Transforming growth factor beta (TGF-β), a master regulator of renal fibrosis, is the hallmark of chronic kidney disease (CKD) progression, and CKD worsens bone remodeling. However, the effects of the dysregulation of signaling on bone remodeling during CKD have not been investigated. Here, we determined the effects of TGF-β receptor I () overexpression under the control of Mx1-Cre on bone remodeling in CKD mice (-CKD mice). Our results demonstrated that kidney fibrosis and serum urea nitrogen levels were elevated in -CKD mice compared to WT-CKD, indicating that overexpression exacerbated renal injury during CKD. Serum calcium was decreased, while PTH was enhanced, in -CKD mice. -CKD mice displayed severe osteopenia as assessed by uCT in both femurs and mandibles. An histomorphometric analysis showed that tibial cancellous bone volume was decreased in -CKD. Likewise, mRNA expression levels of an osteoclastogenesis marker, was increased, and osteoblast marker genes and were decreased in -CKD mice. -CKD mice displayed increased inflammatory cytokines levels. Together, our results indicated that in the setting of CKD, overexpression induced both CKD progression and the dysregulation of bone remodeling, leading to severe bone loss. As such, these data provide an avenue for the future development of therapeutics for CKD-induced osteoporosis.