Prediction of Osteoporotic Fractures by Bone Densitometry and COLIA1 Genotyping: A Prospective, Population-Based Study in Men and Women

Abstract

Osteoporosis is a common disease with a strong genetic component, characterized by reduced bone mineral density and increased fracture risk. Although the genetic basis of osteoporosis is incompletely understood, previous studies have identified a polymorphism affecting an Sp1 binding site in the COLIA1 gene that predicts bone mineral density and osteoporotic fractures in several populations. Here we investigated the role of COLIA1 genotyping and bone densitometry in the prediction of osteoporotic fractures in a prospective, population-based study of men (n = 156) and women (n = 185) who were followed up for a mean (+/- SEM) of 4.88+/-0.03 years. There was no significant difference in bone density, rate of bone loss, body weight, height, or 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 these predominantly occurred in women (45 fractures in 30 individuals). Fractures were significantly more common in females who carried the COLIA1 's' allele (p = 0.001), although there was no significant association between COLIA1 genotype and the occurrence of fractures in men. Logistic regression analysis showed that carriage of the COLIA1 's' allele was an independent predictor 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-score unit) and body weight (OR = 1.05 [1.01-1.10] per kilogram). Moreover, bone densitometry and COLIA1 genotyping interacted significantly to enhance fracture prediction in women (p = 0.01), such that the incidence of fractures 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 mass and interacts with bone densitometry to help identify women who are at high and low risk of sustaining osteoporotic fractures.

Association between COL1A1 gene polymorphisms and bone size in Caucasians

“…29 The T allele of this SNP was reported to act as a risk factor to osteoporotic fracture in some studies, 12,14 but not in other populations. 30,31 We also analyzed the relationship between SNP2 and BMD in this population, and the risk effect of this SNP was not observed (Long J-R, personal communication).…”

Association of the Pro12Ala and C1431T variants of PPARG and their haplotypes with susceptibility to Type 2 diabetes

“…The second group consisted of 489 adults from Tayside, recruited as control subjects for studies of breast cancer, colon cancer and systemic sclerosis [3]. The third population of 380 women was randomly selected from the Aberdeen Prospective Osteoporosis Screening Study (APOSS) [5]. These women had been genotyped for PPARG polymorphisms as part of a prospective study on the genetic and environmental determinants of bone mass, bone loss and osteoporotic fracture.…”

Mechanical Behavior of Osteoporotic Bone at Sub-Lamellar Length Scales

“…Compositional changes in collagen, such as the ratio of α1 to α2 chains in different phenotypes of COLIA1 found in Type 1 collagen, appear to influence the fracture risk of bone that is independent to the changes in bone mass (McGuigan et al, 2001). A corresponding decrease in bone strength is not observed in our www.frontiersin.org work and suggests that the failure of the material does not change with osteoporosis although the interactions between constituents are affected.…”