Dataset Information

Genetic risk score based on the prevalence of vertebral fracture in Japanese women with osteoporosis.

ABSTRACT: A genetic risk score (GRS) was developed for predicting fracture risk based on the prevalence of vertebral fractures in 441 Japanese females with osteoporosis. A total of 979 (858 nonsynonymous and 121 silent) single-nucleotide polymorphisms (SNPs) located in 74 osteoporosis-susceptibility genes were genotyped and evaluated for their association with fracture prevalence. Four SNPs (protein kinase domain containing, cytoplasmic [PKDCC; rs4952590], CDK5-regulatory subunit-associated protein 1-like 1 [CDKAL1; rs4712556], wingless-type MMTV-integration site family member 16 [WNT16; rs2707466], and G-patch domain-containing gene 1 [GPATCH1; rs10416265]) showed a significant association (p < 0.05) with the fracture, in which the minor allele of the former two SNPs was the protective allele and that of the latter two SNPs was the risk allele. Applying a dominant-genetic model, we allotted - 1 point each to the protective-allele carriers and 1 point each to the risk-allele carriers, and GRS values were calculated as the sum of the points. The receiver-operating characteristic curves showed that GRS adequately predicted vertebral fracture. For the model predicted by the GRS with and without the effect of age, areas under the curves were 0.788 (95% confidence interval [CI]: 0.736-0.840) and 0.667 (95% CI: 0.599-0.735), respectively. Multiple logistic regression analysis revealed that the odds ratio for the association between fracture prevalence and GRS was 3.27 (95% CI: 1.36-7.87, p = 0.008) for scores of - 1 to 0 (n = 303) and 12.12 (95% CI: 4.19-35.07, p < 0.001) for scores of 1 to 2 (n = 35) relative to a score of - 2 (n = 103). The GRS based on the four SNPs could help identify at-risk individuals and enable implementation of preventive measures for vertebral fracture.

SUBMITTER: Zhou H

PROVIDER: S-EPMC5440966 | biostudies-literature | 2016 Dec

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Genetic risk score based on the prevalence of vertebral fracture in Japanese women with osteoporosis.

Zhou Heying H Mori Seijiro S Ishizaki Tatsuro T Takahashi Atsushi A Matsuda Koichi K Koretsune Yukihiro Y Minami Shiro S Higashiyama Masahiko M Imai Shinji S Yoshimori Kozo K Doita Minoru M Yamada Akira A Nagayama Satoshi S Kaneko Kazuo K Asai Satoshi S Shiono Masaki M Kubo Michiaki M Ito Hideki H

Bone reports 20160712

A genetic risk score (GRS) was developed for predicting fracture risk based on the prevalence of vertebral fractures in 441 Japanese females with osteoporosis. A total of 979 (858 nonsynonymous and 121 silent) single-nucleotide polymorphisms (SNPs) located in 74 osteoporosis-susceptibility genes were genotyped and evaluated for their association with fracture prevalence. Four SNPs (protein kinase domain containing, cytoplasmic [<i>PKDCC</i>; rs4952590], CDK5-regulatory subunit-associated protein ...[more]

PMID: 28580384

Similar Datasets

Project description:In elderly women with osteoporosis, prior fracture, low BMD, impaired physical functioning, poorer general health, and recent falls were all direct predictors of imminent (in next year) fracture risk. Prior fracture, older age, worse health, impaired cognitive functioning, and recent falls indirectly increased imminent risk by reducing physical functioning/general health. INTRODUCTION:This study was designed to examine determinants of imminent risk of osteoporotic fracture (i.e., next 1-2 years) in postmenopausal women. METHODS:This retrospective cohort study used data from Caucasian women age 65 or older with osteoporosis who participated in the observational Study of Osteoporotic Fractures (SOF). We examined potential direct and indirect predictors of hip and nonvertebral fractures in 1-year follow-up intervals including anthropometric measures, bone mineral density (T-score), fracture since age 50, physical function, cognition, medical conditions, recent (past year) falls, and lifestyle factors. Clinically related variables were grouped into constructs via factor analysis. These constructs and selected individual variables were incorporated into a theoretical structural equation model to evaluate factors that influence imminent risk. RESULTS:Among 2261 patients, 19.4% had a nonvertebral fracture and 5.5% had a hip fracture within 1 year of a study visit between 1992 and 2008. Prior fracture, lower T-scores, lower physical functioning, and recent falls all directly increased 1-year risk of nonvertebral fracture. For both nonvertebral and hip fractures, prior fracture and recent falls influenced risk indirectly through general health, while cognition influenced risk via physical functioning. Age influenced both physical functioning and general health. CONCLUSIONS:Several established risk factors for 10-year fracture risk also played a role in predicting imminent risk of fracture (e.g., T-scores, prior fracture), as did falls, cognition, physical functioning, and general health. Fracture risk assessments should also consider falls and fall risk factors as well as established bone-related risk factors in assessing imminent fracture risk.

Project description:ImportanceThe aging of the population is associated with an increasing burden of fractures worldwide. However, the epidemiological features of fractures in mainland China are not well known.ObjectiveTo assess the prevalence of and factors associated with osteoporosis, clinical fractures, and vertebral fractures in an adult population 40 years or older in mainland China.Design, setting. and participantsThis cross-sectional study, the China Osteoporosis Prevalence Study, was conducted from December 2017 to August 2018. A random sample of individuals aged 20 years or older who represented urban and rural areas of China were enrolled, with a 99% participation rate.Main outcomes and measuresWeighted prevalence of osteoporosis, clinical fracture, and vertebral fracture by age, sex, and urban vs rural residence as determined by x-ray absorptiometry, questionnaire, and radiography.ResultsA total of 20 416 participants were included in this study; 20 164 (98.8%; 11 443 women [56.7%]; mean [SD] age, 53 [13] years) had a qualified x-ray absorptiometry image and completed the questionnaire, and 8423 of 8800 (95.7%) had a qualified spine radiograph. The prevalence of osteoporosis among those aged 40 years or older was 5.0% (95% CI, 4.2%-5.8%) among men and 20.6% (95% CI, 19.3%-22.0%) among women. The prevalence of vertebral fracture was 10.5% (95% CI, 9.0%-12.0%) among men and 9.7% (95% CI, 8.2%-11.1%) among women. The prevalence of clinical fracture in the past 5 years was 4.1% (95% CI, 3.3%-4.9%) among men and 4.2% (95% CI, 3.6%-4.7%) among women. Among men and women, 0.3% (95% CI, 0.0%-0.7%) and 1.4% (95% CI, 0.8%-2.0%), respectively, with osteoporosis diagnosed on the basis of bone mineral density or with fracture were receiving antiosteoporosis treatment to prevent fracture.Conclusions and relevanceIn this cross-sectional study of an adult population in mainland China, the prevalence of osteoporosis and vertebral fracture were high and the prevalence of vertebral fracture and clinical fracture was similarly high in men and women. These findings suggest that current guidelines for screening and treatment of fractures among patients in China should focus equally on men and women and should emphasize the prevention of vertebral fractures.

Project description:Recent studies suggest a positive association between obstructive sleep apnea (OSA), a disorder associated with intermittent hypoxia and sleep fragmentation, and derangements in bone metabolism. However, no prospective study to date has investigated the association between OSA and fracture risk in women. We conducted a prospective study examining the relation between OSA and risk of incident vertebral fracture (VF) and hip fracture (HF) in the Nurses' Health Study. History of physician-diagnosed OSA was assessed by self-reported questionnaires. A previous validation study demonstrated high concordance between self-reports and medical record identification of OSA. OSA severity was further categorized according to the presence or absence of self-reported sleepiness. Self-reports of VF were confirmed by medical record review. Self-reported HF was assessed by biennial questionnaires. Cox proportional-hazards models estimated the hazard ratio for fracture according to OSA status, adjusted for potential confounders, including BMI, physical activity, calcium intake, history of osteoporosis, and falls, and use of sleep medications. Among 55,264 women without prior history of fracture, physician-diagnosed OSA was self-reported in 1.3% in 2002 and increased to 3.3% by 2012. Between 2002 and 2014, 461 incident VF cases and 921 incident HF cases were documented. The multivariable-adjusted hazard ratio (HR) for confirmed VF for women with history of OSA was 2.00 (95% CI, 1.29-3.12) compared with no OSA history, with the strongest association observed for OSA with daytime sleepiness (HR 2.86; 95% CI, 1.31-6.21). No association was observed between OSA history and self-reported HF risk (HR 0.83; 95% CI, 0.49-1.43). History of OSA is independently associated with higher risk of confirmed VF but did not have a statistically significant association with self-reported HF in women. Further research is warranted in understanding the role of OSA and intermittent hypoxia in bone metabolism and health that may differ by fracture site. © 2020 American Society for Bone and Mineral Research (ASBMR).

Project description:BACKGROUND:Osteoporosis and vertebral fractures represent a major health burden worldwide, and the prevalence of osteoporosis is expected to increase as the world's population ages. Suffering from vertebral fracture has a substantial impact on the individual's health-related quality of life (HRQoL), physical function and pain. Complex health challenges experienced by older people with osteoporosis and vertebral fractures call for identification of factors that may influence HRQoL, as some of these factors may be modifiable. The objective is to examine the independent associations between HRQoL, physical function and pain in older women with osteoporosis and vertebral fracture. METHODS:This study has a cross-sectional design, using data from 149 home-dwelling Norwegian women with osteoporosis and vertebral fracture, aged 65+. Data on HRQoL (Short Form 36 (SF-36), Quality of Life Questionnaire of the European Foundation for Osteoporosis (QUALEFFO-41)), physical function (walking speed, balance and strength), pain, as well as sociodemographic information were collected. Simple linear regression analyses were conducted and multivariable regression models were fitted to investigate the associations. RESULTS:Lower levels of HRQoL were significantly associated with lower levels of physical function, measured by walking speed, and higher levels of pain. Pain was significantly associated with all of the subscales in SF-36, with the exception of Mental Health and Mental Component Score, and all the subscales of QUALEFFO-41. Walking speed was significantly associated with 5 of 8 subscales of SF-36 (except Bodily Pain, Vitality, Mental Health and Mental Component Score), and with 4 of 6 subscales of QUALEFFO-41 (except Score Pain and Mood). CONCLUSION:This study shows that pain and walking speed were, independently of one another, associated with HRQoL in older women with osteoporosis and vertebral fracture. These findings can inform clinicians and health managers about the importance of pain management and exercise interventions in health care for this group. Future research should address interventions targeting both physical function and pain with HRQoL as an outcome. REGISTRATION:ClincialTrials.gov Identifier: NCT02781974. Registered 18.05.16. Retrospectively registered.

Project description:INTRODUCTION: Despite vertebral fracture being a significant risk factor for further fracture, vertebral fractures are often unrecognised. A study was therefore conducted to determine the proportion of patients presenting with a non-vertebral fracture who also have an unrecognised vertebral fracture. METHODS: Prospective study of patients presenting with a non-vertebral fracture in South Glasgow who underwent DXA evaluation with vertebral morphometry (MXA) from DV5/6 to LV4/5. Vertebral deformities (consistent with fracture) were identified by direct visualisation using the Genant semi-quantitative grading scale. RESULTS: Data were available for 337 patients presenting with low trauma non-vertebral fracture; 261 were female. Of all patients, 10.4% were aged 50-64 years, 53.2% were aged 65-74 years and 36.2% were aged 75 years or over. According to WHO definitions, 35.0% of patients had normal lumbar spine BMD (T-score -1 or above), 37.4% were osteopenic (T-score -1.1 to -2.4) and 27.6% osteoporotic (T-score -2.5 or lower). Humerus (n=103, 31%), radius-ulna (n=90, 27%) and hand/foot (n=53, 16%) were the most common fractures. For 72% of patients (n=241) the presenting fracture was the first low trauma fracture to come to clinical attention. The overall prevalence of vertebral deformity established by MXA was 25% (n=83); 45% (n=37) of patients with vertebral deformity had deformities of more than one vertebra. Of the patients with vertebral deformity and readable scans for grading, 72.5% (58/80) had deformities of grade 2 or 3. Patients presenting with hip fracture, or spine T-score <or=-2.5, or low BMI, or with more than one prior non-vertebral fracture were all significantly more likely to have evidence of a prevalent vertebral deformity (p<0.05). However, 19.8% of patients with an osteopenic T-score had a vertebral deformity (48% of which were multiple), and 16.1% of patients with a normal T-score had a vertebral deformity (26.3% of which were multiple). Following non-vertebral fracture, some guidelines suggest that anti-resorptive therapy should be reserved for patients with DXA-proven osteoporosis. However, patients who have one or more prior vertebral fractures (prevalent at the time of their non-vertebral fracture) would also become candidates for anti-resorptive therapy-which would have not been the case had their vertebral fracture status not been known. Overall in this study, 8.9% of patients are likely to have had a change in management by virtue of their underlying vertebral deformity status. In other words, 11 patients who present with a non-vertebral fracture would need to undergo vertebral morphometry in order to identify one patient who ought to be managed differently. CONCLUSIONS: Our results support the recommendation to perform vertebral morphometry in patients who are referred for DXA after experiencing a non-vertebral fracture. Treatment decisions will then better reflect any given patient's future absolute fracture risk. The 'Number Needed to Screen' if vertebral morphometry is used in this way would be seven to identify one patient with vertebral deformity, and 14 to identify one patient with two or more vertebral deformities. Although carrying out MXA will increase radiation exposure for the patient, this increased exposure is significantly less than would be obtained if X-rays of the dorso-lumbar spine were obtained.

Dataset Information

Genetic risk score based on the prevalence of vertebral fracture in Japanese women with osteoporosis.

Publications

Genetic risk score based on the prevalence of vertebral fracture in Japanese women with osteoporosis.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure