Dataset Information

Association of Bone Mineral Density With the Risk of Intracranial Aneurysm.

ABSTRACT: Importance:Disruption of extracellular matrix integrity is critically involved in both intracranial aneurysm and bone fragility. Furthermore, both intracranial aneurysm and osteoporosis have a female predominance, and sex hormones are considered to affect this discrepancy. Objective:To evaluate the association between bone mineral density and intracranial aneurysm. Design, Setting, and Participants:A cross-sectional study conducted with 14 328 patients who underwent brain magnetic resonance angiography and bone mineral densitometry as a part of a health examination at a specialized center for comprehensive health examination in Seoul, the largest metropolitan area in the Republic of Korea, between December 2004 and November 2015. After excluding patients with insufficient clinical information (n?=?1102) and with ambiguous intracranial arterial lesion (n?=?441), 12 785 were included in the analysis. Exposures:Bone mineral density was measured at the lumbar vertebrae (L1 to L4), femur neck, and total hip using dual-energy x-ray absorptiometry. Main Outcomes and Measures:Multiple logistic regression or linear regression was used to examine the association between tertiles of bone mineral density and the presence, size, and multiplicity of intracranial aneurysms. In secondary analyses, we analyzed postmenopausal women and men 50 years and older (n?=?8722) because they are particularly at risk of decreased bone mineral density. Results:Among 12 785 patients in the study (7242 women [56.6%]; mean [SD] age, 54.8 [10.1] years) intracranial aneurysms were found in 472 patients (3.7%). Lower bone mineral density was associated with an increased risk of harboring intracranial aneurysm. In multivariable logistic regression analyses, odds ratios for the highest compared with the lowest bone mineral density tertile were 1.30 (95% CI, 1.03-1.64) in the lumbar spine, 1.30 (95% CI, 1.03-1.64) in the femoral neck, and 1.27 (95% CI, 1.01-1.60) in the total hip after adjusting for age, sex, and vascular risk factors. In a linear regression model adjusted for age, sex, and vascular risk factors, the lowest tertile of bone mineral density in the lumbar spine was associated with an increased log-transformed size of aneurysm (?, 0.196; SE, 0.047). In secondary analyses, these associations were more definite and a low T score (<-1 SD) was additionally associated with multiple aneurysms (OR, 1.84; 95% CI, 1.05-3.30) after adjusting for age, sex, and vascular risk factors. Conclusions and Relevance:Bone mineral density may be associated with the presence, size, and multiplicity of intracranial aneurysm. The study findings provide evidence for shared pathophysiology between intracranial aneurysm and bone fragility.

SUBMITTER: Shin YW

PROVIDER: S-EPMC5838803 | biostudies-other | 2018 Feb

REPOSITORIES: biostudies-other

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Association of Bone Mineral Density With the Risk of Intracranial Aneurysm.

Shin Yong-Won YW Park Kyung-Il KI Moon Jangsup J Lee Soon-Tae ST Chu Kon K Lee Sang Kun SK Roh Jae-Kyu JK Jung Keun-Hwa KH

JAMA neurology 20180201 2

<h4>Importance</h4>Disruption of extracellular matrix integrity is critically involved in both intracranial aneurysm and bone fragility. Furthermore, both intracranial aneurysm and osteoporosis have a female predominance, and sex hormones are considered to affect this discrepancy.<h4>Objective</h4>To evaluate the association between bone mineral density and intracranial aneurysm.<h4>Design, setting, and participants</h4>A cross-sectional study conducted with 14 328 patients who underwent brain m ...[more]

PMID: 29049519

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Project description:Osteoporosis, a disease characterized by low bone mineral density (BMD), increases the risk for fractures. Conventional risk factors alone do not completely explain measured BMD or osteoporotic fracture risk. Metabolomics may provide additional information. We aim to identify BMD-associated metabolomic markers that are predictive of fracture risk. We assessed 209 plasma metabolites by liquid chromatography with tandem mass spectrometry (LC-MS/MS) in 1552 Framingham Offspring Study participants, and measured femoral neck (FN) and lumbar spine (LS) BMD 2 to 10 years later using dual-energy X-ray absorptiometry. We assessed osteoporotic fractures up to 27-year follow-up after metabolomic profiling. We identified 27 metabolites associated with FN-BMD or LS-BMD by LASSO regression with internal validation. Incorporating selected metabolites significantly improved the prediction and the classification of osteoporotic fracture risk beyond conventional risk factors (area under the curve [AUC] = 0.74 for the model with identified metabolites and risk factors versus AUC = 0.70 with risk factors alone, p = .001; net reclassification index = 0.07, p = .03). We replicated significant improvement in fracture prediction by incorporating selected metabolites in 634 participants from the Hong Kong Osteoporosis Study (HKOS). The glycine, serine, and threonine metabolism pathway (including four identified metabolites: creatine, dimethylglycine, glycine, and serine) was significantly enriched (false discovery rate [FDR] p value = .028). Furthermore, three causally related metabolites (glycine, phosphatidylcholine [PC], and triacylglycerol [TAG]) were negatively associated with FN-BMD, whereas PC and TAG were negatively associated with LS-BMD through Mendelian randomization analysis. In summary, metabolites associated with BMD are helpful in osteoporotic fracture risk prediction. Potential causal mechanisms explaining the three metabolites on BMD are worthy of further experimental validation. Our findings may provide novel insights into the pathogenesis of osteoporosis. © 2021 American Society for Bone and Mineral Research (ASBMR).

Project description:Background and objectivesLow bone mineral density (BMD) and dementia commonly co-occur in older individuals, with bone loss accelerating in patients with dementia due to physical inactivity and poor nutrition. However, uncertainty persists over the extent to which bone loss already exists before onset of dementia. Therefore, we investigated how dementia risk was affected by BMD at various skeletal regions in community-dwelling older adults.MethodsIn a prospective population-based cohort study, BMD at the femoral neck, lumbar spine, and total body and the trabecular bone score (TBS) were obtained using dual-energy X-ray absorptiometry in 3,651 participants free from dementia between 2002 and 2005. Persons at risk of dementia were followed up until January 1, 2020. For analyses of the association between BMD at baseline and the risk of incident dementia, we used Cox proportional hazards regression analyses, adjusting for age, sex, educational attainment, physical activity, smoking status, body mass index, systolic and diastolic blood pressure, cholesterol level, high-density lipoprotein cholesterol, history of comorbidities (stroke and diabetes mellitus), and APOE genotype.ResultsAmong the 3,651 participants (median age 72.3 ± 10.0 years, 57.9% women), 688 (18.8%) developed incident dementia during a median of 11.1 years, of whom 528 (76.7%) developed Alzheimer disease (AD). During the whole follow-up period, participants with lower BMD at the femoral neck (per SD decrease) were more likely to develop all-cause dementia (hazard ratio [HR] total follow-up 1.12, 95% CI 1.02-1.23) and AD (HRtotal follow-up 1.14, 95% CI 1.02-1.28). Within the first 10 years after baseline, the risk of dementia was greatest for groups with the lowest tertile of BMD (femoral neck BMD, HR0-10 years 2.03; 95% CI 1.39-2.96; total body BMD, HR0-10 years 1.42; 95% CI 1.01-2.02; and TBS, HR0-10 years 1.59; 95% CI 1.11-2.28).DiscussionIn conclusion, participants with low femoral neck and total body BMD and low TBS were more likely to develop dementia. Further studies should focus on the predictive ability of BMD for dementia.

Project description:SummaryPeriostin (POSTN) as a regulator of osteoblast differentiation and bone formation may affect susceptibility to osteoporosis. This study suggests POSTN as a candidate gene for bone mineral density (BMD) variation and vertebral fracture risk, which could better our understanding about the genetic pathogenesis of osteoporosis and will be useful in clinic in the future.IntroductionThe genetic determination of osteoporosis is complex and ill-defined. Periostin (POSTN), an extracellular matrix secreted by osteoblasts and a regulator of osteoblast differentiation and bone formation, may affect susceptibility to osteoporosis.MethodsWe adopted a tag-single nucleotide polymorphism (SNP) based association method followed by imputation-based verification and identification of a causal variant. The association was investigated in 1,572 subjects with extreme-BMD and replicated in an independent population of 2,509 subjects. BMD was measured by dual X-ray absorptiometry. Vertebral fractures were identified by assessing vertebral height from X-rays of the thoracolumbar spine. Association analyses were performed with PLINK toolset and imputation analyses with MACH software. The top imputation finding was subsequently validated by genotyping. Interactions between POSTN and another BMD-related candidate gene sclerostin (SOST) were analyzed using MDR program and validated by logistical regression analyses. The putative transcription factor binding with target sequence was confirmed by electrophoretic mobility shift assay (EMSA).ResultsSeveral SNPs of POSTN were associated with BMD or vertebral fractures. The most significant polymorphism was rs9547970, located at the -2,327 bp upstream (P?=?6.8?×?10(-4)) of POSTN. Carriers of the minor allele G per copy of rs9547970 had 1.33 higher risk of vertebral fracture (P?=?0.007). An interactive effect between POSTN and SOST upon BMD variation was suggested (P?<?0.01). A specific binding of CDX1 to the sequence of POSTN with the major allele A of rs9547970 but not the variant G allele was confirmed by EMSA.ConclusionsOur results suggest POSTN as a candidate gene for BMD variation and vertebral fracture risk.

Dataset Information

Association of Bone Mineral Density With the Risk of Intracranial Aneurysm.

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Association of Bone Mineral Density With the Risk of Intracranial Aneurysm.

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