Genetic predisposition for femoral neck stress fractures in military conscripts

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.Stress fractures are common and potentially serious exertion injuries, especially among athletes and military conscripts [1,2]. Repetitive activities such as running and marching are among the most frequently reported causes, and the approximate incidence of stress fractures in military conscripts ranges from 0.9 to 12.3% [3,4]. Stress fractures occur most commonly in the lower extremities e.g. in the tibia, metatarsals, femur or pelvis, and they manifest as localised pain that increases during exercise.Femoral neck fractures are one of the most serious high-risk stress fractures, because displaced fatigue fractures of the femoral neck lead to long-term morbidity in a high percentage of patients [5,6]. If the fracture is detected quickly and no dislocation has occurred, the recovery rate is usually good, but displaced femoral neck stress fractures can result in devastating complications or even permanent handicap [5,7].The pathoph