Effects of alfacalcidol on cancellous and cortical bone mass in rats treated with glucocorticoid

A bone histomorphometry study

Jun Iwamoto, Azusa Seki, Tsuyoshi Takeda, Harumoto Yamada, Yoshihiro Sato, James K. Yeh

Research output: Contribution to journalArticle

10 Citations (Scopus)

Abstract

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 μg/kg) during the latter 4 wk of treatment (low-dose ALF group); 8-wk administration of GC with administration of a high dose of ALF (0.16 μg/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.

Original languageEnglish
Pages (from-to)191-197
Number of pages7
JournalJournal of Nutritional Science and Vitaminology
Volume53
Issue number3
DOIs
Publication statusPublished - 01-06-2007

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1alpha-hydroxycholecalciferol
glucocorticoids
Glucocorticoids
bones
Bone and Bones
bone resorption
bone formation
Osteogenesis
rats
Bone Resorption
dosage
Methylprednisolone Hemisuccinate
osteopenia
Metabolic Bone Diseases
succinic acid
Sprague Dawley Rats
Cancellous Bone
alfacalcidol
Cortical Bone
sodium

All Science Journal Classification (ASJC) codes

  • Medicine (miscellaneous)
  • Food Science

Cite this

@article{68afb12716d3463ea47cf123f9e24844,
title = "Effects of alfacalcidol on cancellous and cortical bone mass in rats treated with glucocorticoid: A bone histomorphometry study",
abstract = "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 μg/kg) during the latter 4 wk of treatment (low-dose ALF group); 8-wk administration of GC with administration of a high dose of ALF (0.16 μg/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.",
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Effects of alfacalcidol on cancellous and cortical bone mass in rats treated with glucocorticoid : A bone histomorphometry study. / Iwamoto, Jun; Seki, Azusa; Takeda, Tsuyoshi; Yamada, Harumoto; Sato, Yoshihiro; Yeh, James K.

In: Journal of Nutritional Science and Vitaminology, Vol. 53, No. 3, 01.06.2007, p. 191-197.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Effects of alfacalcidol on cancellous and cortical bone mass in rats treated with glucocorticoid

T2 - A bone histomorphometry study

AU - Iwamoto, Jun

AU - Seki, Azusa

AU - Takeda, Tsuyoshi

AU - Yamada, Harumoto

AU - Sato, Yoshihiro

AU - Yeh, James K.

PY - 2007/6/1

Y1 - 2007/6/1

N2 - 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 μg/kg) during the latter 4 wk of treatment (low-dose ALF group); 8-wk administration of GC with administration of a high dose of ALF (0.16 μg/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.

AB - 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 μg/kg) during the latter 4 wk of treatment (low-dose ALF group); 8-wk administration of GC with administration of a high dose of ALF (0.16 μg/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.

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