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1.
Ecotoxicol Environ Saf ; 203: 111031, 2020 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-32888610

RESUMO

Bone mineral density (BMD) changes were reported to be associated with excessive fluoride exposure and abnormal expression of RUNX2. However, whether the alteration of methylation status, a most commonly used marker for the alteration of gene expression in epidemiological investigation, of RUNX2 is associated with low-to-moderate fluoride exposure and BMD changes has not been reported. Our study aims to explore the role of RUNX2 promoter methylation in BMD changes induced by low-to-moderate fluoride exposure. A total of 1124 adults (413 men and 711 women) were recruited from Kaifeng City in 2017. We measured BMD using ultrasound bone densitometer. Concentrations of urinary fluoride (UF) were measured using ion-selective electrode, and the participants were grouped into control group (CG) and excessive fluoride group (EFG) according to the concentration of UF. We extracted DNA from fasting peripheral blood samples and then detected the promoter methylation levels of RUNX2 using quantitative methylation-specific PCR. Relationships between UF concentration, RUNX2 promoter methylation and BMD changes were analyzed using generalized linear model and logistic regression. Results showed in EFG (UF concentration > 1.6 mg/L), BMD was negatively correlated with UF concentration (ß: -0.14; 95%CI: -0.26, -0.01) and RUNX2 promoter methylation (ß: -0.13; 95%CI: -0.22, -0.03) in women. The methylation rate of RUNX2 promoter increased by 2.16% for each 1 mg/L increment in UF concentration of women in EFG (95%CI: 0.37, 3.96). No any significant associations between UF concentration, RUNX2 promoter methylation, and BMD were observed in the individuals in CG. Mediation analysis showed that RUNX2 promoter methylation mediated 18.2% (95% CI: 4.2%, 53.2%) of the association between UF concentration and BMD of women in EFG. In conclusion, excessive fluoride exposure (>1.6 mg/L) is associated with changes of BMD in women, and this association is mediated by RUNX2 promoter methylation.


Assuntos
Densidade Óssea/efeitos dos fármacos , Subunidade alfa 1 de Fator de Ligação ao Core/genética , Exposição Ambiental/análise , Fluoretos/toxicidade , Poluentes Químicos da Água/toxicidade , Absorciometria de Fóton , Adulto , Idoso , Densidade Óssea/genética , China , Subunidade alfa 1 de Fator de Ligação ao Core/metabolismo , Estudos Transversais , Metilação de DNA/efeitos dos fármacos , Feminino , Fluoretos/urina , Humanos , Masculino , Pessoa de Meia-Idade , Regiões Promotoras Genéticas , Inquéritos e Questionários , Poluentes Químicos da Água/urina
2.
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
3.
PLoS One ; 15(7): e0236161, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32730269

RESUMO

BACKGROUND: Periodontitis is a multifactorial inflammatory disease of tooth supporting tissues caused by oral biofilms, influenced by environmental and genetic factors, among others. Ethanol consumption has been considered a factor that enhances alveolar bone loss, especially in high doses. The present study aims to investigate the changes promoted by ethanol binge drinking per se or associated with ligature-induced periodontal breakdown on alveolar bone loss. MATERIALS AND METHODS: Thirty-two Wistar rats were randomly allocated into four groups: control (C), ethanol (3g/kg/day; 3 days On-4 days Off protocol by gavage for 28 days, EtOH), experimental periodontitis (EP) and experimental periodontitis plus ethanol administration (EP+EtOH). On day 14th, periodontitis was induced by ligatures that were placed around the lower first molars. On day 28th, the animals were euthanized and mandibles were submitted to stereomicroscopy for exposed root area analysis and micro-computed tomography (micro-CT) for the evaluation of alveolar bone loss and microstructural parameters. RESULTS: The results revealed that ligature-induced alveolar bone loss is aggravated by ethanol binge drinking compared to controls (1.06 ± 0.10 vs 0.77 ± 0.04; p<0.0001). In addition, binge drinking per se altered the alveolar bone quality and density demonstrating a reduction in trabecular thickness, trabecular number parameter and bone density percentual. Periodontal disorder plus ethanol binge drinking group also demonstrated reduction of the quality of bone measured by trabecular thickness. CONCLUSIONS: In conclusion, intense and episodic ethanol intake decreased alveolar bone quality in all microstructural parameters analyzed which may be considered a modifying factor of periodontitis, intensifying the already installed disease.


Assuntos
Perda do Osso Alveolar/etiologia , Bebedeira/complicações , Densidade Óssea/efeitos dos fármacos , Estimulantes do Sistema Nervoso Central/toxicidade , Etanol/toxicidade , Periodontite/complicações , Animais , Masculino , Periodontite/induzido quimicamente , Periodontite/patologia , Ratos , Ratos Wistar
4.
Expert Opin Pharmacother ; 21(14): 1725-1737, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32605401

RESUMO

INTRODUCTION: Rheumatoid arthritis (RA) is a chronic disabling disease characterized by a symmetrical articular involvement due to ongoing joint inflammation, if left insufficiently treated. Local and generalized bone loss is one of the main extra-articular complications of RA and leads to an increased risk for fragility fractures, which further impair functional ability, quality of life, and life expectancy. Therefore, there is an urgent need for good fracture risk management in the vulnerable RA patient. AREAS COVERED: The authors review: the epidemiology and pathophysiology (i.e. risk factors) of osteoporosis (OP), fracture, and vertebral fracture risk assessment, the effects of anti-rheumatic drugs on bone loss, pharmacological treatment of OP in RA including both bisphosphonates (BP) and newer drugs including anti-resorptives and osteoanabolic treatment options. EXPERT OPINION: Patients with active RA have elevated bone resorption and local bone loss. Moreover, these patients are at increased risk for generalized bone loss, vertebral and non-vertebral fractures. Since general risk factors (such as low BMI, fall risk) and RA-related factors play a role, optimal fracture prevention in RA patients is based on optimal diagnostics based on both of these factors, and on the use of adequate non-medical and medical treatment options.


Assuntos
Antirreumáticos/uso terapêutico , Artrite Reumatoide/tratamento farmacológico , Difosfonatos/uso terapêutico , Fraturas Ósseas/prevenção & controle , Glucocorticoides/uso terapêutico , Osteoporose/tratamento farmacológico , Absorciometria de Fóton , Artrite Reumatoide/complicações , Artrite Reumatoide/epidemiologia , Densidade Óssea/efeitos dos fármacos , Feminino , Fraturas Ósseas/etiologia , Humanos , Osteoporose/complicações , Osteoporose/epidemiologia , Qualidade de Vida , Fatores de Risco , Resultado do Tratamento
5.
Life Sci ; 257: 118033, 2020 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-32621924

RESUMO

The present study aimed to investigate the effects of phosphatidylserine liposomes (PSLs) and phosphatidylserine liposomes containing alendronate (AL-PSLs) on the improvement of methylprednisolone (MP) induced osteoporosis in a rat model. AL-PSLs formulation was prepared, characterized, and evaluated in different pH media to simulate gastrointestinal condition. Osteoporosis was induced by 3 weeks oral administration of MP (10 mg/kg) and then treatment by PSLs, AL-PSLs, and alendronate (AL). Bone metabolic and biomechanical markers were measured in treated rat groups. Also, Tartrate-resistant acid phosphatase (TRAP) staining and histomorphometry were evaluated on bone tissues of treated rats. AL-PSLs were obtained in a size range of 155 nm and negatively surface charge with an entrapment efficiency of 42%. The AL leakage from AL-PSLs did not exhibit a significant difference in acidic or basic media in comparison with the neutral condition. The concentrations of calcium, osteocalcin, bone alkaline phosphatase, and osteoprotegerin (OPG) of serum were significantly increased in PSLs and AL-PSLs treated groups compared to the MP group. Also, PSLs and AL-PSLs significantly improved the thickness and volume of the cortical and trabecular bone mass in treated groups. In addition, TRAP staining indicated a significant decrease of osteoclast number in osteoporotic rats treated with AL-PSLs and PSLs. In this study, AL-PSLs and even PSLs alone made a potential bone mechanical strength in glucocorticoid-induced bone loss more than AL in rats. In conclusion, our findings suggest that PSLs consumption with or without an anti-osteoporotic drug might be an applicable choice in control of osteoporosis.


Assuntos
Alendronato/farmacologia , Osteoporose/tratamento farmacológico , Fosfatidilserinas/farmacologia , Animais , Densidade Óssea/efeitos dos fármacos , Conservadores da Densidade Óssea/farmacologia , Osso e Ossos/metabolismo , Modelos Animais de Doenças , Fêmur/efeitos dos fármacos , Lipossomos/farmacologia , Masculino , Metilprednisolona/farmacologia , Osteocalcina/metabolismo , Osteoclastos/metabolismo , Osteoporose/metabolismo , Fosfatidilserinas/metabolismo , Ratos , Ratos Wistar
6.
Lancet Diabetes Endocrinol ; 8(8): 672-682, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32707115

RESUMO

BACKGROUND: The validation of bone mineral density (BMD) as a surrogate outcome for fracture would allow the size of future randomised controlled osteoporosis registration trials to be reduced. We aimed to determine the association between treatment-related changes in BMD, assessed by dual-energy x-ray absorptiometry, and fracture outcomes, including the proportion of treatment effect explained by BMD changes. METHODS: We did a pooled analysis of individual patient data from multiple randomised placebo-controlled clinical trials. We included data from multicentre, randomised, placebo-controlled, double-blind trials of osteoporosis medications that included women and men at increased osteoporotic fracture risk. Using individual patient data for each trial we calculated mean 24-month BMD percent change together with fracture reductions and did a meta-regression of the association between treatment-related differences in BMD changes (percentage difference, active minus placebo) and fracture risk reduction. We also used individual patient data to determine the proportion of anti-fracture treatment effect explained by BMD changes and the BMD change needed in future trials to ensure fracture reduction efficacy. FINDINGS: Individual patient data from 91 779 participants of 23 randomised, placebo-controlled trials were included. The trials had 1-9 years of follow-up and included 12 trials of bisphosphonate, one of odanacatib, two of hormone therapy (one of conjugated equine oestrogen and one of conjugated equine oestrogen plus medroxyprogesterone acetate), three of PTH receptor agonists, one of denosumab, and four of selective oestrogen receptor modulator trials. The meta-regression revealed significant associations between treatment-related changes in hip, femoral neck, and spine BMD and reductions in vertebral (r2 0·73, p<0·0001; 0·59, p=0·0005; 0·61, p=0·0003), hip (0·41, p=0·014; 0·41, p=0·0074; 0·34, p=0·023) and non-vertebral fractures (0·53, p=0·0021; 0·65, p<0·0001; 0·51, p=0·0019). Minimum 24-month percentage changes in total hip BMD providing almost certain fracture reductions in future trials ranged from 1·42% to 3·18%, depending on fracture site. Hip BMD changes explained substantial proportions (44-67%) of treatment-related fracture risk reduction. INTERPRETATION: Treatment-related BMD changes are strongly associated with fracture reductions across randomised trials of osteoporosis therapies with differing mechanisms of action. These analyses support BMD as a surrogate outcome for fracture outcomes in future randomised trials of new osteoporosis therapies and provide an important demonstration of the value of public access to individual patient data from multiple trials. FUNDING: Foundation for National Institutes of Health.


Assuntos
Conservadores da Densidade Óssea/administração & dosagem , Densidade Óssea/efeitos dos fármacos , Interpretação Estatística de Dados , Fraturas por Osteoporose/diagnóstico por imagem , Fraturas por Osteoporose/prevenção & controle , Ensaios Clínicos Controlados Aleatórios como Assunto/métodos , Absorciometria de Fóton/métodos , Biomarcadores/metabolismo , Densidade Óssea/fisiologia , Humanos , Fraturas por Osteoporose/metabolismo , Análise de Regressão , Comportamento de Redução do Risco , Resultado do Tratamento
7.
Eur J Endocrinol ; 183(3): R75-R93, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32544873

RESUMO

Male osteoporosis has been neglected for too long time and there is need for a change. This condition is clearly under-estimated, under-diagnosed and under-treated. The diagnosis is often made late in the natural history of the pathology or even after a fracture event. Guidelines on screening politics do not agree whether and when men should be considered, and clinical trials are far less performed in men with respect to women. Actually, most of our knowledge on male osteoporosis, especially regarding treatment, is extrapolate from the female counterpart. Male osteoporosis is frequently secondary to other conditions and often associated with comorbidities. Therefore, identification of specific causes of male osteoporosis is essential to drive a correct and personalized treatment. Moreover, men have more osteoporosis-related complications and higher mortality rate associated with fractures. Furthermore, not only fewer men receive a correct and timely diagnosis, but also fewer men receive adequate treatment, and adherence to therapy is far less in men than in women. Of note, very few studies assessed the effect of antiosteoporotic treatments in men and most of them considered only bone density as primary endpoint. This review focuses on the areas that are still nebulous in male osteoporosis field, from identification of subjects who need to be evaluated for osteoporosis and screening programs dealing with primary prevention to diagnostic procedures for good estimates of bone quantity and quality and precise calculation of fracture risk and personalized treatment that take into account the pathophysiology of osteoporosis.


Assuntos
Doenças do Sistema Endócrino/diagnóstico , Osteoporose/diagnóstico , Densidade Óssea/efeitos dos fármacos , Conservadores da Densidade Óssea/uso terapêutico , Doenças do Sistema Endócrino/tratamento farmacológico , Feminino , Humanos , Masculino , Osteoporose/tratamento farmacológico , Fraturas por Osteoporose/tratamento farmacológico , Fraturas por Osteoporose/etiologia , Fatores de Risco
8.
Proc Natl Acad Sci U S A ; 117(25): 14386-14394, 2020 06 23.
Artigo em Inglês | MEDLINE | ID: mdl-32513693

RESUMO

We report that two widely-used drugs for erectile dysfunction, tadalafil and vardenafil, trigger bone gain in mice through a combination of anabolic and antiresorptive actions on the skeleton. Both drugs were found to enhance osteoblastic bone formation in vivo using a unique gene footprint and to inhibit osteoclast formation. The target enzyme, phosphodiesterase 5A (PDE5A), was found to be expressed in mouse and human bone as well as in specific brain regions, namely the locus coeruleus, raphe pallidus, and paraventricular nucleus of the hypothalamus. Localization of PDE5A in sympathetic neurons was confirmed by coimmunolabeling with dopamine ß-hydroxylase, as well as by retrograde bone-brain tracing using a sympathetic nerve-specific pseudorabies virus, PRV152. Both drugs elicited an antianabolic sympathetic imprint in osteoblasts, but with net bone gain. Unlike in humans, in whom vardenafil is more potent than tadalafil, the relative potencies were reversed with respect to their osteoprotective actions in mice. Structural modeling revealed a higher binding energy of tadalafil to mouse PDE5A compared with vardenafil, due to steric clashes of vardenafil with a single methionine residue at position 806 in mouse PDE5A. Collectively, our findings suggest that a balance between peripheral and central actions of PDE5A inhibitors on bone formation together with their antiresorptive actions specify the osteoprotective action of PDE5A blockade.


Assuntos
Disfunção Erétil/tratamento farmacológico , Osteogênese/efeitos dos fármacos , Osteoporose/tratamento farmacológico , Inibidores da Fosfodiesterase 5/farmacologia , Envelhecimento/fisiologia , Animais , Densidade Óssea/efeitos dos fármacos , Densidade Óssea/fisiologia , Osso e Ossos/citologia , Osso e Ossos/efeitos dos fármacos , Osso e Ossos/metabolismo , Encéfalo/citologia , Encéfalo/efeitos dos fármacos , Encéfalo/metabolismo , Diferenciação Celular/efeitos dos fármacos , Nucleotídeo Cíclico Fosfodiesterase do Tipo 5/química , Nucleotídeo Cíclico Fosfodiesterase do Tipo 5/metabolismo , Reposicionamento de Medicamentos , Disfunção Erétil/complicações , Humanos , Masculino , Camundongos , Pessoa de Meia-Idade , Modelos Animais , Modelos Moleculares , Neurônios/efeitos dos fármacos , Neurônios/metabolismo , Osteoblastos/efeitos dos fármacos , Osteoblastos/fisiologia , Osteoclastos/efeitos dos fármacos , Osteoclastos/fisiologia , Osteoporose/complicações , Fraturas por Osteoporose/etiologia , Fraturas por Osteoporose/prevenção & controle , Inibidores da Fosfodiesterase 5/química , Inibidores da Fosfodiesterase 5/uso terapêutico , Cultura Primária de Células , Tadalafila/química , Tadalafila/farmacologia , Tadalafila/uso terapêutico , Dicloridrato de Vardenafila/química , Dicloridrato de Vardenafila/farmacologia , Dicloridrato de Vardenafila/uso terapêutico
9.
Medicine (Baltimore) ; 99(25): e20724, 2020 Jun 19.
Artigo em Inglês | MEDLINE | ID: mdl-32569210

RESUMO

INTRODUCTION: The use of warfarin in patients undergoing hemodialysis is associated with decreased bone mineral density and an increased incidence of bone fracture. However, no studies to date have directly estimated bone quality with bone histomorphometry in patients with bone abnormalities who are taking warfarin and undergoing hemodialysis. PATIENT CONCERNS: A 47-year-old female with Noonan syndrome presented with progressive bilateral lower extremity pain on walking, and skin sclerosis. She had been undergoing maintenance hemodialysis for 25 years following 2 years of peritoneal dialysis for chronic glomerulonephritis. She had been taking warfarin as an anticoagulant agent for 13 years after she underwent an aortic valve replacement. DIAGNOSIS: Warfarin-induced impairment of bone material quality. INTERVENTIONS AND OUTCOMES: Histomorphometric analysis of the bone biopsy specimens showed impairment in bone calcification processes, a high turnover of bone remodeling, low bone volume, and mild fibrosis. The bone abnormality could not be categorized into any type of representative bone disease classification such as osteitis fibrosa, osteomalacia, adynamic bone disease, uremic osteodystrophy, or hyperparathyroidism, but was consistent with warfarin-induced impairment of bone material quality. CONCLUSION: Warfarin can induce impairment of bone material quality in a patient undergoing hemodialysis.


Assuntos
Anticoagulantes/efeitos adversos , Densidade Óssea/efeitos dos fármacos , Distúrbio Mineral e Ósseo na Doença Renal Crônica/terapia , Síndrome de Noonan/complicações , Diálise Renal , Varfarina/efeitos adversos , Feminino , Humanos , Pessoa de Meia-Idade
10.
Zhonghua Zhong Liu Za Zhi ; 42(5): 403-407, 2020 May 23.
Artigo em Chinês | MEDLINE | ID: mdl-32482030

RESUMO

Objective: To investigate the occurrence and development of aromatase inhibitors (AIs) related bone loss in Chinese patients with postmenopausal early-stage breast cancer. Methods: Patients with estrogen receptor (ER) and (or) progesterone receptor(PR) positive postmenopausal early-stage breast cancer who received Letrozole, Anastrozole, or Exemestane as adjuvant therapy were enrolled. Before treatment, baseline bone mineral density (BMD), bone metabolism markers were examined and a lifestyle questionnaire was completed; BMD was examined annually during the treatment; Outpatient visits were conducted to record recurrent and fatal events. Results: From November 2013 to August 2016, 131 patients with breast cancer eligible for enrollment were enrolled. A total of 65 patients had normal baseline bone mass, and 68 patients had reduced bone mass. Letrozole was taken in 69 patients, anastrozole in 52 patients, and exemestane in 10 patients. With a median follow-up of 43.7 months, 100 patients could be evaluated for changes in bone mineral density. Bone mineral density of femoral neck, total hip, and lumbar spine L1 to 4 decreased year by year, and the decrease was the most significant in the first year, which decreased by 2.3%, 2.4%, and 3.9% respectively. Ten new cases of osteoporosis occurred in two years, eight of them occurred in the lumbar spine, all of whom had reduced bone mass at baseline. Among the 131 patients who completed the lifestyle questionnaire, the proportions of daily calcium supplementation and vitamin D were 28.2% and 7.6%, respectively; more than half (52.7%) of them lacked regular exercise. Conclusion: BMD was declining steadily in patients treated with AIs, especially in the first year. Lumbar spine is the most common osteoporosis site, early prevention and health education should be strengthened.


Assuntos
Inibidores da Aromatase/uso terapêutico , Densidade Óssea/efeitos dos fármacos , Neoplasias da Mama/tratamento farmacológico , Pós-Menopausa , Anastrozol/uso terapêutico , Androstadienos/uso terapêutico , Humanos , Letrozol/uso terapêutico , Estudos Prospectivos
11.
Orv Hetil ; 161(21): 867-872, 2020 05.
Artigo em Húngaro | MEDLINE | ID: mdl-32427571

RESUMO

INTRODUCTION: Bisphosphonate-related osteonecrosis of the jaw is a condition that severely affects the quality of life, therefore an early diagnosis is of utmost importance (both from a general and a surgical point of view), alongside with an accurate assessment of the risk of emergence of the disease. AIM: Estimation of the prognosis is not resolved; among several radiological options those used in dentistry seem the most fit for the purpose, with cone-beam computed tomography (CBCT) being superior in this task. Assessment of the risk of BRONJ developed following orally applied bisphosphonate is unemphatic in most case studies - these focus more on the intravenous application carrying a greater risk of BRONJ. METHOD: In contrast with the studies published so far, we performed our measurements on preoperative CBCT scans, thereby directly studying the possibility of risk assessment. Our measurements were conducted through evaluating CBCT scans. We chose the frontal section in the midline of the mental foramen as the representative area. We measured density and thickness of the cortical bone on several given points; the diameter of the mental foramen was also measured. In the first group, we examined patients suffering from osteoporosis who had developed BRONJ following oral bisphosphonate treatment. In the second group, we looked at patients suffering from osteoporosis, who had received oral bisphosphonate therapy for this condition but did not develop BRONJ after oral surgery. As control group, we chose patients suffering from osteoporosis who had not received any of the medications known to cause BRONJ. RESULTS: Based on our results, it is clear that there is no significant difference in the bone density of those patients who developed BRONJ and those who did not, examining the preoperative CBCT scans. CONCLUSIONS: Using CBCT scans (and thereby submitting the patient to radiation exposure) in order to estimate the possibility of BRONJ following oral bisphosphonate treatment for osteoporosis is not recommended. It is important not to expose patients to more radiation than strictly necessary to predict BRONJ following oral bisphosphonate treatment in accordance with the ALARA (as low as reasonably achievable) principle. Orv Hetil. 2020; 161(21): 867-872.


Assuntos
Osteonecrose da Arcada Osseodentária Associada a Difosfonatos/diagnóstico por imagem , Conservadores da Densidade Óssea/efeitos adversos , Densidade Óssea/efeitos dos fármacos , Difosfonatos/efeitos adversos , Medição de Risco/métodos , Tomografia Computadorizada de Feixe Cônico Espiral , Osteonecrose da Arcada Osseodentária Associada a Difosfonatos/psicologia , Conservadores da Densidade Óssea/uso terapêutico , Difosfonatos/administração & dosagem , Humanos , Qualidade de Vida
12.
J Bone Miner Metab ; 38(5): 648-657, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32350616

RESUMO

INTRODUCTION: Lactoferrin has recently been reported for its potent bone growth effects. However, the effects of lactoferrin on the healing process of fragility fracture have not yet been studied, so the purpose of this study is to investigate whether oral administration of lactoferrin can promote the fracture healing in an OVX animal model. MATERIALS AND METHODS: Three months after bilateral ovariectomy, all rats underwent unilateral tibial osteotomy and were then randomly divided into control group and bovine lactoferrin (bLF) group. At 4 and 8 weeks post-fracture, animals were sacrificed, and the fractured tibiae and serum samples were collected for evaluation. RESULTS: Our results showed that bLF treatment not only accelerated the bone growth at an early stage of OPF healing but also shortened the remolding process of OPF healing. When compared to control group, bLF treatment induced a significant rise in callus BMD (by 35.0% at 4 weeks and by 39.7% at 8 weeks; both p < 0.05) consistent with enhanced biomechanical strength of the callus, with ultimate force increased by 3.39-fold at 4 weeks (p < 0.05) and 1.95-fold at 8 weeks (p < 0.05). Besides, bLF administration resulted in a substantial increase in serum levels of BALP and a significant decrease in serum levels of TRAP 5b and TNF-α. Moreover, both the RANKL/OPG mRNA ratio and the expression of TNF-α in the callus of bLF-treated group were markedly lower than those in the control group. CONCLUSIONS: At a dose of 85mg/kg/day orally administrated bLF potently promoted the bone healing following tibial fracture in OVX rats.


Assuntos
Consolidação da Fratura/efeitos dos fármacos , Lactoferrina/administração & dosagem , Lactoferrina/farmacologia , Ovariectomia , Absorciometria de Fóton , Administração Oral , Fosfatase Alcalina/sangue , Animais , Fenômenos Biomecânicos/efeitos dos fármacos , Densidade Óssea/efeitos dos fármacos , Calo Ósseo/diagnóstico por imagem , Calo Ósseo/efeitos dos fármacos , Calo Ósseo/patologia , Feminino , Humanos , Lactoferrina/sangue , Osteoprotegerina/metabolismo , Ligante RANK/metabolismo , Ratos Sprague-Dawley , Fosfatase Ácida Resistente a Tartarato/sangue , Tíbia/efeitos dos fármacos , Tíbia/patologia , Fator de Necrose Tumoral alfa/sangue , Microtomografia por Raio-X
13.
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
14.
Am J Clin Nutr ; 112(1): 48-56, 2020 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-32401318

RESUMO

BACKGROUND: Clinical trials evaluating the effect of calcium supplementation on bone loss in lactating women have been small, with inconsistent results. OBJECTIVES: We aimed to determine the effect of calcium supplementation on bone mineral density (BMD) in lactating women. METHODS: An electronic search of databases was conducted from inception to January 2020. Two authors screened studies, extracted data, and assessed the risk of bias of eligible studies. Percentage change in BMD was pooled using random-effects models and reported as weighted mean differences (WMDs) with 95% CIs. Risk of bias was assessed using the Cochrane risk of bias tool. RESULTS: Five randomized controlled trials including 567 lactating women were included. All had a high risk of bias. Mean baseline calcium intake ranged from 562 to 1333 mg/d. Compared with control groups (placebo/no intervention), calcium supplementation (600/1000 mg/d) had no significant effect on BMD at the lumbar spine (WMD: 0.74%; 95% CI: -0.10%, 1.59%; I2 = 47%; 95% CI: 0%, 81%; n = 527 from 5 trials) or the forearm (WMD: 0.53%; 95% CI: -0.35%, 1.42%; I2 = 55%; 95% CI: 0%, 85%; n = 415 from 4 trials). BMD at other sites was assessed in single trials: calcium supplementation had a small to moderate effect on total-hip BMD (WMD: 3.3%; 95% CI: 1.5%, 5.1%) but no effect on total body or femoral neck BMD. CONCLUSIONS: Overall, the meta-analysis indicates that calcium supplementation does not provide clinically important benefits for BMD in lactating women. However, there was adequate dietary intake before supplementation in some studies, and others did not measure baseline calcium intake. Advising lactating women to meet the current recommended calcium intakes (with supplementation if dietary intake is low) is warranted unless new high-certainty evidence to the contrary from robust clinical trials becomes available. More research needs to be done in larger samples of women from diverse ethnic and racial groups.This systematic review was registered at www.crd.york.ac.uk/prospero as CRD42015022092.


Assuntos
Densidade Óssea/efeitos dos fármacos , Cálcio na Dieta/administração & dosagem , Cálcio/administração & dosagem , Adulto , Suplementos Nutricionais/análise , Feminino , Humanos , Lactação/efeitos dos fármacos , Ensaios Clínicos Controlados Aleatórios como Assunto , Adulto Jovem
15.
Drug Discov Ther ; 14(2): 77-83, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32378649

RESUMO

Tacrolimus, a calcineurin inhibitor, affects bone metabolism and increases the risk of fracture due to marked bone loss. Bisphosphonates increase the bone mineral density (BMD) in osteoporosis patients. Menatetrenone has less positive effects on BMD but reduces the risk of fracture by improving bone quality. In this study, we investigated the effectiveness of the combined administration of risedronate and menatetrenone against bone loss induced by tacrolimus. Wistar rats were divided into four groups: [1] control, [2] tacrolimus at 1.5 mg/kg, [3] tacrolimus + risedronate at 1.0 mg/kg, and [4] tacrolimus + risedronate + menatetrenone at 20 mg/kg. After the drugs were administered for 4 weeks, bone histomorphometric analysis was performed and bone strength was evaluated using a three point bending method. BMD was measured using quantitative computed tomography. Tacrolimus significantly reduced the BMD and strength properties of the lower limb bones. These tacrolimusinduced decreases were suppressed by risedronate treatment. The combined administration of risedronate and menatetrenone more significantly improved bone strength properties than risedronate alone. Bone histomorphometric analysis revealed a significant increase in bone resorption with tacrolimus. Risedronate alone significantly suppressed the tacrolimus-induced increase in bone resorption but simultaneously reduced bone formation. On the other hand, the combined administration of risedronate and menatetrenone suppressed the tacrolimus-induced increase in bone resorption, in addition to the significant risedronate-induced decrease in bone formation. This study suggests that the combined administration of risedronate and menatetrenone improves bone strength in tacrolimus-treated rats by preventing and ameliorating the risedronate-induced suppression of bone formation.


Assuntos
Doenças Ósseas Metabólicas/tratamento farmacológico , Imunossupressores/efeitos adversos , Ácido Risedrônico/uso terapêutico , Tacrolimo/efeitos adversos , Vitamina K 2/análogos & derivados , Animais , Densidade Óssea/efeitos dos fármacos , Doenças Ósseas Metabólicas/induzido quimicamente , Quimioterapia Combinada , Fêmur/efeitos dos fármacos , Fêmur/fisiologia , Masculino , Osteogênese/efeitos dos fármacos , Ratos Wistar , Tíbia/efeitos dos fármacos , Tíbia/fisiologia , Vitamina K 2/uso terapêutico
16.
Chemosphere ; 253: 126616, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32283421

RESUMO

Excessive exposure to fluoride has been reported to affect bone mineral density (BMD). CALCA expression plays a critical part in bone formation. However, the role of CALCA in the association between fluoride and BMD is not known. We conducted a cross-sectional study and recruited 722 women in rural areas of Henan Province, China, to assess the relationship between fluoride exposure, CALCA methylation, and BMD. Urinary levels of fluoride, CALCA methylation, and BMD were measured by a fluoride ion-selective electrode, standalone ultrasound bone densitometer, and quantitative methylation-specific polymerases chain reaction, respectively. The association among fluoride exposure, CALCA methylation, and BMD was age-specific. Specifically, BMD was negatively correlated with methylation (ß: -0.008; 95% CI: -0.016, 0.000) and fluoride exposure (ß: -0.063; 95% CI: -0.129, -0.002) in women over 45 years and 50-54 years of age, respectively, whereas methylation was positively correlated with fluoride exposure (ß: 4.953; 95% CI: 1.162, 8.743) in women aged 40-44 years. Besides, increased BMD in women aged 45-49 years induced by the interactive effect of the highest methylation of CALCA exon 1 (tertile 3) and fluoride exposure was observed (P for interaction < 0.05). Our findings suggest an age-specific association between exposure to excessive fluoride, CALCA methylation, and BMD in a rural population of women in China. Notably, the susceptibility of BMD to fluoride exposure may be modified by CALCA methylation.


Assuntos
Densidade Óssea/fisiologia , Peptídeo Relacionado com Gene de Calcitonina/metabolismo , Exposição Ambiental/estatística & dados numéricos , Fluoretos/toxicidade , Absorciometria de Fóton , Adulto , Idoso , Grupo com Ancestrais do Continente Asiático , Densidade Óssea/efeitos dos fármacos , China/epidemiologia , Estudos Transversais , Feminino , Fluoretos/análise , Humanos , Metilação , Pessoa de Meia-Idade , População Rural
17.
Life Sci ; 253: 117636, 2020 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-32251631

RESUMO

BMAL1 is a core component of the circadian clock loop, which directs the sophisticated circadian expression of clock-controlled genes. Skeletal Bone development is a complex biological process involving intramembranous ossification, endochondral ossification and bone remodeling, as well as specific cells, such as mesenchymal cells, osteoblasts, osteoclasts, chondrocytes, etc. Growing evidences suggest that BMAL1 is indispensable for hard tissue development, including bone, cartilage and teeth. Loss of BMAL1 in animals can inhibit bone and cartilage development, and result in abnormal bone mass. In mesenchymal cells, BMAL1 defect inhibits osteoblastic and chondrocytic differentiation. Inactivation of BMAL1 also can promote the differentiation and formation of osteoclasts and increase bone resorption. Specifically, preclinical data demonstrate that the abnormity of BMAL1 expression is associated with skeletal disorders such as skeletal mandibular hypoplasia, osteoarthritis, osteoporosis, etc. In this review, we systemically describe the impact of BMAL1 in skeletal development and homeostasis, and devote to searching new therapy strategies for bone disorders.


Assuntos
Fatores de Transcrição ARNTL/metabolismo , Desenvolvimento Ósseo/efeitos dos fármacos , Fatores de Transcrição ARNTL/genética , Animais , Densidade Óssea/efeitos dos fármacos , Reabsorção Óssea/metabolismo , Osso e Ossos/metabolismo , Cartilagem/metabolismo , Diferenciação Celular , Condrócitos/metabolismo , Condrogênese/efeitos dos fármacos , Relógios Circadianos/genética , Regulação da Expressão Gênica , Humanos , Células-Tronco Mesenquimais/metabolismo , Osteoblastos/metabolismo , Osteoclastos/metabolismo , Osteogênese , Dente/metabolismo
18.
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
19.
Lancet Diabetes Endocrinol ; 8(5): 407-417, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32333877

RESUMO

BACKGROUND: Medical treatment options for primary hyperparathyroidism are scarce. We aimed to assess the efficacy of denosumab and combined with cinacalcet in patients with primary hyperparathyroidism. METHODS: In this randomised, single-centre, proof-of-concept, double-blind trial, patients aged at least 18 years with primary hyperparathyroidism were recruited from the Department of Endocrinology, Aalborg University Hospital, Aalborg, Denmark. Key eligibility criteria were a T-score between -1·0 and -3·5 at the lumbar spine, femoral neck, or total hip. Patients were assigned (1:1:1) via permuted block randomisation to receive 30 mg cinacalcet per day plus 60 mg denosumab subcutaneously every 6 months (n=14; combination group) for 1 year, denosumab plus placebo (n=16; denosumab group) for 1 year, or placebo plus placebo injection (n=15; placebo group) for 1 year. Primary outcomes were changes in bone mineral density (BMD) measured by dual x-ray absorptiometry at the lumbar spine, total hip, femoral neck, and distal forearm after 1 year. Additionally, effects on bone-metabolic biochemistry were explored. Patients and investigators were masked. All enrolled patients were included in efficacy analyses. The trial was done in an outpatient setting and is registered at ClinicalTrials.gov, NCT03027557, and has been completed. FINDINGS: Between March 14, 2017, and March 16, 2018 we recruited 285 participants. 16 patients were randomly allocated to the denosumab group, 15 to the combination group, and 15 to the placebo group. Dropout was limited to one patient in the combination group. Compared with placebo, BMD improved in groups receiving denosumab: lumbar spine (combination group 5·4% [95% CI 2·7-8·1], denosumab group 6·9% [95% CI 4·2-9·6]; p<0·0001), total hip (combination group 5·0% [3·0-6·9], denosumab group 4·1% [2·5-5·8]; p<0·0001), and femoral neck (combination group 4·5% [1·9-7·9]; p=0·0008, denosumab group 3·8% [1·4-6·3]; p=0·0022]). Changes in BMD at the third distal forearm were borderline significant. Six non-fatal serious adverse events occurred (combination group [n=2], denosumab group [n=1], placebo group [n=3]). The overall prevalence of adverse events did not differ between treatment groups, and no fatal adverse events occurred. INTERPRETATION: Evidence suggested denosumab was effective in improving BMD and lowering bone turnover in patients with primary hyperparathyroidism irrespective of cinacalcet treatment and might be a valid option for patients in which surgery is undesirable. FUNDING: Aalborg University Hospital and Aalborg University, Denmark.


Assuntos
Cinacalcete/uso terapêutico , Denosumab/uso terapêutico , Hiperparatireoidismo Primário/tratamento farmacológico , Idoso , Densidade Óssea/efeitos dos fármacos , Remodelação Óssea/efeitos dos fármacos , Cinacalcete/efeitos adversos , Denosumab/efeitos adversos , Método Duplo-Cego , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
20.
Nutrients ; 12(1)2020 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-32284510

RESUMO

Studies investigating the effect of the caudal-type homeobox protein 2 (Cdx2) polymorphism in the vitamin D receptor gene and calcium intake on bone mass have shown inconsistent results. This study investigated whether the effect of calcium intake on peak bone mass is affected by Cdx2 polymorphism in young Japanese women. A cross-sectional study of 500 young women was conducted. Dietary intake was assessed by the Food Frequency Questionnaire. The osteo sono-assessment index (OSI), assessed by the qualitative ultrasound method, was used as a bone mass index. The subjects were divided into two groups by the median calcium intake. The OSI was not different among Cdx2 genotypes and between calcium groups (p = 0.960, p = 0.191, respectively). The interaction between calcium and Cdx2 genotypes on the OSI approached significance (GG versus GA and AA genotypes, p = 0.092). The difference in the OSI between calcium groups was significant in the GG genotype (p = 0.028), but not in the GA or AA genotypes (p = 0.501, p = 0.306, respectively). Adjustment for covariates (body mass index and physical activity) did not change the results. In conclusion, the relationship between dietary calcium intake and peak bone mass may vary according to Cdx2 polymorphism.


Assuntos
Densidade Óssea/genética , Osso e Ossos/efeitos dos fármacos , Fator de Transcrição CDX2/genética , Cálcio na Dieta/farmacologia , Cálcio/farmacologia , Polimorfismo Genético , Receptores de Calcitriol/metabolismo , Adulto , Densidade Óssea/efeitos dos fármacos , Osso e Ossos/metabolismo , Estudos Transversais , Feminino , Genótipo , Humanos , Japão , Adulto Jovem
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