Prediction of osteoporotic fractures by bone densitometry and COLIA1 genotyping: A prospective, population-based study in men and women

Osteoporosis is a common disease with a strong genetic component, character ized by reduced bone mineral density and increased fracture risk. Although the genetic basis of osteoporosis is incompletely understood, previous stud ies have identified a polymorphism affecting an Sp1 binding site in the COL IA1 gene that predicts bone mineral density and osteoporotic fractures in s everal populations. Here we investigated the role of COLIA1 genotyping and bone densitometry in the prediction of osteoporotic fractures in a prospect ive, population-based study of men (n = 156) and women (n = 185) who were f ollowed up for a mean (+/- SEM) of 4.88 +/- 0.03 years. There was no signif icant difference in bone density, rate of bone loss, body weight, height, o r years since menopause between the genotype groups but women with the 'ss' genotype were significantly older than the other genotype groups (p = 0.03 ). Thirty-nine individuals sustained 54 fractures during follow-up and thes e predominantly occurred in women (45 fractures in 30 individuals). Fractur es were significantly more common in females who carried the COLIA1 's' all ele (p = 0.001), although there was no significant association between COLI A1 genotype and the occurrence of fractures in men. Logistic regression ana lysis showed that carriage of the COLIA1 's' allele was an independent pred ictor of fracture in women with an odds ratio (OR) [95% CI] of 2.59 [1.23-5 .45], along with spine bone mineral density (OR = 1.57 [1.04-2.37] per Z-sc ore unit) and body weight (OR = 1.05 [1.01-1.10] psr kilogram). Moreover, b one densitometry and COLIA1 genotyping interacted significantly to enhance fracture prediction in women (p = 0.01), such that the incidence of fractur es was 45 times higher in those with low BMD who carried the 's' allele (24 .3 fractures/100 patient-years) compared with those with high BMD who were 'SS' homozygotes (0.54 fracture/100 patient-years). We conclude that in our population, COLIA1 genotyping predicts fractures independently of bone mas s and interacts with bone densitometry to help identify women who are at hi gh and low risk of sustaining osteoporotic fractures.