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

McGuigan, F E A LU ; Armbrecht, G; Smith, R; Felsenberg, D; Reid, D M and Ralston, S H (2001) In Osteoporosis International 12(2). p.91-96
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,... (More)

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.

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published
keywords
Absorptiometry, Photon, Aged, Aged, 80 and over, Bone Density, Collagen, Female, Fractures, Bone, Genetic Predisposition to Disease, Genotype, Humans, Male, Middle Aged, Osteoporosis, Osteoporosis, Postmenopausal, Prospective Studies, Sensitivity and Specificity, Journal Article, Research Support, Non-U.S. Gov't
in
Osteoporosis International
volume
12
issue
2
pages
91 - 96
publisher
Springer
external identifiers
  • scopus:0035082507
ISSN
0937-941X
DOI
10.1007/s001980170139
language
English
LU publication?
no
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4c154be0-3e3a-43d5-9f59-30b53f721494
date added to LUP
2018-01-02 11:06:05
date last changed
2018-01-12 11:09:46
@article{4c154be0-3e3a-43d5-9f59-30b53f721494,
  abstract     = {<p>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.</p>},
  author       = {McGuigan, F E A and Armbrecht, G and Smith, R and Felsenberg, D and Reid, D M and Ralston, S H},
  issn         = {0937-941X},
  keyword      = {Absorptiometry, Photon,Aged,Aged, 80 and over,Bone Density,Collagen,Female,Fractures, Bone,Genetic Predisposition to Disease,Genotype,Humans,Male,Middle Aged,Osteoporosis,Osteoporosis, Postmenopausal,Prospective Studies,Sensitivity and Specificity,Journal Article,Research Support, Non-U.S. Gov't},
  language     = {eng},
  number       = {2},
  pages        = {91--96},
  publisher    = {Springer},
  series       = {Osteoporosis International},
  title        = {Prediction of osteoporotic fractures by bone densitometry and COLIA1 genotyping : a prospective, population-based study in men and women},
  url          = {http://dx.doi.org/10.1007/s001980170139},
  volume       = {12},
  year         = {2001},
}