[Genetic determinants of osteoporosis]. / Genetická determinace osteoporózy.

Osteoporosis is a chronic progressive disease, characterized by higher bone resorption than bone mass accumulation. This leads to reduction of the bone mass, to microarchitectural deterioration of the bone tissue and to the increased risk of bone fracture. Osteoporosis affects predominately postmenopausal females, but it is also diagnosed at elderly males. Although osteoporosis is influenced by various environmental factors (mainly by dietary habits and physical activity), analysis of results obtained from studies with different designs (population-, family-, association- studies) confirmed, that risk of osteoporosis development and risk of osteoporotic fractures are significantly influenced by genetic predispositions. The genetic determination of osteoporosis is not yet completely understood. However, it is clear, that although there are mutations in some genes causing rare form of osteoporosis, osteoporosis is a polygenic disease--it is influenced by common variants (polymorphisms) of several different genes. For example genes for vitamin D receptor, estrogen receptor alpha, collagen type I alpha1, transforming growth factor beta-1 and some others are indicated to play a role in genetic determination of osteoporosis. In this review we summarize our recent knowledge about the genetic determination of osteoporosis.

The risk of Colles' fracture is associated with the collagen I alpha1 Sp1 polymorphism and ultrasound transmission velocity in the calcaneus only in heavier postmenopausal women.

To compare the ability of the bone mineral density (BMD) at the distal forearm, collagen I alpha 1 (COLIA1) polymorphism, and ultrasound stiffness to identify individuals with increased risk of wrist fracture, we studied 183 postmenopausal Czech women with a wrist fracture and 178 postmenopausal controls, ages 45-70 years. The genotypes "Ss" and "ss" were significantly overrepresented among fracture cases. The BMD measurements at the femoral neck, total femur, and distal forearm as well as ultrasound stiffness of the heel, broadband ultrasound attenuation (BUA), and speed of sound (SOS) were significantly lower in the fracture cohort. BMD of the distal forearm was the main determinant of susceptibility to the wrist fracture. Weight, the COLIA1 genotype, and ultrasound SOS further strengthened the predictive value of BMD. However, we found interaction between weight and both the COLIA1 Sp1 polymorphism and ultrasound parameters. Presence of the "s" allele as well as low SOS acted as significant predictors of wrist fracture only in heavier women, (> or =62 kg) but not in women with a body weight of less than 62 kg. In heavier women, both the COLIA1 Sp1 polymorphism and ultrasound parameters acted as independent markers that contributed to BMD to enhance fracture prediction. However, the COLIA1 enabled a higher specificity (specificity 72.4%, sensitivity 44.2%), whereas SOS enabled a higher sensitivity (sensitivity 73.9%, specificity, 45.7%). We conclude that BMD at total forearm, the COLIA1 polymorphism, and ultrasound SOS are independent predictors of wrist fracture in postmenopausal women. The effect of the COLIA1 Sp1 polymorphism and SOS on wrist fracture risk is more pronounced in patients with a higher body weight.

[X-ray densitometry and ultrasonography of the heel bone--sensitivity and comparison with densitometry of the axial skeleton]. / Rentgenová denzitometrie a ultrasonometrie patní kosti--presnost a srovnání s denzitometrií osového skeletu.

BACKGROUND: The aim of the study was to determine the relationship between dual energy x-ray absorptiometry (DXA) and quantitative ultrasonometry (QUS) of calcaneus and their correlation with axial bone mineral density. METHODS AND RESULTS: 1284 subjects were tested for BMD (Bone Mineral Density) by DXA at the spine and hip (707 subjects by DPX-L, Lunar, and 577 subjects by QDR-4500 A, Hologic) and calcaneus (by PIXI, Lunar). The calcaneus was also measured using the QUS (Achilles Plus, Lunar), on the same day. The mean age of the patients was 56.5 +/- 11.6 years, mean height 166 cm, mean weight 70 kg. Three subjects were selected for precision error measurement with low, medium and high BMD of calcaneus (T-score of -2.2, -0.77 and 2.02, respectively) and scanned with re-positioning at the right heel (PIXI and Achilles Plus) 21 times on one day for short term precision error and over 21 consecutive days for long term precision error. The in vivo short term precision error of the heel measurement (BMD, SOS, BUA) in subjects with normal BMD was 0.67%, 0.47% and 1.87%, respectively; the long term in vivo precision error was 1.14%, 0.26% and 2.95%, respectively. No significant difference was found between BMD values on the right and left heel. A statistically significant correlation (p < 0.001) was found between BUA and BMD (r = 0.71), SOS and BMD (r = 0.73), Stiffness and BMD (r = 0.77). The heel BMD was also significantly correlated to BMD of the femoral neck (r = 0.64) and BMD of total femur (r = 0.70) and BMD of lumbar spine (r = 0.59). CONCLUSIONS: The DXA of the heel underestimates the prevalence of osteoporosis. The results of the heel QUS (Stiffness) appear to be better correlated to femoral BMD than heel BMD. The observed correlation coefficient of 0.77 between QUS and DXA at the heel was statistically significant, but it explains only 60% of variability of the QUS of the heel.

COLIA1 polymorphism contributes to bone mineral density to assess prevalent wrist fractures.

Wrist fractures associated with postmenopausal women are only partially explained by osteoporosis. Recent studies have shown that polymorphism of an Spl binding site in the first intron of the collagen I alpha 1 gene (COLIA1) may determine risk for vertebral and nonvertebral fractures in post-menopausal women independent of bone mass. We investigated the relationship between the COLIA1 polymorphism, lumbar spine and femoral neck bone mineral density (BMD), ultrasound stiffness of the heel, anthropometric variables, and risk for wrist fractures in 126 Czech postmenopausal women with low bone mass who suffered one or more wrist fracture in the last 5 years and in 126 postmenopausal women with low bone mass without any fracture. Genotypes for the Spl COLIA1 polymorphism were determined by polymerase chain reaction, digestion with Ball restriction enzyme, and agarose gel electrophoresis. The test discriminates two alleles, S and s, which correspond to the presence of guanine and thymidine, respectively, at the first bases in the Spl-binding site in the first intron of the gene for CO-LIA1. No significant differences were found between the fracture and control group with regard to age, weight, and years since menopause. However, BMD of the lumbar spine and femoral neck and ultrasound stiffness of the heel were significantly lower in patients with prevalent wrist fracture. Femoral neck BMD was the strongest determinant of prevalent fracture of the wrist. COLIA1 genotyping significantly strengthened prediction of prevalent fracture of the wrist. After multivariate adjustment, women in the Ss group had 2.0 times the risk of the women in the SS group (95% confidence interval [CI] = 1.1-3.8), and the women in the ss group had 2.8 times the risk of the women in the SS group (95% CI = 0.5-14.6). The overall gene-dose effect was an odds ratio of 2.1 per copy of the "s" allele (95% CI = 1.2-3.8). In the stepwise logistic regression, COLIA1 acted synergistically with femoral neck BMD and weight in increasing prediction of wrist fracture. The results demonstrate that COLIA1 Sp1 polymorphism is associated with an increased risk of wrist fracture in postmenopausal women independent of BMD and may be helpful in clinical practice by identifying patients with an increased fracture risk.