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1.
Gene ; 725: 144167, 2020 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-31639434

RESUMO

Osteoporosis in advanced cholestatic and end-stage liver disease is related to low bone formation. Previous studies have demonstrated the deleterious consequences of lithocholic acid (LCA) and bilirubin on osteoblastic cells. These effects are partially or completely neutralized by ursodeoxycholic acid (UDCA). We have assessed the differential gene expression of osteoblastic cells under different culture conditions. The experiments were performed in human osteosarcoma cells (Saos-2) cultured with LCA (10 µM), bilirubin (50 µM) or UDCA (10 and 100 µM) at 2 and 24 h. Expression of 87 genes related to bone metabolism and other signalling pathways were assessed by TaqMan micro fluidic cards. Several genes were up-regulated by LCA, most of them pro-apoptotic (BAX, BCL10, BCL2L13, BCL2L14), but also MGP (matrix Gla protein), BGLAP (osteocalcin), SPP1 (osteopontin) and CYP24A1, and down-regulated bone morphogenic protein genes (BMP3 and BMP4) and DKK1 (Dickkopf-related protein 1). Parallel effects were observed with bilirubin, which up-regulated apoptotic genes and CSF2 (colony-stimulating factor 2) and down-regulated antiapoptotic genes (BCL2 and BCL2L1), BMP3, BMP4 and RUNX2. UDCA 100 µM had specific consequences since differential expression was observed, up-regulating BMP2, BMP4, BMP7, CALCR (calcitonin receptor), SPOCK3 (osteonectin), BGLAP (osteocalcin) and SPP1 (osteopontin), and down-regulating pro-apoptotic genes. Furthermore, most of the differential expression changes induced by both LCA and bilirubin were partially or completely neutralized by UDCA. Conclusion: Our observations reveal novel target genes, whose regulation by retained substances of cholestasis may provide additional insights into the pathogenesis of osteoporosis in cholestatic and end-stage liver diseases.


Assuntos
Bilirrubina/metabolismo , Osteoblastos/metabolismo , Osteoporose/genética , Apoptose/efeitos dos fármacos , Ácidos e Sais Biliares/metabolismo , Linhagem Celular Tumoral , Colestase/genética , Regulação para Baixo/efeitos dos fármacos , Perfil Genético , Humanos , Ácido Litocólico/farmacologia , Fígado/metabolismo , Fígado/fisiologia , Hepatopatias/genética , Hepatopatias/metabolismo , Hepatopatias/fisiopatologia , Osteoporose/metabolismo , Osteossarcoma/genética , Osteossarcoma/metabolismo , Regulação para Cima/efeitos dos fármacos , Ácido Ursodesoxicólico/farmacologia
2.
JAMA ; 322(23): 2344, 2019 12 17.
Artigo em Inglês | MEDLINE | ID: mdl-31846011
3.
JAMA ; 322(23): 2344, 2019 12 17.
Artigo em Inglês | MEDLINE | ID: mdl-31846013
4.
Medicine (Baltimore) ; 98(52): e18226, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31876703

RESUMO

BACKGROUND: Primary osteoporosis (POP) is a common disease among elderly, which increase the risk of fracture and impact to the quality of life. As a Chinese traditional therapy, moxibustion has been commonly applied in treating chronic musculoskeletal diseases in China. Many trails have shown that moxibustion therapy is effective in treating primary osteoporosis. The protocol aims to present the methods used to access the effectiveness and safety of moxibustion therapy for patients with primary osteoporosis. METHODS: The following databases will be searched from their inception: the Cochrane Central Register of Controlled Trails(CENTRAL), Pubmed, EMBASE, China National Knowledge Infrastructure(CNKI), Chinese Biomedical Literature Database(CBM), Chinese Scientific Journal Database (VIP database), and Wan-Fang Database. Clinical randomized controlled trials related to moxibustion therapy for treating primary osteoporosis will be included, regardless of publication status and languages. Study selection, data collection, and quality assessment will be independently conducted by 2 researchers. We will select the fixed-effects or random-effects model according to the heterogeneity assessment for data synthesis. Bone mineral density(BMD) will be the primary outcomes. Visual analogue scale(VAS), response rate, TCM Syndrome scale(TCMSS), bone gla protein(BGP), alkaline phosphatase(BALP), blood calcium(Ca), blood phosphate(P), quality of life(QOL) will be the second outcomes. If it is appropriate for meta-analysis, RevMan V.5.3 statistical software will be used. Otherwise, a systematic narrative synthesis will be conducted. The results will be presented as risk ratio (RR) with 95% confidence intervals (CIs) for dichotomous data and weight mean difference(WMD) or standard mean difference (SMD) 95% CIs for continuous data. TRIAL REGISTRATION NUMBER: PROSPERO CRD42019129507.


Assuntos
Moxibustão , Osteoporose/terapia , Idoso , Humanos , Moxibustão/efeitos adversos , Moxibustão/métodos , Resultado do Tratamento
5.
Indian J Dent Res ; 30(5): 747-750, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31854367

RESUMO

Background: Osteoporosis and periodontitis are both diseases that induce bone resorption. The objective of this study was to verify through panoramic radiography analysis whether patients with osteoporosis have a greater risk of periodontal disease (horizontal alveolar bone defect and vertical alveolar bone defect) when compared with patients without osteoporosis. Methods: In all, 100 women were selected: 50 with osteoporosis (T-score < -2.5 DP) and 50 without osteoporosis (T-score > -2.5 DP), using the T-score of proximal radius. Logistic regression test was performed to assess the risk of panoramic radiographic periodontal defects (horizontal and vertical bone defect), age, and bone mineral density influence. Results: Advanced age women were three times more likely to present osteoporosis. Patients with osteoporosis have significantly higher risk (4.46 times) of presenting horizontal alveolar bone defect. Vertical alveolar bone defect results were nonsignificant. Conclusion: Our study results corroborate the literature trend that osteoporosis may influence the progression of alveolar ridge height loss (horizontal alveolar bone defect). Panoramic radiography may be used as a screening tool to help the diagnosis of periodontal bone loss in patients with osteoporosis.


Assuntos
Perda do Osso Alveolar , Osteoporose , Periodontite , Processo Alveolar , Densidade Óssea , Feminino , Humanos , Radiografia Panorâmica
6.
Beijing Da Xue Xue Bao Yi Xue Ban ; 51(6): 1085-1090, 2019 Dec 18.
Artigo em Chinês | MEDLINE | ID: mdl-31848509

RESUMO

OBJECTIVE: To explore the screening value of osteoporosis self-assessment tool for Asians (OSTA) and the optimal cut-off value in Chinese healthy physical examination population. METHODS: We selected a healthy physical examination population for bone mineral density screening at the Health Examination Center in Peking University Third Hospital from 2013 to 2016. Quantitative ultrasound (QUS) results were used as the gold standard, and T value ≤-2.5 was defined as osteoporosis patients. Diagnostic test methods were used to analyze the sensitivity, specificity, likelihood ratio and area under curve (AUC) of different cut points of OSTA. The screening accuracy of OSTA at different cut points was compared and the optimal cut-point value determined. RESULTS: A total of 5 833 subjects were included in the study, with an average age of (48.3±17.5) years and 2 594 women (44.5%). The QUS test showed 403 patients with osteoporosis (6.9% of the total population), 343 female osteoporosis patients (13.22% of the female population). In the whole age group, AUC at the international routine cut-off value (OSTA ≤-1) screening for osteoporosis was 0.815 (95%CI: 0.804-0.825), and screening accuracy was higher in the women (AUC=0.837, 95%CI: 0.823-0.851) than that in the men (AUC=0.767, 95%CI: 0.752-0.781; P<0.05). In the whole age group, when the optimal cut-off value was 0, its AUC 0.842 (95%CI: 0.832-0.851) was significantly higher than that when the cut-off value was -1 (P<0.01), and net reclassification improvement (NRI) increased by 5.5%. In the 40 to 65-year-old group, when OSTA cut-off value ≤0, the screening accuracy was significantly higher (NRI=19.5%, P=0.003) than that when it was -1. CONCLUSION: The OSTA screening tool had good osteoporosis screening value in healthy people, and the screening accuracy in women is higher than that in men. Increasing the screening cut-off value of OSTA would be helpful to improve the screening accuracy in the whole and 40 to 65-year-old population. There may be different optimal cut-off values for different age group population.


Assuntos
Osteoporose , Autoavaliação , Absorciometria de Fóton , Adulto , Idoso , Grupo com Ancestrais do Continente Asiático , Densidade Óssea , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Exame Físico , Medição de Risco , Sensibilidade e Especificidade
7.
Adv Exp Med Biol ; 1182: 263-269, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31777023

RESUMO

The anti-osteoporosis effect of Ganoderma lucidum (G. lucidum, Lingzhi) is closely associated with inhibition of osteoclastogenesis in the charge of osteoclasts. This article reviewed the anti-osteoporosis effect of Ganoderma and its active components, including a kind of triterpenoids, a polysaccharide and a protein named Ling Zhi-8 (LZ-8). Triterpenoids are a kind of active compounds as candidates for the treatment of osteoporosis. Among these, ganoderic acids are currently considered as the most important and potential components, and their structure-activity relationship highlights the essential group to hamper osteoclast differentiation. The data confirmed that the active compounds isolated from triterpenoids and meroterpenoids could suppress bone resorption of osteoclast via RANKL/RANK pathway and/or its downstream signaling transduction related to ERK, JNK and p38 MAPKs, contributing to inhibition of the level of c-Fos and NFATc1, two key target genes of osteoclast for osteoclastogenesis. However, the comprehensive mechanism remains to be elucidated in the future.


Assuntos
Produtos Biológicos/farmacologia , Osteogênese/efeitos dos fármacos , Osteoporose/tratamento farmacológico , Reishi/química , Diferenciação Celular , Humanos , Osteoclastos/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos
8.
Sichuan Da Xue Xue Bao Yi Xue Ban ; 50(5): 679-683, 2019 Sep.
Artigo em Chinês | MEDLINE | ID: mdl-31762237

RESUMO

OBJECTIVE: To test the effects of Guben Zenggu Decoction on bone metabolism and bone microstructure in ovariectomized rats for the purpose of preventing and treating postmenopausal osteoporosis. METHODS: Osteoporosis rat models were established by ovariectomy. The model rats were randomly divided into control, estradiol valerate treatment, and Guben Zenggu Decoction treatment groups with high, medium and low dosages. After 12 weeks of treatments, 10 rats from each group were randomly selected for cardiac blood sampling after abdominal anesthesia. The serum levels of estradiol (E2), osteocalcin (BGP), carboxyterminal of type Ⅰ procollagen (PICP), collagen type Ⅰ pyridine crosslinking peptide (ICTP) and acid tartaric acid phosphatase-5b (TRAP-5b) were determined by ELISA. Bone histomorphometric analysis was performed on the right femoral specimen of rats using micro-CT imaging. RESULTS: The models rats had lower levels of E2, bone alkaline phosphatase (BALP) and relative bone volume fraction (BV/TV), trabecular thickness (Tb.Th), number of trabeculae (Tb.N) and connectivity density (Conn.D), and higher levels of BGP, ICTP, PICP, TRAP-5b and degree of trabecular separation (Tb.Sp), structural model index (SMI) than their normal counterparts (P < 0.05). Estradiol valerate and Guben Zenggu Decoction treatments increased the levels of E2, BALP, BV/TV, Tb.Th, Tb.N, and Conn.D significantly (P < 0.05). Higher doses of Guben Zenggu Decoction resulted in higher changes (P < 0.05). CONCLUSION: Guben Zenggu Decoction can improve bone metabolism and bone micro-structure in ovariectomized rats, thus playing a preventive and therapeutic role in postmenopausal osteoporosis.


Assuntos
Densidade Óssea/efeitos dos fármacos , Osso e Ossos/metabolismo , Medicamentos de Ervas Chinesas/farmacologia , Osteoporose/tratamento farmacológico , Animais , Osso e Ossos/efeitos dos fármacos , Feminino , Ovariectomia , Distribuição Aleatória , Ratos , Ratos Sprague-Dawley , Microtomografia por Raio-X
10.
Recurso na Internet em Português | LIS - Localizador de Informação em Saúde, LIS-bvsms | ID: lis-LISBR1.1-46834

RESUMO

Viver com medo de cair e quebrar um osso a qualquer momento é parte da realidade das pessoas que vivem com a osteoporose. A doença, caracterizada pela diminuição da massa óssea, faz com que os ossos fiquem mais frágeis, aumentando a possibilidade de fraturas.


Assuntos
Osteoporose
11.
Prague Med Rep ; 120(2-3): 84-94, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31586507

RESUMO

Ageing is associated with the accumulation of damage to all the macromolecules within and outside cells leading to progressively more cellular and tissue defects and resulting in age-related frailty, disability and disease. As a result of the aging process the bone deteriorates in composition, structure and function. Age-related musculoskeletal losses are a major public health burden because they can cause physical disability and increased mortality. We tried to find out on a small set of old women, without risk factors for osteoporosis, what caused them the loss of bone minerals. All 492 women had just only one risk factor - the old age. Laboratory findings have shown a decreased serum C telopeptide and low serum alkaline phosphatase circulating markers, used to quantify bone resorption and formation, and very low level of vitamin D. Very low level of vitamin D that disrupted calcium absorption through the intestine, and decreased calcemia increased parathyroid hormone levels with resulting bone effect. The manifestation of physiological aging is worsening eyesight, peripheral neuropathy, depression, worsening of physical condition, skin aging, sarcopenia and bone mineral loss. Senile osteoporosis, which is not caused by known risk factors for osteoporosis, does not appear to be a separate disease, but is part of the physiological process of aging. Treatment of senile osteoporosis should be focused on the control of secondary hyperparathyroidism by administration of vitamin D and calcium. The risk of fractures in the advanced age is determined by a large number of factors ranging from hazards in the home environment to frailty and poor balance.


Assuntos
Envelhecimento/sangue , Envelhecimento/patologia , Fosfatase Alcalina/sangue , Densidade Óssea , Cálcio/metabolismo , Colágeno Tipo I/sangue , Feminino , Humanos , Osteogênese , Osteoporose/sangue , Hormônio Paratireóideo/sangue , Peptídeos/sangue , Vitamina D/sangue
12.
Wiad Lek ; 72(9 cz 1): 1641-1645, 2019.
Artigo em Polonês | MEDLINE | ID: mdl-31586976

RESUMO

Basing on European, American and Polish recommendation reviewed are strategy of treatment of osteoporosis. In Poland, rules of reimbursement reinforced general use of antiresorbtive drugs (bisphosponates, demosumab) in the treatment of osteoporosis. For effective therapy the key points are keeping the patient in the treatment and treatment monitoring with potential use of densitometry and bone markers.


Assuntos
Conservadores da Densidade Óssea/uso terapêutico , Osteoporose/tratamento farmacológico , Quimioterapia Combinada , Humanos , Polônia
13.
Life Sci ; 237: 116890, 2019 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-31606379

RESUMO

AIMS: Telmisartan (TEL), an angiotensin II type I receptor blocker and PPARγ partial agonist, has been used for to treat hypertension. It is known that PPARγ activation induces bone loss. Therefore, we evaluate the effects of telmisartan on PPARγ protein expression, biomechanics, density and bone microarchitecture of femurs and lumbar vertebrae in SHR ovariectomized animals, a model of hypertension in which preexisting bone impairment has been demonstrated. MAIN METHODS: SHR females (3 months old) were distributed into four groups: sham (S), sham + TEL (ST), OVX (C) and OVX + TEL (CT). TEL (5 mg/kg/day) or vehicle were administered according to the groups. After the protocol, blood pressure was measured and density, microarchitecture and biomechanics of bone were analyzed. Western blotting analysis was performed to evaluate PPARγ protein expression in the bones. KEY FINDINGS: Castration induced a deleterious effect on mineral density and trabecular parameters, with telmisartan enhancing such effects. Telmisartan increased PPARγ levels, which were at their highest when the treatment was combined with castration. As to biomechanical properties, telmisartan reduced the stiffness in the castration group (CT vs. S or C group), as well as resilience and failure load in ST group (vs. all others groups). SIGNIFICANCE: These results demonstrated that telmisartan compromised bone density and microarchitecture in animals that shows preexisting osteoporotic bone disorders, probably via mechanisms associated with increased PPARγ. If this translates to humans, a need for greater caution in the use of telmisartan by patients that have preexisting bone problems, as in the postmenopausal period, may be in order.


Assuntos
Bloqueadores do Receptor Tipo 1 de Angiotensina II/farmacologia , Doenças Ósseas/tratamento farmacológico , Osso Esponjoso/efeitos dos fármacos , Regulação da Expressão Gênica/efeitos dos fármacos , Osteoporose/tratamento farmacológico , PPAR gama/metabolismo , Telmisartan/farmacologia , Animais , Densidade Óssea/efeitos dos fármacos , Doenças Ósseas/metabolismo , Doenças Ósseas/fisiopatologia , Osso Esponjoso/diagnóstico por imagem , Osso Esponjoso/patologia , Feminino , Osteoporose/metabolismo , Osteoporose/fisiopatologia , PPAR gama/genética , Ratos , Ratos Endogâmicos SHR , Tomografia Computadorizada por Raios X
14.
Clin Exp Rheumatol ; 37 Suppl 120(5): 73-87, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31621570

RESUMO

Osteoarthritis (OA) is a disease of the whole joint, including synovium, bone and cartilage. OA is a slow degenerative and very heterogeneous disease, with both varying levels of disease activity and progression. Biomarkers are urgently needed to assist drug developers in selecting and developing the projects with the highest chance of success. Biomarkers for enrichment of clinical studies, early efficacy as well as other diagnostic tools are needed. Osteoporosis and OA have many similarities. In osteoporosis an armamentarium of treatments are now available with high clinical efficacy and well-described effects on biomarkers. Possibly, lessons learned from the osteoporosis field in the use of biomarkers may be applied in the OA field, from both technical and scientific perspectives. To help guide the way, the FDA has recently published the BEST guidelines, to facilitate obtaining a common vocabulary to assist biomarker researchers. In the current review, we will review the biomarkers of OA, with emphasis on bone, cartilage and synovial biomarkers, and draw clear perspectives to the use of biomarkers for drug development and clinical practice in the osteoporosis field.


Assuntos
Biomarcadores/análise , Cartilagem Articular , Osteoartrite , Biomarcadores/metabolismo , Cartilagem Articular/metabolismo , Humanos , Osteoartrite/metabolismo , Osteoporose/metabolismo , Membrana Sinovial
15.
Wiad Lek ; 72(9 cz 2): 1834-1838, 2019.
Artigo em Polonês | MEDLINE | ID: mdl-31622275

RESUMO

The adipose and osseous tissue, although both derived from the connective tissues, perform different functions. In the common opinion, obesity might be a protective factor against bone loss and osteoporosis. The adipose tissue is a recognized major endocrine organ, producing a number of active biological substances, which affect the bone mass. Adipocyte and osteoblast are derived from the same mesenchymal stem cells. Therefore abnormal secretion of adipocytokines may play an important role not only in pathogenesis of the obesity, but also can influence the bone . It is supposed that obesity might have a protective effect on bone tissue in postmenopausal women, by increasing the load on the axial skeleton and because of its hormonal activity.


Assuntos
Tecido Adiposo/fisiopatologia , Osso e Ossos/fisiopatologia , Obesidade/patologia , Osteoporose/patologia , Adipocinas/fisiologia , Densidade Óssea , Feminino , Humanos , Células-Tronco Mesenquimais
16.
Int J Nanomedicine ; 14: 7839-7849, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31576127

RESUMO

Background: Nobiletin (NOB), a polymethoxy flavonoid, possesses anti-cancer and anti-inflammatory activities, has been reported that it played role in anti-osteoporosis treatment. However, previous research did not focus on practical use due to lack of hydrophilicity and cytotoxicity at high concentrations. The aim of this study was to develop a therapeutic formulation for osteoporosis based on the utilization of NOB. Methods: In this study, NOB-loaded poly(ethylene glycol)-block-poly(e-caprolactone) (NOB-PEG-PCL) was prepared by dialysis method. The effects on osteoclasts and anti-osteoporosis functions were investigated in a RANKL-induced cell model and ovariectomized (OVX) mice. Results: Dynamic light scattering and transmission electron microscopy examination results revealed that the NOB-PEG-PCL had a round shape, with a mean diameter around 124 nm. The encapsulation efficiency and drug loading were 76.34±3.25% and 7.60±0.48%, respectively. The in vitro release of NOB from NOB-PEG-PCL showed a remarkably sustained releasing characteristic and could be retained at least 48 hrs in pH 7.4 PBS. Anti-osteoclasts effects demonstrated that the NOB-PEG-PCL significantly inhibited the formation of tartrate-resistant acid phosphatase (TRAP)-positive multinuclear cells stimulated by RANKL. Furthermore, the NOB-PEG-PCL did not produce cytotoxicity on bone marrow-derived macrophages (BMMs). The mRNA expressions of genetic markers of osteoclasts including TRAP and cathepsin K were significantly decreased in the presence of NOB-PEG-PCL. In addition, the NOB-PEG-PCL inhibited OC differentiation of BMMs through RANKL-induced MAPK signal pathway. After administration of the NOB-PEG-PCL, NOB-PEG-PCL prevented bone loss and improved bone density in OVX mice. These findings suggest that NOB-PEG-PCL might have great potential in the treatment of osteoporosis. Conclusion: The results suggested that NOB-PEG-PCL micelles could effectively prevent NOB fast release from micelles and extend circulation time. The NOB-PEG-PCL delivery system may be a promising way to prevent and treat osteoporosis.


Assuntos
Reabsorção Óssea/tratamento farmacológico , Reabsorção Óssea/etiologia , Flavonas/uso terapêutico , Micelas , Osteoclastos/patologia , Osteogênese , Ovariectomia/efeitos adversos , Animais , Morte Celular/efeitos dos fármacos , Citocinas/metabolismo , Liberação Controlada de Fármacos , Feminino , Flavonas/química , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Camundongos Endogâmicos C57BL , Osteoclastos/efeitos dos fármacos , Osteogênese/efeitos dos fármacos , Osteoporose/tratamento farmacológico , Poliésteres/química , Polietilenoglicóis/química , Transdução de Sinais/efeitos dos fármacos
17.
Adv Exp Med Biol ; 1164: 153-160, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31576547

RESUMO

Skeletal aging begins after peak bone mass is reached; progressive bone loss then occurs. Peak bone mass may occur at different ages in different skeletal sites and varies between sexes. Accelerated loss of bone occurs in the perimenopausal period in women, whereas more gradual but progressive loss of bone occurs in aging men. Changes in bone quality as well as bone quantity occur during growth and subsequent aging. These include changes in bone microarchitecture which may differ between cortical and trabecular compartments and in different sites, and may impact on bone size and geometry. Changes in material properties of bone matrix may also occur with aging. Loss of bone quantity and altered bone quality with aging may weaken bones and culminate in osteoporosis with an increased risk of fractures. Both genetic and epigenetic mechanisms may predispose to osteoporosis. Cellular and molecular events underlie the alterations in bone quantity and quality. Osteoclastic bone resorption and osteoblastic bone formation, tightly regulated by hormones, growth factors, and cytokines, are organized in coordinated activities resulting in remodeling and modeling. Malignancies, and anti-neoplastic therapies, may impact on the cellular and molecular events in the aging skeleton and produce focal or diffuse skeletal lesions and fractures.


Assuntos
Envelhecimento , Reabsorção Óssea , Osso e Ossos , Densidade Óssea , Osso e Ossos/fisiologia , Feminino , Humanos , Masculino , Osteoporose , Fatores Sexuais
18.
Se Pu ; 37(8): 863-871, 2019 Aug 08.
Artigo em Chinês | MEDLINE | ID: mdl-31642257

RESUMO

Exosomes are tiny vesicles secreted by cells, can be important mediators of cell-to-cell communication, and play unique roles in disease diagnosis and treatment. Osteoporosis is a metabolic bone disease with high incidence in the elderly, characterized by low bone mineral density and deterioration of bone microstructure. Highly specific diagnostic methods capable of identifying early-stage osteoporosis are urgently needed. In this study, serum exosomes were comprehensively enriched and characterized. In total, 179 exosomal proteins were identified using liquid chromatography-mass spectrometry, most of which are involved in important biological processes such as defense and immune responses. Through label free quantification of serum exosomes, 188, 224, and 185 proteins were identified in the normal, osteopenia, and osteoporosis groups, respectively. Quantitative results also showed that 17 proteins were significantly (p <0.05) dysregulated in the osteoporosis and osteopenia groups, including Integrin ß 3, Integrin α 2 ß 1, Talin 1, and Gelsolin. This study provides potential molecular markers for osteoporosis studs and will contributes to the elucidating the pathogenesis of osteoporosis.


Assuntos
Exossomos , Osteoporose/sangue , Proteômica , Cromatografia Líquida , Humanos , Espectrometria de Massas
19.
Z Rheumatol ; 78(10): 904-909, 2019 Dec.
Artigo em Alemão | MEDLINE | ID: mdl-31654138

RESUMO

The occurrence of multiple vertebral fractures after discontinuation of denosumab in the treatment of osteoporosis has reopened the debate on the optimal treatment duration and drug holidays.In principle, there is a difference in this regard between the discontinuation of medications such as bisphosphonates and substances without bone retention such as selective estrogen receptor modulators (SERMs), denosumab or teriparatide. Even after the end of application bisphosphonates have a very long half-life in the bones. After cessation of drug intake there is a slow, slight increase of bone turnover markers. Even after cessation of the SERM raloxifene, a decline in bone density can be observed, as with the termination of teriparatide. In contrast to these osteoporosis medications, after cessation of denosumab, a steep and rapid increase in markers of bone resorption above baseline levels ("rebound") and a reduction in bone mineral density to initial values can be observed.Osteoporosis is a disease that carries an increased risk of fracture, which is reduced for the duration of osteoporosis treatment. In certain situations, the fracture risk is only temporarily raised. In these situations, cessation of the osteoporosis treatment is possible. Beyond these special clinical situations, however, osteoporosis needs to be addressed as a chronic disease with a permanently increased fracture risk and the indication for therapy should be evaluated according to the extent of the risk of fracture.What happens after discontinuation of anti-osteoporosis drugs? The various effects on bone turnover markers, bone mineral density and fracture incidence of the individual drug groups are presented in detail, as are the resulting recommendations of the task forces of the American Society of Bone and Mineral Research (ASBMR) and the European Calcified Tissue Society (ECTS).


Assuntos
Conservadores da Densidade Óssea , Osteoporose , Densidade Óssea , Conservadores da Densidade Óssea/uso terapêutico , Denosumab , Difosfonatos , Humanos , Osteoporose/tratamento farmacológico
20.
Bone Joint J ; 101-B(10): 1285-1291, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31564154

RESUMO

AIMS: Currently, periprosthetic fractures are excluded from the American Society for Bone and Mineral Research (ASBMR) definition of atypical femoral fracture (AFFs). This study aims to report on a series of periprosthetic femoral fractures (PFFs) that otherwise meet the criteria for AFFs. Secondary aims were to identify predictors of periprosthetic atypical femoral fractures (PAFFs) and quantify the complications of treatment. PATIENTS AND METHODS: This was a retrospective case control study of consecutive patients with periprosthetic femoral fractures between 2007 and 2017. Two observers identified 16 PAFF cases (mean age 73.9 years (44 to 88), 14 female patients) and 17 typical periprosthetic fractures in patients on bisphosphonate therapy as controls (mean age 80.7 years (60 to 86, 13 female patients). Univariate and multivariate analysis was performed to identify predictors of PAFF. Management and complications were recorded. RESULTS: Interobserver agreement for the PAFF classification was excellent (kappa = 0.944; p < 0.001). On univariate analysis compared with controls, patients with PAFFs had higher mean body mass indices (28.6 kg/m2 (sd 8.9) vs 21.5 kg/m2 (sd 3.3); p = 0.009), longer durations of bisphosphonate therapy (median 5.5 years (IQR 3.2 to 10.6) vs 2.4 years (IQR 1.0 to 6.4); p = 0.04), and were less likely to be on alendronate (50% vs 94%; p = 0.02) with an indication of secondary osteoporosis (19% vs 0%; p = 0.049). Duration of bisphosphonate therapy was an independent predictor of PAFF on multivariate analysis (R2 = 0.733; p = 0.05). Following primary fracture management, complication rates were higher in PAFFs (9/16, 56%) than controls (5/17, 29%; p = 0.178) with a relative risk of any complication following PAFF of 1.71 (95% confidence interval (CI) 0.77 to 3.8) and of reoperation 2.56 (95% CI 1.3 to 5.2). CONCLUSION: AFFs do occur in association with prostheses. Longer duration of bisphosphonate therapy is an independent predictor of PAFF. Complication rates are higher following PAFFs compared with typical PFFs, particularly of reoperation and infection. Cite this article: Bone Joint J 2019;101-B:1285-1291.


Assuntos
Artroplastia de Quadril/efeitos adversos , Difosfonatos/efeitos adversos , Osteoporose/tratamento farmacológico , Fraturas Periprotéticas/induzido quimicamente , Fraturas Periprotéticas/cirurgia , Idoso , Idoso de 80 Anos ou mais , Artroplastia de Quadril/métodos , Estudos de Casos e Controles , Intervalos de Confiança , Difosfonatos/uso terapêutico , Relação Dose-Resposta a Droga , Feminino , Fraturas do Fêmur/induzido quimicamente , Fraturas do Fêmur/cirurgia , Seguimentos , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Variações Dependentes do Observador , Osteoporose/complicações , Fraturas Periprotéticas/diagnóstico por imagem , Estudos Retrospectivos , Medição de Risco , Fatores de Tempo , Estados Unidos
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