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1.
Int J Mol Sci ; 22(12)2021 Jun 18.
Artigo em Inglês | MEDLINE | ID: mdl-34207275

RESUMO

The aim of the study was to quantify the micro-architectural changes of the jaw bone in response to ovariectomy, exposed or not to bisphosphonate treatment. A total of 47 Wistar rats were ovariectomized (OVX) or sham-operated (shOVX) and exposed to osteoporosis preventive treatment for eight weeks either with bisphosphonates (alendronate, ALN; group OVX-ALN) three days/week at a dose of 2 mg/kg or with saline solution (untreated control condition; group OVX). The bone morphometric parameters of the trabecular jaw bone were assessed using ex vivo micro-computed tomography. The regions of interest investigated in the maxilla were the inter-radicular septum of the second molar and the tuber. The regions quantified in the mandible included the three molar regions and the condyle. A one-way analysis of variance followed by pairwise comparison using Tukey's HSD and the Games-Howell test was conducted to explore significant differences between the groups. In the maxilla, OVX decreased the bone volume in the inter-radicular septum of the second molar. Bisphosphonate treatment was able to prevent this deterioration of the jaw bone. The other investigated maxillary regions were not affected by (un)treated ovariectomy. In the mandible, OVX had a significant negative impact on the jaw bone in the buccal region of the first molar and the inter-radicular region of the third molar. Treatment with ALN was able to prevent this jaw bone loss. At the condyle site, OVX significantly deteriorated the trabecular connectivity and shape, whereas preventive bisphosphonate treatment showed a positive effect on this trabecular bone region. No significant results between the groups were observed for the remaining regions of interest. In summary, our results showed that the effects of ovariectomy-induced osteoporosis are manifested at selected jaw bone regions and that bisphosphonate treatment is capable to prevent these oral bone changes.


Assuntos
Conservadores da Densidade Óssea/uso terapêutico , Difosfonatos/uso terapêutico , Mandíbula/ultraestrutura , Maxila/ultraestrutura , Osteoporose Pós-Menopausa/tratamento farmacológico , Animais , Osso Esponjoso/ultraestrutura , Feminino , Humanos , Ratos , Ratos Wistar
2.
Int J Mol Sci ; 22(12)2021 Jun 18.
Artigo em Inglês | MEDLINE | ID: mdl-34207344

RESUMO

Osteoporosis is a chronic disease characterized by low bone mass caused by increased bone turnover and impaired bone microarchitecture. In treatment, we use antiresorptive or anabolic drugs, which usually have a unidirectional effect, i.e., they inhibit the activity of osteoclasts or stimulate the effect of osteoblasts. Strontium ranelate is an anti-osteoporosis drug with a unique mechanism of action (used primarily in postmenopausal women). Unlike other medicines, it has a multidirectional effect on bone tissue, intensifying osteoblastogenesis while inhibiting osteoclastogenesis. It turns out that this effect is demonstrated by strontium ions, an element showing physical and chemical similarity to calcium, the basic element that builds the mineral fraction of bone. As a result, strontium acts through the calcium-sensing receptor (CaSR) receptor in bone tissue cells. In recent years, there has been a significant increase in interest in the introduction of strontium ions in place of calcium ions in ceramics used as bone replacement materials for the treatment of bone fractures and defects caused by osteoporosis. The aim of this study was to summarize current knowledge about the role of strontium in the treatment of osteoporosis, its effects (in various forms), and the ways in which it is administered.


Assuntos
Conservadores da Densidade Óssea/farmacologia , Osteoporose/tratamento farmacológico , Estrôncio/farmacologia , Animais , Conservadores da Densidade Óssea/uso terapêutico , Cálcio/metabolismo , Humanos , Osteoblastos/efeitos dos fármacos , Osteoblastos/metabolismo , Osteoclastos/efeitos dos fármacos , Osteoclastos/metabolismo , Osteoporose/metabolismo , Estrôncio/uso terapêutico
3.
Int J Mol Sci ; 22(13)2021 Jun 26.
Artigo em Inglês | MEDLINE | ID: mdl-34206757

RESUMO

Metastatic bone cancer occurs in every type of cancer but is prevalent in lung, breast, and prostate cancers. These metastases can cause extensive morbidity, including a range of skeletal-related events, often painful and linked with substantial hospital resource usage. The treatment used is a combination of chemotherapy and surgery. However, anticancer drugs are still limited due to severe side effects, drug resistance, poor blood supply, and non-specific drug uptake, necessitating high toxic doses. Bisphosphonates are the main class of drugs utilized to inhibit metastatic bone cancer. It is also used for the treatment of osteoporosis and other bone diseases. However, bisphosphonate also suffers from serious side effects. Thus, there is a serious need to develop bisphosphonate conjugates with promising therapeutic outcomes for treating metastatic bone cancer and osteoporosis. This review article focuses on the biological outcomes of designed bisphosphonate-based conjugates for the treatment of metastatic bone cancer and osteoporosis.


Assuntos
Conservadores da Densidade Óssea/uso terapêutico , Neoplasias Ósseas/tratamento farmacológico , Difosfonatos/uso terapêutico , Osteoporose/tratamento farmacológico , Animais , Conservadores da Densidade Óssea/química , Neoplasias Ósseas/patologia , Neoplasias Ósseas/secundário , Difosfonatos/química , Humanos
4.
BMJ Case Rep ; 14(6)2021 Jun 02.
Artigo em Inglês | MEDLINE | ID: mdl-34083190

RESUMO

Hypercalcaemia due to immobilisation is an uncommon diagnosis and requires extensive evaluation to rule out common causes of hypercalcaemia such as primary hyperparathyroidism and malignancy.We report an unusual case of profound hypercalcaemia due to immobilisation in a young man due to acute spinal cord ischaemia, leading to paraplegia. Other causes of hypercalcaemia were ruled out and elevated bone turnover markers supported our hypothesis. Conventional treatment with intravenous fluids, bisphosphonates and diuretics was insufficient. Subcutaneous calcitonin lowered the plasma calcium acutely and was continued for 8 weeks. Subsequent normocalcaemia was sustained for 2 years.


Assuntos
Conservadores da Densidade Óssea , Hipercalcemia , Traumatismos da Medula Espinal , Conservadores da Densidade Óssea/uso terapêutico , Calcitonina , Cálcio , Difosfonatos/uso terapêutico , Humanos , Hipercalcemia/diagnóstico , Hipercalcemia/etiologia , Masculino , Traumatismos da Medula Espinal/complicações
5.
Nat Commun ; 12(1): 3247, 2021 05 31.
Artigo em Inglês | MEDLINE | ID: mdl-34059688

RESUMO

The Wnt signaling pathway is intricately connected with bone mass regulation in humans and rodent models. We designed an antibody-based platform that generates potent and selective Wnt mimetics. Using this platform, we engineer bi-specific Wnt mimetics that target Frizzled and low-density lipoprotein receptor-related proteins and evaluate their effects on bone accrual in murine models. These synthetic Wnt agonists induce rapid and robust bone building effects, and correct bone mass deficiency and bone defects in various disease models, including osteoporosis, aging, and long bone fracture. Furthermore, when these Wnt agonists are combined with antiresorptive bisphosphonates or anti-sclerostin antibody therapies, additional bone accrual/maintenance effects are observed compared to monotherapy, which could benefit individuals with severe and/or acute bone-building deficiencies. Our data support the continued development of Wnt mimetics for the treatment of diseases of low bone mineral density, including osteoporosis.


Assuntos
Conservadores da Densidade Óssea/farmacologia , Reabsorção Óssea/tratamento farmacológico , Fraturas do Fêmur/tratamento farmacológico , Osteoporose Pós-Menopausa/tratamento farmacológico , Proteínas Wnt/agonistas , Idoso , Envelhecimento/fisiologia , Animais , Densidade Óssea/efeitos dos fármacos , Densidade Óssea/fisiologia , Conservadores da Densidade Óssea/uso terapêutico , Reabsorção Óssea/fisiopatologia , Difosfonatos/farmacologia , Difosfonatos/uso terapêutico , Modelos Animais de Doenças , Avaliação Pré-Clínica de Medicamentos , Sinergismo Farmacológico , Quimioterapia Combinada/métodos , Feminino , Fraturas do Fêmur/patologia , Fêmur/efeitos dos fármacos , Fêmur/lesões , Fêmur/patologia , Humanos , Camundongos , Osteoporose Pós-Menopausa/fisiopatologia , Via de Sinalização Wnt/efeitos dos fármacos , Adulto Jovem
6.
Int J Mol Sci ; 22(11)2021 May 23.
Artigo em Inglês | MEDLINE | ID: mdl-34071042

RESUMO

Osteoporosis is a chronic disease that has become a serious public health problem due to the associated reduction in quality of life and its increasing financial burden. It is known that inhibiting osteoclast differentiation and promoting osteoblast formation prevents osteoporosis. As there is no drug with this dual activity without clinical side effects, new alternatives are needed. Here, we demonstrate that austalide K, isolated from the marine fungus Penicillium rudallenes, has dual activities in bone remodeling. Austalide K inhibits the receptor activator of nuclear factor-κB ligand (RANKL)-induced osteoclast differentiation and improves bone morphogenetic protein (BMP)-2-mediated osteoblast differentiation in vitro without cytotoxicity. The nuclear factor of activated T cells c1 (NFATc1), tartrate-resistant acid phosphatase (TRAP), dendritic cell-specific transmembrane protein (DC-STAMP), and cathepsin K (CTSK) osteoclast-formation-related genes were reduced and alkaline phosphatase (ALP), runt-related transcription factor 2 (Runx2), osteocalcin (OCN), and osteopontin (OPN) (osteoblast activation-related genes) were simultaneously upregulated by treatment with austalide K. Furthermore, austalide K showed good efficacy in an LPS-induced bone loss in vivo model. Bone volume, trabecular separation, trabecular thickness, and bone mineral density were recovered by austalide K. On the basis of these results, austalide K may lead to new drug treatments for bone diseases such as osteoporosis.


Assuntos
Conservadores da Densidade Óssea/uso terapêutico , Reabsorção Óssea/prevenção & controle , Osteoblastos/efeitos dos fármacos , Osteoclastos/efeitos dos fármacos , Penicillium/química , Animais , Conservadores da Densidade Óssea/isolamento & purificação , Conservadores da Densidade Óssea/farmacologia , Reabsorção Óssea/induzido quimicamente , Diferenciação Celular/efeitos dos fármacos , Modelos Animais de Doenças , Avaliação Pré-Clínica de Medicamentos , Regulação da Expressão Gênica/efeitos dos fármacos , Sedimentos Geológicos/microbiologia , Lipopolissacarídeos/toxicidade , Masculino , Camundongos , Camundongos Endogâmicos ICR , Estrutura Molecular , Fatores de Transcrição NFATC/biossíntese , Fatores de Transcrição NFATC/genética , Osteoporose , Penicillium/isolamento & purificação , Ligante RANK/farmacologia , Fosfatase Ácida Resistente a Tartarato/antagonistas & inibidores
7.
BMC Musculoskelet Disord ; 22(1): 412, 2021 May 04.
Artigo em Inglês | MEDLINE | ID: mdl-33947363

RESUMO

BACKGROUND: Lumbar spinal stenosis (LSS) can cause various neurological symptoms and reduce the daily activity of patients. Many studies have shown that free physical activities and exercise can improve bone mineral density (BMD) in patients with osteoporosis. However, the effect of LSS on BMD has not been reported. The purpose of this study was to investigate the effects of LSS on BMD in patients treated with ibandronate for newly diagnosed osteoporosis. METHODS: Group 1 included 83 patients treated for osteoporosis alone, and group 2 included 76 patients treated for both osteoporosis and symptomatic LSS. We confirmed four BMD values presented as T-score at initial, and 1-, 2-, and 3-year follow-ups. Mean BMD and annual changes of BMD for three years were compared between the two groups. Correlations between initial BMD and total change of BMD, and related factors for continuous BMD improvement for three years were also evaluated. RESULTS: Mean annual BMDs were significantly higher in group 1 compared than in group 2 (-3.39 vs. -3.58 at 1-year; -3.27 vs. -3.49 at 2-year; -3.13 vs. -3.45 at 3-year; all p < 0.05). Annual change of BMD at 1-year follow-up (0.32 vs. 0.21, p = 0.036) and total change of BMD for three years (0.57 vs. 0.35, p = 0.002) were significantly higher in group 1. Group 1 had a strong negative correlation (r = -0.511, P = 0.000) between initial BMD and total change of BMD, whereas group 2 showed a weak negative correlation (r = -0.247, p = 0.032). In multivariate analysis, symptomatic LSS was the only independent risk factor for continuous BMD improvement (Odds ratio = 0.316, p = 0.001). CONCLUSIONS: Symptomatic LSS may interfere with BMD improvement in the treatment of osteoporosis with ibandronate. Active treatment for LSS with more potent treatment for osteoporosis should be taken to increase BMD for patients with osteoporosis and LSS.


Assuntos
Conservadores da Densidade Óssea , Osteoporose , Estenose Espinal , Densidade Óssea , Conservadores da Densidade Óssea/uso terapêutico , Difosfonatos/uso terapêutico , Humanos , Ácido Ibandrônico , Vértebras Lombares/diagnóstico por imagem , Osteoporose/diagnóstico por imagem , Osteoporose/tratamento farmacológico , Osteoporose/epidemiologia , Estenose Espinal/diagnóstico por imagem , Estenose Espinal/tratamento farmacológico , Resultado do Tratamento
9.
Cancer Radiother ; 25(5): 484-493, 2021 Jul.
Artigo em Francês | MEDLINE | ID: mdl-33836955

RESUMO

The identification of the different risk factors for mandibular osteoradionecrosis (ORN) must be done before and after the management of patients with head and neck cancer. Various clinical criteria for this severe radiation-induced complication are related to the patient (intrinsic radiosensitivity, malnutrition associated with thin weight loss, active smoking intoxication, microcapillary involvement, precarious oral status, hyposalivation) and/or related to the disease (oral cavity, large tumor size, tumor mandibular invasion). Therapeutic risk factors are also associated with a higher risk of ORN (primary tumor surgery, concomitant radio-chemotherapy, post-irradiation dental avulsion, preventive non-observance with the absence of stomatological follow-up and daily installation of gutters fluoride and, non-observance curative healing treatments). Finally, various dosimetric studies have specified the parameters in order to target the dose values distributed in the mandible, which increases the risk of ORN. An mean mandibular dose greater than 48-54Gy and high percentages of mandibular volume receiving 40 to 60Gy appear to be discriminating in the risk of developing an ORN.


Assuntos
Neoplasias de Cabeça e Pescoço/radioterapia , Doenças Mandibulares/etiologia , Doenças Mandibulares/terapia , Osteorradionecrose/etiologia , Osteorradionecrose/terapia , Conservadores da Densidade Óssea/uso terapêutico , Ácido Clodrônico/uso terapêutico , Quimioterapia Combinada , Humanos , Oxigenação Hiperbárica , Osteorradionecrose/classificação , Osteorradionecrose/diagnóstico , Pentoxifilina/uso terapêutico , Dosagem Radioterapêutica , Fatores de Risco , Tocoferóis/uso terapêutico
10.
Osteoporos Int ; 32(6): 1217-1219, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33903925

RESUMO

In patients with surgical repair of a low-trauma hip fracture, zoledronic acid (ZA) reduced the risk of subsequent fractures regardless of pretreatment femoral neck and total hip bone mineral density (BMD). INTRODUCTION: Zoledronic acid reduces the risk of subsequent fractures after repair of a hip fracture. It is still unclear whether the benefits in fracture reduction with ZA depend upon hip bone mineral density at the time of fracture. METHODS: We preformed additional post hoc analyses of data from the HORIZON Recurrent Fracture Trial to determine if ZA treatment reduced the risk of new clinical fractures regardless of pretreatment BMD. We modeled femoral neck and total hip BMD as both continuous and dichotomous variables (BMD T-score above and below -2.5). RESULTS: There are no evidence that baseline femoral neck and total hip BMD modified the anti-fracture efficacy of ZA when pretreatment BMD was analyzed as a continuous or a dichotomous variable (interaction p-values > 0.20). The clinical fracture efficacy of ZA was similar among patients with pretreatment femoral neck BMD values above and below -2.5 (relative hazards = 0.60 and 0.67, respectively, interaction p-value = 0.95). A similar result was obtained using pretreatment total hip BMD values (relative hazards = 0.72 and 0.57, respectively, interaction p-value = 0.41). CONCLUSION: There data should provide more comfort in prescribing ZA after surgical repair of a hip fracture, regardless of pretreatment BMD.


Assuntos
Conservadores da Densidade Óssea , Fraturas do Quadril , Densidade Óssea , Conservadores da Densidade Óssea/uso terapêutico , Colo do Fêmur/cirurgia , Fraturas do Quadril/prevenção & controle , Fraturas do Quadril/cirurgia , Humanos , Ácido Zoledrônico/uso terapêutico
11.
Int J Mol Sci ; 22(9)2021 Apr 24.
Artigo em Inglês | MEDLINE | ID: mdl-33923233

RESUMO

Pyogenic spondylodiscitis can cause severe osteolytic and destructive lesions in the spine. Elderly or immunocompromised individuals are particularly susceptible to infectious diseases; specifically, infections in the spine can impair the ability of the spine to support the trunk, causing patients to be bedridden, which can also severely affect the physical condition of patients. Although treatments for osteoporosis have been well studied, treatments for bone loss secondary to infection remain to be elucidated because they have pathological manifestations that are similar to but distinct from those of osteoporosis. Recently, we encountered a patient with severely osteolytic pyogenic spondylodiscitis who was treated with romosozumab and exhibited enhanced bone formation. Romosozumab stimulated canonical Wnt/ß-catenin signaling, causing robust bone formation and the inhibition of bone resorption, which exceeded the bone loss secondary to infection. Bone loss due to infections involves the suppression of osteoblastogenesis by osteoblast apoptosis, which is induced by the nuclear factor-κB and mitogen-activated protein kinase pathways, and osteoclastogenesis with the receptor activator of the nuclear factor-κB ligand-receptor combination and subsequent activation of the nuclear factor of activated T cells cytoplasmic 1 and c-Fos. In this study, we review and discuss the molecular mechanisms of bone loss secondary to infection and analyze the efficacy of the medications for osteoporosis, focusing on romosozumab, teriparatide, denosumab, and bisphosphonates, in treating this pathological condition.


Assuntos
Conservadores da Densidade Óssea/uso terapêutico , Reabsorção Óssea/tratamento farmacológico , Discite/complicações , Terapia de Alvo Molecular , Osteoporose/tratamento farmacológico , Transdução de Sinais/efeitos dos fármacos , Animais , Reabsorção Óssea/etiologia , Reabsorção Óssea/patologia , Humanos
12.
Int J Mol Sci ; 22(7)2021 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-33806209

RESUMO

Multiple myeloma (MM) is a B-cell neoplasm characterized by clonal plasma-cell proliferation. The survival and prognosis of this condition have been significantly improved by treatment with active anti-MM drugs such as bortezomib or lenalidomide. Further, the discovery of novel agents has recently paved the way for new areas of investigation. However, MM, including myeloma-related bone diseases, remains fatal. Bone disease or bone destruction in MM is a consequence of skeletal involvement with bone pain, spinal cord compression, and bone fracture resulting from osteolytic lesions. These consequences affect disease outcomes, including patients' quality of life and survival. Several studies have sought to better understand MM bone disease (MBD) through the classification of its molecular mechanisms, including osteoclast activation and osteoblast inhibition. Bisphosphonates and the receptor activator of the nuclear factor-kappa B (NF-κB) ligand (RANKL) inhibitor, denosumab, prevent skeletal-related events in MM. In addition, several other bone-targeting agents, including bone-anabolic drugs, are currently used in preclinical and early clinical evaluations. This review summarizes the current knowledge of the pathogenesis of MBD and discusses novel agents that appear very promising and will soon enter clinical development.


Assuntos
Doenças Ósseas/terapia , Mieloma Múltiplo/terapia , Animais , Antineoplásicos/farmacologia , Biomarcadores Tumorais/metabolismo , Conservadores da Densidade Óssea/uso terapêutico , Doenças Ósseas/etiologia , Remodelação Óssea , Osso e Ossos , Bortezomib/farmacologia , Denosumab/farmacologia , Difosfonatos/farmacologia , Humanos , Mieloma Múltiplo/complicações , Subunidade p50 de NF-kappa B/metabolismo , Osteoblastos/metabolismo , Osteoclastos/metabolismo , Osteólise/complicações , Ligante RANK/metabolismo , Proteínas Wnt/antagonistas & inibidores
13.
J Int Med Res ; 49(4): 3000605211001643, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33845598

RESUMO

An atypical femoral fracture (AFF) is a rare complication associated with excessive inhibition of osteoclast expression during treatment of osteoporosis. We herein describe a patient who had been treated with alendronate for more than 10 years and subsequently developed an AFF that healed after treatment with vitamin K2 (VK2). We also discuss the potential beneficial effects of VK2 on the healing of AFFs. A 48-year-old Asian man with secondary osteoporosis was treated with alendronate for more than 10 years. The patient underwent surgical treatment for a complete AFF of the right femur. Six months postoperatively, he complained of pain in his left thigh. X-ray examination revealed an incomplete AFF of the left femoral shaft. He was then treated with VK2. After 4 months of VK2 treatment, the patient reported that the pain in his left thigh had decreased, and follow-up X-ray examination demonstrated healing of the left AFF line. This case report indicates that VK2 may be a potential direction for pharmacological treatment of AFFs in future research.


Assuntos
Conservadores da Densidade Óssea , Fraturas do Fêmur , Osteoporose , Conservadores da Densidade Óssea/uso terapêutico , Difosfonatos , Fraturas do Fêmur/diagnóstico por imagem , Fraturas do Fêmur/tratamento farmacológico , Fraturas do Fêmur/cirurgia , Fêmur/diagnóstico por imagem , Fêmur/cirurgia , Humanos , Masculino , Pessoa de Meia-Idade , Osteoporose/complicações , Osteoporose/diagnóstico por imagem , Osteoporose/tratamento farmacológico , Vitamina K 2/uso terapêutico
14.
Arch Osteoporos ; 16(1): 75, 2021 04 22.
Artigo em Inglês | MEDLINE | ID: mdl-33890181

RESUMO

PURPOSE: A fracture liaison service (FLS) was established in England to support patients with fragility fractures, and it was introduced in Japan as the osteoporosis liaison service (OLS). The study aim was to determine if the Japanese OLS/FLS prevents secondary fractures in patients with fragility fractures and assess the value of the OLS/FLS. Our OLS/FLS evaluated the status of osteoporosis in patients and their life circumstances. Additionally, it introduced osteoporosis therapies during the patients' hospitalization period and then continued periodical examinations and prescription of drug after discharge. PATIENTS AND METHODS: This study was conducted in consecutive patients: 400 were assigned to the non-OLS group and 406 to the OLS group. The mean age of the patients was 81.7 ± 9.7 years in the non-OLS group (154 patients with vertebral fractures and 246 with hip fractures; 100 males, 300 females) and 82.4 ± 9.3 years in the OLS group (245 patients with hip fractures and 161 with vertebral fractures; 101 males, 305 females). RESULTS: During hospitalization, 74.9% of the OLS group patients started medications and 63.9% of patients continued after discharge, while 35.8% and 53.5% of non-OLS group. The incidence rate of secondary fractures was 89.8/1000 person-years in the non-OLS group, and 55.2/1000 person-years in the OLS group. The multivariate Cox hazards test showed that secondary fractures after vertebral or hip fractures increased with age, and the risk was 0.58-fold in patients in the OLS group. CONCLUSION: OLS was effective in reducing secondary fractures in patients with osteoporosis with fragility fractures.


Assuntos
Conservadores da Densidade Óssea , Osteoporose , Fraturas por Osteoporose , Idoso , Idoso de 80 Anos ou mais , Conservadores da Densidade Óssea/uso terapêutico , Feminino , Hospitais Privados , Humanos , Japão/epidemiologia , Masculino , Osteoporose/complicações , Osteoporose/tratamento farmacológico , Osteoporose/epidemiologia , Fraturas por Osteoporose/epidemiologia , Prevenção Secundária
15.
Nutr Metab Cardiovasc Dis ; 31(5): 1375-1390, 2021 05 06.
Artigo em Inglês | MEDLINE | ID: mdl-33812734

RESUMO

Bone fragility is one of the possible complications of diabetes, either type 1 (T1D) or type 2 (T2D). Bone fragility can affect patients of different age and with different disease severity depending on type of diabetes, disease duration and the presence of other complications. Fracture risk assessment should be started at different stages in the natural history of the disease depending on the type of diabetes and other risk factors. The risk of fracture in T1D is higher than in T2D, imposing a much earlier screening and therapeutic intervention that should also take into account a patient's life expectancy, diabetes complications etc. The therapeutic armamentarium for T2D has been enriched with drugs that may influence bone metabolism, and clinicians should be aware of these effects. Considering the complexity of diabetes and osteoporosis and the range of variables that influence treatment choices in a given individual, the Working Group on bone fragility in patients with diabetes mellitus has identified and issued recommendations based on the variables that should guide screening of bone fragility and management of diabetes and bone fragility: (A)ge, (B)MD, (C)omplications, (D)uration of disease, & (F)ractures (ABCD&F). Consideration of these parameters may help clinicians identify the best time for screening, the appropriate glycaemic target and anti-osteoporosis drug for patients with diabetes at risk of or with bone fragility.


Assuntos
Diabetes Mellitus Tipo 1/complicações , Diabetes Mellitus Tipo 2/complicações , Osteoporose/etiologia , Densidade Óssea , Conservadores da Densidade Óssea/uso terapêutico , Remodelação Óssea , Consenso , Diabetes Mellitus Tipo 1/diagnóstico , Diabetes Mellitus Tipo 1/tratamento farmacológico , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diagnóstico Precoce , Controle Glicêmico/efeitos adversos , Humanos , Hipoglicemiantes/efeitos adversos , Resistência à Insulina , Osteoporose/diagnóstico , Osteoporose/prevenção & controle , Fraturas por Osteoporose/diagnóstico , Fraturas por Osteoporose/etiologia , Fraturas por Osteoporose/prevenção & controle , Medição de Risco , Fatores de Risco , Resultado do Tratamento
16.
Arch Osteoporos ; 16(1): 60, 2021 04 04.
Artigo em Inglês | MEDLINE | ID: mdl-33813663

RESUMO

We analyzed the long-term persistence of treatment in a FLS. During follow-up, 15.2% of patients had a refracture and 23.8% died. At the 5-year checkup, 74% had started treatment (associated with female sex, previous use of bisphosphonate, and referral to an osteoporosis clinic). Persistence at 1 and 5 years was 70.6% and 46.5%, respectively. INTRODUCTION: To analyze the long-term persistence of treatment in a fracture liaison service (FLS). METHODS: Patients ≥ 50 years with a fragility fracture attended between 2012 and 2016 who were recommended for treatment to prevent new fractures were included. Baseline data included demographics, type of fracture, previous treatment, and FRAX® items. Five years later, patient records were reviewed and the following data were collected: [1] survival; [2] refracture; [3] initiation of treatment, persistence, and medication possession ratio (MPR) > 80%. RESULTS: We included 888 patients, mean age 75 years, 83% women, and mean follow-up 56 months. During follow-up, 135 patients (15.2%) had a refracture (109 major fractures, 50 hip refractures) and 212 patients died (23.8%); at the 5-year checkup, 657 patients (74%) had started some type of treatment. Factors associated with the start of treatment were female sex (OR 2.10; 95% CI: 1.42-3.11), previous use of bisphosphonate (OR 3.91; 95% CI: 2.23-6.86), and referral to an osteoporosis clinic (OR 1.46; 95% CI: 1.02-2.07). Persistence decreased from 70.6% at 12 months to 46.5% at 60 months. An MPR > 80% was confirmed in 449 patients, 68.3% of whom were under treatment. A total of 521 and 447 patients received treatment for at least 24 and 36 months, respectively (79.3% and 68.0% of those who started treatment). CONCLUSIONS: Patients with fragility fractures attended at an FLS showed optimal long-term persistence of treatment. These data can help healthcare managers better calculate the cost-effectiveness of implementing the FLS model.


Assuntos
Conservadores da Densidade Óssea , Osteoporose , Fraturas por Osteoporose , Idoso , Conservadores da Densidade Óssea/uso terapêutico , Difosfonatos/uso terapêutico , Feminino , Humanos , Masculino , Osteoporose/tratamento farmacológico , Fraturas por Osteoporose/epidemiologia , Fraturas por Osteoporose/prevenção & controle , Prevenção Secundária
17.
J Orthop Traumatol ; 22(1): 10, 2021 Mar 09.
Artigo em Inglês | MEDLINE | ID: mdl-33687578

RESUMO

BACKGROUND: Osteoarthritis (OA) is a disease with multiple endotypes. A hallmark of OA is loss of cartilage; however, it is evident that the rate of cartilage loss differs among patients, which may partly be attributed to differential capacity for cartilage repair. We hypothesize that a low cartilage repair endotype exists and that such endotypes are more likely to progress radiographically. The aim of this study is to examine the associations of level of cartilage formation with OA severity and radiographic OA progression. We used the blood-based marker PRO-C2, reflecting type II collagen formation, to assess levels of cartilage formation. MATERIALS AND METHODS: The type II collagen propeptide PRO-C2 was measured in the serum/plasma of knee OA subjects from New York University (NYU, n = 106) and a subcohort of the phase III oral salmon calcitonin (sCT) trial SMC021-2301 (SMC, n = 147). Risk of radiographic medial joint space narrowing (JSN) over 24 months was compared between quartiles (very low, low, moderate, and high) of PRO-C2. Associations were adjusted for age, gender, BMI, race, baseline pain levels, and baseline joint space width. RESULTS: In both the NYU and SMC cohorts, subjects with low PRO-C2 levels had greater JSN compared with subjects with high PRO-C2. Mean difference in JSN between subjects with very low and high levels of PRO-C2 was 0.65 mm (p = 0.002), corresponding to a 3.4 (1.4-8.6)-fold higher risk of progression. There was no significant effect of sCT treatment, compared with placebo, on JSN over 2 years before stratification based on baseline PRO-C2. However, there were proportionately fewer progressors in the sCT arm of the very low/low PRO-C2 group compared with the moderate/high group (Chi squared = 6.5, p = 0.011). CONCLUSION: Serum/plasma level of type II collagen formation, PRO-C2, may be an objective indicator of a low cartilage repair endotype, displaying radiographic progression and superior response to a proanabolic drug. LEVEL OF EVIDENCE: Level III post hoc exploratory analysis of one longitudinal cohort and a sub-study from one phase III clinical trial.


Assuntos
Proteínas de Ligação ao Cálcio/sangue , Cartilagem Articular/diagnóstico por imagem , Condrogênese/fisiologia , Colágeno Tipo II/sangue , Osteoartrite do Joelho/sangue , Osteoartrite do Joelho/diagnóstico por imagem , Idoso , Biomarcadores/sangue , Conservadores da Densidade Óssea/uso terapêutico , Calcitonina/uso terapêutico , Estudos de Coortes , Progressão da Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Osteoartrite do Joelho/tratamento farmacológico , Valor Preditivo dos Testes , Radiografia
18.
Biomed Pharmacother ; 137: 111382, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33761603

RESUMO

Accumulating studies have indicated that reactive oxygen species (ROS) may be implicated into the destructive pathological events of rheumatoid arthritis (RA). As an effective antioxidant, artesunate (ARS) was reported to exert antiarthritic effects. However, whether ARS attenuates the bone erosion during RA progression by regulating ROS production remains to be defined. To address this problem, the inhibitive effects of ARS on osteoclastogenesis were observed in vitro. Mechanically, ARS significantly inhibited the NFATc1 signaling accompanied by markedly suppressing ROS production, which was abnormally enhanced during the pathological process of bone erosion. In addition, ARS may function as a potent ROS scavenger and significantly elevate the expression of HO-1 and NQO1 by activating Nrf2. Moreover, p62 accumulation induced by ARS was responsible for the activation of Nrf2, while the knockdown of p62 in osteoclast precursor cells diminished the suppressive effect of ARS on ROS production during osteoclastogenesis. Consistently, we also demonstrated that ARS effectively suppressed ROS production, leading to the inhibition of arthritic bone destruction by activating antioxidant enzyme and Nrf2/p62 signaling in the knee and ankle tissues of CIA rats. Collectively, our data offer the convincing evidence that ARS may inhibit osteoclastogenesis and ameliorate arthritic bone erosion through suppressing the generation of ROS via activating the p62/Nrf2 signaling.


Assuntos
Antioxidantes/farmacologia , Artesunato/farmacologia , Artrite Reumatoide/tratamento farmacológico , Conservadores da Densidade Óssea/farmacologia , Doenças Ósseas/tratamento farmacológico , Fator 2 Relacionado a NF-E2/efeitos dos fármacos , Espécies Reativas de Oxigênio/antagonistas & inibidores , Transdução de Sinais/efeitos dos fármacos , Animais , Antioxidantes/uso terapêutico , Antirreumáticos/farmacologia , Antirreumáticos/uso terapêutico , Artesunato/uso terapêutico , Artrite Reumatoide/patologia , Conservadores da Densidade Óssea/uso terapêutico , Doenças Ósseas/patologia , Reabsorção Óssea/tratamento farmacológico , Heme Oxigenase-1/metabolismo , Articulações/efeitos dos fármacos , Articulações/metabolismo , Proteínas de Membrana/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Fator 2 Relacionado a NF-E2/genética , Osteoclastos/efeitos dos fármacos , Osteogênese/efeitos dos fármacos
19.
Bone ; 147: 115907, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33676057

RESUMO

The skeleton is the most common site of secondary disease in breast cancer and prostate cancer, with up to 80% of patients with advanced disease developing bone metastases (BM). The proportion is also substantial in advanced lung cancer (20%-40%). Because of the high prevalence of cancers of the breast, prostate and lung, these cancers account for more than 80% of cases of metastatic bone disease occurring in solid tumours. Metastatic bone disease is associated with greatly increased bone resorption by osteoclasts, leading to moderate to severe pain and other skeletal complications, with major impact on quality of life (QoL). Skeletal Related Events (SREs) have been defined as: pathological long bone or vertebral fractures; spinal cord compression; need for radiation for pain relief or to prevent fracture/spinal cord compression, need for surgery to bone and hypercalcaemia. More recently, Symptomatic Skeletal Events (SSEs) have been defined to monitor QoL. Although there are currently no curative treatments for metastatic bone disease, patients with breast or prostate cancer and BM are now surviving for several years and sometimes longer, and prevention of SREs is the key aim to optimization of QoL. Since their discovery 50 years ago and their introduction more than 30 years ago into the field of metastatic bone disease, a range of oral and intravenous bisphosphonate drugs have made a major contribution to prevention of SREs. Large trials have clearly demonstrated the clinical value of different bisphosphonate-based drugs (including the oral drugs ibandronate and clodronate and intravenous agents such as zoledronate and pamidronate), in treatment of hypercalcaemia of malignancy and the reduction of SREs and SSEs in a range of cancers. Despite the success of denosumab in reducing osteolysis, bisphosphonates also remain mainstay drugs for treatment of metastatic bone disease. Recognizing the 50th Anniversary of the discovery of bisphosphonates, this review focuses on their continuing value in BM treatment and their future potential, for example in providing a bone-targeting vehicle for cytotoxic drugs.


Assuntos
Conservadores da Densidade Óssea , Neoplasias Ósseas , Neoplasias da Mama , Conservadores da Densidade Óssea/uso terapêutico , Neoplasias Ósseas/complicações , Neoplasias Ósseas/tratamento farmacológico , Difosfonatos/uso terapêutico , Humanos , Masculino , Qualidade de Vida , Ácido Zoledrônico
20.
Arch Osteoporos ; 16(1): 49, 2021 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-33646403

RESUMO

The Brazilian guidelines for prevention and treatment of glucocorticoid-induced osteoporosis were updated and important topics were included such as assessment of risk fracture using FRAX Brazil, use of denosumab, and also recommendations for the use of glucocorticoid pulse therapy and inhaled glucocortiocoid. INTRODUCTION: Glucocorticoids (GCs) are used in almost all medical specialties and the incidences of vertebral/nonvertebral fractures range from 30 to 50% in individuals treated with GCs for over 3 months. Thus, osteoporosis and frailty fractures should be prevented and treated in patients initiating treatment or already being treated with GCs. The Committee for Osteoporosis and Bone Metabolic Disorders of the Brazilian Society of Rheumatology (BSR) established in 2012 the Brazilian Guidelines for glucocorticoid-induced osteoporosis (GIO). Herein, we provide a comprehensive update of the original guidelines based on improved available scientific evidence and/or expert experience. METHODS: From March to June 2020, the Osteoporosis Committee of the BRS had meetings to update the questions presented in the first consensus (2012). Thus, twenty-six questions considered essential for the preparation of the recommendations were selected. A systematic literature review based on real-life scenarios was undertaken to answer the proposed questions. The MEDLINE, EMBASE, and SCOPUS databases were searched using specific search keywords. RESULTS: Based on the review and expert opinion, the recommendations were updated for each of the 26 questions. We included 48 new bibliographic references that became available after the date of the publication of the first version of the consensus. CONCLUSION: We updated the Brazilian guidelines for the prevention/treatment of GIO. New topics were added in this update, such as the assessment of risk fracture using FRAX Brazil, the use of denosumab, and approaches for the treatment of children and adolescents. Furthermore, we included recommendations for the use of inhaled GCs and GC pulse therapy in clinical settings.


Assuntos
Conservadores da Densidade Óssea , Fraturas Ósseas , Osteoporose , Reumatologia , Adolescente , Conservadores da Densidade Óssea/uso terapêutico , Brasil , Criança , Glucocorticoides/efeitos adversos , Humanos , Osteoporose/induzido quimicamente , Osteoporose/tratamento farmacológico , Osteoporose/prevenção & controle
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