Linked Life Data

15525588

Source:http://linkedlifedata.com/resource/pubmed/id/15525588

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
2004-11-4
pubmed:abstractText
Thiazolidinediones (TZDs) increase peripheral tissue insulin sensitivity in patients with type 2 diabetes mellitus by activating the nuclear receptor peroxisome proliferator-activated receptor gamma (PPARgamma). In bone marrow stromal cell cultures and in vivo, activation of PPARgamma by high doses (20 mg/kg/day) of TZDs has been reported to alter stem cell differentiation by promoting commitment of progenitor cells to the adipocytic lineage while inhibiting osteoblastogenesis. Here, we have examined the in vivo effects of low-dose rosiglitazone (3 mg/kg/day) on bone, administered to mice by gavage for 90 days. Rosiglitazone-treated mice had increased weight when compared with controls, with no significant alterations in serum levels of glucose, calcium or parathyroid hormone (PTH). Bone mineral density (BMD) at the lumbar vertebrae (L1-L4), ilium/sacrum, and total body was diminished by rosiglitazone treatment. Histologically, bone was characterized by decreased trabecular bone volume and increased marrow space with no significant change in bone marrow adipocity. Decreased osteoblast number and activity due to increased apoptotic death of osteoblasts and osteocytes was apparent while osteoclast parameters and serum levels of osteocalcin, alkaline phosphatase activity, and leptin were unaltered by rosiglitazone treatment. Therefore, the imbalance in bone remodeling that follows rosiglitazone administration arises from increased apoptotic death of osteogenic cells and diminished bone formation leading to the observed decrease in trabecular bone volume and BMD. These novel in vivo effects of TZDs on bone are of clinical relevance as patients with type 2 diabetes mellitus and other insulin resistant states treated with these agents may potentially be at increased risk of osteoporosis.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Oct
pubmed:issn
0022-0795
pubmed:author
pubmed:issnType
Print
pubmed:volume
183
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
203-16
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed-meshheading:15525588-Animals, pubmed-meshheading:15525588-Apoptosis, pubmed-meshheading:15525588-Biological Markers, pubmed-meshheading:15525588-Blood Glucose, pubmed-meshheading:15525588-Bone Density, pubmed-meshheading:15525588-Bone and Bones, pubmed-meshheading:15525588-Calcium, pubmed-meshheading:15525588-Cells, Cultured, pubmed-meshheading:15525588-Diabetes Mellitus, pubmed-meshheading:15525588-Histocytochemistry, pubmed-meshheading:15525588-Hypoglycemic Agents, pubmed-meshheading:15525588-Image Processing, Computer-Assisted, pubmed-meshheading:15525588-Leptin, pubmed-meshheading:15525588-Male, pubmed-meshheading:15525588-Mice, pubmed-meshheading:15525588-Mice, Inbred C57BL, pubmed-meshheading:15525588-Osteoblasts, pubmed-meshheading:15525588-Osteocalcin, pubmed-meshheading:15525588-Osteocytes, pubmed-meshheading:15525588-Parathyroid Hormone, pubmed-meshheading:15525588-Thiazolidinediones
pubmed:year
2004
pubmed:articleTitle
Rosiglitazone impacts negatively on bone by promoting osteoblast/osteocyte apoptosis.
pubmed:affiliation
Department of Medicine and Lady Davis Institute for Medical Research, Sir Mortimer B. Davis-Jewish General Hospital, McGill University, Montréal, Canada H3T 1E2.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't