Genetic predisposition for femoral neck stress fractures in military conscripts

Abstract

BackgroundStress fractures are a significant problem among athletes and soldiers and may result in devastating complications or even permanent handicap. Genetic factors may increase the risk, but no major susceptibility genes have been identified. The purpose of this study was to search for possible genetic factors predisposing military conscripts to femoral neck stress fractures.ResultsEight genes involved in bone metabolism or pathology (COL1A1, COL1A2, OPG, ESR1, VDR, CTR, LRP5, IL-6) were examined in 72 military conscripts with a femoral neck stress fracture and 120 controls. The risk of femoral neck stress fracture was significantly higher in subjects with low weight and body mass index (BMI). An interaction between the CTR (rs1801197) minor allele C and the VDR C-A haplotype was observed, and subjects lacking the C allele in CTR and/or the C-A haplotype in VDR had a 3-fold higher risk of stress fracture than subjects carrying both (OR = 3.22, 95% CI 1.38-7.49, p = 0.007). In addition, the LRP5 haplotype A-G-G-C alone and in combination with the VDR haplotype C-A was associated with stress fractures through reduced body weight and BMI.ConclusionsOur findings suggest that genetic factors play a role in the development of stress fractures in individuals subjected to heavy exercise and mechanical loading. The present results can be applied to the design of future studies that will further elucidate the genetics of stress fractures.

RANK/RANKL/OPG pathway: Genetic associations with stress fracture period prevalence in elite athletes

“…Associations were shown for SNPs and haplotype blocks within the vitamin D receptor (13) and an androgen receptor repeat sequence (14). However, other studies have shown no association for the same SNPs in similar military populations (15).…”

Association of LRP5 Ala1330Val polymorphism with fracture risk: a meta-analysis

“…It is possible that the observed rare variants may contribute to fractures in association with other unfavorable environmental and genetic factors. Previous studies found that the LRP5 haplotype (E644E, V667M, V1119V, and A1330V), in combination with the vitamin D receptor haplotype, was associated with stress fractures (Korvala et al, 2010).…”

“…The HWE test was performed on genotype distribution of the controls, and all of them were in agreement with HWE, except Saarinen et al (2010). There were 3 studies conducted on Asian populations (Mizuguchi et al, 2004;Liu et al, 2010;Xuan et al, 2014) and 4 studies on Caucasian populations (Ferrari et al, 2005;Hartikka et al, 2005;Korvala et al, 2010;Saarinen et al, 2010). Table 2 lists the main results of the pooled analysis and Figure 2 shows the association of the LRP5 Ala1330Val polymorphism with fracture risk in the form of forest plots.…”

“…In total, 110 papers were retrieved by the literature search. Seven full-text papers were included in this meta-analysis and 103 studies were excluded (Mizuguchi et al, 2004;Ferrari et al, 2005;Hartikka et al, 2005;Korvala et al, 2010;Liu et al, 2010;Saarinen et al, 2010;Xuan et al, 2014). Based on the 7 selected studies, 808 cases and 1586 controls were included in the pooled analysis.…”

Stress Fracture of the Femoral Neck in Patient With Excessive Acetabular Anteversion and Coxa Profunda: A Case Report

“…Genetic factors may play a role in the development of stress fractures in individuals subjected to heavy exercise and mechanical loading [5]. Also stress fracture of the femoral neck in active adults is known to be related with coxa vara [1].…”