## Abstract As a candidate for active vitamin D analogs that have selective effects on bone, 1α,25‐dihydroxy‐2β‐(3‐hydroxypropoxy)vitamin D3 (ED‐71) has been synthesized and is currently under clinical trials. In ovariectomized rat model for osteoporosis, ED‐71 caused an increase bone mass at the l
Effects of a synthetic vitamin D analog, ED-71, on bone dynamics and strength in cancellous and cortical bone in prednisolone-treated rats
✍ Scribed by Yuzo Tanaka; Dr. Toshitaka Nakamura; Satoshi Nishida; Katsumi Suzuki; Satoshi Takeda; Katsuhiko Sato; Yasuho Nishii
- Publisher
- American Society for Bone and Mineral Research
- Year
- 2009
- Tongue
- English
- Weight
- 998 KB
- Volume
- 11
- Category
- Article
- ISSN
- 0884-0431
No coin nor oath required. For personal study only.
✦ Synopsis
To determine the action of corticosteroid on bone metabolism and assess the effects of a synthetic vitamin D analog, ED-71, on them, 56 SD rats, 8 weeks of age, were assigned to seven groups of eight animals each. Group I was the basal control. Group 2 was the nontreated control. Groups 3-7 were given prednisolone at 30 mg/kg of body weight (BW) twice a week and concomitantly administered ED-71 with respective doses of 0, 0.0125, 0.025, 0.05, and 0.1 &kg of BW for 12 weeks. In group 3, urinary calcium (U-Ca) and deoxypyridinoline (U-Dpy) were significantly increased compared with group 2. In groups 4-7, U-Ca values were increased but U-Dpy values were dose-dependently decreased. Age-dependent increases in the parameter values of BMD, compressive strength, trabecular bone volume ( B V W , and trabecular thickness (Tb.Th) of the lumbar body were significantly suppressed in group 3 but dose-dependently increased in groups 4-7, and the values of group 7 exceeded those of group 2. The parameters of bone mineral density (BMD) and the bending strength of the femur in groups 4-7 were larger than the values in group 3 but did not reach the levels of group 2. The trabecular bone formation rate (BFIUBS) of the lumbar body measured by calcein labeling in group 3 was reduced when compared with group 2, but the values were not further decreased in groups 4-7. The perimeter ratios of double labels over single labels (dLS/sLS) greatly decreased by prednisolone, were dose-dependently increased to the level of the normal control by ED-71. Double-labeled perimeters and the dLS/sLS ratios were also increased in the periosteal envelope of the midfemur. These findings clearly demonstrate that prednisolone administration affects the age-related changes in bone metabolism, and ED-71 administration counteracts the effects by increasing intestinal calcium absorption, reducing bone resorption, and enhancing mineralization. The action of ED-71, however, seems to be less potent in the cortical bone. (
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