Genetic association between bone mineral density and the fracture of distal radius: A case-control study.

ABSTRACT: Low bone mineral density (BMD) was significantly related to the fracture of distal radius. Serum brain-derived neurotrophic factor (BDNF) level was closely related to BMD in spine and osteoporotic fractures. In this study, we aimed to explore the association of BDNF polymorphisms (rs6265 and rs7124442) with BMD and the fracture of distal radius.This retrospective study included 152 patients with distal radius fractures and 148 healthy controls. BDNF polymorphisms were detected via TaqMan allelic discrimination assay. BMD was evaluated through X-ray. Difference in features between cases and controls were compared adopting Chi-square test or t test. The associations of BDNF polymorphisms with fracture risk of distal radius and BMD were assessed employing χ2 test and expressed by odd ratios (ORs) with 95% confidence intervals (95% CIs).BMD was significantly decreased in patients with the fracture of distal radius than in healthy controls. The polymorphism rs6265 significantly increased the risk of distal radius fracture (adjustment: GA: OR = 1.724, 95%CI = 1.003 -2.951, P = .049; GG: OR = 2.415, 95%CI = 1.0219 -3.674, P = .005). Moreover, rs6265 genotypes GA (OR = 4.326, 95%CI = 1.725 -11.896, P = .003) and GG (OR = 13.285, 95%CI = 3.659 -51.072, P = .001) significantly increased BMD reduction. However, BDNF polymorphism rs7124442 had no obvious correlation with BMD or fracture risk.BMD was associated with BDNF rs6265 polymorphism. BDNF polymorphism rs6265 could elevate the risk of osteoporosis and distal radius fracture.

COL1A1, CCDC170, and ESR1 single nucleotide polymorphisms associated with distal radius fracture in postmenopausal Mexican women.

Objective: The aim of this study was to analyze the genetic association of five ESR1 single nucleotide polymorphisms (SNPs) (rs3020331, rs851982, rs1999805, rs2234693, rs3020404), four COL1A1 SNPs (rs1800012, rs2075555, rs2412298, rs1107946), and two SNPs on the CCDC170 gene (rs9479055, rs4870044) with distal radius fracture (DRF) in a group of postmenopausal Mexican women.Methods: A case-control study was conducted. Cases (n = 182) were women above the age of 38 years with low-energy DRF, and controls (n = 201) were women without. Analysis was done through real-time polymerase chain reaction. Frequencies and Hardy-Weinberg equilibrium were calculated. A multivariate analysis including bone mass index, age, menarche, and menopause as covariables was carried out. Finally, haplotype and linkage disequilibrium (LD) analyses were performed.Results:COL1A1 rs1107946 was strongly associated with DRF. Both CCDC170 SNPs showed strong association with DRF. For the ESR1 gene, four SNPs (rs2234693, 3020404, rs3020331, and rs851982) showed very strong association with DRF. Additionally, the region between the latter two showed strong LD.Conclusions: A strong association of DRF with variants in these genes was found, including haplotypes and a region with strong LD on ESR1. The results suggest that these SNPs could be useful to detect the population at risk of presenting DRF among Mexican perimenopausal women.

Altered gene and protein expressions of vitamin D receptor in skeletal muscle in sarcopenic patients who sustained distal radius fractures.

Despite the presence of vitamin D receptor (VDR) in skeletal muscle cells, the relationship between VDR expressions and muscle mass or function has not been well studied. The purpose of this study was to compare VDR gene and protein expression in the forearm muscle between sarcopenic and non-sarcopenic individuals who have sustained distal radius fractures. Twenty samples of muscle tissue from sarcopenic patients (mean age 63.4 ± 8.1 years) and 20 age- and sex-matched control tissues (62.1 ± 7.9 years) were acquired from the edge of dissected pronator quadratus muscle during surgery for distal radius fractures. The mRNA expression levels of VDR as well as the myokines of interest that may be associated with muscle mass change (myogenin and myostatin) were analyzed with real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR). In addition, Western blot assay and immunohistochemistry for VDR were performed. Sarcopenic patients showed a significantly lower level of gene expression for VDR and myogenin, but a greater level of gene expression for myostatin than the controls according to qRT-PCR analysis. The density of VDR protein expressions was 2.1 times greater, while that of myostatin was 2.6 times lower, in the control group than in the sarcopenic group according to Western blot analysis. On immunohistochemical analysis, the density of the cells expressing VDR was significantly decreased in the sarcopenic patients. Sarcopenic patients who sustained distal radius fractures presented lower vitamin D receptor gene and protein expression in skeletal muscles compared to non-sarcopenic individuals.

Study of bone mass in young daughters of women with fracture of the distal end of the radius.

The main aim was to assess whether young and healthy daughters of women with fractures of the distal end of the radius (DER) had less bone mass than the control group. In an observational study of cases and controls (1:1), the daughters of women with fractures of DER (96) were selected at the age of reaching the peak of bone mass and compared with a control group (91). All women underwent medical history, analytical determinations, and densitometry. In the case group, we found lower bone mass values at the spine and femoral neck than the control group. We also found a lower bone mass at the hips of daughters of women with 1 or more osteoporotic fractures associated with DER and at the lumbar spine in those whose mothers had densitometric osteoporosis. In conclusion, young daughters of women with fractures of DER had lower levels of bone mass density, with a possible "location-specific" occurrence based on the presence of 1 or more osteoporotic fractures associated with DER or on the presence of maternal densitometric osteoporosis.

Genetic influences on vitamin D status and forearm fracture risk in African American children.

We sought to investigate the relationship between newly identified genetic variants and vitamin D levels and fracture risk in healthy African American (black) children. This case-control study included children of both sexes, ages 5 to 9 years, with and without forearm fractures. Serum 25-hydroxy vitamin D levels, bone mineral density, body mass index, and calcium/vitamin D intake were measured in 130 individuals (n = 60 cases and n = 70 controls). The 5 variants tested were located in the GC gene (rs2282679), in the NADSYN1 gene (rs12785878 and rs3829251), and in the promoter region of the CYP2R1 gene (rs2060793 and rs104741657). Associations between single nucleotide polymorphisms (SNPs) and vitamin D levels were tested using an analysis of covariance. Associations between SNPs and fracture status were tested using logistic regression. The GC gene variant was associated with vitamin D levels (P = 0.038). None of the SNPs were associated with fracture status in young blacks. These results suggest that the variants tested, which are associated with circulating vitamin D levels in whites, are not associated with fracture status in healthy black children. Additional research is required to discover the genetics of fracture risk in blacks.

Association of the G-174C variant in the interleukin-6 promoter region with bone loss and fracture risk in older women.

UNLABELLED: We analyzed the association between the IL-6 G-174C polymorphism and osteoporosis phenotypes in 3376 older women. Women with the C/C genotype had a significantly slower rate of decline in hip BMD and a 33% lower risk of wrist fracture than women with the G/G genotype. Variation at the IL-6 locus may contribute to the genetic susceptibility to bone fragility. INTRODUCTION: Interleukin 6 (IL-6) promotes osteoclast formation and bone resorption. The C allele of the G-174C polymorphism in the IL-6 promoter region has been related to lower gene transcription and plasma IL-6 levels. MATERIALS AND METHODS: In this study, we evaluated the relationship between the IL-6 G-174C polymorphism and BMD, the rate of decline in BMD, and the risk of fracture in 3376 women 65 years of age and older participating in the Study of Osteoporotic Fractures. BMD was measured at the distal and proximal radius using single photon absorptiometry and at the hip using DXA. Hip BMD was measured again an average of 3.5 years later. Incident fractures over an average of 10.8 years of follow-up were confirmed by physician adjudication of radiology reports. RESULTS: Distal and proximal radius BMD was lowest among women with the G/G genotype, intermediate in the heterozygotes, and highest in women with the C/C genotype (p = 0.016 and p = 0.049, respectively), although the differences between the genotypes were small. While there were no differences by genotype with initial hip BMD, women with the C/C genotype experienced a slower rate of decline in total hip and femoral neck BMD compared with women with the G/G genotype (p = 0.004 and p = 0.029, respectively). Women with the C/C genotype also had 33% lower risk of wrist fracture compared with women with the G/G genotype, independent of age, body mass index, estrogen use, and study center (RR, 0.67; 95% CI, 0.45, 1.00; p = 0.048), whereas heterozygous women had a more intermediate risk (RR, 0.85; 95% CI, 0.65, 1.12; p = 0.256). No association was found between genotype and risk of hip or all non-spine fractures. CONCLUSIONS: These results suggest that the IL-6 G-174C promoter polymorphism may be a genetic marker for bone loss and wrist fracture among older women.

Congenital pseudarthrosis of the ulna and radius in two cases of neurofibromatosis type 1.

Two children with neurofibromatosis type 1 who presented at birth with congenital pseudarthrosis of the ulna and radius are described. The patients were treated with broad resections. As a consequence, the forearms were reduced in length. The osteotomies were stabilized in one patient first with endomedullary nailing and then with a free vascularized fibular graft. In the second patient the osteotomy was stabilized by external fixation. Using these techniques, rapid and excellent healing and normal function were achieved. In contrast to the lower extremity, reduction of the length of the forearm can be accepted to a certain extent. If necessary, an extension osteotomy can be performed at a later date.

Vitamin D receptor genotype and the risk of bone fractures in women.

Several studies have confirmed an initial report of a relation between bone density and polymorphic forms of the calcitriol (vitamin D) receptor gene, whereas others have failed to find an association. We examined whether variants of the vitamin D receptor gene are associated with the risk of bone fracture, using a nested case-control analysis within the Nurses' Health Study cohort. The study women all were Caucasian and were 43-69 years of age when they provided a blood sample. Cases included the 54 proximal femur (hip) fractures and 163 distal radius (forearm) fractures that occurred subsequent to the blood draw. Cases and controls were genotyped by polymerase chain reaction for the BsmI polymorphism. The BB genotype, previously associated with lower bone density, was associated with a more than twofold increased risk of hip fracture compared with the bb genotype. Risk was greater for women who were older, leaner, or less physically active or who had a lower calcium intake. The heterozygous genotype was not associated with any increased risk of hip fracture, and we observed little association between vitamin D receptor genotype and forearm fracture. This study supports an association between vitamin D receptor genotype and hip fracture. It also implies that modification by other risk factors may have contributed to the conflicting results from previous studies of vitamin D receptor genotype and femoral bone density.

[The experimental study on expression of BMP3 gene during fracture healing].

The role of BMP3 in fracture repair and its basic mechanisms at the molecular aspect has been studied. Fourty-eight New Zealand white rabbits with the fractures in the middle of bilateral radial shafts were used as animal models, and divided randomly into six groups for calluses at the 1st, 2nd, 3rd, 4th, 6th and 8th week after the onset of fracture. The levels and the cellular localizations of expression of BMP3 mRNA were investigated with the nucleotide hybridization techniques. The results revealed that BMP3 gene expression was highly increased in the early phase of fracture repair, and reached its peak at the second week (about 3.4-fold of that of the normal control). The strong expression of BMP3 gene was localized in mesenchymal cells, chondroblasts and osteoblasts. The results suggest that BMP3 plays an important role of bone-induction in the early stage of fracture repair and it works by the way of autocrine or/and paracrine pathway.