Association between COLIA1 Sp1 alleles and femoral neck geometry

Genetic factors play an important role in the pathogenesis of osteoporosis by affecting bone mineral density and other predictors of osteoporotic fracture risk such as ultrasound properties of bone and skeletal geometry. We previously identified a polymorphism of a Sp1 binding site in the Collagen Type 1 Alpha 1 gene (COL1A1) that has been associated with reduced BMD and an increased risk of osteoporotic fractures in several populations. Here we looked for evidence of an association between COL1A1 Sp I alleles and femoral neck geometry. The study group comprised 153 patients with hip fracture, and 183 normal subjects drawn at random from the local population. Femoral neck geometry was assessed by analysis of pelvic radiographs in the fracture patients and DXA scan printouts in the population-based subjects. The COL1A1 genotypes were detected by polymerase chain reaction and were in Hardy Weinberg equilibrium: "SS" = 222 (66%); "Ss" = 105 (31.3%); and "ss" = 9 (2.7%). There was no significant difference in hip axis length or femoral neck width between the genotype groups, but femoral neck-shaft angle was increased by about 2 degrees in the Ss/ss genotype groups (n = 114) when compared with SS homozygotes (n = 222) (P = 0.001). Previous studies have suggested that an increased femoral neck-shaft angle may increase the risk of hip fracture in the event of a sideways fall by influencing the forces that act on the femoral neck. The association COL1A1 genotype and increased femoral neck angle noted here may therefore contribute to the BMD-independent increase in hip fracture risk noted in previous studies of individuals who carry the 's' allele.