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Published in: Osteoporosis International 4/2013

01-04-2013 | Original Article

Positive skeletal effects of cladrin, a naturally occurring dimethoxydaidzein, in osteopenic rats that were maintained after treatment discontinuation

Authors: K. Khan, K. Sharan, G. Swarnkar, B. Chakravarti, M. Mittal, T. K. Barbhuyan, S. P. China, M. P. Khan, G. K. Nagar, D. Yadav, P. Dixit, R. Maurya, N. Chattopadhyay

Published in: Osteoporosis International | Issue 4/2013

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Abstract

Summary

Effects of cladrin treatment and withdrawal in osteopenic rats were studied. Cladrin improved trabecular microarchitecture, increased lumbar vertebral compressive strength, augmented coupled remodeling, and increased bone osteogenic genes. A significant skeletal gain was maintained 4 weeks after cladrin withdrawal. Findings suggest that cladrin has significant positive skeletal effects.

Introduction

We showed that a standardized extract of Butea monosperma preserved trabecular bone mass in ovariectomized (OVx) rats. Cladrin, the most abundant bioactive compound of the extract, promoted peak bone mass achievement in growing rats by stimulating osteoblast function. Here, we studied the effects of cladrin treatment and withdrawal on the osteopenic bones.

Methods

Adult female Sprague–Dawley rats were OVx and left untreated for 12 weeks to allow for significant estrogen deficiency-induced bone loss, at which point cladrin (1 and 10 mg/kg/day) was administered orally for another 12 weeks. Half of the rats were killed at the end of the treatments and the other half at 4 weeks after treatment withdrawal. Sham-operated rats and OVx rats treated with PTH or 17β-estradiol (E2) served as various controls. Efficacy was evaluated by bone microarchitecture using microcomputed tomographic analysis and fluorescent labeling of bone. qPCR and western blotting measured mRNA and protein levels in bone and uterus. Specific ELISA was used for measuring levels of serum PINP and urinary CTx.

Results

In osteopenic rats, cladrin treatment dose dependently improved trabecular microarchitecture, increased lumbar vertebral compression strength, bone formation rate (BFR), cortical thickness (Cs.Th), serum PINP levels, and expression of osteogenic genes in bones; and reduced expression of bone osteoclastogenic genes and urinary CTx levels. Cladrin had no uterine estrogenicity. Cladrin at 10 mg/kg maintained acquired skeletal gains 4 weeks after withdrawal.

Conclusion

Cladrin had positive skeletal effects in osteopenic rats that were maintained after treatment withdrawal.
Appendix
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Metadata
Title
Positive skeletal effects of cladrin, a naturally occurring dimethoxydaidzein, in osteopenic rats that were maintained after treatment discontinuation
Authors
K. Khan
K. Sharan
G. Swarnkar
B. Chakravarti
M. Mittal
T. K. Barbhuyan
S. P. China
M. P. Khan
G. K. Nagar
D. Yadav
P. Dixit
R. Maurya
N. Chattopadhyay
Publication date
01-04-2013
Publisher
Springer-Verlag
Published in
Osteoporosis International / Issue 4/2013
Print ISSN: 0937-941X
Electronic ISSN: 1433-2965
DOI
https://doi.org/10.1007/s00198-012-2121-8

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