Changes in bone biological markers after treatment of Iranian diabetic patients with pioglitazone: No relation to polymorphism of PPAR‑γ (Pro12Ala)

Background: Thiazolidinediones (TZDs) improves insulin sensitivity by activating the peroxisome proliferator‑activated receptor γ (PPAR‑γ). 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. Materials and 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). Conclusion: 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.