PMID- 22267280
OWN - NLM
STAT- MEDLINE
DCOM- 20120524
LR  - 20201209
IS  - 1479-683X (Electronic)
IS  - 0804-4643 (Linking)
VI  - 166
IP  - 4
DP  - 2012 Apr
TI  - Distinct effects of pioglitazone and metformin on circulating sclerostin and 
      biochemical markers of bone turnover in men with type 2 diabetes mellitus.
PG  - 711-6
LID - 10.1530/EJE-11-1061 [doi]
AB  - OBJECTIVE: Patients with type 2 diabetes mellitus (T2DM) have an increased risk 
      of fractures and thiazolidinediones (TZDs) increase this risk. TZDs stimulate the 
      expression of sclerostin, a negative regulator of bone formation, in vitro. 
      Abnormal sclerostin production may, therefore, be involved in the pathogenesis of 
      increased bone fragility in patients with T2DM treated with TZDs. METHODS: We 
      measured serum sclerostin, procollagen type 1 amino-terminal propeptide (P1NP), 
      and carboxy-terminal cross-linking telopeptide of type I collagen (CTX) in 71 men 
      with T2DM treated with either pioglitazone (PIO) (30 mg once daily) or metformin 
      (MET) (1000 mg twice daily). Baseline values of sclerostin and P1NP were compared 
      with those of 30 healthy male controls. RESULTS: Compared with healthy controls, 
      patients with T2DM had significantly higher serum sclerostin levels (59.9 vs 45.2 
      pg/ml, P<0.001) but similar serum P1NP levels (33.6 vs 36.0 ng /ml, P=0.39). 
      After 24 weeks of treatment, serum sclerostin levels increased by 11% in 
      PIO-treated patients and decreased by 1.8% in MET-treated patients (P=0.018). 
      Changes in serum sclerostin were significantly correlated with changes in serum 
      CTX in all patients (r=0.36, P=0.002) and in PIO-treated patients (r=0.39, 
      P=0.020), but not in MET-treated patients (r=0.17, P=0.31). CONCLUSIONS: Men with 
      T2DM have higher serum sclerostin levels than healthy controls, and these levels 
      further increase after treatment with PIO, which is also associated with 
      increased serum CTX. These findings suggest that increased sclerostin production 
      may be involved in the pathogenesis of increased skeletal fragility in patients 
      with T2DM in general and may specifically contribute to the detrimental effect of 
      TZDs on bone.
FAU - van Lierop, A H
AU  - van Lierop AH
AD  - Departments of Endocrinology and Metabolic Diseases Radiology, Leiden University 
      Medical Center, Albinusdreef 2, Leiden, The Netherlands.
FAU - Hamdy, N A T
AU  - Hamdy NA
FAU - van der Meer, R W
AU  - van der Meer RW
FAU - Jonker, J T
AU  - Jonker JT
FAU - Lamb, H J
AU  - Lamb HJ
FAU - Rijzewijk, L J
AU  - Rijzewijk LJ
FAU - Diamant, M
AU  - Diamant M
FAU - Romijn, J A
AU  - Romijn JA
FAU - Smit, J W A
AU  - Smit JW
FAU - Papapoulos, S E
AU  - Papapoulos SE
LA  - eng
PT  - Journal Article
PT  - Multicenter Study
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
DEP - 20120120
PL  - England
TA  - Eur J Endocrinol
JT  - European journal of endocrinology
JID - 9423848
RN  - 0 (Adaptor Proteins, Signal Transducing)
RN  - 0 (Biomarkers)
RN  - 0 (Bone Morphogenetic Proteins)
RN  - 0 (Genetic Markers)
RN  - 0 (Hypoglycemic Agents)
RN  - 0 (SOST protein, human)
RN  - 0 (Thiazolidinediones)
RN  - 9100L32L2N (Metformin)
RN  - X4OV71U42S (Pioglitazone)
SB  - IM
MH  - Adaptor Proteins, Signal Transducing
MH  - Adult
MH  - Aged
MH  - Biomarkers/analysis/*blood/metabolism
MH  - Bone Morphogenetic Proteins/analysis/*blood
MH  - Bone Remodeling/*drug effects/physiology
MH  - Bone and Bones/metabolism
MH  - Diabetes Mellitus, Type 2/*blood/drug therapy/metabolism
MH  - Double-Blind Method
MH  - Genetic Markers
MH  - Humans
MH  - Hypoglycemic Agents/administration & dosage/adverse effects/pharmacology
MH  - Male
MH  - Metformin/administration & dosage/adverse effects/*pharmacology
MH  - Middle Aged
MH  - Pioglitazone
MH  - Thiazolidinediones/administration & dosage/adverse effects/*pharmacology
EDAT- 2012/01/24 06:00
MHDA- 2012/05/25 06:00
CRDT- 2012/01/24 06:00
PHST- 2012/01/24 06:00 [entrez]
PHST- 2012/01/24 06:00 [pubmed]
PHST- 2012/05/25 06:00 [medline]
AID - EJE-11-1061 [pii]
AID - 10.1530/EJE-11-1061 [doi]
PST - ppublish
SO  - Eur J Endocrinol. 2012 Apr;166(4):711-6. doi: 10.1530/EJE-11-1061. Epub 2012 Jan 
      20.