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Does Vitamin D affects changes in volumetric bone mineral density and architecture in postmenopausal women after conservatively treated distal radius fractures?
Raptis, K, Makris, K, Trovas, G, Galanos, A, Koutserimpas, C, Papaioannou, N, Vlamis, I, Vlasis, K, Tournis, S
Journal of musculoskeletal & neuronal interactions. 2021;(1):93-103
Abstract
OBJECTIVE We examined the role of vitamin D on volumetric bone mineral density (vBMD) and architecture during the first week's post-fracture in postmenopausal women (PMW) with distal radial fractures (DRF) treated conservatively using peripheral Quantitative Computed Tomography (pQCT). METHODS Patients were classified into 2 groups according to initial median 25(OH)D level; Group A (25(OH)D ≥15 ng/ml) and group B (25(OH)D <15 ng/ml). All patients were followed for 12 weeks at three visits: baseline, 6 weeks and 12 weeks post fracture. pQCT was performed at baseline in fractured and contralateral non-fractured radius and at 6th and 12th week on the fractured side. RESULTS 39 patients completed the protocol. Mean 25(OH)D levels were 15.60±7.35 ng/ml (3.5-41.7). Trabecular (trab) bone mineral content (BMC) and trabvBMD increased at 6 wk. vs. baseline (p<0.001). Cortical BMC, cortvBMD and cross- sectional area (CSA) progressively decreased (p<0.001) during the 12 weeks. There was no interaction between baseline 25(OH)D levels and changes in trabecular and cortical BMC, vBMD and CSA. Advanced age and higher CTX and P1NP were associated with higher cortical bone loss. CONCLUSION Vitamin D deficiency does not affect the early architectural changes after a DRF. Advanced age and higher bone remodeling were associated with higher cortical bone loss, probably related to immobilization and independent of vitamin D levels.
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Testosterone, sex hormone-binding globulin, insulin-like growth factor-1 and endometrial cancer risk: observational and Mendelian randomization analyses.
Mullee, A, Dimou, N, Allen, N, O'Mara, T, Gunter, MJ, Murphy, N
British journal of cancer. 2021;(9):1308-1317
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BACKGROUND Dysregulation of endocrine pathways related to steroid and growth hormones may modify endometrial cancer risk; however, prospective data on testosterone, sex hormone-binding globulin (SHBG) and insulin-like growth factor (IGF)-1 are limited. To elucidate the role of these hormones in endometrial cancer risk we conducted complementary observational and Mendelian randomization (MR) analyses. METHODS The observational analyses included 159,702 women (80% postmenopausal) enrolled in the UK Biobank. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using Cox proportional hazards models. For MR analyses, genetic variants associated with hormone levels were identified and their association with endometrial cancer (12,906 cases/108,979 controls) was examined using two-sample MR. RESULTS In the observational analysis, higher circulating concentrations of total (HR per unit inverse normal scale = 1.38, 95% CI = 1.22-1.57) and free testosterone (HR per unit log scale = 2.07, 95% CI = 1.66-2.58) were associated with higher endometrial cancer risk. An inverse association was found for SHBG (HR per unit inverse normal scale = 0.76, 95% CI = 0.67-0.86). Results for testosterone and SHBG were supported by the MR analyses. No association was found between genetically predicted IGF-1 concentration and endometrial cancer risk. CONCLUSIONS Our results support probable causal associations between circulating concentrations of testosterone and SHBG with endometrial cancer risk.
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Denosumab vs. zoledronic acid treatment in post-menopausal breast cancer: a 2-year prospective observational study.
Buch-Larsen, K, Jørgensen, NR, Jensen, LT, Andersson, M, Schwarz, P
Scandinavian journal of clinical and laboratory investigation. 2021;(6):425-431
Abstract
Adjuvant treatment for post-menopausal women with early breast cancer (BC) includes aromatase inhibitors (AI), known to decrease bone mineral density (BMD). In this study, we investigate whether denosumab is a valid second option for patients unable to receive standard adjuvant i.v. zoledronic acid (ZA). In total, 212 patients have been evaluated after they did not receive ZA. Of those 194 were included. After evaluation by an endocrinologist, all patients were offered ZA as their first choice and 15% accepted (N = 29). The remaining 85% were offered denosumab (N = 165). All patients were followed prospectively with blood tests up to 24 months. DXA scans were performed at baseline and 24 months. No difference was observed between the two treatment groups at baseline, with regard to anthropometry and standard biochemistry. Markers of bone turnover (p-PINP, p-CTX, p-bone-specific alkaline phosphatase and p-osteocalcin) all showed significant suppression compared to baseline and remained suppressed throughout the 2 years. BMD showed small and significant increases at the spine (0.024 g/cm2) and total hip (0.019 g/cm2) in the denosumab group but no change at the femoral neck(-0.011g/cm2). In the ZA group, we observed no significant change at the spine (0.015 g/cm2) and total hip (-0.001g/cm2) and a small significant decrease at the femoral neck (-0.037 g/cm2). However, when we compared BMD change between the treatment groups, we found no significant difference.Conclusions: Our data indicate that for BC patients in AI treatment who refused or were not able to receive ZA treatment, denosumab might be recommended as a second choice. Regarding markers of bone turnover and BMD denosumab is equal to ZA.Summary: Women with early breast cancer receiving anti-estrogen treatment are at risk of developing osteoporosis.We followed 194 women receiving zoledronic acid (ZA) or denosumab for up to 2 years.We find that with regard to bone protection, denosumab is a viable alternative to ZA and might be recommended as a second choice.
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Carbohydrate antigen 125, carbohydrate antigen 15-3 and low-density lipoprotein as risk factors for intraocular metastases in postmenopausal breast cancer.
Tang, J, Yan, B, Li, GF, Li, QY, Liu, WF, Liang, RB, Ge, QM, Shao, Y
Medicine. 2021;(43):e27693
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The prognosis of patients with postmenopausal breast cancer (PBC) could be improved by the early detection of intraocular metastases (IOMs). However, serum biomarkers for IOMs in PBC remain elusive. In the current study, we investigated patients with PBC, and compared serum parameters in an IOM and a non-IOM group, and then differentiated the risk factors related to IOMs. A comparison between an IOM and a non-IOM (NIOM) group was performed using Student t-test and a Chi-Squared test. After constructing a Poisson regression model to identify risk factors, we plotted receiver operating characteristic curves to evaluate the predictive value of significant risk factors in detecting IOMs. The incidence of IOMs in PBC was 1.16%. The histopathology results were not significantly different between the 2 groups. The levels of serum carbohydrate antigen 125 (CA-125), carbohydrate antigen 15-3 (CA15-3) and alkaline phosphatase were significantly elevated in IOMs compared with NIOMs (P = .082, P < .001, and P < .001, respectively). Compared with NIOMs, age, carbohydrate antigen 19 to 9, hemoglobin, calcium, total cholesterol, low-density lipoprotein (LDL) and apolipoprotein A1 were remarkably lower in IOMs (P = .038, P < .001, P < .001, P = .032, P = .041, P < .001, and P = .001, respectively). Poisson regression suggested that CA-125, CA15-3 and LDL were contributing to IOMs in PBC as risk factors (OR = 1.003, 95% CI: 1.001-1.005; OR = 1.025, 95% CI: 1.019-1.033; OR = 0.238, 95% CI: 0.112-0.505, respectively). A receiver operating characteristic curve revealed that the cut-off values for CA-125, CA15-3 and LDL were 16.78 0 U/mL, 63.175 U/mL, and 2.415 mmol/L, respectively. The combination of CA-125 and CA15-3 showed significant diagnostic value (area under the curve [AUC] = 0.982, P < .001). Our investigation suggests that CA-125, CA15-3 and LDL remarkably predict IOMs in PBC as risk factors, and the combination of CA-125 and CA15-3 shows considerable diagnostic value.
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Race-specific associations of 25-hydroxyvitamin D and parathyroid hormone with cardiometabolic biomarkers among US white and black postmenopausal women.
Xia, J, Tu, W, Manson, JE, Nan, H, Shadyab, AH, Bea, JW, Cheng, TD, Hou, L, Song, Y
The American journal of clinical nutrition. 2020;(2):257-267
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BACKGROUND Concentrations of 25-hydroxyvitamin D [25(OH)D] tend to be lower in African Americans than in non-Hispanic whites, but whether adding information on parathyroid hormone (PTH) can help explain the higher cardiometabolic risk among African Americans is unknown. OBJECTIVES This study examined race (black/white)-specific independent and joint associations of 25(OH)D and PTH with cardiometabolic biomarkers including high-sensitivity C-reactive protein (hs-CRP), estimated glomerular filtration rate (eGFR), and homeostasis model assessment of insulin resistance (HOMA-IR) and β-cell function (HOMA-B). METHODS Among 1500 white and 1300 black postmenopausal women without cardiovascular disease from the Women's Health Initiative Observational Study, a weighted linear regression analysis and a novel penalized spline-based semiparametric model with contour plots, accounting for possible nonlinear relations and interactions simultaneously, were used to investigate the race-specific independent and joint associations of 25(OH)D and PTH with each biomarker. RESULTS Black women had lower concentrations of 25(OH)D and higher PTH, HOMA-IR, HOMA-B, hs-CRP, and eGFR than white women (all P values < 0.0001). Lower 25(OH)D and higher PTH were each independently and jointly associated with higher HOMA-IR in both white and black women, whereas a similar joint relation with HOMA-B was observed in white women only. In contrast, PTH was nonlinearly associated with HOMA-B in black women and positively associated with hs-CRP in white women, independently of 25(OH)D. Whereas there was an inverse linear relation between PTH and eGFR in white women after accounting for 25(OH)D, PTH and 25(OH)D were jointly and nonlinearly associated with eGFR in black women. CONCLUSIONS We found that the joint association of 25(OH)D and PTH with β-cell function, systemic inflammation, and kidney function apparently differed between white and black women. Further studies are needed to determine whether differences in the vitamin D-PTH endocrine system contribute to racial disparities in cardiovascular health.
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Spinal Osteoarthritis Is Associated With Stature Loss Independently of Incident Vertebral Fracture in Postmenopausal Women.
Nakano, M, Nakamura, Y, Suzuki, T, Takahashi, J, Shiraki, M
Spine. 2020;(21):E1400-E1404
Abstract
STUDY DESIGN Retrospective observational study from the Nagano Cohort Study. OBJECTIVE Clarify the association between spinal osteoarthritis and loss of stature in postmenopausal women. SUMMARY OF BACKGROUND DATA Loss of stature with aging is known to deteriorate health-related quality of life and has been implicated with increased mortality. Although the association of vertebral fracture with height loss has been well documented, the relationship between stature loss and spinal osteoarthritis remains unclear. METHODS We retrospectively investigated Japanese postmenopausal women recruited from the Nagano Cohort Study. The participants were outpatients at a primary care institute in Nagano prefecture, Japan. A total of 977 postmenopausal patients (mean age: 65.8 yr) completed a minimum of 1 year of follow-up, with an average observation period of 7.6 years. Quartile analysis on the prevalence of spinal osteoarthritis and occurrence of incident fracture was performed based on the rate of stature change per year (Δ cm/yr). Multiple regression analysis was also conducted to identify the determinants of stature change. RESULTS The lower quartiles of stature change rate (i.e., more rapid stature loss) displayed a significantly higher prevalence of spinal osteoarthritis (P < 0.001) and incident vertebral fracture (P < 0.001). A statistically significant independent negative association for spinal osteoarthritis prevalence with change in stature was revealed by multiple regression analysis after adjusting for confounders including incident vertebral fracture. The partial regression coefficient for spinal osteoarthritis was -0.18 (95% confidence interval -0.33 to -0.03; P = 0.016). CONCLUSION This study demonstrated an independent association of spinal osteoarthritis with stature loss in postmenopausal women. Adequate understanding of this relationship and appropriate treatment approaches will help improve health-related quality of life in elderly patients. LEVEL OF EVIDENCE 3.
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Effect of Health-Promoting Lifestyle Modification Education on Knowledge, Attitude, and Quality of Life of Postmenopausal Women.
Rathnayake, N, Alwis, G, Lenora, J, Mampitiya, I, Lekamwasam, S
BioMed research international. 2020;:3572903
Abstract
Limited knowledge and negative attitudes about menopause among postmenopausal women (PMW) create a multitude of health-related issues leading to impaired quality of life (QOL) among them. This study evaluated the impact of a health-promoting lifestyle education intervention (HPLEI) on knowledge, attitude, and QOL in a group of PMW in Sri Lanka. A quasi-experimental study was conducted with 72 PMW, matched for sociodemographic status of the community from two geographically separated areas in Galle, and they were allocated to intervention (n = 37) and control (n = 35) groups. HPLEI is comprised of health education sessions focused on postmenopausal health management with lifestyle modifications provided only for the intervention group for 8 weeks and follow-up for 6 months. The control group was not given any planned education programme and was allowed to proceed with the usual lifestyle during this period. Knowledge, attitude, menopause-specific QOL (MENQOL), and overall QOL were evaluated in both groups with self-administered questionnaires at the baseline, after 8 weeks of education sessions and at the end of 6 months of follow-up. The mean (SD) ages of the intervention and control groups were 54.6 (4.5) and 56.5 (3.4) (p = 0.06) years, respectively. All evaluated variable scores were not different between the intervention and control groups (p > 0.05) at the baseline. In the intervention group, knowledge (mean ± SD; 21.70 ± 1.05) and attitude (mean ± SD; 44.02 ± 5.33) scores increased at the end (p < 0.001). In the control group, a marginal increase in all dimensions of knowledge scores (mean ± SD; 9.71 ± 2.21) and unchanged attitude scores (mean ± SD; 23.91 ± 7.56) were seen. All MENQOL scores decreased during the follow-up in the intervention group (mean ± SD; 138.51 ± 18.47) (p < 0.001) except the sexual domain (p = 0.32). MENQOL scores were increased in the control group (mean ± SD; 92.05 ± 28.87) (p < 0.001) with time. Overall QOL scores increased (mean ± SD; 74.85 ± 9.71) (p < 0.001) in the intervention group during the study period and in the control group overall QOL (mean ± SD; 51.03 ± 13.61) showed a reduction (p < 0.001) at the end. Health education focused on health-promoting lifestyle modifications was effective in improving knowledge, attitude, MENQOL, and overall QOL of PMW.
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The synergistic effects of vitamin D and estradiol deficiency on metabolic syndrome in Chinese postmenopausal women.
Huang, H, Guo, J, Chen, Q, Chen, X, Yang, Y, Zhang, W, Liu, Y, Chen, X, Yang, D
Menopause (New York, N.Y.). 2019;(10):1171-1177
Abstract
OBJECTIVE Recent studies show that vitamin D (VitD) deficiency is associated with metabolic syndrome (MetS). Current evidence suggests that estrogen and VitD have similar physiological functions and potentially interact with bone health. We investigated the association between estradiol (E2) and 25-hydroxyvitamin-D [25(OH)D] with MetS and its components in Chinese postmenopausal women. METHODS In this cross-sectional study, we examined 616 postmenopausal women (aged 49-86 y) from southern China who were not taking estrogen and VitD/calcium supplements. At the end of data collection, serum E2 and 25(OH)D were measured for each participant. MetS was defined according to the 2006 International Diabetes Federation standard. RESULTS There was a positive correlation between 25(OH)D and E2. Higher 25(OH)D was associated with a favorable lipid profile, blood pressure, and glucose level. E2 was negatively associated with cholesterol, triglycerides, and blood pressure. The odds ratio for MetS was 2.19 (95% CI, 1.19-4.01, P value for trend=0.009) for deficient compared with sufficient women after multivariable adjustment. This association remained unchanged after further adjusting for E2 levels. After stratified analysis by VitD status, low E2 increased MetS risk in women with VitD deficiency (odds ratio = 3.49, 95% CI, 1.45-8.05 for the lowest vs the highest tertile). CONCLUSIONS These results suggest a synergistic role of VitD and E2 deficiency in MetS in Chinese postmenopausal women.
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Physical activity and weight gain after smoking cessation in postmenopausal women.
Luo, J, Manson, JE, Hendryx, M, Shadyab, AH, Johnson, KC, Dinh, PC, Going, SB, Chlebowski, R, Stefanick, ML, Margolis, KL
Menopause (New York, N.Y.). 2019;(1):16-23
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OBJECTIVE Weight gain frequently occurs after smoking cessation. The objective of this study was to examine whether weight gain after smoking cessation was attenuated by physical activity (PA) in postmenopausal women. METHODS A total of 4,717 baseline smokers from the Women's Health Initiative were followed for 3 years. One thousand two hundred eighty-two women quit smoking, and 3,435 continued smoking. Weight was measured at baseline and at the year 3 visit. PA was assessed at both times by self-report, summarized as metabolic equivalent task-hours per week. Multiple linear regression models were used to assess the association between PA and postcessation weight gain, adjusting for potential confounding factors. RESULTS Compared with continuing smokers, quitters gained an average of 3.5 kg (SD = 5.6) between the baseline and year 3 visit. Quitters with decreased PA had the highest amount of weight gain (3.88 kg, 95% CI: 3.22-4.54); quitters with increased PA (≥15 metabolic equivalent task-hours /week) had the lowest weight gain (2.55 kg, 95% CI: 1.59-3.52). Increased PA had a stronger beneficial association for postcessation weight gain for women with obesity compared to normal weight women. Quitters who had low PA at baseline and high PA at year 3 and were also enrolled in a dietary modification intervention had nonsignificant weight gain (1.88 kg, 95% CI: -0.21-3.96) compared with continuing smokers. CONCLUSIONS Our data demonstrate that even a modest increase in PA (equivalent to current recommendations) can attenuate weight gain after quitting smoking among postmenopausal women, especially in combination with improved diet.
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Racial/Ethnic Differences in 25-Hydroxy Vitamin D and Parathyroid Hormone Levels and Cardiovascular Disease Risk Among Postmenopausal Women.
Zhang, X, Tu, W, Manson, JE, Tinker, L, Liu, S, Cauley, JA, Qi, L, Mouton, C, Martin, LW, Hou, L, et al
Journal of the American Heart Association. 2019;(4):e011021
Abstract
Background Recent evidence suggests that racial/ethnic differences in circulating levels of free or bioavailable 25-hydroxy vitamin D (25[ OH ]D) rather than total 25( OH )D may explain apparent racial disparities in cardiovascular disease ( CVD ). We prospectively examined black-white differences in the associations of total, free, and bioavailable 25( OH )D, vitamin D-binding protein, and parathyroid hormone levels at baseline with incident CVD (including nonfatal myocardial infarction, nonfatal stroke, and CVD death) in postmenopausal women. Methods and Results We conducted a case-cohort study among 79 705 postmenopausal women, aged 50 to 79 years, who were free of CVD at baseline in the WHI-OS (Women's Health Initiative Observational Study). A subcohort of 1300 black and 1500 white participants were randomly chosen as controls; a total of 550 black and 1500 white women who developed incident CVD during a mean follow-up of 11 years were chosen as cases. We directly measured total 25( OH )D, vitamin D-binding protein, albumin, parathyroid hormone, and calculated free and bioavailable 25( OH )D. Weighted Cox proportional hazards models were used to examine their associations with CVD risk. Although vitamin D-binding protein and total, free, and bioavailable 25( OH )D were not significantly associated with CVD risk in black or white women, a significant positive association between parathyroid hormone and CVD risk persisted in white women (hazard ratio comparing the highest quartile with the lowest, 1.37; 95% CI , 1.06-1.77) but not in black women (hazard ratio comparing the highest quartile with the lowest, 1.12; 95% CI, 0.79-1.58), independent of total, free, and bioavailable 25( OH )D or vitamin D-binding protein. Conclusions Circulating levels of vitamin D biomarkers are not related to CVD risk in either white or black women. Higher parathyroid hormone levels may be an independent risk factor for CVD in white women.