PMID- 18671797
OWN - NLM
STAT- MEDLINE
DCOM- 20100122
LR  - 20090309
IS  - 1463-1326 (Electronic)
IS  - 1462-8902 (Linking)
VI  - 11
IP  - 4
DP  - 2009 Apr
TI  - Thiazolidinedione-induced skeletal fragility--mechanisms and implications.
PG  - 275-84
LID - 10.1111/j.1463-1326.2008.00931.x [doi]
AB  - Recent evidence suggests that the risk of several types of fracture is increased 
      in type 2 diabetes mellitus (T2DM). Thiazolidinediones (TZDs) are now widely used 
      in the management of T2DM, and their use may increase in other diseases 
      characterized by insulin resistance. The PPAR-gamma, the molecular target of the 
      TZDs currently in clinical use, is expressed in skeletal tissue. Evidence from 
      preclinical studies has demonstrated that activation of PPAR-gamma (i) inhibits 
      bone formation by diverting mesenchymal stem cells from the osteogenic to the 
      adipocytic lineage and (ii) may increase bone resorption by stimulating the 
      development of osteoclasts. There is also potential for indirect adverse skeletal 
      effects of PPAR-gamma activation by modulation of circulating levels of hormones 
      and cytokines known to influence bone metabolism. Recent studies in humans have 
      demonstrated that TZDs decrease markers of bone formation decrease bone mass, and 
      increase fracture rates, at least in women. The implication of these findings is 
      that fracture risk should be considered in patients with T2DM for whom TZD 
      therapy is being considered, and appropriate therapy instigated to prevent 
      fractures in individuals ascertained to be at high risk.
FAU - Grey, Andrew
AU  - Grey A
AD  - Department of Medicine, University of Auckland, Auckland, New Zealand. 
      a.grey@auckland.ac.nz
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Review
DEP - 20080729
PL  - England
TA  - Diabetes Obes Metab
JT  - Diabetes, obesity & metabolism
JID - 100883645
RN  - 0 (Hypoglycemic Agents)
RN  - 0 (PPAR gamma)
RN  - 0 (Thiazolidinediones)
SB  - IM
MH  - Animals
MH  - Bone Density/drug effects
MH  - Diabetes Mellitus, Type 2/drug therapy
MH  - Female
MH  - Fractures, Bone/*chemically induced/physiopathology
MH  - Humans
MH  - Hypoglycemic Agents/*adverse effects
MH  - Osteoporosis/chemically induced/physiopathology
MH  - PPAR gamma/drug effects/physiology
MH  - Thiazolidinediones/*adverse effects
RF  - 84
EDAT- 2008/08/02 09:00
MHDA- 2010/01/23 06:00
CRDT- 2008/08/02 09:00
PHST- 2008/08/02 09:00 [pubmed]
PHST- 2010/01/23 06:00 [medline]
PHST- 2008/08/02 09:00 [entrez]
AID - DOM931 [pii]
AID - 10.1111/j.1463-1326.2008.00931.x [doi]
PST - ppublish
SO  - Diabetes Obes Metab. 2009 Apr;11(4):275-84. doi: 
      10.1111/j.1463-1326.2008.00931.x. Epub 2008 Jul 29.