Effects of alfacalcidol on cancellous and cortical bone mass in rats treated with glucocorticoid: a bone histomorphometry study.
The beneficial effects of alfacalcidol (ALF) on bone mass, bone formation, and bone resorption have been established in ovariectomized rats. Our previous studies showed that high-dose glucocorticoid (GC) administration (methylprednisolone sodium succinate, 5.0 mg/kg, s.c., 3 times a week) for 4 wk induced cancellous osteopenia without significantly affecting cortical bone mass in Sprague-Dawley rats, and that high-dose GC administration for 8 wk also resulted in cortical osteopenia. The purpose of the present study was to examine the effects of ALF on cancellous and cortical bone mass in GC-treated rats. Forty female Sprague-Dawley rats, 3 mo of age, were randomized by the stratified weight method into four groups of 10 rats each, as follows: age-matched control group (CON); 8-wk GC administration with administration of vehicle during the latter 4 wk of treatment (GC group); 8-wk GC administration with administration of a low dose of ALF (0.08 Ag/kg) during the latter 4 wk of treatment (low-dose ALF group); 8-wk administration of GC with administration of a high dose ofALF (0.16 microg/kg) during the latter 4 wk of treatment (high-dose ALF group). The GC (methylprednisolone sodium succinate, 5.0 mg/kg) was administered subcutaneously 3 times a week, and ALF was administered orally 5 times a week. At the end of the experiment, static and dynamic bone histomorphometric analyses were performed on cancellous bone of the proximal tibial metaphysis and cortical bone of the tibial diaphysis. Eight-week GC administration resulted in loss of the cancellous bone volume/total tissue volume (BV/TV) and percent cortical area (Ct Ar) as a result of decreased trabecular bone formation, increased trabecular and endocortical bone resorption, and decreased periosteal bone formation. Low-dose ALF restored the cancellous BV/TV by mildly suppressing bone resorption and restoring bone formation, whereas high-dose ALF increased it beyond the value observed in the age-matched controls by strongly suppressing bone resorption and markedly increasing bone formation. Both low- and high-dose ALF prevented the GC-induced reduction of the percent Ct Ar by increasing periosteal bone formation and suppressing endocortical bone resorption. The effects of ALF on cancellous bone mass, bone formation, and bone resorption were all dose-dependent. The present study showed the beneficial effects of ALF on cancellous and cortical bone mass in GC-treated rats.
Iwamoto
Jun
J
Department of Sports Medicine, Keio University School of Medicine, Shinjuku-ku, Tokyo 160-8582, Japan. jiwamoto@sc.itc.keio.ac.jp
Seki
Azusa
A
Takeda
Tsuyoshi
T
Yamada
Harumoto
H
Sato
Yoshihiro
Y
Yeh
James K
JK
D000704:Analysis of Variance; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D015519:Bone Density / Q000187:drug effects*; D050071:Bone Density Conservation Agents / Q000494:pharmacology*; D001862:Bone Resorption / Q000517:prevention & control; D002118:Calcium / Q000097:blood; D003404:Creatinine / Q000097:blood; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005260:Female; D005269:Femur / Q000187:drug effects; D005938:Glucocorticoids; D006887:Hydroxycholecalciferols / Q000494:pharmacology*; D008776:Methylprednisolone Hemisuccinate / Q000008:administration & dosage; D010024:Osteoporosis / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control*; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D013977:Tibia / Q000187:drug effects
D050071:Bone Density Conservation Agents; D005938:Glucocorticoids; D006887:Hydroxycholecalciferols; D008776:Methylprednisolone Hemisuccinate; D003404:Creatinine; D002118:Calcium; C008088:alfacalcidol