Treatment with anti-Sclerostin antibody to stimulate mandibular bone formation

Head Neck. 2018 Jul;40(7):1453-1460. doi: 10.1002/hed.25128. Epub 2018 Mar 9.

Abstract

Background: Anti-Sclerostin antibody (Scl-Ab) is a promising new bone anabolic therapy. Although anti-Scl-Ab stimulates bone formation and repair in the appendicular and axial skeleton, its efficacy in the craniofacial skeleton is still poorly understood.

Methods: Using an established model of Down syndrome-dependent bone deficiency, 10 Ts65Dn mice and 10 wild-type mice were treated weekly via i.v. tail vein injection with vehicle or anti-Sclerostin for 3 weeks and euthanized 1 week after.

Results: Wild-type mice treated with the anti-Scl-Ab had increased mandibular bone, trabecular thickness, and alveolar height compared with controls. Anti-Scl-Ab increased Ts65Dn mandibular bone parameters such that they were statistically indistinguishable from those in vehicle-treated wild-type mandibles.

Conclusion: Treatment with anti-Scl-Ab significantly increased mandibular bone mass and alveolar height in wild type mice and normalized mandibular bone mass and alveolar height in Ts65Dn mice. The anti-Scl-Ab therapy represents a novel method for increasing mandibular bone formation.

Keywords: head and neck reconstruction; mandible; micro-CT; osteoradionecrosis; sclerostin.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Adaptor Proteins, Signal Transducing
  • Alveolar Process / drug effects
  • Alveolar Process / physiology
  • Animals
  • Antibodies / pharmacology*
  • Bone Morphogenetic Proteins / immunology*
  • Disease Models, Animal
  • Glycoproteins / immunology*
  • Intercellular Signaling Peptides and Proteins
  • Mandible / drug effects
  • Mandible / physiology*
  • Mice, Mutant Strains
  • Osteogenesis / drug effects*
  • Osteogenesis / physiology

Substances

  • Adaptor Proteins, Signal Transducing
  • Antibodies
  • Bone Morphogenetic Proteins
  • Glycoproteins
  • Intercellular Signaling Peptides and Proteins
  • Sost protein, mouse