Sclerostin Antibody Treatment Increases Bone Formation, Bone Mass, and Bone Strength in a Rat Model of Postmenopausal Osteoporosis

• DOI: 10.1359/jbmr.081206
• Publication Date: 2008-12-02T17:32:07Z
• Authors: Xiaodong Li; Michael S Ominsky; Kelly S Warmington; Sean Morony; Jianhua Gong; Jin Cao; Yongming Gao; Victoria Shalhoub; Barbara Tipton; Raj Haldankar; Qing Chen; Aaron Winters; Tom Boone; Zhaopo Geng; Qing-Tian Niu; Hua Zhu Ke; Paul J Kostenuik; W Scott Simonet; David L Lacey; Chris Paszty
• Keywords: Sclerostin; Bone disease; Anabolic Agents; Bone remodeling

The development of bone-rebuilding anabolic agents for potential use in the treatment bone loss conditions, such as osteoporosis, has been a long-standing goal. Genetic studies humans and mice have shown that secreted protein sclerostin is key negative regulator formation, although magnitude extent sclerostin's role control formation aging skeleton still unclear. To study this unexplored area biology to assess pharmacologic effects inhibition, we used cell culture model identify neutralizing monoclonal antibody (Scl-AbII) testing an aged ovariectomized rat postmenopausal osteoporosis. Six-month-old female rats were left untreated 1 yr allow significant estrogen deficiency-induced loss, at which point Scl-AbII was administered 5 wk. these animals had robust effects, with marked increases on trabecular, periosteal, endocortical, intracortical surfaces. This not only resulted complete reversal, several skeletal sites, but also further increased mass strength levels greater than those found non-ovariectomized rats. Taken together, preclinical results establish pivotal and, furthermore, suggest antibody-mediated inhibition represents promising new therapeutic approach bone-related disorders,