PMID- 22752619
OWN - NLM
STAT- MEDLINE
DCOM- 20121121
LR  - 20211021
IS  - 1432-0827 (Electronic)
IS  - 0171-967X (Print)
IS  - 0171-967X (Linking)
VI  - 91
IP  - 2
DP  - 2012 Aug
TI  - Rosiglitazone inhibits bone regeneration and causes significant accumulation of 
      fat at sites of new bone formation.
PG  - 139-48
LID - 10.1007/s00223-012-9623-4 [doi]
AB  - Thiazolidinediones (TZDs), peroxisome proliferator-activated receptor gamma 
      activators, and insulin sensitizers represent drugs used to treat hyperglycemia 
      in diabetic patients. Type 2 diabetes mellitus (T2DM) is associated with a 
      twofold increase in fracture risk, and TZDs use increases this risk by an 
      additional twofold. In this study, we analyzed the effect of systemic 
      administration of the TZD rosiglitazone on new bone formation in two in vivo 
      models of bone repair, a model of drilled bone defect regeneration (BDR) and 
      distraction osteogenesis (DO) and a model of extended bone formation. 
      Rosiglitazone significantly inhibited new endosteal bone formation in both 
      models. This effect was correlated with a significant accumulation of fat cells, 
      specifically at sites of bone regeneration. The diminished bone regeneration in 
      the DO model in rosiglitazone-treated animals was associated with a significant 
      decrease in cell proliferation measured by the number of cells expressing 
      proliferating cell nuclear antigen and neovascularization measured by both the 
      number of vascular sinusoids and the number of cells producing proangiogenic 
      vascular endothelial growth factor at the DO site. In summary, rosiglitazone 
      decreased new bone formation in both BDR and DO models of bone repair by 
      mechanisms which include both intrinsic changes in mesenchymal stem cell 
      proliferation and differentiation and changes in the local environment supporting 
      angiogenesis and new bone formation. These studies suggest that bone regeneration 
      may be significantly compromised in T2DM patients on TZD therapy.
FAU - Liu, Lichu
AU  - Liu L
AD  - Arkansas Children's Hospital Research Institute, University of Arkansas for 
      Medical Sciences, Little Rock, AR, USA.
FAU - Aronson, James
AU  - Aronson J
FAU - Huang, Shilong
AU  - Huang S
FAU - Lu, Yalin
AU  - Lu Y
FAU - Czernik, Piotr
AU  - Czernik P
FAU - Rahman, Sima
AU  - Rahman S
FAU - Kolli, Vipula
AU  - Kolli V
FAU - Suva, Larry J
AU  - Suva LJ
FAU - Lecka-Czernik, Beata
AU  - Lecka-Czernik B
LA  - eng
GR  - R01 AG028935/AG/NIA NIH HHS/United States
GR  - AG 028935/AG/NIA NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20120701
PL  - United States
TA  - Calcif Tissue Int
JT  - Calcified tissue international
JID - 7905481
RN  - 0 (Hypoglycemic Agents)
RN  - 0 (Thiazolidinediones)
RN  - 05V02F2KDG (Rosiglitazone)
SB  - IM
MH  - *Adipose Tissue
MH  - Animals
MH  - Bone Diseases/*chemically induced/diagnostic imaging
MH  - Bone Regeneration/*drug effects
MH  - Choristoma/*chemically induced
MH  - Down-Regulation/drug effects
MH  - Drug Evaluation, Preclinical
MH  - Hypoglycemic Agents/adverse effects/pharmacology
MH  - Male
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Osteogenesis/*drug effects/physiology
MH  - Rosiglitazone
MH  - Thiazolidinediones/*adverse effects/pharmacology
MH  - X-Ray Microtomography
PMC - PMC3630993
MID - NIHMS443900
COIS- The authors have stated that they have no conflict of interest.
EDAT- 2012/07/04 06:00
MHDA- 2012/12/10 06:00
PMCR- 2013/08/01
CRDT- 2012/07/04 06:00
PHST- 2012/05/02 00:00 [received]
PHST- 2012/06/11 00:00 [accepted]
PHST- 2012/07/04 06:00 [entrez]
PHST- 2012/07/04 06:00 [pubmed]
PHST- 2012/12/10 06:00 [medline]
PHST- 2013/08/01 00:00 [pmc-release]
AID - 10.1007/s00223-012-9623-4 [doi]
PST - ppublish
SO  - Calcif Tissue Int. 2012 Aug;91(2):139-48. doi: 10.1007/s00223-012-9623-4. Epub 
      2012 Jul 1.