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1.
Medicine (Baltimore) ; 99(39): e22172, 2020 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-32991410

RESUMO

Osteoporosis is a severe chronic skeletal disorder that increases the risks of disability and mortality; however, the mechanism of this disease and the protein markers for prognosis of osteoporosis have not been well characterized. This study aims to characterize the imbalanced serum proteostasis, the disturbed pathways, and potential serum markers in osteoporosis by using a set of bioinformatic analyses. In the present study, the large-scale proteomics datasets (PXD006464) were adopted from the Proteome Xchange database and processed with MaxQuant. The differentially expressed serum proteins were identified. The biological process and molecular function were analyzed. The protein-protein interactions and subnetwork modules were constructed. The signaling pathways were enriched. We identified 209 upregulated and 230 downregulated serum proteins. The bioinformatic analyses revealed a highly overlapped functional protein classification and the gene ontology terms between the upregulated and downregulated protein groups. Protein-protein interactions and pathway analyses showed a high enrichment in protein synthesis, inflammation, and immune response in the upregulated proteins, and cell adhesion and cytoskeleton regulation in the downregulated proteins. Our findings greatly expand the current view of the roles of serum proteins in osteoporosis and shed light on the understanding of its underlying mechanisms and the discovery of serum proteins as potential markers for the prognosis of osteoporosis.


Assuntos
Mineração de Dados/métodos , Osteoporose/sangue , Proteoma/fisiologia , Biomarcadores , Adesão Celular/fisiologia , Biologia Computacional , Citoesqueleto/metabolismo , Regulação para Baixo , Humanos , Mediadores da Inflamação/metabolismo , Mapas de Interação de Proteínas/fisiologia , Proteômica , Regulação para Cima
2.
J Bone Miner Metab ; 38(6): 806-818, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32656644

RESUMO

INTRODUCTION: Our previous studies demonstrated that a high bone turnover state under osteoporotic changes decreased the threshold of skeletal pain. Recent studies reported that the incidence of joint pain due to osteoarthritis (OA) in postmenopausal women was higher than that in males even with the same radiographic OA grade. The aim of this study was to evaluate whether a high bone turnover state affects the induction of pain-like behaviors in mild OA model mice. MATERIALS AND METHODS: We established mild OA model mice with accompanying osteoporotic changes by monosodium iodoacetate injection after ovariectomy. We assessed pain-like behaviors by von Frey test and paw-flick test; histological changes in OA joints; the expression of Runx2, Osterix, Osteocalcin, and Rankl; bone micro-architecture by µCT and measured serum tartrate-resistant acid-phosphatase 5b levels in the model mice. RESULTS: Pain-like behaviors in mice with OA and osteoporotic changes were significantly increased in comparison with those in OA mice without osteoporotic changes. The severity of histological OA changes did not differ significantly between the OA mice with and without osteoporotic changes. Bisphosphonate significantly improved pain-like behaviors accompanied with improvement in the high bone turnover state in the OA mice with osteoporosis, while it had no significant effect on pain-like behaviors in the OA mice without osteoporosis. In addition, the improvement was maintained for more than 4 weeks even after the discontinuation of bisphosphonate treatment. CONCLUSION: These results indicated that a high bone turnover state under osteoporotic changes could affect the induction of pain-like behaviors in mild OA model mice.


Assuntos
Comportamento Animal , Remodelação Óssea , Osteoartrite/complicações , Osteoporose/complicações , Osteoporose/fisiopatologia , Dor/etiologia , Animais , Remodelação Óssea/efeitos dos fármacos , Cartilagem/patologia , Diferenciação Celular/efeitos dos fármacos , Diferenciação Celular/genética , Inibidores de Ciclo-Oxigenase/farmacologia , Difosfonatos/farmacologia , Modelos Animais de Doenças , Feminino , Regulação da Expressão Gênica/efeitos dos fármacos , Iodoacetatos , Masculino , Camundongos Endogâmicos C57BL , Osteoartrite/sangue , Osteoartrite/patologia , Osteoartrite/fisiopatologia , Osteoblastos/efeitos dos fármacos , Osteoblastos/metabolismo , Osteoblastos/patologia , Osteocalcina/genética , Osteocalcina/metabolismo , Osteoclastos/efeitos dos fármacos , Osteoclastos/metabolismo , Osteoclastos/patologia , Osteoporose/sangue , Ovariectomia , Dor/sangue , Fosfatase Ácida Resistente a Tartarato/sangue , Microtomografia por Raio-X
3.
J Bone Miner Metab ; 38(6): 894-902, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32656645

RESUMO

INTRODUCTION: Rapid descent in bone mineral density (BMD) and ascent in bone turnover marker (BTM) occur within the short period following denosumab (Dmab) discontinuation. In addition, the incidence of vertebral fracture also rises within the short period. The purpose of this study is to investigate the effects of sequential therapy using zoledronic acid (ZOL) on any adverse events after Dmab discontinuation. MATERIALS AND METHODS: This study was a multicenter retrospective observational study, and the subjects were osteoporosis patients who visited our institutions between 2013 and 2018. We performed sequential therapy using ZOL for 30 patients who had difficulty continuing Dmab, due to physical or social reasons, and investigated the fracture incidence and BMD/BTM changes at 4 time points (at the start of Dmab, the start of ZOL, 6 months after ZOL and 12 months after ZOL). RESULTS: No new vertebral/nonvertebral fractures were observed at each time point after switching from Dmab to ZOL in any of the 30 patients. The BMD/BTM changes were evaluated in 18 of the 30 cases, since all data of lumbar/femoral neck BMDs and TRACP-5b at 4 time points was only available in 18 cases. BMDs significantly increased at each time point compared with that at the start of Dmab. Serum TRACP-5b significantly decreased at each time point compared with that at the start of Dmab. CONCLUSION: It was suggested that sequential therapy using ZOL could suppress the decrease of BMD, and increase of BTM, if the period of Dmab administration was less than 3 years.


Assuntos
Denosumab/uso terapêutico , Suspensão de Tratamento , Ácido Zoledrônico/uso terapêutico , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/sangue , Densidade Óssea/efeitos dos fármacos , Conservadores da Densidade Óssea/efeitos adversos , Conservadores da Densidade Óssea/uso terapêutico , Remodelação Óssea/efeitos dos fármacos , Denosumab/efeitos adversos , Feminino , Fraturas Ósseas/sangue , Fraturas Ósseas/epidemiologia , Fraturas Ósseas/fisiopatologia , Humanos , Masculino , Pessoa de Meia-Idade , Osteoporose/sangue , Estudos Retrospectivos , Fosfatase Ácida Resistente a Tartarato/sangue , Ácido Zoledrônico/efeitos adversos
4.
PLoS Biol ; 18(6): e3000731, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32479501

RESUMO

The nuclear lamina protein lamin A/C is a key component of the nuclear envelope. Mutations in the lamin A/C gene (LMNA) are identified in patients with various types of laminopathy-containing diseases, which have features of accelerated aging and osteoporosis. However, the underlying mechanisms for laminopathy-associated osteoporosis remain largely unclear. Here, we provide evidence that loss of lamin A/C in skeletal muscles, but not osteoblast (OB)-lineage cells, results in not only muscle aging-like deficit but also trabecular bone loss, a feature of osteoporosis. The latter is due in large part to elevated bone resorption. Further cellular studies show an increase of osteoclast (OC) differentiation in cocultures of bone marrow macrophages/monocytes (BMMs) and OBs after treatment with the conditioned medium (CM) from lamin A/C-deficient muscle cells. Antibody array screening analysis of the CM proteins identifies interleukin (IL)-6, whose expression is markedly increased in lamin A/C-deficient muscles. Inhibition of IL-6 by its blocking antibody in BMM-OB cocultures diminishes the increase of osteoclastogenesis. Knockout (KO) of IL-6 in muscle lamin A/C-KO mice diminishes the deficits in trabecular bone mass but not muscle. Further mechanistic studies reveal an elevation of cellular senescence marked by senescence-associated beta-galactosidase (SA-ß-gal), p16Ink4a, and p53 in lamin A/C-deficient muscles and C2C12 muscle cells, and the p16Ink4a may induce senescence-associated secretory phenotype (SASP) and IL-6 expression. Taken together, these results suggest a critical role for skeletal muscle lamin A/C to prevent cellular senescence, IL-6 expression, hyperosteoclastogenesis, and trabecular bone loss, uncovering a pathological mechanism underlying the link between muscle aging/senescence and osteoporosis.


Assuntos
Envelhecimento/patologia , Lamina Tipo A/deficiência , Músculo Esquelético/patologia , Osteoporose/patologia , Animais , Anticorpos Bloqueadores/farmacologia , Fenômenos Biomecânicos , Reabsorção Óssea/complicações , Reabsorção Óssea/patologia , Osso Esponjoso/efeitos dos fármacos , Osso Esponjoso/patologia , Diferenciação Celular/efeitos dos fármacos , Senescência Celular/efeitos dos fármacos , Interleucina-6/metabolismo , Camundongos Knockout , Fibras Musculares Esqueléticas/efeitos dos fármacos , Fibras Musculares Esqueléticas/metabolismo , Músculo Esquelético/efeitos dos fármacos , Tamanho do Órgão/efeitos dos fármacos , Osteoclastos/efeitos dos fármacos , Osteoclastos/patologia , Osteogênese/efeitos dos fármacos , Osteoporose/sangue , Fenótipo
5.
Medicine (Baltimore) ; 99(26): e20864, 2020 Jun 26.
Artigo em Inglês | MEDLINE | ID: mdl-32590789

RESUMO

Osteoporosis is defined as a metabolic skeletal disease characterized by a decrease of the bone mass per unit volume, caused by a variety of reasons. Increasing evidence indicate that the host inflammatory response was correlated with the occurrence and development of osteoporosis, and it has been recognized that T lymphocytes and B lymphocytes play a critical role in pathogenesis of inflammatory bone disease. Between January 2018 and December 2018, retrospective analysis of 487 patients (exclusion of patients with recent infections and hematologic disorders whose leukocyte counts or classifications are markedly abnormal) who underwent bone mineral density (BMD) examinations in Huzhou Central Hospital. The patients were divided into normal bone density group, osteopenia group, and osteoporosis group according to the T score of BMD in the left femoral neck, respectively. Statistics of the lymphocyte ratio and the monocyte ratio in the blood routine examination results during the same period were performed so as to make a comparison of the differences among the groups. The correlation of the lymphocyte ratio and monocyte ratio with the T score of BMD in the left femoral neck was also analyzed. The difference between neutrocyte ratio lymphocyte ratio and the monocyte ratio was statistically significant in both males and females among the normal bone density group, osteopenia group and osteoporosis group (P < .01 or P < .05). Inflammation plays an important role in the progression of osteoporosis. By monitoring these three indicators in blood routine examination, early intervention for osteoporosis may become possible.


Assuntos
Biomarcadores/análise , Células Sanguíneas/microbiologia , Osteoporose/diagnóstico , Idoso , Biomarcadores/sangue , Índice de Massa Corporal , Densidade Óssea/fisiologia , China , Correlação de Dados , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Osteoporose/sangue , Estudos Retrospectivos , Fatores de Risco
6.
J Bone Miner Res ; 35(6): 1009-1013, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32406536

RESUMO

Osteoporosis is a chronic condition that reflects reduced bone strength and an associated increased risk for fracture. As a chronic condition, osteoporosis generally requires sustained medical intervention(s) to limit the risks for additional bone loss, compromise of skeletal integrity, and fracture occurrence. Further complicating this issue is the fact that the abrupt cessation of some therapies can be associated with an increased risk for harm. It is in this context that the COVID-19 pandemic has brought unprecedented disruption to the provision of health care globally, including near universal requirements for social distancing. In this Perspective, we provide evidence, where available, regarding the general care of patients with osteoporosis in the COVID-19 era and provide clinical recommendations based primarily on expert opinion when data are absent. Particular emphasis is placed on the transition from parenteral osteoporosis therapies. It is hoped that these recommendations can be used to safely guide care for patients with osteoporosis until a return to routine clinical care standards is available. © 2020 American Society for Bone and Mineral Research.


Assuntos
Infecções por Coronavirus , Osteoporose/terapia , Pandemias , Pneumonia Viral , Absorciometria de Fóton , Biomarcadores/sangue , Densidade Óssea , Conservadores da Densidade Óssea/administração & dosagem , Conservadores da Densidade Óssea/efeitos adversos , Conservadores da Densidade Óssea/uso terapêutico , Continuidade da Assistência ao Paciente , Infecções por Coronavirus/sangue , Infecções por Coronavirus/complicações , Denosumab/efeitos adversos , Denosumab/uso terapêutico , Gerenciamento Clínico , Esquema de Medicação , Terapia de Reposição de Estrogênios/efeitos adversos , Fraturas Espontâneas/prevenção & controle , Fraturas Espontâneas/terapia , Serviços de Assistência Domiciliar , Humanos , Imunossupressão/efeitos adversos , Osteoporose/sangue , Osteoporose/diagnóstico por imagem , Osteoporose/tratamento farmacológico , Pneumonia Viral/sangue , Pneumonia Viral/complicações , Cloridrato de Raloxifeno/efeitos adversos , Cloridrato de Raloxifeno/uso terapêutico , Recidiva , Telemedicina , Trombofilia/induzido quimicamente , Trombofilia/etiologia , Procedimentos Desnecessários
7.
Ann Hematol ; 99(8): 1873-1882, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32451708

RESUMO

Bone turnover markers (BTMs) are useful parameters for assessing fracture risk and unlike bone mineral density (BMD), can be measured at any institution. However, BTM values have not been established in patients post-allogeneic hematopoietic stem cell transplantation (allo-HSCT). We investigated the practicality of BTMs in patients who underwent allo-HSCT by measuring levels of the serum bone resorption marker, tartrate-resistant acid phosphatase-5b (TRACP-5b), and the bone formation marker, bone-specific alkaline phosphatase (BAP), together with BMD, 1 month before and 6 months after allo-HSCT. Patients were classified into either the alendronate group (n = 14) if alendronate treatment (35 mg orally per week) was administered before allo-HSCT or within 1 month after allo-HSCT, or the control group (n = 16), in which patients did not receive alendronate treatment. Despite the high frequency of corticosteroids users in the alendronate group (71.4 vs. 18.9%; p < 0.01), the mean percentage changes in BMD at the lumbar spine (- 2.9 vs. - 3.1%; p = 0.44) and femoral neck (- 3.2 vs. - 4.1%; p = 1.00), TRACP-5b levels (- 4.8 vs. 9.9%; p = 0.45), and BAP levels (6.9 vs. 1.0%; p = 0.85) during 6 months did not differ significantly between the alendronate and control groups. Additionally, the percentage changes in BMD at the lumbar spine were negatively associated with the TRACP-5b levels 6 months after allo-HSCT (p = 0.03, r = 0.40). Our results indicate the possible effectiveness of alendronate treatment in allo-HSCT patients. BTM levels could be useful to monitor the BMD changes.


Assuntos
Fosfatase Alcalina/sangue , Densidade Óssea , Remodelação Óssea , Transplante de Células-Tronco Hematopoéticas , Osteoporose/sangue , Fosfatase Ácida Resistente a Tartarato/sangue , Adulto , Idoso , Alendronato/administração & dosagem , Aloenxertos , Biomarcadores/sangue , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Osteoporose/tratamento farmacológico , Osteoporose/etiologia
8.
Clin Interv Aging ; 15: 501-518, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32308378

RESUMO

Serum biomarkers of osteoarticular diseases have been in the limelight of current clinical research trends. Laboratory validation of defined and candidate biomarkers for both osteoarthritis and osteoporosis is of key importance for future decisional algorithms in the diagnosis, monitoring, and prognosis of these diseases. The current guidelines recommend the use of collagen degradation remnants, eg, CTX-I and CTX-II, in the complementary diagnosis of both osteoporosis and osteoarthritis. Besides the collagen degradation markers, enzymes that regulate bone and articular metabolism are useful in the clinical evaluation of osteoarticular pathologies. Along these, several other recommended and new nominee molecules have been recently studied. Wnts and Wnt-related molecules have a cardinal role in the bone-joint homeostasis, making them a promising target not only for pharmaceutical modulation, but also to be considered as soluble biomarkers. Sclerostin and dickkopf, two inhibitor molecules of the Wnt/ß-catenin signaling, might have a dual role in the assessment of the clinical manifestations of the osteoarticular unit. In osteoarthritis, besides fragments of collagen type II many pathway-related molecules have been studied and proposed for biomarker validation. The most serious limitation is that a significant proportion of studies lack statistical power due to the reduced number of cases enrolled. Serum biomarkers of bone and joint turnover markers represent an encouraging possibility for the diagnosis and prognosis of osteoarticular diseases, although further studies and laboratory validations should be carried out as to solely rely on them.


Assuntos
Osteoartrite/sangue , Osteoporose/sangue , Biomarcadores , Osso e Ossos/metabolismo , Colágeno Tipo I/sangue , Colágeno Tipo II/sangue , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Peptídeos/sangue , Via de Sinalização Wnt/fisiologia
9.
Maturitas ; 135: 47-52, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32252964

RESUMO

OBJECTIVE: With the current aging of the world's population, primary hyperparathyroidism (PHPT) is increasingly detected in the elderly. Yet data on the presentation and outcome of PHPT in this group are scarce. The objective was to describe a cohort of patients aged 75 years or more with PHPT observed in our endocrine clinic. STUDY DESIGN: A retrospective analysis of medical records in an endocrine clinic at a tertiary hospital. We evaluated 182 patients with PHPT, aged 75 years or more at their last follow-up, all diagnosed at age 65 or more. Laboratory data were compared at diagnosis and last follow-up. RESULTS: Mean age at diagnosis was 73 ± 4 years, last follow-up was at 83 ± 4 years, and mean follow-up was 11.3 ± 5.5 years. Osteoporosis, fractures, and nephrolithiasis were diagnosed in 114(63 %), 84(46 %), and 43(24 %) patients, respectively. Overall, 150 patients had an indication for surgery; of them, the 29 who underwent parathyroidectomy were younger than the non-operated patients and had higher rates of hypercalciuria. During the follow-up of the 141 patients who did not undergo operation, serum and urinary calcium levels significantly had decreased, and vitamin D level had increased at last visit (10.4 ± 0.5 mg/dl, 161 ± 70 mg/24 h, 69 ± 17 nmol/l, p < 0.01 respectively) compared with levels at diagnosis (10.6 ± 0.2 mg/dl, 223 ± 95 mg/24 h, 53 ± 15 nmol/l, respectively, p = 0.001). Overall, 38 of the 182 patients (20 %) died during follow-up; these patients were significantly older at diagnosis (76 ± 5 vs. 72 ± 4 years) but there were no differences in laboratory variables. CONCLUSIONS: While most patients had a formal indication for surgery, few underwent parathyroidectomy. Serum and urinary calcium significantly decreased during follow-up in patients who did not undergo surgery. Our data are reassuring and support at least the consideration of conservative treatment for these patients.


Assuntos
Tratamento Conservador , Hiperparatireoidismo Primário/terapia , Idoso , Idoso de 80 Anos ou mais , Cálcio/sangue , Cálcio/urina , Feminino , Fraturas Ósseas/sangue , Fraturas Ósseas/urina , Humanos , Hiperparatireoidismo Primário/sangue , Hiperparatireoidismo Primário/urina , Masculino , Nefrolitíase/sangue , Nefrolitíase/terapia , Nefrolitíase/urina , Osteoporose/sangue , Osteoporose/terapia , Osteoporose/urina , Paratireoidectomia , Estudos Retrospectivos , Vitamina D/sangue
10.
Arch Osteoporos ; 15(1): 43, 2020 03 12.
Artigo em Inglês | MEDLINE | ID: mdl-32166543

RESUMO

In two population-based study of middle-aged and older people, we investigated if platelet count was associated with bone mineral density and determined whether the association remained over time. Highest platelet counts within the normal range are significantly associated with osteopenia and osteoporosis in middle-aged and elderly people. PURPOSE: Recently, platelets were found to play a role in bone remodeling. However, data on the association between platelet count and osteoporosis are lacking. Our study aimed to investigate the association between platelet counts, osteopenia, and osteoporosis in middle-aged and elderly Koreans. METHODS: We analyzed cross-sectional data from 5181 adults (postmenopausal women and men over 50 years of age) in the 2008-2011 Korea National Health and Nutrition Examination Survey (KNHANES) and longitudinal prospective data from 3312 adults over 50 years of age in the Korean Genome and Epidemiology Study (KoGES). Bone mineral density (BMD) was measured using dual-energy X-ray absorptiometry in the KNHANES and quantitative ultrasound in the KoGES. The platelet counts were categorized into quintiles within normal ranges (150-450 × 103 µL). The associations between platelet counts, osteopenia, and osteoporosis were estimated using a multinomial logistic model. RESULTS: BMD of the femur neck, total femur, and lumbar spine all decreased with increasing platelet counts. The cut-off points of the platelet counts to differentiate normal BMD from osteopenia and osteopenia from osteoporosis were 217 × 103/µL and 269 × 103/µL, respectively. The odds ratios (95% confidence intervals) in the highest platelet quartile were 1.39 (1.03-1.88) for osteopenia and 1.60 (1.07-2.37) for osteoporosis after adjusting for confounding factors. The distal radius T-score was significantly decreased in the highest platelet tertile group at a follow-up of 10 years. CONCLUSION: Highest platelet counts within the normal range are significantly associated with osteopenia and osteoporosis in middle-aged and elderly people.


Assuntos
Densidade Óssea , Doenças Ósseas Metabólicas/sangue , Osteoporose/sangue , Contagem de Plaquetas/estatística & dados numéricos , Absorciometria de Fóton/métodos , Idoso , Idoso de 80 Anos ou mais , Doenças Ósseas Metabólicas/epidemiologia , Estudos Transversais , Feminino , Fêmur/diagnóstico por imagem , Colo do Fêmur/diagnóstico por imagem , Humanos , Modelos Logísticos , Vértebras Lombares/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade , Inquéritos Nutricionais , Razão de Chances , Osteoporose/epidemiologia , Estudos Prospectivos , República da Coreia/epidemiologia
11.
Toxicology ; 436: 152412, 2020 04 30.
Artigo em Inglês | MEDLINE | ID: mdl-32145347

RESUMO

We investigated the effects of Kalach 360 SL (KL), Glyphosate (G)-based herbicide, on bone tissue in different groups of female Wistar rats. Group 1 (n = 6) received a standard diet and served as a control, groups 2 and 3 (n = 6 each) received 0.07 ml (D1: 126 mg/Kg) and 0.175 ml (D2: 315 mg/Kg) of KL dissolved in the water for 60 days. The plasma was used to examine the metabolic balance markers (calcium, phosphorus, phosphatase alkaline (PAL), and vitamin D (vit D) and hormonal status (oestrogen and thyroid hormones). As a result, sub-chronic exposure to KL induced a perturbation of bone metabolism (calcium and phosphorus) and hormonal status disturbance. The histological and immunohistochemical study of the thyroid gland revealed a disturbance in morphological structure and thyroid cells function. Moreover, the KL disrupting eff ;ect on thyroid function was investigated by measuring changes in plasma levels of thyroid hormones. Free triiodothyronine (FT3) and thyroxine (FT4) were decreased in female rats breast-fed from rats treated with D and D2 of KL. This eff ;ect was associated with an increase in the plasma level of thyroid-stimulating hormone (TSH). Thus, that KL leads to hypothyroidism. Decrease in levels of oestrogen and thyroid dysfunction led to a disruption in the skeletal bone. The histological study and SEM in bone results allowed us to observe, in rats exposed to KL, the thinning and discontinuity of bone trabecular with a significant decrease in the number of nodes (intertrabecular links).In conclusion, KL sub-chronic exposure caused an aspect of osteoporosis.


Assuntos
Densidade Óssea/efeitos dos fármacos , Remodelação Óssea/efeitos dos fármacos , Fêmur/efeitos dos fármacos , Glicina/análogos & derivados , Herbicidas/toxicidade , Animais , Biomarcadores/sangue , Estrogênios/sangue , Feminino , Fêmur/metabolismo , Fêmur/ultraestrutura , Glicina/toxicidade , Hipotireoidismo/sangue , Hipotireoidismo/induzido quimicamente , Hipotireoidismo/patologia , Osteoporose/sangue , Osteoporose/induzido quimicamente , Osteoporose/patologia , Ratos Wistar , Glândula Tireoide/efeitos dos fármacos , Glândula Tireoide/metabolismo , Glândula Tireoide/patologia , Hormônios Tireóideos/sangue
12.
Intern Med ; 59(10): 1247-1256, 2020 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-32101831

RESUMO

Objective With the aging of society, both osteoporosis and fatty liver disease (FLD) are becoming important issues. However, the relationship between osteoporosis and FLD remains controversial. We investigated the association between bone metabolism and FLD in a Japanese community in a cross-sectional study. Methods A total of 1,020 participants were enrolled in a health survey. FLD was diagnosed by ultrasonography. Bone metabolism was evaluated based on bone mineral density (BMD), which was assessed using dual-energy X-ray absorptiometry, and with the bone formation index (total type I procollagen N-terminal propeptide/bone-alkaline phosphatase ratio; P1NP/BAP ratio) and the bone resorption index (crosslinked N-telopeptide of type I collagen/tartrate-resistant acid phosphatase-5b ratio; NTx/TRACP-5b ratio) calculated from serum bone turnover markers. Results The BMD (percentage of the young adult mean) was the same level in both male and female participants with and without FLD. Both men and women showed an age-dependent decrease in their bone formation index and bone resorption index values. Men of ≥70 years of age and women of 60-69 years of age with FLD had significantly lower bone formation index values and higher bone resorption index values. However, similar findings were not seen in women of ≥70 years of age. Conclusion Although the BMD levels were the same, regardless of the presence or absence of FLD, elderly participants with FLD showed decreased bone formation and increased bone resorption, with sex differences. Because our results suggest that FLD in elderly individuals is detrimental for bone metabolism, and that it leads to bone loss and osteoporosis, further studies using a cohort population are warranted.


Assuntos
Envelhecimento/fisiologia , Hepatopatia Gordurosa não Alcoólica/epidemiologia , Osteoporose/epidemiologia , Absorciometria de Fóton , Idoso , Fosfatase Alcalina/sangue , Densidade Óssea , Remodelação Óssea , Reabsorção Óssea/fisiopatologia , Osso e Ossos , Colágeno Tipo I/metabolismo , Estudos Transversais , Feminino , Humanos , Japão/epidemiologia , Masculino , Pessoa de Meia-Idade , Osteoporose/sangue , Fragmentos de Peptídeos/metabolismo , Pró-Colágeno/metabolismo , Fosfatase Ácida Resistente a Tartarato/metabolismo
13.
Int J Mol Sci ; 21(4)2020 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-32093165

RESUMO

Increased plasma homocysteine is a risk factor for several pathological disorders. The present review focused on the role of homocysteine (Hcy) in different population groups, especially in risk conditions (pregnancy, infancy, old age), and on its relevance as a marker or etiological factor of the diseases in these age groups, focusing on the nutritional treatment of elevated Hcy levels. In pregnancy, Hcy levels were investigated in relation to the increased risk of adverse pregnancy outcomes such as small size for gestational age at birth, preeclampsia, recurrent abortions, low birth weight, or intrauterine growth restriction. In pediatric populations, Hcy levels are important not only for cardiovascular disease, obesity, and renal disease, but the most interesting evidence concerns study of elevated levels of Hcy in autism spectrum disorder (ASD) and attention deficit hyperactivity disorder (ADHD). Finally, a focus on the principal pathologies of the elderly (cardiovascular and neurodegenerative disease, osteoporosis and physical function) is presented. The metabolism of Hcy is influenced by B vitamins, and Hcy-lowering vitamin treatments have been proposed. However, clinical trials have not reached a consensus about the effectiveness of vitamin supplementation on the reduction of Hcy levels and improvement of pathological condition, especially in elderly patients with overt pathologies, suggesting that other dietary and non-dietary factors are involved in high Hcy levels. The importance of novel experimental designs focusing on intra-individual variability as a complement to the typical case-control experimental designs and the study of interactions between different factors it should be emphasized.


Assuntos
Envelhecimento/sangue , Transtorno do Deficit de Atenção com Hiperatividade , Transtorno do Espectro Autista , Doenças Cardiovasculares , Homocisteína/sangue , Doenças Neurodegenerativas , Osteoporose , Pré-Eclâmpsia , Transtorno do Deficit de Atenção com Hiperatividade/sangue , Transtorno do Deficit de Atenção com Hiperatividade/terapia , Transtorno do Espectro Autista/sangue , Transtorno do Espectro Autista/terapia , Doenças Cardiovasculares/sangue , Doenças Cardiovasculares/terapia , Feminino , Humanos , Recém-Nascido , Recém-Nascido Pequeno para a Idade Gestacional/sangue , Masculino , Doenças Neurodegenerativas/sangue , Doenças Neurodegenerativas/terapia , Osteoporose/sangue , Osteoporose/terapia , Pré-Eclâmpsia/sangue , Pré-Eclâmpsia/terapia , Gravidez , Fatores de Risco
14.
J Cancer Res Clin Oncol ; 146(4): 945-951, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31980928

RESUMO

PURPOSE: Systemic mastocytosis (SM) is characterized by the expansion of clonal mast cells that infiltrate various organ systems. The extent of organ infiltration and subsequent organ damage distinguishes between indolent SM (ISM) defined by a nearly normal life expectancy and advanced SM (AdvSM) defined by poor prognosis. In ISM, measurement of the bone mineral density (BMD) frequently reveals osteoporosis. In contrast, the clinical implication of an increased BMD and osteosclerosis remains unclear. METHODS: BMD was evaluated in 61 patients with mastocytosis (ISM, n = 29, 48%; AdvSM, n = 32, 52%). We correlated the prevalence of osteoporosis, increased BMD and osteosclerosis with clinical parameters, disease variant and prognosis. RESULTS: Osteoporosis was detected in 11/29 (38%) patients with ISM but only in 2/32 (6%) patients with AdvSM (p = 0.004). An increased BMD was detected in 1/29 (3%) patients with ISM and 24/32 (75%) patients with AdvSM (p < 0.001) while osteosclerosis was only detected in AdvSM patients (16/32, 50%). AdvSM patients with increased BMD had higher levels of bone marrow mast cell infiltration, higher serum tryptase and alkaline phosphatase levels compared to ISM as well as higher number of high-molecular risk mutations (p < 0.05). In addition, we found that the prognosis of AdvSM patients with increased BMD is inferior compared to those without increased BMD (median overall survival 3.6 years versus not reached, p = 0.031). CONCLUSIONS: Osteoporosis is a common feature in ISM but not in AdvSM. An increased BMD is frequently present in AdvSM but not in ISM and is associated with more advanced disease and inferior outcome.


Assuntos
Mastocitose Sistêmica/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Densidade Óssea , Doenças Ósseas Metabólicas/sangue , Doenças Ósseas Metabólicas/diagnóstico por imagem , Doenças Ósseas Metabólicas/patologia , Estudos de Coortes , Humanos , Masculino , Mastocitose Sistêmica/sangue , Mastocitose Sistêmica/diagnóstico por imagem , Pessoa de Meia-Idade , Osteoporose/sangue , Osteoporose/diagnóstico por imagem , Osteoporose/patologia , Osteosclerose/sangue , Osteosclerose/diagnóstico por imagem , Osteosclerose/patologia , Prognóstico , Estudos Retrospectivos
15.
Brain Dev ; 42(3): 256-263, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31982226

RESUMO

OBJECTIVES: We assessed the severity and pathology of osteoporosis in children and adults with severe motor and intellectual disabilities (SMID) by evaluating bone enzymes, by which we aimed to determine adequate treatment approaches for preventing fractures. METHODS: Ninety patients (44 men, 46 women; mean age, 34.5 years) underwent bone quality assessment. Quantitative ultrasonography (QUS) was used to measure the T-score and Z-score of the calcaneus, and blood tests were used to measure bone-specific alkaline phosphatase and tartrate-resistant acid phosphatase 5b levels as bone formation and resorption markers, as well as calcium, phosphorous, and parathyroid hormone levels as routine examination. RESULTS: Bone formation and resorption marker levels were within normal ranges in adults, although they were high during the growth period in children and adolescents and in elderly women. Patients receiving tube feeding showed a significantly lower Z-score than those without tube feeding. Tube feeding was a significant factor for the Z-score, whereas age, vitamin supplements, and anti-epileptic drugs were not. CONCLUSIONS: The severity of osteoporosis in SMID started during the growth period and seems to be caused by a lack of an effective increase in bone mineral density. Any treatment should be started during the growth period. More study about tube feeding is needed.


Assuntos
Densidade Óssea , Nutrição Enteral , Deficiência Intelectual , Limitação da Mobilidade , Transtornos Motores , Osteoporose/diagnóstico , Fosfatase Ácida Resistente a Tartarato/sangue , Adolescente , Adulto , Idoso , Criança , Pré-Escolar , Comorbidade , Nutrição Enteral/estatística & dados numéricos , Feminino , Humanos , Deficiência Intelectual/epidemiologia , Masculino , Pessoa de Meia-Idade , Transtornos Motores/epidemiologia , Osteoporose/sangue , Osteoporose/diagnóstico por imagem , Osteoporose/epidemiologia , Tóquio/epidemiologia , Ultrassonografia , Adulto Jovem
16.
Exp Mol Pathol ; 113: 104366, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-31891679

RESUMO

The increasing level of osteogenic (OS) differentiation of bone marrow derived mesenchymal stem cells (MSCs) could be potentially used to relieve the signs and symptoms associated with osteoporosis (OP). Inhibition of osteoprotegerin (OPG)/Receptor Activator of Nuclear factor-Kappa B Ligand (RANKL) pathway plays an important role in OS differentiation, leading to excessive osteoclasts and reduction of osteoblasts, and finally causing OP. Recent studies revealed that microRNAs exert an essential role in regulating OS differentiation. Here, we investigated the dysregulation of miR-212 and miR-384 and the mechanism by which they are involved in OS differentiation-induced MSCs. Quantitative real-time PCR revealed that miR-212 and miR-384 were significantly upregulated in an OP animal model, but markedly downregulated in OS differentiation-induced MSCs. Interference of miR-212 and miR-384 promoted OS differentiation and alleviated OP by targeting RUNX2 in vitro and in vivo. Notably, the inhibition of miR-212 and miR-384 promoted OS differentiation via upregulating RUNX2, and activating OPG/RANKL pathway. Together, our findings demonstrated that interference of miR-212 and miR-384 alleviated OP via RUNX2/OPG/RANKL pathway, providing a novel target of treating OP.


Assuntos
Diferenciação Celular/genética , Subunidade alfa 1 de Fator de Ligação ao Core/metabolismo , MicroRNAs/genética , Osteogênese/genética , Osteoporose/genética , Animais , Sequência de Bases , Modelos Animais de Doenças , Regulação para Baixo/genética , Feminino , Humanos , Células-Tronco Mesenquimais/metabolismo , Camundongos Endogâmicos C57BL , MicroRNAs/sangue , MicroRNAs/metabolismo , Osteoporose/sangue , Osteoprotegerina/metabolismo , Ligante RANK/metabolismo , Regulação para Cima/genética
17.
Exp Clin Endocrinol Diabetes ; 128(3): 152-157, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31117148

RESUMO

BACKGROUND: Adipokines derived from adipocytes are one of the important factors that act as circulating regulators of bone metabolism. Complement C1q/tumor necrosis factor-related protein-3 (CTRP3), a paralog of adiponectin, is are member of the CTRP superfamily. The aim of this study was to investigate the role of serum CTRP3 in the development of osteoporosis in patients with primary hyperparathyroidism. METHODS: This study included 53 patients with diagnosed primary hyperparathyroidism and 30 healthy controls. Laboratory tests for the diagnosis of primary hyperparathyroidism and serum levels of CTRP3 measured for all patients. Bone mineral density was obtained on lumbar spine 1 and 4 by dual energy X-ray absorptiometry. RESULTS: Serum CTRP3 levels were lower in patients with primary hyperparathyroidism than in the control group (p<0.001). In addition, primary hyperparathyroidism patients are were divided into two groups as, with and without osteoporosis; the levels of CTRP3 were lower in patients with osteoporosis than in patients without osteoporosis (p=0.004). In logistic regression analysis, only CTRP3 levels independently determined the patients to be osteoporosis (p<0.05). According to this analysis, decreased CTRP3 (per 1 ng/mL) levels were found to increase the risk of patients for osteoporosis by 6.9%. When the CTRP3 cut-off values were taken as 30 ng/mL, it determined osteoporosis with 76.4% sensitivity and 73.2% specificity. CTRP3 and urine calcium levels were independently associated with T score in dual energy X-ray absorptiometry. CONCLUSIONS: CTRP3 levels were significantly decreased in patients with primary hyperparathyroidism, and it is also related to osteoporosis.


Assuntos
Densidade Óssea , Hiperparatireoidismo Primário/sangue , Osteoporose/sangue , Fatores de Necrose Tumoral/administração & dosagem , Absorciometria de Fóton , Adulto , Idoso , Biomarcadores/sangue , Feminino , Humanos , Hiperparatireoidismo Primário/complicações , Hiperparatireoidismo Primário/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade , Osteoporose/diagnóstico por imagem , Osteoporose/etiologia , Estudos Prospectivos , Sensibilidade e Especificidade
18.
Support Care Cancer ; 28(5): 2265-2271, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-31468192

RESUMO

PURPOSE: Medication-related osteonecrosis of the jaw (MRONJ) has been reported as a side effect of bisphosphonate (BP). The aim of this study was to identify the prevalence of MRONJ in women taking BP for osteoporosis and for metastatic breast cancer and correlate it with risk factors and biochemical markers of bone metabolism. METHODS: Patients taking oral or intravenous BP with osteoporosis (G1; n = 153; median 72.8 years) and with metastatic breast cancer (G2; n = 134; median 58.2 years) had their hospital charts reviewed, were submitted to dental inspection, and answered a health questionnaire. Fasting blood samples were randomly collected from both groups to measure osteocalcin, carboxy-terminal cross-linking telopeptide of type I collagen, intact parathyroid hormone and procollagen type 1 amino-terminal propeptide (P1NP), 25 hydroxyvitamin D (25OHD), creatinine, and total calcium. RESULTS: G1 was older (p = 0.001) and had more cases of diabetes (p = 0.043). P1NP was higher (p = 0.022) and 25OHD lower (p = 0.004) in G2 compared with G1. MRONJ was not found in the G1, whereas 4 cases (3%) were detected in G2. Positive risk factors for MRONJ were number of BP doses and number of visits to the dentist and dental extractions. The biochemical parameters, however, could not identify those who developed MRONJ. CONCLUSIONS: The prevalence of MRONJ was 3% in women with metastatic breast cancer receiving BP. No cases were identified in women receiving oral BP chronically for osteoporosis. P1NP was higher in women with metastatic breast cancer, even during treatment with antiresorptives, but could not differentiate those with MRONJ.


Assuntos
Osteonecrose da Arcada Osseodentária Associada a Difosfonatos/epidemiologia , Neoplasias da Mama/sangue , Neoplasias da Mama/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/sangue , Osteonecrose da Arcada Osseodentária Associada a Difosfonatos/sangue , Conservadores da Densidade Óssea/efeitos adversos , Conservadores da Densidade Óssea/uso terapêutico , Estudos Transversais , Difosfonatos/efeitos adversos , Difosfonatos/uso terapêutico , Feminino , Humanos , Pessoa de Meia-Idade , Osteocalcina/sangue , Osteoporose/sangue , Osteoporose/tratamento farmacológico , Hormônio Paratireóideo/sangue , Prevalência , Fatores de Risco , Vitamina D/análogos & derivados , Vitamina D/sangue
19.
Surgery ; 167(1): 144-148, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31582307

RESUMO

BACKGROUND: Parathyroidectomy (PTX) increases bone mineral density and decreases fracture risk in patients with primary hyperparathyroidism. This study examined the effect of adding bisphosphonates either before or after PTX on skeletal outcomes. METHODS: A retrospective cohort study of bisphosphonate-naïve patients (1995-2016) with osteoporosis and primary hyperparathyroidism (calcium >10.5 mg/dL; PTH >65) was performed. Time-varying Cox regression was used to estimate an adjusted risk of any fracture in 5 comparison groups: observation, bisphosphonates alone, PTX alone, bisphosphonates then PTX, and PTX then bisphosphonates. The secondary outcome was change in bone mineral density of the hip. RESULTS: The cohort comprised 1,737 patients, of whom 303 underwent PTX (17%), 433 received bisphosphonates only (25%), 125 had bisphosphonates then PTX (7%), and 69 had PTX then bisphosphonates (4%). PTX was associated with a decrease in fracture risk (HR 0.55, 95% CI 0.35-0.84), as was bisphosphonates then PTX (HR 0.46, 95% CI 0.25-0.83). In contrast, the fracture risks associated with PTX then bisphosphonates (HR 1.09, 95% CI 0.65-1.81) and bisphosphonates alone (HR 0.82, 95% CI 0.62-1.08) were similar to observation. Hip bone mineral density increased after both PTX (5.50%, 95% CI 3.39-7.61) and PTX then bisphosphonates (6.30%, 95% CI 2.53-10.07). CONCLUSION: Bisphosphonate initiation after PTX may interfere with the beneficial effects of PTX on fracture risk in osteoporotic patients with primary hyperparathyroidism.


Assuntos
Conservadores da Densidade Óssea/administração & dosagem , Hiperparatireoidismo Primário/terapia , Osteoporose/diagnóstico por imagem , Fraturas por Osteoporose/epidemiologia , Paratireoidectomia , Absorciometria de Fóton , Idoso , Densidade Óssea/efeitos dos fármacos , Cálcio/sangue , Terapia Combinada/métodos , Difosfonatos/administração & dosagem , Feminino , Humanos , Hiperparatireoidismo Primário/sangue , Hiperparatireoidismo Primário/complicações , Masculino , Pessoa de Meia-Idade , Osteoporose/sangue , Osteoporose/etiologia , Osteoporose/prevenção & controle , Fraturas por Osteoporose/sangue , Fraturas por Osteoporose/etiologia , Fraturas por Osteoporose/prevenção & controle , Hormônio Paratireóideo/sangue , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Resultado do Tratamento
20.
J Bone Miner Metab ; 38(2): 240-247, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31667583

RESUMO

INTRODUCTION: In terms of the balance between benefits and risks of long-term treatment with bisphosphonate, uncertainties remain regarding the optimal treatment duration. We investigated effects of continuous long-term treatment for 10 years with bisphosphonate in postmenopausal osteoporosis patients. MATERIALS AND METHODS: Fifty five patients in the outpatient clinic of our hospital have been continuously treated with alendronate or risedronate for 10 years. All data were retrospectively collected. The age, height, weight, total muscle volume, total fat volume, and BMD at the lumbar spine, total hip and distal 1/3 radius, alkaline phosphatase (ALP), urinary type I collagen cross-linked N-telopeptide (uNTX) and tartrate-resistant acid phosphatase-5b (TRAP5b), calcium (Ca) and phosphate (P) levels were measured pre- and after the start of 10-year continuous treatment. RESULTS: BMD at the lumbar spine increased continuously over the 10-year period, while BMD at the total hip slightly but significantly decreased, and that at the 1/3 radius did not show any significant change over the 10 years. Serum Ca value was significantly decreased after the start of treatment, and became stable within the reference range from the second year. Bone resorption markers such as uNTX and TRAP5b significantly decreased from the second year after the start of treatment and no significant changes were observed thereafter. There were no serious medical adverse events including atypical femoral fractures and osteonecrosis of the jaw. CONCLUSION: We believe that the continuous use of alendronate and risedronate for 10 years could be an option for the treatment of postmenopausal osteoporosis patients.


Assuntos
Grupo com Ancestrais do Continente Asiático , Difosfonatos/uso terapêutico , Osteoporose/tratamento farmacológico , Idoso , Idoso de 80 Anos ou mais , Alendronato/farmacologia , Alendronato/uso terapêutico , Fosfatase Alcalina/sangue , Densidade Óssea/efeitos dos fármacos , Cálcio/sangue , Colágeno Tipo I/sangue , Difosfonatos/farmacologia , Feminino , Humanos , Japão , Osteoporose/sangue , Osteoporose/induzido quimicamente , Osteoporose/fisiopatologia , Osteoporose Pós-Menopausa/tratamento farmacológico , Peptídeos/sangue , Fósforo/sangue , Estudos Retrospectivos , Ácido Risedrônico/uso terapêutico , Fosfatase Ácida Resistente a Tartarato/sangue , Fatores de Tempo , Resultado do Tratamento
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