title: Changes in bone biological markers after treatment of Iranian diabetic patients with pioglitazone: No relation to polymorphism of PPAR-γ (Pro12Ala).
abstract: BACKGROUND
  Thiazolidinediones (TZDs) improves insulin sensitivity by activating the peroxisome proliferator-activated receptor γ (PPAR-g). We aimed to study any association between variation in bone biochemical markers and single nucleotide polymorphism (SNP) in PPAR-γ (Pro12Ala) and investigate if these genetic variants affect bone turnover markers in Iranian diabetic population before and after treatment with pioglitazone.
  
  
  METHODS
  A total of 101 patients (type 2 diabetic (T2D) were treated for 12 weeks with pioglitazone (15 mg/day). Bone Biological markers, osteocalcin, and C-terminal telopeptide of type 1 collagen (CTx) were measured before and after pioglitazone therapy. We genotyped 128 nondiabetic controls and 101 T2D patients as well. Pro12Ala polymorphism in PPAR-γ was done by real-time polymerase chain reaction (RT-PCR) using TaqMan assay.
  
  
  RESULTS
  There were statistically significant differences in allele frequencies of Pro12Ala while comparing the controls with T2D subjects. Ala frequency was 7 vs 3%, P = 0.036 and genotypic frequency of Pro/Ala was 5.94 vs 14.06%, P = 0.04. After treatment, the homeostasis model of assessment of insulin resistance (HOMA-IR) as a maker of insulin resistance was significantly decreased (P < 0.001). In respect of bone turnover markers, CTx values decreased and osteocalcin significantly increased. (P < 0.001).
  
  
  CONCLUSIONS
  Our findings did not reveal a significant association between this polymorphism and bone turnover markers after pioglitazone treatment. The reduced insulin resistance might be the reason that CTx values decreased and osteocalcin increased significantly after short-term pioglitazone treatment. These findings suggest the need for further studies on the possible role of insulin in regulation of bone metabolism.
authors.affiliation: Department of Pharmacology, College of Medicine, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Fatemeh
authors.initials: F
authors.lastname: Namvaran
authors.forename: Parvaneh
authors.initials: P
authors.lastname: Rahimi-Moghaddam
authors.forename: Negar
authors.initials: N
authors.lastname: Azarpira
authors.forename: Mohammad Hossien
authors.initials: MH
authors.lastname: Dabbaghmanesh
authors.forename: Marzieh
authors.initials: M
authors.lastname: Bakhshayeshkaram
authors.forename: Mohamad Mahdi
authors.initials: MM
authors.lastname: Namvaran
keywords: Bone biological markers; Iranian population; diabetic patient; insulin resistance; osteoporosis; pioglitazone; polymorphisms PPAR-γ