RESUMO
The current study evaluated the efficacy and safety of a denosumab biosimilar, QL1206 (60 mg), compared to placebo in postmenopausal Chinese women with osteoporosis and high fracture risk. At 31 study centers in China, a total of 455 postmenopausal women with osteoporosis and high fracture risk were randomly assigned to receive QL1206 (60 mg subcutaneously every 6 months) or placebo. From baseline to the 12-month follow-up, the participants who received QL1206 showed significantly increased bone mineral density (BMD) values (mean difference and 95% CI) in the lumbar spine: 4.780% (3.880%, 5.681%), total hip :3.930% (3.136%, 4.725%), femoral neck 2.733% (1.877%, 3.589%) and trochanter: 4.058% (2.791%, 5.325%) compared with the participants who received the placebo. In addition, QL1206 injection significantly decreased the serum levels of C-terminal crosslinked telopeptides of type 1 collagen (CTX): -77.352% (-87.080%, -66.844%), and N-terminal procollagen of type l collagen (P1NP): -50.867% (-57.184%, -45.217%) compared with the placebo over the period from baseline to 12 months. No new or unexpected adverse events were observed. We concluded that compared with placebo, QL1206 effectively increased the BMD of the lumbar spine, total hip, femoral neck and trochanter in postmenopausal Chinese women with osteoporosis and rapidly decreased bone turnover markers. This study demonstrated that QL1206 has beneficial effects on postmenopausal Chinese women with osteoporosis and high fracture risk.
Assuntos
Medicamentos Biossimilares , Conservadores da Densidade Óssea , Osteoporose Pós-Menopausa , Osteoporose , Feminino , Humanos , Medicamentos Biossimilares/efeitos adversos , Densidade Óssea , Conservadores da Densidade Óssea/uso terapêutico , Remodelação Óssea , Denosumab/uso terapêutico , Denosumab/farmacologia , Método Duplo-Cego , População do Leste Asiático , Osteoporose/tratamento farmacológico , Osteoporose Pós-Menopausa/complicações , Osteoporose Pós-Menopausa/tratamento farmacológico , Pós-MenopausaRESUMO
AIM: To investigate the effects of calcium and vitamin D supplementation on bone turnover marker levels, muscle strength and quality of life in postmenopausal Chinese women. METHODS: A total of 485 healthy postmenopausal Chinese women (63.44±5.04 years) were enrolled in this open-label, 2-year, prospective, community-based trial. The participants were divided into group A, B, C, which were treated with calcium (600 mg/d) alone, calcium (600 mg/d) and cholecalciferol (800 IU/d) or calcium (600 mg/d) and calcitriol (0.25 µg/d), respectively, for 2 years. Serum levels of 25-hydroxyvitamin D, parathyroid hormone, ß-CTX and P1NP were measured, and the muscle strength and quality of life were assessed at baseline and at 12- and 24-month follow-ups. RESULTS: Four hundred and sixty one participants completed this study. Serum levels of 25-hydroxyvitamin D were significantly increased in group C, but not changed in groups A and B at 24-month follow-up. Serum levels of parathyroid hormone, bone turnover marker ß-CTX and bone formation marker P1NP were significantly decreased in group C, while serum levels of ß-CTX were increased in group A at 24-month follow-up. The participants in group C maintained the grip strength, while those in groups A and B exhibited decreased grip strength at 24-month follow-up. The quality of life for the participants in groups B and C remained consistent, but that in group A was deteriorated at 24-month follow-up. CONCLUSION: Supplementation with calcitriol and calcium modifies the bone turnover marker levels, and maintains muscle strength and quality of life in postmenopausal Chinese women, whereas supplementation with cholecalciferol and calcium prevents aging-mediated deterioration in quality of life.
Assuntos
Calcitriol/farmacologia , Cálcio/farmacologia , Colecalciferol/farmacologia , Pós-Menopausa , Qualidade de Vida , Vitaminas/farmacologia , Idoso , Conservadores da Densidade Óssea/administração & dosagem , Conservadores da Densidade Óssea/farmacologia , Remodelação Óssea/efeitos dos fármacos , Calcitriol/administração & dosagem , Cálcio/administração & dosagem , China , Colecalciferol/administração & dosagem , Suplementos Nutricionais/análise , Feminino , Força da Mão , Humanos , Pessoa de Meia-Idade , Força Muscular/efeitos dos fármacos , Estudos Prospectivos , Vitamina D/análogos & derivados , Vitamina D/sangue , Vitaminas/administração & dosagemRESUMO
AIM: Oral risedronate is effective in the treatment of postmenopausal osteoporosis when administered daily, weekly, or monthly. In this 1-year, randomized, double-blind, multicenter study we compared the weekly 35-mg and daily 5-mg risedronate dosing regimens in the treatment of Chinese postmenopausal women with osteoporosis or osteopenia. METHODS: Postmenopausal women with primary osteoporosis or osteopenia were randomly assigned to the weekly group or daily group (n=145 for each) that received oral risedronate 35 mg once a week or 5 mg daily, respectively, for 1 year. The subjects' bone mineral densities (BMDs), bone turnover markers (P1NP and ß-CTX), new vertebral fractures, and adverse events were assessed at baseline and during the treatments. RESULTS: All subjects in the weekly group and 144 subjects in the daily group completed the study. The primary efficacy endpoint after 1 year, ie the mean percent changes in the lumbar spine BMD (95% CI) were 4.87% (3.92% to 5.81%) for the weekly group and 4.35% (3.31% to 5.39%) for the daily group. The incidences of clinical adverse events were 48.3% in the weekly group and 54.2% in the daily group. CONCLUSION: The weekly 35-mg and daily 5-mg risedronate dosing regimens during 1 year of follow-up show similar efficacy in improving BMDs and biochemical markers of bone turnover in Chinese postmenopausal women with osteoporosis or osteopenia. Moreover, the two dosing regimens exhibit similar safety and tolerability.
Assuntos
Povo Asiático , Conservadores da Densidade Óssea/administração & dosagem , Doenças Ósseas Metabólicas/tratamento farmacológico , Osteoporose Pós-Menopausa/tratamento farmacológico , Ácido Risedrônico/administração & dosagem , Idoso , Densidade Óssea/efeitos dos fármacos , Conservadores da Densidade Óssea/efeitos adversos , Doenças Ósseas Metabólicas/diagnóstico , Doenças Ósseas Metabólicas/epidemiologia , China/epidemiologia , Método Duplo-Cego , Esquema de Medicação , Feminino , Seguimentos , Gastroenteropatias/induzido quimicamente , Humanos , Pessoa de Meia-Idade , Osteoporose Pós-Menopausa/diagnóstico , Osteoporose Pós-Menopausa/epidemiologia , Estudos Prospectivos , Ácido Risedrônico/efeitos adversos , Fatores de Tempo , Resultado do TratamentoRESUMO
Dent disease comprises a group of X-linked recessive inherited renal tubular disorders, the symptoms of which include low-molecular-weight proteinuria (LMWP), hypercalciuria, nephrocalcinosis, and progressive renal failure. We sought to characterize the clinical manifestations and to identify the mutations associated with this disease in Chinese patients. In total, 155 DNA samples were collected from one affected individual, four of his family members, and 150 healthy donors. All 12 exons and the exon-intron boundaries of the CLCN5 gene were amplified and directly sequenced in this Chinese family. The proband demonstrated osteomalacia, which had resulted in more than 10 fractures, LMWP, and renal failure. A single base 'G' deletion at nucleotide 246 (c. 246delG) was identified in exon 5 of the CLCN5 gene in this patient, resulting in a frame shift mutation (fsX) that changed the Threonine (Thr) residue in position 83 to Proline (Pro). The proband's mother was found to be a carrier of this mutation. The present study suggests that a novel frameshift mutation (c. 246delG) in exon 5 of the CLCN5 gene is responsible for Dent disease in this case. Our findings also expand the known spectrum of CLCN5 mutations.
Assuntos
Canais de Cloreto/genética , Doenças Genéticas Ligadas ao Cromossomo X/genética , Mutação , Nefrolitíase/genética , Adulto , Humanos , Masculino , Proteinúria/genéticaRESUMO
AIM: PRD1-BF-1-RIZ1 homologous domain containing protein-16 (PRDM16) is a cell-autonomous transcriptional component that stimulates the development of brown fat cells. The aim of this study was to investigate the contribution of genetic variants of PRDM16 to obesity-related phenotype variations in Chinese. METHODS: A total of 3204 subjects (consisting of 400 male-offspring nuclear families, 401 female-offspring nuclear families, and 729 unrelated older males) were recruited. Ten tag single nucleotide polymorphisms (SNPs) within the PRDM16 gene were genotyped using multiplex quantitative real-time PCR by Taqman assay. Body compositions were measured by dual-energy X-ray absorptiometry (DXA). The associations of the SNPs with the obesity-related phenotypes were analyzed using the quantitative transmission disequilibrium test (QTDT), GLM-ANOVA and PLINK statistical methods. RESULTS: Rs2236518 was the only SNP that was associated with BMI in young (aged 20-40 years) males (P=0.011) using QTDT, and in the older men (aged 50-80 years) (P=0.003) using GLM-ANOVA. No significant associations were detected in the females. Nor was a relationship found between any haplotype and obesity-related phenotypes. When PLINK was used, no significant relationship was detected between 10 SNPs and obesity-related phenotypes in any of the studied cohorts. CONCLUSION: Rs2236518 is associated with BMI in the young males (using QTDT), and the older males (using GLM-ANOVA).However, the result is not confirmed using PLINK. The discrepancy needs to be further addressed.
Assuntos
Povo Asiático/genética , Índice de Massa Corporal , Proteínas de Ligação a DNA/genética , Polimorfismo de Nucleotídeo Único , Fatores de Transcrição/genética , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Estudos de Coortes , Feminino , Haplótipos , Humanos , Masculino , Pessoa de Meia-Idade , Obesidade/genética , FenótipoRESUMO
Zoledronic acid (ZOL) is a potent antiresorptive agent that increases bone mineral density (BMD) and reduces fracture risk in postmenopausal osteoporosis (PMOP). The anti-osteoporotic effect of ZOL is determined by annual BMD measurement. In most cases, bone turnover markers function as early indicators of therapeutic response, but they fail to reflect long-term effects. We used untargeted metabolomics to characterize time-dependent metabolic shifts in response to ZOL and to screen potential therapeutic markers. In addition, bone marrow RNA-seq was performed to support plasma metabolic profiling. Sixty rats were assigned to sham-operated group (SHAM, n = 21) and ovariectomy group (OVX, n = 39) and received sham operation or bilateral ovariectomy, respectively. After modeling and verification, rats in the OVX group were further divided into normal saline group (NS, n = 15) and ZOL group (ZA, n = 18). Three doses of 100 µg/kg ZOL were administrated to the ZA group every 2 weeks to simulate 3-year ZOL therapy in PMOP. An equal volume of saline was administered to the SHAM and NS groups. Plasma samples were collected at five time points for metabolic profiling. At the end of the study, selected rats were euthanatized for bone marrow RNA-seq. A total number of 163 compound were identified as differential metabolites between the ZA and NS groups, including mevalonate, a critical molecule in target pathway of ZOL. In addition, prolyl hydroxyproline (PHP), leucyl hydroxyproline (LHP), 4-vinylphenol sulfate (4-VPS) were identified as differential metabolites throughout the study. Moreover, 4-VPS negatively correlated with increased vertebral BMD after ZOL administration as time-series analysis revealed. Bone marrow RNA-seq showed that the PI3K-AKT signaling pathway was significantly associated with ZOL-mediated changes in expression (adjusted-p = 0.018). In conclusion, mevalonate, PHP, LHP, and 4-VPS are candidate therapeutic markers of ZOL. The pharmacological effect of ZOL likely occurs through inhibition of the PI3K-AKT signaling pathway.
RESUMO
Dominant inheritance of osteogenesis imperfecta (OI) is caused by mutations in COL1A1 or COL1A2, the genes that encode type I collagen, and CRTAP, LEPRE1, PPIB, FKBP10, SERPINH1, and SP7 mutations were recently detected in a minority of patients with autosomal recessive OI. However, these findings have been mostly restricted to Western populations. The proportion of mutations and the correlations between genotype and phenotype in Chinese patients with OI are completely unknown. In this study, mutation analyses were performed for COL1A1, COL1A2, CRTAP, and LEPRE1 in a cohort of 58 unrelated Chinese patients with OI; the relationship between collagen type I mutations and clinical features was examined. A total of 56 heterozygous mutations were identified in COL1A1 and COL1A2, including 43 mutations in COL1A1 and 13 mutations in COL1A2. Among the 56 causative COL1A1 and COL1A2 mutations, 24 novel mutations were found, and 25 (44.6%) resulted in the substitution of a glycine within the Gly-X-Y triplet domain of the triple helix. Compared with COL1A1 haploinsufficiency (n = 23), patients with mutations affecting glycine residues had a severe skeletal phenotype. In patients 18 years of age or older, on average patients with COL1A1 haploinsufficiency were taller and had higher femoral neck bone mineral density than with patients with helical mutations. Interestingly, we found two novel compound heterozygous mutations in the LEPRE1 gene in two unrelated families with autosomal recessive OI. Although the genotype-phenotype correlation is still unclear, our findings are useful to understand the genetic basis of Chinese patients with OI.
Assuntos
Povo Asiático/genética , Colágeno Tipo I/genética , Predisposição Genética para Doença , Glicoproteínas de Membrana/genética , Mutação/genética , Osteogênese Imperfeita/genética , Proteoglicanas/genética , Adolescente , Adulto , Substituição de Aminoácidos/genética , Sequência de Bases , Criança , Pré-Escolar , China , Cadeia alfa 1 do Colágeno Tipo I , Análise Mutacional de DNA , Proteínas da Matriz Extracelular/genética , Feminino , Fêmur/diagnóstico por imagem , Genes Recessivos/genética , Humanos , Masculino , Pessoa de Meia-Idade , Chaperonas Moleculares , Dados de Sequência Molecular , Osteogênese Imperfeita/diagnóstico por imagem , Prolil Hidroxilases , Radiografia , Adulto JovemRESUMO
Osteopetrosis is a heritable bone disorder resulting from a deficiency of or a functional defect in osteoclasts. We aimed to characterize the molecular defects and clinical manifestations in Chinese patients with osteopetrosis by studying 12 unrelated osteopetrosis families. The entire coding region and adjacent splice sites of the CLCN7, TCIRG1, LRP5 and SOST genes were amplified and directly sequenced. X-rays of hip and lumbar spine, bone mineral density and bone turnover markers were examined simultaneously. Family history and fracture history were collected using a questionnaire. Among 12 unrelated families, 10 families were diagnosed with autosomal dominant osteopetrosis type II (ADOII) with 10 probands and 3 affected subjects. Two individuals in the other two families were diagnosed with uncategorized osteopetrosis because no mutations were detected in any of the four studied genes. Eight mutations, including two reported mutations (R767W and E798FS) and six novel mutations (E313K, A316G, R743W, G741R, W127G and S290F), were detected in the CLCN7 gene from 12 living ADOII patients. Among them, R767W and R743W mutations were two common mutations that were each found in 20% of 10 ADOII probands. In CLCN7-related ADOII patients, long bone fractures and elevated serum CK level were two major clinical phenotypes, especially in patients younger than 18 years. Further functional studies of the above eight mutations in the CLCN7 gene are needed in the future.
Assuntos
Povo Asiático/genética , Canais de Cloreto/genética , Mutação/genética , Osteopetrose/genética , Osteopetrose/patologia , Adolescente , Adulto , Densidade Óssea , Criança , Pré-Escolar , China , Família , Feminino , Estudos de Associação Genética , Saúde , Heterozigoto , Quadril/diagnóstico por imagem , Quadril/fisiopatologia , Humanos , Vértebras Lombares/diagnóstico por imagem , Vértebras Lombares/fisiopatologia , Masculino , Osteopetrose/diagnóstico por imagem , Osteopetrose/fisiopatologia , Fenótipo , Radiografia , Doadores de Tecidos , Virulência/genética , Adulto JovemRESUMO
To increase awareness of the rarity of Paget's disease of bone (PDB) in the Chinese population, we characterized the clinical manifestations and features of 13 Chinese sporadic PDB patients. The clinical features of our Chinese PDB patients show similarities with cases reported in Western countries. The most common lesion sites were the pelvis, femur, and tibia; the next most common lesion sites were the spine and skull. Most patients had a higher serum alkaline phosphatase (ALP) level. Treatment with bisphosphonates was effective. In addition, we screened for PDB-causing mutations and performed a functional analysis in an attempt to elucidate the molecular pathogenesis of PDB. A total of 216 persons, including 13 sporadic PDB patients, three unaffected relatives of 1 patient, and 200 healthy donors, were recruited. All eight exons and exon-intron boundaries of the SQSTM1 gene were amplified by polymerase chain reaction (PCR) and directly sequenced. We identified a 53-year-old man who harbored a heterozygous T-to-C transversion at position 1250 in exon 8 (1250T > C), which resulted in a methionine-to-threonine (ATG > ACG) substitution at codon 404 (M404T). The M404T mutant SQSTM1 protein exhibited increased NF-κB activation and drove a significantly increased number of osteoclast-like cells (OLCs) that formed in response to RANKL and an increased number of OLC nuclei. This is the first report of an SQSTM1 genetic mutation that contributes to the pathogenesis of PDB in Chinese patients. These results may partially explain the mechanism by which this SQSTM1 mutation contributes to the pathogenesis of sporadic PDB in Chinese patients.
Assuntos
Proteínas Adaptadoras de Transdução de Sinal/genética , Mutação de Sentido Incorreto , Osteíte Deformante/genética , Mutação Puntual , Adulto , Idoso , Idoso de 80 Anos ou mais , Fosfatase Alcalina/sangue , Povo Asiático , Linhagem Celular , Núcleo Celular/genética , Núcleo Celular/metabolismo , Difosfonatos/uso terapêutico , Éxons , Feminino , Heterozigoto , Humanos , Íntrons , Masculino , Pessoa de Meia-Idade , NF-kappa B/metabolismo , Osteíte Deformante/tratamento farmacológico , Osteíte Deformante/metabolismo , Osteíte Deformante/patologia , Osteoclastos/efeitos dos fármacos , Osteoclastos/metabolismo , Ligante RANK/metabolismo , Proteína Sequestossoma-1RESUMO
AIM: To compare the effects of cholecalciferol (800 IU/d) and calcitriol (0.25 µg/d) on calcium metabolism and bone turnover in Chinese postmenopausal women with vitamin D insufficiency. METHODS: One hundred Chinese postmenopausal women aged 63.8±7.0 years and with serum 25-hydroxyvitamin D [25(OH)D] concentration <30 ng/mL were recruited. The subjects were divided into 2 groups based on the age and serum 25(OH)D concentration: 50 subjects (group A) received cholecalciferol (800 IU/d), and 50 subjects (group B) received calcitriol (0.25 µg/d) for 3 months. In addition, all the subjects received Caltrate D (calcium plus 125 IU cholecalciferol) daily in the form of one pill. The markers of calcium metabolism and bone turnover, including the serum levels of calcium, phosphorus, alkaline phosphatase, intact parathyroid hormone, 25(OH)D and ß-CrossLaps of type I collagen containing cross-linked C-telopeptide (ß-CTX), were measured before and after the intervention. RESULTS: After the 3-month intervention, the serum 25(OH)D concentration in group A was significantly increased from 16.01 ± 5.0 to 20.02 ± 4.5 ng/mL, while that in group B had no significant change. The serum calcium levels in both the groups were significantly increased (group A: from 2.36 ± 0.1 to 2.45 ± 0.1 mmol/L; group B: from 2.36 ± 0.1 to 2.44 ± 0.1 mmol/L). The levels of serum intact parathyroid hormone in both the groups were significantly decreased (group A: from 48.56 ± 12.8 to 39.59 ± 12.6 pg/mL; group B: from 53.67 ± 20.0 to 40.32 ± 15.4 pg/mL). The serum levels of ß-CTX in both the groups were also significantly decreased (group A: from 373.93 ± 135.3 to 325.04 ± 149.0 ng/L; group B: from 431.00 ± 137.1 to 371.74 ± 185.0 ng/L). CONCLUSION: We concluded that both cholecalciferol (800 IU/d) and calcitriol (0.25 µg/d) plus Caltrate D modifies the serum calcium and bone turnover markers in Chinese postmenopausal women with vitamin D insufficiency. In addition, cholecalciferol (800 IU/d) significantly increased the serum 25(OH)D concentration.
Assuntos
Conservadores da Densidade Óssea/farmacologia , Calcitriol/farmacologia , Cálcio/sangue , Colecalciferol/farmacologia , Pós-Menopausa/efeitos dos fármacos , Deficiência de Vitamina D/sangue , Idoso , Osso e Ossos/efeitos dos fármacos , Cálcio/metabolismo , Feminino , Humanos , Pessoa de Meia-Idade , Vitamina D/análogos & derivados , Vitamina D/sangue , Deficiência de Vitamina D/complicaçõesRESUMO
AIM: Myostatin gene is a member of the transforming growth factor-ß (TGF-ß) family that negatively regulates skeletal muscle growth. Genetic polymorphisms in Myostatin were found to be associated with the peak bone mineral density (BMD) in Chinese women. The purpose of this study was to investigate whether myostatin played a role in the normal variation in peak BMD, lean mass (LM), and fat mass (FM) of Chinese men. METHODS: Four hundred male-offspring nuclear families of Chinese Han ethnic group were recruited. Anthropometric measurements, including the peak BMD, body LM and FM were measured using dual-energy X-ray absorptiometry (DXA). The single nucleotide polymorphisms (SNPs) studied were tag-SNPs selected by sequencing. Both rs2293284 and +2278GA were genotyped using TaqMan assay, and rs3791783 was genotyped with PCR-restriction fragment length polymorphism (RFLP) analysis. The associations of the SNPs with anthropometric variations were analyzed using the quantitative transmission disequilibrium test (QTDT). RESULTS: Using QTDT to detect within-family associations, neither single SNP nor haplotype was found to be associated with peak BMD at any bone site. However, rs3791783 was found to be significantly associated with fat mass of the trunk (P<0.001). Moreover, for within-family associations, haplotypes AGG, AAA, and TGG were found to be significantly associated with the trunk fat mass (all P<0.001). CONCLUSION: Our results suggest that genetic variation within myostatin may play a role in regulating the variation in fat mass in Chinese males. Additionally, the myostatin gene may be a candidate that determines body fat mass in Chinese men.
Assuntos
Adiposidade/genética , Povo Asiático/genética , Peso Corporal/genética , Densidade Óssea/genética , Miostatina/genética , Polimorfismo de Nucleotídeo Único , Absorciometria de Fóton , Tecido Adiposo/química , Adolescente , Adulto , Análise de Variância , Distribuição de Qui-Quadrado , China , Frequência do Gene , Haplótipos , Humanos , Desequilíbrio de Ligação , Masculino , Músculo Esquelético/química , Fenótipo , RNA Mensageiro/análise , Valores de Referência , Fatores Sexuais , Adulto JovemRESUMO
AIM: Genetic variation in ALOX12, which encoded human 12-lipoxygenase, was found to be associated with fat mass in young Chinese men. The objective of this study was to investigate the relationship between single nucleotide polymorphisms (SNPs) and haplotypes in the ALOX15 gene and obesity-related phenotypes in Chinese nuclear families with male offspring. METHODS: We recruited 1,296 subjects from 427 nuclear families with male offspring and genotyped five SNPs (rs9894225, rs748694, rs2619112, rs2619118, and rs916055) in the ALOX15 gene locus. The total fat mass (TFM), trunk fat mass (tFM), leg fat mass (LFM) and arm fat mass (AFM) were measured using dual-energy X-ray absorptiometry (DXA). The percentage of fat mass (PFM) was the ratio of TFM and body weight. The association between SNPs and haplotypes of ALOX15 and obesity-related phenotypic variation was measured using quantitative transmission disequilibrium test (QTDT). RESULTS: Using QTDT to measure family-based genetic association, we found that rs916055 had a statistically significant association with PFM (P=0.038), whereas rs916055 had a marginal but statistically insignificant association with tFM (P=0.093). The multiple-parameter 1000 permutations test agreed with the family-based association results: both showed that rs916055 had a statistically significant association with PFM (P=0.033). CONCLUSION: rs916055 in ALOX15 gene was significantly associated with the percentage of fat mass in Chinese nuclear families with male offspring in the family-based association study using QTDT approach.
Assuntos
Araquidonato 15-Lipoxigenase/genética , Povo Asiático/genética , Obesidade/genética , Polimorfismo Genético , Absorciometria de Fóton , Adulto , Idoso , Gorduras/metabolismo , Feminino , Haplótipos , Humanos , Masculino , Pessoa de Meia-Idade , Núcleo Familiar , Fenótipo , Adulto JovemRESUMO
Previous studies have suggested that changes in hip geometry increase the risk of hip fracture. The aim of this study was to identify whether body composition were associated with hip geometry or bone mineral density (BMD) in a large sample of Chinese people. A total of 2072 subjects aged 20-79 yr (including 700 males and 1372 females) were selected. The following measurements were taken: lumbar spine (L1-4); proximal femur BMD; lean mass (LM); fat mass (FM); and hip geometric parameters, including hip axis length (HAL), cross-sectional moment of inertia (CSMI), cross-sectional area (CSA), neck-shaft angle, and femur strength index (SI) by dual-energy X-ray absorptiometry. FM and LM were positively correlated with HAL, CSMI, and CSA, and negatively correlated with SI in both men and women. Multiple regression analysis showed that leg LM contributions to HAL, CSMI, and CSA variance were 12.6-37.6%. Compared with FM, LM was generally more strongly related to hip geometry and BMD in young and old men and women. Body composition was a good predictor for hip geometry parameter variation and BMD variation.
Assuntos
Absorciometria de Fóton/métodos , Composição Corporal , Densidade Óssea , Quadril/diagnóstico por imagem , Vértebras Lombares/diagnóstico por imagem , Obesidade/epidemiologia , Adulto , Distribuição por Idade , Fatores Etários , Idoso , China/epidemiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Obesidade/diagnóstico por imagem , Prevalência , Estudos Retrospectivos , Distribuição por Sexo , Fatores Sexuais , Adulto JovemRESUMO
PURPOSES: In order to investigate the association between serum periostin levels and the variation of its encoding gene POSTN and the prevalence of vertebral fractures and bone mineral density (BMD) in Chinese postmenopausal women, an association study was performed. MATERIALS AND METHODS: 385 postmenopausal women were recruited. For participants without a history of vertebral fracture, lateral X-rays of the spine covering the fourth thoracic spine to the fifth lumbar spine were performed to detect any asymptomatic vertebral fractures. Ten tag-single nucleotide polymorphisms (SNP) of POSTN were genotyped. Serum periostin levels, biochemical parameters, and BMD were measured individually. RESULTS: rs9603226 was significantly associated with vertebral fractures. Compared to allele G, the minor allele A carriers of rs9603226 had a 1.722-fold higher prevalence of vertebral fracture (p = 0.037). rs3923854 was significantly associated with the serum periostin level. G/G genotype of rs3923854 had a higher serum periostin level than C/C and C/G (67.26 ± 19.90 ng/mL vs. 54.57 ± 21.44 ng/mL and 54.34 ± 18.23 ng/mL). Furthermore, there was a negative correlation between the serum level of periostin and BMD at trochanter and total hip. CONCLUSION: Our study suggested that genetic variation of POSTN could be a predicting factor for the risk of vertebral fractures. The serum level of periostin could be a potential biochemical parameter for osteoporosis in Chinese postmenopausal women.
Assuntos
Fraturas por Osteoporose , Fraturas da Coluna Vertebral , Densidade Óssea/genética , China , Feminino , Humanos , Fraturas por Osteoporose/genética , Polimorfismo de Nucleotídeo Único , Pós-Menopausa/genética , Fraturas da Coluna Vertebral/epidemiologia , Fraturas da Coluna Vertebral/genéticaRESUMO
AIM: To study whether genetic polymorphisms of COL1A1 and COL1A2 genes affected the onset of fracture in postmenopausal Chinese women. METHODS: SNPs in COL1A1 and COL1A2 genes were identified via direct sequencing in 32 unrelated postmenopausal Chinese women. Ten SNPs were genotyped in 1252 postmenopausal Chinese women. The associations were examined using both single-SNP and haplotype tests using logistic regression. RESULTS: Twenty four (4 novel) and 28 (7 novel) SNPs were identified in COL1A1 and COL1A2 gene, respectively. The distribution frequencies of 2 SNPs in COL1A1 (rs2075554 and rs2586494) and 3 SNPs in COL1A2 (rs42517, rs1801182, and rs42524) were significantly different from those documented for the European Caucasian population. No significant difference was observed between fracture and control groups with respect to allele frequency or genotype distribution in 9 selected SNPs and haplotype. No significant association was found between fragility fracture and each SNP or haplotype. The results remained the same after additional corrections for other risk factors such as weight, height, and bone mineral density. CONCLUSION: Our results show no association between common genetic variations of COL1A1 and COL1A2 genes and fracture, suggesting the complex genetic background of osteoporotic fractures.
Assuntos
Povo Asiático/genética , Colágeno Tipo I/genética , Fraturas por Osteoporose/genética , Pós-Menopausa , Idoso , Idoso de 80 Anos ou mais , Cadeia alfa 1 do Colágeno Tipo I , Feminino , Genótipo , Haplótipos , Humanos , Desequilíbrio de Ligação , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo ÚnicoRESUMO
BACKGROUND: The Wnt/beta-catenin signaling pathway plays an important role in skeletal development. Polymorphisms of frizzled-related protein (FRZB), an antagonist of this pathway, may generate variations in bone mineral density (BMD). In this study, we analyzed the association between FRZB genotypes and peak BMD variation in the spines and hips of two relatively large samples of Chinese female-offspring and male-offspring nuclear families. METHODS: We recruited 1,260 subjects from 401 female-offspring nuclear families and 1,296 subjects from 427 male-offspring nuclear families and genotyped four tagging single nucleotide polymorphisms (tagSNPs) (rs6433993, rs409238, rs288324, and rs4666865) spanning the entire FRZB gene. The SNPs rs288326 and rs7775, which are associated with hip osteoarthritis, were not selected in this study because of their low minor allele frequencies (MAFs) in Chinese people. The quantitative transmission disequilibrium test (QTDT) was used to analyze the association between each SNP and haplotype with peak BMD in female- and male-offspring nuclear families. RESULTS: In the female-offspring nuclear families, we found no evidence of an association between either single SNPs or haplotypes and peak BMD in the spine or hip. In the male-offspring nuclear families, no within-family association was observed for either SNPs or haplotypes, although a significant total association was found between rs4666865 and spine BMD (P = 0.0299). CONCLUSION: Our results suggest that natural variation in FRZB is not a major contributor to the observed variability in peak BMD in either Chinese females or males. Because ethnic differences in the FRZB genotypes may exist, other studies in different population are required to confirm such results.
Assuntos
Densidade Óssea/genética , Glicoproteínas/genética , Adulto , Idoso , Alelos , China , Feminino , Frequência do Gene , Estudos de Associação Genética , Genótipo , Haplótipos , Humanos , Peptídeos e Proteínas de Sinalização Intracelular , Desequilíbrio de Ligação , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo ÚnicoRESUMO
AIM: To determine the associations between HOXD4 gene polymorphisms with peak bone mineral density (BMD) throughing measuring three tagging single nucleotide polymorphisms (tagSNPs), including rs1867863, rs13418078, and rs4972504, in HOXD4. METHODS: Four hundred Chinese nuclear families with male offspring (1215 subjects) and 401 Chinese nuclear families with female offspring (1260 subjects) were recruited. BMD of the lumbar spine 1-4 (L1-4) and left proximal femur including total hip and femoral neck were measured by dual-energy X-ray absorptiometry. The quantitative transmission disequilibrium test (QTDT) was performed to investigate the association among the tagging SNPs, haplotypes and peak BMD. RESULTS: Only the CC genotype was identified in rs13418078 in the Chinese population, unlike other populations. We failed to find significant within-family association among these SNPs, haplotypes and peak BMD at any bone site in either male- or female-offspring nuclear families. CONCLUSION: The results suggest that genetic polymorphisms in HOXD4 may not be a major contributor to the observed variability in peak BMD in the lumbar spine and the hip in Chinese men and women.
Assuntos
Povo Asiático/genética , Densidade Óssea/genética , Proteínas de Homeodomínio/genética , Absorciometria de Fóton , Adolescente , Adulto , China , Feminino , Colo do Fêmur , Haplótipos , Quadril , Humanos , Desequilíbrio de Ligação , Vértebras Lombares , Masculino , Polimorfismo de Nucleotídeo Único , Adulto JovemRESUMO
AIM: To investigate the effect of low-density lipoprotein receptor-related protein 5 (LRP5) gene polymorphisms on bone and obesity phenotypes in young Chinese men. METHODS: A total of 1244 subjects from 411 Chinese nuclear families were genotyped by using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) technique at the Q89R, N740N, and A1330V sites in the LRP5 gene. Bone mineral density (BMD) in the lumbar spine and the hip, total fat mass and total lean mass were measured using dual-energy X-ray absorptiometry. The association between LRP5 gene polymorphisms and peak BMD, body mass index (BMI), total fat mass, total lean mass and percentage of fat mass was assessed using a quantitative transmission disequilibrium test (QTDT). RESULTS: No significant within-family associations were found between genotypes or haplotypes of the LRP5 gene and peak BMD, BMI, total fat mass, total lean mass and percentage of fat mass. The 1000 permutations that were subsequently simulated were in agreement with these within-family association results. CONCLUSION: Our results suggest that common polymorphic variations of the LRP5 gene do not influence peak bone mass acquisition and obesity phenotypes in young Chinese men.
Assuntos
Povo Asiático/genética , Densidade Óssea/genética , Proteínas Relacionadas a Receptor de LDL/genética , Obesidade/genética , Polimorfismo de Fragmento de Restrição , Polimorfismo de Nucleotídeo Único , Adiposidade/genética , Adulto , Análise do Polimorfismo de Comprimento de Fragmentos Amplificados , Índice de Massa Corporal , Peso Corporal/genética , Distribuição de Qui-Quadrado , DNA/genética , Feminino , Fêmur/metabolismo , Frequência do Gene , Genótipo , Humanos , Proteína-5 Relacionada a Receptor de Lipoproteína de Baixa Densidade , Masculino , Núcleo Familiar , Fenótipo , Coluna Vertebral/metabolismo , Adulto JovemRESUMO
AIM: The goal of this study was to determine whether polymorphisms in the vitamin D receptor (VDR) and estrogen receptor alpha (ESR1) genes are associated with variations of peak bone mineral density (BMD) and obesity phenotypes in young Chinese men. METHODS: A total of 1215 subjects from 400 Chinese nuclear families were genotyped by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and allele-specific multiple PCR (ASM-PCR) analysis at the ApaI, FokI, and CDX2 sites in the VDR gene and the PvuII and XbaI sites in the ESR1 gene. BMD at the lumbar spine and hip, total fat mass, and total lean mass were measured using dual energy X-ray absorptiometry. The associations between VDR and ESR1 gene polymorphisms with peak BMD, body mass index (BMI), total fat mass, total lean mass, and percentage fat mass (PFM) were determined using quantitative transmission disequilibrium tests (QTDTs). RESULTS: Using QTDTs, no significant within-family associations were obtained between genotypes or haplotypes of the VDR and ESR1 genes and peak BMD. For the obesity phenotypes, the within-family associations were significant between CDX2 genotypes and BMI (P=0.046), fat mass (P=0.004), and PFM (P=0.020). Further, PvuII was significantly associated with the variation of fat mass and PFM (P=0.002 and P=0.039, respectively). A subsequent 1000 permutations were in agreement with these within-family association results. CONCLUSION: Our findings showed that VDR and ESR1 polymorphisms were associated with total fat mass in young Chinese men, but we failed to find a significant association between VDR and ESR1 genotypes and peak BMD. These findings suggested that the VDR and ESR1 genes are quantitative trait loci (QTL) underlying fat mass variation in young Chinese men.
Assuntos
Densidade Óssea/genética , Receptor alfa de Estrogênio/genética , Obesidade/genética , Polimorfismo de Fragmento de Restrição , Receptores de Calcitriol/genética , Adulto , Idoso , Alelos , Índice de Massa Corporal , Feminino , Estudos de Associação Genética , Humanos , Masculino , Pessoa de Meia-Idade , Núcleo Familiar , Adulto JovemRESUMO
AIM: Osteoclastic activity is mainly assessed by measurement of urinary markers (eg C-terminal cross-linked telopeptides of type I collagen, N-terminal crosslinked telopeptides of type I collagen, etc), the levels of which could often be affected by renal clearance. Recently, serum tartrate-resistant acid phosphatase 5b (TRACP5b) has been used as an alternative serum marker to evaluate osteoclastic activity. We investigated the age-related changes of TRACP5b level and its association with bone mineral density (BMD) in Chinese women. METHODS: Seven-hundred and twenty-two Chinese mainland women aged 20-79 years were recruited in the study. Serum TRACP5b level was measured using immunoassay to evaluate the state of bone resorption. Bone mineral density (BMD) (g/cm2) at lumbar spine 1-4 and proximal femur were measured by duelenergy X-ray absorptiometry. RESULTS: The serum TRACP5b level reached a bottom value in premenopausal women aged 30-39, gradually increased in women aged 40-49, rapidly rose in women aged 50-59, and culminated with a maximum value in women aged 60-69 before a slow drop in women aged 70- 79. The average level of TRACP5b was significantly higher in postmenopausal women [(3.29+/-1.07) U/L] than in premenopausal women ([1.70+/-0.59] U/L). The levels of TRACP5b were inversely correlated with BMD at all measured sites (P<0.001). Furthermore, the level of TRACP5b was obviously higher in women with osteoporosis and osteopenia than those with normal bone mass (P<0.001). CONCLUSION: We have established the reference values of serum TRACP5b in Chinese mainland women, and found that postmenopausal women had higher TRACP5b concentration than younger women. The results showed that serum TRACP5b was a sensitive and useful parameter for the evaluation of age-related changes of bone absorption.