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

Abstract

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 4weeks after cladrin withdrawal. Findings suggest that cladrin has significant positive skeletal effects. 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. Adult female Sprague-Dawley rats were OVx and left untreated for 12weeks to allow for significant estrogen deficiency-induced bone loss, at which point cladrin (1 and 10mg/kg/day) was administered orally for another 12weeks. Half of the rats were killed at the end of the treatments and the other half at 4weeks 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. 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 10mg/kg maintained acquired skeletal gains 4weeks after withdrawal. Cladrin had positive skeletal effects in osteopenic rats that were maintained after treatment withdrawal.