Comparative effects of risedronate and calcitriol on cancellous bone in rats with glucocorticoid-induced osteopenia.
OBJECTIVE
To compared the effects of risedronate (Ris) and calcitriol (Cal) on cancellous bone in rats with glucocorticoid (GC)-induced osteopenia.


METHODS
Thirty female Sprague-Dawley rats, 4 mo of age, were randomly divided by the stratified weight method into three groups of 10 rats each according to the following treatment schedule: 8-wk GC administration with 4-wk vehicle (control), Ris, and Cal as therapeutic treatment initiated after 4-wk GC administration. The GC (methylprednisolone sodium succinate, 5.0 mg/kg, s.c.), Ris (10 microg/kg, s.c.), and Cal (0.1 microg/kg. p.o.) were administered 3 times a week. At the end of the 8-wk treatment period, two-dimensional (2D) bone histomorphometric analysis was performed for cancellous bone of the proximal tibial metaphysis, 3D micro-computed tomographic analysis was performed for the distal femoral metaphysis, and the mechanical strength of the distal femoral metaphysis was evaluated by a compression test.


RESULTS
Ris and Cal treatment increased both 2D and 3D cancellous bone mass. However, Ris treatment exhibited more pronounced effects on 2D and 3D cancellous bone mass than Cal treatment, and the effects of both Ris and Cal treatment were greater on 3D cancellous bone mass than on 2D cancellous bone mass. The response of 2D and 3D cancellous bone mass to Ris treatment was characterized by its effect on trabecular number and thickness, which was associated with markedly suppressed bone resorption and bone formation in terms of suppressed bone turnover. On the other hand, the response of 2D cancellous bone mass to Cal treatment was attributed to the effect of Cal on 2D trabecular thickness, and the response of 3D cancellous bone mass to Cal treatment might be characterized by the effect of Cal on 3D trabecular number and thickness, with a more marked effect of trabecular thickness. These effects were primarily due to mildly suppressed bone resorption and maintained or even increased bone formation. Despite the differential effect of Ris and Cal treatment on the cancellous bone structure and bone metabolism, both treatment increased the maximum load and braking energy of the distal femoral metaphysis to a similar extent, suggesting different mechanisms for improving bone strength.


CONCLUSIONS
This study showed the differential effects of Ris and Cal on cancellous bone in rats with GC-induced osteopenia.
Iwamoto
Jun
J
Department of Sports Medicine, Keio University School of Medicine, Tokyo, Japan. jiwamoto@sc.itc.keio.ac.jp
Seki
Azusa
A
Takeda
Tsuyoshi
T
Sato
Yoshihiro
Y
Yamada
Harumoto
H
Shen
Chwan-Li
CL
Yeh
James K
JK
D000818:Animals; D001696:Biomechanical Phenomena; D001835:Body Weight; D015519:Bone Density / Q000187:drug effects; D001851:Bone Diseases, Metabolic / Q000139:chemically induced* / Q000188:drug therapy* / Q000503:physiopathology; D016723:Bone Remodeling / Q000187:drug effects; D001862:Bone Resorption / Q000188:drug therapy; D001842:Bone and Bones / Q000187:drug effects* / Q000503:physiopathology; D002117:Calcitriol / Q000627:therapeutic use*; D002118:Calcium / Q000097:blood; D012968:Etidronic Acid / Q000031:analogs & derivatives* / Q000627:therapeutic use; D005260:Female; D005269:Femur; D010758:Phosphorus / Q000097:blood; D051381:Rats; D017207:Rats, Sprague-Dawley; D000068296:Risedronic Acid; D013977:Tibia; D014057:Tomography, X-Ray Computed
D010758:Phosphorus; D002117:Calcitriol; D000068296:Risedronic Acid; D012968:Etidronic Acid; D002118:Calcium