title: Increased bone formation and bone mass induced by sclerostin antibody is not affected by pretreatment or cotreatment with alendronate in osteopenic, ovariectomized rats.
abstract: 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.
authors: Department of Metabolic Disorders, Amgen, Inc., Thousand Oaks, California 91320, USA. hke@amgen.com
authors: Xiaodong
authors: X
authors: Li
authors: Michael S
authors: MS
authors: Ominsky
authors: Kelly S
authors: KS
authors: Warmington
authors: Qing-Tian
authors: QT
authors: Niu
authors: Franklin J
authors: FJ
authors: Asuncion
authors: Mauricio
authors: M
authors: Barrero
authors: Denise
authors: D
authors: Dwyer
authors: Mario
authors: M
authors: Grisanti
authors: Marina
authors: M
authors: Stolina
authors: Paul J
authors: PJ
authors: Kostenuik
authors: William S
authors: WS
authors: Simonet
authors: Chris
authors: C
authors: Paszty
authors: Hua Zhu
authors: HZ
authors: Ke
mesh_terms: D000135:Acid Phosphatase / Q000097:blood; D019386:Alendronate / Q000494:pharmacology* / Q000627:therapeutic use; D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology* / Q000627:therapeutic use; D015519:Bone Density / Q000187:drug effects* / Q000276:immunology; D050071:Bone Density Conservation Agents / Q000494:pharmacology* / Q000627:therapeutic use; D001851:Bone Diseases, Metabolic / Q000097:blood / Q000188:drug therapy* / Q000276:immunology; D019485:Bone Morphogenetic Proteins / Q000276:immunology*; D001842:Bone and Bones / Q000187:drug effects / Q000276:immunology; D004195:Disease Models, Animal; D005260:Female; D005819:Genetic Markers / Q000276:immunology*; D007527:Isoenzymes / Q000097:blood; D015675:Osteocalcin / Q000097:blood; D010012:Osteogenesis / Q000187:drug effects* / Q000276:immunology; D010052:Ovariectomy; D051381:Rats; D017207:Rats, Sprague-Dawley; D000071681:Tartrate-Resistant Acid Phosphatase
chemical_list: D000911:Antibodies, Monoclonal; D050071:Bone Density Conservation Agents; D019485:Bone Morphogenetic Proteins; D005819:Genetic Markers; D007527:Isoenzymes; C486031:Sost protein, rat; D015675:Osteocalcin; D000135:Acid Phosphatase; D000071681:Tartrate-Resistant Acid Phosphatase; D019386:Alendronate