Dataset Information

Polymorphisms in the P2X7 receptor gene are associated with low lumbar spine bone mineral density and accelerated bone loss in post-menopausal women.

ABSTRACT: The P2X7 receptor gene (P2RX7) is highly polymorphic with five previously described loss-of-function (LOF) single-nucleotide polymorphisms (SNP; c.151+1G>T, c.946G>A, c.1096C>G, c.1513A>C and c.1729T>A) and one gain-of-function SNP (c.489C>T). The purpose of this study was to determine whether the functional P2RX7 SNPs are associated with lumbar spine (LS) bone mineral density (BMD), a key determinant of vertebral fracture risk, in post-menopausal women. We genotyped 506 post-menopausal women from the Aberdeen Prospective Osteoporosis Screening Study (APOSS) for the above SNPs. Lumbar spine BMD was measured at baseline and at 6-7 year follow-up. P2RX7 genotyping was performed by homogeneous mass extension. We found association of c.946A (p.Arg307Gln) with lower LS-BMD at baseline (P=0.004, ?=-0.12) and follow-up (P=0.002, ?=-0.13). Further analysis showed that a combined group of subjects who had LOF SNPs (n=48) had nearly ninefold greater annualised percent change in LS-BMD than subjects who were wild type at the six SNP positions (n=84; rate of loss=-0.94%/year and -0.11%/year, respectively, P=0.0005, unpaired t-test). This is the first report that describes association of the c.946A (p.Arg307Gln) LOF SNP with low LS-BMD, and that other LOF SNPs, which result in reduced or no function of the P2X7 receptor, may contribute to accelerated bone loss. Certain polymorphic variants of P2RX7 may identify women at greater risk of developing osteoporosis.

SUBMITTER: Gartland A

PROVIDER: S-EPMC3330223 | biostudies-literature | 2012 May

REPOSITORIES: biostudies-literature

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Polymorphisms in the P2X7 receptor gene are associated with low lumbar spine bone mineral density and accelerated bone loss in post-menopausal women.

Gartland Alison A Skarratt Kristen K KK Hocking Lynne J LJ Parsons Claire C Stokes Leanne L Jørgensen Niklas Rye NR Fraser William D WD Reid David M DM Gallagher James A JA Wiley James S JS

European journal of human genetics : EJHG 20120111 5

The P2X7 receptor gene (P2RX7) is highly polymorphic with five previously described loss-of-function (LOF) single-nucleotide polymorphisms (SNP; c.151+1G>T, c.946G>A, c.1096C>G, c.1513A>C and c.1729T>A) and one gain-of-function SNP (c.489C>T). The purpose of this study was to determine whether the functional P2RX7 SNPs are associated with lumbar spine (LS) bone mineral density (BMD), a key determinant of vertebral fracture risk, in post-menopausal women. We genotyped 506 post-menopausal women fr ...[more]

PMID: 22234152

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Project description:ObjectiveTeriparatide has been increasingly utilized in the management of osteoporosis. The efficacy of low and high dose teriparatide on lumbar spine bone mineral density, vertebral fracture incidence and pain is unknown. We sought to determine the efficacy of teriparatide on these patient-important outcomes using a systematic review and meta-analysis.MethodsA systematic search of electronic databases (MEDLINE, EMBASE, CENTRAL, CINAHL) was performed to identify randomized controlled trials (RCTs) that evaluate teriparatide to any comparator for the treatment of osteoporosis in postmenopausal women. The Grades of Recommendation Assessment, Development and Evaluation (GRADE) criteria were used by two independent reviewers to assess the strength and quality of evidence.ResultsA total of 20 studies (n = 6024) were included in this review, with 2855 patients receiving teriparatide and 3169 patients receiving placebo or control treatment. A teriparatide dose of 20 μg/day increased lumbar spine bone mineral density (BMD) (standardized mean difference (SMD) 0.34 standard deviation (SD) units higher (95% CI 0.19-0.48 SDs higher) in comparison to placebo. Relative to anti-resorptive agents, 20 μg/day of teriparatide had a range from 0.14 SD units to 0.96 SD units higher (95% CI, 0.08 SDs lower to 0.36 SDs higher, CI, 0.33-1.59 SDs higher, respectively). 20 μg/day teriparatide had a significant effect on pain severity to placebo or control (SMD 0.80, 95% CI, 1.16-0.43 SDs lower) and also decreased the incidence of vertebral fractures compared to placebo (relative risk 0.31, 95% CI 0.21 to 0.46). Arthralgia and extremity pain incidence were also calculated; there were 15 and 8 fewer events per 1000 patients with the use of 20 μg/day of teriparatide compared to placebo or control, respectively.ConclusionHigh quality evidence supports the utilization of teriparatide 20 μg/day dose to significantly improve lumbar spine BMD and decrease incidence of vertebral fractures and pain severity relative to all comparators. 40 μg/day dose of teriparatide demonstrated significantly better results with prolonged treatment. This data is valuable for clinicians involved in the care of this growing demographic of patients. Further investigation on the safety and efficacy of teriparatide in higher doses for the long-term treatment of osteoporosis in postmenopausal women should be conducted through high-quality clinical trials.

Project description:The spatial heterogeneity in trabecular bone density within the vertebral centrum is associated with vertebral strength and could explain why volumetric bone mineral density (vBMD) exhibits low sensitivity in identifying fracture risk. This study evaluated whether the heterogeneity and spatial distribution of trabecular vBMD are associated with prevalent vertebral fracture. We examined the volumetric quantitative computed tomography (QCT) scans of the L3 vertebra in 148 participants in the Framingham Heart Study Multidetector CT study. Of these individuals, 37 were identified as cases of prevalent fracture, and 111 were controls, matched on sex and age with three controls per case. vBMD was calculated within 5-mm contiguous cubic regions of the centrum. Two measures of heterogeneity were calculated: (i) interquartile range (IQR); and (ii) quartile coefficient of variation (QCV). Ratios in the spatial distributions of the trabecular vBMD were also calculated: anterior/posterior, central/outer, superior/mid-transverse, and inferior/mid-transverse. Heterogeneity and spatial distributions were compared between cases and controls using Wilcoxon rank sum tests and t tests and tested for association with prevalent fractures with conditional logistic regressions independent of integral vBMD. Prevalent fracture cases had lower mean ± SD integral vBMD (134 ± 38 versus165 ± 42 mg/cm3 , p < .001), higher QCV (0.22 ± 0.13 versus 0.17 ± 0.09, p = .003), and lower anterior/posterior rBMD (0.65 ± 0.13 versus 0.78 ± 0.16, p < .001) than controls. QCV was positively associated with increased odds of prevalent fracture (OR 1.61; 95% CI, 1.04 to 2.49; p = .034), but this association was not independent of integral vBMD (p = .598). Increased anterior/posterior trabecular vBMD ratio was associated with decreased odds of prevalent fracture independent of integral vBMD (OR 0.38; 95% CI, 0.20 to 0.71; p = .003). In conclusion, increased trabecular vBMD in the anterior versus posterior centrum, but not trabecular vBMD heterogeneity, was associated with decreased risk of prevalent fracture independent of integral vBMD. Regional measurements of trabecular vBMD could aid in determining the risk and underlying mechanisms of vertebral fracture. © 2019 American Society for Bone and Mineral Research.

Dataset Information

Polymorphisms in the P2X7 receptor gene are associated with low lumbar spine bone mineral density and accelerated bone loss in post-menopausal women.

Publications

Polymorphisms in the P2X7 receptor gene are associated with low lumbar spine bone mineral density and accelerated bone loss in post-menopausal women.

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