Abstract:
:Sclerostin monoclonal antibody (Scl-Ab) has been shown to increase bone mass and bone strength by stimulating bone formation in an ovariectomy-induced bone loss rat model. The purpose of this study was to determine the effects of Scl-Ab in a rat immobilization/disuse model in which there was both a decrease in bone formation and an increase in bone resorption. Ten-month-old female Sprague Dawley rats were divided into normal weight-bearing (normal-loaded, NL) and right hindlimb-immobilization (under-loaded, UL) groups. Both NL and UL rats were treated with vehicle or Scl-Ab at 5 or 25 mg/kg, twice per week for 4 weeks. Trabecular and cortical bone histomorphometric analyses were performed on the proximal tibial metaphysis (PTM) and tibial shaft (TS). Compared to NL controls, UL rats had reduced body and muscle weights, increased bone marrow fat cells in the PTM, increased trabecular bone resorption and periosteal mineral apposition rate (MAR) as well as decreased trabecular MAR and bone formation rate (BFR/BS). In NL bones, treatment with Scl-Ab significantly increased bone formation and decreased bone resorption, resulting in increased trabecular and cortical bone mass. In UL trabecular bone, treatment with Scl-Ab at 5 or 25 mg/kg induced significant and dose-dependent increases in trabecular bone volume and thickness, mineralized surfaces (MS/BS), MAR and BFR/BS, and a significant decrease in eroded surface (Er.S/BS) compared with UL controls. In UL cortical bone, Scl-Ab treatment induced significant increases in cortical width, periosteal and endocortical MS/BS, MAR and BFR/BS, and significant decreases in endocortical Er.S/BS compared with UL controls. Taken together, these findings suggest that antibody-mediated blockade of sclerostin represents a promising new therapeutic approach for the anabolic treatment of immobilization-induced osteopenia.
journal_name
Bonejournal_title
Boneauthors
Tian X,Jee WS,Li X,Paszty C,Ke HZdoi
10.1016/j.bone.2010.09.009subject
Has Abstractpub_date
2011-02-01 00:00:00pages
197-201issue
2eissn
8756-3282issn
1873-2763pii
S8756-3282(10)01454-7journal_volume
48pub_type
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