Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 2.850
Filtrar
1.
Medicine (Baltimore) ; 100(1): e24164, 2021 Jan 08.
Artigo em Inglês | MEDLINE | ID: mdl-33429799

RESUMO

ABSTRACT: The most common site for metastasis in patients with breast cancer is the bone. In this case series, we investigated patients whose surgical and medical treatment for primary breast cancer was conducted at our center and first disease recurrence was limited to only 1 bone.We analyzed 910 breast cancer patients, 863 had no metastasis and 47 cases had a single bone metastasis ≥ 6 months after their first diagnosis. Demographic, epidemiological, histopathological and intrinsic tumor subtype differences between the non-metastatic group and the group with solitary bone metastases and their statistical significance were examined. Among established breast cancer risk factors, we studied twenty-nine variables.Three variables (Type of tumor surgery, TNM Stage III tumors and mixed type (invasive ductalcarsinoma + invasive lobular carcinoma) histology) were significant in multivariate logistic regression analysis. Accordingly, the risk of developing single bone metastasis was approximately 15 times higher in patients who underwent mastectomy and 4.8 and 2.8 times higher in those with TNM Stage III tumors and with mixed type (invasive ductal carcinoma + invasive lobular carcinoma) histology, respectively.In conclusion, the risk of developing single bone metastasis is likely in non-metastatic patients with Stage III tumors and possibly in mixed type tumors. Knowing this risk, especially in patients with mixed type tumors, may be instrumental in taking measures with different adjuvant therapies in future studies. Among these, treatment modalities such as prolonged hormone therapy and addition of bisphosphonates to the adjuvant treatments of stage III and mixed breast cancer patients may be considered.


Assuntos
Neoplasias Ósseas/classificação , Osso e Ossos/patologia , Neoplasias da Mama/complicações , Metástase Neoplásica/fisiopatologia , Adulto , Idoso , Neoplasias Ósseas/patologia , Osso e Ossos/fisiopatologia , Feminino , Humanos , Pessoa de Meia-Idade
2.
Nat Metab ; 3(1): 11-20, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-33398192

RESUMO

The skeleton is diverse in its functions, which include mechanical support, movement, blood cell production, mineral storage and endocrine regulation. This multifaceted role is achieved through an interplay of osteoblasts, chondrocytes, bone marrow adipocytes and stromal cells, all generated from skeletal stem cells. Emerging evidence shows the importance of cellular metabolism in the molecular control of the skeletal system. The different skeletal cell types not only have distinct metabolic demands relating to their particular functions but also are affected by microenvironmental constraints. Specific metabolites control skeletal stem cell maintenance, direct lineage allocation and mediate cellular communication. Here, we discuss recent findings on the roles of cellular metabolism in determining skeletal stem cell fate, coordinating osteoblast and chondrocyte function, and organizing stromal support of haematopoiesis. We also consider metabolic dysregulation in skeletal ageing and degenerative diseases, and provide an outlook on how the field may evolve in the coming years.


Assuntos
Doenças Ósseas/fisiopatologia , Osso e Ossos/citologia , Animais , Células da Medula Óssea , Osso e Ossos/fisiologia , Osso e Ossos/fisiopatologia , Comunicação Celular , Linhagem da Célula , Senescência Celular , Humanos , Osteoblastos/metabolismo , Células-Tronco/metabolismo
4.
PLoS One ; 15(7): e0235135, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32628733

RESUMO

BACKGROUND: In patients on hemodialysis (HD), the various chemical elements in the dialysate may influence survival rates. In particular, calcium modifies mineral and bone metabolism and the vascular calcification rate. We studied the influence of the dialysate calcium concentration and the treatments prescribed for mineral bone disease (MBD) on survival. METHODS: All patients in REIN having initiated HD from 2010 to 2013 were classified according to their exposure to the different dialysate calcium concentrations in their dialysis unit. Data on the individual patients' treatments for MBD were extracted from the French national health database. Cox proportional hazard models were used to estimate mortality hazard ratios (HR) associated with time-dependent exposure to dialysate calcium concentrations and MBD therapies, adjusted for comorbidities, laboratory and technical data. RESULTS: Dialysate calcium concentration of 1.5 mmol/L was used by 81% of the dialysis centers in 2010 and in 83% in 2014. Most centers were using several formulas in up to 78% for 3 formulas in 2010 to 86% in 2014. In full adjusted Cox survival analyses, the percentage of calcium >1.5 mmol/L and <1.5 mmol/l by center and the number of formula used per center were not associated with survival. Depending on the daily dose used, the MBD therapies were associated with survival improvement for calcium, native vitamin D, active vitamin D, sevelamer, lanthanum and cinacalcet in the second and third tertiles of dose. CONCLUSION: No influence of the dialysate calcium concentration was evidenced on survival whereas all MBD therapies were associated with a survival improvement depending on the daily dose used.


Assuntos
Osso e Ossos/efeitos dos fármacos , Cálcio/análise , Soluções para Hemodiálise/análise , Sistema de Registros , Diálise Renal , Insuficiência Renal Crônica/terapia , Idoso , Vasos Sanguíneos/efeitos dos fármacos , Vasos Sanguíneos/metabolismo , Vasos Sanguíneos/fisiopatologia , Osso e Ossos/metabolismo , Osso e Ossos/fisiopatologia , Calcinose/epidemiologia , Calcinose/metabolismo , Calcinose/fisiopatologia , Cálcio/administração & dosagem , Cálcio/metabolismo , Cinacalcete/análise , Feminino , França/epidemiologia , Soluções para Hemodiálise/administração & dosagem , Soluções para Hemodiálise/química , Humanos , Lantânio/análise , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Insuficiência Renal Crônica/epidemiologia , Insuficiência Renal Crônica/mortalidade , Insuficiência Renal Crônica/fisiopatologia , Sevelamer/análise , Vitamina D/análise , Vitamina D/metabolismo
5.
J Am Acad Orthop Surg ; 28(18): 737-741, 2020 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-32618680

RESUMO

Lymphatic flow plays a notable role in the regulation of bone formation and remodeling. Chronic accumulation of the lymph fluid within tissues may lead to issues with proper bone healing after fractures, emphasizing the importance of proper management of lymphedema after trauma. Many associated risk factors place patients at risk for lymphedema, including previous surgery with nodal dissection, radiation therapy, infection, malignancy, family history of congenital lymphedema, and trauma. The benchmark imaging technique for the diagnosis of lymphedema is lymphoscintigraphy. Other modalities include duplex ultrasonography, CT, and MRI. First-line conservative treatment of lymphedema is compression. Complete decongestive therapy or complex physical therapy, also known as decongestive lymphatic therapy (DLT), has shown positive results in reducing lymphedema. Surgical interventions aim to either reconstruct and restore function of the lymphatic system or debulk and reduce tissues and fluids. Understanding the significance of lymphedema on bone healing and techniques available to recognize it are important factors in preventing delay in diagnosis and ensuring proper management of lymphedema after trauma.


Assuntos
Osso e Ossos/lesões , Fraturas Ósseas/complicações , Linfedema/etiologia , Linfedema/terapia , Osso e Ossos/fisiopatologia , Bandagens Compressivas , Tratamento Conservador/métodos , Diagnóstico por Imagem , Fraturas Ósseas/fisiopatologia , Humanos , Linfedema/diagnóstico , Linfedema/cirurgia , Procedimentos Ortopédicos/métodos , Modalidades de Fisioterapia , Cicatrização
6.
J Bone Joint Surg Am ; 102(14): 1197-1204, 2020 07 15.
Artigo em Inglês | MEDLINE | ID: mdl-32675661

RESUMO

Coronavirus disease 2019 (COVID-19) is an emerging pandemic disease caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Although the majority of patients who become infected with SARS-CoV-2 are asymptomatic or have mild symptoms, some patients develop severe symptoms that can permanently detract from their quality of life. SARS-CoV-2 is closely related to SARS-CoV-1, which causes severe acute respiratory syndrome (SARS). Both viruses infect the respiratory system, and there are direct and indirect effects of this infection on multiple organ systems, including the musculoskeletal system. Epidemiological data from the SARS pandemic of 2002 to 2004 identified myalgias, muscle dysfunction, osteoporosis, and osteonecrosis as common sequelae in patients with moderate and severe forms of this disease. Early studies have indicated that there is also considerable musculoskeletal dysfunction in some patients with COVID-19, although long-term follow-up studies have not yet been conducted. The purpose of this article was to summarize the known musculoskeletal pathologies in patients with SARS or COVID-19 and to combine this with computational modeling and biochemical signaling studies to predict musculoskeletal cellular targets and long-term consequences of the SARS-CoV-2 infection.


Assuntos
Infecções por Coronavirus/complicações , Sistema Musculoesquelético/fisiopatologia , Pneumonia Viral/complicações , Betacoronavirus , Osso e Ossos/fisiopatologia , Simulação por Computador , Humanos , Articulações/fisiopatologia , Debilidade Muscular/virologia , Músculo Esquelético/fisiopatologia , Mialgia/virologia , Pandemias , Peptidil Dipeptidase A/genética , Serina Endopeptidases/genética
7.
J Bone Miner Metab ; 38(6): 826-838, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32519249

RESUMO

INTRODUCTION: Second-generation high-resolution peripheral quantitative computed tomography (HR-pQCT) has provide higher quality of bone images with a voxel size of 61 µm, enabling direct measurements of trabecular thickness. In addition to the standard parameters, the non-metric trabecular parameters such as trabecular morphology (plate to rod-like structures), connectivity, and anisotropy can also be analyzed. The purpose of this study is to investigate deterioration of bone microstructure in healthy Japanese women by measuring standard and non-metric parameters using HR-pQCT. MATERIALS AND METHODS: Study participants were 61 healthy Japanese women (31-70 years). The distal radius and tibia were scanned using second-generation HR-pQCT, and microstructures of trabecular and cortical bone were measured. Non-metric trabecular parameters included structure model index (SMI), trabecular bone pattern factor (TBPf), connectivity density (Conn.D), number of nodes (N.Nd/TV), degree of anisotropy (DA), and star volume of marrow space (V*ms). Estimated bone strength was evaluated by micro finite element analysis. Associations between bone microstructure, estimated bone strength, age, and menopause were analyzed. RESULTS: Trabecular number declined with age, and trabecular separation increased. SMI and TBPf increased, Conn.D and N.Nd/TV declined, and V*ms increased. Cortical BMD and thickness declined with age, and porosity increased. Stiffness and failure load decreased with age. Cortical thickness and estimated bone strength were affected by menopause. Cortical thickness was most associated with estimated bone strength. CONCLUSIONS: Trabecular and cortical bone microstructure were deteriorated markedly with age. Cortical thickness decreased after menopause and was most related to bone strength. Non-metric parameters give additional information about osteoporotic changes of trabecular bone.


Assuntos
Envelhecimento/patologia , Grupo com Ancestrais do Continente Asiático , Osso e Ossos/diagnóstico por imagem , Osso e Ossos/patologia , Menopausa , Tomografia Computadorizada por Raios X , Absorciometria de Fóton , Adulto , Idoso , Densidade Óssea , Osso e Ossos/fisiopatologia , Osso Esponjoso/diagnóstico por imagem , Osso Esponjoso/patologia , Osso Cortical/diagnóstico por imagem , Osso Cortical/patologia , Feminino , Análise de Elementos Finitos , Humanos , Japão , Modelos Lineares , Pessoa de Meia-Idade , Porosidade
8.
J Bone Miner Metab ; 38(4): 501-510, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32140785

RESUMO

INTRODUCTION: High-turnover bone disease is a major consequence of SHPT and may explain the high risk for fracture in patients with advanced chronic kidney disease (CKD). Bisphosphonates suppress bone turnover and improve bone strength, but their effects have not been fully characterized in advanced CKD with severe SHPT. Bisphosphonates also increase 1,25-dihydroxyvitamin D levels in normal and uremic rats, but the underlying mechanism remains to be determined. MATERIALS AND METHODS: We investigated the skeletal and mineral metabolic effects of RIS, a pyridinyl bisphosphonate, in rats with severe SHPT induced by 5/6 nephrectomy plus a high phosphate diet. RESULTS: Nephrectomized rats developed severe SHPT, along with hyperphosphatemia, low 1,25-dihydroxyvitamin D, and markedly increased FGF23. Moreover, these rats exhibited characteristic features of high-turnover renal osteodystrophy, including increased indices of trabecular bone turnover, decreased cortical bone thickness, inferior cortical biomechanical properties, and a prominent increase in peritrabecular fibrosis. RIS treatment increased bone volume and partially attenuated trabecular bone remodeling, cortical bone loss, and mechanical properties, whereas it produced a marked improvement in peritrabecular fibrosis along with a corresponding decrease in osteogenic gene markers. RIS treatment also suppressed the elevation of FGF23, which was associated with increased 1,25-dihydroxyvitamin D. CONCLUSIONS: In a rat model of severe SHPT, treatment with RIS partially attenuated histological manifestations of high-turnover bone disease. RIS treatment also suppressed the elevation of FGF23, which may explain the increased 1,25-dihydroxyvitamin D production during the treatment.


Assuntos
Remodelação Óssea , Osso e Ossos/patologia , Distúrbio Mineral e Ósseo na Doença Renal Crônica/tratamento farmacológico , Distúrbio Mineral e Ósseo na Doença Renal Crônica/fisiopatologia , Minerais/metabolismo , Ácido Risedrônico/uso terapêutico , Animais , Fenômenos Biomecânicos , Nitrogênio da Ureia Sanguínea , Remodelação Óssea/efeitos dos fármacos , Osso e Ossos/efeitos dos fármacos , Osso e Ossos/fisiopatologia , Cálcio/sangue , Distúrbio Mineral e Ósseo na Doença Renal Crônica/sangue , Creatinina/sangue , Modelos Animais de Doenças , Regulação da Expressão Gênica/efeitos dos fármacos , Humanos , Masculino , Nefrectomia , Fragmentos de Peptídeos/sangue , Fósforo/sangue , Pró-Colágeno/sangue , Ratos Sprague-Dawley , Ácido Risedrônico/farmacologia
9.
J Acquir Immune Defic Syndr ; 84(1): 101-106, 2020 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-32141960

RESUMO

BACKGROUND: Reduced bone mineral mass by dual x-ray absorptiometry is reported in children living with HIV (CLWH), but few studies of bone microarchitecture, particularly in sub-Saharan Africa, have been conducted. Here, we compare bone architecture and strength in black South African CLWH and uninfected control children by peripheral quantitative computed tomography (pQCT). SETTING AND METHODS: One hundred seventy-two CLWH on antiretroviral therapy (ART) and 98 controls in the CHANGES Bone Study in Johannesburg, South Africa received pQCT scans of the radius and tibia. Measurements included trabecular and cortical volumetric bone mineral density (vBMD) and bone strength, estimated by the polar strength strain index (SSI), a validated measure of fracture risk. RESULTS: CLWH (51% boys) and controls (63% boys) were an average of age 10.4 years. Mean ART duration for CLWH was 9.5 years, with 70.9% on an efavirenz-based, 28.5% on a lopinavir/ritonavir-based, and 1 child on an atazanavir/ritonavir-based regimen. Male CLWH had lower trabecular vBMD at the radius than controls after adjustment for age, radial length, and Tanner stage (ß = -17.3, standard error = 7.2, P = 0.018). Bone strength by polar SSI was lower in CLWH than controls (778 vs. 972 mm, P < 0.01). CLWH on an LPV/r-based regimen had lower trabecular vBMD (199 vs. 222 mg/cm, P < 0.001) and cortical vBMD (1074 vs. 1093 mg/cm, P = 0.004) than those on an efavirenz-based regimen. No difference in bone strength by polar SSI was observed between treatment groups. CONCLUSION: CLWH initiated on ART early in life with well-controlled HIV have deficits in bone architecture and reductions in bone strength as detected by pQCT.


Assuntos
Fármacos Anti-HIV/uso terapêutico , Densidade Óssea , Osso e Ossos/patologia , Infecções por HIV/tratamento farmacológico , Infecções por HIV/patologia , Osso e Ossos/diagnóstico por imagem , Osso e Ossos/fisiopatologia , Estudos de Casos e Controles , Criança , Feminino , Infecções por HIV/fisiopatologia , Humanos , Masculino , Tomografia Computadorizada por Raios X
10.
Horm Metab Res ; 52(3): 168-178, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32215888

RESUMO

Critically ill patients have low circulating 25-hydroxyvitamin D (25OHD), vitamin D binding protein (DBP), and 1,25-dihydroxyvitamin D [1,25(OH)2D]. Low 25OHD is associated with poor outcomes, possibly explained by its effect on bone and immunity. In this prospective, randomized double-blind, placebo-controlled study, we investigated the feasibility of normalizing 25OHD in prolonged (>10 days) critically ill patients and the effects thereof on 1,25(OH)2D, bone metabolism, and innate immunity. Twenty-four patients were included and compared with 24 matched healthy subjects. Patients were randomized to either intravenous bolus of 200 µg 25OHD followed by daily infusion of 15 µg 25OHD for 10 days, or to placebo. Parameters of vitamin D, bone and mineral metabolism, and innate immune function were measured. As safety endpoints, ICU length of stay and mortality were registered. Infusion of 25OHD resulted in a sustained increase of serum 25OHD (from median baseline 9.2 -16.1 ng/ml at day 10), which, however, remained below normal levels. There was no increase in serum 1,25(OH)2D but a slight increase in serum 24,25(OH)2D. Mineral homeostasis, innate immunity and clinical safety endpoints were unaffected. Thus, intravenous 25OHD administration during critical illness increased serum 25OHD concentrations, though less than expected from data in healthy subjects, which suggests illness-induced alterations in 25OHD metabolism and/or increased 25OHD distribution volume. The increased serum 25OHD concentrations were not followed by a rise in 1,25(OH)2D nor were bone metabolism or innate immunity affected, which suggests that low 25OHD and 1,25OHD levels are part of the adaptive response to critical illness.


Assuntos
Osso e Ossos/efeitos dos fármacos , Estado Terminal/terapia , Imunidade Inata/efeitos dos fármacos , Vitamina D/análogos & derivados , Adulto , Idoso , Remodelação Óssea/efeitos dos fármacos , Osso e Ossos/fisiopatologia , Estado Terminal/mortalidade , Método Duplo-Cego , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Vitamina D/administração & dosagem
11.
J Bone Miner Metab ; 38(4): 597-604, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32144577

RESUMO

INTRODUCTION: In chronic hemodialysis, high-turnover bone disease was associated with decreased bone mineral density (BMD), poor bone quality (chemical and structural), and increased fracture risk. Our aim was to correlate bone turnover markers (BTMs) with bone microarchitecture measured by trabecular bone score (TBS) before and after correction for BMD. MATERIALS AND METHODS: We measured lumbar spine (LS), femoral neck, and 1/3 radius BMD and LS TBS by dual X-ray absorptiometry in 81 patients on permanent hemodialysis. Bone turnover was assessed using serum parathyroid hormone, osteocalcin, C-terminal crosslaps of type 1 collagen, procollagen 1 N-terminal propeptide (P1NP), and alkaline phosphatase (ALP). No patient had any partial or total parathyroidectomy and no previous or current treatment with anti-osteoporotic drugs. RESULTS: All BTMs correlated significantly with each other. Univariate regressions showed significant negative correlations between BTMs and BMD (best r = - 0.53, between P1NP and 1/3 radius Z-score) or BTMs and TBS (best r = - 0.27, p < 0.05 between ALP and TBS T-score). TBS correlated significantly with BMD at all three sites (best r = 0.5, between LS BMD and TBS T-score). Multivariate regression showed that TBS, crude or adjusted, correlated with LS BMD. No model retained any of the BTMs as independent variables due to the better prediction of BMD and multicollinearity. CONCLUSION: We showed a progressively impaired bone microarchitecture with increasing bone turnover in chronic hemodialysis. However, this correlation is no longer present when controlling for bone mass. This suggests that impaired bone microarchitecture and increased fracture risk are dependent upon factors other than high bone turnover.


Assuntos
Remodelação Óssea/fisiologia , Osso e Ossos/patologia , Osso e Ossos/fisiopatologia , Diálise Renal , Idoso , Biomarcadores/metabolismo , Densidade Óssea , Osso Esponjoso/patologia , Osso Esponjoso/fisiopatologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Análise de Regressão
12.
Scand J Med Sci Sports ; 30(5): 894-903, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32034797

RESUMO

Injuries are common in elite adolescent athletics, but few studies have addressed risk factors for injury. Growth and maturation are potential risk factors in this population; however, the current body of literature is both inconclusive and considered at high risk of bias. The aim of this study was therefore to examine whether growth rate, maturity status, and maturity tempo are associated with injury risk in an elite sports academy. Anthropometric, skeletal maturity and injury data collected prospectively over four seasons (117 athlete-seasons) were included in the analyses. Growth rate for stature was associated with greater risk of bone (incidence rate ratio (IRR): 1.5 per one standard deviation increase above the mean; 95% CI: 1.1-1.9) and growth plate injuries (IRR: 2.1; 1.5-3.1). Growth rate for leg length was associated with greater overall injury risk (IRR: 1.3; 1.0-1.7) as well as the risk of bone (IRR: 1.4; 1.0-1.9) and growth plate injuries (IRR: 2.1; 1.4-3.0). Athletes with greater skeletal maturity, expressed as skeletal age (IRR: 0.6 per year; 0.5-0.9) and percentage of predicted mature height (IRR: 0.8 per percent increase; 0.7-1.0), were less prone to growth plate injuries. Rate of change in skeletal age was associated with an increased risk of bone injuries (IRR: 1.5; 1.0-2.3). The results of this study suggest that rapid growth in stature and leg length, skeletal maturity status, and maturity tempo represent risk factors for certain injury types in adolescent athletics.


Assuntos
Desenvolvimento do Adolescente , Determinação da Idade pelo Esqueleto , Traumatismos em Atletas/fisiopatologia , Osso e Ossos/lesões , Osso e Ossos/fisiopatologia , Lâmina de Crescimento/fisiopatologia , Adolescente , Fatores Etários , Antropometria , Criança , Humanos , Fatores de Risco , Esportes
13.
Genet Sel Evol ; 52(1): 13, 2020 Feb 24.
Artigo em Inglês | MEDLINE | ID: mdl-32093603

RESUMO

BACKGROUND: Skeletal damage is a challenge for laying hens because the physiological adaptations required for egg laying make them susceptible to osteoporosis. Previously, we showed that genetic factors explain 40% of the variation in end of lay bone quality and we detected a quantitative trait locus (QTL) of large effect on chicken chromosome 1. The aim of this study was to combine data from the commercial founder White Leghorn population and the F2 mapping population to fine-map this QTL and understand its function in terms of gene expression and physiology. RESULTS: Several single nucleotide polymorphisms on chromosome 1 between 104 and 110 Mb (galGal6) had highly significant associations with tibial breaking strength. The alternative genotypes of markers of large effect that flanked the region had tibial breaking strengths of 200.4 vs. 218.1 Newton (P < 0.002) and, in a subsequent founder generation, the higher breaking strength genotype was again associated with higher breaking strength. In a subsequent generation, cortical bone density and volume were increased in individuals with the better bone genotype but with significantly reduced medullary bone quality. The effects on cortical bone density were confirmed in a further generation and was accompanied by increased mineral maturity of the cortical bone as measured by infrared spectrometry and there was evidence of better collagen cross-linking in the cortical bone. Comparing the transcriptome of the tibia from individuals with good or poor bone quality genotypes indicated four differentially-expressed genes at the locus, one gene, cystathionine beta synthase (CBS), having a nine-fold higher expression in the genotype for low bone quality. The mechanism was cis-acting and although there was an amino-acid difference in the CBS protein between the genotypes, there was no difference in the activity of the enzyme. Plasma homocysteine concentration, the substrate of CBS, was higher in the poor bone quality genotype. CONCLUSIONS: Validated markers that predict bone strength have been defined for selective breeding and a gene was identified that may suggest alternative ways to improve bone health in addition to genetic selection. The identification of how genetic variants affect different aspects of bone turnover shows potential for translational medicine.


Assuntos
Galinhas/genética , Osteoporose/veterinária , Doenças das Aves Domésticas/genética , Locos de Características Quantitativas , Animais , Densidade Óssea , Osso e Ossos/fisiopatologia , Galinhas/fisiologia , Cromossomos/genética , Feminino , Genótipo , Osteoporose/genética , Osteoporose/fisiopatologia , Oviposição , Polimorfismo de Nucleotídeo Único , Doenças das Aves Domésticas/fisiopatologia
14.
Sensors (Basel) ; 20(1)2020 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-31906330

RESUMO

The total number of total hip arthroplasties is increasing every year, and approximately 10% of these surgeries are revisions. New implant design and surgical techniques are evolving quickly and demand accurate preclinical evaluation. The initial stability of cementless implants is one of the main concerns of these preclinical evaluations. A broad range of initial stability test methods is currently used, which can be categorized into two main groups: Load-to-failure tests and relative micromotion measurements. Measuring relative micromotion between implant and bone is recognized as the golden standard for implant stability testing as this micromotion is directly linked to the long-term fixation of cementless implants. However, specific custom-made set-ups are required to measure this micromotion, with the result that numerous studies opt to perform more straightforward load-to-failure tests. A custom-made micromotion test set-up for artificial acetabular bone models was developed and used to compare load-to-failure (implant push-out test) with micromotion and to assess the influence of bone material properties and press-fit on the implant stability. The results showed a high degree of correlation between micromotion and load-to-failure stability metrics, which indicates that load-to-failure stability tests can be an appropriate estimator of the primary stability of acetabular implants. Nevertheless, micromotions still apply as the golden standard and are preferred when high accuracy is necessary. Higher bone density resulted in an increase in implant stability. An increase of press-fit from 0.7 mm to 1.2 mm did not significantly increase implant stability.


Assuntos
Artroplastia de Quadril/instrumentação , Osso e Ossos/cirurgia , Prótese de Quadril/normas , Próteses e Implantes/normas , Fenômenos Biomecânicos , Osso e Ossos/química , Osso e Ossos/fisiopatologia , Humanos , Desenho de Prótese , Amplitude de Movimento Articular/fisiologia
15.
J Bone Miner Metab ; 38(4): 563-569, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31974675

RESUMO

INTRODUCTION: Monoclonal gammopathy of uncertain significance (MGUS) is highly prevalent in older adults and affects bone structure, with osteoporosis and increased risk of fractures in up to 14% of affected patients. Dual-energy X-ray absorptiometry (DXA), the standard technique for diagnosing osteoporosis, is ineffective to reveal microstructure and bone quality in this disease. MATERIALS AND METHODS: We conducted a cross-sectional study of patients with MGUS, recruited consecutively from the Hematology and Internal Medicine Departments of Hospital del Mar, Barcelona, between January 2011 and January 2018. Medical records, clinical results and spinal X-ray images were collected. Bone mineral density (BMD) at hip and spine was measured by DXA and Bone Material Strength index (BMSi) by impact microindentation on the tibial mid-shaft. RESULTS: Thirty-nine patients with MGUS and 65 age-matched controls without previous fractures were included. In the MGUS group, 11 (28.2%) patients had prevalent fractures, nearly half of them vertebral (n = 5, 45.45%). Compared to controls, MGUS patients had significantly lower BMSi, a mean (SD) of 70.72 (9.70) vs. 78.29 (8.70), p = 0.001, and lower spinal BMD values (0.900 [0.159] vs. 1.003 [0.168], respectively, p = 0.012), but no significant differences at femoral neck and total hip. No association was observed between BMSi and DXA. Bone remodeling markers (procollagen type-1 N propeptide, bone-alkaline phosphatase and C-terminal telopeptide of type I collagen) did not differ between the two groups. CONCLUSIONS: Spinal BMD and mechanical properties of bone tissue, as measured by impact microindentation, were impaired in patients with MGUS. These changes in bone tissue mechanical resistance were independent of DXA levels.


Assuntos
Osso e Ossos/fisiopatologia , Gamopatia Monoclonal de Significância Indeterminada/fisiopatologia , Idoso , Índice de Massa Corporal , Densidade Óssea , Estudos de Casos e Controles , Feminino , Humanos , Masculino
16.
Cir Cir ; 88(1): 41-48, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31967601

RESUMO

Background: The mechanical fixation of the spine in patients with osteoporotic vertebral degeneration is a challenge for surgeons, the vertebrae selected to insert the screws may fail, endangering health and even patient's life. Objective: The objective of the study was to study the effect of the variation of the bone density in the bone-screw interface from a three-dimensional model of the lumbar section. Materials and methods: The finite element method was used to model the behavior of the lumbar vertebral section when applying compression loads. Results: The stresses between 2 and 3 MPa were located on the contact surface with the screw, both in the vertebral body and in the apophysis, being slightly higher in the vertebral body. Conclusions: Regardless of bone density, the contact zones between the screws are susceptible to bone tissue failure. The posterior half of the vertebral body was the most sensitive to high values of stress, while in the areas furthest from the axis of the screw stress tended to their minimum.


Assuntos
Densidade Óssea , Parafusos Ósseos , Osso e Ossos/diagnóstico por imagem , Imageamento Tridimensional/métodos , Vértebras Lombares/diagnóstico por imagem , Estresse Mecânico , Fenômenos Biomecânicos , Osso e Ossos/fisiopatologia , Análise de Elementos Finitos , Humanos , Vértebras Lombares/fisiopatologia , Osteoporose/complicações , Osteoporose/diagnóstico por imagem , Software , Fraturas da Coluna Vertebral , Fusão Vertebral/instrumentação , Coluna Vertebral/diagnóstico por imagem , Coluna Vertebral/cirurgia
17.
Artigo em Inglês | MEDLINE | ID: mdl-31483238

RESUMO

BACKGROUND: Bone is an important tissue and its normal function requires tight coordination of transcriptional networks and signaling pathways, and many of these networks/ pathways are dysregulated in pathological conditions affecting cartilage and bones. Long non-coding RNA (lncRNA) refers to a class of RNAs with a length of more than 200 nucleotides, lack of protein-coding potential, and exhibiting a wide range of biological functions. Although studies on lcnRNAs are still in their infancy, they have emerged as critical players in bone biology and bone diseases. The functions and exact mechanism of bone-related lncRNAs have not been fully classified yet. OBJECTIVE: The objective of this article is to summarize the current literature on lncRNAs on the basis of their role in bone biology and diseases, focusing on their emerging molecular mechanism, pathological implications and therapeutic potential. DISCUSSION: A number of lncRNAs have been identified and shown to play important roles in multiple bone cells and bone disease. The function and mechanism of bone-related lncRNA remain to be elucidated. CONCLUSION: At present, majority of knowledge is limited to cellular levels and less is known on how lncRNAs could potentially control the development and homeostasis of bone. In the present review, we highlight some lncRNAs in the field of bone biology and bone disease. We also delineate some lncRNAs that might have deep impacts on understanding bone diseases and providing new therapeutic strategies to treat these diseases.


Assuntos
Desenvolvimento Ósseo , Doenças Ósseas/metabolismo , Remodelação Óssea , Osso e Ossos/metabolismo , RNA Longo não Codificante/metabolismo , Animais , Doenças Ósseas/genética , Doenças Ósseas/patologia , Doenças Ósseas/fisiopatologia , Osso e Ossos/patologia , Osso e Ossos/fisiopatologia , Regulação da Expressão Gênica , Humanos , MicroRNAs/genética , MicroRNAs/metabolismo , RNA Longo não Codificante/genética , Transdução de Sinais
18.
Aging Clin Exp Res ; 32(2): 207-214, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31535334

RESUMO

BACKGROUND: Alterations in bone and muscle parameters related to advanced aging and physical inactivity have never been investigated in oldest-old women. AIMS: To investigate the impact of physical inactivity on bone mineral density (BMD) and body composition at the systemic and regional levels in oldest-old (> 75 years old) women. We hypothesized that, further to aging, alterations in bone and body composition parameters are exacerbated in the locomotor limbs that have experienced physical inactivity. METHODS: Whole-body and regional (lower limbs and trunk) BMD and fat-free soft tissue mass (FFSTM) were measured by means of dual-energy X-ray absorptiometry in 11 oldest-old wheelchair-bound women (OIW), 11 oldest-old mobile women (OMW), and 11 young healthy women (YW), all matched for weight (± 10 kg), height (± 10 cm). RESULTS: Whole-body BMD was reduced by 15% from YW to OMW and 10% from OMW to OIW. Whole-body FFSTM was also reduced from YW to OIW (- 13%). Lower limb BMD was progressively reduced among YW, OMW and OIW (- 23%). Similarly, lower limb FFSTM was reduced among YW (12,816 ± 1797 g), OMW (11,999 ± 1512 g) and OIW (10,037 ± 1489 g). Trunk BMD was progressively reduced among YW, OMW and OIW (- 19%), while FFSTM was similar among the three groups ~ 19801 g. CONCLUSIONS: The results of the present study suggest that the alterations in bone and body composition parameters are exacerbated in the physical inactive oldest-old. These negative effects of physical inactivity are not confined to the locomotor limbs, and a systemic decline of bone and muscle parameters are likely associated with the physical inactivity.


Assuntos
Osso e Ossos/fisiopatologia , Músculo Esquelético/fisiopatologia , Comportamento Sedentário , Absorciometria de Fóton , Adulto , Idoso , Idoso de 80 Anos ou mais , Composição Corporal , Peso Corporal , Densidade Óssea , Feminino , Humanos
19.
J Bone Miner Metab ; 38(1): 7-13, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31583540

RESUMO

Sarcopenia is an age-related loss of skeletal muscle mass and strength. It has been widely recognized that low muscle mass was essential in the diagnosis of sarcopenia, whereas recent studies have emphasized the importance of muscle strength. In practice, muscle quality as well as muscle mass might determine the strength and physical performance. A new diagnostic algorithm of sarcopenia has recently been established, in which low muscle strength is a key characteristic factor for the diagnosis of sarcopenia. Although many factors are supposed to be involved in the pathology and development of sarcopenia, precise mechanisms remain to be elucidated. Recent studies have also focused on the crosstalk between muscles and bones, including functional involvement of myokines and osteokines.


Assuntos
Osso e Ossos/fisiopatologia , Músculo Esquelético/fisiopatologia , Sarcopenia/fisiopatologia , Envelhecimento/patologia , Humanos , Força Muscular/fisiologia , Estresse Oxidativo , Sarcopenia/diagnóstico
20.
Aging Cell ; 19(2): e13095, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31880094

RESUMO

To determine whether 1,25-dihydroxyvitamin D (1,25(OH)2 D) can exert an anti-osteoporosis role through anti-aging mechanisms, we analyzed the bone phenotype of mice with 1,25(OH)2 D deficiency due to deletion of the enzyme, 25-hydroxyvitamin D 1α-hydroxylase, while on a rescue diet. 1,25(OH)2 D deficiency accelerated age-related bone loss by activating the p16/p19 senescence signaling pathway, inhibiting osteoblastic bone formation, and stimulating osteoclastic bone resorption, osteocyte senescence, and senescence-associated secretory phenotype (SASP). Supplementation of exogenous 1,25(OH)2 D3 corrected the osteoporotic phenotype caused by 1,25(OH)2 D deficiency or natural aging by inhibiting the p16/p19 pathway. The proliferation, osteogenic differentiation, and ectopic bone formation of bone marrow mesenchymal stem cells derived from mice with genetically induced deficiency of the vitamin D receptor (VDR) were significantly reduced by mechanisms including increased oxidative stress, DNA damage, and cellular senescence. We also demonstrated that p16 deletion largely rescued the osteoporotic phenotype caused by 1,25(OH)2 D3 deficiency, whereas 1,25(OH)2 D3 could up-regulate the enzyme Ezh2 via VDR-mediated transcription thereby enriching H3K27me3 and repressing p16/p19 transcription. Finally, we demonstrated that treatment with 1,25(OH)2 D3 improved the osteogenic defects of human BM-MSCs caused by repeated passages by stimulating their proliferation and inhibiting their senescence via the VDR-Ezh2-p16 axis. The results of this study therefore indicate that 1,25(OH)2 D3 plays a role in preventing age-related osteoporosis by up-regulating Ezh2 via VDR-mediated transcription, increasing H3K27me3 and repressing p16 transcription, thus promoting the proliferation and osteogenesis of BM-MSCs and inhibiting their senescence, while also stimulating osteoblastic bone formation, and inhibiting osteocyte senescence, SASP, and osteoclastic bone resorption.


Assuntos
25-Hidroxivitamina D3 1-alfa-Hidroxilase/metabolismo , Inibidor p16 de Quinase Dependente de Ciclina/metabolismo , Células-Tronco Mesenquimais/efeitos dos fármacos , Osteoporose/tratamento farmacológico , Receptores de Calcitriol/metabolismo , Vitamina D/análogos & derivados , 25-Hidroxivitamina D3 1-alfa-Hidroxilase/genética , Envelhecimento/genética , Animais , Osso e Ossos/diagnóstico por imagem , Osso e Ossos/efeitos dos fármacos , Osso e Ossos/metabolismo , Osso e Ossos/fisiopatologia , Células Cultivadas , Inibidor de Quinase Dependente de Ciclina p19/metabolismo , Dano ao DNA/genética , Proteína Potenciadora do Homólogo 2 de Zeste/metabolismo , Feminino , Histonas/metabolismo , Masculino , Células-Tronco Mesenquimais/metabolismo , Camundongos , Camundongos Knockout , Osteócitos/efeitos dos fármacos , Osteócitos/metabolismo , Osteogênese/genética , Osteoporose/enzimologia , Osteoporose/metabolismo , Osteoporose/fisiopatologia , Estresse Oxidativo/genética , Receptores de Calcitriol/genética , Vitamina D/farmacologia , Vitamina D/uso terapêutico
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA