Genetic factors play an important role in the pathogenesis of osteoporosis
by affecting bone mineral density and other predictors of osteoporotic frac
ture risk such as ultrasound properties of bone and skeletal geometry. We p
reviously identified a polymorphism of a Sp1 binding site in the Collagen T
ype 1 Alpha 1 gene (COL1A1) that has been associated with reduced BMD and a
n increased risk of osteoporotic fractures in several populations. Here we
looked for evidence of an association between COL1A1 Sp I alleles and femor
al 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 fractu
re patients and DXA scan printouts in the population-based subjects. The CO
L1A1 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 ne
ck width between the genotype groups, but femoral neck-shaft angle was incr
eased by about 2 degrees in the Ss/ss genotype groups (n = 114) when compar
ed with SS homozygotes (n = 222) (P = 0.001). Previous studies have suggest
ed 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 incr
ease in hip fracture risk noted in previous studies of individuals who carr
y the 's' allele.