Positive skeletal effects of cladrin, a naturally occurring dimethoxydaidzein, in osteopenic rats that were maintained a
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ORIGINAL ARTICLE
Positive skeletal effects of cladrin, a naturally occurring dimethoxydaidzein, in osteopenic rats that were maintained after treatment discontinuation 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 Received: 11 February 2012 / Accepted: 6 August 2012 / Published online: 30 August 2012 # International Osteoporosis Foundation and National Osteoporosis Foundation 2012
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. Keywords Bone formation . Bone strength . Microarchitecture . Phytoestrogen . Treatment withdrawal
Introduction Electronic supplementary material The online version of this article (doi:10.1007/s00198-012-2121-8) contains supplementary material, which is available to authorized users. K. Khan : K. Sharan : G. Swarnkar : B. Chakravarti : M. Mittal : T. K. Barbhuyan : S. P. China : M. P. Khan : G. K. Nagar : D. Yadav : N. Chattopadhyay (*) Division of Endocrin
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