Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
2006-1-17
pubmed:abstractText
Osteoprotegerin (OPG) acts by neutralizing the receptor activator of nuclear factor-kappaB ligand (RANKL), the primary mediator of osteoclast differentiation, function, and survival. We examined whether OPG could affect the bone loss associated with chronic kidney disease (CKD) in a rodent model of CKD and secondary hyperparathyroidism (SHPT). SHPT was induced in rats by 5/6 nephrectomy (5/6 Nx) and a 1.2% P/0.6% Ca(2+) diet. Starting 1 week after 5/6 Nx, rats were treated with vehicle (veh) or OPG-Fc (3 mg/kg, intravenously) every 2 weeks for 9 weeks. At baseline, 3, 6, and 9 weeks, blood was taken and bone mineral density (BMD) and bone mineral content (BMC) were assessed by dual-energy X-ray absorptiometry. Serum parathyroid hormone (sPTH) levels reached 912 pg/ml in 5/6 Nx rats vs. 97 pg/ml in shams at 9 weeks. OPG-Fc had no effect on sPTH or Ca(2+) levels throughout the 9-week study, indicating that SHPT was a renal effect independent of bone changes. At 3 weeks, 5/6 Nx-veh rats had osteopenia compared with sham-veh rats and 5/6 Nx-OPG-Fc rats had significantly higher percent changes in whole-body BMC, leg BMD, and lumbar BMD versus 5/6 Nx-veh rats. By 6-9 weeks, elevated sPTH was associated with reversal of bone loss and osteitis fibrosa in the proximal tibial metaphysis. OPG-Fc decreased this sPTH-driven high bone turnover, resulting in augmented thickness of proximal tibial trabeculae in 5/6 Nx rats. Thus, RANKL inhibition with OPG-Fc can block the deleterious effects of continuously elevated sPTH on bone, suggesting that RANKL may be an important therapeutic target for protecting bone in patients with CKD and SHPT.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
http://linkedlifedata.com/resource/pubmed/chemical/Carrier Proteins, http://linkedlifedata.com/resource/pubmed/chemical/Glycoproteins, http://linkedlifedata.com/resource/pubmed/chemical/Membrane Glycoproteins, http://linkedlifedata.com/resource/pubmed/chemical/Osteoprotegerin, http://linkedlifedata.com/resource/pubmed/chemical/Parathyroid Hormone, http://linkedlifedata.com/resource/pubmed/chemical/RANK Ligand, http://linkedlifedata.com/resource/pubmed/chemical/Receptor Activator of Nuclear..., http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Cytoplasmic and Nuclear, http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Tumor Necrosis Factor, http://linkedlifedata.com/resource/pubmed/chemical/TNFRSF11A protein, human, http://linkedlifedata.com/resource/pubmed/chemical/TNFRSF11B protein, human, http://linkedlifedata.com/resource/pubmed/chemical/TNFSF11 protein, human, http://linkedlifedata.com/resource/pubmed/chemical/Tnfrsf11b protein, rat
pubmed:status
MEDLINE
pubmed:month
Jan
pubmed:issn
0171-967X
pubmed:author
pubmed:issnType
Print
pubmed:volume
78
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
35-44
pubmed:dateRevised
2007-11-15
pubmed:meshHeading
pubmed-meshheading:16362459-Absorptiometry, Photon, pubmed-meshheading:16362459-Animals, pubmed-meshheading:16362459-Carrier Proteins, pubmed-meshheading:16362459-Disease Models, Animal, pubmed-meshheading:16362459-Glycoproteins, pubmed-meshheading:16362459-Humans, pubmed-meshheading:16362459-Hyperparathyroidism, pubmed-meshheading:16362459-Kidney Failure, Chronic, pubmed-meshheading:16362459-Male, pubmed-meshheading:16362459-Membrane Glycoproteins, pubmed-meshheading:16362459-Osteoprotegerin, pubmed-meshheading:16362459-Parathyroid Hormone, pubmed-meshheading:16362459-RANK Ligand, pubmed-meshheading:16362459-Rats, pubmed-meshheading:16362459-Rats, Sprague-Dawley, pubmed-meshheading:16362459-Receptor Activator of Nuclear Factor-kappa B, pubmed-meshheading:16362459-Receptors, Cytoplasmic and Nuclear, pubmed-meshheading:16362459-Receptors, Tumor Necrosis Factor
pubmed:year
2006
pubmed:articleTitle
The receptor activator of nuclear factor-kappaB ligand inhibitor osteoprotegerin is a bone-protective agent in a rat model of chronic renal insufficiency and hyperparathyroidism.
pubmed:affiliation
Department of Metabolic Disorders, Amgen Inc, One Amgen Center Drive, Thousand Oaks, CA 91320, USA.
pubmed:publicationType
Journal Article, Comparative Study