Although collapse of femoral head is the distinctive feature in radiography which is easy to be identified, it commonly happens in the middle stage. Before that, bone marrow edema, cystic degeneration, bone density loss and other manifestations are all nonspecific signs. Then, the forthcoming subchondral fracture (crescent signs) and calcification zone is reasonable proof for diagnosis but they also mean that the best time for treatment has been past. In addition, pain-the major symptom in early stage, may occurs in lower back, hip or even knees that makes it even more difficult to be diagnosed. Histopathological study reveals that, steroid-induced ONFH suffered diffusive lesions in whole femoral head. Due to the inhibiting effects of steroid on osteoblast the bone repairing course becomes much slower. Furthermore, insufficient blood flow caused by steroid further compromise the repairing process. Consequently, the collapse may develop much faster. Take into account these unfavorable characteristics of steroid-induced ONFH, predicting factors of this disease are needed for prevention and early intervention.
This study was conducted to identify a genetic factor contributing to onset of steroid-induced ONFH. The result indicated that, under the overdominant model, A/G carriers were less susceptible to steroid-induced ONFH than A/A and G/G carriers among patients managed by steroid, suggesting that A/G carriers may have a lower sensitivity to GC than A/A and G/G carriers. In a word, our data suggest for the first time that SNP (rs662) of the PON-1 gene was associated with the risk of steroid-induced ONFH.
As mentioned above, accumulating studies were performed to investigate the relationship between SNP of rs662 (Q192R) and other vascular ischemic diseases. However, their results were not consistent. Two cohort studies in Britain which found no evidence that PON-1 Q192R polymorphism is associated with CHD risk in Caucasian women or men [22, 23]. However, the investigation in Thai population turned out to be opposite—a firm association between polymorphism of Q192R and CHD was observed . For stroke, a study in Chinese population showed that Q192R polymorphism (the R allele and RR genotype) was associated with an increased risk of ischemic stroke . On the contrary, a research in Greece indicated that no links between Q192R and stroke was detected [25, 26]. The demographic factors as ethic background may contribute to this paradox.
There are several highlights in the current study as following: first, PON-1 polymorphism has been a hot issue, however, very few researches was designed to investigate its relationship with ONFH; Second, differences in PON-1 activity, concentration and genotype distribution have long been known to occur between different populations and geographical regions throughout the world. Accordingly, this is deemed as one of the major controversies between studies concerning relationship between PON-1 polymorphism and other diseases. In this study, all participants were confined as Han Chinese lived in north areas of the Yellow River that is designed to avoid deviation caused by ethical and geographical factors. Last but not the least, unlike some other studies that using healthy people as controls, this research recruit steroid users without developing ONFH as reference group. This scheme is of an obvious advantage that it excludes the influence of steroid—a pathogenic factor on subjects of different groups. Consequently, it increases the reliability of the result.
However, there are several limitations in this study. First, the sample size is relative small, which may influence the reliability of our results because the heterogeneity of concurrent diseases of subjects may lead to selection bias of the result. Second, it is still unknown that by which way it facilitates ONFH. Though PON-1 polymorphism is linked to Atherosclerosis, it could not explain its relationship with steroid-induced ONFH. Not like the chronic course of the former one, the latter one is a medical condition happened much faster. Therefore, the exact mechanisms by which the polymorphisms of the PON-1 gene are involved in the development of steroid-induced ONFH require further investigations. And its result may provoke more deep understanding on safe protocol of steroid administration.
In conclusion, our data provide the convincing evidence for the first time that rs662 SNP of PON-1 may be associated with the risk of steroid-induced ONFH, suggesting that the genetic variations of this gene may play an important role in the disease development. Following study is needed for its prospecting result.