| Summary: | <p>Abstract</p> <p>Background</p> <p>Stress 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.</p> <p>Results</p> <p>Eight genes involved in bone metabolism or pathology (<it>COL1A1</it>, <it>COL1A2</it>, <it>OPG</it>, <it>ESR1, VDR</it>, <it>CTR</it>, <it>LRP5</it>, <it>IL-6</it>) 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 <it>CTR </it>(rs1801197) minor allele C and the <it>VDR </it>C-A haplotype was observed, and subjects lacking the C allele in <it>CTR </it>and/or the C-A haplotype in <it>VDR </it>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 <it>LRP5 </it>haplotype A-G-G-C alone and in combination with the <it>VDR </it>haplotype C-A was associated with stress fractures through reduced body weight and BMI.</p> <p>Conclusions</p> <p>Our 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.</p>
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