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1.
Bone ; 164: 116513, 2022 11.
Artigo em Inglês | MEDLINE | ID: mdl-35944891

RESUMO

Men with distal forearm fractures have reduced bone density, an increased risk of osteoporosis and of further fractures. The aim of the study was to investigate the structural determinants of these observations using quantitative CT (qCT). Ninety six men with low-trauma distal forearm fracture and 101 age-matched healthy control subjects were recruited. All subjects underwent a quantitative CT on a standard 64-slice whole body CT scanner. These were analysed on Mindways QCT PRO™ Software to generate volumetric and geometric data at the lumbar spine, femoral neck and total hip, ultra-distal and distal 33 % radius. Biochemical investigations, health questionnaires and measurements of bone turnover were made. Men with fracture had significantly lower total and trabecular vBMD at all sites. The greatest percentage reduction was at the ultra-distal radius (13.5 % total and 11.7 % trabecular vBMD). In the fracture group cortical vBMD was significantly higher in the femoral neck (p < 0.001) and maintained at the ultra-distal radius compared with control subjects. However, cortical cross-sectional area (CSA) and thickness were significantly reduced at the femoral neck (p < 0.001 and p = 0.002 respectively) and forearm sites (CSA ultradistal radius p = 0.001, cortical thickness p = 0.002, CSA distal one third radius p = 0.045 and cortical thickness p = 0.005). Cross sectional moment of inertia (CSMI) and section moduli were significantly reduced at the femoral neck (CSMI1 p = 0.002, CSMI2 p = 0.012 and section moduli Z1 p < 0.001, Z2 p = 0.004) and the ultra-distal radius (CSMI1 p = 0.008 and section moduli Z1 p = 0.018, Z2 p = 0.007). In stepwise logistic regression analysis distal forearm fracture showed the strongest association with a model comprising ultra-distal forearm trabecular vBMD (negative), procollagen type I N-terminal propeptide (PINP, positive) and sex hormone binding globulin (SHBG, negative). In conclusion, these observations explain the structural reasons for the increased fracture risk in men with distal forearm fractures.


Assuntos
Osteólise , Fraturas por Osteoporose , Absorciometria de Fóton , Densidade Óssea , Antebraço , Humanos , Vértebras Lombares , Masculino , Rádio (Anatomia) , Globulina de Ligação a Hormônio Sexual , Tomografia Computadorizada por Raios X
3.
Int J Mol Sci ; 23(6)2022 Mar 09.
Artigo em Inglês | MEDLINE | ID: mdl-35328378

RESUMO

Mechanical loading exerts a profound influence on bone density and architecture, but the exact mechanism is unknown. Our study shows that expression of the neurological transcriptional factor zinc finger of the cerebellum 1 (ZIC1) is markedly increased in trabecular bone biopsies in the lumbar spine compared with the iliac crest, skeletal sites of high and low mechanical stress, respectively. Human trabecular bone transcriptome analyses revealed a strong association between ZIC1 mRNA levels and gene transcripts characteristically associated with osteoblasts, osteocytes and osteoclasts. This supposition is supported by higher ZIC1 expression in iliac bone biopsies from postmenopausal women with osteoporosis compared with age-matched control subjects, as well as strongly significant inverse correlation between ZIC1 mRNA levels and BMI-adjusted bone mineral density (BMD) (Z-score). ZIC1 promoter methylation was decreased in mechanically loaded vertebral bone compared to unloaded normal iliac bone, and its mRNA levels correlated inversely with ZIC1 promoter methylation, thus linking mechanical stress to epigenetic control of gene expression. The findings were corroborated in cultures of rat osteoblast progenitors and osteoblast-like cells. This study demonstrates for the first time how skeletal epigenetic changes that are affected by mechanical forces give rise to marked alteration in bone cell transcriptional activity and translate to human bone pathophysiology.


Assuntos
Osteoporose Pós-Menopausa , Animais , Densidade Óssea/genética , Epigênese Genética , Feminino , Humanos , Ílio/metabolismo , Vértebras Lombares/metabolismo , Osteoporose Pós-Menopausa/genética , Osteoporose Pós-Menopausa/patologia , RNA Mensageiro/genética , Ratos , Estresse Mecânico , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo
4.
BMJ Open ; 11(12): e051021, 2021 12 24.
Artigo em Inglês | MEDLINE | ID: mdl-34952875

RESUMO

OBJECTIVES: To evaluate a method of quantitative X-ray (QXR) for obtaining bone health information from standard radiographs aimed at identifying early signs of osteoporosis to enable improved referral and treatment. This QXR measurement is performed by postexposure analysis of standard radiographs, meaning bone health data can be acquired opportunistically, alongside routine imaging. DESIGN: The relationship between QXR and dual energy X-ray absorptiometry (DEXA) was demonstrated with a phantom study. A prospective clinical study was conducted to establish areal bone mineral density (aBMD) prediction model and a risk prediction model of a non-normal DEXA outcome. This was then extrapolated to a larger patient group with DEXA referral data. SETTING: Secondary care National Health Service Hospital. PARTICIPANTS: 126 consenting adult patients from a DEXA clinic. INTERVENTIONS: All participants underwent a DEXA scan to determine BMD at the lumbar spine (L2-L4) and both hips. An additional Antero-Posterior pelvis X-ray on a Siemens Ysio, fixed digital radiograph system was performed for the study. OUTCOME: Performance of QXR as a risk predictor for non-normal (osteoporotic) BMD. RESULTS: Interim clinical study data from 78 patients confirmed a receiver operator curve (area under the ROC curve) of 0.893 (95% CI 0.843 to 0.942) for a risk prediction model of non-normal DEXA outcome. Extrapolation of these results to a larger patient group of 11 029 patients indicated a positive predictive value of 0.98 (sensitivity of 0.8) for a population of patients referred to DEXA under current clinical referral criteria. CONCLUSIONS: This study confirms that the novel QXR method provides accurate prediction of a DEXA outcome. TRIAL REGISTRATION NUMBER: ISRCTN98160454; Pre-results.


Assuntos
Densidade Óssea , Atenção Secundária à Saúde , Absorciometria de Fóton/métodos , Adulto , Humanos , Vértebras Lombares/diagnóstico por imagem , Estudos Prospectivos , Medicina Estatal , Raios X
5.
Calcif Tissue Int ; 108(5): 634-639, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33388897

RESUMO

Paget's disease of bone (PDB) is the second commonest metabolic bone disorder in the UK after osteoporosis and is both underdiagnosed and undertreated. PDB is often found incidentally on plain X-rays. There is effective treatment so identification of affected individuals is important. The aim was to conduct an audit to determine what proportion of individuals with X-ray evidence of PDB were referred to secondary care. A retrospective audit of X-rays reports in men and women over 55 years of age was undertaken over 18 months searching for the key word "Paget's." The images of possible cases were reviewed and the presence of PDB confirmed. The proportion already known to secondary care was determined and those that had had isotope bone scans and treatment. Data recorded included site of lesion, age, gender, level of total alkaline phosphatase (ALP) and complications. A total of 68,873 X-rays were screened and 43 cases found. Pelvic images had the highest proportion of positive findings at 0.2% and 65% of the cases. 74% had not been referred to secondary care. The mean age was 86.7 years (range 65-95) and the ALP was elevated in 65% with a mean of 189u/L (range 47-804u/L). In 33 individuals, PDB had been recorded in the reports of previous X-rays. The rate of referral for specialist care remains low. The prevalence of the condition appears to be falling.


Assuntos
Osteíte Deformante , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Lactente , Masculino , Osteíte Deformante/diagnóstico por imagem , Encaminhamento e Consulta , Estudos Retrospectivos , Atenção Secundária à Saúde , Raios X
6.
Clin Med (Lond) ; 20(6): 568-571, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-33199322

RESUMO

Adult Paget's disease of bone is the second commonest metabolic bone condition after osteoporosis. The condition is characterised by increased bone cell activity, with bone-resorbing osteoclasts often larger and containing more nuclei than normal and osteoblasts producing increased amounts of disorganised bone. This leads to expanded bone of poor quality possessing both sclerotic and lytic areas. Paget's disease of bone has a strong genetic element, with a family history being noted in 10-20% of cases. A number of genetic defects have been found to be associated with the condition. The most common disease-associated variants identified affect the SQSTM1 gene, providing insights into disease aetiology, with the clinical value of knowledge of SQSTM1 mutation status currently under active investigation. The diagnosis may be suggested by an isolated raised total alkaline phosphatase (ALP) without other identifiable causes. This can be confirmed on plain X-ray and the extent determined by isotope bone scan. The mainstay of treatment are the bisphosphonates, especially intravenous zoledronate which results in long-term suppression of bone turnover. ALP is the usual means of monitoring the condition, although more specific bone turnover markers can be helpful, especially in coincident liver disease. Patients should be followed up to monitor for biochemical relapse or development of complications, which may require medical or surgical intervention.


Assuntos
Osteíte Deformante , Osteoporose , Adulto , Remodelação Óssea , Difosfonatos/uso terapêutico , Humanos , Mutação , Osteíte Deformante/diagnóstico , Osteíte Deformante/genética
8.
J Clin Densitom ; 23(3): 418-425, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31160147

RESUMO

The Mr F study investigates the pathogenesis of low trauma distal forearm fractures in men and includes volumetric bone mineral density (vBMD) measurements at the ultradistal forearm as there are no current data. A standard 64 slice CT scanner was used to determine if it was possible to adapt the existing Mindways quantitative computed tomography Pro software for measuring vBMD values at the hip and spine sites. For calculation of intra- and interobserver reliability 40 forearm scans out of the 300 available were chosen randomly. The images were analyzed using the Slice Pick module and Bone Investigational Toolkit. The 4% length of the radius was chosen by measuring the length of the radius from the scaphoid fossa distally to the radial head. The acquired image then underwent extraction, isolation, rotation, and selection of region of interest in order to generate a report on vBMD. A cross-sectional image was created to allow the generation of data on the cortical and trabecular components separately. Repeat analyses were undertaken by 3 independent observers who were blinded as to whether the image was from a participant with or without fracture. The images were presented in random order at each time point. The following parameters were recorded: cortical cross sectional area, total vBMD, trabecular vBMD, and cortical vBMD (CvBMD). Data were analyzed by calculating intraclass correlation coefficients for intra- and interobserver reliability. The lowest values occurred at the CvBMD with intraobserver reliability of 0.92 (95% confidence interval [CI] of 0.86-0.96) and interobserver reliability of 0.92 (95% CI 0.89-0.96). All other parameters had reliability values between 0.97 and 0.99 with tighter 95% CI than for CvBMD. The method of adapting the Mindways Pro software using a standard CT to produce vBMD and structural data at the ultradistal radius is reliable.


Assuntos
Densidade Óssea , Osso Esponjoso/diagnóstico por imagem , Osso Cortical/diagnóstico por imagem , Processamento de Imagem Assistida por Computador/métodos , Osteoporose/diagnóstico por imagem , Rádio (Anatomia)/diagnóstico por imagem , Software , Tomografia Computadorizada Espiral/métodos , Ulna/diagnóstico por imagem , Idoso , Traumatismos do Antebraço , Humanos , Masculino , Pessoa de Meia-Idade , Fraturas por Osteoporose/diagnóstico por imagem , Fraturas do Rádio/diagnóstico por imagem , Reprodutibilidade dos Testes , Tomógrafos Computadorizados , Tomografia Computadorizada Espiral/instrumentação , Fraturas da Ulna/diagnóstico por imagem
10.
Ann Hum Biol ; 46(5): 430-433, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31448632

RESUMO

In this study, VDR gene ApaI (rs7975232), BsmI (rs 1544410) and TaqI (rs731236) genotypes were compared in men with osteoporosis and male controls. Osteoporosis affects around 20% of all men and overall mortality in the first year after hip fracture is significantly higher in men than women, yet the genetic basis of osteoporosis is less well studied in males. This study consisted of White British males; 69 osteoporosis patients and 122 controls. BMDs at the lumbar spine (vertebrae L1-L4) and hip (femur neck) were measured by dual-energy X-ray absorptiometry (DEXA). The VDR gene ApaI, BsmI and TaqI genotypes were determined by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and association analysis was carried out at genotype and haplotype level. Our study suggests that TaqI polymorphism CC genotype frequency is lower in controls and further analysis of genotypes and BMD revealed a significant effect of TaqI polymorphism on Lumbar spine BMD. Two haplotypes (GCC and AAT) were associated with increased osteoporosis risk. In conclusion, VDR gene TaqI polymorphism in recessive mode had a significant effect on lumbar spine BMD within our study. Haplotypes GCC and AAT increase the risk of osteoporosis among White British males.


Assuntos
Densidade Óssea/genética , Osteoporose/genética , Polimorfismo Genético , Receptores de Calcitriol/genética , Absorciometria de Fóton , Idoso , Estudos de Casos e Controles , Colo do Fêmur/fisiologia , Genótipo , Haplótipos , Humanos , Vértebras Lombares/fisiologia , Masculino , Pessoa de Meia-Idade , Osteoporose/epidemiologia , Fatores de Risco , Reino Unido/epidemiologia
11.
J Bone Miner Res ; 34(4): 579-604, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30803025

RESUMO

An evidence-based clinical guideline for the diagnosis and management of Paget's disease of bone (PDB) was developed using GRADE methodology, by a Guideline Development Group (GDG) led by the Paget's Association (UK). A systematic review of diagnostic tests and pharmacological and nonpharmacological treatment options was conducted that sought to address several key questions of clinical relevance. Twelve recommendations and five conditional recommendations were made, but there was insufficient evidence to address eight of the questions posed. The following recommendations were identified as the most important: 1) Radionuclide bone scans, in addition to targeted radiographs, are recommended as a means of fully and accurately defining the extent of metabolically active disease in patients with PDB. 2) Serum total alkaline phosphatase (ALP) is recommended as a first-line biochemical screening test in combination with liver function tests in screening for the presence of metabolically active PDB. 3) Bisphosphonates are recommended for the treatment of bone pain associated with PDB. Zoledronic acid is recommended as the bisphosphonate most likely to give a favorable pain response. 4) Treatment aimed at improving symptoms is recommended over a treat-to-target strategy aimed at normalizing total ALP in PDB. 5) Total hip or knee replacements are recommended for patients with PDB who develop osteoarthritis in whom medical treatment is inadequate. There is insufficient information to recommend one type of surgical approach over another. The guideline was endorsed by the European Calcified Tissues Society, the International Osteoporosis Foundation, the American Society of Bone and Mineral Research, the Bone Research Society (UK), and the British Geriatric Society. The GDG noted that there had been a lack of research on patient-focused clinical outcomes in PDB and identified several areas where further research was needed. © 2019 The Authors. Journal of Bone and Mineral Research Published by Wiley Periodicals Inc.


Assuntos
Fosfatase Alcalina/sangue , Osteíte Deformante , Ácido Zoledrônico/uso terapêutico , Adulto , Biomarcadores/sangue , Humanos , Osteíte Deformante/sangue , Osteíte Deformante/diagnóstico , Osteíte Deformante/tratamento farmacológico , Guias de Prática Clínica como Assunto
12.
PLoS One ; 13(8): e0201527, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30080871

RESUMO

Data describing the effect of in vivo B cell depletion on general bone loss in patients with rheumatoid arthritis (RA) are limited. Given the pathogenetic role of B cells in RA, it is tempting to speculate that B cell depletion might have a beneficial effect on bone loss. We prospectively investigated the changes in bone mineral density (BMD), bone turnover, inflammation and disease activity before and after rituximab in 45 RA patients over a 12 month period, 36 patients of whom completed the study and were included in the analysis. There was no significant change in our primary endpoint; lumbar spine BMD after 12 months. However, we found a significant decrease in neck of femur (mean -0.017 g/cm2, 95% CI -0.030, -0.004 p = 0.011) and total femur BMD (mean -0.016 g/cm2, 95% CI -0.025, -0.007 p = 0.001). Additionally, there was a significant increase in procollagen type 1 amino-terminal propeptide (P1NP) and bone specific alkaline phosphatase (BAP); biomarkers of bone formation (median change from baseline to 12 months; P1NP 11.3 µg/L, 95% CI -1.1, 24.8 p = 0.025; BAP 2.5 µg/L, 95% CI 1.2, 3.6 p = 0.002), but no significant change in bone resorption or osteocyte markers. The fall in BMD occurred despite improvement in disease control. Post-menopausal women had the lowest mean lumbar spine, femoral and forearm BMD at baseline and after 12 months, additionally they had a higher level of bone turnover throughout the study. In conclusion, BMD was maintained at the lumbar spine and forearm, but fell at the femur sites. A high prevalence of vitamin D deficiency was observed and these patients had lower BMD and evidence of higher bone turnover.


Assuntos
Antirreumáticos/farmacologia , Artrite Reumatoide/tratamento farmacológico , Densidade Óssea/efeitos dos fármacos , Remodelação Óssea/efeitos dos fármacos , Reabsorção Óssea/prevenção & controle , Rituximab/farmacologia , Absorciometria de Fóton , Idoso , Antirreumáticos/uso terapêutico , Artrite Reumatoide/complicações , Biomarcadores/análise , Reabsorção Óssea/diagnóstico por imagem , Reabsorção Óssea/etiologia , Feminino , Colo do Fêmur/diagnóstico por imagem , Colo do Fêmur/patologia , Humanos , Vértebras Lombares/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Rituximab/uso terapêutico , Resultado do Tratamento , Deficiência de Vitamina D/diagnóstico por imagem , Deficiência de Vitamina D/epidemiologia , Deficiência de Vitamina D/patologia
13.
Age Ageing ; 47(3): 334-339, 2018 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-29315354

RESUMO

The development of clinical guidelines is now a more uniform process, with formalised methods to ensure that recommendations are based on current best available evidence from randomised controlled trials and systematic reviews. Over the past 20 years we have seen a growth in guidelines including those relating to osteoporosis, with recommendations varying between and within countries. Some guidelines are concerned with case finding and primary or secondary prevention, such as those produced by the National Institute for Health and Care Excellence (NICE CG146, TA-160, -161, -464), while others focus on specific conditions or risk factors associated with osteoporosis, such as the menopause, coeliac disease and eating disorder. Clinicians can be confused as to which to follow in any particular clinical scenario. International guidelines, such as those from North America (NOF, CAROC, AACE) and Scotland (SIGN 142), differ from those of England, Wales and Northern Ireland, with recent recommendations from NICE (TA464) shifting the focus of treatment from those at greatest fracture risk to an apparent blanket approach, based on cost-effectiveness, rather than clinical effectiveness.Osteoporosis treatment should be targeted at those who can benefit most, outweighing the potential for harm. If the low health economic threshold of NICE TA464 were adopted as a clinical threshold, the most important group-older people at greatest risk of fracture, would not be prioritised. We risk overwhelming clinical services, while causing harm to some at low fracture risk from adverse effects of treatment, yet failing to treat the older population at highest fracture risk.


Assuntos
Medicina Baseada em Evidências/normas , Osteoporose/terapia , Fraturas por Osteoporose/prevenção & controle , Guias de Prática Clínica como Assunto/normas , Padrões de Prática Médica/normas , Fatores Etários , Análise Custo-Benefício , Medicina Baseada em Evidências/economia , Fidelidade a Diretrizes/normas , Custos de Cuidados de Saúde/normas , Humanos , Osteoporose/economia , Osteoporose/epidemiologia , Fraturas por Osteoporose/economia , Fraturas por Osteoporose/epidemiologia , Padrões de Prática Médica/economia , Medição de Risco , Fatores de Risco
14.
Rheumatology (Oxford) ; 56(12): 2050-2059, 2017 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-28339664

RESUMO

Adult PD of bone is the second commonest metabolic bone condition after osteoporosis. The condition is characterized by increased bone cell activity, with bone-resorbing osteoclasts often larger and containing more nuclei than normal, and osteoblasts producing increased amounts of disorganized bone. This leads to expanded bone of poor quality possessing both sclerotic and lytic areas. PD of bone has a strong genetic element, with a family history being noted in 10-20% of cases. A number of genetic defects have been found to be associated with the condition. The most common disease-associated variants identified affect the SQSTM1 gene, providing insights into disease aetiology, with the clinical value of knowledge of SQSTM1 mutation status currently under active investigation. The diagnosis may be suggested by an isolated raised total ALP without other identifiable causes. This can be confirmed on plain X-rays and the extent determined by isotope bone scan. The mainstays of treatment are the bisphosphonates, especially i.v. zoledronate, which results in long-term suppression of bone turnover. ALP is the usual means of monitoring the condition, although more specific bone turnover markers can be helpful, especially in coincident liver disease. Patients should be followed up to monitor for biochemical relapse or development of complications, which may require medical or surgical intervention.


Assuntos
Fosfatase Alcalina/sangue , Difosfonatos/uso terapêutico , Osteíte Deformante/genética , Proteína Sequestossoma-1/genética , Adulto , Reabsorção Óssea , Predisposição Genética para Doença/genética , Humanos , Mutação , Osteíte Deformante/sangue , Osteíte Deformante/tratamento farmacológico , Osteoclastos/fisiologia
17.
J Transl Med ; 11: 201, 2013 Aug 29.
Artigo em Inglês | MEDLINE | ID: mdl-23984630

RESUMO

Osteoporosis is characterised by low bone mass and structural deterioration of bone tissue, resulting in increased fragility and susceptibility to fracture. Osteoporotic fractures are a significant cause of morbidity and mortality. Direct medical costs from such fractures in the UK are currently estimated at over two billion pounds per year, resulting in a substantial healthcare burden that is expected to rise exponentially due to increasing life expectancy. Currently bone mineral density is the WHO standard for diagnosis of osteoporosis, but poor sensitivity means that potential fractures will be missed if it is used alone. During the past decade considerable progress has been made in the identification and characterisation of specific biomarkers to aid the management of metabolic bone disease. Technological developments have greatly enhanced assay performance producing reliable, rapid, non-invasive cost effective assays with improved sensitivity and specificity. We now have a greater understanding of the need to regulate pre-analytical sample collection to minimise the effects of biological variation. However, bone turnover markers (BTMs) still have limited clinical utility. It is not routinely recommended to use BTMs to select those at risk of fractures, but baseline measurements of resorption markers are useful before commencement of anti-resorptive treatment and can be checked 3-6 months later to monitor response and adherence to treatment. Similarly, formation markers can be used to monitor bone forming agents. BTMs may also be useful when monitoring patients during treatment holidays and aid in the decision as to when therapy should be recommenced. Recent recommendations by the Bone Marker Standards Working Group propose to standardise research and include a specific marker of bone resorption (CTX) and bone formation (P1NP) in all future studies. It is hoped that improved research in turn will lead to optimised markers for the clinical management of osteoporosis and other bone diseases.


Assuntos
Biomarcadores/metabolismo , Osso e Ossos/metabolismo , Testes Diagnósticos de Rotina/métodos , Osteoporose/diagnóstico , Osteoporose/metabolismo , Remodelação Óssea , Humanos
18.
Curr Osteoporos Rep ; 11(1): 11-20, 2013 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-23355097

RESUMO

Adenocarcinoma of the prostate is one of the commonest cancers in the world. Due to a combination of earlier detection and better treatments, survival has increased dramatically. Prostate cancer itself is associated with lower bone density and increased fractures. This is compounded by the use of androgen deprivation therapy, which causes dramatic falls in circulating testosterone and estrogen, resulting in rapid falls in bone density, decreased muscle mass, and increased fracture rates. Bisphosphonates have been demonstrated to prevent and reverse this bone loss, but there are no anti-fracture data. Denosumab, a monoclonal antibody to RANKL, has recently been shown to increase bone density and reduce fracture rates. Prostate cancer also commonly metastasizes to bone where it can cause complications such as fracture and pain. Both zoledronic acid and denosumab have been demonstrated to reduce skeletal related events. Comparative studies would suggest that densosumab may have an advantage over zoledronic acid.


Assuntos
Adenocarcinoma/complicações , Osteoporose/epidemiologia , Osteoporose/prevenção & controle , Neoplasias da Próstata/complicações , Adenocarcinoma/tratamento farmacológico , Antagonistas de Androgênios/efeitos adversos , Antagonistas de Androgênios/uso terapêutico , Anticorpos Monoclonais Humanizados/uso terapêutico , Conservadores da Densidade Óssea/uso terapêutico , Neoplasias Ósseas/epidemiologia , Denosumab , Difosfonatos/uso terapêutico , Humanos , Imidazóis/uso terapêutico , Masculino , Osteoporose/fisiopatologia , Neoplasias da Próstata/tratamento farmacológico , Fatores de Risco , Ácido Zoledrônico
20.
J Osteoporos ; 2011: 243465, 2011.
Artigo em Inglês | MEDLINE | ID: mdl-22013543

RESUMO

Introduction. The association of bone morphogenetic protein 2 (BMP2) with BMD and risk of fracture was suggested by a recent linkage study, but subsequent studies have been contradictory. We report the results of a study of the relationship between BMP2 genotypes and BMD, annual change in BMD, and risk of fracture in male subjects. Materials and Methods. We tested three single-nucleotide polymorphisms (SNPs) across the BMP2 gene, including Ser37Ala SNP, in 342 Caucasian Englishmen, comprising 224 control and 118 osteoporotic subjects. Results. BMP2 SNP1 (Ser37Ala) genotypes were found to have similar low frequency in control subjects and men with osteoporosis. The major informative polymorphism, BMP2 SNP3 (Arg190Ser), showed no statistically significant association with weight, height, BMD, change in BMD at hip or lumbar spine, and risk of fracture. Conclusion. There were no genotypic or haplotypic effects of the BMP2 candidate gene on BMD, change in BMD, or fracture risk identified in this cohort.

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