changes in bone biological markers after treatment of iranian diabetic patients with pioglitazone: no relation to polymorphism of ppar- î³ (pro12ala)

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. 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.