However, for the above reason care should be taken when translating our findings to the general population. Second, although statistical power was adequate to detect effects of common polymorphisms in the P2RX7, it was limited for detecting small effect sizes for the more rare polymorphisms, especially in men. Third, we did not have access to reliable information on additional risk factors for osteoporosis, such as vitamin D intake, calcium intake, years since menopause and physical activity. selleck compound These factors could therefore not be taken into account in our analyses.
Especially a possible interaction between physical activity and P2X7 SNPs in relation to osteoporosis risk would have been interesting to investigate, since previous selleck chemical animal studies using P2X7 knock-out models demonstrated that bone formation in response to mechanical loading as a result of enhanced
production of prostaglandin-E2 via P2X7R activation was diminished in P2X7 knock-outs [15, 35]. Finally, in view of multiple statistical testing it could be debated whether, for instance, Bonferroni p value adjustments should have been applied. However, it previously has been argued that the use of Bonferroni p value adjustments is impractical and likely too conservative when testing a priori hypotheses [36]. Since we were able to formulate plausible a priori hypotheses regarding most of the P2RX7 SNPs, based on data from previous studies, eltoprazine we did not apply Bonferroni correction in our analyses. Furthermore, almost all associations observed in our study were in accordance with previously published functional effects of the polymorphisms, further strengthening the plausibility of our results. If, however, we
had adjusted for the number of independent polymorphisms (n = 12) the significance level would have been 0.0042. In that case, most of the observed associations between the selleck chemicals individual SNPs and BMD would not have reached statistical significance, but the association between the Ala348Thr in women with lumbar spine BMD would still be significant. No information was available on causes of the fractures of our study participants, which prevented us from distinguishing between traumatic and non-traumatic, i.e. possible osteoporotic, fractures. However, since traumatic fractures are probably unrelated to BMD while non-traumatic fractures are likely associated with lower BMD values, a wider range in BMD values was realized in our study population by not excluding patients with traumatic fractures. Moreover, the lack of information on the cause of fractures was not essential for investigating the association between P2X7R SNPs and BMD, i.e. the risk of osteoporosis.