UNLABELLED: The strength of both femurs was estimated in 198 post-menopausal women through subject-specific finite element models. Important random differences between contralateral femurs were found in a significant number of subjects, pointing to the usefulness of further studies to understand if strength-based classification of patients at risk of fracture can be affected by laterality issues. INTRODUCTION: Significant, although small, differences exist in mineral density and anatomy of contralateral proximal femurs. These differences, and their combined effect, may result in a side difference in femurs' strength. However, this has never been tested on a large sample of a homogenous population. METHODS: The strength of both femurs was estimated in 198 post-menopausal women through CT-derived finite element models, built using a validated procedure, in sideways fall conditions. The impact of the resulting asymmetry on the classification of subjects at risk of fracture was analysed. RESULTS: The small difference observed between sides (the right femur on average 4 % stronger than the left) was statistically significant but mechanically negligible. In contrast, higher random differences (absolute difference between sides with respect to mean value) were found: on average close to 15 % (compared to 9.2 % for areal bone mineral density (aBMD) alone), with high scatter among the subjects. When using a threshold-based classification, the right and left femurs were discordant up to over 20 % of cases (K always lower than 0.60) but the left femur was concordant (mean K = 0.84) with the minimum strength between right and left. CONCLUSION: Considering both femurs may be important when trying to classify subjects at risk of failure with strength estimates. Future studies including fracture assessment would be necessary to quantify the real impact.

• Klíčová slova
• Computed tomography, Finite element, Multicentric study, Post-menopausal women, Proximal femur’s strength, Side differences,
• MeSH
• absorpční fotometrie metody   MeSH
• analýza metodou konečných prvků MeSH
• femur anatomie a histologie   diagnostické zobrazování   fyziologie   MeSH
• kostní denzita fyziologie   MeSH
• krček femuru anatomie a histologie   fyziologie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• počítačová rentgenová tomografie metody   MeSH
• postmenopauza fyziologie   MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• zatížení muskuloskeletálního systému fyziologie   MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• multicentrická studie MeSH
• práce podpořená grantem MeSH
• Research Support, N.I.H., Extramural MeSH
• Research Support, N.I.H., Intramural MeSH

BACKGROUND AND AIMS: Bone structure, geometry and mineral content represent complex traits with a significant heritable component. However, the specific contributing genes have not been unambiguously identified. The aim of the present cross-sectional study was to analyse an association between heel ultrasound measurements, partly reflecting bone quality, and VDR (Vitamin D receptor) gene polymorphisms in post-menopausal women, and to assess whether these associations differ from those of bone density or not. METHODS: BUA (broadband ultrasound attenuation, dB/MHz) at the right heel and BMD (bone mineral density, g/cm2) at the lumbar spine and hip were measured in 114 post-menopausal women of Caucasian origin (62.4 +/- 9.8 years). All probands were genotyped for common VDR polymorphisms--FokI, BsmI, Apal and TaqI--by restriction analysis of the PCR product. RESULTS: ANCOVA revealed significant associations between calcaneal BUA adjusted for BMI (body mass index) and YSM (years since menopause), and BsmI, Apal and TaqI genotypes in the VDR gene (p < 0.02; p < 0.0003; p < 0.02 ANCOVA, respectively). BMI- and YSM-adjusted BMD was significantly associated with Fokl genotypes in the VDR gene (p < 0.028 at lumbar spine, p < 0.007 at hip). CONCLUSIONS: The present data show that post-menopausal BMD and BUA are determined by different polymorphisms within the VDR gene. Non-coding polymorphisms in the 3' end of the VDR gene (BsmI, Apal, TaqI) are related to heel ultrasound while the FokI polymorphism in exon 2, located at the opposite site of the VDR gene, is associated with BMD measurements. Further studies are required to determine whether different polymorphic markers within a single gene independently determine various components of post-menopausal bone.

• MeSH
• genotyp MeSH
• kosti a kostní tkáň diagnostické zobrazování   MeSH
• kostní denzita * MeSH
• lidé MeSH
• polymorfismus genetický * MeSH
• postmenopauza metabolismus   MeSH
• receptory kalcitriolu genetika   MeSH
• senioři MeSH
• ultrasonografie MeSH
• Check Tag
• lidé MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• receptory kalcitriolu MeSH

The polymorphisms within the FTO gene play an important role in the genetic determination of body weight and body mass index and have been associated with cardiovascular disease, but the causal mechanism is still a matter of debate. The possible effect on the platelet count as a marker of hemocoagulation status as a possible cardiovascular risk factor was suggested in Japanese population. We have analyzed both rs1558902 FTO polymorphism (T > A) and platelet counts in the Prague Pre and Post Menopausal Females (3PMFs) study, including those of 669 women (mean age, 55.7 ± 2.7 years). The frequencies of the FTO genotypes were similar to other populations (TT, 30.4%; TA, 48.1%; and AA, 21.5%). We have not detected a significant association between the FTO rs1558902 variant and platelet counts in white women (TT, 242 ± 55 × 10; TA, 246 ± 67 × 10; and AA, 247 ± 55 × 10; F[2.642] = 0.30, P = 0.75). At least in white persons, platelet count seems not to be a link between the FTO variation and risk of cardiovascular disease.

• MeSH
• běloši genetika   MeSH
• gen pro FTO MeSH
• genetická predispozice k nemoci * MeSH
• jednonukleotidový polymorfismus * MeSH
• kardiovaskulární nemoci epidemiologie   genetika   MeSH
• lidé středního věku MeSH
• lidé MeSH
• počet trombocytů MeSH
• postmenopauza genetika   MeSH
• premenopauza genetika   MeSH
• proteiny genetika   MeSH
• rizikové faktory MeSH
• trombocyty MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Geografické názvy
• Česká republika epidemiologie   MeSH
• Názvy látek
• FTO protein, human MeSH Prohlížeč
• gen pro FTO MeSH
• proteiny MeSH

OBJECTIVE: High extracellular calcium concentration (Cao(2+)) acts to inhibit calcium sensing receptor (CaR) signalling on cellular surfaces in parathyroid glands. This receptor is, however, also expressed on the membranes of some non-calciotropic endocrine cells, including pituitary-derived cells. The aim of our study was to analyse relationships between the CaR gene and the circulating FSH and LH in normal post-menopausal women. METHODS: A total of 95 untreated euparathyroid post-menopausal women were investigated in the study. The serum FSH and LH levels were evaluated in relationship to allele combinations of the CaR gene (C/T polymorphism in the intron 5 and A986S polymorphism in exon 7), using an analysis of co-variance (ANCOVA) model. RESULTS: Distribution of TT, TC and CC allele combinations (intron 5 C/T polymorphism) was 51, 43 and 6 %, respectively. Higher serum FSH and LH levels were found in carriers of C allele than in women without this allele (p < 0.002 and p < 0.03, respectively). No correlations were found between A986S polymorphism and serum FSH and LH levels. CONCLUSIONS: Serum FSH and LH levels are associated with intron 5 C/T (but not A986S) polymorphism of the CaR gene in untreated post-menopausal women. The physiological role of the CaR gene in the regulation of the gonadotropic function needs to be further investigated.

• MeSH
• alely MeSH
• dospělí MeSH
• folikuly stimulující hormon krev   MeSH
• genotyp MeSH
• introny * MeSH
• lidé MeSH
• luteinizační hormon krev   MeSH
• polymorfismus genetický * MeSH
• postmenopauza * MeSH
• průřezové studie MeSH
• receptory "calcium-sensing" genetika   metabolismus   MeSH
• statistika jako téma MeSH
• vápník metabolismus   MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• folikuly stimulující hormon MeSH
• luteinizační hormon MeSH
• receptory "calcium-sensing" MeSH
• vápník MeSH

BACKGROUND: Impaired physical performance and muscle strength are recognized risk factors for fragility fractures, frequently associated with osteoporosis and sarcopenia. However, the integration of muscle strength and physical performance in the comprehensive assessment of fracture risk is still debated. Therefore, this cross-sectional study aimed to assess the potential role of hand grip strength (HGS) and short physical performance battery (SPPB) for predicting fragility fractures and their correlation with Fracture Risk Assessment Tool (FRAX) with a machine learning approach. METHODS: In this cross-sectional study, a group of postmenopausal women underwent assessment of their strength, with the outcome measured using the HSG, their physical performance evaluated using the SPPB, and the predictive algorithm for fragility fractures known as FRAX. The statistical analysis included correlation analysis using Pearson's r and a decision tree model to compare different variables and their relationship with the FRAX Index. This machine learning approach allowed to create a visual decision boundaries plot, providing a dynamic representation of variables interactions in predicting fracture risk. RESULTS: Thirty-four patients (mean age 63.8±10.7 years) were included. Both HGS and SPPB negatively correlate with FRAX major (r=-0.381, P=0.034; and r=-0.407, P=0.023 respectively), whereas only SPPB significantly correlated with an inverse proportionality to FRAX hip (r=-0.492, P=0.001). According to a machine learning approach, FRAX major ≥20 and/or hip ≥3 might be reported for an SPPB<6. Concurrently, HGS<17.5 kg correlated with FRAX major ≥20 and/or hip ≥3. CONCLUSIONS: In light of the major findings, this cross-sectional study using a machine learning model related SPPB and HGS to FRAX. Therefore, a precise assessment including muscle strength and physical performance might be considered in the multidisciplinary assessment of fracture risk in post-menopausal women.

• MeSH
• hodnocení rizik MeSH
• kostní denzita * fyziologie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• osteoporotické fraktury * epidemiologie   etiologie   MeSH
• postmenopauza MeSH
• průřezové studie MeSH
• rizikové faktory MeSH
• senioři MeSH
• síla ruky MeSH
• tělesná a funkční výkonnost MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

BACKGROUND: Bioelectric impedance analysis (BIA) is commonly used in research to assess body composition. However, studies that validate the accuracy of BIA exclusively in post-menopausal women are lacking. The main purpose of the present study was to evaluate the agreement of multi-frequency (MF)-BIA and single-frequency (SF)-BIA with dual-energy X-ray absorptiometry (DXA) in the estimation of fat mass (FM) and fat-free mass (FFM) among post-menopausal women with variation in body mass index (BMI) and physical activity (PA). METHODS: FM and FFM were estimated by BIA and DXA in 146 post-menopausal women with a mean (SD) age of 62.8 (5.2) years. PA was determined by an accelerometer. RESULTS: The mean (SD) difference between MF-BIA and DXA was -1.8 (1.8) kg (P = 0.08) and 1.3 (1.8) kg (P = 0.01) for FM and FFM, respectively. SF-BIA provided a significantly lower estimate of FM [-2.0 (2.2) kg; P = 0.04] and a higher estimate of FFM [1.8 (2.4) kg; P < 0.01] compared to DXA. MF-BIA provided significantly better estimates of FM and FFM with narrower limits of agreement than SF-BIA in obese and insufficiently active subjects. In other BMI and PA groups, both BIA devices showed a similar deviation from DXA. CONCLUSIONS: BIA tends to underestimate FM and overestimate FFM relative to DXA. MF-BIA appears to be a more appropriate method for the assessment of body composition than SF-BIA in post-menopausal woman with BMI >30 kg/m(2) and in those who are insufficiently active.

• Klíčová slova
• Bland-Altman analysis, fat mass, fat-free mass, moderate physical activity, obesity, validity,
• MeSH
• absorpční fotometrie * MeSH
• akcelerometrie MeSH
• cvičení fyziologie   MeSH
• elektrická impedance * MeSH
• index tělesné hmotnosti * MeSH
• lidé středního věku MeSH
• lidé MeSH
• obezita patofyziologie   MeSH
• postmenopauza fyziologie   MeSH
• sedavý životní styl MeSH
• senioři MeSH
• složení těla * MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• srovnávací studie MeSH

BACKGROUND: No clinical trials have compared osteoporosis drugs with incident fractures as the primary outcome. We compared the anti-fracture efficacy of teriparatide with risedronate in patients with severe osteoporosis. METHODS: In this double-blind, double-dummy trial, we enrolled post-menopausal women with at least two moderate or one severe vertebral fracture and a bone mineral density T score of less than or equal to -1·50. Participants were randomly assigned to receive 20 μg of teriparatide once daily plus oral weekly placebo or 35 mg of oral risedronate once weekly plus daily injections of placebo for 24 months. The primary outcome was new radiographic vertebral fractures. Secondary, gated outcomes included new and worsened radiographic vertebral fractures, clinical fractures (a composite of non-vertebral and symptomatic vertebral), and non-vertebral fractures. This study is registered with ClinicalTrials.gov (NCT01709110) and EudraCT (2012-000123-41). FINDINGS: We enrolled 680 patients in each group. At 24 months, new vertebral fractures occurred in 28 (5·4%) of 680 patients in the teriparatide group and 64 (12·0%) of 680 patients in the risedronate group (risk ratio 0·44, 95% CI 0·29-0·68; p<0·0001). Clinical fractures occurred in 30 (4·8%) of 680 patients in the teriparatide group compared with 61 (9·8%) of 680 in the risedronate group (hazard ratio 0·48, 95% CI 0·32-0·74; p=0·0009). Non-vertebral fragility fractures occurred in 25 (4·0%) patients in the teriparatide group and 38 (6·1%) in the risedronate group (hazard ratio 0·66; 95% CI 0·39-1·10; p=0·10). INTERPRETATION: Among post-menopausal women with severe osteoporosis, the risk of new vertebral and clinical fractures is significantly lower in patients receiving teriparatide than in those receiving risedronate. FUNDING: Lilly.

• MeSH
• dvojitá slepá metoda MeSH
• incidence MeSH
• inhibitory kostní resorpce škodlivé účinky   terapeutické užití   MeSH
• kostní denzita účinky léků   MeSH
• kyselina risedronová škodlivé účinky   terapeutické užití   MeSH
• lidé středního věku MeSH
• lidé MeSH
• osteoporotické fraktury diagnostické zobrazování   etiologie   patofyziologie   prevence a kontrola   MeSH
• postmenopauzální osteoporóza komplikace   farmakoterapie   epidemiologie   patofyziologie   MeSH
• radiografie MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• teriparatid škodlivé účinky   terapeutické užití   MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• multicentrická studie MeSH
• práce podpořená grantem MeSH
• randomizované kontrolované studie MeSH
• Geografické názvy
• Amerika epidemiologie   MeSH
• Evropa epidemiologie   MeSH
• Názvy látek
• inhibitory kostní resorpce MeSH
• kyselina risedronová MeSH
• teriparatid MeSH

BACKGROUND: Resistance to endocrine therapies in hormone receptor-positive breast cancer is challenging. We aimed to assess the next-generation oral selective oestrogen receptor degrader (SERD) and complete oestrogen receptor antagonist, camizestrant, versus the first-approved SERD, fulvestrant, in post-menopausal women with oestrogen receptor-positive, HER2-negative, advanced breast cancer. METHODS: SERENA-2 is an open-label, randomised, phase 2 trial that is being conducted at 74 study centres across Asia, Europe, the Middle East, and North America. Female patients aged 18 years or older who were post-menopausal with histologically or cytologically confirmed metastastic or locoregional oestrogen receptor-positive, HER2-negative breast cancer, an Eastern Cooperative Oncology Group or WHO performance status of 0 or 1, and disease recurrence or progression on at least one line of endocrine therapy, and no more than one previous endocrine therapy in the advanced setting. Patients were initially randomly assigned (1:1:1:1) to receive oral camizestrant once daily at 75 mg, 150 mg, or 300 mg (until the 300 mg group was closed), or fulvestrant intramuscularly at 500 mg (per label). Randomisation was managed through an interactive web-based system and stratified by previous treatment with CDK4/6 inhibitors and presence of liver and/or lung metastases. The primary objective was to determine clinical efficacy of camizestrant versus fulvestrant at each dose level using the primary endpoint of investigator-assessed progression-free survival, per Response Evaluation Criteria in Solid Tumours (version 1.1), assessed by intention to treat in all randomly assigned patients (full analysis set). No formal statistical comparison for the efficacy analysis of the camizestrant 300 mg dose versus fulvestrant was to be performed. Safety analyses included all randomly assigned patients who received at least one dose of study treatment. This study is registered with ClinicalTrials.gov, NCT04214288, and is ongoing. FINDINGS: Between May 11, 2020, and Aug 10, 2021, 240 patients were randomly assigned to receive camizestrant 75 mg (n=74), 150 mg (n=73), 300 mg (n=20), or fulvestrant (n=73), and were included in the full analysis set. All patients received at least one dose of study drug. Median follow-up was 16·6 months (IQR 12·9-19·4) for the camizestrant 75 mg group, 16·3 months (12·9-18·3) for the camizestrant 150 mg group, and 14·7 months (12·7-20·1) for the fulvestrant 500 mg group. Median progression-free survival was 7·2 months (90% CI 3·7-10·9) with camizestrant 75 mg, 7·7 months (5·5-12·9) with camizestrant 150 mg, and 3·7 months (2·0-6·0) with fulvestrant. The hazard ratio for camizestrant 75 mg versus fulvestrant was 0·59 (90% CI 0·42-0·82; p=0·017), and the hazard ratio for camizestrant 150 mg versus fulvestrant was 0·64 (0·46-0·89; p=0·0090). Treatment-related adverse events occurred in 39 (53%) of 74 patients in the camizestrant 75 mg group, 49 (67%) of 73 patients in the camizestrant 150 mg group, 14 (70%) of 20 patients in the camizestrant 300 mg group, and 13 (18%) of 73 patients in the fulvestrant group. No single grade 3 or worse treatment-emergent adverse event occurred in more than two (3%) patients in any group. Serious treatment-emergent adverse events occurred in six (8%) patients in the camizestrant 75 mg group, seven (10%) patients in the camizestrant 150 mg group, two (10%) patients in the camizestrant 300 mg group, and four (5%) patients in the fulvestrant group. No treatment-related deaths occurred. INTERPRETATION: Camizestrant at 75 and 150 mg showed a significant benefit in progression-free survival versus fulvestrant. These results support further development of camizestrant for the treatment of oestrogen receptor-positive, HER2-negative breast cancer. FUNDING: AstraZeneca.

• MeSH
• antagonisté estrogenového receptoru aplikace a dávkování   terapeutické užití   MeSH
• aplikace orální MeSH
• azetidiny MeSH
• dospělí MeSH
• fulvestrant * aplikace a dávkování   MeSH
• hormonální protinádorové látky aplikace a dávkování   terapeutické užití   MeSH
• isochinoliny MeSH
• lidé středního věku MeSH
• lidé MeSH
• nádory prsu * farmakoterapie   patologie   mortalita   MeSH
• postmenopauza * MeSH
• receptor erbB-2 * analýza   metabolismus   MeSH
• receptory pro estrogeny * metabolismus   analýza   MeSH
• senioři MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• klinické zkoušky, fáze II MeSH
• multicentrická studie MeSH
• randomizované kontrolované studie MeSH
• srovnávací studie MeSH
• Názvy látek
• antagonisté estrogenového receptoru MeSH
• AZD9833 MeSH Prohlížeč
• azetidiny MeSH
• ERBB2 protein, human MeSH Prohlížeč
• fulvestrant * MeSH
• hormonální protinádorové látky MeSH
• isochinoliny MeSH
• receptor erbB-2 * MeSH
• receptory pro estrogeny * MeSH

OBJECTIVES: The aim of the study was the evaluation of the rs1107946 polymorphism of the COLIA1 gene impact on bone mineral density and fracture risk in Slovak postmenopausal women. METHODS: One hundred and twenty-seven postmenopausal Slovak women with a diagnosis of osteopenia/osteoporosis were genotyped for rs1107946 polymorphism of the COLIA1 gene. Clinical and anthropometric data were obtained. DNA isolation was performed using a standard protocol. Genetic analyses of the rs1107946 polymorphism of the COLIA1 gene were performed by the TaqMan SNP genotyping assays. RESULTS: The study confirmed a statistically significant relationship using an association analysis between the rs1107946 polymorphism of the COLIA1 gene genotypes and body weight of the Slovak postmenopausal women with osteopenia/osteoporosis (p = 0.03). The study revealed a significant association of the risk T allele of the rs1107946 polymorphism of the COLIA1 gene with osteoporotic fractures (p = 0.038). The odds ratio confirmed 2.060 times higher risk of osteoporotic fractures in Slovak postmenopausal women with the presence of risk T allele of the rs1107946 COLIA1 gene polymorphism (OR = 2.060; 95% CI: 1.024-4.144). CONCLUSION: The results of this study revealed an association of T allele of the rs1107946 COLIA1 gene polymorphism with osteoporotic fractures in Slovak postmenopausal women with osteopenia/osteoporosis and suggest that the rs1107946 polymorphism of the COLIA1 gene may be a molecular biomarker usable in the management of osteoporosis.

• Klíčová slova
• COLIA1 gene - rs1107946 polymorphism, fracture risk, osteoporosis, postmenopausal women,
• MeSH
• genotyp MeSH
• kostní denzita genetika   MeSH
• lidé MeSH
• osteoporotické fraktury * komplikace   MeSH
• osteoporóza * komplikace   genetika   MeSH
• polymorfismus genetický MeSH
• postmenopauza MeSH
• postmenopauzální osteoporóza * genetika   komplikace   MeSH
• Check Tag
• lidé MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Geografické názvy
• Slovenská republika epidemiologie   MeSH

Atherosclerosis pathology is the interplay between high intravascular LDL particle concentration and monocyte/macrophage presence within the sub-endothelial space of the artery. In this project, phenotypes of macrophages connected with subclinical inflammation in adipose tissue of living kidney donors were studied. Samples of subcutaneous adipose tissue of living kidney donors (n=36) were exposed to collagenase. Stromal vascular fraction (SVF) was eluted from the samples, then labeled with monoclonal antibodies (anti-CD14 and anti-calprotectin), conjugated with fluorochromes and analyzed by flow cytometry. The positive correlation between the number of total macrophages and calprotectin-positive macrophages with BMI in the subcutaneous adipose tissue of postmenopausal women was demonstrated (p<0.05; R=0.43 and p<0.01; R=0.60), whereas no positive correlation in premenopausal women and men was shown. In conclusion, we documented a significant effect of BMI increase on the presence of total macrophages in adipose tissue of postmenopausal women, in contrast to premenopausal women. This difference was much more pronounced when proinflammatory macrophages with membrane-bound calprotectin were analyzed.

• MeSH
• dospělí MeSH
• fenotyp * MeSH
• index tělesné hmotnosti * MeSH
• lidé středního věku MeSH
• lidé MeSH
• makrofágy metabolismus   MeSH
• podkožní tuk metabolismus   MeSH
• postmenopauza metabolismus   MeSH
• tuková tkáň metabolismus   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH