Increased bone formation and bone mass induced by sclerostin antibody is not affected by pretreatment or cotreatment with alendronate in osteopenic, ovariectomized rats

Endocrinology. 2011 Sep;152(9):3312-22. doi: 10.1210/en.2011-0252. Epub 2011 Jul 5.


Clinical studies have revealed a blunting of the bone anabolic effects of parathyroid hormone treatment in osteoporotic patients in the setting of pre- or cotreatment with the antiresorptive agent alendronate (ALN). Sclerostin monoclonal antibody (Scl-Ab) is currently under clinical investigation as a new potential anabolic therapy for postmenopausal osteoporosis. The purpose of these experiments was to examine the influence of pretreatment or cotreatment with ALN on the bone anabolic actions of Scl-Ab in ovariectomized (OVX) rats. Ten-month-old osteopenic OVX rats were treated with ALN or vehicle for 6 wk, before the start of Scl-Ab treatment. ALN-pretreated OVX rats were switched to Scl-Ab alone or to a combination of ALN and Scl-Ab for another 6 wk. Vehicle-pretreated OVX rats were switched to Scl-Ab or continued on vehicle to serve as controls. Scl-Ab treatment increased areal bone mineral density, volumetric bone mineral density, trabecular and cortical bone mass, and bone strength similarly in OVX rats pretreated with ALN or vehicle. Serum osteocalcin and bone formation rate on trabecular, endocortical, and periosteal surfaces responded similarly to Scl-Ab in ALN or vehicle-pretreated OVX rats. Furthermore, cotreatment with ALN did not have significant effects on the increased bone formation, bone mass, and bone strength induced by Scl-Ab in the OVX rats that were pretreated with ALN. These results indicate that the increases in bone formation, bone mass, and bone strength with Scl-Ab treatment were not affected by pre- or cotreatment with ALN in OVX rats with established osteopenia.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acid Phosphatase / blood
  • Alendronate / pharmacology*
  • Alendronate / therapeutic use
  • Animals
  • Antibodies, Monoclonal / pharmacology*
  • Antibodies, Monoclonal / therapeutic use
  • Bone Density / drug effects*
  • Bone Density / immunology
  • Bone Density Conservation Agents / pharmacology*
  • Bone Density Conservation Agents / therapeutic use
  • Bone Diseases, Metabolic / blood
  • Bone Diseases, Metabolic / drug therapy*
  • Bone Diseases, Metabolic / immunology
  • Bone Morphogenetic Proteins / immunology*
  • Bone and Bones / drug effects
  • Bone and Bones / immunology
  • Disease Models, Animal
  • Female
  • Genetic Markers / immunology*
  • Isoenzymes / blood
  • Osteocalcin / blood
  • Osteogenesis / drug effects*
  • Osteogenesis / immunology
  • Ovariectomy
  • Rats
  • Rats, Sprague-Dawley
  • Tartrate-Resistant Acid Phosphatase


  • Antibodies, Monoclonal
  • Bone Density Conservation Agents
  • Bone Morphogenetic Proteins
  • Genetic Markers
  • Isoenzymes
  • Sost protein, rat
  • Osteocalcin
  • Acid Phosphatase
  • Tartrate-Resistant Acid Phosphatase
  • Alendronate