Association between bile acid metabolism and bone mineral density in postmenopausal women

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elderly people: a triple-blinded randomized controlled trial" "tienePdf" => "en" "tieneTextoCompleto" => "en" "tieneResumen" => "en" "contieneResumen" => array:1 [ "en" => true ] "contieneTextoCompleto" => array:1 [ "en" => true ] "contienePdf" => array:1 [ "en" => true ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "fig1" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 1519 "Ancho" => 1756 "Tamanyo" => 151614 ] ] "descripcion" => array:1 [ "en" => "Flowchart." ] ] ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "Raquel Henriques Jacomo, Aline Teixeira Alves, Adélia Lucio, Patrícia Azevedo Garcia, Dayanne Cristina Ramos Lorena, João Batista de Sousa" "autores" => array:6 [ 0 => array:2 [ "nombre" => "Raquel Henriques" "apellidos" => "Jacomo" ] 1 => array:2 [ "nombre" => "Aline Teixeira" "apellidos" => 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"referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "I" "identificador" => "aff1" ] ] ] 1 => array:3 [ "nombre" => "Yu-Wen" "apellidos" => "Song" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "II" "identificador" => "aff2" ] ] ] 2 => array:3 [ "nombre" => "Liang" "apellidos" => "Zhang" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "II" "identificador" => "aff2" ] ] ] 3 => array:3 [ "nombre" => "Feng-Jie" "apellidos" => "Zheng" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "II" "identificador" => "aff2" ] ] ] 4 => array:3 [ "nombre" => "Xue-Meng" "apellidos" => "Wang" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "II" "identificador" => "aff2" ] ] ] 5 => array:3 [ "nombre" => "Xiang-Hua" "apellidos" => "Zhuang" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "II" "identificador" => "aff2" ] ] ] 6 => array:3 [ "nombre" => "Fei" "apellidos" => "Wu" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "II" "identificador" => "aff2" ] ] ] 7 => array:4 [ "nombre" => "Jian" "apellidos" => "Liu" "email" => array:1 [ 0 => "21294005@qq.com" ] "referencia" => array:2 [ 0 => array:2 [ "etiqueta" => "III" "identificador" => "aff3" ] 1 => array:2 [ "etiqueta" => "*" "identificador" => "cor1" ] ] ] ] "afiliaciones" => array:3 [ 0 => array:3 [ "entidad" => "Nanchang University Queen Mary School, Nanchang, Jiangxi, 330031, China" "etiqueta" => "I" "identificador" => "aff1" ] 1 => array:3 [ "entidad" => "Department of Endocrinology, The Second Hospital of Shandong University, Jinan, Shandong, 250033, China" "etiqueta" => "II" "identificador" => "aff2" ] 2 => array:3 [ "entidad" => "Department of Emergency Medicine, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, 330006, China" "etiqueta" => "III" "identificador" => "aff3" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor1" "etiqueta" => "*" "correspondencia" => "Corresponding author." ] ] ] ] "textoCompleto" => "INTRODUCTIONOsteoporosis is the most common bone disease, and it is characterized by low bone mass, destruction of bone microstructure, and increased bone fragility. An epidemiological survey conducted in 2018 has shown that the prevalence of osteoporosis in the population aged over 50 years in China is 19.2%. Moreover, the prevalence rate of osteoporosis in men was 6.0%, and that in women is as high as 32.1%. Meanwhile, the prevalence rate of osteoporosis among women aged over 65 years is as high as 51.6%, and this rate is significantly higher than that in women in European and American countries (<a class="elsevierStyleCrossRef" href="#bib1">1</a>,<a class="elsevierStyleCrossRef" href="#bib2">2</a>). Osteoporosis can easily lead to fracture and other complications. Thus, it is one of the main causes of disability and death among elderly individuals (<a class="elsevierStyleCrossRef" href="#bib3">3</a>).Bile acid, which is synthesized and secreted by liver cells, is a component of bile and an important signaling molecule that plays a role in glucose and lipid metabolism, energy metabolism, and intestinal flora regulation (<a class="elsevierStyleCrossRef" href="#bib4">4</a>,<a class="elsevierStyleCrossRef" href="#bib5">5</a>). Recent studies have found that bile acid has protective effects on the bones (<a class="elsevierStyleCrossRef" href="#bib6">6</a>). Moreover, it transduces signals mainly by activating the nuclear receptor, farnesoid X receptor (FXR), membrane receptor, and G protein-coupled bile acid receptor 5 (TGR5) (<a class="elsevierStyleCrossRef" href="#bib7">7</a>). A previous study has revealed the occurrence of rapid and severe bone loss after ovariectomy in FXR knockout mice (<a class="elsevierStyleCrossRef" href="#bib8">8</a>). FXR gene knockout has bidirectional effects on the bones. That is, it does not only promote the differentiation and function of osteoclasts but also inhibits the differentiation and function of osteoblasts. Moreover, a research has found that bile acid may have therapeutic effects against osteoporosis. In this study, the bone mineral density (BMD) of the mouse models of osteoporosis significantly increased after the administration of a bile acid receptor agonist. However, to date, only few clinical studies have shown the association between bile acid metabolism and BMD. Moreover, the underlying mechanisms remain unknown (<a class="elsevierStyleCrossRef" href="#bib9">9</a>,<a class="elsevierStyleCrossRef" href="#bib10">10</a>).Therefore, in this study, we aimed to examine the bile acid metabolism of patients with postmenopausal osteoporosis by evaluating the levels of total bile acid and fibroblast growth factor 19 (FGF19). Moreover, we analyzed the correlation between bile acid metabolism as well as bone turnover marker levels and BMD and the mechanisms underlying the effect of bile acid on bone metabolism.SUBJECTS AND METHODSStudy populationThe study was approved by the Scientific Research Ethics Committee of The Second Hospital of Shandong University (KYLL-2018[KJ]P-001). All participants provided a written informed consent for medical research.This was a single-center cross-sectional study. Altogether, 150 postmenopausal women who were initially treated in the Department of Endocrinology of the Second Hospital of Shandong University from January 2019 to May 2019 were enrolled. According to BMD, the participants were divided into three groups, which were as follows: osteoporosis group, osteopenia group, and healthy control group. The inclusion criteria were (1) women who had been postmenopausal for more than 1 year and (2) age over 50 years. Meanwhile, the exclusion criteria were the presence of (1) metabolic or genetic bone diseases, such as rickets, osteomalacia, fibrous dysplasia of the bone, and hyperparathyroidism (2) endocrine diseases affecting bone metabolism, including hyperthyroidism, diabetes, and Cushing syndrome; (3) diseases affecting bone metabolism, such as chronic liver and kidney diseases, severe gastrointestinal diseases, neoplastic diseases, and autoimmune diseases; (4) use of long-term medication or hormone replacement therapy affecting bone metabolism; and (5) new-onset fractures within the last 3 months.Laboratory testsA detailed medical history was obtained, and information about the patients' age, height, and weight and other data were obtained. After the participants fasted overnight, blood samples were collected to assess the levels of biochemical indicators, including calcium (Ca), phosphorus (P), total alkaline phosphatase (TALP), alanine aminotransferase (ALT), creatinine (Cr), 25-hydroxy vitamin D [25(OH)D], intact parathyroid hormone (PTH), procollagen type I N-peptide (P1NP), β-CrossLaps of type I collagen containing cross-linked C-terminal telopeptide (β-CTX), total bile acid, and FGF19. The Ca, P, TALP, PTH, ALT, Cr, and total bile acid concentrations were measured using an automatic biochemistry analyzer in the Laboratory Medicine Center of the Second Hospital of Shandong University. The concentrations of other compounds, including 25(OH)D, P1NP, β-CTX, and FGF19 (Cusabio, Wuhan, China), were determined using an enzyme-linked immunosorbent assay based on well-established methods (<a class="elsevierStyleCrossRef" href="#bib10">10</a>).Measurement of BMDDual energy X-ray absorptiometry was used to measure the areal BMD (unit g/cm2) of lumbar spines 1-4, femoral neck, and total hip using the Lunar Prodigy device (GE Lunar Corp.). Trained technicians from the Department of Radiology performed the tests. Before using the instruments, an accuracy test was conducted with a general phantom to ensure the stability of the system. If there were serious bone deformities or surgical implants in the measurement area, the BMD results were considered unreliable and were not included in the statistical analysis.Statistical methodsThe general characteristics of the patients were expressed using descriptive statistics. All continuous variables were tested for normality and were expressed as mean±standard deviation (SD) or percentages unless stated otherwise. The three groups were compared using chi-square test and one-way analysis of variance. The correlation between bile acid metabolism and BMD was analyzed using Spearman correlation coefficient test.p-values <0.05 were considered statistically significant. All statistical analyses were performed using the Statistical Package for the Social Sciences version 24.0 (SPSS Inc., Chicago, IL, the USA).RESULTSGeneral characteristics of the participantsAltogether, 150 postmenopausal women aged over 50 years (mean age: 59.0±4.3 [range: 50-68] years) were included, and 52, 75, and 23 patients were classified under the osteoporosis, osteopenia, and control groups, respectively. 1 - Osteoporosis: Presence of fragility fractures in the absence of other metabolic bone disorders or a BMD T-score of -2.5 or lower in the lumbar spine, femoral neck or total hip measured by DXA; 2 - Osteopenia: -2.5<a class="elsevierStyleCrossRef" href="#tbl1">Tables 1</a>, <a class="elsevierStyleCrossRef" href="#tbl2">2</a>). In terms of bone turnover biomarker levels, no significant difference was observed in TALP or P1NP level between the three groups (<a class="elsevierStyleCrossRef" href="#tbl2">Table 2</a>). The serum β-CTX levels of the three groups were 572.3±154.4, 543.6±96.3, and 479.4±83.2 pg/mL, respectively, thereby indicating a gradual decrease in the values and a significant difference in the pair-wise comparisons between the three groups (all p<0.05). The healthy control group had the highest BMD and T values of the lumbar spine, femoral neck, and total hip, followed by the osteopenia and osteoporosis groups, and significant differences were observed in the pair-wise comparisons between the three groups (all p<0.05) (<a class="elsevierStyleCrossRef" href="#tbl2">Table 2</a>).<elsevierMultimedia ident="tbl1"></elsevierMultimedia><elsevierMultimedia ident="tbl2"></elsevierMultimedia>Changes in the level of bile acid metabolism-related indicators in patients with osteoporosisThe serum bile acid levels were lower in the osteoporosis and osteopenia groups (5.28±1.56 and 5.31±1.56 umol/L, respectively) than in the control group (6.33±2.04 umol/L; p=0.002 and 0.018, respectively). The FGF19 levels were lower in the osteoporosis and osteopenia groups (5105.0±2567.1 and 4915.1±2413.2 pg/mL, respectively) than in the healthy control group (7107.7±4240.1 pg/mL; p=0.006 and 0.016, respectively).Correlation between bile acid metabolism as well as bone turnover indicator levels and BMDSpearman's correlation analysis revealed that serum bile acid level positively correlated to lumbar spine BMD (R=0.249, p=0.012), T value of the lumbar spine BMD (R=0.245, p=0.013), total hip BMD (R=0.197, p=0.048), T value of the total hip BMD (R=0.200, p=0.044), femoral neck BMD (R=0.205, p=0.018), and T value of the femoral neck BMD (R=0.243, p=0.046). However, it was negatively associated with β-CTX level (R=−0.309, p<0.001). Serum FGF19 level was positively correlated to femoral neck BMD (R=0.197, p=0.037), total hip BMD (R=0.235, p=0.013), and T value of the total hip BMD (R=0.193, p=0.041), but not to β-CTX level (R=−0.350, p<0.001).DISCUSSIONIn this study, we evaluated the changes in serum bile acid and FGF19 levels in Chinese women with postmenopausal osteoporosis, and the relationship between BMD and bile acid metabolism was assessed. The bile acid and FGF19 levels were significantly lower in patients with postmenopausal osteoporosis than in healthy controls. A positive correlation was observed between serum bile acid level and BMD in postmenopausal women.Only few relative studies have focused on the association between bile acid and bone metabolism. An animal study has found that bone loss in TGR5-/- knockout mice is more rapid than that in normal mice after aging or ovariectomy, and this even can be attributed to the regulation of osteoclast generation by TGR5 via the AMP-activated protein kinase signaling pathway. Another study has found that the BMD in FXR knockout mice decreases rapidly (up to 4.3%-6.6%) from 8 to 20 weeks; however, the administration of chenodeoxycholic acid or FXR receptor agonist can promote osteoblast differentiation and inhibit osteoclast differentiation, thereby resulting in increased BMD (<a class="elsevierStyleCrossRef" href="#bib11">11</a>). According to a recent study, FXR agonists could promote the expression of osteogenesis-related genes, including those regulating bone sialoglycoprotein, osteocalcin, osteopontin, and alkaline phosphatase (<a class="elsevierStyleCrossRef" href="#bib12">12</a>). To date, relevant studies are mostly based on basic research, and the serum bile acid levels of patients with osteoporosis have not been assessed in previous studies. This study found that the serum total bile acid level was significantly lower in women with postmenopausal osteoporosis and osteopenia than in healthy controls, which is consistent with the results of previous basic research. This finding also indicates that bile acid plays an important role in bone metabolism based on clinical evidence.The specific mechanism underlying the effect of bile acid on bone metabolism is not clearly elucidated. FGF19 is the downstream molecule of bile acid. In the small intestine, bile acid is reabsorbed into the small intestine cells and binds to and activates FXR to induce the upregulation of FGF19 (<a class="elsevierStyleCrossRef" href="#bib13">13</a>). FGF19 enters the blood circulation after it is secreted by the intestinal tract, and it plays an important role in metabolic regulation, such as controlling bile acid metabolism, gallbladder filling, and blood glucose; promoting energy metabolism; and reducing weight (<a class="elsevierStyleCrossRef" href="#bib5">5</a>,<a class="elsevierStyleCrossRefs" href="#bib14">14–16</a>). However, the effect of FGF19 on bone metabolism is not fully elucidated. In addition, bile acid can activate TGR5 on the surface of small intestine cells and mediate the secretion of GLP-1 and GLP-2 by the endocrine cells in the intestine (<a class="elsevierStyleCrossRef" href="#bib17">17</a>,<a class="elsevierStyleCrossRef" href="#bib18">18</a>). Several studies have shown that GLP-1 can increase bone density and improve bone mass by increasing the number of osteoblasts and upregulating the expression of bone formation-related genes (<a class="elsevierStyleCrossRefs" href="#bib19">19–22</a>). Our study has found that the serum FGF19 levels were lower in patients with osteoporosis and osteopenia than in healthy controls, which is consistent with the results of the above mentioned studies. Thus, the decrease in bile acid synthesis may lead to a reduction in GLP-1 levels via the downregulation of FGF19 expression. However, further studies must be conducted to validate such notion. In addition, a decrease in bile acid synthesis can cause gastrointestinal abnormalities via the downregulation of FGF19 expression, which can then result in a reduction in BMD.We found that serum total bile acid and FGF19 levels were positively associated with the BMD of the lumbar spine and hip. Zhenxi Li et al. have found that the administration of SH-479, which is a bile acid receptor agonist, to mice with postmenopausal osteoporosis increases BMD and improves bone microstructure (<a class="elsevierStyleCrossRef" href="#bib8">8</a>). Moreover, the use of bile acid was found to be an effective treatment for type 2 diabetes, hyperlipidemia, obesity, and other diseases. Thus, bile acid may be a new therapeutic target for postmenopausal osteoporosis (<a class="elsevierStyleCrossRef" href="#bib23">23</a>,<a class="elsevierStyleCrossRef" href="#bib24">24</a>). However, a more in-depth research must be conducted to validate further the specific mechanism underlying the effect of bile acid on bone metabolism and its therapeutic effects.This study had some limitations. First, the sample size was relatively small, and the number of participants in the control group was smaller than that in the osteoporosis and osteopenia groups. Second, since FXR and TGR5 are membrane receptors and are not expressed in the serum, changes in the expression of FXR and TGR5 in patients with osteoporosis could not be assessed. Third, this was a clinical study. Thus, the interference in bile acid detection in individuals with biliary tract diseases, abnormal glucose levels, lipid metabolism disorders, and other conditions could not be eliminated. Lastly, the study was conducted on Chinese patients only.In summary, this cross-sectional study has found that the levels of serum bile acid and FGF19 were significantly lower in women with postmenopausal osteoporosis and osteopenia than in healthy women. Serum total bile acid and FGF19 levels were positively associated with BMD. Our findings indicate that the bile acid metabolic pathways can be new therapeutic targets for postmenopausal osteoporosis.AUTHOR CONTRIBUTIONSZhao YX, Zhuang XH, and Liu J designed the study. Zhao YX, Song YW, Zhang L, and Wang XM conducted the investigation and collected data. Wu F and Liu J performed the statistical analysis. Zhao YX and Song YW and Zheng FJ wrote the main manuscript. All authors reviewed and edited the manuscript and approved the final version." "textoCompletoSecciones" => array:1 [ "secciones" => array:8 [ 0 => array:2 [ "identificador" => "xpalclavsec1580052" "titulo" => "KEYWORDS" ] 1 => array:2 [ "identificador" => "cesec10" "titulo" => "INTRODUCTION" ] 2 => array:3 [ "identificador" => "cesec20" "titulo" => "SUBJECTS AND METHODS" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "cesec30" "titulo" => "Study population" ] 1 => array:2 [ "identificador" => "cesec40" "titulo" => "Laboratory tests" ] 2 => array:2 [ "identificador" => "cesec50" "titulo" => "Measurement of BMD" ] 3 => array:2 [ "identificador" => "cesec60" "titulo" => "Statistical methods" ] ] ] 3 => array:3 [ "identificador" => "cesec70" "titulo" => "RESULTS" "secciones" => array:3 [ 0 => array:2 [ "identificador" => "cesec80" "titulo" => "General characteristics of the participants" ] 1 => array:2 [ "identificador" => "cesec90" "titulo" => "Changes in the level of bile acid metabolism-related indicators in patients with osteoporosis" ] 2 => array:2 [ "identificador" => "cesec100" "titulo" => "Correlation between bile acid metabolism as well as bone turnover indicator levels and BMD" ] ] ] 4 => array:2 [ "identificador" => "cesec110" "titulo" => "DISCUSSION" ] 5 => array:2 [ "identificador" => "cesec120" "titulo" => "AUTHOR CONTRIBUTIONS" ] 6 => array:2 [ "identificador" => "xack638073" "titulo" => "ACKNOWLEDGMENTS" ] 7 => array:1 [ "titulo" => "REFERENCES" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "fechaRecibido" => "2019-09-18" "fechaAceptado" => "2020-01-02" "PalabrasClave" => array:1 [ "en" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "KEYWORDS" "identificador" => "xpalclavsec1580052" "palabras" => array:3 [ 0 => "Postmenopausal Osteoporosis" 1 => "Bile Acid Metabolism" 2 => "FGF19" ] ] ] ] "tieneResumen" => true "resumen" => array:1 [ "en" => array:2 [ "resumen" => "OBJECTIVES:Previous studies have not shown any correlation between bile acid metabolism and bone mineral density (BMD) in women with postmenopausal osteoporosis. Thus, the current study evaluated the association between bile acid levels as well as BMD and bone turnover marker levels in this group of women. METHODS:This single-center cross-sectional study included 150 postmenopausal Chinese women. According to BMD, the participants were divided into three groups: osteoporosis group, osteopenia group, and healthy control group. Serum bile acid, fibroblast growth factor 19 (FGF19), and bone turnover biomarker levels were assessed. Moreover, the concentrations of parathyroid hormone, 25-hydroxy vitamin D [25(OH)D], procollagen type I N-peptide (P1NP), and beta-CrossLaps of type I collagen containing cross-linked C-terminal telopeptide (β-CTX) were evaluated. The BMD of the lumbar spine and proximal femur were examined via dual-energy X-ray absorptiometry. RESULTS:The serum total bile acid levels in the osteoporosis and osteopenia groups (5.28±1.56 and 5.31±1.56 umol/L, respectively) were significantly lower than that in the healthy control group (6.33±2.04 umol/L; p=0.002 and 0.018, respectively). Serum bile acid level was positively associated with the BMD of the lumbar spine, femoral neck, and total hip. However, it negatively correlated with β-CTX concentration. Moreover, no correlation was observed between bile acid and P1NP levels, and the levels of the other biomarkers that were measured did not differ between the groups. CONCLUSION:Serum bile acid was positively correlated with BMD and negatively correlated with bone turnover biomarkers reflecting bone absorption in postmenopausal women. Thus, bile acid may play an important role in bone metabolism." "secciones" => array:4 [ 0 => array:2 [ "identificador" => "ceabs10" "titulo" => "OBJECTIVES:" ] 1 => array:2 [ "identificador" => "ceabs20" "titulo" => "METHODS:" ] 2 => array:2 [ "identificador" => "ceabs30" "titulo" => "RESULTS:" ] 3 => array:2 [ "identificador" => "ceabs40" "titulo" => "CONCLUSION:" ] ] ] ] "NotaPie" => array:1 [ 0 => array:1 [ "nota" => "No potential conflict of interest was reported." ] ] "multimedia" => array:2 [ 0 => array:7 [ "identificador" => "tbl1" "etiqueta" => "Table 1" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "tabla" => array:2 [ "leyenda" => "BMI: body mass index; TG: triglyceride; TC: total cholesterol; HDL-C: high-density lipoprotein cholesterol; LDL-C: low-density lipoprotein cholesterol." "tablatextoimagen" => array:1 [ 0 => array:1 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col"> \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col">Osteoporosis group \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col">Osteopenia group \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col">Control group \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col">p-value \t\t\t\t\t\t\n \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">number \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">52 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">75 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">23 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">age (years) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">59.8±3.8 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">58.6±4.4 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">58.4±4.5 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.220 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">height (cm) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">157.9±5.4 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">159.1±4.1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">158.4±3.7 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.354 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">weight (kg) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">57.1±8.5 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">63.2±7.6 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">67.0±6.8 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.221 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">BMI (kg/m2) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">22.9±2.8 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">25.0±2.9 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">26.7±2.7 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.109 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">TG (mmol/L) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1.32±0.68 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1.50±1.07 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1.28±0.59 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.397 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">TC (mmol/L) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">4.86±0.73 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">5.03±0.86 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">5.19±0.95 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.246 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">HDL-C (mmol/L) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1.67±0.44 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1.67±0.33 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1.71±0.35 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.880 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">LDL-C (mmol/L) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">2.56±0.78 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">2.58±0.77 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">2.71±0.79 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.707 \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] ] ] ] "descripcion" => array:1 [ "en" => "Demographic characteristics of the participants." ] ] 1 => array:7 [ "identificador" => "tbl2" "etiqueta" => "Table 2" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "tabla" => array:3 [ "leyenda" => "*,**, and ΔΔ indicate significant differences between the two groups after a pairwise comparison.P1NP: procollagen type I N-peptide; β-CTX: cross-linked C-terminal telopeptide of type I collagen; BMD: bone mineral density; LS: lumbar spine; FN: femoral neck; TH: total hip." "tablatextoimagen" => array:1 [ 0 => array:1 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col"> \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col">Osteoporosis group \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col">Osteopenia group \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col">Control group \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col">p-value \t\t\t\t\t\t\n \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Number \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">52 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">75 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">23 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">P1NP (pg/ml) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">13.87±5.84 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">12.60±4.54 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">11.66±3.31 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.184 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">β-CTX (pg/ml) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">572.3±154.4<a class="elsevierStyleCrossRef" href="#TFN03t02">**</a><a class="elsevierStyleCrossRef" href="#TFN04t02">Δ</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">543.6±96.3<a class="elsevierStyleCrossRef" href="#TFN02t02">*</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">479.4±83.2 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.020 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Grip strength (kg) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">25.1±4.9 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">27.1±5.5 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">25.1±5.1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.083 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">LS BMD (g/cm2) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.717±0.102<a class="elsevierStyleCrossRef" href="#TFN03t02">**</a><a class="elsevierStyleCrossRef" href="#TFN04t02">ΔΔ</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.900±0.101<a class="elsevierStyleCrossRef" href="#TFN03t02">**</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1.033±0.066 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><0.001 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">LS BMD T score \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">-3.048±0.812<a class="elsevierStyleCrossRef" href="#TFN03t02">**</a><a class="elsevierStyleCrossRef" href="#TFN04t02">ΔΔ</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">-1.280±0.877<a class="elsevierStyleCrossRef" href="#TFN03t02">**</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">-0.087±0.578 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><0.001 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">FN BMD (g/cm2) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.603±0.076<a class="elsevierStyleCrossRef" href="#TFN03t02">**</a><a class="elsevierStyleCrossRef" href="#TFN04t02">ΔΔ</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.709±0.070<a class="elsevierStyleCrossRef" href="#TFN03t02">**</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.807±0.048 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><0.001 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">FN BMD T score \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">-2.354±0.505<a class="elsevierStyleCrossRef" href="#TFN03t02">**</a><a class="elsevierStyleCrossRef" href="#TFN04t02">ΔΔ</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">-1.310±0.426<a class="elsevierStyleCrossRef" href="#TFN03t02">**</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">-0.302±0.127 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><0.001 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">TH BMD (g/cm2) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.722±0.083<a class="elsevierStyleCrossRef" href="#TFN03t02">**</a><a class="elsevierStyleCrossRef" href="#TFN04t02">ΔΔ</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.853±0.089<a class="elsevierStyleCrossRef" href="#TFN03t02">**</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.958±0.096 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><0.001 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">TH BMD T score \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">-2.281±0.665<a class="elsevierStyleCrossRef" href="#TFN03t02">**</a><a class="elsevierStyleCrossRef" href="#TFN04t02">ΔΔ</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">-1.252±0.653<a class="elsevierStyleCrossRef" href="#TFN03t02">**</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">-0.378±0.416 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><0.001 \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] ] ] "notaPie" => array:3 [ 0 => array:3 [ "identificador" => "TFN02t02" "etiqueta" => "*" "nota" => "p<0.05 compared with the control group;" ] 1 => array:3 [ "identificador" => "TFN03t02" "etiqueta" => "**" "nota" => "p<0.01 compared with the control group, and" ] 2 => array:3 [ "identificador" => "TFN04t02" "etiqueta" => "ΔΔ" "nota" => "p-value<0.01 compared with the osteopenia group." ] ] ] "descripcion" => array:1 [ "en" => "Comparison of bone turnover biomarker levels and BMD between the three groups." ] ] ] "bibliografia" => array:2 [ "titulo" => "REFERENCES" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "cebibsec10" "bibliografiaReferencia" => array:24 [ 0 => array:3 [ "identificador" => "bib1" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Osteoporosis" 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We sincerely thank all participants of this research." "vista" => "all" ] ] ] "idiomaDefecto" => "en" "url" => "/18075932/000000750000000C/v1_202211290815/S1807593222002940/v1_202211290815/en/main.assets" "Apartado" => null "PDF" => "https://static.elsevier.es/multimedia/18075932/000000750000000C/v1_202211290815/S1807593222002940/v1_202211290815/en/main.pdf?idApp=UINPBA00004N&text.app=https://www.elsevier.es/" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S1807593222002940?idApp=UINPBA00004N"]

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ORIGINAL ARTICLE

Yu-Xiao ZhaoI, Yu-Wen SongII, Liang ZhangII, Feng-Jie ZhengII, Xue-Meng WangII, Xiang-Hua ZhuangII, Fei WuII, Jian LiuIII,

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21294005@qq.com

Corresponding author.

I Nanchang University Queen Mary School, Nanchang, Jiangxi, 330031, China

II Department of Endocrinology, The Second Hospital of Shandong University, Jinan, Shandong, 250033, China

III Department of Emergency Medicine, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, 330006, China

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    "textoCompleto" => "<span class="elsevierStyleSections"><span id="cesec10" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cestitle60">INTRODUCTION</span><p id="para10" class="elsevierStylePara elsevierViewall">Osteoporosis is the most common bone disease&#44; and it is characterized by low bone mass&#44; destruction of bone microstructure&#44; and increased bone fragility&#46; An epidemiological survey conducted in 2018 has shown that the prevalence of osteoporosis in the population aged over 50 years in China is 19&#46;2&#37;&#46; Moreover&#44; the prevalence rate of osteoporosis in men was 6&#46;0&#37;&#44; and that in women is as high as 32&#46;1&#37;&#46; Meanwhile&#44; the prevalence rate of osteoporosis among women aged over 65 years is as high as 51&#46;6&#37;&#44; and this rate is significantly higher than that in women in European and American countries &#40;<a class="elsevierStyleCrossRef" href="#bib1">1</a>&#44;<a class="elsevierStyleCrossRef" href="#bib2">2</a>&#41;&#46; Osteoporosis can easily lead to fracture and other complications&#46; Thus&#44; it is one of the main causes of disability and death among elderly individuals &#40;<a class="elsevierStyleCrossRef" href="#bib3">3</a>&#41;&#46;</p><p id="para20" class="elsevierStylePara elsevierViewall">Bile acid&#44; which is synthesized and secreted by liver cells&#44; is a component of bile and an important signaling molecule that plays a role in glucose and lipid metabolism&#44; energy metabolism&#44; and intestinal flora regulation &#40;<a class="elsevierStyleCrossRef" href="#bib4">4</a>&#44;<a class="elsevierStyleCrossRef" href="#bib5">5</a>&#41;&#46; Recent studies have found that bile acid has protective effects on the bones &#40;<a class="elsevierStyleCrossRef" href="#bib6">6</a>&#41;&#46; Moreover&#44; it transduces signals mainly by activating the nuclear receptor&#44; farnesoid X receptor &#40;FXR&#41;&#44; membrane receptor&#44; and G protein-coupled bile acid receptor 5 &#40;TGR5&#41; &#40;<a class="elsevierStyleCrossRef" href="#bib7">7</a>&#41;&#46; A previous study has revealed the occurrence of rapid and severe bone loss after ovariectomy in FXR knockout mice &#40;<a class="elsevierStyleCrossRef" href="#bib8">8</a>&#41;&#46; FXR gene knockout has bidirectional effects on the bones&#46; That is&#44; it does not only promote the differentiation and function of osteoclasts but also inhibits the differentiation and function of osteoblasts&#46; Moreover&#44; a research has found that bile acid may have therapeutic effects against osteoporosis&#46; In this study&#44; the bone mineral density &#40;BMD&#41; of the mouse models of osteoporosis significantly increased after the administration of a bile acid receptor agonist&#46; However&#44; to date&#44; only few clinical studies have shown the association between bile acid metabolism and BMD&#46; Moreover&#44; the underlying mechanisms remain unknown &#40;<a class="elsevierStyleCrossRef" href="#bib9">9</a>&#44;<a class="elsevierStyleCrossRef" href="#bib10">10</a>&#41;&#46;</p><p id="para30" class="elsevierStylePara elsevierViewall">Therefore&#44; in this study&#44; we aimed to examine the bile acid metabolism of patients with postmenopausal osteoporosis by evaluating the levels of total bile acid and fibroblast growth factor 19 &#40;FGF19&#41;&#46; Moreover&#44; we analyzed the correlation between bile acid metabolism as well as bone turnover marker levels and BMD and the mechanisms underlying the effect of bile acid on bone metabolism&#46;</p></span><span id="cesec20" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cestitle70">SUBJECTS AND METHODS</span><span id="cesec30" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cestitle80">Study population</span><p id="para40" class="elsevierStylePara elsevierViewall">The study was approved by the Scientific Research Ethics Committee of The Second Hospital of Shandong University &#40;KYLL-2018&#91;KJ&#93;P-001&#41;&#46; All participants provided a written informed consent for medical research&#46;</p><p id="para50" class="elsevierStylePara elsevierViewall">This was a single-center cross-sectional study&#46; Altogether&#44; 150 postmenopausal women who were initially treated in the Department of Endocrinology of the Second Hospital of Shandong University from January 2019 to May 2019 were enrolled&#46; According to BMD&#44; the participants were divided into three groups&#44; which were as follows&#58; osteoporosis group&#44; osteopenia group&#44; and healthy control group&#46; The inclusion criteria were &#40;1&#41; women who had been postmenopausal for more than 1 year and &#40;2&#41; age over 50 years&#46; Meanwhile&#44; the exclusion criteria were the presence of &#40;1&#41; metabolic or genetic bone diseases&#44; such as rickets&#44; osteomalacia&#44; fibrous dysplasia of the bone&#44; and hyperparathyroidism &#40;2&#41; endocrine diseases affecting bone metabolism&#44; including hyperthyroidism&#44; diabetes&#44; and Cushing syndrome&#59; &#40;3&#41; diseases affecting bone metabolism&#44; such as chronic liver and kidney diseases&#44; severe gastrointestinal diseases&#44; neoplastic diseases&#44; and autoimmune diseases&#59; &#40;4&#41; use of long-term medication or hormone replacement therapy affecting bone metabolism&#59; and &#40;5&#41; new-onset fractures within the last 3 months&#46;</p></span><span id="cesec40" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cestitle90">Laboratory tests</span><p id="para60" class="elsevierStylePara elsevierViewall">A detailed medical history was obtained&#44; and information about the patients&#39; age&#44; height&#44; and weight and other data were obtained&#46; After the participants fasted overnight&#44; blood samples were collected to assess the levels of biochemical indicators&#44; including calcium &#40;Ca&#41;&#44; phosphorus &#40;P&#41;&#44; total alkaline phosphatase &#40;TALP&#41;&#44; alanine aminotransferase &#40;ALT&#41;&#44; creatinine &#40;Cr&#41;&#44; 25-hydroxy vitamin D &#91;25&#40;OH&#41;D&#93;&#44; intact parathyroid hormone &#40;PTH&#41;&#44; procollagen type I N-peptide &#40;P1NP&#41;&#44; &#946;-CrossLaps of type I collagen containing cross-linked C-terminal telopeptide &#40;&#946;-CTX&#41;&#44; total bile acid&#44; and FGF19&#46; The Ca&#44; P&#44; TALP&#44; PTH&#44; ALT&#44; Cr&#44; and total bile acid concentrations were measured using an automatic biochemistry analyzer in the Laboratory Medicine Center of the Second Hospital of Shandong University&#46; The concentrations of other compounds&#44; including 25&#40;OH&#41;D&#44; P1NP&#44; &#946;-CTX&#44; and FGF19 &#40;Cusabio&#44; Wuhan&#44; China&#41;&#44; were determined using an enzyme-linked immunosorbent assay based on well-established methods &#40;<a class="elsevierStyleCrossRef" href="#bib10">10</a>&#41;&#46;</p></span><span id="cesec50" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cestitle100">Measurement of BMD</span><p id="para70" class="elsevierStylePara elsevierViewall">Dual energy X-ray absorptiometry was used to measure the areal BMD &#40;unit g&#47;cm2&#41; of lumbar spines 1-4&#44; femoral neck&#44; and total hip using the Lunar Prodigy device &#40;GE Lunar Corp&#46;&#41;&#46; Trained technicians from the Department of Radiology performed the tests&#46; Before using the instruments&#44; an accuracy test was conducted with a general phantom to ensure the stability of the system&#46; If there were serious bone deformities or surgical implants in the measurement area&#44; the BMD results were considered unreliable and were not included in the statistical analysis&#46;</p></span><span id="cesec60" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cestitle110">Statistical methods</span><p id="para80" class="elsevierStylePara elsevierViewall">The general characteristics of the patients were expressed using descriptive statistics&#46; All continuous variables were tested for normality and were expressed as mean&#177;standard deviation &#40;SD&#41; or percentages unless stated otherwise&#46; The three groups were compared using chi-square test and one-way analysis of variance&#46; The correlation between bile acid metabolism and BMD was analyzed using Spearman correlation coefficient test&#46;</p><p id="para90" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">p</span>-values &#60;0&#46;05 were considered statistically significant&#46; All statistical analyses were performed using the Statistical Package for the Social Sciences version 24&#46;0 &#40;SPSS Inc&#46;&#44; Chicago&#44; IL&#44; the USA&#41;&#46;</p></span></span><span id="cesec70" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cestitle120">RESULTS</span><span id="cesec80" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cestitle130">General characteristics of the participants</span><p id="para100" class="elsevierStylePara elsevierViewall">Altogether&#44; 150 postmenopausal women aged over 50 years &#40;mean age&#58; 59&#46;0&#177;4&#46;3 &#91;range&#58; 50-68&#93; years&#41; were included&#44; and 52&#44; 75&#44; and 23 patients were classified under the osteoporosis&#44; osteopenia&#44; and control groups&#44; respectively&#46; 1 - Osteoporosis&#58; Presence of fragility fractures in the absence of other metabolic bone disorders or a BMD T-score of -2&#46;5 or lower in the lumbar spine&#44; femoral neck or total hip measured by DXA&#59; 2 - Osteopenia&#58; -2&#46;5<a class="elsevierStyleCrossRef" href="#tbl1">Tables 1</a>&#44; <a class="elsevierStyleCrossRef" href="#tbl2">2</a>&#41;&#46; In terms of bone turnover biomarker levels&#44; no significant difference was observed in TALP or P1NP level between the three groups &#40;<a class="elsevierStyleCrossRef" href="#tbl2">Table 2</a>&#41;&#46; The serum &#946;-CTX levels of the three groups were 572&#46;3&#177;154&#46;4&#44; 543&#46;6&#177;96&#46;3&#44; and 479&#46;4&#177;83&#46;2 pg&#47;mL&#44; respectively&#44; thereby indicating a gradual decrease in the values and a significant difference in the pair-wise comparisons between the three groups &#40;all <span class="elsevierStyleItalic">p</span>&#60;0&#46;05&#41;&#46; The healthy control group had the highest BMD and T values of the lumbar spine&#44; femoral neck&#44; and total hip&#44; followed by the osteopenia and osteoporosis groups&#44; and significant differences were observed in the pair-wise comparisons between the three groups &#40;all <span class="elsevierStyleItalic">p</span>&#60;0&#46;05&#41; &#40;<a class="elsevierStyleCrossRef" href="#tbl2">Table 2</a>&#41;&#46;</p><elsevierMultimedia ident="tbl1"></elsevierMultimedia><elsevierMultimedia ident="tbl2"></elsevierMultimedia></span><span id="cesec90" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cestitle140">Changes in the level of bile acid metabolism-related indicators in patients with osteoporosis</span><p id="para110" class="elsevierStylePara elsevierViewall">The serum bile acid levels were lower in the osteoporosis and osteopenia groups &#40;5&#46;28&#177;1&#46;56 and 5&#46;31&#177;1&#46;56 umol&#47;L&#44; respectively&#41; than in the control group &#40;6&#46;33&#177;2&#46;04 umol&#47;L&#59; <span class="elsevierStyleItalic">p</span>&#61;0&#46;002 and 0&#46;018&#44; respectively&#41;&#46; The FGF19 levels were lower in the osteoporosis and osteopenia groups &#40;5105&#46;0&#177;2567&#46;1 and 4915&#46;1&#177;2413&#46;2 pg&#47;mL&#44; respectively&#41; than in the healthy control group &#40;7107&#46;7&#177;4240&#46;1 pg&#47;mL&#59; <span class="elsevierStyleItalic">p</span>&#61;0&#46;006 and 0&#46;016&#44; respectively&#41;&#46;</p></span><span id="cesec100" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cestitle150">Correlation between bile acid metabolism as well as bone turnover indicator levels and BMD</span><p id="para120" class="elsevierStylePara elsevierViewall">Spearman&#39;s correlation analysis revealed that serum bile acid level positively correlated to lumbar spine BMD &#40;R&#61;0&#46;249&#44; <span class="elsevierStyleItalic">p</span>&#61;0&#46;012&#41;&#44; T value of the lumbar spine BMD &#40;R&#61;0&#46;245&#44; <span class="elsevierStyleItalic">p</span>&#61;0&#46;013&#41;&#44; total hip BMD &#40;R&#61;0&#46;197&#44; <span class="elsevierStyleItalic">p</span>&#61;0&#46;048&#41;&#44; T value of the total hip BMD &#40;R&#61;0&#46;200&#44; <span class="elsevierStyleItalic">p</span>&#61;0&#46;044&#41;&#44; femoral neck BMD &#40;R&#61;0&#46;205&#44; <span class="elsevierStyleItalic">p</span>&#61;0&#46;018&#41;&#44; and T value of the femoral neck BMD &#40;R&#61;0&#46;243&#44; <span class="elsevierStyleItalic">p</span>&#61;0&#46;046&#41;&#46; However&#44; it was negatively associated with &#946;-CTX level &#40;R&#61;&#8722;0&#46;309&#44; <span class="elsevierStyleItalic">p</span>&#60;0&#46;001&#41;&#46; Serum FGF19 level was positively correlated to femoral neck BMD &#40;R&#61;0&#46;197&#44; <span class="elsevierStyleItalic">p</span>&#61;0&#46;037&#41;&#44; total hip BMD &#40;R&#61;0&#46;235&#44; <span class="elsevierStyleItalic">p</span>&#61;0&#46;013&#41;&#44; and T value of the total hip BMD &#40;R&#61;0&#46;193&#44; <span class="elsevierStyleItalic">p</span>&#61;0&#46;041&#41;&#44; but not to &#946;-CTX level &#40;R&#61;&#8722;0&#46;350&#44; <span class="elsevierStyleItalic">p</span>&#60;0&#46;001&#41;&#46;</p></span></span><span id="cesec110" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cestitle160">DISCUSSION</span><p id="para130" class="elsevierStylePara elsevierViewall">In this study&#44; we evaluated the changes in serum bile acid and FGF19 levels in Chinese women with postmenopausal osteoporosis&#44; and the relationship between BMD and bile acid metabolism was assessed&#46; The bile acid and FGF19 levels were significantly lower in patients with postmenopausal osteoporosis than in healthy controls&#46; A positive correlation was observed between serum bile acid level and BMD in postmenopausal women&#46;</p><p id="para140" class="elsevierStylePara elsevierViewall">Only few relative studies have focused on the association between bile acid and bone metabolism&#46; An animal study has found that bone loss in TGR5-&#47;- knockout mice is more rapid than that in normal mice after aging or ovariectomy&#44; and this even can be attributed to the regulation of osteoclast generation by TGR5 via the AMP-activated protein kinase signaling pathway&#46; Another study has found that the BMD in FXR knockout mice decreases rapidly &#40;up to 4&#46;3&#37;-6&#46;6&#37;&#41; from 8 to 20 weeks&#59; however&#44; the administration of chenodeoxycholic acid or FXR receptor agonist can promote osteoblast differentiation and inhibit osteoclast differentiation&#44; thereby resulting in increased BMD &#40;<a class="elsevierStyleCrossRef" href="#bib11">11</a>&#41;&#46; According to a recent study&#44; FXR agonists could promote the expression of osteogenesis-related genes&#44; including those regulating bone sialoglycoprotein&#44; osteocalcin&#44; osteopontin&#44; and alkaline phosphatase &#40;<a class="elsevierStyleCrossRef" href="#bib12">12</a>&#41;&#46; To date&#44; relevant studies are mostly based on basic research&#44; and the serum bile acid levels of patients with osteoporosis have not been assessed in previous studies&#46; This study found that the serum total bile acid level was significantly lower in women with postmenopausal osteoporosis and osteopenia than in healthy controls&#44; which is consistent with the results of previous basic research&#46; This finding also indicates that bile acid plays an important role in bone metabolism based on clinical evidence&#46;</p><p id="para150" class="elsevierStylePara elsevierViewall">The specific mechanism underlying the effect of bile acid on bone metabolism is not clearly elucidated&#46; FGF19 is the downstream molecule of bile acid&#46; In the small intestine&#44; bile acid is reabsorbed into the small intestine cells and binds to and activates FXR to induce the upregulation of FGF19 &#40;<a class="elsevierStyleCrossRef" href="#bib13">13</a>&#41;&#46; FGF19 enters the blood circulation after it is secreted by the intestinal tract&#44; and it plays an important role in metabolic regulation&#44; such as controlling bile acid metabolism&#44; gallbladder filling&#44; and blood glucose&#59; promoting energy metabolism&#59; and reducing weight &#40;<a class="elsevierStyleCrossRef" href="#bib5">5</a>&#44;<a class="elsevierStyleCrossRefs" href="#bib14">14&#8211;16</a>&#41;&#46; However&#44; the effect of FGF19 on bone metabolism is not fully elucidated&#46; In addition&#44; bile acid can activate TGR5 on the surface of small intestine cells and mediate the secretion of GLP-1 and GLP-2 by the endocrine cells in the intestine &#40;<a class="elsevierStyleCrossRef" href="#bib17">17</a>&#44;<a class="elsevierStyleCrossRef" href="#bib18">18</a>&#41;&#46; Several studies have shown that GLP-1 can increase bone density and improve bone mass by increasing the number of osteoblasts and upregulating the expression of bone formation-related genes &#40;<a class="elsevierStyleCrossRefs" href="#bib19">19&#8211;22</a>&#41;&#46; Our study has found that the serum FGF19 levels were lower in patients with osteoporosis and osteopenia than in healthy controls&#44; which is consistent with the results of the above mentioned studies&#46; Thus&#44; the decrease in bile acid synthesis may lead to a reduction in GLP-1 levels via the downregulation of FGF19 expression&#46; However&#44; further studies must be conducted to validate such notion&#46; In addition&#44; a decrease in bile acid synthesis can cause gastrointestinal abnormalities via the downregulation of FGF19 expression&#44; which can then result in a reduction in BMD&#46;</p><p id="para160" class="elsevierStylePara elsevierViewall">We found that serum total bile acid and FGF19 levels were positively associated with the BMD of the lumbar spine and hip&#46; Zhenxi Li et al&#46; have found that the administration of SH-479&#44; which is a bile acid receptor agonist&#44; to mice with postmenopausal osteoporosis increases BMD and improves bone microstructure &#40;<a class="elsevierStyleCrossRef" href="#bib8">8</a>&#41;&#46; Moreover&#44; the use of bile acid was found to be an effective treatment for type 2 diabetes&#44; hyperlipidemia&#44; obesity&#44; and other diseases&#46; Thus&#44; bile acid may be a new therapeutic target for postmenopausal osteoporosis &#40;<a class="elsevierStyleCrossRef" href="#bib23">23</a>&#44;<a class="elsevierStyleCrossRef" href="#bib24">24</a>&#41;&#46; However&#44; a more in-depth research must be conducted to validate further the specific mechanism underlying the effect of bile acid on bone metabolism and its therapeutic effects&#46;</p><p id="para170" class="elsevierStylePara elsevierViewall">This study had some limitations&#46; First&#44; the sample size was relatively small&#44; and the number of participants in the control group was smaller than that in the osteoporosis and osteopenia groups&#46; Second&#44; since FXR and TGR5 are membrane receptors and are not expressed in the serum&#44; changes in the expression of FXR and TGR5 in patients with osteoporosis could not be assessed&#46; Third&#44; this was a clinical study&#46; Thus&#44; the interference in bile acid detection in individuals with biliary tract diseases&#44; abnormal glucose levels&#44; lipid metabolism disorders&#44; and other conditions could not be eliminated&#46; Lastly&#44; the study was conducted on Chinese patients only&#46;</p><p id="para180" class="elsevierStylePara elsevierViewall">In summary&#44; this cross-sectional study has found that the levels of serum bile acid and FGF19 were significantly lower in women with postmenopausal osteoporosis and osteopenia than in healthy women&#46; Serum total bile acid and FGF19 levels were positively associated with BMD&#46; Our findings indicate that the bile acid metabolic pathways can be new therapeutic targets for postmenopausal osteoporosis&#46;</p></span><span id="cesec120" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cestitle170">AUTHOR CONTRIBUTIONS</span><p id="para190" class="elsevierStylePara elsevierViewall">Zhao YX&#44; Zhuang XH&#44; and Liu J designed the study&#46; Zhao YX&#44; Song YW&#44; Zhang L&#44; and Wang XM conducted the investigation and collected data&#46; Wu F and Liu J performed the statistical analysis&#46; Zhao YX and Song YW and Zheng FJ wrote the main manuscript&#46; All authors reviewed and edited the manuscript and approved the final version&#46;</p></span></span>"
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          "titulo" => "INTRODUCTION"
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          "titulo" => "RESULTS"
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              "titulo" => "General characteristics of the participants"
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              "titulo" => "Changes in the level of bile acid metabolism-related indicators in patients with osteoporosis"
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              "titulo" => "Correlation between bile acid metabolism as well as bone turnover indicator levels and BMD"
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          "titulo" => "DISCUSSION"
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          "titulo" => "REFERENCES"
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    "pdfFichero" => "main.pdf"
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    "fechaRecibido" => "2019-09-18"
    "fechaAceptado" => "2020-01-02"
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            0 => "Postmenopausal Osteoporosis"
            1 => "Bile Acid Metabolism"
            2 => "FGF19"
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        "resumen" => "<span id="ceabs10" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cestitle10">OBJECTIVES&#58;</span><p id="spara30" class="elsevierStyleSimplePara elsevierViewall">Previous studies have not shown any correlation between bile acid metabolism and bone mineral density &#40;BMD&#41; in women with postmenopausal osteoporosis&#46; Thus&#44; the current study evaluated the association between bile acid levels as well as BMD and bone turnover marker levels in this group of women&#46;</p></span> <span id="ceabs20" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cestitle20">METHODS&#58;</span><p id="spara40" class="elsevierStyleSimplePara elsevierViewall">This single-center cross-sectional study included 150 postmenopausal Chinese women&#46; According to BMD&#44; the participants were divided into three groups&#58; osteoporosis group&#44; osteopenia group&#44; and healthy control group&#46; Serum bile acid&#44; fibroblast growth factor 19 &#40;FGF19&#41;&#44; and bone turnover biomarker levels were assessed&#46; Moreover&#44; the concentrations of parathyroid hormone&#44; 25-hydroxy vitamin D &#91;25&#40;OH&#41;D&#93;&#44; procollagen type I N-peptide &#40;P1NP&#41;&#44; and beta-CrossLaps of type I collagen containing cross-linked C-terminal telopeptide &#40;&#946;-CTX&#41; were evaluated&#46; The BMD of the lumbar spine and proximal femur were examined via dual-energy X-ray absorptiometry&#46;</p></span> <span id="ceabs30" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cestitle30">RESULTS&#58;</span><p id="spara50" class="elsevierStyleSimplePara elsevierViewall">The serum total bile acid levels in the osteoporosis and osteopenia groups &#40;5&#46;28&#177;1&#46;56 and 5&#46;31&#177;1&#46;56 umol&#47;L&#44; respectively&#41; were significantly lower than that in the healthy control group &#40;6&#46;33&#177;2&#46;04 umol&#47;L&#59; <span class="elsevierStyleItalic">p</span>&#61;0&#46;002 and 0&#46;018&#44; respectively&#41;&#46; Serum bile acid level was positively associated with the BMD of the lumbar spine&#44; femoral neck&#44; and total hip&#46; However&#44; it negatively correlated with &#946;-CTX concentration&#46; Moreover&#44; no correlation was observed between bile acid and P1NP levels&#44; and the levels of the other biomarkers that were measured did not differ between the groups&#46;</p></span> <span id="ceabs40" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cestitle40">CONCLUSION&#58;</span><p id="spara60" class="elsevierStyleSimplePara elsevierViewall">Serum bile acid was positively correlated with BMD and negatively correlated with bone turnover biomarkers reflecting bone absorption in postmenopausal women&#46; Thus&#44; bile acid may play an important role in bone metabolism&#46;</p></span>"
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            "titulo" => "RESULTS&#58;"
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        "nota" => "<p class="elsevierStyleNotepara" id="cenpara40">No potential conflict of interest was reported&#46;</p>"
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          "leyenda" => "<p id="TFN01t01" class="elsevierStyleSimplePara elsevierViewall">BMI&#58; body mass index&#59; TG&#58; triglyceride&#59; TC&#58; total cholesterol&#59; HDL-C&#58; high-density lipoprotein cholesterol&#59; LDL-C&#58; low-density lipoprotein cholesterol&#46;</p>"
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                  """
              ]
            ]
          ]
        ]
        "descripcion" => array:1 [
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        ]
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      1 => array:7 [
        "identificador" => "tbl2"
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        "tipo" => "MULTIMEDIATABLA"
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          "leyenda" => "<p id="TFN01t02" class="elsevierStyleSimplePara elsevierViewall">&#42;&#44;&#42;&#42;&#44; and &#916;&#916; indicate significant differences between the two groups after a pairwise comparison&#46;</p><p id="TFN05t02" class="elsevierStyleSimplePara elsevierViewall">P1NP&#58; procollagen type I N-peptide&#59; &#946;-CTX&#58; cross-linked C-terminal telopeptide of type I collagen&#59; BMD&#58; bone mineral density&#59; LS&#58; lumbar spine&#59; FN&#58; femoral neck&#59; TH&#58; total hip&#46;</p>"
          "tablatextoimagen" => array:1 [
            0 => array:1 [
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                  \t\t\t\t">LS BMD &#40;g&#47;cm<span class="elsevierStyleSup">2</span>&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">0&#46;900&#177;0&#46;101<a class="elsevierStyleCrossRef" href="#TFN03t02">&#42;&#42;</a>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">1&#46;033&#177;0&#46;066&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">LS BMD T score&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
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                  \t\t\t\t">-1&#46;280&#177;0&#46;877<a class="elsevierStyleCrossRef" href="#TFN03t02">&#42;&#42;</a>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">-0&#46;087&#177;0&#46;578&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">FN BMD &#40;g&#47;cm<span class="elsevierStyleSup">2</span>&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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Article information

ISSN: 18075932
Original language: English

DOI:10.6061/clinics/2020/e1486

The statistics are updated each day

Year/Month	Html	Pdf	Total

2024 November	7	5	12
2024 October	49	26	75
2024 September	34	22	56
2024 August	39	20	59
2024 July	44	18	62
2024 June	28	17	45
2024 May	45	11	56
2024 April	36	19	55
2024 March	41	9	50
2024 February	25	15	40
2024 January	13	16	29
2023 December	16	14	30
2023 November	23	17	40
2023 October	23	24	47
2023 September	22	24	46
2023 August	33	5	38
2023 July	15	19	34
2023 June	25	5	30
2023 May	11	1	12
2023 April	6	1	7
2023 March	4	1	5
2023 February	0	0	0
2023 January	4	2	6
2022 December	13	2	15
2022 November	1	0	1

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