Genetic predisposition for femoral neck stress fractures in military conscripts
- Equal contributors
1 Oulu Center for Cell-Matrix Research, Biocenter and Department of Medical Biochemistry and Molecular Biology, University of Oulu, Oulu, Finland
2 Department of Orthopaedic Surgery, National Military Hospital, Helsinki, Finland
3 Centre for Military Medicine, Research Department, Helsinki, Finland
4 Centre of Expertise for Health and Work Ability, Finnish Institute of Occupational Health, Helsinki, Finland
5 Department of Public Health, University of Helsinki, Helsinki, Finland
6 Gertrude H. Sergievsky Center, College for Physicians and Surgeons, Columbia University, New York, USA
7 Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing, China
8 Connective Tissue Gene Tests, Allentown, PA, USA
BMC Genetics 2010, 11:95 doi:10.1186/1471-2156-11-95Published: 21 October 2010
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.
Eight 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.
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.