High- and low-dose OPG-Fc cause osteopetrosis-like changes in infant mice. Academic Article uri icon

Overview

abstract

  • BACKGROUND: Receptor activator of nuclear factor-κB ligand (RANKL) inhibitors are being considered for use in children with osteogenesis imperfecta (OI). We sought to assess efficacy of two doses of a RANKL inhibitor, osteoprotegerin-immunoglobulin Fc segment complex (OPG-Fc), in a growing animal model of OI, the col1α2-deficient mouse (oim/oim) and its wild-type controls (+/+). METHODS: Treated mice showed runting and radiographic evidence of osteopetrosis with either high- (20 mg/kg twice weekly) or low-dose (1 mg/kg/week) OPG-Fc. Because of this adverse event, OPG-Fc treatment was halted, and the mice were killed or monitored for recovery with monthly radiographs and assessment of serum osteoclast activity (tartrate-resistant acid phosphatase 5b, TRACP-5b) until 25 wk of age. RESULTS: Twelve weeks of OPG-Fc treatment resulted in radiographic and histologic osteopetrosis with no evidence of bone modeling and negative tartrate-resistant acid phosphatase staining, root dentin abnormalities, and TRACP-5b activity suppression. Signs of recovery appeared 4-8 wk post-treatment. CONCLUSION: Both high- and low-dose OPG-Fc treatment resulted in osteopetrotic changes in infant mice, an outcome that was not seen in studies with the RANKL inhibitor RANK-immunoglobulin Fc segment complex (RANK-Fc) or in studies with older animals. Further investigations of RANKL inhibitors are necessary before their consideration for use in children.

publication date

  • August 27, 2012

Research

keywords

  • Immunoconjugates
  • Immunoglobulin Fc Fragments
  • Osteogenesis Imperfecta
  • Osteopetrosis
  • Osteoprotegerin
  • RANK Ligand

Identity

PubMed Central ID

  • PMC3888234

Scopus Document Identifier

  • 84870552239

Digital Object Identifier (DOI)

  • 10.1038/pr.2012.118

PubMed ID

  • 22926546

Additional Document Info

volume

  • 72

issue

  • 5