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1.
Med Clin North Am ; 104(5): 873-884, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32773051

RESUMO

Osteoporosis and osteoporosis-related fractures are common causes of morbidity and mortality in older adults. Healthy adults should be counseled about measures to prevent osteoporosis. Women should be screened for osteoporosis beginning at age 65. Screening for osteoporosis in men should be considered when risk factors are present. Appropriate screening intervals are controversial. Women and men with osteoporosis should be offered pharmacologic therapy. Choice of therapy should be based on safety, cost, convenience, and other patient-related factors. Bisphosphonates are a first-line therapy for many patients with osteoporosis. Other treatments for osteoporosis include denosumab, teriparatide, abaloparatide, romosozumab, and selective estrogen receptor modulators.


Assuntos
Conservadores da Densidade Óssea/farmacologia , Osteoporose Pós-Menopausa/terapia , Osteoporose/terapia , Fraturas por Osteoporose/prevenção & controle , Idoso , Feminino , Avaliação Geriátrica/métodos , Humanos , Masculino , Fatores de Risco
2.
Proc Natl Acad Sci U S A ; 117(29): 17187-17194, 2020 07 21.
Artigo em Inglês | MEDLINE | ID: mdl-32636266

RESUMO

Osteoprotegerin (OPG), a secreted decoy receptor for receptor activator of nuclear factor B ligand (RANKL), plays an essential role in regulating bone resorption. While much is known about the function of the N-terminal domains of OPG, which is responsible for binding to RANKL, the exact biological functions of the three C-terminal domains of OPG remain uncertain. We have previously shown that one likely function of the C-terminal domains of OPG is to bind cell surface heparan sulfate (HS), but the in vivo evidence was lacking. To investigate the biological significance of OPG-HS interaction in bone remodeling, we created OPG knock-in mice (opg AAA ). The mutated OPG is incapable of binding to HS but binds RANKL normally. Surprisingly, opg AAA/AAA mice displayed a severe osteoporotic phenotype that is very similar to opg-null mice, suggesting that the antiresorption activity of OPG requires HS. Mechanistically, we propose that the HS immobilizes secreted OPG at the surface of osteoblasts lineage cells, which facilitates binding of OPG to membrane-anchored RANKL. To further support this model, we altered the structure of osteoblast HS genetically to make it incapable of binding to OPG. Interestingly, osteocalcin-Cre;Hs2st f/f mice also displayed osteoporotic phenotype with similar severity to opg AAA/AAA mice. Combined, our data provide strong genetic evidence that OPG-HS interaction is indispensable for normal bone homeostasis.


Assuntos
Conservadores da Densidade Óssea/metabolismo , Conservadores da Densidade Óssea/farmacologia , Heparitina Sulfato/metabolismo , Osteoprotegerina/metabolismo , Osteoprotegerina/farmacologia , Animais , Sítios de Ligação , Reabsorção Óssea/metabolismo , Reabsorção Óssea/patologia , Osso e Ossos/metabolismo , Linhagem Celular , Modelos Animais de Doenças , Feminino , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Osteoblastos/metabolismo , Osteoclastos/metabolismo , Osteogênese/genética , Osteogênese/fisiologia , Osteoporose/genética , Osteoporose/metabolismo , Osteoporose/patologia , Osteoprotegerina/genética , Ligante RANK/metabolismo , Transcriptoma
3.
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
4.
Clin Interv Aging ; 15: 1023-1033, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32636617

RESUMO

Osteoporosis is a common and debilitating condition characterized by diminished bone mass and architecture leading to bone fragility. Antiresorptive medicines like bisphosphonates (and less commonly denosumab) are the typical first-line agents for the medical treatment of osteoporosis. However, newer anabolic agents have been shown to improve bone mass and architecture, as well as reduce fracture risk, to a greater degree than traditional antiresorptive therapies. Teriparatide (human recombinant parathyroid hormone (PTH) 1-34, Forteo, Ely Lilly, Indianapolis, IN), which was the first in class to be approved in the United States, is the most widely used anabolic osteoporosis medicine and has shown significant benefit over traditional antiresorptive therapies. However, abaloparatide (synthetic parathyroid-related peptide (PTHrP), Tymlos, Radius Health, Waltham, MA), the second drug in this family, has recently become available for use. In this narrative review, we review the mechanism, effects, and benefits of abaloparatide compared to alternative treatments as well as discuss the current literature in regard to its effect on osteoporosis-related complications in the spine.


Assuntos
Anabolizantes/uso terapêutico , Conservadores da Densidade Óssea/uso terapêutico , Osteoporose/tratamento farmacológico , Proteína Relacionada ao Hormônio Paratireóideo/uso terapêutico , Anabolizantes/farmacologia , Densidade Óssea/efeitos dos fármacos , Conservadores da Densidade Óssea/farmacologia , Difosfonatos/uso terapêutico , Humanos , Osteoporose/prevenção & controle , Proteína Relacionada ao Hormônio Paratireóideo/farmacologia , Coluna Vertebral , Teriparatida/uso terapêutico
6.
Chem Biol Interact ; 327: 109179, 2020 Aug 25.
Artigo em Inglês | MEDLINE | ID: mdl-32534990

RESUMO

Excessive osteoclast leads to the imbalance in bone reconstruction and results in osteolytic diseases, such as osteoporosis and rheumatic arthritis. Integrin αvß3 abundantly expresses on osteoclast and plays a critical role in the formation and function of osteoclast, therefore, blockage of αvß3 has become an attractive therapeutic option for osteolytic diseases. In this study, we find that Tablysin-15, a RGD motif containing disintegrin, concentration-dependently suppresses RANKL-induced osteoclastogenesis, F-actin ring formation and bone resorption without affecting the cell viabilities. Tablysin-15 binds to integrin αvß3 and inhibits the activation of FAK-associated signaling pathways. Tablysin-15 also suppresses the activation of NF-кB, MAPK, and Akt-NFATc1 signaling pathways, which are crucial transcription factors during osteoclast differentiation. Moreover, Tablysin-15 decreases the osteoclastogenesis marker gene expression, including MMP-9, TRAP, CTSK, and c-Src. Finally, Tablysin-15 significantly inhibits LPS-induced bone loss in a mouse model. Taken together, our results indicate that Tablysin-15 significantly suppresses osteoclastogenesis in vitro and in vivo, thus it might be a excellent candidate for treating osteolytic-related diseases.


Assuntos
Conservadores da Densidade Óssea/farmacologia , Reabsorção Óssea/prevenção & controle , Proteínas de Insetos/farmacologia , Osteogênese/efeitos dos fármacos , Proteínas e Peptídeos Salivares/farmacologia , Animais , Conservadores da Densidade Óssea/toxicidade , Reabsorção Óssea/induzido quimicamente , Fêmur/efeitos dos fármacos , Fêmur/patologia , Proteínas de Insetos/toxicidade , Integrina alfaVbeta3/metabolismo , Lipopolissacarídeos , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Fatores de Transcrição NFATC/metabolismo , Osteoclastos/efeitos dos fármacos , Ligante RANK/metabolismo , Células RAW 264.7 , Proteínas e Peptídeos Salivares/toxicidade , Fator de Transcrição RelA/metabolismo , Regulação para Cima/efeitos dos fármacos
7.
Scand J Rheumatol ; 49(4): 312-322, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32484386

RESUMO

OBJECTIVE: This is the first randomized double-blinded, placebo-controlled pilot trial to investigate the efficacy of pamidronate in reducing radiological and clinical disease activity in chronic non-bacterial osteomyelitis (CNO). METHOD: Patients received pamidronate or placebo at baseline and weeks 12 and 24. Whole-body magnetic resonance imaging was performed at baseline and weeks 12 and 36, and computed tomography of the anterior chest wall (ACW) at baseline and week 36. Radiological disease activity was systematically scored in the ACW and spine. Patient-reported outcomes [visual analogue scale (VAS) pain, VAS global health, Health Assessment Questionnaire (HAQ), EuroQol-5 Dimensions (EQ-5D), and 36-item Short-Form Health Survey (SF-36)] and biomarkers of bone turnover and inflammation were assessed at baseline and weeks 1, 4, 12, 24, and 36. Data are expressed as median [interquartile range]. RESULTS: Fourteen patients were randomized and 12 were analysed. From baseline to week 36, the radiological disease activity score in the ACW decreased from 5 [4-7] to 2.5 [1-3] in the pamidronate group, but did not change in the placebo group (p = 0.04). From baseline to week 36, VAS pain and VAS global health tended to decrease more in the pamidronate than in the placebo group (p = 0.11, p = 0.08). Physical functioning (HAQ) and health-related quality of life (EQ-5D, SF-36) did not change. Biomarkers of bone turnover decreased only in the pamidronate group (p ≤ 0.02). CONCLUSION: Pamidronate may improve radiological and clinical disease activity in CNO. Methods to score radiological disease activity in adult CNO were suggested. Clinical Trials: NCT02594878.


Assuntos
Conservadores da Densidade Óssea/uso terapêutico , Osteomielite/tratamento farmacológico , Pamidronato/uso terapêutico , Coluna Vertebral/efeitos dos fármacos , Parede Torácica/efeitos dos fármacos , Adulto , Biomarcadores/sangue , Conservadores da Densidade Óssea/farmacologia , Remodelação Óssea/efeitos dos fármacos , Método Duplo-Cego , Feminino , Humanos , Imagem por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Osteomielite/sangue , Osteomielite/diagnóstico por imagem , Pamidronato/farmacologia , Medidas de Resultados Relatados pelo Paciente , Projetos Piloto , Coluna Vertebral/diagnóstico por imagem , Parede Torácica/diagnóstico por imagem , Imagem Corporal Total , Adulto Jovem
8.
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
9.
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
10.
Arch Osteoporos ; 15(1): 48, 2020 03 18.
Artigo em Inglês | MEDLINE | ID: mdl-32185512

RESUMO

PURPOSE: To investigate the effects of dairy products on bone mineral density (BMD) in healthy postmenopausal women. METHODS: The EMBASE, Cochrane Library, Medline, and Web of Science databases were systematically searched for relevant studies. The pooled standardized mean difference (SMD) with its 95% confidence interval (CI) was used as the effect size. Subgroup analysis and Begg's test were conducted. RESULTS: Six studies with a total of 618 participants were included in the meta-analysis. Milk was the main dairy product used in the trials. There was a significant association between dairy product consumption and BMD of the lumbar spine (SMD 0.21, 95% CI 0.05-0.37, P = 0.009), femoral neck (SMD 0.36, 95% CI 0.19-0.53, P < 0.001), total hip (SMD 0.37, 95% CI 0.20-0.55, P < 0.001), and total body (SMD 0.58, 95% CI 0.39-0.77, P < 0.001). Subgroup analysis suggested that there was a positive effect of dairy product consumption on the BMD of the total hip starting from 12 months and the femoral neck starting from 18 months. There was also a positive association with the BMD in the four sites in people living in low-calcium intake countries. CONCLUSION: This meta-analysis provides evidence that dairy products can increase BMD in healthy postmenopausal women. Dairy product consumption should be considered an effective public health measure to prevent osteoporosis in postmenopausal women.


Assuntos
Densidade Óssea/fisiologia , Laticínios , Dieta/métodos , Osteoporose Pós-Menopausa/prevenção & controle , Pós-Menopausa/fisiologia , Conservadores da Densidade Óssea/farmacologia , Dieta/efeitos adversos , Feminino , Colo do Fêmur/diagnóstico por imagem , Colo do Fêmur/fisiopatologia , Voluntários Saudáveis , Humanos , Vértebras Lombares/diagnóstico por imagem , Vértebras Lombares/fisiopatologia , Pessoa de Meia-Idade , Osteoporose Pós-Menopausa/etiologia , Ensaios Clínicos Controlados Aleatórios como Assunto
11.
J Pharmacol Sci ; 143(2): 117-121, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32220570

RESUMO

There are several animal models of glucocorticoid-induced osteoporosis (GIOP), but each requires a long time to evaluate drug effects. Zebrafish scales are classified as dermal bone and potentially represent a convenient animal model of GIOP because they rapidly regenerate following their removal. We clarified that dexamethasone-treated regenerating scales showed malformations, decreased size and circularity. Anti-osteoporosis drugs rescued the scale malformation phenotype eight-days following the removal of scales. Hence, the dexamethasone-induced regenerating scale malformation model may be a useful animal model for discovering drugs to treat GIOP.


Assuntos
Escamas de Animais/patologia , Escamas de Animais/fisiologia , Conservadores da Densidade Óssea/uso terapêutico , Dexametasona/efeitos adversos , Modelos Animais de Doenças , Osteoporose/induzido quimicamente , Osteoporose/tratamento farmacológico , Regeneração , Animais , Conservadores da Densidade Óssea/farmacologia , Fenótipo , Regeneração/efeitos dos fármacos , Peixe-Zebra
13.
Int J Mol Sci ; 21(3)2020 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-32019244

RESUMO

As the population of western societies on average ages, the number of people affected by bone remodeling-associated diseases such as osteoporosis continues to increase. The development of new therapeutics is hampered by the high failure rates of drug candidates during clinical testing, which is in part due to the poor predictive character of animal models during preclinical drug testing. Co-culture models of osteoblasts and osteoclasts offer an alternative to animal testing and are considered to have the potential to improve drug development processes in the future. However, a robust, scalable, and reproducible 3D model combining osteoblasts and osteoclasts for preclinical drug testing purposes has not been developed to date. Here we review various types of osteoblast-osteoclast co-culture models and outline the remaining obstacles that must be overcome for their successful translation.


Assuntos
Conservadores da Densidade Óssea/farmacologia , Remodelação Óssea/efeitos dos fármacos , Avaliação Pré-Clínica de Medicamentos , Osteoblastos/citologia , Osteoclastos/citologia , Osteoporose/tratamento farmacológico , Animais , Técnicas de Cocultura , Humanos , Osteoblastos/efeitos dos fármacos , Osteoclastos/efeitos dos fármacos
14.
FASEB J ; 34(2): 2595-2608, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31919918

RESUMO

Dendritic cells are an important link between innate and adaptive immune response. The role of dendritic cells in bone homeostasis, however, is not understood. Osteoporosis medications that inhibit osteoclasts have been associated with osteonecrosis, a condition limited to the jawbone, thus called medication-related osteonecrosis of the jaw. We propose that disruption of the local immune response renders the oral microenvironment conducive to osteonecrosis. We tested whether zoledronate (Zol) treatment impaired dendritic cell (DC) functions and increased bacterial load in alveolar bone in vivo and whether DC inhibition alone predisposed the animals to osteonecrosis. We also analyzed the role of Zol in impairment of differentiation and function of migratory and tissue-resident DCs, promoting disruption of T-cell activation in vitro. Results demonstrated a Zol induced impairment in DC functions and an increased bacterial load in the oral cavity. DC-deficient mice were predisposed to osteonecrosis following dental extraction. Zol treatment of DCs in vitro caused an impairment in immune functions including differentiation, maturation, migration, antigen presentation, and T-cell activation. We conclude that the mechanism of Zol-induced osteonecrosis of the jaw involves disruption of DC immune functions required to clear bacterial infection and activate T cell effector response.


Assuntos
Conservadores da Densidade Óssea/farmacologia , Osso e Ossos/efeitos dos fármacos , Células Dendríticas/metabolismo , Homeostase/imunologia , Doenças Maxilomandibulares/imunologia , Osteonecrose/tratamento farmacológico , Ácido Zoledrônico/farmacologia , Animais , Diferenciação Celular/efeitos dos fármacos , Diferenciação Celular/imunologia , Células Dendríticas/imunologia , Homeostase/efeitos dos fármacos , Imidazóis/farmacologia , Doenças Maxilomandibulares/tratamento farmacológico , Osteoclastos/efeitos dos fármacos , Osteoclastos/imunologia , Osteonecrose/imunologia , Extração Dentária/métodos , Cicatrização/efeitos dos fármacos
15.
Molecules ; 25(1)2020 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-31947859

RESUMO

Receptor activator of nuclear factor-κB ligand (RANKL) is a cytokine responsible for bone resorption. It binds its receptor RANK, which activates osteoporosis. High levels of osteoprotegerin (OPG) competitively binding RANKL limit formation of ligand-receptor complexes and enable bone mass maintenance. The new approach to prevent osteoporosis is searching for therapeutics that can bind RANKL and support OPG function. The aim of the study was to verify the hypothesis that isoflavones can form complexes with RANKL limiting binding of the cytokine to its receptor. Interactions of five isoflavones with RANKL were investigated by isothermal titration calorimetry (ITC), by in silico docking simulation and on Saos-2 cells. Daidzein and biochanin A showed the highest affinity for RANKL. Among studied isoflavones coumestrol, formononetin and biochanin A showed the highest potential for Saos-2 mineralization and were able to regulate the expression of RANKL and OPG at the mRNA levels, as well as osteogenic differentiation markers: alkaline phosphatase (ALP), collagen type 1, and Runt-related transcription factor 2 (Runx2). Comparison of the osteogenic activities of isoflavones showed that the use of physicochemical techniques such as ITC or in silico docking are good tools for the initial selection of substances showing a specific bioactivity.


Assuntos
Conservadores da Densidade Óssea , Isoflavonas , Simulação de Acoplamento Molecular , Osteogênese/efeitos dos fármacos , Osteoporose , Ligante RANK , Conservadores da Densidade Óssea/química , Conservadores da Densidade Óssea/farmacologia , Linhagem Celular Tumoral , Avaliação Pré-Clínica de Medicamentos , Humanos , Isoflavonas/química , Isoflavonas/farmacologia , Osteoporose/tratamento farmacológico , Osteoporose/metabolismo , Osteoporose/patologia , Ligante RANK/agonistas , Ligante RANK/química , Ligante RANK/metabolismo
16.
Int Immunopharmacol ; 79: 106085, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31901621

RESUMO

MPMBP is a novel non-nitrogen-containing bisphosphonate (non-NBP) which possesses anti-bone resorptive activity and an antioxidant side chain. This study aimed to assess the effects of MPMBP on the production of proinflammatory cytokines and chemokines by the macrophage-like cell line, J774.1, in the presence of Toll-like receptor (TLR) agonists. J774.1 cells were pretreated with or without MPMBP for 5 min, and then incubated with or without Pam3Cys-Ser-(Lys)4 (Pam3CSK4, a TLR2 agonist) or lipid A (a TLR4 agonist) for 24 h. MPMBP down-regulated TLR2 ligand-induced production of IL-6, MCP-1, MIP-1α, and TNF-α, but not TLR4 ligand-induced proinflammatory cytokine production, and was not cytotoxic in J774.1 cells. Cu-CPT22, a TLR2 antagonist, down-regulated Pam3CSK4-induced production of IL-6, MCP-1, and MIP-1α, but not TNF-α. MPMBP inhibited the translocation of NF-κB p65, but not p50, RelB, or p52, and inhibited the activation of JNK, but not p38 MAPK or ERK, in J774.1 cells stimulated with Pam3CSK4. Moreover, MPMBP did not down-regulate AP-1 activation in J774.1 cells stimulated with Pam3CSK4 or lipid A. Our findings suggest that MPMBP inhibits proinflammatory cytokine production in J774.1 cells by suppressing NF-κB p65 activation in the TLR2, but not TLR4, pathway.


Assuntos
Conservadores da Densidade Óssea/farmacologia , Citocinas/metabolismo , Receptor 2 Toll-Like/metabolismo , Fator de Transcrição AP-1/metabolismo , Animais , Conservadores da Densidade Óssea/química , Linhagem Celular , Citocinas/genética , Regulação da Expressão Gênica/efeitos dos fármacos , Inflamação/tratamento farmacológico , Inflamação/metabolismo , Macrófagos , Camundongos , NF-kappa B/genética , NF-kappa B/metabolismo , Receptor 2 Toll-Like/genética , Fator de Transcrição AP-1/genética
17.
Knee ; 27(2): 580-586, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31928902

RESUMO

BACKGROUND: Periprosthetic bone quality is one of the most important factors preventing early prosthesis migration and long-term failure. Although denosumab, which binds to the receptor activator of nuclear factor kappa-B ligand (RANKL), has been linked with periprosthetic bone mineral density (BMD), the effectiveness of denosumab against bone loss remains unclear. We hypothesized that denosumab treatment after total knee arthroplasty (TKA) could prevent periprosthetic bone resorption. METHODS: In this prospective cohort study, 28 patients with primary knee osteoarthritis were divided into two groups: denosumab (denosumab and vitamin D) and control (vitamin D only) groups. All patients underwent TKA with the same implant model and received medication after surgery. We used dual-energy X-ray absorptiometry to measure periprosthetic BMD after TKA. RESULTS: In the control group, the BMD of the proximal medial tibia decreased drastically at 12 months after TKA (-19.7%). Denosumab treatment significantly preserved this BMD loss (0.7%). The linear regression analysis revealed that denosumab intervention had the highest significantly positive relationship with BMD. CONCLUSIONS: Our results indicate that denosumab treatment significantly reduces periprosthetic BMD loss, even at the early stages after TKA. This therapeutic strategy may facilitate early stable fixation of the prosthesis which, in turn, may help to prevent early implant migration and reduce the need for revision surgery.


Assuntos
Artroplastia do Joelho/efeitos adversos , Densidade Óssea/efeitos dos fármacos , Reabsorção Óssea/prevenção & controle , Denosumab/farmacologia , Articulação do Joelho/cirurgia , Osteoartrite do Joelho/cirurgia , Tíbia/diagnóstico por imagem , Absorciometria de Fóton , Idoso , Conservadores da Densidade Óssea/farmacologia , Reabsorção Óssea/diagnóstico , Reabsorção Óssea/etiologia , Feminino , Humanos , Articulação do Joelho/diagnóstico por imagem , Masculino , Osteoartrite do Joelho/diagnóstico , Estudos Prospectivos , Reoperação , Tíbia/metabolismo
18.
J Ethnopharmacol ; 248: 112329, 2020 Feb 10.
Artigo em Inglês | MEDLINE | ID: mdl-31672526

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Mesenchymal stem cells (MSCs) are multipotent stem cells possessing regenerative potential. Symphytum officinale (SO) is a medicinal plant and in homoeopathic literature, believed to accelerate bone healing. AIM OF THE STUDY: This study aimed to determine if homoeopathic doses of SO could augment osteogenesis in MSCs as they differentiate into osteoblasts in vitro. MATERIALS AND METHODS: Bone marrow samples were obtained from patients who underwent bone grafting procedures (n = 15). MSCs were isolated, expanded and characterized by flow cytometry (CD90, CD105). Cytotoxicity of SO was evaluated by MTT assay. Osteogenic differentiation was induced in MSCs with ß-glycerophosphate, ascorbic acid and dexamethasone over 2 weeks. Different homoeopathic doses of SO (MT, 3C, 6C, 12C and 30C) were added to the basic differentiation medium (BDM) and efficiency of MSCs differentiating into osteoblasts were measured by evaluating expression of Osteocalcin using flow cytometry, and alkaline phosphatase activity using ELISA. Gene expression analyses for osteoblast markers (Runx-2, Osteopontin and Osteocalcin) were evaluated in differentiated osteoblasts using qPCR. RESULTS: Flow cytometry (CD90, CD105) detected MSCs isolated from bone marrow (93-98%). MTT assay showed that the selected doses of SO did not induce any cytotoxicity in MSCs (24 hours). The efficiency of osteogenic differentiation (2 weeks) for different doses of Symphytum officinale was determined by flow cytometry (n = 10) for osteoblast marker, Osteocalcin, and most doses of Symphytum officinale enhanced osteogenesis. Interestingly, gene expression analysis for Runx-2 (n = 10), Osteopontin (n = 10), Osteocalcin (n = 10) and alkaline phosphatase activity (n = 8) also showed increased osteogenesis with the addition of Symphytum officinale to BDM, specially mother tincture. CONCLUSIONS: Our findings suggest that homoeopathic dose (specially mother tincture) of Symphytum officinale has the potential to enhance osteogenesis.


Assuntos
Conservadores da Densidade Óssea/farmacologia , Diferenciação Celular/efeitos dos fármacos , Confrei , Homeopatia , Células-Tronco Mesenquimais/efeitos dos fármacos , Osteoblastos/efeitos dos fármacos , Osteogênese/efeitos dos fármacos , Extratos Vegetais/farmacologia , Fosfatase Alcalina/metabolismo , Conservadores da Densidade Óssea/isolamento & purificação , Diferenciação Celular/genética , Linhagem Celular , Confrei/química , Subunidade alfa 1 de Fator de Ligação ao Core/genética , Subunidade alfa 1 de Fator de Ligação ao Core/metabolismo , Relação Dose-Resposta a Droga , Regulação da Expressão Gênica , Humanos , Células-Tronco Mesenquimais/metabolismo , Osteoblastos/metabolismo , Osteocalcina/genética , Osteocalcina/metabolismo , Osteogênese/genética , Osteopontina/genética , Osteopontina/metabolismo , Fenótipo , Extratos Vegetais/isolamento & purificação
19.
J Bone Miner Metab ; 38(1): 44-53, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31297652

RESUMO

The objective of the present multicenter randomized study was to compare weekly teriparatide with alendronate in their inhibition of vertebral collapse, effects on delayed union, pain relief, and improvement of quality of life (QOL) in women with new osteoporotic vertebral fractures within 1 week after onset of the fracture. Patients were randomly allocated to the teriparatide and alendronate groups. Vertebral collapse, low back pain assessed by a visual analog scale, and QOL assessed by EuroQol 5 dimension at weeks 1, 2, 4, 8, and 12 after the start of the treatment were compared between the groups. Lumbar bone mineral density (BMD) at baseline and week 12 and the rate of delayed union at week 12 were also compared. Each group consisted of 48 subjects. Vertebral collapse progressed over time in both groups, with no significant difference between the groups. Pain on rising up from lying position, turning over in bed, and resting in the lying position improved over time in both groups, with no significant difference between the groups. There were no significant differences in increase in BMD and delayed union. QOL in the teriparatide group showed significant improvement in comparison with that in the alendronate group at week 12. The weekly formulation of teriparatide showed comparable inhibition of vertebral collapse, increase in BMD, promotion of bone union, and improvement of pain and significant improvement of QOL at week 12 in comparison with alendronate in patients with a new osteoporotic vertebral fracture within 1 week after onset of the fracture. The weekly formulation of teriparatide may have improved components of QOL other than pain at week 12.


Assuntos
Alendronato/uso terapêutico , Fraturas da Coluna Vertebral/tratamento farmacológico , Teriparatida/uso terapêutico , Idoso , Idoso de 80 Anos ou mais , Alendronato/farmacologia , Densidade Óssea/efeitos dos fármacos , Conservadores da Densidade Óssea/farmacologia , Conservadores da Densidade Óssea/uso terapêutico , Esquema de Medicação , Feminino , Humanos , Qualidade de Vida , Fraturas da Coluna Vertebral/diagnóstico por imagem , Fraturas da Coluna Vertebral/fisiopatologia , Teriparatida/farmacologia , Escala Visual Analógica
20.
Breast J ; 26(1): 65-68, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31876101

RESUMO

Bisphosphonates alter the tumor microenvironment, possibly preventing cancer cell growth in the bone. Analyses of data from numerous clinical trials and a large individual patient-level data meta-analysis have suggested an anti-tumor effect for bisphosphonates in patients with early-stage breast cancer who are postmenopausal. The absolute benefit from the use of bisphosphonates on breast cancer-related mortality reduction mirrors that seen with the use of anthracycline-based chemotherapy versus a first-generation chemotherapy regimen (CMF). In this review, we discuss the evidence base for the use of adjuvant bisphosphonates in early-stage breast cancer and provide recommendations for clinical use.


Assuntos
Conservadores da Densidade Óssea/administração & dosagem , Neoplasias Ósseas/secundário , Neoplasias da Mama/tratamento farmacológico , Difosfonatos/administração & dosagem , Conservadores da Densidade Óssea/efeitos adversos , Conservadores da Densidade Óssea/farmacologia , Neoplasias Ósseas/prevenção & controle , Quimioterapia Adjuvante/métodos , Difosfonatos/efeitos adversos , Difosfonatos/farmacologia , Feminino , Humanos , Microambiente Tumoral/efeitos dos fármacos
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