Integrating real-world data and modeling to project changes in femoral neck bone mineral density and fracture risk in premenopausal women.
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SUBMITTER: Beck D
PROVIDER: S-EPMC8301565 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Purpose/introductionTooth loss has been found to be associated with fractures and osteoporosis. However, the associations between number of teeth with bone mineral density as well as with hip fractures have not been explored in the same study setting.MethodsData from the cross-sectional National Health and Nutrition Examination Survey (2005-2010, 2013-2014, and 2017-2018) with completed femoral neck bone mineral density (BMD) measurements, osteoporosis questionnaires, and dentition examinations were analyzed. A total of 15,198 participants, with a mean age of 53.9 and diverse ethnicity, males (52%), and females (48%), were analyzed. Multivariate logistic regression analyses for self-reported hip fractures, self-reported osteoporosis, and measured low femoral BMD accounting for traditional risk factors were tested for the total number of natural teeth (NoT) present, or by NoT in the anterior or posterior segments.ResultsSubjects with fewer natural teeth present were more likely to report a hip fracture, osteoporosis, or having lower levels of femoral neck BMD. With one additional tooth present in the mouth, there was a decreased association with self-reported hip fracture [OR(95%CI) = 0.98(0.96-0.99); P = 0.005] or with less likelihood of having low femoral neck BMD [OR(95%CI) = 0.99(0.97-1.00); P = 0.007].ConclusionsWith the limitation of the cross-sectional study design, results should be interpreted cautiously, yet our analyses point to an association between a decreased number of natural teeth present and self-reported hip fractures or low femoral neck BMD. The number of teeth present could be potentially utilized for assessing risks of hip fracture and osteoporosis. Future research is needed to validate our findings.
| S-EPMC8312725 | biostudies-literature
Project description:In the Health Outcomes and Reduced Incidence with Zoledronic Acid Once Yearly - Pivotal Fracture Trial (HORIZON-PFT), zoledronic acid (ZOL) 5 mg significantly reduced fracture risk.The aim of the study was to identify factors associated with greater efficacy during ZOL 5 mg treatment.We conducted a subgroup analysis (preplanned and post hoc) of a multicenter, double-blind, placebo-controlled, 36-month trial in 7765 women with postmenopausal osteoporosis.A single infusion of ZOL 5 mg or placebo was administered at baseline, 12, and 24 months.Primary endpoints were new vertebral fracture and hip fracture. Secondary endpoints were nonvertebral fracture and change in femoral neck bone mineral density (BMD). Baseline risk factor subgroups were age, BMD T-score and vertebral fracture status, total hip BMD, race, weight, geographical region, smoking, height loss, history of falls, physical activity, prior bisphosphonates, creatinine clearance, body mass index, and concomitant osteoporosis medications.Greater ZOL induced effects on vertebral fracture risk were seen with younger age (treatment-by-subgroup interaction, P = 0.05), normal creatinine clearance (P = 0.04), and body mass index >or= 25 kg/m(2) (P = 0.02). There were no significant treatment-factor interactions for hip or nonvertebral fracture or for change in BMD.ZOL appeared more effective in preventing vertebral fracture in younger women, overweight/obese women, and women with normal renal function. ZOL had similar effects irrespective of fracture risk factors or femoral neck BMD.
| S-EPMC5101059 | biostudies-literature
Project description:ContextRecent studies have shown that β-blocker (BB) users have a decreased risk of fracture and higher bone mineral density (BMD) compared to nonusers, likely due to the suppression of adrenergic signaling in osteoblasts, leading to increased BMD. There is also variability in the effect size of BB use on BMD in humans, which may be due to pharmacogenomic effects.ObjectiveTo investigate potential single-nucleotide variations (SNVs) associated with the effect of BB use on femoral neck BMD, we performed a cross-sectional analysis using clinical data, dual-energy x-ray absorptiometry, and genetic data from the Framingham Heart Study's (FHS) Offspring Cohort. We then sought to validate our top 4 genetic findings using data from the Rotterdam Study, the BPROOF Study, the Malta Osteoporosis Fracture Study (MOFS), and the Hertfordshire Cohort Study.MethodsWe used sex-stratified linear mixed models to determine SNVs that had a significant interaction effect with BB use on femoral neck (FN) BMD across 11 gene regions. We also evaluated the association of our top SNVs from the FHS with microRNA (miRNA) expression in blood and identified potential miRNA-mediated mechanisms by which these SNVs may affect FN BMD.ResultsOne variation (rs11124190 in HDAC4) was validated in females using data from the Rotterdam Study, while another (rs12414657 in ADRB1) was validated in females using data from the MOFS. We performed an exploratory meta-analysis of all 5 studies for these variations, which further validated our findings.ConclusionThis analysis provides a starting point for investigating the pharmacogenomic effects of BB use on BMD measures.
| S-EPMC8237849 | biostudies-literature
Project description:BackgroundGenome-wide association studies (GWASs) routinely identify loci associated with risk factors for osteoporosis. However, GWASs with relatively small sample sizes still lack sufficient power to ascertain the majority of genetic variants with small to modest effect size, which may together truly influence the phenotype. The loci identified only account for a small percentage of the heritability of osteoporosis. This study aims to identify novel genetic loci associated with DXA-derived femoral neck (FNK) bone mineral density (BMD) and quantitative ultrasound of the heel calcaneus estimated BMD (eBMD), and to detect shared/causal variants for the two traits, to assess whether the SNPs or putative causal SNPs associated with eBMD were also associated with FNK-BMD.MethodsNovel loci associated with eBMD and FNK-BMD were identified by the genetic pleiotropic conditional false discovery rate (cFDR) method. Shared putative causal variants between eBMD and FNK-BMD and putative causal SNPs for each trait were identified by the colocalization method. Mendelian randomization analysis addresses the causal relationship between eBMD/FNK-BMD and fracture.ResultsWe identified 9,500 (cFDR < 9.8E-6), 137 (cFDR < 8.9E-4) and 124 SNPs associated with eBMD, FNK-BMD, and both eBMD and FNK-BMD, respectively, with 37 genomic regions where there was a SNP that influences both eBMD and FNK-BMD. Most genomic regions only contained putative causal SNPs associated with eBMD and 3 regions contained two distinct putative causal SNPs influenced both traits, respectively. We demonstrated a causal effect of FNK-BMD/eBMD on fracture.ConclusionMost of SNPs or putative causal SNPs associated with FNK-BMD were also associated with eBMD. However, most of SNPs or putative causal SNPs associated with eBMD were not associated with FNK-BMD. The novel variants we identified may help to account for the additional proportion of variance of each trait and advance our understanding of the genetic mechanisms underlying osteoporotic fracture.
| S-EPMC7388689 | biostudies-literature
Project description:BACKGROUND:Nutritional factors including vitamin D, magnesium, and fat are known to affect bone mineral accrual. This study aimed to evaluate associations between dietary nutrient intakes (both macronutrients and micronutrients) and bone mineral density (BMD) in children and adolescents. METHODS:Data for this cross-sectional, population-based study were derived from the National Health and Nutrition Examination Survey (NHANES). Participants aged from 8 to 19?years were included. The primary outcome was femoral neck BMD. RESULTS:Multivariate analyses revealed that for participants aged 8 to 11, daily sodium intake was significantly and positively associated with femoral neck BMD (B?=?0.9?×? 10-?5, p?=?0.031); in particular, subgroup analyses by sex found that in male participants aged 8-11, daily total cholesterol intake (B?=?5.3?×?10-?5, p?=?0.030) and calcium intake (B?=?-?2.0?×?10-?5, p?<?0.05) were significantly associated with femoral neck BMD in a positive and negative manner, respectively, but neither were observed in female participants of this age group. In contrast, daily intakes of vitamin D and magnesium were significantly and positively associated with femoral neck BMD in female participants aged 8-11 (B?=?246.8?×?10-?5 and 16.3?×?10-?5, p?=?0.017 and 0.033, respectively). For participants aged 16 to 19, daily total fat intake was significantly and negatively associated with femoral neck BMD (B?=?-?58?×?10-?5, p?=?0.048); further stratification by sex found that magnesium and sodium intakes were significantly and positively associated with femoral neck BMD only in females of this age group (B?=?26.9?×?10-?5 and 2.1?×?10-?5, respectively; both p?<?0.05). However, no significant associations between daily nutrient intakes and femoral neck BMD were identified in participants aged 12-15 before or after subgroup stratification. CONCLUSION:The study found that associations of specific nutrition-related variables with BMD of the femoral neck is dependent upon age and gender.
| S-EPMC6839089 | biostudies-literature
Project description:We aimed to analyze the associations of bone mineral density (BMD) of femoral heads, age and gender, and compare the differences in BMD between fracture side and non-fracture side by "3D Spine Exam Analysis" module in QCT Pro software. In this study, we identified patients who had undergone quantitative computed tomography (QCT) examinations between March 2016 and July 2018 and measured their trabecular volumetric BMD (vBMD) of femoral heads. This retrospective study enrolled 367 subjects. A total of 149 participants with images were randomly selected to verify the repeatability of this method. The relationship among the vBMD, age and gender was analyzed (n?=?367), and the difference of vBMD between non-fracture side and fracture side were studied in subjects (n?=?75) with low-energy hip fracture on one side and compared the image quality of bilateral hip joints. The intraclass correlation coefficients (ICCs) between the results measured by 2 operators and the results measured by the same operator showed excellent agreement (ICCs?>?0.9). Multivariate regression equation of vBMD of femoral head, age and gender showed statistical significance (P?<?0.05). vBMD showed negative correlation with age (P?<?0.05), and showed no statistically significant relation with gender (P?>?0.05). vBMD of non-fracture side was higher than that of fracture side, but the difference was statistically significant only at the middle layer (Pmiddle?<?0.05). In conclusions, the vBMD of femoral head as measured by "3D Spine Exam Analysis" module in QCT Pro software showed good repeatability. The trabecular vBMD of femoral head was negatively correlated with age, and not related with gender. The vBMD of femoral head was higher on non-fracture side than that on the fracture side.
| S-EPMC7400568 | biostudies-literature
Project description:Bone mineral density (BMD) is an established measure used to diagnose patients with osteoporosis. In clinical trials, change in BMD has been shown to provide a reliable estimate of fracture risk reduction, and achieved BMD T-score has been shown to reflect the near-term risk of fracture. We aimed to test the association between BMD T-score and fracture risk in patients treated for osteoporosis in a real-world setting. This retrospective, observational cohort study included Swedish females aged ≥55 years who had a total hip BMD measurement at one of three participating clinics. Patients were separated into two cohorts: bisphosphonate-treated and bisphosphonate-naïve prior to BMD measurement, stratified by age and prior nonvertebral fracture status. The primary outcome was cumulative incidence of clinical fractures within 24 months of BMD measurement, with other fracture types included as secondary outcomes. Associations between T-score and fracture risk were estimated using proportional hazards regression and restricted cubic splines. A total of 15,395 patients were analyzed: 11,973 bisphosphonate-naïve and 3422 bisphosphonate-treated. In the 24 months following BMD measurement, 6.3% (95% confidence interval [CI], 5.9-6.7) of bisphosphonate-naïve and 8.4% (95% CI, 7.5-9.4) of bisphosphonate-treated patients experienced a clinical fracture. Strong inverse relationships between BMD T-score and fracture incidence were observed in both cohorts. Among bisphosphonate-naïve patients, this relationship appeared to plateau around T-score -1.5, indicating smaller marginal reductions in fracture risk above this value; bisphosphonate-treated patients showed a more consistent marginal change in fracture risk across the evaluated T-scores (-3.0 to -0.5). Trends remained robust regardless of age and prior fracture status. This real-world demonstration of a BMD-fracture risk association in both bisphosphonate-naïve and bisphosphonate-treated patients extends evidence from clinical trials and recent meta-regressions supporting the suitability of total hip BMD as a meaningful outcome for the clinical management of patients with osteoporosis. © 2021 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).
| S-EPMC9298264 | biostudies-literature
Project description:UNLABELLED:Research has not examined changes in bone mineral density (BMD) between men and women following hip fracture. The aim was to evaluate sex differences in BMD following hip fracture. Men experienced significant declines in BMD, while not statistically greater than women, underscoring the necessity for better osteoporosis care in men. INTRODUCTION:Each year in the USA, approximately 260,000 older adults experience a hip fracture. Women experiencing hip fracture have excess decline in BMD in the year following fracture compared to expected decrements due to aging, but few studies have assessed sex differences in the sequelae of hip fracture. Thus, our objective was to examine sex differences in BMD change in the year after hip fracture. METHODS:The sample (n?=?286) included persons enrolled in the Baltimore Hip Studies 7th cohort, a study that matched (1:1) men and women experiencing hip fracture. Weighted estimating equations that accounted for missing data and selective survival were used to estimate sex differences in 12-month total hip (TH) and femoral neck (FN) BMD changes. RESULTS:Men had larger average adjusted percent decline in TH and FN BMD. Adjusted 12-month decreases at the FN showed a statistically significant decline of -4.60% (95% confidence interval [CI] -7.76%, -0.20%) in men and an insignificant change of -1.62% (95% CI -4.57%, 1.32%) in women. Yet, the difference in change between men and women was not statistically significant (P?=?0.17). The estimated sex differences for TH BMD loss were smaller in magnitude. CONCLUSIONS:There is evidence of significant BMD loss among men at the FN in the year after hip fracture. Although not statistically greater than women, these clinically significant findings highlight the need for improved osteoporosis care among men prior to and after hip fracture.
| S-EPMC4983447 | biostudies-literature
Project description:In contrast to conventional dual-energy X-ray absorptiometry, quantitative computed tomography separately measures trabecular and cortical volumetric bone mineral density (vBMD). Little is known about the genetic variants associated with trabecular and cortical vBMD in humans, although both may be important for determining bone strength and osteoporotic risk. In the current analysis, we tested the hypothesis that there are genetic variants associated with trabecular and cortical vBMD at the femoral neck by genotyping 4608 tagging and potentially functional single-nucleotide polymorphisms (SNPs) in 383 bone metabolism candidate genes in 822 Caucasian men aged 65 years or older from the Osteoporotic Fractures in Men Study (MrOS). Promising SNP associations then were tested for replication in an additional 1155 men from the same study. We identified SNPs in five genes (IFNAR2, NFATC1, SMAD1, HOXA, and KLF10) that were robustly associated with cortical vBMD and SNPs in nine genes (APC, ATF2, BMP3, BMP7, FGF18, FLT1, TGFB3, THRB, and RUNX1) that were robustly associated with trabecular vBMD. There was no overlap between genes associated with cortical vBMD and trabecular vBMD. These findings identify novel genetic variants for cortical and trabecular vBMD and raise the possibility that some genetic loci may be unique for each bone compartment.
| S-EPMC3153388 | biostudies-literature
Project description:BackgroundCow milk contains more calcium, magnesium, potassium, zinc, and phosphorus minerals. For a long time, people have believed that increasing milk intake is beneficial to increasing bone density. Many confounding factors can affect milk consumption, and thus the association described to date may not be causal. We explored the causal relationship between genetically predicted milk consumption and Bone Mineral Density (BMD) of the femoral neck and lumbar spine based on 53,236 individuals from 27 studies of European ancestry using the Mendelian randomization (MR) study. 32,961 individuals of European and East Asian ancestry were used for sensitivity analysis.MethodsA genetic instrument used for evaluating milk consumption is rs4988235, a locus located at 13,910 base pairs upstream of the LCT gene. A Mendelian randomization (MR) analysis was conducted to study the effect of selected single nucleotide polymorphisms (SNPs) and BMD. The summary-level data for BMD of the femoral neck and lumbar spine were obtained from two GWAS meta-analyses ['Data Release 2012' and 'Data Release 2015' in the GEnetic Factors for OSteoporosis Consortium (GEFOS)].Resultswe found that genetically predicted milk consumption was not associated with FN-BMD(OR 1.007; 95% CI 0.991-1.023; P = 0.385), LS-BMD(OR 1.003; 95% CI 0.983-1.024; P = 0.743) by performing a meta-analysis of several different cohort studies. High levels of genetically predicted milk intake were positively associated with increased FN-BMD in Women. The OR for each additional milk intake increasing allele was 1.032 (95%CI 1.005-1.059; P = 0.014). However, no causal relationship was found between milk consumption and FN-BMD in men (OR 0.996; 95% CI 0.964-1.029; P = 0.839). Genetically predicted milk consumption was not significantly associated with LS-BMD in women (OR 1.017; 95% CI 0.991-1.043; P = 0.198) and men (OR 1.011; 95% CI 0.978-1.045; P = 0.523).ConclusionOur study found that women who consume more milk have a higher FN-BMD. When studying the effect of milk consumption on bone density in further studies, we need to pay more attention to women.
| S-EPMC9251187 | biostudies-literature