Are polymorphisms of molecules involved in bone healing correlated to aseptic femoral and tibial shaft non‐unions?

Abstract

Fracture healing is a well-organized process between several molecules and mediators. As known from other diseases, genetic polymorphisms may exhibit different expression patterns in these mediators. Concerning fracture healing, this may lead to an extended healing process or non-union. We investigated the incidence of polymorphisms in patients with aseptic non-unions after femoral and tibial shaft fractures as compared to patients with uneventful healing. Exclusion criteria were smoking, diabetes, bilateral fractures, systemic corticoid therapy, and septic non-unions. Analysis of allele frequencies and genotype distribution of various mediators were carried out following PCR. Clinical parameters such as injury severity and in-hospital were analyzed. Fifty patients following non-union (group NU) were enrolled, the control group consisted of 44 patients (group H). A significant association of a PDGF haplotype and non-unions following fracture could be observed. There was a significantly increased in-hospital time and amount of surgical procedures in group NU. Polymorphisms within the PDGF gene seem to be a genetic risk factor for the development of nonunions of the lower extremity following fracture. The early identification of high risk patients could result in an adapted therapeutical strategy and might contribute to a significant decrease of posttraumatic non-unions. ß

Single Nucleotide Polymorphisms in Osteogenic Genes in Atrophic Delayed Fracture-Healing

“…In the present study, the presence of the G allele at SNP rs3819089 on the MMP13 gene was found to be protective from nonunion (OR = 0.26, p = 0.026). Zeckey et al found a similar result in their earlier study 43 .…”

Circulating bone morphogenetic protein levels and delayed fracture healing

“…Earlier studies demonstrated a possible BMP-related genetic predisposition for impaired fracture healing (e.g. in the BMP inhibitor noggin) [11][12][13]. Consequently, low basal levels of BMPs should be determinable even years after the fracture has healed.…”

Polymorphisms in BMP4 and FGFR1 genes are associated with fracture non‐union

“…Moreover, the BMP4 expression increases significantly during fracture healing and in cases of fibrodysplasia ossificans progressiva in humans . Previous studies have shown that C > T polymorphism in BMP4 rs17563 is associated with ossification of the posterior longitudinal ligament, but show no association with fracture NU …”