourasky Medical Center, Tel-Aviv, Israel. dalias@tasmc.health.gov.il
Katzburg
S
S
Posner
G H
GH
Livne
E
E
Kaye
A M
AM
D000818:Animals; D003402:Creatine Kinase / Q000378:metabolism; D018483:Diaphyses / Q000187:drug effects; D004789:Enzyme Activation / Q000187:drug effects; D004958:Estradiol / Q000494:pharmacology*; D005260:Female; D006132:Growth Plate / Q000033:anatomy & histology / Q000187:drug effects / Q000378:metabolism; D015394:Molecular Structure; D010052:Ovariectomy; D051381:Rats; D017208:Rats, Wistar; D013977:Tibia / Q000033:anatomy & histology / Q000187:drug effects* / Q000378:metabolism; D013997:Time Factors; D014807:Vitamin D / Q000031:analogs & derivatives / Q000737:chemistry / Q000494:pharmacology*; D014815:Vitamins / Q000494:pharmacology
D014815:Vitamins; D014807:Vitamin D; D004958:Estradiol; D003402:Creatine Kinase