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Serum free estradiol and estrogen receptor-? mediated activity are related to decreased incident hip fractures in older women.

ABSTRACT: There is paucity of data from Asian women on the association between serum estrogens and osteoporotic hip fracture risk. We conducted a case-control study nested within a population-based prospective cohort, The Singapore Chinese Health Study, to evaluate serum estrogens levels, ER?-mediated estrogenic activity and hip fracture risk in postmenopausal Asian women. Among 35,298 women who were recruited between 1993 and 1998, 15,410 women donated blood for research between 1999 and 2004. From this subcohort, we identified 140 cases who subsequently suffered hip fracture after blood donation, and 278 age-matched controls. Serum levels of total estrone, estradiol and sex hormone binding globulin levels were measured in a blinded fashion among cases and controls. ER?-mediated estrogenic activity of serum samples was quantified using a sensitive ER?-driven cell bioassay. Women with hip fracture had lower serum estrogens than control women. Compared to the lowest quintile, women in the highest quintile of free estradiol exhibited a statistically significant 57% reduction in risk of hip fracture (95% confidence interval (CI), 6-80%), with a dose-dependent relationship (p for trend=0.021). High levels of ER?-mediated estrogenic activity were also associated with decreased risk of hip fracture (p for trend=0.048). Overall, women with relatively high levels of both free estradiol and ER?-mediated estrogenic activity had a 55% reduction in hip fracture risk (95% CI, 17-76%) compared to women with low levels of both. High levels of free estradiol and ER?-mediated estrogen activity in sera were associated with reduced hip fracture risk in Chinese postmenopausal women.

SUBMITTER: Lim VW

PROVIDER: S-EPMC3353105 | biostudies-literature | 2012 Jun

REPOSITORIES: biostudies-literature

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Serum free estradiol and estrogen receptor-α mediated activity are related to decreased incident hip fractures in older women.

Lim Vanessa W VW Li Jun J Gong Yinhan Y Yuan Jian-Min JM Wu Tsung Sheng TS Hammond Geoffrey L GL Jin Aizhen A Koh Woon-Puay WP Yong E L EL

Bone 20120316 6

There is paucity of data from Asian women on the association between serum estrogens and osteoporotic hip fracture risk. We conducted a case-control study nested within a population-based prospective cohort, The Singapore Chinese Health Study, to evaluate serum estrogens levels, ERα-mediated estrogenic activity and hip fracture risk in postmenopausal Asian women. Among 35,298 women who were recruited between 1993 and 1998, 15,410 women donated blood for research between 1999 and 2004. From this ...[more]

PMID: 22445734

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Project description:There are currently no robust noninvasive markers of fragility fractures. Secreted frizzled related protein-1 (sFRP-1), dickkopf-related protein 1 (DKK1) and DKK2, and sclerostin (SOST) inhibit Wnt signaling and interfere with osteoblast-mediated bone formation. We evaluated associations of serum levels of sFRP-1, DKK1, DKK2, and SOST with incident low-impact fracture and BMD in 828 women aged ≥65 years from EpiDoC, a longitudinal population-based cohort. A structured questionnaire during a baseline clinical appointment assessed prevalent fragility fractures and clinical risk factors (CRFs) for fracture. Blood was collected to measure serum levels of bone turnover markers and Wnt regulators. Lumbar spine and hip BMD were determined by DXA scanning. Follow-up assessment was performed through a phone interview; incident fragility fracture was defined by any new self-reported low-impact fracture. Multivariate Cox proportional hazard models were used to analyze fracture risk adjusted for CRFs and BMD. During a mean follow-up of 2.3 ± 1.0 years, 62 low-impact fractures were sustained in 58 women. A low serum DKK2 level (per 1 SD decrease) was associated with a 1.5-fold increase in fracture risk independently of BMD and CRFs. Women in the two lowest DKK2 quartiles had a fracture incidence rate of 32 per 1000 person-years, whereas women in the two highest quartiles had 14 fragility fractures per 1000 person-years. A high serum sFRP1 level was associated with a 1.6-fold increase in fracture risk adjusted for CRFs, but not independently of BMD. Serum levels of SOST (r = 0.191; p = 0.0025) and DKK1(r = -0.1725; p = 0.011) were correlated with hip BMD, but not with incident fragility fracture. These results indicate that serum DKK2 and sFRP1 may predict low-impact fracture. The low number of incident fractures recorded is a limitation and serum levels of Wnt regulators should be further studied in other populations as potential noninvasive markers of fragility fractures. © 2019 The Authors. JBMR Plus published by Wiley Periodicals, Inc. on behalf of American Society for Bone and Mineral Research.

Project description:BackgroundSituational factors during a fall among three common types of fractures of the distal forearm, hip, and vertebrae among older women in Taiwan were investigated.MethodsIn 2016 ~ 2017, study participants were identified from those aged ≥65 years who visited emergency departments due to a fall in two university-affiliated hospitals in Taipei. In addition to individual characteristics, situational factors during the fall (location, activity, change of center of mass, fall mode, fall direction, initiating a protective response, and being hit) were collected. A sample of 203 distal-forearm fractures, 189 vertebral fractures, and 375 hip fractures was recruited, while 717 women with a soft-tissue injury were used as a control group. The identification of situational risk factors for each type of fracture was validated by using those who sustained one of the other two types of fracture as a control group.ResultsAfter adjusting for age and other individual characteristics, compared to soft-tissue injuries, distal-forearm fractures were significantly more likely to occur with slips (odds ratio [OR] = 11.0; 95% confidence interval [CI] = 4.76 ~ 25.4), trips (OR = 3.40; 95% CI = 1.42 ~ 8.17), step-downs (OR = 4.95; 95% CI = 2.15 ~ 11.4), and from sideways falls (OR = 1.73; 95% CI = 1.12 ~ 2.67) and significantly less likely to occur indoors (OR = 0.62; 95% CI = 0.42 ~ 0.90) or from backwards falls (OR = 0.62; 95% CI = 0.41 ~ 0.95). Hip fractures were significantly more likely to occur with step-downs (OR = 1.76; 95% CI = 1.13 ~ 2.75) and from backwards (OR = 3.16; 95% CI = 2.15 ~ 4.64) or sideways falls (OR = 5.56; 95% CI = 3.67 ~ 8.41) and significantly less likely when hitting an object (OR = 0.26; 95% CI = 0.13 ~ 0.52) or initiating a protective response (OR = 0.58; 95% CI = 0.36 ~ 0.93). Vertebral fractures were significantly more likely to occur with slips (OR = 2.42; 95% CI = 1.30 ~ 4.50), step-downs (OR = 2.53; 95% CI = 1.43 ~ 4.48), and backwards falls (OR = 2.15; 95% CI = 1.39 ~ 3.32). Similar results were found in the validation analyses.ConclusionsLarge variations in situational risk factors for the three types of fracture in older women existed. A combination of individual and situational risk factors may display a more-comprehensive risk profile for the three types of fracture, and an intervention that adds training programs on safe landing strategies and effective compensatory reactions may be valuable in preventing serious injuries due to a fall.

Project description:BackgroundDisplaced intracapsular hip fractures are typically treated with hemiarthroplasty (HA) or total hip arthroplasty (THA). A number of professional bodies recommend considering THA for patients that were independently mobile and cognitively intact before injury. The aim of this study was to compare the outcomes between HA and THA for independently mobile older adults with hip fractures.MethodsA systematic review and meta-analysis of RCTs was undertaken alongside analysis of a propensity score matched national cohort of older adults (aged > 60) with hip fractures. Participants were identified for the propensity score matched cohort from the National Hip Fracture Database (NHFD), which was linked to Hospital Episode Statistics (HES) and civil death registration data. The primary outcomes were 12-month dislocation, revision, and mortality. The secondary outcomes were length of stay, discharge home, unplanned re-admission, functional outcomes, and health-related quality of life.ResultsFive RCTs reported higher THA dislocation but this was not statistically significant (THA risk ratio [RR] 2.77, 95% CI 0.81 to 9.48). However, THA dislocation was significantly higher in the national observational dataset (sub-distribution hazard ratio [SHR] 1.73, 95% CI 1.24 to 2.41). Meta-analysis of data from four RCTs did not identify a significant difference in terms of revision (RR 1.52, 95% CI 0.56 to 4.14). However, THA revision was significantly lower in the national dataset (SHR 0.66, 95% CI 0.48 to 0.90). Meta-analysis of data from 5 RCTs suggested higher mortality amongst patients undergoing HA (RR 0.63, 95% CI 0.38 to 1.04), which was also observed within the national registry dataset (hazard ratio 0.45, 95% CI 0.37 to 0.54).ConclusionsNational clinical registries can provide important context when interpreting RCT data, which may alone be inadequate for comparing the safety profile of surgical interventions. These data suggest that THA is at significantly higher risk of dislocation but lower risk of revision within 12 months. The finding from both RCT and clinical registry data that THA is associated with lower 12-month mortality amongst the fittest patients with hip fractures requires urgent further study to determine whether or not this can be replicated in other balanced populations.

Project description:BackgroundVitamin D supplements are widely recommended for bone health in the general population, but data on whether they prevent fractures have been inconsistent.MethodsIn an ancillary study of the Vitamin D and Omega-3 Trial (VITAL), we tested whether supplemental vitamin D3 would result in a lower risk of fractures than placebo. VITAL was a two-by-two factorial, randomized, controlled trial that investigated whether supplemental vitamin D3 (2000 IU per day), n-3 fatty acids (1 g per day), or both would prevent cancer and cardiovascular disease in men 50 years of age or older and women 55 years of age or older in the United States. Participants were not recruited on the basis of vitamin D deficiency, low bone mass, or osteoporosis. Incident fractures were reported by participants on annual questionnaires and adjudicated by centralized medical-record review. The primary end points were incident total, nonvertebral, and hip fractures. Proportional-hazards models were used to estimate the treatment effect in intention-to-treat analyses.ResultsAmong 25,871 participants (50.6% women [13,085 of 25,871] and 20.2% Black [5106 of 25,304]), we confirmed 1991 incident fractures in 1551 participants over a median follow-up of 5.3 years. Supplemental vitamin D3, as compared with placebo, did not have a significant effect on total fractures (which occurred in 769 of 12,927 participants in the vitamin D group and in 782 of 12,944 participants in the placebo group; hazard ratio, 0.98; 95% confidence interval [CI], 0.89 to 1.08; P = 0.70), nonvertebral fractures (hazard ratio, 0.97; 95% CI, 0.87 to 1.07; P = 0.50), or hip fractures (hazard ratio, 1.01; 95% CI, 0.70 to 1.47; P = 0.96). There was no modification of the treatment effect according to baseline characteristics, including age, sex, race or ethnic group, body-mass index, or serum 25-hydroxyvitamin D levels. There were no substantial between-group differences in adverse events as assessed in the parent trial.ConclusionsVitamin D3 supplementation did not result in a significantly lower risk of fractures than placebo among generally healthy midlife and older adults who were not selected for vitamin D deficiency, low bone mass, or osteoporosis. (Funded by the National Institute of Arthritis and Musculoskeletal and Skin Diseases; VITAL ClinicalTrials.gov number, NCT01704859.).

Dataset Information

Serum free estradiol and estrogen receptor-? mediated activity are related to decreased incident hip fractures in older women.

Publications

Serum free estradiol and estrogen receptor-α mediated activity are related to decreased incident hip fractures in older women.

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