RESUMO
No disponible
Assuntos
Humanos, Masculino, Pessoa de Meia-Idade, Infecções por Klebsiella/tratamento farmacológico, Klebsiella pneumoniae/patogenicidade, Bacteriemia/tratamento farmacológico, Ceftazidima/administração & dosagem, Farmacorresistência Bacteriana Múltipla, Serviços Hospitalares de Assistência Domiciliar/tendênciasAssuntos
Compostos Azabicíclicos/uso terapêutico, Bacteriemia/tratamento farmacológico, Ceftazidima/uso terapêutico, Infecções por Klebsiella/tratamento farmacológico, Inibidores de beta-Lactamases/uso terapêutico, Combinação de Medicamentos, Serviços de Assistência Domiciliar, Humanos, Klebsiella pneumoniae/enzimologia, Masculino, Pessoa de Meia-Idade, beta-Lactamases/biossínteseRESUMO
Osteoporosis is defined as a reduction in bone mass and impairment of bone quality that lead to bone fragility and fracture risk. Bone quality includes a hierarchy of properties from macroscopic to nanoscale level. Several techniques have been developed in an attempt to measure these non-density properties. Densitometry, high-resolution images (radiography, CT scan), and MRI can measure the geometry and microarchitecture of bone. Tissue mineralization and composition can be assessed by use of microradiography, Fourier-transform infrared spectroscopy, or Raman microspectroscopy. Finite-element analysis is an image-based method that enables calculation of bone strength. More recently, microindentation has enabled direct estimation of bone material strength, measured in the cortical bone of the tibia. Most of these techniques are of limited use to clinics, although finite-element analysis and microindentation have high potential for clinical use and can enable more comprehensive and accurate evaluation of bone fragility and fracture susceptibility.
Assuntos
Osteoporose/diagnóstico, Absorciometria de Fóton/métodos, Densidade Óssea/fisiologia, Remodelação Óssea/fisiologia, Análise de Elementos Finitos, Humanos, Osteoporose/fisiopatologia, Fraturas por Osteoporose/diagnóstico, Fraturas por Osteoporose/fisiopatologia, Estresse MecânicoRESUMO
A major side effect of aromatase inhibitor (AI) therapy is AI-related arthralgia (AIA), which often leads to therapy discontinuation. We aimed to identify genetic variants associated with AIA and therapy discontinuation in the first year of AI treatment. Our prospective cohort study included 343 postmenopausal women with early breast cancer starting AI therapy. Single nucleotide polymorphisms (SNPs) in candidate genes involved in estrogen and vitamin D signaling were selected. Univariate and multivariate linear/logistic regressions were fitted in order to asses the association between studied SNPs and AIA intensity (visual analogic scale score) at 3 and 12 months of follow-up, worsening pain, and therapy discontinuation. We also tested for a priori-defined interactions by introducing multiplicative terms in the regression equations. SNPs in CYP17A1 and VDR genes appeared significantly associated with AIA (P = 0.003, P = 0.012, respectively). One SNP in CYP27B1 gene was related to therapy discontinuation [P = 0.02; OR 0.29 (0.09-0.99)]. We revealed interactions between CYP27B1 and both CYP17A1 (P = 0.01) and VDR SNPs (P = 0.06). Furthermore, an additive effect on pain intensity was shown for unfavorable alleles, with two points higher mean absolute pain increase and up to 5.3-fold higher risk of worsening pain compared to favorable genotypes. SNPs in CYP17A1, VDR, and CYP27B1 genes predict the risk of AIA. Their determination would be useful to trigger the monitoring strategies in women at risk of therapy discontinuation.
Assuntos
Inibidores da Aromatase/administração & dosagem, Artralgia/induzido quimicamente, Neoplasias da Mama/tratamento farmacológico, 25-Hidroxivitamina D3 1-alfa-Hidroxilase/genética, Idoso, Inibidores da Aromatase/efeitos adversos, Artralgia/genética, Artralgia/patologia, Neoplasias da Mama/genética, Neoplasias da Mama/patologia, Estudos de Coortes, Feminino, Genótipo, Humanos, Pessoa de Meia-Idade, Estadiamento de Neoplasias, Polimorfismo de Nucleotídeo Único, Pós-Menopausa, Estudos Prospectivos, Receptores de Calcitriol/genética, Esteroide 17-alfa-Hidroxilase/genéticaRESUMO
Atypical femoral fractures (AFF) associated with long-term bisphosphonates (LTB) are a growing concern. Their etiology is unknown, but bone material properties might be deteriorated. In an AFF series, we analyzed the bone material properties by microindentation. Four groups of patients were included: 6 AFF, 38 typical osteoporotic fractures, 6 LTB, and 20 controls without fracture. Neither typical osteoporotic fractures nor controls have received any antiosteoporotic medication. A general laboratory workup, bone densitometry by dual-energy X-ray absorptiometry (DXA), and microindentation testing at the tibia were done in all patients. Total indentation distance (Total ID), indentation distance increase (IDI), and creep indentation distance (Creep ID) were measured (microns). Age-adjusted analysis of covariance (ANCOVA) was used for comparisons. Controls were significantly younger than fracture groups. Bisphosphonate exposure was on average 5.5 years (range 5 to 12 years) for the AFF and 5.4 years (range 5 to 8 years) for the LTB groups. Total ID (microns) showed better material properties (lower Total ID) for controls 36 (± 6; mean ± SD) than for AFF 46 (± 4) and for typical femoral fractures 47 (± 13), respectively. Patients on LTB showed values between controls and fractures, 38 (± 4), although not significantly different from any of the other three groups. IDI values showed a similar pattern 13 (± 2), 16 (± 6), 19 (± 3), and 18 (± 5). After adjusting by age, significant differences were seen between controls and typical (p < 0.001) and atypical fractures (p = 0.03) for Total ID and for IDI (p < 0.001 and p < 0.05, respectively). There were no differences in Creep ID between groups. Our data suggest that patients with AFF have a deep deterioration in bone material properties at a tissue level similar to that for the osteoporotic fracture group. The LTB group shows levels that are in between controls and both type of fractures, although not statistically different. These results suggest that bisphosphonate therapy probably does not put the majority of patients at risk for AFF.
