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1.
PLoS One ; 15(9): e0237566, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32870946

RESUMO

BACKGROUND: Giving patients anti-osteoporotic agents peri-operatively is a well-accepted strategy to increase fusion rate and prevent complications. The purpose of this study was to investigate effectiveness of teriparatide and bisphosphonate on fusion surgery of thoracic and lumbar spine. METHODS: We searched EMBASE and PubMed for randomized clinical trials (RCTs) and prospective comparative studies using teriparatide or bisphosphonate in peri-operative spinal fusion surgery. Our synthesized data of fusion rate, Oswestry disability index (ODI), and adverse event in contrast-based network meta-analysis. Pooled results were presented in risk ratio (RR) or mean difference (MD) with 95% confidence interval (CI). RESULTS: Our search hit eight RCTs and three prospective studies with 676 patients receiving spinal surgery. Pooled result showed that teriparatide+Denosumab leads to significantly higher fusion rate than placebo (RR, 2.84; 95% CI: 1.22 to 6.60) and bisphosphonate (RR, 2.59; 95% CI: 1.13 to 5.96). We did not observe significant finding among placebo, teriparatide, and bisphosphonate in the two network models. CONCLUSION: This is the first network meta-analysis providing an overview of the use of teriparatide and bisphosphonate for spinal fusion surgery. Teriparatide treatments are worth to be consider for spinal fusion surgery.


Assuntos
Conservadores da Densidade Óssea/uso terapêutico , Hormônios e Agentes Reguladores de Cálcio/uso terapêutico , Difosfonatos/uso terapêutico , Fusão Vertebral/métodos , Teriparatida/uso terapêutico , Humanos , Vértebras Lombares/efeitos dos fármacos , Vértebras Lombares/cirurgia , Doenças da Coluna Vertebral/tratamento farmacológico , Doenças da Coluna Vertebral/cirurgia , Vértebras Torácicas/efeitos dos fármacos , Vértebras Torácicas/cirurgia , Resultado do Tratamento
2.
Life Sci ; 258: 118213, 2020 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-32768583

RESUMO

AIMS: Intermittent cyclic tension stimulation(ICMT) was shown to promote degeneration of endplate chondrocytes and induce autophagy. However, enhancing autophagy can alleviate degeneration partly. Studies have shown that curcumin can induce autophagy and protect chondrocytes, we speculated that regulation of autophagy by curcumin might be an effective method to improve the stress resistance of endplate cartilage. In this study, human cervical endplate cartilage specimens were collected, and expression of autophagy markers was detected and compared. MAIN METHODS: Human cervical endplate chondrocytes were cultured to establish a tension-induced degeneration model, for which changes of functional metabolism and autophagy levels were detected under different tension loading conditions. Changes in functional metabolism of endplate chondrocytes were observed under high-intensity tension loading in the presence of inhibitors, inducers, and curcumin to regulate the autophagy level of cells. In addition, a rat model of lumbar instability was established to observe the degeneration of lumbar disc after curcumin administration. KEY FINDINGS: Through a series of experiments, we found that low-intensity tension stimulation can maintain a stable phenotype of endplate chondrocytes, but high-intensity tension stimulation has a negative effect. Moreover, with increasing tension intensity, the degree of degeneration of endplate chondrocytes was gradually aggravated and the level of autophagy increased. Besides, curcumin upregulated autophagy, inhibited apoptosis, and reduced phenotype loss of endplate chondrocytes induced by high-intensity tension loading, thereby relieving intervertebral disc degeneration induced by mechanical imbalance. SIGNIFICANCE: Curcumin mediated autophagy and enhanced the adaptability of endplate chondrocytes to high-intensity tension load, thereby relieving intervertebral disc degeneration.


Assuntos
Anti-Inflamatórios não Esteroides/uso terapêutico , Autofagia/efeitos dos fármacos , Cartilagem/efeitos dos fármacos , Curcumina/uso terapêutico , Degeneração do Disco Intervertebral/tratamento farmacológico , Animais , Anti-Inflamatórios não Esteroides/farmacologia , Autofagia/fisiologia , Cartilagem/patologia , Curcumina/farmacologia , Feminino , Degeneração do Disco Intervertebral/patologia , Vértebras Lombares/efeitos dos fármacos , Vértebras Lombares/patologia , Masculino , Ratos , Ratos Sprague-Dawley
3.
J Comput Assist Tomogr ; 44(4): 562-568, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32697527

RESUMO

OBJECTIVE: The objective of this article was to study the association of aspirin and other nonsteroidal anti-inflammatory drugs (NSAIDs) with bone mineral density (BMD). METHODS: Spine BMD was evaluated in a subset of 2028 participants from the Multiethnic Study of Atherosclerosis cohort who were NSAID users (including aspirin) and underwent both lumbar and thoracic imaging. Multiethnic Study of Atherosclerosis is a prospective cohort study that includes 4 ethnic groups (white, Asian, African American, and Hispanic). Trabecular BMD was evaluated by quantitative computed tomography based on cardiac computed tomography images, which were obtained during coronary calcium scans. The analyses were cross sectional using baseline examination data for exposure and outcomes. RESULTS: After adjustment for potential confounders including age, sex, race, and traditional cardiovascular risk factors, a small association between trabecular BMD and baseline use of COX-2-selective NSAID was observed. COX-2-selective NSAID use was associated with 7.4 mg/cm (95% confidence interval [CI], 1.6-13.3; P = 0. 013) higher trabecular BMD in thoracic spine and 10.6 mg/cm higher at lumbar spine (95% CI, 5.1-16.1; P < 0.001). Among regular aspirin users, there was no association between drug use and trabecular BMD. Considering all spine fractures together, the prevalence ratio of fractures among aspirin users was 1.0 (95% CI, 0.6-1.6) and 1.1 (95% CI, 0.5-2.3) among COX-2-selective NSAID users. CONCLUSIONS: Regular use of aspirin has no significant association with trabecular BMD in either the thoracic or lumbar spine and no association with fracture prevalence. COX-2-selective NSAIDs may have modest positive association with BMD, but the mechanisms were not assessed and the observational study design makes residual confounding a possible alternate explanation. Potential pathological mechanisms warrant further longitudinal exploration.


Assuntos
Anti-Inflamatórios não Esteroides/administração & dosagem , Aspirina/administração & dosagem , Osso Esponjoso/diagnóstico por imagem , Fraturas Ósseas/epidemiologia , Vértebras Lombares/diagnóstico por imagem , Vértebras Torácicas/diagnóstico por imagem , Idoso , Anti-Inflamatórios não Esteroides/efeitos adversos , Aspirina/efeitos adversos , Densidade Óssea/efeitos dos fármacos , Osso Esponjoso/efeitos dos fármacos , Estudos Transversais , Feminino , Fraturas Ósseas/diagnóstico por imagem , Humanos , Vértebras Lombares/efeitos dos fármacos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Vértebras Torácicas/efeitos dos fármacos , Tomografia Computadorizada por Raios X , Estados Unidos/etnologia
4.
Niger J Clin Pract ; 23(6): 835-841, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32525120

RESUMO

Aims: This study aims to investigate the effectiveness of transforaminal epidural steroid injection (TFESI) in patients with lumbar radicular pain or radiculopathy caused by different spinal pathologies. Methods: One hundred and seventy seven patients who underwent single transforaminal epidural steroid injection were included in the study group and divided into 3 subgroups (central spinal stenosis + lateral recess stenosis, foraminal stenosis, lumbar disc herniation) according to existing spinal pathology. Patients' visuel analogue scale (VAS) measures and Oswestry Disability Index (ODI) scores were recorded and the patients who give favourable response to treatment were called respondents and who were not called as non-respondents. Subgroups were compared statistically at the end of 12 months. Results: Sixty patients (33.9%) were considered as respondents and 117 patients (66.1%) were non-respondents in the entire study group. Patients with foraminal stenosis included the vast majority of the respondents and showed better results of pain relief as opposed to patients of other groups at the end of 12 months (P < 0.001). Conclusion: TFESI was an effective treatment modality for pain relief and functional improvement in patients with foraminal stenosis. However, it could not produce the same results in patients with central spinal stenosis and lumbar disc herniations.


Assuntos
Dor nas Costas/tratamento farmacológico , Injeções Epidurais/efeitos adversos , Deslocamento do Disco Intervertebral/diagnóstico , Vértebras Lombares/fisiopatologia , Medição da Dor/métodos , Radiculopatia/tratamento farmacológico , Estenose Espinal/tratamento farmacológico , Esteroides/administração & dosagem , Adulto , Idoso , Dor nas Costas/etiologia , Feminino , Humanos , Vértebras Lombares/efeitos dos fármacos , Região Lombossacral/fisiopatologia , Imagem por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Manejo da Dor/métodos , Medição da Dor/efeitos dos fármacos , Estudos Retrospectivos , Estenose Espinal/complicações , Estenose Espinal/diagnóstico , Esteroides/efeitos adversos , Resultado do Tratamento , Escala Visual Analógica
5.
Medicine (Baltimore) ; 99(26): e20925, 2020 Jun 26.
Artigo em Inglês | MEDLINE | ID: mdl-32590804

RESUMO

To explore a suitable indication of interspinous process distraction device for lumbar spinal stenosis with BacFuse.Patients of lumbar spinal stenosis (LSS) who experienced interspinous process distraction device surgery with BacFuse from June 2014 to January 2015 in our institute were included. We classified LSS into central and lateral types, and then divided these into severe and moderate according to the degree of stenosis. Each type was divided into 2 groups. Patients in group A underwent distraction without bone decompression (stand-alone), while patients in group B underwent bone decompression combined with distraction. Follow-up was performed at 1 month, 3 months, 6 months, 2 years, and 5 years after surgery. Zurich Claudication Questionnaire (ZCQ) was recorded to assess the patient's postoperative condition at each follow-up.A total of 142 patients were available for follow up at each time interval. There was a significant difference between the preoperative and final follow-up ZCQ scores for every LSS type. In addition, there was no difference between group A and group B in the postoperative ZCQ scores with the exception of the lateral severe type. In the study, 22 of the 23 patients (95.65%) in the lateral moderate type were considered to have a satisfactory result in group B, with a similar result of 93.33% (14/15) in group A (P = .75). In the lateral severe type, the patient satisfaction rate was 65.22% (15/23) and 90.63% (29/32) in group A and group B (P = .02), respectively. In the central moderate type, the patient satisfaction rate was 81.82% (15/23) and 76.92% (10/13) in group A and group B (P = .77), respectively. Satisfaction rate for the follow-up results in the central severe type reached 57.14% (4/7) in group A, and 54.55% (6/11) in group B (P = .91). Moreover, no relationship was found between satisfaction and neurogenic intermittent claudication.The most suitable indication for BacFuse treatment was the lateral moderate type. For lateral severe patients, distraction combined with decompression is suggested for a higher satisfaction rate. Severe central spinal stenosis was shown to be a relative contraindication for BacFuse.


Assuntos
Descompressão Cirúrgica/instrumentação , Desenho de Equipamento/normas , Vértebras Lombares/efeitos dos fármacos , Estenose Espinal/tratamento farmacológico , Estenose Espinal/cirurgia , Idoso , Descompressão Cirúrgica/métodos , Feminino , Seguimentos , Humanos , Vértebras Lombares/anormalidades , Vértebras Lombares/cirurgia , Masculino , Pessoa de Meia-Idade , Satisfação do Paciente , Período Pós-Operatório , Psicometria/instrumentação , Psicometria/métodos , Psicometria/estatística & dados numéricos , Estudos Retrospectivos , Inquéritos e Questionários , Resultado do Tratamento
6.
J Bone Miner Metab ; 38(5): 730-736, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32405760

RESUMO

INTRODUCTION: Aromatase inhibitors are known to accelerate bone loss in patients with breast cancer. However, how much AIs affect the efficacy of antiresorptive agents has not been studied. The study aimed to compare the effect of alendronate on bone mineral density (BMD) between patients with and without AI treatment. MATERIALS AND METHODS: In this retrospective study, 90 postmenopausal women with early breast cancer who were being treated with both AI and alendronate 70 mg weekly (ALN + AI), and 90 age- and body mass index (BMI)-matched patients who were only taking alendronate (ALN-only) were analyzed. BMD and bone turnover markers (BTMs) were assessed at the baseline and 12 months. RESULTS: The mean age was 63 years. At baseline, the ALN-only group had lower lumbar spine (LS), femur neck (FN), and total hip (TH) BMD than ALN + AI group. After 1-year of alendronate treatment, the LS and FN BMD were improved more in the ALN-only group than those in the ALN + AI group after adjustments for age, BMI, baseline BMD, diabetes, hypertension, renal function, and previous fracture history [LS BMD: 6.2% (3.1%; 9.2%) in ALN-only, 3.5% (-0.5%; 6.5%) in ALN + AI, p = 0.001; FN BMD: 2.5% (0.3%; 5.7%) in ALN-only, 0.9% (- 1.8%; 3.6%) in ALD + AI, p = 0.032]. BTMs were significantly decreased in both groups, but the changes between groups were similar. CONCLUSION: The effect of alendronate on the LS and FN BMD was attenuated in postmenopausal women who were taking AI compared to those who were not on AI.


Assuntos
Alendronato/uso terapêutico , Inibidores da Aromatase/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Alendronato/farmacologia , Inibidores da Aromatase/farmacologia , Densidade Óssea/efeitos dos fármacos , Conservadores da Densidade Óssea/farmacologia , Remodelação Óssea/efeitos dos fármacos , Neoplasias da Mama/fisiopatologia , Feminino , Colo do Fêmur/efeitos dos fármacos , Colo do Fêmur/fisiopatologia , Humanos , Vértebras Lombares/efeitos dos fármacos , Vértebras Lombares/fisiopatologia , Pessoa de Meia-Idade , Estudos Retrospectivos
7.
Medicine (Baltimore) ; 99(15): e18964, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32282692

RESUMO

BACKGROUND: We performed a systematic review and meta-analysis of the efficacy and safety of teriparatide and bisphosphonates in managing postmenopausal osteoporosis. METHODS: PubMed, EMBASE, Web of Science, and China National Knowledge Infrastructure were searched for relevant randomized controlled trials that were published before April 2018 and compared teriparatide and bisphosphonates in treating postmenopausal osteoporosis. Stata 12.0 was used for the meta-analysis. The pooled risk ratio (RR) or weighted mean difference and 95% confidence interval (CI) were calculated using a fixed effects or random effects meta-analysis. RESULTS: A total of 14 randomized controlled trials were included in this meta-analysis. The teriparatide group was associated with a lower total occurrence of vertebral fractures (RR = 0.55, 95% CI: 0.40-0.77; P = .001) and nonvertebral fractures (RR = 0.65, 95% CI: 0.46-0.90; P = .009) than the bisphosphonate group. Moreover, compared with the bisphosphonate group, the teriparatide group had improved bone mineral density at the lumbar spine and femoral neck at the final follow-up (P < .05). There was no significant difference between the teriparatide and bisphosphonate groups in terms of complications (RR = 1.05, 95% CI: 0.90, 1.22, P = .516). CONCLUSIONS: Teriparatide significantly reduced the occurrence of vertebral and nonvertebral fractures in osteoporosis patients. More studies should focus on the quality of life of patients using these 2 drugs.


Assuntos
Conservadores da Densidade Óssea/uso terapêutico , Densidade Óssea/efeitos dos fármacos , Difosfonatos/uso terapêutico , Osteoporose Pós-Menopausa/tratamento farmacológico , Teriparatida/uso terapêutico , Conservadores da Densidade Óssea/farmacologia , Difosfonatos/farmacologia , Colo do Fêmur/efeitos dos fármacos , Humanos , Vértebras Lombares/efeitos dos fármacos , Osteoporose Pós-Menopausa/complicações , Fraturas da Coluna Vertebral/etiologia , Fraturas da Coluna Vertebral/prevenção & controle , Teriparatida/farmacologia
8.
J Bone Miner Metab ; 38(4): 522-532, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32140784

RESUMO

INTRODUCTION: Eldecalcitol increases bone mineral density (BMD) and reduces vertebral fracture in patients with primary osteoporosis. However, the effect of eldecalcitol on BMD and fracture in glucocorticoid-induced osteoporosis (GIO) patients is unknown. This study was undertaken to compare the effect of eldecalcitol on BMD and fracture with that of alfacalcidol in GIO patients. MATERIALS AND METHODS: A randomized, open-label, parallel group study was conducted to identify the effectiveness and safety of monotherapy with 0.75 µg eldecalcitol compared with 1.0 µg alfacalcidol in GIO patients. RESULTS: Lumbar spine BMD increased with eldecalcitol, but decreased with alfacalcidol at 12 and 24 months (between group difference 1.29%, p < 0.01, and 1.10%, p < 0.05, respectively). Total hip and femoral neck BMD were maintained until 24 months by eldecalcitol, but decreased by alfacalcidol (between group difference 0.97%, p < 0.05 and 1.22%, p < 0.05, respectively). Both bone formation and resorption markers were more strongly suppressed by eldecalcitol than by alfacalcidol. Eldecalcitol showed better effect on BMD than alfacalcidol in patients with no prevalent fracture and BMD > 70% of the young adult mean, and with ≤ 3 months of previous glucocorticoid treatment. No significant difference in the incidence of vertebral fracture was found, and the incidence of adverse events was similar between the two groups. CONCLUSIONS: Eldecalcitol was more effective than alfacalcidol in maintaining BMD in GIO patients. Because eldecalcitol was effective in patients with no or short-term previous glucocorticoid treatment, as well as those without prevalent fracture or low BMD, eldecalcitol can be a good candidate for primary prevention of GIO. CLINICAL TRIAL REGISTRATION NUMBER: UMIN000011700.


Assuntos
Densidade Óssea , Glucocorticoides/efeitos adversos , Hidroxicolecalciferóis/uso terapêutico , Osteoporose/tratamento farmacológico , Osteoporose/fisiopatologia , Vitamina D/análogos & derivados , Biomarcadores/metabolismo , Densidade Óssea/efeitos dos fármacos , Conservadores da Densidade Óssea/uso terapêutico , Remodelação Óssea/efeitos dos fármacos , Feminino , Colo do Fêmur/efeitos dos fármacos , Colo do Fêmur/fisiopatologia , Quadril/fisiopatologia , Humanos , Hidroxicolecalciferóis/efeitos adversos , Hidroxicolecalciferóis/farmacologia , Estimativa de Kaplan-Meier , Vértebras Lombares/efeitos dos fármacos , Vértebras Lombares/fisiopatologia , Masculino , Pessoa de Meia-Idade , Fraturas da Coluna Vertebral/epidemiologia , Vitamina D/efeitos adversos , Vitamina D/farmacologia , Vitamina D/uso terapêutico
9.
Spine (Phila Pa 1976) ; 45(13): 863-871, 2020 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-32049937

RESUMO

STUDY DESIGN: Multicenter, prospective randomized study. OBJECTIVE: Evaluate the impact of weekly teriparatide (WT) and bone contact (BC) status of grafted bone in patients recovering from multilevel lumbar interbody fusion (M-LIF). SUMMARY OF BACKGROUND DATA: WT has been reported to significantly improve bone fusion following posterior or transforaminal interbody fusion in osteoporosis patients. METHODS: Patients older than 50 years and osteoporotic were recruited. We defined the fusion of two or more consecutive intervertebral levels as M-LIF. All patients were instrumented with pedicle, iliac, or S-2 alar iliac screws after transplanting cages and autogenous bone between vertebral bodies. After surgical indication for M-LIF, the subjects were randomly allocated to receive either subcutaneous WT from 1 week to 6 months postoperatively (WT arm, N = 50) or a bisphosphonate (BP; BP arm, N = 54). Blinded radiological evaluations were performed using computed tomography (CT). Evaluation of bone fusion was performed at the intervertebral disc located at the bottom of the fixed range. The degree of bone fusion was calculated as a score from 2 to 6 points, with 2 defined as complete fusion. Bone fusion rate was also compared at 6 months postoperatively based on BC status of the grafted bone on CT immediately after surgery. RESULTS: Mean bone fusion score at 6 months postoperatively was 3.9 points in the WT group and 4.2 points in the BP group. The bone fusion rate at 6 months postoperatively tended to be higher in the WT group (46.8% vs. 32.7% in the BP group). The 6-month postoperative fusion rate of immediately postoperative of BC+ patients was significantly higher than that of BC- patients (47.4% vs. 9.5%). CONCLUSION: In M-LIF, there were no significant differences in bone fusion score between WT- and BP-treated patients. In contrast, BC status immediately postoperatively had a major impact on 6-month bone fusion. LEVEL OF EVIDENCE: 1.


Assuntos
Difosfonatos/uso terapêutico , Disco Intervertebral/efeitos dos fármacos , Vértebras Lombares/efeitos dos fármacos , Osteoporose/cirurgia , Teriparatida/uso terapêutico , Adulto , Idoso , Feminino , Humanos , Ílio/transplante , Disco Intervertebral/cirurgia , Articulações , Vértebras Lombares/cirurgia , Região Lombossacral/cirurgia , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Distribuição Aleatória , Fusão Vertebral/métodos , Resultado do Tratamento
10.
Spine (Phila Pa 1976) ; 45(12): E729-E741, 2020 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-31923133

RESUMO

STUDY DESIGN: This is a systematic literature review and meta-analysis. OBJECTIVE: We aimed to evaluate the efficacy and safety of recombinant human bone morphogenetic protein (RhBMP) and autologous iliac crest bone graft (ICBG) in lumbar fusion. SUMMARY OF BACKGROUND DATA: RhBMP has been emphasized in lumbar fusion due to high fusion success rate. However, ICBG remains the criterion standard graft approach for lumbar fusion. The safety and effectiveness of rhBMP are controversial. METHODS: Prospective randomized controlled trials were searched from PubMed, EMBASE, and Cochrane Central Register of Controlled Trails by using Medical Subject Headings terms "bone morphogenetic protein,' "bone transplantation,' and "spinal fusion.' Two independent investigators screened eligible studies, assessed the bias of original articles, extracted data including fusion success, Oswestry disability index improvement, improved short form 36 questionnaire scores, adverse events and re-operation, and a subgroup analysis. The GRADE approach was used to grade quality of evidence. RESULTS: Twenty randomized controlled trials (2185 patients) met the inclusion criteria. There were higher fusion success rate (odds ratio [OR] 3.79, 95% confidence interval [CI] 1.88-7.63, P = 0.0002), better improvement of Oswestry Disability Index (mean difference 1.54, 95% CI 0.18-2.89, P = 0.03), and lower re-operation rate (OR 0.59, 95% CI 0.43-0.80, P = 0.0007) in rhBMP group. Heterogeneity was obvious in fusion success rate (I = 58%); hence, a subgroup analysis, based on protein type (rhBMP-2 or rhBMP-7), was performed, which suggested that only rhBMP-2 was better than ICBG for lumbar fusion. There was no difference in the incidence of adverse events between rhBMP and ICBG (OR 0.91, 95% CI 0.70-1.18, P = 0.47). CONCLUSION: In lumbar fusion, rhBMP-2 exhibited a higher fusion success rate and reduced the risk of re-operation. No difference in complication rate is between rhBMP (rhBMP-2 and rhBMP-7) and ICBG. We suggest rhBMP especially rhBMP-2 as an effective substitute for ICBG for lumbar fusion. LEVEL OF EVIDENCE: 1.


Assuntos
Autoenxertos/transplante , Proteínas Morfogenéticas Ósseas/uso terapêutico , Vértebras Lombares/efeitos dos fármacos , Vértebras Lombares/cirurgia , Adulto , Proteína Morfogenética Óssea 2 , Transplante Ósseo , Feminino , Humanos , Ílio/transplante , Região Lombossacral , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Ensaios Clínicos Controlados Aleatórios como Assunto , Proteínas Recombinantes , Reoperação , Fusão Vertebral/efeitos adversos , Fator de Crescimento Transformador beta , Transplante Autólogo , Resultado do Tratamento
11.
J Bone Miner Metab ; 38(2): 179-187, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31587108

RESUMO

INTRODUCTION: Postmenopausal osteoporosis and dyslipidemia are well-known skeletal and metabolic changes in middle-aged women. We investigated the effects of combined treatments with a selective estrogen receptor modulator (SERM) and exercise on bone and fat parameters in ovariectomized (OVX) rats. MATERIALS AND METHODS: Sixteen-week-old female Sprague-Dawley rats underwent bilateral ovariectomy, and rats were randomized to BZA (bazedoxifene at 0.3 mg/kg/day), Exe (treadmill exercise at 12-15 m/min, 60 min/day, 5 days/week), Comb (BZA and Exe), and Cont (control treated with vehicle and no exercise) groups 8 weeks after ovariectomy. After 4 or 8 weeks of treatment, bone mineral density (BMD) of the total femur and lumbar spine and whole-body percentage fat mass were determined by dual-energy X-ray absorptiometry, and mechanical testing of the femoral shaft, and bone and fat histomorphometric analyses of the proximal tibia were performed. RESULTS: Treadmill exercise had decreased bone marrow adipocytes from 4 weeks of treatment and whole-body percentage fat mass at 8 weeks. BZA increased BMD at the lumbar spine and decreased the whole-body percentage fat mass from 4 weeks and bone marrow adipocytes at 8 weeks. Combination therapy increased BMD for the lumbar spine and decreased bone marrow adipocytes and whole-body percentage fat mass from 4 weeks. CONCLUSION: Combination therapy with BZA and exercise appears effective to improve bone and fat parameters in OVX rats.


Assuntos
Adiposidade/efeitos dos fármacos , Indóis/farmacologia , Ovariectomia , Condicionamento Físico Animal , Absorciometria de Fóton , Animais , Fenômenos Biomecânicos , Peso Corporal/efeitos dos fármacos , Densidade Óssea/efeitos dos fármacos , Feminino , Humanos , Vértebras Lombares/efeitos dos fármacos , Tamanho do Órgão/efeitos dos fármacos , Ratos Sprague-Dawley
12.
J Clin Endocrinol Metab ; 105(3)2020 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-31674641

RESUMO

CONTEXT: In the Denosumab and High-Dose Teriparatide Administration (DATA-HD) study, we reported that 15 months of combined high-dose (HD) teriparatide and denosumab increased mean areal bone mineral density (aBMD) at the hip and spine more than combined denosumab and standard-dose (SD) teriparatide. OBJECTIVE: In the current analysis, we compare the individual rates of aBMD response between the treatment groups. DESIGN: Single-site, open-label, randomized controlled trial in which postmenopausal women received either teriparatide 20-µg daily (SD) or 40-µg daily (HD) given months 0 through 9, overlapped with denosumab 60 mg, given months 3 through 15 (15 months' total duration). The proportion of participants in the SD and HD groups experiencing total hip, femoral neck, and lumbar spine aBMD gains of >3%, >6%, and >9% were compared. PARTICIPANTS: Postmenopausal women with osteoporosis completing all study visits (n = 60). MAIN OUTCOME MEASURE(S): aBMD (dual x-ray absorptiometry). RESULTS: At the end of the 15-month treatment period, a higher proportion of women in the HD group had aBMD increases >3% (83% vs. 58%, P = .037) and >6% (45% vs. 19%, P = .034) at the total hip, and >3% at the femoral neck (86% vs. 63%, P = .044). At the lumbar spine, >3% response rates were similar, whereas the >6% and >9% response rates were greater in the HD group (100% vs. 79%, P = .012 and 93% vs. 59%, P = .003, respectively). CONCLUSION: Compared with the SD regimen, more women treated with the HD regimen achieved clinically meaningful and rapid gains in hip and spine aBMD. These results suggest that this approach may provide unique benefits in the treatment of postmenopausal osteoporosis.


Assuntos
Conservadores da Densidade Óssea/administração & dosagem , Densidade Óssea/efeitos dos fármacos , Denosumab/administração & dosagem , Osteoporose Pós-Menopausa/tratamento farmacológico , Teriparatida/administração & dosagem , Absorciometria de Fóton , Idoso , Relação Dose-Resposta a Droga , Quimioterapia Combinada/métodos , Feminino , Colo do Fêmur/diagnóstico por imagem , Colo do Fêmur/efeitos dos fármacos , Colo do Fêmur/fisiopatologia , Humanos , Vértebras Lombares/diagnóstico por imagem , Vértebras Lombares/efeitos dos fármacos , Vértebras Lombares/fisiopatologia , Pessoa de Meia-Idade , Osteoporose Pós-Menopausa/complicações , Osteoporose Pós-Menopausa/diagnóstico , Osteoporose Pós-Menopausa/fisiopatologia , Resultado do Tratamento
13.
J Clin Endocrinol Metab ; 105(3)2020 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-31674644

RESUMO

CONTEXT: The ACTIVE study demonstrated the antifracture efficacy of abaloparatide in postmenopausal women with osteoporosis. ACTIVExtend demonstrated sustained fracture risk reduction with alendronate in abaloparatide-treated participants from ACTIVE. A direct comparison of the efficacy of abaloparatide and antiresorptive therapies has not been performed. OBJECTIVE: The objective of this analysis is to compare the antifracture efficacy of abaloparatide in ACTIVE with that of alendronate in ACTIVExtend. DESIGN: In this post hoc analysis, the rate of new vertebral fractures for women in ACTIVExtend (N = 1139) was calculated based on baseline and endpoint radiographs for placebo or abaloparatide in ACTIVE and alendronate in ACTIVExtend. Vertebral fracture rates between abaloparatide and alendronate were compared in a Poisson regression model. Fracture rates for nonvertebral and clinical fractures were compared based on a Poisson model during 18 months of abaloparatide or placebo treatment in ACTIVE and 18 months of alendronate treatment in ACTIVExtend. RESULTS: The vertebral fracture rate was lower during abaloparatide treatment in ACTIVE (0.47 fractures/100 patient-years) than alendronate treatment in ACTIVExtend (1.66 fractures/100 patient-years) (relative risk reduction 71%; P = .027). Although the comparisons did not meet statistical significance, after switching from placebo (ACTIVE) to alendronate (ACTIVExtend), the rate of new vertebral fractures decreased from 2.49 to 1.66 fractures per 100 patient-years, and after switching from abaloparatide to alendronate from 0.47 to 0.19 fractures per 100 patient-years. The rates of nonvertebral fractures and clinical fractures were not significantly different. CONCLUSION: Initial treatment with abaloparatide may result in greater vertebral fracture reduction compared with alendronate in postmenopausal women with osteoporosis.


Assuntos
Alendronato/administração & dosagem , Conservadores da Densidade Óssea/administração & dosagem , Osteoporose Pós-Menopausa/tratamento farmacológico , Fraturas por Osteoporose/prevenção & controle , Proteína Relacionada ao Hormônio Paratireóideo/administração & dosagem , Fraturas da Coluna Vertebral/prevenção & controle , Idoso , Alendronato/efeitos adversos , Densidade Óssea/efeitos dos fármacos , Densidade Óssea/fisiologia , Conservadores da Densidade Óssea/efeitos adversos , Quimioterapia Combinada/efeitos adversos , Quimioterapia Combinada/métodos , Feminino , Colo do Fêmur/diagnóstico por imagem , Colo do Fêmur/efeitos dos fármacos , Colo do Fêmur/fisiopatologia , Humanos , Vértebras Lombares/diagnóstico por imagem , Vértebras Lombares/efeitos dos fármacos , Vértebras Lombares/fisiopatologia , Pessoa de Meia-Idade , Osteoporose Pós-Menopausa/complicações , Osteoporose Pós-Menopausa/diagnóstico , Osteoporose Pós-Menopausa/fisiopatologia , Fraturas por Osteoporose/diagnóstico , Fraturas por Osteoporose/epidemiologia , Fraturas por Osteoporose/etiologia , Proteína Relacionada ao Hormônio Paratireóideo/efeitos adversos , Placebos/administração & dosagem , Placebos/efeitos adversos , Radiografia , Fatores de Risco , Fraturas da Coluna Vertebral/diagnóstico , Fraturas da Coluna Vertebral/epidemiologia , Fraturas da Coluna Vertebral/etiologia , Resultado do Tratamento
14.
Nagoya J Med Sci ; 81(4): 571-585, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31849375

RESUMO

We investigated 2-year outcomes of denosumab treatment for osteoporosis in patients with rheumatoid arthritis (RA) and predictors of good outcomes. Study participants were 74 females treated with denosumab for 24 months. After investigating baseline demographics and overall time course for each patient, we divided all cases into two groups according to percent change (%) in bone mineral density (BMD) of lumbar spine (LS-) and total hip (TH-) at 24 months (-24m); two thirds of the patients were allocated to the good outcome group (LS-GO and TH-GO), and the other third to the non-good outcome group (LS-NG and TH-NG). We performed multivariate analysis to confirm predictors of greater increases in LS- and TH-BMD. LS-BMD-24m and TH-BMD-24m increased significantly from baseline. We observed greater %LS-BMD-24m in LS-GO group than in LS-NG group, while %TH-BMD-24m showed no significant group-dependent difference. N-terminal propeptide of type 1 collagen (P1NP) and tartrate-resistant acid phosphatase (TRACP)-5b decreased more in LS-GO group than in LS-NG group at each time point. We observed greater %TH-BMD-24m in TH-GO group than in TH-NG group, while %LS-BMD-24m showed no significant group-dependent difference. Only P1NP-6m showed a larger decrease in TH-GO group relative to TH-NG group. Multivariate analysis confirmed that the larger decrease in P1NP-6m was associated with the greater increase in LS-BMD-24m, while the combined use of biologics was associated with the greater increase in TH-BMD-24m. In conclusions, denosumab increased BMD in RA patients with osteoporosis. The combined use of biologics and denosumab may provide useful treatment options.


Assuntos
Artrite Reumatoide/tratamento farmacológico , Conservadores da Densidade Óssea/uso terapêutico , Denosumab/uso terapêutico , Vértebras Lombares/efeitos dos fármacos , Osteoporose/tratamento farmacológico , Idoso , Densidade Óssea/efeitos dos fármacos , Feminino , Humanos , Pessoa de Meia-Idade , Estudos Multicêntricos como Assunto , Estudos Retrospectivos , Resultado do Tratamento
15.
Eur J Pharmacol ; 865: 172785, 2019 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-31712059

RESUMO

Postmenopausal osteoporosis is a common and disabling disorder that increases the risk of bone fractures due to estrogen deprivation; this can be simulated in rats by ovariectomy. Hypoxia inducible factor-1 alpha (HIF-1α) expression in osteoclasts predominantly leads to its activation increasing bone resorption. Premenopausal, estrogen prevents HIF-1α expression maintaining bone density. Unfortunately postmenopausal estrogen replacement therapy is not recommended due to its potential tumor development risk. Isoquercitrin, a common edible plants phytoestrogen, is known to inhibit HIF-1α. This study was conducted to investigate the potential antiosteoporotic activity of isoquercitrin (15, 30 and 60 mg/kg/day) in ovariectomized rats with reference to 17ß-estradiol (25 mcg/kg/day). Animals were bilaterally ovariectomized to induce osteoporosis and one month later they were assigned into groups and administered isoquercitrin and 17ß-estradiol for 8 weeks. Ovariectomy reduced lumbar compression strength, distorted bone microscopic architecture, inducing cartilage and trabecular dystrophy, and increased the markers of bone turnover (serum alkaline phosphatase and osteocalcin and urinary calcium, phosphorus and creatinine). It also increased the gene expression of HIF-1α and the levels of nuclear factor-kappa B (NF-κB) and decreased the expression of vascular endothelial growth factor (VEGF) and ß-catenin in the femurs. Isoquercitrin was found to improve bone histological features, increase lumbar strength and improve most of the biochemical markers of bone turnover in a manner comparable to 17ß-estradiol. Isoquercitrin also attenuated the increased HIF-1α expression while increased that of the VEGF and ß-catenin. It also decreased the levels of NF-κB. Therefore isoquercitrin may be considered a safer alternative for managing osteoporosis.


Assuntos
Subunidade alfa do Fator 1 Induzível por Hipóxia/antagonistas & inibidores , Osteoporose/tratamento farmacológico , Quercetina/análogos & derivados , Animais , Feminino , Fêmur/efeitos dos fármacos , Fêmur/metabolismo , Fêmur/patologia , Subunidade alfa do Fator 1 Induzível por Hipóxia/genética , Vértebras Lombares/efeitos dos fármacos , Vértebras Lombares/fisiologia , NF-kappa B/metabolismo , Ovariectomia , Quercetina/uso terapêutico , Ratos Wistar , Fator A de Crescimento do Endotélio Vascular/genética , beta Catenina/genética
16.
BMC Musculoskelet Disord ; 20(1): 515, 2019 Nov 06.
Artigo em Inglês | MEDLINE | ID: mdl-31694630

RESUMO

BACKGROUND: Quantification of vertebral bone marrow (VBM) water-fat composition has been proposed as advanced imaging biomarker for osteoporosis. Estrogen deficiency is the primary reason for trabecular bone loss in postmenopausal women. By reducing estrogen levels aromatase inhibitors (AI) as part of breast cancer therapy promote bone loss. Bisphosphonates (BP) are recommended to counteract this adverse drug effect. The purpose of our study was to quantify VBM proton density fat fraction (PDFF) changes at the lumbar spine using chemical shift encoding-based water-fat MRI (CSE-MRI) and bone mineral density (BMD) changes using dual energy X-ray absorptiometry (DXA) related to AI and BP treatment over a 12-month period. METHODS: Twenty seven postmenopausal breast cancer patients receiving AI therapy were recruited for this study. 22 subjects completed the 12-month study. 14 subjects received AI and BP (AI+BP), 8 subjects received AI without BP (AI-BP). All subjects underwent 3 T MRI. An eight-echo 3D spoiled gradient-echo sequence was used for CSE-based water-fat separation at the lumbar spine to generate PDFF maps. After manual segmentation of the vertebral bodies L1-L5 PDFF values were extracted for each vertebra and averaged for each subject. All subjects underwent DXA of the lumbar spine measuring the average BMD of L1-L4. RESULTS: Baseline age, PDFF and BMD showed no significant difference between the two groups (p > 0.05). There was a relative longitudinal increase in mean PDFF (∆relPDFF) in both groups (AI+BP: 5.93%; AI-BP: 3.11%) which was only significant (p = 0.006) in the AI+BP group. ∆relPDFF showed no significant difference between the two groups (p > 0.05). There was no significant longitudinal change in BMD (p > 0.05). CONCLUSIONS: Over a 12-month period, VBM PDFF assessed with CSE-MRI significantly increased in subjects receiving AI and BP. The present results contradict previous results regarding the effect of only BP therapy on bone marrow fat content quantified by magnetic resonance spectroscopy and bone biopsies. Future longer-term follow-up studies are needed to further characterize the effects of combined AI and BP therapy.


Assuntos
Tecido Adiposo/diagnóstico por imagem , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Inibidores da Aromatase/efeitos adversos , Medula Óssea/diagnóstico por imagem , Neoplasias da Mama/tratamento farmacológico , Osteoporose/diagnóstico por imagem , Absorciometria de Fóton , Tecido Adiposo/efeitos dos fármacos , Tecido Adiposo/patologia , Idoso , Densidade Óssea/efeitos dos fármacos , Conservadores da Densidade Óssea/administração & dosagem , Medula Óssea/efeitos dos fármacos , Medula Óssea/patologia , Osso Esponjoso/diagnóstico por imagem , Osso Esponjoso/efeitos dos fármacos , Osso Esponjoso/patologia , Feminino , Seguimentos , Humanos , Imageamento Tridimensional , Vértebras Lombares/diagnóstico por imagem , Vértebras Lombares/efeitos dos fármacos , Vértebras Lombares/patologia , Imagem por Ressonância Magnética , Pessoa de Meia-Idade , Osteoporose/induzido quimicamente , Osteoporose/fisiopatologia , Osteoporose/prevenção & controle , Pós-Menopausa/fisiologia , Ácido Zoledrônico/administração & dosagem
17.
Nutrients ; 11(10)2019 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-31618965

RESUMO

This study aimed to investigate the relationship between the consumption of various nutrients and bone mineral density (BMD) in middle-aged women. This cross-sectional survey was conducted based on the clinical records of 157 women aged 38-76. Their lumbar spine BMD was measured with dual-energy X-ray absorptiometry and dietary habits were assessed with the brief-type self-administered diet history questionnaire. Participants were divided into premenopausal (n = 46) and postmenopausal (n = 111) groups and the correlation between the BMD Z-score (Z-score) and the intakes of 43 nutrients was investigated separately for each group. In premenopausal women, the daily intake of ash, calcium, and α-tocopherol was positively correlated with the Z-score (Pearson's correlation coefficient, R = 0.31, 0.34, 0.33, p = 0.037, 0.020, 0.027, respectively). When dividing the consumption of ash, calcium, and α-tocopherol into low, middle, and high tertiles, the Z-score significantly differed only between the α-tocopherol tertiles. After adjustment for age, body mass index, and lifestyle factors, daily intake of α-tocopherol remained significantly associated with the Z-score (regression coefficient = 0.452, p = 0.022). No nutrient was found to be significantly correlated with the Z-score in postmenopausal women. Increase in the intake of α-tocopherol could help maintain bone mass in premenopausal women.


Assuntos
Densidade Óssea/efeitos dos fármacos , Dieta , Comportamento Alimentar , Vértebras Lombares/efeitos dos fármacos , Pré-Menopausa , alfa-Tocoferol/administração & dosagem , Absorciometria de Fóton , Adulto , Idoso , Estudos Transversais , Feminino , Humanos , Japão , Vértebras Lombares/diagnóstico por imagem , Pessoa de Meia-Idade , Estado Nutricional , Estudos Retrospectivos
18.
Alcohol Clin Exp Res ; 43(12): 2494-2503, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31557335

RESUMO

BACKGROUND: Chronic heavy alcohol consumption is an established risk factor for bone fracture, but comorbidities associated with alcohol intake may contribute to increased fracture rates in alcohol abusers. To address the specific effects of alcohol on bone, we used a nonhuman primate model and evaluated voluntary alcohol consumption on: (i) global markers of bone turnover in blood and (ii) cancellous bone mass, density, microarchitecture, turnover, and microdamage in lumbar vertebra. METHODS: Following a 4-month induction period, 6-year-old male rhesus macaques (Macaca mulatta, n = 13) voluntarily self-administered water or ethanol (EtOH; 4% w/v) for 22 h/d, 7 d/wk, for a total of 12 months. Control animals (n = 9) consumed an isocaloric maltose-dextrin solution. Tetracycline hydrochloride was administered orally 17 and 3 days prior to sacrifice to label mineralizing bone surfaces. Global skeletal response to EtOH was evaluated by measuring plasma osteocalcin and carboxyterminal collagen cross-links (CTX). Local response was evaluated in lumbar vertebra using dual-energy X-ray absorptiometry, microcomputed tomography, static and dynamic histomorphometry, and histological assessment of microdamage. RESULTS: Monkeys in the EtOH group consumed an average of 2.8 ± 0.2 (mean ± SE) g/kg/d of EtOH (30 ± 2% of total calories), resulting in an average blood EtOH concentration of 88.3 ± 8.8 mg/dl 7 hours after the session onset. Plasma CTX and osteocalcin tended to be lower in EtOH-consuming monkeys compared to controls. Significant differences in bone mineral density in lumbar vertebrae 1 to 4 were not detected with treatment. However, cancellous bone volume fraction (in cores biopsied from the central region of the third vertebral body) was lower in EtOH-consuming monkeys compared to controls. Furthermore, EtOH-consuming monkeys had lower osteoblast perimeter and mineralizing perimeter, no significant difference in osteoclast perimeter, and higher bone marrow adiposity than controls. No significant differences between groups were detected in microcrack density (2nd lumbar vertebra). CONCLUSIONS: Voluntary chronic heavy EtOH consumption reduces cancellous bone formation in lumbar vertebra by decreasing osteoblast-lined bone perimeter, a response associated with an increase in bone marrow adiposity.


Assuntos
Adiposidade/fisiologia , Consumo de Bebidas Alcoólicas/efeitos adversos , Medula Óssea/fisiopatologia , Osso Esponjoso/crescimento & desenvolvimento , Etanol/efeitos adversos , Animais , Densidade Óssea/efeitos dos fármacos , Colágeno/sangue , Etanol/sangue , Vértebras Lombares/efeitos dos fármacos , Macaca mulatta , Masculino , Osteocalcina/sangue
19.
Osteoporos Int ; 30(11): 2321-2331, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31392401

RESUMO

A 48-week, multicenter, randomized, double-blind, double-dummy, active-controlled, non-inferiority trial (the TWICE study) conducted in Japanese primary osteoporosis patients with a high risk of fractures demonstrated that a 28.2-µg twice-weekly regimen of teriparatide can provide comparable efficacy to a 56.5-µg once-weekly regimen of teriparatide, while also improving safety. INTRODUCTION: While a 56.5-µg once-weekly regimen of teriparatide has high efficacy for osteoporosis, treatment continuation rates are low, with one of the major causes being adverse drug reactions such as nausea or vomiting. The TWICE study was therefore conducted to investigate whether a twice-weekly regimen with 28.2-µg teriparatide can provide comparable efficacy to the 56.5-µg once-weekly regimen while improving safety. METHODS: A 48-week, multicenter, randomized, double-blind, double-dummy, active-controlled, non-inferiority trial was conducted in Japan. Patients with primary osteoporosis aged ≥ 65 years at high risk of fractures (n = 553) were randomly allocated to the 28.2-µg twice-weekly group (n = 277) or the 56.5-µg once-weekly group (n = 276). The primary endpoint was the percentage change in lumbar spine (L2-L4) bone mineral density (BMD) at final follow-up. RESULTS: The percentage changes in lumbar spine (L2-L4) BMD at final follow-up in the 28.2-µg twice-weekly and 56.5-µg once-weekly groups were 7.3% and 5.9%, respectively; the difference (95% confidence interval [CI]) in percentage change was 1.3% (0.400-2.283%). Since the lower limit of the 95% CI was above the pre-specified non-inferiority margin (- 1.6%), non-inferiority of the 28.2-µg twice-weekly group was demonstrated. Adverse drug reactions were significantly less frequent in the 28.2-µg twice-weekly group (39.7% vs 56.2%; p < 0.01); the incidence of major adverse drug reactions was lower, and the number of subjects who discontinued due to adverse drug reactions was less in the 28.2-µg twice-weekly group. CONCLUSIONS: A 28.2-µg twice-weekly regimen of teriparatide can provide comparable efficacy to a 56.5-µg once-weekly regimen while improving safety. CLINICAL TRIAL REGISTRATION: JapicCTI-163477 .


Assuntos
Conservadores da Densidade Óssea/administração & dosagem , Osteoporose/tratamento farmacológico , Teriparatida/administração & dosagem , Idoso , Idoso de 80 Anos ou mais , Densidade Óssea/efeitos dos fármacos , Conservadores da Densidade Óssea/efeitos adversos , Método Duplo-Cego , Esquema de Medicação , Feminino , Humanos , Japão , Vértebras Lombares/efeitos dos fármacos , Vértebras Lombares/fisiopatologia , Masculino , Fraturas por Osteoporose/epidemiologia , Fatores de Risco , Teriparatida/efeitos adversos , Resultado do Tratamento
20.
Neurotox Res ; 36(4): 700-711, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31367921

RESUMO

Prenatal and early life exposure of chlorpyrifos (CPF), a widely used pesticide, is known to cause neuronal deficits and Parkinson's disease (PD). However, data about the effect of its exposure at adult stages on PD-like symptoms and associated bone loss is scanty. In the present study, we investigated the impact of CPF on the behavioral alterations seen in PD using adult Swiss albino mice. PD is often associated with bone loss. Hence, skeletal changes were also evaluated using micro-computed tomography and histology. MPTP was used as a positive control. Cell culture studies using MC3T3E-1, SHSY5Y, and primary osteoclast cultures were done to understand the cellular mechanism for the behavioral and skeletal changes. Our results showed that CPF treatment leads to PD-like symptoms due to the loss of dopaminergic neurons. Moreover, CPF has a deleterious effect on the trabecular bone through both indirect changes in circulating factors and direct stimulation of multinucleate osteoclast cell formation. The impact on the bone mass was even stronger than MPTP. In conclusion, this is the first report demonstrating that CPF induces parkinsonian features in adult Swiss albino mice and it is accompanied by loss of trabecular bone.


Assuntos
Clorpirifos/toxicidade , Inseticidas/toxicidade , Osteoporose/induzido quimicamente , Osteoporose/patologia , Transtornos Parkinsonianos/induzido quimicamente , Transtornos Parkinsonianos/patologia , Acetilcolinesterase/metabolismo , Animais , Comportamento Animal/efeitos dos fármacos , Reabsorção Óssea/metabolismo , Diferenciação Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Corpo Estriado/efeitos dos fármacos , Corpo Estriado/metabolismo , Dopamina/metabolismo , Neurônios Dopaminérgicos/efeitos dos fármacos , Humanos , Vértebras Lombares/efeitos dos fármacos , Vértebras Lombares/patologia , Masculino , Camundongos , Osteoblastos/efeitos dos fármacos , Osteoporose/metabolismo , Transtornos Parkinsonianos/metabolismo
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