Effects of a synthetic vitamin D analog, ED-71, on bone dynamics and strength in cancellous and cortical bone in prednisolone-treated rats.
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 1 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 micrograms/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 (BV/TV), 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 (BFR/BS) 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.
Tanaka
Y
Y
Department of Orthopedic Surgery, University of Occupational and Environmental Health, Kitakyushu, Japan.
Nakamura
T
T
Nishida
S
S
Suzuki
K
K
Takeda
S
S
Sato
K
K
Nishii
Y
Y
D015502:Absorptiometry, Photon; D000375:Aging / Q000378:metabolism; D000596:Amino Acids / Q000652:urine; D000704:Analysis of Variance; D000818:Animals; D001696:Biomechanical Phenomena; D015519:Bone Density / Q000187:drug effects*; D001846:Bone Development / Q000187:drug effects; D001862:Bone Resorption / Q000517:prevention & control; D002113:Calcification, Physiologic / Q000187:drug effects; D002117:Calcitriol / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D002118:Calcium / Q000652:urine; D004305:Dose-Response Relationship, Drug; D005269:Femur / Q000187:drug effects / Q000378:metabolism; D007408:Intestinal Absorption / Q000187:drug effects; D008159:Lumbar Vertebrae / Q000187:drug effects / Q000378:metabolism; D008297:Male; D011239:Prednisolone / Q000008:administration & dosage / Q000633:toxicity*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014807:Vitamin D / Q000031:analogs & derivatives
D000596:Amino Acids; D014807:Vitamin D; C036020:deoxypyridinoline; D011239:Prednisolone; D002117:Calcitriol; C547512:eldecalcitol; D002118:Calcium