No association between the vitamin D pathway gene polymorphisms and bone biomarkers response to calcium and low dose calcitriol supplementation in postmenopausal Chinese women: a one-year prospective study

Abstract

Introduction: The aim of the study was to explore the association between the vitamin D pathway gene variations and the bone biomarkers response to calcium and low dose calcitriol supplementation in postmenopausal Chinese women.

Methods: A total of 110 healthy postmenopausal Chinese women (61.51?±?6.93?years) were enrolled. The participants were supplemented with calcium (600?mg/d) and calcitriol (0.25?μg/d), for 1?year. Four biomarkers, serum levels of beta C-terminal cross-linked telopeptides of type I collagen (β-CTX), amino-terminal propeptide of type I collagen (P1NP), parathyroid hormone (PTH) and 25-hydroxyvitamin D [25(OH)D] were measured at baseline and 12-month follow-up. Multivariate regression models were established to explore the statistical association between the change rate of the four biomarkers and 15?key genes within the vitamin D metabolic pathway.

Results: This exclusion process left 98 participants for analysis. Serum levels of P1NP, β-CTX and PTH were significantly decreased at the 12-month follow-up (all p?<?0.05). Serum 25(OH)D level had no significant change (p?>?0.05). No association was found between the vitamin D pathway gene polymorphisms and bone biomarkers response to calcium and low dose calcitriol supplementation.

Conclusions: Genetic background of postmenopausal Chinese women might not influence supplemental response of the biomarkers to calcium and low dose calcitriol.     

Breast cancer risk and the interaction between adolescent body size and weight gain in later life: A case-control study

BackgroundWhile the breast cancer risk associated with increasing adult BMI in postmenopausal women can be explained by increases in concentrations of endogenous estrogens the biologic mechanisms behind the inverse association between adolescent BMI and breast cancer risk are still a subject of controversial debate.MethodsWe investigated the association of breast cancer with body size and changes in body size across life time estimated by age-specific BMI Z scores and changes in BMI Z scores from teenage years to middle age in an age-matched population-based case-control study of 2994 Australian women. Logistic regression adjusted for the matching factor age and further potential confounders was used.ResultsAdolescent body leanness in postmenopausal women and excess adult weight gain in all study participants were associated with an increased breast cancer risk with an odds ratio [95% confidence interval] of 1.29 [1.08,1.54] and 1.31 [1.09,1.59], respectively. Interaction analyses restricted to postmenopausal women revealed an increased risk of breast cancer in those who were lean during adolescence and gained excess weight during adulthood (odds ratio [95% confidence interval]: 1.52 [1.19,1.95]) but not in women who were lean during adolescence and did not gain excess weight during adulthood (1.20 [0.97,1.48]) and not in women who were not lean during adolescence and but gained excess weight during adulthood (1.10 [0.95,1.27]) compared to postmenopausal women who were neither lean during adolescence nor gained excess weight.ConclusionIn postmenopausal women adolescent leanness was only associated with increased breast cancer risk when excess weight was gained during adulthood.     

Serum Estradiol Correlates With Benign Paroxysmal Positional Vertigo in Postmenopausal Women

BackgroundA high incidence of benign paroxysmal positional vertigo (BPPV) is reported in postmenopausal women, and the association between estradiol (E2) deficiency and the occurrence of BPPV was investigated.MethodsPostmenopausal women with and without BPPV were included from 2016 to 2019, and 1-year follow-up was performed. Serum otolin-1 and E2 levels were assayed before the canalith repositioning treatment. Bone mineral density (BMD) was measured with a dual-energy x-ray absorptiometry scan. Receiver operating characteristic analysis was performed to determine the occurrence of BPPV, and Pearson analysis was performed to indicate the correlation between E2, otolin-1, and BMD.ResultsEighty-six postmenopausal women with BPPV and 80 age-, demographics-, and clinical characteristics-matched normal postmenopausal women were enrolled. Decreased E2 levels, increased otolin-1 levels, and decreased BMD were observed in postmenopausal women with BPPV, and increased BMD and decreased otolin-1 levels were observed in patients with higher levels of serum E2. Receiver operating characteristic analysis revealed that E2, otolin-1, and BMD showed low sensitivity and moderate specificity to determine the occurrence of BPPV. On the other hand, a low correlation coefficient was found between E2 and otolin-1, or BMD. It is worth noting that low E2 levels were found in the relapsed patients with BPPV after a 1-year follow-up.ConclusionE2 deficiency is correlated with the occurrence of BPPV, which may be a potential risk biomarker for postmenopausal women.     

Association of T869C gene polymorphism of transforming growth factor-β1 with low protein levels and anthropometric indices in osteopenia/osteoporosis postmenopausal Thai women

Osteoporosis is the most common metabolic bone disease; it is an important health problem among postmenopausal women. We evaluated the association of three polymorphisms, T869C, C-509T and G915C, of the TGF-β1 gene with bone mineral density (BMD) serum TGF-β1 levels in 278 postmenopausal female osteopenia/osteoporosis subjects and 95 postmenopausal female control subjects. Serum TGF-β1 levels were significantly lower in osteopenia/osteoporosis subjects than in control subjects. Serum TGF-β1 levels of the CT+CC (T869C) genotype group were significantly lower in osteopenia/osteoporosis subjects than in control subjects (11.3 vs 15.8 ng/mL). There was a significant difference in the CT+CC (T869C) genotype frequencies between the osteopenia/osteoporosis and control subjects (74.18 vs 60.22%; OR = 1.90, 95%CI = 1.16-3.12). In the age group of more than 50 years, subjects with the TC+CC genotype of T869C polymorphism had significantly increased risk of osteopenic/ osteoporotic bones at L1 (OR = 2.36, 95%CI = 1.37-4.07), L2 (OR = 1.71, 95%CI = 1.01-2.90), L3 (OR = 2.21, 95%CI = 1.23-3.98), L4 (OR = 1.74, 95%CI = 1.00-3.03) and the femoral neck (OR = 1.80, 95%CI = 1.04-3.12). The CT+CC genotype of the T869C polymorphism of the TGF-β1 gene was found to be associated with lower serum TGF-β1 in osteopenia/osteoporosis subjects and increased risk of osteopenic and osteoporotic fracture at L1-4, femoral neck and total hip in postmenopausal Thai women. Logistic regression analysis showed that T869C polymorphism is a significant risk factor for osteopenia/ osteoporosis. We concluded that T869C polymorphism of the TGF-β1 gene has an impact on decreased serum TGF-β1 levels and influences susceptibility to osteopenia/osteoporosis in Thai women.     

Reproductive and external hormonal factors and the risk of renal cell cancer in the Netherlands Cohort Study

BackgroundSeveral reproductive and hormonal factors, like age at menarche, parity, age at menopause, use of oral contraceptives and postmenopausal treatment, have been associated with the risk of renal cell cancer (RCC) in women, but results have not always been consistent. We therefore investigated the association between these factors and the risk of RCC in postmenopausal women participating in the Netherlands Cohort Study on Diet and Cancer.MethodsInformation on reproductive history, exogenous hormone use and gynecological surgery was obtained through a self-administered questionnaire at baseline in 1986. After 20.3 years of follow-up, 204 cases and 2280 subcohort members were available for case-cohort analysis. Multivariable hazard ratios (HR) were calculated using Cox Proportional Hazard analysis.ResultsWomen who reported a hysterectomy had an increased RCC risk compared to women who did not (HR, 1.42, 95%CI, 1.01–2.00). Women with a natural age at menopause between 45 and 49 years compared to 50–54 years had an increased RCC risk (HR, 1.61; 95%CI, 1.10–2.35). RCC risk was slightly and not statistically significant increased among parous women with three or more children and age at first birth before 25 years compared to nulliparous women (HR, 1.36; 95% confidence interval (CI), 0.84–2.20). No associations were observed with RCC risk for age at menarche, use of oral contraceptives and use of hormonal replacement therapy.ConclusionHysterectomy and age at natural menopause were associated with an increased RCC risk. Other hormonal and reproductive factors and RCC risk were not increased. Further studies are required to establish the mechanism(s) that explain the observed association.     

Association of CYP19 Gene Polymorphism with Vertebral Fractures in Japanese Postmenopausal Women

This study investigates aromatase gene polymorphism, which might influence bone strength in terms of mineral density and quality. We explored the relationship between CYP19 polymorphisms and vertebral fractures in postmenopausal Japanese women. In addition, we compared estrogen and testosterone levels in Japanese postmenopausal women with and without fractures. Osteoporotic postmenopausal women showed higher incidences of vertebral fractures than osteopenic women or women with normal lumbar bone mineral density (L2-4 BMD). Estrogen concentrations in postmenopausal women were associated with BMD; however, no association was found between sex hormone levels and the presence of fractures. The C allele rs2470152 was significantly associated with increased risk of vertebral fractures (P = 0.04), whereas none of the CYP19 polymorphisms showed differences in sex steroid levels between subjects with and without fractures. Allelic variants of aromatase genes appear to interact to influence the risk of vertebral fractures in postmenopausal Japanese women.     

Investigation of the common paraoxonase 1 variants with paraoxonase activity on bone fragility in Turkish patients

There is increasing evidence of a biochemical link between oxidative stress and bone metabolism. Oxidative stress has been shown to be involved in bone resorption as it causes loss of bone mineral density (BMD). Paraoxonase 1 (PON1), can prevent these effects of the oxidative stress on bone formation. It has been suggested that the PON1 gene as possibly implicated in reduced BMD in bone fragility cases. It has been hypothesized that PON1 gene polymorphisms may influence both the risk of osteoporosis and osteopenia occurrence and prognosis. The aim of our study is to evaluate the relationship between PON1 polymorphisms and bone fragility development. Seventy-four osteoporotic, 121 osteopenic and 79 nonosteoporotic postmenopausal women were recruited. For detection of the polymorphisms, polymerase chain reaction-restriction fragment length polymorphism techniques have been used. BMD was measured at the lumbar spine and hip by dual-energy X-ray absorptiometry. Distributions of PON1 (PON 192 and PON 55) polymorphisms in study groups were not significantly different. But, there was medium strength connection between in the osteopenic with control groups regarding PON1 55–PON1 192 haplotypes and we found a power strength connection between in the osteoporosis with control groups regarding PON1 55–PON1 192 haplotypes. Furthermore, subjects with PON1 192RR and PON1 55LL genotypes had lower PON activity values of osteoporotic subject compared to healthy control and this difference was statistically significant (p < 0.05). This result suggest that PON1 genotypes could be higher risk for osteoporosis, as determined by reduced BMD.     

The Relationship between Serum Ferritin Levels and Insulin Resistance in Pre- and Postmenopausal Korean Women: KNHANES 2007–2010

BackgroundSerum ferritin levels increase in postmenopausal women, and they are reported to be linked to major health problems. Here, we investigated the association between serum ferritin levels and insulin resistance (IR) in postmenopausal women.MethodsA total of 6632 healthy Korean women (4357 premenopausal and 2275 postmenopausal) who participated in the Korean National Health and Nutrition Examination Survey (KNHANES) in 2007–2010 were enrolled in the study. Serum ferritin values were divided into six groups for the premenopausal and postmenopausal groups. IR and obesity indices were evaluated according to the six serum ferritin groups. Statistical analysis was carried out using SAS software, version 9.2 (SAS Institute Inc., Cary, NC, USA).ResultsThe association between the IR indices and ferritin groups had a higher level of statistical significance in the postmenopausal group than in the premenopausal group. In addition, for the postmenopausal group, the estimates increased significantly in the sixth ferritin group compared to those in the first ferritin group. However, the association between the obesity indices and ferritin levels was not significantly different between the premenopausal and postmenopausal groups.ConclusionElevated serum ferritin levels were associated with an increased risk of insulin resistance in postmenopausal women.     

Reproductive factors,exogenous hormone use,and risk of pancreatic cancer in postmenopausal women

IntroductionThe epidemiologic literature on menstrual and reproductive factors associated with pancreatic cancer has yielded weak and inconsistent evidence of an association. Furthermore, few cohort studies have examined the association of exogenous hormone use, including type and duration, with this disease. The aim of this study was to assess the association of these exposures with risk of pancreatic cancer in a large cohort of postmenopausal women.MethodsWe used data from the Women’s Health Initiative on 1003 cases of pancreatic cancer diagnosed among 158,298 participants over 14.3 years of follow-up. Cox proportional hazards models were used to estimate hazard ratios (HR) and 95% confidence intervals (95% CI) for the associations of interest.ResultsBeing parous vs. nulliparous was associated with reduced risk (HR = 0.84, 95% CI 0.70–1.00), and women who had 1–2 and 3–4 births were at decreased risk compared to nulliparous women, whereas women who had >5 births showed no decrease in risk. Compared to women who gave birth between the ages of 20–29, women who gave birth at age 30 or above were at increased risk (HR 1.23, 95% CI 1.00–1.53, p for trend 0.003). Other reproductive factors and exogenous hormone use were not associated with risk.ConclusionsTogether with the existing literature on this topic, our results suggest that reproductive and hormonal exposures are unlikely to play an important role in the etiology of pancreatic cancer.     

Comparing auditory,visual and vibrotactile cues in individuals with Parkinson’s disease for reducing risk of falling over different types of soil

Introduction: Several researchers have demonstrated the positive benefits of auditory and visual cueing in the gait improvements among individuals with Parkinson’s disease (PD). However, few studies have evaluated the role of vibrotactile cueing when compared to auditory and visual cueing. This paper compares how these stimuli affect the risk of falling while walking on six types of soil (concrete, sand, parquet, broken stone, two types of carpet).

Methods: An instrumented Timed Up and Go (iTUG) test served to evaluate how audio, visual and vibrotactile cueing can affect the risk of falling of elderly. This pilot study proposes 12 participants with PD (67.7?±?10.07?years) and nine age-matched controls (66.8?±?8.0?years). Both groups performed the iTUG test with and without cueing. The cueing frequency was set at 10% above the cadence computed at the lower risk level of falling (walking over the concrete). A computed risk of falling (ROFA) index has been compared to the TUG time (total TUG duration).

Results: The index for evaluating the risk of falling appears to have a good reliability (ICC >?0.88) in this pilot study. In addition, the minimal detectable change (MDC) suggests that the proposed index could be more sensitive to the risk of falling variation compared to the TUG time. Moreover, while using the cueing, observed results suggest a significant decrease in the computed risk of falling compared to ‘without cueing’ for most of types of soil, especially for deformable soils, which can lead to falls.

Conclusion: When compared to other cueing, it seems that audio could be a better neurofeedback for reducing the risk of falling over different walking surfaces, which represent important risk factors for persons with gait disorder or lost functional autonomy.     

Uso de sujeciones físicas en relación con el riesgo de caídas en una residencia de ancianos

Backgrounds and objectivesThe use of physical restraints (PR) is common in the care of the elderly. However, their efficacy and safety are not supported by scientific evidence. The aim of this study was to determine the role of PR in preventing falls.Materials and methodsA retrospective cohort study design was used, in which each fall incident (n = 575) was examined in the residents over 65 years of age who resided at the one nursing homes from February 2009 to September 2013. An analysis was made of the association between the use of PR and risk of falls using a multivariate logistic regression, adjusting for the characteristics of residents that were associated with the use of PR according to a bivariate analysis.ResultsRisk factors for falls after accounting for PR use, include: risk of falling (Tinetti test) (OR 4.57; 95% CI 1.76-11.75); ability to walk (OR 6.40; 95% CI 2.78-14.74); hearing impairment (OR 2.12; 95% CI 1.05-4.29); and history of a previous fall (OR 17.81; 95% CI 8.83-35.93). The risk of falls was greater in restrained, ambulatory residents with cognitive impairment (OR 18.95; 95% CI 7.06-50.85). No differences were found in injuries between falls that occurred with and without PR.ConclusionsRestraint use was not significantly associated with fewer falls and injuries. The risk of falls could increase in ambulatory residents with cognitive impairment. The study results suggest the need to consider whether restraints provide adequate protection against the risk of falls.     

Linkage of osteoporosis to chromosome 20p12 and association to BMP2

Osteoporotic fractures are a major cause of morbidity and mortality in ageing populations. Osteoporosis, defined as low bone mineral density (BMD) and associated fractures, have significant genetic components that are largely unknown. Linkage analysis in a large number of extended osteoporosis families in Iceland, using a phenotype that combines osteoporotic fractures and BMD measurements, showed linkage to Chromosome 20p12.3 (multipoint allele-sharing LOD, 5.10; p value, 6.3 × 10⁻⁷), results that are statistically significant after adjusting for the number of phenotypes tested and the genome-wide search. A follow-up association analysis using closely spaced polymorphic markers was performed. Three variants in the bone morphogenetic protein 2 (BMP2) gene, a missense polymorphism and two anonymous single nucleotide polymorphism haplotypes, were determined to be associated with osteoporosis in the Icelandic patients. The association is seen with many definitions of an osteoporotic phenotype, including osteoporotic fractures as well as low BMD, both before and after menopause. A replication study with a Danish cohort of postmenopausal women was conducted to confirm the contribution of the three identified variants. In conclusion, we find that a region on the short arm of Chromosome 20 contains a gene or genes that appear to be a major risk factor for osteoporosis and osteoporotic fractures, and our evidence supports the view that BMP2 is at least one of these genes.     

Linkage of Osteoporosis to Chromosome 20p12 and Association to BMP2

Osteoporotic fractures are a major cause of morbidity and mortality in ageing populations. Osteoporosis, defined as low bone mineral density (BMD) and associated fractures, have significant genetic components that are largely unknown. Linkage analysis in a large number of extended osteoporosis families in Iceland, using a phenotype that combines osteoporotic fractures and BMD measurements, showed linkage to Chromosome 20p12.3 (multipoint allele-sharing LOD, 5.10; p value, 6.3 × 10⁻⁷), results that are statistically significant after adjusting for the number of phenotypes tested and the genome-wide search. A follow-up association analysis using closely spaced polymorphic markers was performed. Three variants in the bone morphogenetic protein 2 (BMP2) gene, a missense polymorphism and two anonymous single nucleotide polymorphism haplotypes, were determined to be associated with osteoporosis in the Icelandic patients. The association is seen with many definitions of an osteoporotic phenotype, including osteoporotic fractures as well as low BMD, both before and after menopause. A replication study with a Danish cohort of postmenopausal women was conducted to confirm the contribution of the three identified variants. In conclusion, we find that a region on the short arm of Chromosome 20 contains a gene or genes that appear to be a major risk factor for osteoporosis and osteoporotic fractures, and our evidence supports the view that BMP2 is at least one of these genes.     

Birth weight,adult body size,and risk of colorectal cancer

BackgroundEvidence suggests that birth weight may be associated with colorectal cancer (CRC) risk later in life. Whether the association is mediated by adult body size remains unexamined.MethodCox proportional hazards models (Hazard Ratio (HR) and 95 % Confidence Intervals (CI)) were used to evaluate the association between self-reported birth weight (<6 lbs, 6-<8 lbs, ≥8 lbs) and CRC risk among 70,397 postmenopausal women from the Women’s Health Initiative. Further, we assessed whether this association was mediated by adult body size using multiple mediation analyses.ResultsCompared with birth weights of 6-< 8 lbs, birth weight ≥ 8 lbs was associated with higher CRC risk in postmenopausal women (HR = 1.31, 95 % CI 1.16–1.48). This association was significantly mediated by adult height (proportion mediated =11.4 %), weight (11.2 %), waist circumference (10.9 %), and body mass index at baseline (4.0 %). The joint effect of adult height and weight explained 21.6 % of this positive association.ConclusionOur data support the hypothesis that the intrauterine environment and fetal development may be related to the risk of developing CRC later in life. While adult body size partially explains this association, further investigation is required to identify other factors that mediate the link between birth weight and CRC.     

Levothyroxine Liquid Solution Versus Tablet for Replacement Treatment in Hypothyroid Patients

BackgroundAlthough replacement treatment with L-thyroxine (LT4) seems easy to manage, about one-third of hypothyroid patients show thyroid-stimulating hormone (TSH) values outside the normal range.ObjectivesTo explore whether LT4 liquid formulation (monodose vials or drops) affects TSH stability values and to assess its ability to maintain TSH within the normal range compared to tablets.MethodsA total of 100 hypothyroid patients on replacement treatment with LT4 liquid solution were enrolled (Liquid Group) at a follow-up visit (revisit). The inclusion criteria were 1) treatment for surgical hypothyroidism for at least 2 years or autoimmune hypothyroidism for at least 5 years, 2) normal TSH at the previous visit 12 months before enrollment (baseline visit), and 3) maintenance of the same LT4 dosage during the time interval between the baseline and the follow-up visit. Using the same selection process, we also enrolled 100 hypothyroid patients on replacement treatment with LT4 tablets (Tablet Group).ResultsAt the follow-up visit, 19 patients of the Tablet Group and 8 patients of the Liquid Group had abnormal TSH values (P = .023). Weekly and daily LT4 dosage per kilogram were higher in Tablet Group (P = .016 and .006, respectively). The magnitude of TSH change from baseline to follow-up visit was greater in the Tablet Group (P < .001).ConclusionThe use of LT4 liquid formulation compared to tablet resulted in a significantly higher number of hypothyroid patients who maintained the euthyroid state in a 12-month follow-up period and a reduced variability in TSH values. (Endocr Pract. 2014;20:901-906)     

Predicting Falls in Parkinson Disease: What Is the Value of Instrumented Testing in OFF Medication State?

BackgroundFalls are a common complication of advancing Parkinson''s disease (PD). Although numerous risk factors are known, reliable predictors of future falls are still lacking. The objective of this prospective study was to investigate clinical and instrumented tests of balance and gait in both OFF and ON medication states and to verify their utility in the prediction of future falls in PD patients.MethodsForty-five patients with idiopathic PD were examined in defined OFF and ON medication states within one examination day including PD-specific clinical tests, instrumented Timed Up and Go test (iTUG) and computerized dynamic posturography. The same gait and balance tests were performed in 22 control subjects of comparable age and sex. Participants were then followed-up for 6 months using monthly fall diaries and phone calls.ResultsDuring the follow-up period, 27/45 PD patients and 4/22 control subjects fell one or more times. Previous falls, fear of falling, more severe motor impairment in the OFF state, higher PD stage, more pronounced depressive symptoms, higher daily levodopa dose and stride time variability in the OFF state were significant risk factors for future falls in PD patients. Increased stride time variability in the OFF state in combination with faster walking cadence appears to be the most significant predictor of future falls, superior to clinical predictors.ConclusionIncorporating instrumented gait measures into the baseline assessment battery as well as accounting for both OFF and ON medication states might improve future fall prediction in PD patients. However, instrumented testing in the OFF state is not routinely performed in clinical practice and has not been used in the development of fall prevention programs in PD. New assessment methods for daylong monitoring of gait, balance and falls are thus required to more effectively address the risk of falling in PD patients.     

Healthy lifestyle and breast cancer risk: A case-control study in Morocco

BackgroundSome modifiable risk factors have been independently associated with breast cancer (BC) risk in Moroccan women, but no studies have investigated their joint association. This study aimed to investigate the association between a Healthy Lifestyle Index (HLI) score and BC risk among Moroccan women.MethodsIn this case–control study, 300 incident BC cases and 300 controls, matched by age and area of residence were recruited. Cases were women newly-diagnosed with histopathologically–confirmed BC at the University Hospital in Fez, Morocco. Controls were randomly selected healthy women recruited from 6 primary health centers in Fez. HLI scores developed within this study were assigned to participants based on 11 factors (red and processed meat, white meat, cream, cheese, fish, fruit and vegetables, physical activity, BMI, smoking, alcohol consumption, and breastfeeding), where 0 was given to unhealthy and 0.5 or 1 to healthy levels of each factor. Conditional and unconditional logistic regression models were used to assess the association between HLI scores and BC risk.ResultsMean of HLI scores were 8.1 (±1.1) and 9.0 (±0.9) in cases and controls, respectively, p < 0.01. After adjusting for potential confounders, one-point increment in the HLI score was associated with 56% (95% CI, CI: 39–68%), 49% (95% CI: 30–63%), and 59% (95% CI: 40–72%) lower risks of BC in all, premenopausal, and postmenopausal women, respectively.ConclusionHigh HLI scores were associated with decreased risk of BC in Moroccan women. These findings suggest that BC prevention policies should include strategies for engaging Moroccan women in healthy lifestyles.     

Risk factors for breast cancer in women biopsied for benign breast disease: A nested case-control study

Aim: Women with a history of benign breast disease are at increased risk of subsequent breast cancer. However, few studies have examined whether established breast cancer risk factors other than histology are associated with an altered risk of breast cancer in women with benign breast disease. We used a nested case-control design within a large, multi-center cohort of women biopsied for benign breast disease (BBD) to estimate odds ratios for breast cancer in association with exposure to a range of personal and lifestyle factors. Methods: Cases were women biopsied for BBD who subsequently developed breast cancer; controls were individually matched to cases on center and age at diagnosis and were women biopsied for BBD who did not develop breast cancer in the same follow-up interval as that for the cases. After excluding women with prevalent breast cancer, 1357 records (661 case records and 696 records) were available for analysis. We used conditional logistic regression to obtain crude and multivariable-adjusted estimates of the association between specific factors and risk of breast cancer. Results: In multivariable analyses age at first live birth, number of pregnancies, and postmenopausal status were inversely associated with risk of breast cancer. The odds ratio for women with age at first birth <25 years and ≥3 pregnancies, relative to nulliparous women, was 0.49, 95% confidence interval 0.13–0.79, and that for postmenopausal women relative to premenopausal women was 0.60, 95% CI 0.37–0.99. Conclusions: Further study of personal factors influencing the risk of breast cancer in women with BBD may help to identify subgroups of the population at increased risk of invasive disease.     

Evaluation of <Emphasis Type="Italic">ERα</Emphasis> and <Emphasis Type="Italic">VDR</Emphasis> gene polymorphisms in relation to bone mineral density in Turkish postmenopausal women

It has been suggested that the estrogen receptor alpha (ERα) and vitamin D receptor (VDR) genes as possibly implicated in reduced bone mineral density (BMD) in osteoporosis. The present study investigated the relation of ERα PvuII/XbaI polymorphisms and VDR FokI/TaqI polymorphisms with BMD in Turkish postmenopausal women. Eighty-one osteoporotic and 122 osteopenic postmenopausal women were recruited. For detection of the polymorphisms, polymerase chain reaction-restriction fragment lenght polymorphism techniques have been used. BMD was measured at the lumbar spine and hip by dual-energy X-ray absorptiometry. Distributions of ERα (PvuII dbSNP: rs2234693, XbaI dbSNP: rs9340799) and VDR genotypes (FokI dbSNP rs10735810, TaqI dbSNP: rs731236) were similar in study population. Although overall prevalence of osteoporosis had no association with these genotypes, the prevalence of decreased femoral neck BMD values were higher in the subjects with ERα PvuII “PP” and ERα XbaI “XX” genotypes than in those with “Pp/pp” genotypes and “xx” genotype, respectively (P < 0.05). Furthermore, subjects with VDR FokI “FF” genotype had lower BMD values of femoral neck and total hip compared to those with “Ff” genotype (P < 0.05). In the logistic regression analysis, we confirmed the presence of relationships between the VDR FokI “FF” genotypes, BMI ≤ 27.5, age ≥ 55 and the increased risk of femoral neck BMD below 0.8 value in postmenopausal women. The present data suggests that the ERα PvuII/XbaI and VDR FokI polymorphisms may contribute to the determination of bone mineral density in Turkish postmenopausal women.     

Estudio de la evolución del síndrome de temor a caerse entre pacientes mayores con mareos,caídas y síncopes

Aimsto study fear of falling (FOF) syndrome at 1 year in a population of elderly individuals referred to a specific outpatient clinic for dizziness, falls and syncope. To analyse which variables gathered at the beginning of the study were related with FOF at that time and 1 year later.Methodsa prospective cohort study was performed from April 2000 to December 2001. Sixty-six elderly individuals referred to a specific outpatient clinic for dizziness, falls and syncope were classified in a group with FOF (n = 31) or a group without FOF (n = 35). Patients without all the tests and those lost to follow-up were excluded. The protocol included medical history, physical examination, tilt test and routine or specific complementary tests, when deemed necessary. FOF was determined through the direct question: Are you afraid of falling?ResultsFOF disappeared in 14 patients (45.2%) who had this syndrome at the beginning of the study and developed in five patients (14.3%) who did not (p = 0.06). After multivariate analyses, the variables associated with FOF at the beginning of the study were: taking benzodiazepines, recurrent dizziness, higher blood urea levels and a drop in systolic blood pressure with upright position. The variables significantly associated with fear of falling 1 year later were: angiotensin-converting enzyme inhibitors, positive Hallpike's manoeuvre and a drop in diastolic blood pressure with the head-up-tilt test. The model also included taking benzodiazepines and symptom reproduction with movement of the neck.Conclusionsat 1 year, FOF syndrome decreased in nearly half the patients who had this syndrome at the beginning of the study but developed in other patients without this syndrome at that time. No association was found with falls at the beginning or end of the study. At 1 year of follow-up, FOF was associated with intake of certain medications and data from the tilt test.