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1.
J Bone Miner Metab ; 38(6): 894-902, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32656645

RESUMO

INTRODUCTION: Rapid descent in bone mineral density (BMD) and ascent in bone turnover marker (BTM) occur within the short period following denosumab (Dmab) discontinuation. In addition, the incidence of vertebral fracture also rises within the short period. The purpose of this study is to investigate the effects of sequential therapy using zoledronic acid (ZOL) on any adverse events after Dmab discontinuation. MATERIALS AND METHODS: This study was a multicenter retrospective observational study, and the subjects were osteoporosis patients who visited our institutions between 2013 and 2018. We performed sequential therapy using ZOL for 30 patients who had difficulty continuing Dmab, due to physical or social reasons, and investigated the fracture incidence and BMD/BTM changes at 4 time points (at the start of Dmab, the start of ZOL, 6 months after ZOL and 12 months after ZOL). RESULTS: No new vertebral/nonvertebral fractures were observed at each time point after switching from Dmab to ZOL in any of the 30 patients. The BMD/BTM changes were evaluated in 18 of the 30 cases, since all data of lumbar/femoral neck BMDs and TRACP-5b at 4 time points was only available in 18 cases. BMDs significantly increased at each time point compared with that at the start of Dmab. Serum TRACP-5b significantly decreased at each time point compared with that at the start of Dmab. CONCLUSION: It was suggested that sequential therapy using ZOL could suppress the decrease of BMD, and increase of BTM, if the period of Dmab administration was less than 3 years.


Assuntos
Denosumab/uso terapêutico , Suspensão de Tratamento , Ácido Zoledrônico/uso terapêutico , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/sangue , Densidade Óssea/efeitos dos fármacos , Conservadores da Densidade Óssea/efeitos adversos , Conservadores da Densidade Óssea/uso terapêutico , Remodelação Óssea/efeitos dos fármacos , Denosumab/efeitos adversos , Feminino , Fraturas Ósseas/sangue , Fraturas Ósseas/epidemiologia , Fraturas Ósseas/fisiopatologia , Humanos , Masculino , Pessoa de Meia-Idade , Osteoporose/sangue , Estudos Retrospectivos , Fosfatase Ácida Resistente a Tartarato/sangue , Ácido Zoledrônico/efeitos adversos
2.
Inorg Chem ; 59(13): 8699-8706, 2020 Jul 06.
Artigo em Inglês | MEDLINE | ID: mdl-32530609

RESUMO

A novel quadruple perovskite oxide CeCu3Co4O12 has been synthesized in high-pressure and high-temperature conditions of 12 GPa and 1273 K. Rietveld refinement of the synchrotron X-ray powder diffraction pattern reveals that this oxide crystallizes in a cubic quadruple perovskite structure with the 1:3-type ordering of Ce and Cu ions at the A-site. X-ray absorption spectroscopy analysis demonstrates the valence-state transitions in the ACu3Co4O12 series (A = Ca, Y, Ce) from Ca2+Cu3+3Co3.25+4O12 to Y3+Cu3+3Co3+4O12 to Ce4+Cu2.67+3Co3+4O12, where the electrons are doped in the order from B-site (Co3.25+ → Co3+) to A'-site (Cu3+ → Cu2.67+). This electron-doping sequence is in stark contrast to the typical B-site electron doping for simple ABO3-type perovskite and quadruple perovskites CaCu3B4O12 (B = V, Cr, Mn), further differing from the monotonical A'-site electron doping for Na1-xLaxMn3Ti4O12 and A'- and B-site electron doping for AMn3V4O12 (A = Na, Ca, La). The differences in the electron-doping sequences are interpreted by rigid-band models, proposing a wide variety of electronic states for the complex transition-metal oxides containing the multiple valence-variable ions.

3.
J Bone Miner Metab ; 38(2): 230-239, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31586241

RESUMO

INTRODUCTION: Zoledronic acid infusion is used to treat osteoporosis but patients, especially Japanese patients, often experience acute-phase reactions (APRs). In this multicenter, randomized, open-label, parallel-group study, we examined the efficacy of the most commonly used non-steroidal anti-inflammatory drug loxoprofen in Japan in reducing the incidence rate of zoledronic acid-induced APRs and body temperature, and investigated risk/protective factors for APRs in this population. MATERIALS AND METHODS: Patients aged ≥ 60 years with primary osteoporosis (n = 368) were allocated randomly to zoledronic acid plus loxoprofen (ZOL + LOX) or zoledronic acid alone (ZOL). All patients received 5-mg zoledronic acid infusion on day 1, and patients in the ZOL + LOX group also received 120 mg and 180 mg of oral loxoprofen on days 1 and 2, respectively. Adverse events and body temperature were recorded during the 7-day observation period. RESULTS: The incidence rates of APRs were 34.4% (64/186 patients) and 47.8% (87/182 patients) in the ZOL + LOX and ZOL groups, respectively (P = 0.0109). The proportions of patients with increased body temperature (≥ 1 °C and ≥ 37.5 °C) were similar in both groups (P = 0.1186). Past bisphosphonate users had a significantly lower incidence rate of APRs than treatment-naïve patients (odds ratio 0.444, 95% confidence interval 0.285-0.692, P = 0.0003). CONCLUSIONS: Zoledronic acid-induced APRs appeared to be suppressed by loxoprofen. Known risk/protective factors, including prior osteoporosis treatment, were applicable to Japanese patients.


Assuntos
Reação de Fase Aguda/induzido quimicamente , Reação de Fase Aguda/tratamento farmacológico , Anti-Inflamatórios não Esteroides/uso terapêutico , Grupo com Ancestrais do Continente Asiático , Conservadores da Densidade Óssea/uso terapêutico , Ácido Zoledrônico/efeitos adversos , Reação de Fase Aguda/epidemiologia , Idoso , Temperatura Corporal , Difosfonatos/uso terapêutico , Feminino , Humanos , Incidência , Japão , Modelos Logísticos , Masculino , Análise Multivariada , Razão de Chances , Fatores de Risco , Resultado do Tratamento , Ácido Zoledrônico/uso terapêutico
4.
Health Sci Rep ; 2(1): e107, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30697599

RESUMO

Background and aims: Clinical data regarding alendronate jelly are limited. We compared the efficacy and safety of once-weekly alendronate oral jelly with once-weekly alendronate tablet formulations in the context of primary osteoporosis. Methods: In this 6-month, open-label, prospective, observational study, Japanese patients aged ≥60 years with primary osteoporosis were included from 14 primary care centres in Japan. The effects of once-weekly alendronate oral jelly and tablet formulations on bone mineral density (BMD), bone turnover markers, and quality of life related to gastrointestinal symptoms were assessed at baseline and 6 months. Treatment was allocated by patient preference. This potentially confounding factor was adjusted for statistically. Results: In total, 170 patients were enrolled (jelly, n = 97; tablet, n = 73). Mean percent changes in radius, lumbar spine, femoral neck, and hip BMD were similar in both treatment groups at 6 months. Both formulations decreased tartrate-resistant acid phosphatase 5b (TRACP-5b) and procollagen 1 N-terminal peptide (P1NP) between baseline and 6 months (by about 50% and 60%, respectively); no significant differences in mean changes were noted in these markers between groups. At 6 months, no significant differences were noted in visual analogue scale or EuroQOL five-dimension questionnaire scores between groups. The jelly group had significantly lower scores than the tablet group in the Izumo scale domains of heartburn (-0.81, P = 0.0040), epigastralgia (-0.94, P = 0.0003), and epigastric fullness (-0.49, P = 0.044). During treatment, more patients discontinued for upper gastrointestinal symptoms in the tablet group (n = 4) than the jelly group (n = 1). Conclusions: Once-weekly alendronate oral jelly 35 mg may be a suitable alternative therapeutic agent for primary osteoporosis in Japan.

5.
Int Orthop ; 39(6): 1057-64, 2015 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-25488511

RESUMO

PURPOSE: This study assessed the accuracy of cup and stem positioning and limb length adjustment for developmental dysplasia of the hip (DDH) using our new mechanical technique compared with imageless navigation or a computed tomography (CT)-based navigation system. METHODS: One hundred thirteen primary total hip arthroplasties (THAs) for DDH were evaluated. At pre-operative positioning, patients were placed in a precise lateral decubitus position by tilting the surgical table using simple ready-made devices (two shot pipe, metal chain, level gauge and goniometer). During surgery, cups were intentionally placed at 45° inclination and 15° anteversion on radiograph by using a level gauge and goniometer. RESULTS: Cup inclination was 44.2° ± 3.4° (range, 32.0-51.2°), cup anteversion was 19.6° ± 6.1° (range, 3.0-33.1°), stem alignment was 0.04° ± 0.8° valgus (range, 2.1° varus to 1.9° valgus), and leg length discrepancy was -0.37 ± 3.7 mm (range, -12.8 to 8.8 mm) in postoperative radiographs. Outliers (outside ±10° from intentional position) occurred in 15 cases (13.3 %) in inclination or anteversion. Postoperative dislocation did not occur in any cases. CONCLUSIONS: Cup and stem positioning in THAs with our new mechanical technique yielded satisfactory results compared with previously reported imageless navigation or CT-based navigation. Our results were superior with regard to being non-invasive and low cost and involving minimum radiation exposure.


Assuntos
Artroplastia de Quadril/métodos , Luxação Congênita de Quadril/cirurgia , Articulação do Quadril/cirurgia , Desigualdade de Membros Inferiores/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Prótese de Quadril , Humanos , Masculino , Pessoa de Meia-Idade , Posicionamento do Paciente , Período Pós-Operatório , Estudos Prospectivos , Cirurgia Assistida por Computador/métodos , Tomografia Computadorizada por Raios X
6.
Bone ; 65: 42-8, 2014 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-24815919

RESUMO

Maximizing peak bone mass is an important factor in osteoporosis prevention. Resistance exercise increases bone mass and strength, while nutritional supplements have beneficial effects on bone loss reduction. We have previously shown that the combined intake of sucrose and amino acids (AA), which is strongly insulinogenic, efficiently increased muscle protein synthesis. To investigate the effects of sugar and an AA solution immediately after resistance exercise, we compared insulinogenic sucrose and non-insulinogenic fructose combined with an AA solution with or without resistance exercise. Sucrose intake immediately after resistance exercise increased the trabecular bone mass and compressive maximum load compared with fructose+AA intake after exercise. Additionally, combined sucrose+AA and exercise increased trabecular bone formation and decreased bone resorption more than combined fructose and exercise. Serum insulin levels were greatly increased by sucrose+AA intake with exercise. In culture experiments, neither sugar+AA affected osteoblast and osteoclast differentiation. In a gene expression study, sucrose+AA intake after resistance exercise was shown to upregulate the Runx2 expression level and decrease RANKL/OPG ratio. These results suggest that the combined intake of sucrose and an AA solution immediately after resistance exercise exerts anabolic effects on bone by altering gene expression related to bone remodeling. Although translation of our bone remodeling findings from animal to human studies has been challenging, our findings suggest that exercise with sugar+AA intake may contribute to improved bone health.


Assuntos
Aminoácidos/administração & dosagem , Osso e Ossos/fisiologia , Frutose/administração & dosagem , Insulina/biossíntese , Condicionamento Físico Animal , Sacarose/administração & dosagem , Células 3T3 , Absorciometria de Fóton , Animais , Sequência de Bases , Densidade Óssea , Primers do DNA , Camundongos , Ratos , Reação em Cadeia da Polimerase em Tempo Real
7.
DNA Cell Biol ; 22(11): 727-35, 2003 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-14659045

RESUMO

We studied tumorigenic and phenotypic characteristics of pre- and postimmortal human B-lymphoblastoid cell lines (LCLs) transformed by Epstein-Barr virus (EBV): preimmortal LCLs showed low telomerase activity and a normal diploid karyotype while postimmortal LCLs showed much higher telomerase activity and maintained a clonal aneuploidic state. Among five postimmortal LCLs tested, LCLs N0005 and N6803 formed colonies in agar medium and showed marked aneuploidy, and N6803 was transplantable into nude mice indicating that it had a complete malignant phenotype, but all preimmortal LCLs and the remaining three postimmortal LCLs lacked these characteristics. The products of tumor suppresser genes, p16(INK4A) and pRb, were downregulated in these two LCLs, and the p53 gene was mutated in N0005 LCL. We believe these results showed for the first time that some postimmortal EBV-transformed LCLs can become tumorigenic, contrary to previous reports, and that these LCLs provide an in vitro model of tumorigenesis induced by EBV.


Assuntos
Linfócitos B , Linhagem Celular Tumoral , Transformação Celular Neoplásica , Aneuploidia , Animais , Linfócitos B/enzimologia , Linfócitos B/patologia , Linfócitos B/virologia , Transformação Celular Viral , Diploide , Regulação para Baixo , Genes do Retinoblastoma , Genes Supressores de Tumor , Genes p16 , Genes p53 , Herpesvirus Humano 4 , Humanos , Técnicas In Vitro , Camundongos , Camundongos Nus , Mutação , Fenótipo , Telomerase/metabolismo
8.
J Bone Miner Res ; 18(11): 2002-9, 2003 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-14606513

RESUMO

UNLABELLED: To investigate the relationship between the effects of bone turnover and bone marrow cell development in bone cells, we developed a mouse voluntary climbing exercise model. Climbing exercise increased bone volume and transient osteogenic potential of bone marrow. This model would be suitable for investigating the mechanistic roles of mechanical loading. INTRODUCTION: The relationship between bone mass gain and local bone formation and resorption in mechanically loaded bone is not well understood. MATERIALS AND METHODS: Sixty-five C57BL/6J mice, 8 weeks of age, were assigned to five groups: a baseline control and two groups each of ground control and climbing exercise mice for 2 and 4 weeks. Mice were housed in a 100-cm tower and had to climb toward a bottle placed at the top to drink water. RESULTS: Compared with the ground control, bone mineral density of the left femur increased in the climbing mice at 4 weeks. At 2 and 4 weeks, bone formation rate (BFR/BS) of periosteal surface, the cross-sectional area, and moment of inertia were increased in the climbing mice, whereas BFR/BS and eroded surface (ES/BS) of endosteal surface did not differ. The trabecular bone volume (BV/TV) of the proximal tibia increased in climbing mice, and osteoclast surface (Oc.S/BS) and osteoclast number decreased at 2 weeks. At 4 weeks, there were increases in BV/TV and parameters of bone formation, including mineralized surface, mineral apposition rate, and bone formation rate. In marrow cell cultures from the tibia, the number of alkaline phosphatase+ colony forming units-fibroblastic and the area of mineralized nodule formation in climbing mice were increased, and the number of osteoclast-like TRACP+ multinucleated cells was lower at 2 weeks. At 4 weeks, these parameters recovered to the levels of the ground controls. CONCLUSION: Our results indicate that climbing increased trabecular bone volume and reduced bone resorption, with a subsequent increase in bone formation. Intermittent climbing downregulates marrow osteoclastogenic cells and upregulates osteogenic cells initially, but further exercise seemed to desensitize them. Cortical envelopes were enlarged earlier, but the response seems to differ from trabecular bone.


Assuntos
Desenvolvimento Ósseo/fisiologia , Remodelação Óssea/fisiologia , Osso e Ossos/fisiologia , Osteoclastos/fisiologia , Condicionamento Físico Animal/fisiologia , Animais , Peso Corporal , Densidade Óssea/fisiologia , Células da Medula Óssea/fisiologia , Fêmur/anatomia & histologia , Fêmur/fisiologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Tamanho do Órgão , Osteoclastos/citologia
9.
J Bone Miner Res ; 18(1): 140-9, 2003 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-12510816

RESUMO

To determine both the preventive and recovery effects of tower climbing exercise on mass, strength, and local turnover of bone in ovariectomized (OVX) rats, we carried out two experiments. In experiment I, 60 Sprague-Dawley rats, 12 months of age, were assigned to four groups: a Baseline Control, Sham-Operated Sedentary, OVX-Sedentary and OVX-Exercise rats. Rats voluntarily climbed a 200-cm tower to drink water from a bottle set at the top. At 3 months, OVX elevated both the femoral cortex and lumbar trabecular turnover, leading to a reduction in bone mass and strength. However, in OVX-Exercise rats, those values were maintained at the same level as in the Sham-Sedentary rats. Thus, the climbing exercise, started after 3 days of OVX, prevented OVX-induced cortical and trabecular bone loss by depressing turnover elevation. After confirming the preventive effect, we evaluated the recovery effect of exercise. In experiment II, 90 Sprague-Dawley rats, 12 months of age, were assigned to six groups: a Baseline control, two groups of Sham-Operated Sedentary and OVX-Sedentary, and OVX-Exercise rats. The exercise started 3 months after the OVX operation. At 3 months, OVX increased the trabecular bone formation rate and osteoclast surface, leading to a decrease in compressive strength. In the midfemur, the cross-sectional area, moment of inertia, and bending load values decreased. At 6 months, in the OVX-Exercise rats, the parameters of breaking load in both the lumbar and midfemur, lumbar bone mass, and the total cross-sectional area recovered to the same levels as those in the Sham-Sedentary rats. However, the cortical bone area did not recover. Periosteal bone formation increased, while endosteal bone formation decreased. These results showed that the climbing exercise had both a preventive and recovery effect on bone strength in OVX rats. In the mid-femur, effects on bone formation were site-specific, and the cross-sectional morphology was improved without an increase in cortical bone area, supporting cortical drift by mechanical stimulation.


Assuntos
Doenças Ósseas Metabólicas/terapia , Animais , Fenômenos Biomecânicos , Densidade Óssea , Doenças Ósseas Metabólicas/etiologia , Doenças Ósseas Metabólicas/fisiopatologia , Feminino , Fêmur/fisiopatologia , Vértebras Lombares/fisiopatologia , Osteogênese , Ovariectomia , Condicionamento Físico Animal , Ratos , Ratos Sprague-Dawley , Estresse Mecânico , Fatores de Tempo
10.
J Appl Physiol (1985) ; 93(3): 1152-8, 2002 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-12183513

RESUMO

To determine the effects of a tower climbing exercise on mass, strength, and local turnover of bone, 70 9-wk-old Sprague-Dawley rats were assigned to seven groups: a baseline control and three groups of sham-operated sedentary, orchidectomized (ORX)-sedentary and ORX-exercise rats. Rats voluntarily climbed a 200-cm tower to drink water from a bottle set at the top. At 4 wk, the periosteal bone formation rate (BFR), moment of inertia, bone mineral content, bone mineral density, and bending load at the midfemur were maintained in ORX-exercise rats, whereas these parameters were reduced in ORX-sedentary rats. At 8 wk, the periosteal mineral apposition rate and BFR in ORX-exercise rats were significantly higher, whereas the parameters in ORX-sedentary rats did not differ compared with sham-sedentary rats. In ORX-exercise rats, the trabecular mineralizing surface, BFR, and bone volume of the lumbar vertebrae were maintained at the same levels as those in the sham-sedentary group, whereas the osteoclast surface decreased compared with the ORX-sedentary group. However, the climbing exercise did not affect bone mineral content, bone mineral density, or the compression load of the lumbar vertebrae. These results show that, in the midfemur, the voluntary climbing exercise maintained cortical bone mass and strength by stimulating periosteal bone formation and partially prevented ORX-induced trabecular bone loss, depressing the elevation of turnover. Interestingly, in ORX rats, the climbing exercise had the opposite effect on bone formation at the periosteal femoral cortical bone, where the exercise increased the bone formation compared with vertebral trabecular bone, where the exercise decreased it.


Assuntos
Envelhecimento/fisiologia , Densidade Óssea/fisiologia , Remodelação Óssea/fisiologia , Osso e Ossos/fisiologia , Atividade Motora/fisiologia , Orquiectomia , Abdome , Tecido Adiposo/anatomia & histologia , Animais , Biomarcadores , Peso Corporal , Reabsorção Óssea/fisiopatologia , Fêmur/anatomia & histologia , Fêmur/fisiologia , Membro Posterior , Vértebras Lombares/fisiologia , Masculino , Músculo Esquelético/fisiologia , Ratos , Ratos Sprague-Dawley , Resistência à Tração , Fatores de Tempo
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