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1.
Comput Methods Programs Biomed ; 250: 108172, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38669718

RESUMO

BACKGROUND AND OBJECTIVE: Degenerative diseases of the spine have a negative impact on the quality of life of patients. This study presents the results of numerical modelling of the mechanical behaviour of the lumbar spine with patient-specific conditions at physiological loads. This paper aims to numerically study the influence of degenerative changes in the spine and the presence of an endoprosthesis on the creation of conditions for tissue regeneration. METHODS: A numerical model of the mechanical behaviour of lumbar spine at healthy and after total disc replacement under low-energy impacts equivalent to physiological loads is presented. The model is based on the movable cellular automaton method (discrete elements), where the mechanical behaviour of bone tissue is described using the Biot poroelasticity accounting for the presence and transfer of interstitial biological fluid. The nutritional pathways of the intervertebral disc in cases of healthy and osteoporotic bone tissues were predicted based on the analysis of the simulation results according to the mechanobiological principles. RESULTS: Simulation of total disc replacement showed that osseointegration of the artificial disc plates occurs only in healthy bone tissue. With total disc replacement in a patient with osteoporosis, there is an area of increased risk of bone resorption in the near-contact area, approximately 1 mm wide, around the fixators. Dynamic loads may improve the osseointegration of the implant in pathological conditions of the bone tissue. CONCLUSIONS: The results obtained in the case of healthy spine and osteoporotic bone tissues correspond to the experimental data on biomechanics and possible methods of IVD regeneration from the position of mechanobiological principles. The results obtained with an artificial disc (with keel-type fixation) showed that the use of this type of endoprosthesis in healthy bone tissues allows to reproduce the function of the natural intervertebral disc and does not contribute to the development of neoplastic processes. In the case of an artificial disc with osteoporosis of bone tissues, there is a zone with increased risk of tissue resorption and development of neoplastic processes in the area near the contact of the implant attachment. This circumstance can be compensated by increasing the loading level.


Assuntos
Simulação por Computador , Disco Intervertebral , Vértebras Lombares , Substituição Total de Disco , Humanos , Vértebras Lombares/cirurgia , Disco Intervertebral/cirurgia , Disco Intervertebral/fisiopatologia , Regeneração , Fenômenos Biomecânicos , Osteoporose/fisiopatologia , Osseointegração
2.
J Bone Joint Surg Am ; 106(9): 801-808, 2024 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-38346100

RESUMO

BACKGROUND: Physical skeletal loading can affect the bone mineral density (BMD). This study investigated the association between BMD and dynamic foot pressure during gait. METHODS: A total of 104 patients (mean age, 62.6 ± 12.4 years; 23 male and 81 female) who underwent dual x-ray absorptiometry and pedobarography were included. BMD values of the lumbar spine, femoral neck, and total femur were assessed. The mean and maximum pressures were measured at the hallux, lesser toes, 1st metatarsal head, 2nd and 3rd metatarsal heads, 4th and 5th metatarsal heads, midfoot, medial heel, and lateral heel. Multivariable regression analysis was performed to identify factors significantly associated with BMD. RESULTS: The lumbar spine BMD was significantly associated with the mean pressure at the 4th and 5th metatarsal heads (p = 0.041, adjusted R 2 of model = 0.081). The femoral neck BMD was significantly associated with the maximum pressure at the 2nd and 3rd metatarsal heads (p = 0.002, adjusted R 2 = 0.213). The total femoral BMD also showed a significant association with the maximum pressure at the 2nd and 3rd metatarsal heads (p = 0.003, adjusted R 2 = 0.360). CONCLUSIONS: Foot plantar pressure during gait was significantly associated with BMD, and could potentially be used to predict the presence of osteoporosis. LEVEL OF EVIDENCE: Prognostic Level III . See Instructions for Authors for a complete description of levels of evidence.


Assuntos
Absorciometria de Fóton , Densidade Óssea , , Pressão , Caminhada , Humanos , Feminino , Masculino , Pessoa de Meia-Idade , Densidade Óssea/fisiologia , Idoso , Pé/fisiologia , Caminhada/fisiologia , Osteoporose/fisiopatologia , Colo do Fêmur/diagnóstico por imagem , Colo do Fêmur/fisiologia , Vértebras Lombares , Marcha/fisiologia
3.
Front Endocrinol (Lausanne) ; 13: 891313, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35909545

RESUMO

Osteoporosis is a bone metabolic disorder characterized by decreased bone density and deteriorated microstructure, which increases the risk of fractures. The imbalance between bone formation and bone resorption results in the occurrence and progression of osteoporosis. Osteoblast-mediated bone formation, osteoclast-mediated bone resorption and macrophage-regulated inflammatory response play a central role in the process of bone remodeling, which together maintain the balance of the osteoblast-osteoclast-macrophage (OB-OC-MΦ) axis under physiological conditions. Bone formation and bone resorption disorders caused by the imbalance of OB-OC-MΦ axis contribute to osteoporosis. Many microRNAs are involved in the regulation of OB-OC-MΦ axis homeostasis, with microRNA-23a (miR-23a) being particularly crucial. MiR-23a is highly expressed in the pathological process of osteoporosis, which eventually leads to the occurrence and further progression of osteoporosis by inhibiting osteogenesis, promoting bone resorption and inflammatory polarization of macrophages. This review focuses on the role and mechanism of miR-23a in regulating the OB-OC-MΦ axis to provide new clinical strategies for the prevention and treatment of osteoporosis.


Assuntos
Reabsorção Óssea , MicroRNAs , Osteoporose , Reabsorção Óssea/genética , Reabsorção Óssea/metabolismo , Humanos , Macrófagos/metabolismo , MicroRNAs/genética , MicroRNAs/metabolismo , Osteoblastos/metabolismo , Osteoclastos/metabolismo , Osteoporose/etiologia , Osteoporose/genética , Osteoporose/fisiopatologia , Osteoporose/terapia
4.
Comput Math Methods Med ; 2022: 2565391, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35265168

RESUMO

Osteoporosis and degenerative spinal disease are still an unsolvable surgical problem. It is still difficult to solve the complications related to postoperative osteoporosis, such as cage subsidence, displacement, and retraction. Expandable interbody cage is a recent innovation and an increasingly popular alternative to standard static cage. However, the clinical efficacy of MIS-TLIF combined with expandable cage for the treatment of osteoporosis has limited reports. The purpose of this paper was to analyze the efficacy of MIS-TLIF with expandable cage in patients with degenerative lumbar disease with osteoporosis. Patients with osteoporosis who received single-level MIS-TLIF and were followed up for at least 1 year were included. The outcome measures are as follows: clinical features, perioperative period, and neurological complications. JOA score and VAS pain score were used to analyze the improvement of patients' function. Imaging analysis included segmental lordosis (SL), lumbar lordosis (LL), intervertebral disc height (DH), and the ratio of cage height to preoperative DH (RCD). The final data analysis included 284 patients with osteoporosis. 178 patients used static cages, and 106 patients used expandable cages. There was no significant difference in baseline characteristics, surgical indexes, and JOA and VAS scores between the two groups. There was no difference in SL or LL between static group and expandable group. There was no significant difference in preoperative DH between the two groups. The RCD in the expansion group was significantly lower than that in the static group. The intraoperative and postoperative sedimentation rate in the static group was significantly higher than that in the expandable group. The use of expandable cages in MIS-TLIF has shown good results for the treatment of degenerative lumbar diseases with osteoporosis. Through appropriate surgical techniques, the expandable cage can reduce the risk of cage sinking.


Assuntos
Vértebras Lombares/cirurgia , Osteoporose/cirurgia , Fusão Vertebral/instrumentação , Idoso , Biologia Computacional , Feminino , Humanos , Disco Intervertebral/diagnóstico por imagem , Disco Intervertebral/cirurgia , Vértebras Lombares/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade , Procedimentos Cirúrgicos Minimamente Invasivos/métodos , Procedimentos Cirúrgicos Minimamente Invasivos/estatística & dados numéricos , Osteoporose/diagnóstico por imagem , Osteoporose/fisiopatologia , Medição da Dor , Estudos Retrospectivos , Fusão Vertebral/efeitos adversos , Fusão Vertebral/métodos , Resultado do Tratamento
5.
Life Sci ; 290: 119480, 2022 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-33862113

RESUMO

AIMS: Bone defect repair in osteoporosis remains a tremendous challenge for clinicians due to increased bone metabolism resulted from estrogen deficiency. This study aims to investigate the effect of bone marrow mesenchymal stem cells (BMSCs) combined with fibrin glue (FG) in the extraction socket healing process of osteoporosis rats, as well as estimate the role of estrogen receptors (ERs) played in BMSCs differentiation in vitro and in the alveolar bone reconstruction process in vivo. MAIN METHODS: Forty rats were randomly divided into four groups, under general anesthesia, three groups underwent bilateral ovariectomy(OVX) and one group with the sham operation. Three months later, the osteogenic ability of BMSCs, isolated from healthy and osteoporosis rats, respectively, was tested. The ERα and ERß mRNA expression in BMSCs was also evaluated by RT-PCR analysis. In vivo experiment, Micro-CT detection, histological and immunofluorescent analysis, tissue PCR was conducted up to 2, 4 and 6 weeks after transplantation of BMSCs/FG to assess the newly formed bone in the extraction socket. KEY FINDINGS: The BMSCs from osteoporosis rats displayed weaker osteogenic potential and lower ERs expression compared with the BMSCs from healthy rats. Newly formed bone tissue filled the socket defect in BMSCs/FG treated VOX rats after six weeks, which was comparable to the sham group, while reduced ERs expression was found in the regenerated bone of the OVX group. SIGNIFICANCE: The BMSCs seeded within FG might provide an alternative therapeutic method for repairing the extraction socket defect in osteoporosis condition.


Assuntos
Regeneração Óssea/efeitos dos fármacos , Adesivo Tecidual de Fibrina/farmacologia , Transplante de Células-Tronco Mesenquimais/métodos , Osteoporose/terapia , Alvéolo Dental/efeitos dos fármacos , Animais , Densidade Óssea , Regeneração Óssea/fisiologia , Diferenciação Celular , Modelos Animais de Doenças , Feminino , Regulação da Expressão Gênica , Maxila/efeitos dos fármacos , Maxila/fisiopatologia , Células-Tronco Mesenquimais/citologia , Osteoporose/patologia , Osteoporose/fisiopatologia , Ovariectomia , Ratos Sprague-Dawley , Receptores de Estrogênio/genética , Extração Dentária/efeitos adversos
6.
PLoS One ; 16(11): e0257310, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34735461

RESUMO

Inflammatory bowel disease (IBD) is characterized by chronic inflammation of the intestinal tract and is associated with decreased bone mineral density. IBD patients are at higher risk of osteopenia, osteoporosis and fracture compared to non-IBD patients. The impact of IBD on the performance of orthopedic implants has not been well studied. We hypothesized that a history of IBD at the time of primary total hip arthroplasty (THA) would increase the risk of subsequent failure as assessed by revision surgery. A retrospective implant survival analysis was completed using the Swedish Hip Arthroplasty Registry and the Sweden National Patient Register. A total of 150,073 patients undergoing THA for osteoarthritis within an 18-year period were included in the study. THA patients with (n = 2,604) and without (n = 147,469) a history of IBD at the time of THA were compared with primary revision as the main endpoint and adjusted using sex, age category and comorbidity (Elixhauser scores) as covariates. We found that patients with a history of IBD had a relatively higher risk of revision surgery for septic causes while the non-IBD patients had a relatively higher risk of revision for aseptic causes (p = 0.004). Our findings suggest there may be an association between gut health and THA performance.


Assuntos
Densidade Óssea , Doenças Inflamatórias Intestinais/cirurgia , Osteoartrite/cirurgia , Reoperação , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Artroplastia de Quadril/efeitos adversos , Doenças Ósseas Metabólicas/etiologia , Doenças Ósseas Metabólicas/fisiopatologia , Doenças Ósseas Metabólicas/cirurgia , Feminino , Prótese de Quadril/efeitos adversos , Humanos , Doenças Inflamatórias Intestinais/complicações , Doenças Inflamatórias Intestinais/fisiopatologia , Masculino , Pessoa de Meia-Idade , Osteoartrite/etiologia , Osteoartrite/fisiopatologia , Osteoporose/etiologia , Osteoporose/fisiopatologia , Osteoporose/cirurgia , Falha de Prótese/efeitos adversos , Sistema de Registros , Fatores de Risco , Suécia
7.
Med Clin North Am ; 105(6): 1117-1134, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34688418

RESUMO

Osteoporosis is a metabolic bone disease characterized by low bone mass and microarchitectural deterioration of bone tissue leading to an increased risk of fragility fractures. Central dual-energy X-ray absorptiometry measurements are the gold standard for determining bone mineral density. A well-balanced diet containing adequate amounts of calcium and vitamin D, exercise, smoking cessation, and limited alcohol intake are important to maintain bone health. Pharmacologic agents should be recommended in postmenopausal women who are at high risk for fractures. Newer anabolic therapies including teriparatide, abaloparatide, and romosozumab have emerged for use in severe osteoporosis.


Assuntos
Osteoporose/diagnóstico , Osteoporose/fisiopatologia , Absorciometria de Fóton , Acidentes por Quedas/prevenção & controle , Envelhecimento/fisiologia , Densidade Óssea , Conservadores da Densidade Óssea/uso terapêutico , Dieta , Exercício Físico , Feminino , Fraturas Ósseas/epidemiologia , Humanos , Menopausa/fisiologia , Pessoa de Meia-Idade , Osteoporose/tratamento farmacológico , Osteoporose/epidemiologia , Osteoporose Pós-Menopausa , Grupos Raciais , Fatores de Risco , Moduladores Seletivos de Receptor Estrogênico/uso terapêutico
8.
Int J Mol Sci ; 22(19)2021 Sep 29.
Artigo em Inglês | MEDLINE | ID: mdl-34638883

RESUMO

Projected life expectancy continues to grow worldwide owing to the advancement of new treatments and technologies leading to rapid growth of geriatric population. Thus, age-associated diseases especially in the musculoskeletal system are becoming more common. Loss of bone (osteoporosis) and muscle (sarcopenia) mass are conditions whose prevalence is increasing because of the change in population distribution in the world towards an older mean age. The deterioration in the bone and muscle functions can cause severe disability and seriously affects the patients' quality of life. Currently, there is no treatment to prevent and reverse age-related musculoskeletal frailty. Existing interventions are mainly to slow down and control the signs and symptoms. Mesenchymal stem cell (MSC) transplantation is a promising approach to attenuate age-related musculoskeletal frailty. This review compiles the present knowledge of the causes and changes of the musculoskeletal frailty and the potential of MSC transplantation as a regenerative therapy for age-related musculoskeletal frailty.


Assuntos
Envelhecimento/metabolismo , Fragilidade , Transplante de Células-Tronco Mesenquimais , Células-Tronco Mesenquimais/metabolismo , Osteoporose , Sarcopenia , Fragilidade/metabolismo , Fragilidade/fisiopatologia , Fragilidade/terapia , Humanos , Osteoporose/metabolismo , Osteoporose/fisiopatologia , Osteoporose/terapia , Sarcopenia/metabolismo , Sarcopenia/fisiopatologia , Sarcopenia/terapia
9.
J Exp Med ; 218(12)2021 12 06.
Artigo em Inglês | MEDLINE | ID: mdl-34698806

RESUMO

Osteoporosis is caused by an imbalance of osteoclasts and osteoblasts, occurring in close proximity to hematopoietic cells in the bone marrow. Recurrent somatic mutations that lead to an expanded population of mutant blood cells is termed clonal hematopoiesis of indeterminate potential (CHIP). Analyzing exome sequencing data from the UK Biobank, we found CHIP to be associated with increased incident osteoporosis diagnoses and decreased bone mineral density. In murine models, hematopoietic-specific mutations in Dnmt3a, the most commonly mutated gene in CHIP, decreased bone mass via increased osteoclastogenesis. Dnmt3a-/- demethylation opened chromatin and altered activity of inflammatory transcription factors. Bone loss was driven by proinflammatory cytokines, including Irf3-NF-κB-mediated IL-20 expression from Dnmt3a mutant macrophages. Increased osteoclastogenesis due to the Dnmt3a mutations was ameliorated by alendronate or IL-20 neutralization. These results demonstrate a novel source of osteoporosis-inducing inflammation.


Assuntos
Hematopoiese Clonal/genética , DNA Metiltransferase 3A/genética , Osteoporose/genética , Adulto , Idoso , Alendronato/farmacologia , Animais , Anticorpos Neutralizantes/farmacologia , Diferenciação Celular/genética , Hematopoiese Clonal/fisiologia , DNA Metiltransferase 3A/metabolismo , Feminino , Humanos , Interleucinas/imunologia , Interleucinas/metabolismo , Masculino , Camundongos Knockout , Pessoa de Meia-Idade , Osteoclastos/patologia , Osteoporose/sangue , Osteoporose/tratamento farmacológico , Osteoporose/fisiopatologia
10.
Nat Rev Rheumatol ; 17(10): 608-620, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34480164

RESUMO

Blood vessels form a versatile transport network that is best known for its critical roles in processes such as tissue oxygenation, metabolism and immune surveillance. The vasculature also provides local, often organ-specific, molecular signals that control the behaviour of other cell types in their vicinity during development, homeostasis and regeneration, and also in disease processes. In the skeletal system, the local vasculature is actively involved in both bone formation and resorption. In addition, blood vessels participate in inflammatory processes and contribute to the pathogenesis of diseases that affect the joints, such as rheumatoid arthritis and osteoarthritis. This Review summarizes the current understanding of the architecture, angiogenic growth and functional properties of the bone vasculature. The effects of ageing and pathological conditions, including arthritis and osteoporosis, are also discussed.


Assuntos
Desenvolvimento Ósseo , Doenças Ósseas/fisiopatologia , Osso e Ossos , Endotélio Vascular , Homeostase , Artropatias/fisiopatologia , Envelhecimento/fisiologia , Animais , Artrite/fisiopatologia , Desenvolvimento Ósseo/fisiologia , Doenças Ósseas/tratamento farmacológico , Regeneração Óssea/efeitos dos fármacos , Regeneração Óssea/fisiologia , Osso e Ossos/irrigação sanguínea , Osso e Ossos/fisiologia , Osso e Ossos/fisiopatologia , Condrócitos/fisiologia , Endotélio Vascular/fisiologia , Endotélio Vascular/fisiopatologia , Fraturas Ósseas/fisiopatologia , Homeostase/fisiologia , Humanos , Artropatias/tratamento farmacológico , Macrófagos/fisiologia , Camundongos , Neovascularização Patológica/tratamento farmacológico , Neovascularização Patológica/fisiopatologia , Neovascularização Fisiológica/fisiologia , Osteoblastos/fisiologia , Osteogênese/fisiologia , Osteoporose/tratamento farmacológico , Osteoporose/fisiopatologia , Receptor Cross-Talk/fisiologia , Sinoviócitos/fisiologia
11.
Nutrients ; 13(7)2021 Jul 13.
Artigo em Inglês | MEDLINE | ID: mdl-34371899

RESUMO

Introduction: Chronic pancreatitis (CP) can lead to malnutrition, an established risk factor for low bone mineral density (BMD) and fractures. This study aims to determine the prevalence of low BMD, assess fracture incidence and explore risk factors for fractures in patients with CP. Patients and methods: We performed a retrospective analysis of all patients treated for CP at Karolinska University Hospital between January 1999 and December 2020. Electronic medical records were retrieved to assess demographic, laboratory and clinical data. Patients subjected to dual-energy X-ray absorptiometry (DXA) were categorised as either low BMD or normal BMD. We investigated whether the rate of fractures, defined by chart review, differed between these groups using Cox regression, adjusting the model for age, sex and body mass index (BMI). Additional within-group survival analysis was conducted to identify potential risk factors. Results: DXA was performed in 23% of patients with definite CP. Some 118 patients were included in the final analysis. Low BMD was present in 63 (53.4%) patients. Mean age at CP diagnosis in the total cohort was 53.1 years and was significantly lower in patients with normal BMD than in patients with low BMD (45.5 vs. 59.8, p < 0.001). Significant differences were observed in smoking status and disease aetiology, i.e., a higher proportion of patients with low BMD were current or former smokers, with nicotine or alcohol being a more common cause of CP (p < 0.05). Total follow-up time was 898 person-years. Fractures were found in 33 (28.0%) patients: in 5 of 55 patients (16.7%) with normal DXA and in 28 of 63 patients (44.4%) with low BMD (adjusted hazard ratio = 3.4, 95% confidence interval (CI) = 1.2-9.6). Patients with at least 3 months of consecutive pancreatic enzyme replacement therapy (PERT) or vitamin D treatment had a longer median time to fracture after CP diagnosis. Conclusion: DXA was only performed in 23% of patients with definite CP in this study, indicating a low adherence to current European guidelines. A low BMD was found in 53.4% of patients with CP, and 44% of the patients with a low BMD experienced a fracture during follow-up. Moreover, the fracture rate in patients with low BMD increased compared to those with normal BMD.


Assuntos
Densidade Óssea , Insuficiência Pancreática Exócrina/epidemiologia , Osteoporose/epidemiologia , Fraturas por Osteoporose/epidemiologia , Pancreatite Crônica/epidemiologia , Absorciometria de Fóton , Adulto , Idoso , Insuficiência Pancreática Exócrina/diagnóstico por imagem , Insuficiência Pancreática Exócrina/fisiopatologia , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Osteoporose/diagnóstico por imagem , Osteoporose/fisiopatologia , Fraturas por Osteoporose/diagnóstico por imagem , Fraturas por Osteoporose/fisiopatologia , Pancreatite Crônica/diagnóstico por imagem , Pancreatite Crônica/fisiopatologia , Prevalência , Prognóstico , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Suécia/epidemiologia
12.
PLoS One ; 16(8): e0256294, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34428249

RESUMO

OBJECTIVE: To synthesize evidence on the prevalence and incidence of physical health conditions in people with intellectual disability (ID). METHODS: We searched Medline, PsycInfo, and Embase for eligible studies and extracted the prevalence, incidence, and risk of physical health conditions in people with ID. RESULTS: Of 131 eligible studies, we synthesized results from 77 moderate- to high-quality studies, which was mainly limited to high-income countries. The highest prevalence estimates were observed for epilepsy, ear and eye disorders, cerebral palsy, obesity, osteoporosis, congenital heart defects, and thyroid disorders. Some conditions were more common in people with a genetic syndrome. Compared with the general population, many health conditions occur more frequently among people with ID, including asthma and diabetes, while some conditions such as non-congenital circulatory diseases and solid cancers occur at the same or lower rate. The latter associations may reflect under-detection. CONCLUSIONS: People with ID have a health profile more complex than previously known. There is a pressing need for targeted, evidence-informed population health initiatives including preventative programs for this population.


Assuntos
Deficiência Intelectual/epidemiologia , Deficiência Intelectual/fisiopatologia , Prevalência , Asma/epidemiologia , Asma/fisiopatologia , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/fisiopatologia , Paralisia Cerebral/epidemiologia , Paralisia Cerebral/fisiopatologia , Diabetes Mellitus/epidemiologia , Diabetes Mellitus/fisiopatologia , Epilepsia/epidemiologia , Epilepsia/fisiopatologia , Oftalmopatias/epidemiologia , Oftalmopatias/fisiopatologia , Feminino , Cardiopatias Congênitas/epidemiologia , Cardiopatias Congênitas/fisiopatologia , Humanos , Deficiência Intelectual/complicações , Masculino , Obesidade/epidemiologia , Obesidade/fisiopatologia , Osteoporose/epidemiologia , Osteoporose/fisiopatologia , Doenças da Glândula Tireoide/epidemiologia , Doenças da Glândula Tireoide/fisiopatologia
13.
Nutrients ; 13(8)2021 Aug 23.
Artigo em Inglês | MEDLINE | ID: mdl-34445056

RESUMO

Musculoskeletal deficits are among the most commonly reported extra-intestinal manifestations and complications of inflammatory bowel disease (IBD), especially in those with Crohn's disease. The adverse effects of IBD on bone and muscle are multifactorial, including the direct effects of underlying inflammatory disease processes, nutritional deficits, and therapeutic effects. These factors also indirectly impact bone and muscle by interfering with regulatory pathways. Resultantly, individuals with IBD are at increased risk of osteoporosis and sarcopenia and associated musculoskeletal morbidity. In paediatric IBD, these factors may contribute to suboptimal bone and muscle accrual. This review evaluates the main pathogenic factors associated with musculoskeletal deficits in children and adults with IBD and summarises the current literature and understanding of the musculoskeletal phenotype in these patients.


Assuntos
Colite Ulcerativa/complicações , Doença de Crohn/complicações , Doenças Musculoesqueléticas/etiologia , Sarcopenia/etiologia , Fatores Etários , Composição Corporal , Remodelação Óssea , Colite Ulcerativa/sangue , Colite Ulcerativa/fisiopatologia , Doença de Crohn/sangue , Doença de Crohn/tratamento farmacológico , Doença de Crohn/fisiopatologia , Citocinas/sangue , Glucocorticoides/efeitos adversos , Humanos , Mediadores da Inflamação/sangue , Doenças Musculoesqueléticas/sangue , Doenças Musculoesqueléticas/fisiopatologia , Estado Nutricional , Osteoporose/sangue , Osteoporose/etiologia , Osteoporose/fisiopatologia , Medição de Risco , Fatores de Risco , Sarcopenia/sangue , Sarcopenia/fisiopatologia
14.
PLoS One ; 16(8): e0256281, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34403451

RESUMO

Height loss starting in middle age is reported to be associated with increased all-cause and cardiovascular mortality later in life. However, the mechanisms underlying this association are unclear. Hypoxia and oxidative stress, which are known causes of cardiovascular disease, could be reduced by hemoglobin. Therefore, hemoglobin could be inversely associated with height loss. However, high body mass index (BMI) is a known risk factor for intervertebral disc disorder, a known cause of height loss in adults. High BMI might confound the association between hemoglobin and height loss. Therefore, we performed analyses stratified by BMI status. To clarify the association between hemoglobin and height loss, we conducted a retrospective study of Japanese workers (6,471 men and 3,180 women) aged 40-74 years. Height loss was defined as being in the highest quintile of height decrease per year. In men overall and men with BMI <25 kg/m2, hemoglobin was significantly inversely associated with height loss; but no association was observed for men with high BMI (BMI ≥25 kg/m2) and for women. For men, after adjusting for known cardiovascular risk factors, adjusted odds ratios (ORs) and 95% confidence intervals (CIs) for height loss with each 1 standard deviation (SD) increase in hemoglobin (1.0 g/dL for men and 0.8g/dL for women) were 0.89 (0.83, 0.95) for men overall, 0.82 (0.75, 0.89) for men who do not have high BMI, and 1.01 (0.92, 1.12) for men with high BMI. For women, the corresponding values were 0.97 (0.89, 1.06), 0.98 (0.89, 1.09), and 0.93 (0.75, 1.15) respectively. Hemoglobin is significantly inversely associated with height loss in men who do not have high BMI, but not in men with high BMI or women. These results help clarify the mechanisms underlying height loss, which has been reported to be associated with a higher risk of mortality in adults.


Assuntos
Estatura , Doenças Cardiovasculares/epidemiologia , Dislipidemias/epidemiologia , Hemoglobinas/metabolismo , Hipóxia/epidemiologia , Degeneração do Disco Intervertebral/epidemiologia , Deslocamento do Disco Intervertebral/epidemiologia , Osteoporose/epidemiologia , Adulto , Idoso , Consumo de Bebidas Alcoólicas/epidemiologia , Consumo de Bebidas Alcoólicas/fisiopatologia , Índice de Massa Corporal , Doenças Cardiovasculares/etiologia , Doenças Cardiovasculares/fisiopatologia , Fumar Cigarros/epidemiologia , Fumar Cigarros/fisiopatologia , Dislipidemias/complicações , Dislipidemias/fisiopatologia , Feminino , Humanos , Hipóxia/complicações , Hipóxia/fisiopatologia , Degeneração do Disco Intervertebral/complicações , Degeneração do Disco Intervertebral/fisiopatologia , Deslocamento do Disco Intervertebral/complicações , Deslocamento do Disco Intervertebral/fisiopatologia , Japão/epidemiologia , Masculino , Pessoa de Meia-Idade , Razão de Chances , Osteoporose/complicações , Osteoporose/fisiopatologia , Estresse Oxidativo , Estudos Retrospectivos , Fatores de Risco , Fatores Sexuais
15.
Biosci Rep ; 41(7)2021 07 30.
Artigo em Inglês | MEDLINE | ID: mdl-34196345

RESUMO

BACKGROUND: Alopecia areata is an autoimmune hair loss disease with infiltration of pro-inflammatory cells into hair follicles. The role of Tgr5 in dermatitis has attracted considerable attention. The present study aimed to investigate the effect of Tgr5 in the development of Alopecia areata. METHODS: The study utilized a comparison control group design with four groups of wild-type group, wild-type+INT777 group, Tgr5-/- group, and Tgr5-/-+INT777 group. The mice were treated with INT777 (30 mg/kg/day) or the carrier solution (DMSO) intraperitoneally for 7 weeks, and the back skin was collected and analyzed by histology and immunohistochemistry staining. The lumbar vertebrae 4 has also been analyzed by DXA and Micro-CT. RESULTS: Tgr5-/- mice displayed the decreasingly significant in hair area and length, skin thickness, and the ratio of anagen and telogen, collagen, and mast cell number and loss the bone mass than WT group. After treating with INT777, the appearance of alopecia areata and bone microstructure has improved. Immunohistochemistry and qPCR analysis showed that activation of Tgr5 can down-regulate the express of JAK1, STAT3, IL-6, TNF-α, and VEGF. CONCLUSION: These findings indicate that activation of Tgr5 mediated amelioration of alopecia areata and osteoporosis by down-regulated JAK1-STAT3 signaling pathway.


Assuntos
Alopecia em Áreas/tratamento farmacológico , Anti-Inflamatórios/farmacologia , Densidade Óssea/efeitos dos fármacos , Ácidos Cólicos/farmacologia , Folículo Piloso/efeitos dos fármacos , Vértebras Lombares/efeitos dos fármacos , Osteoporose/tratamento farmacológico , Receptores Acoplados a Proteínas G/agonistas , Alopecia em Áreas/genética , Alopecia em Áreas/metabolismo , Alopecia em Áreas/fisiopatologia , Animais , Modelos Animais de Doenças , Folículo Piloso/crescimento & desenvolvimento , Folículo Piloso/metabolismo , Interleucina-6/genética , Interleucina-6/metabolismo , Janus Quinase 1/genética , Janus Quinase 1/metabolismo , Vértebras Lombares/metabolismo , Vértebras Lombares/fisiopatologia , Masculino , Camundongos Endogâmicos C57BL , Camundongos Knockout , Osteoporose/genética , Osteoporose/metabolismo , Osteoporose/fisiopatologia , Receptores Acoplados a Proteínas G/genética , Receptores Acoplados a Proteínas G/metabolismo , Fator de Transcrição STAT3/genética , Fator de Transcrição STAT3/metabolismo , Transdução de Sinais , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/metabolismo , Fator A de Crescimento do Endotélio Vascular/genética , Fator A de Crescimento do Endotélio Vascular/metabolismo
16.
PLoS One ; 16(7): e0253892, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34197518

RESUMO

INTRODUCTION: Osteoporosis and metabolic syndrome (MetS) are diseases that have serious public health consequences, reducing the quality of life of patients and increasing morbidity and mortality, with substantial healthcare expenditures. OBJECTIVE: To evaluate the impact of MetS on bone mineral density (BMD) and biochemical markers of bone formation and resorption in adolescents with excess weight. METHOD: A descriptive and analytical cross-sectional study was performed that evaluated 271 adolescents of both sexes (10 to 16 years). From the total sample, 42 adolescents with excess weight and the presence of MetS (14%) were selected. A further 42 adolescents with excess weight and without MetS were chosen, matched for chronological age, bone age, and pubertal developmental criteria to those with MetS, for each sex. Anthropometric measurements, blood pressure collection, and biochemical tests were performed in all adolescents, as well as evaluation of BMD and the bone biomarkers osteocalcin (OC), bone alkaline phosphatase (BAP), and carboxy-terminal telopeptide (S-CTx). RESULTS: The adolescents with excess weight and MetS exhibited significantly lower transformed BMD and concentrations of BAP, OC, and S-CTx compared to the matched group, except for OC in boys. A negative and significant correlation was observed between total body BMD and BAP (r = -0.55568; p = 0.005), OC (r = -0.81760; p = < .000), and S-CTx (r = -0.53838; p = 0.011) in girls. CONCLUSION: Metabolic syndrome may be associated with reduced bone mineral density and biochemical markers of bone formation and resorption in adolescents with excess weight.


Assuntos
Desenvolvimento do Adolescente/fisiologia , Densidade Óssea/fisiologia , Remodelação Óssea , Síndrome Metabólica/complicações , Osteoporose/epidemiologia , Adolescente , Fosfatase Alcalina/sangue , Biomarcadores/sangue , Criança , Colágeno Tipo I/sangue , Estudos Transversais , Feminino , Humanos , Masculino , Síndrome Metabólica/sangue , Síndrome Metabólica/fisiopatologia , Osteocalcina/sangue , Osteoporose/sangue , Osteoporose/etiologia , Osteoporose/fisiopatologia , Peptídeos/sangue , Qualidade de Vida , Fatores de Risco
17.
Int J Mol Med ; 48(2)2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34278442

RESUMO

Osteoporotic fracture healing is a complex clinical issue. The present study was conducted to investigate the repair properties of 11R­VIVIT on osteoporotic fractures and to examine the potential effects of 11R­VIVIT on osteoporotic bone marrow­derived mesenchymal stem cells (BMSCs), A rat model of osteoporotic femoral fracture was established, and the effects of the daily local injection of 11R­VIVIT or saline on fracture repairing were evaluated by micro­CT scans and H&E staining. Moreover, BMSCs from osteoporotic rats were treated with 11R­VIVIT, and the osteogenic and adipogenic differentiation of BMSCs was evaluated. The results revealed that 11R­VIVIT promoted bone formation and increased fracture healing. In addition, 11R­VIVIT promoted the differentiation of osteoporotic BMSCs into osteoblasts rather than adipocytes. Furthermore, mechanistic analysis revealed that 11R­VIVIT promoted autophagy by blocking the protein kinase B (AKT)/nuclear factor of activated T­cells (NFATc1) signaling pathway. Consistently, the activation and inhibition of autophagy using rapamycin and LY294002 confirmed the regulatory effects of 11R­VIVIT on autophagy. On the whole, the findings of the present study demonstrate that 11R­VIVIT promotes fracture healing in osteoporotic rats and enhances the osteogenic differentiation of osteoporotic BMSCs by dysregulating the AKT/NFATc1 signaling pathway.


Assuntos
Diferenciação Celular/efeitos dos fármacos , Consolidação da Fratura/efeitos dos fármacos , Regulação da Expressão Gênica/efeitos dos fármacos , Células-Tronco Mesenquimais/efeitos dos fármacos , Osteoporose/genética , Peptídeos/farmacologia , Adipogenia/efeitos dos fármacos , Adipogenia/genética , Animais , Autofagia/efeitos dos fármacos , Autofagia/genética , Diferenciação Celular/genética , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/genética , Células Cultivadas , Feminino , Consolidação da Fratura/genética , Consolidação da Fratura/fisiologia , Células-Tronco Mesenquimais/metabolismo , Osteogênese/efeitos dos fármacos , Osteogênese/genética , Osteoporose/metabolismo , Osteoporose/fisiopatologia , Ratos Sprague-Dawley , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/genética
18.
Inflamm Res ; 70(8): 859-875, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34272579

RESUMO

BACKGROUND: The physiological balance between bone resorption and bone formation is now known to be mediated by a cascade of events parallel to the classic osteoblast-osteoclast interaction. Thus, osteoimmunology now encompasses the role played by other cell types, such as cytokines, lymphocytes and chemokines, in immunological responses and how they help modulate bone metabolism. All these factors have an impact on the RANK/RANKL/OPG pathway, which is the major pathway for the maturation and resorption activity of osteoclast precursor cells, responsible for osteoporosis development. Recently, immunoporosis has emerged as a new research area in osteoimmunology dedicated to the immune system's role in osteoporosis. METHODS: The first part of this review presents theoretical concepts on the factors involved in the skeletal system and osteoimmunology. Secondly, existing treatments and novel therapeutic approaches to treat osteoporosis are summarized. These were selected from to the most recent studies published on PubMed containing the term osteoporosis. All data relate to the results of in vitro and in vivo studies on the osteoimmunological system of humans, mice and rats. FINDINGS: Treatments for osteoporosis can be classified into two categories. They either target osteoclastogenesis inhibition (denosumab, bisphosphonates), or they aim to restore the number and function of osteoblasts (romozumab, abaloparatide). Even novel therapies, such as resolvins, gene therapy, and mesenchymal stem cell transplantation, fall within this classification system. CONCLUSION: This review presents alternative pathways in the pathophysiology of osteoporosis, along with some recent therapeutic breakthroughs to restore bone homeostasis.


Assuntos
Remodelação Óssea , Reabsorção Óssea/metabolismo , Osteoblastos/metabolismo , Osteoclastos/metabolismo , Osteoporose/fisiopatologia , Osteoporose/terapia , Animais , Quimiocinas/metabolismo , Quitosana/química , Terapia Genética/métodos , Humanos , Sistema Imunitário , Linfócitos/metabolismo , Sistema de Sinalização das MAP Quinases , Camundongos , Nanopartículas/química , Osteócitos/metabolismo , Osteogênese , Osteoprotegerina/metabolismo , Ligante RANK/metabolismo , RNA Interferente Pequeno/metabolismo , Ratos
19.
J Orthop Surg Res ; 16(1): 429, 2021 Jul 03.
Artigo em Inglês | MEDLINE | ID: mdl-34217340

RESUMO

STUDY DESIGN: A retrospective cohort study. OBJECTIVE: To investigate the radiological and clinical outcomes of patients with or without pedicle-screw rod fixation (PSRF) in OLIF surgery. METHODS: Between June 2017 and December 2019, 66 consecutive patients who underwent OLIF surgery at two centers were divided into stand-alone and combined groups according to whether or not PSRF was used. Imaging and clinical data were collected preoperatively, postoperatively, 3 and 6 months postoperatively, and at the last follow-up. Related coefficient and multiple linear regression analysis was used to detect the influencing factors of cage subsidence (CS). RESULTS: There was a lower baseline BMD in the combined group (p = 0.005). The combined group showed superior VAS score at 3 months postoperatively, although there was no difference in long-term VAS and ODI scores between the two groups. The foraminal height (FH) of the two groups was comparable at preoperatively, postoperatively, and 3 months postoperatively, but the combined group showed better maintenance of FH at 6 months postoperatively (p = 0.049) and last follow-up (p = 0.019). The total CS (tCS) of the combined group was lower than that of the stand-alone group during the whole follow-up period (all p ≤ 0.001). Multiple linear regression suggested that lower BMD was the risk factor for main CS, and PSRF could significantly reduce the BMD threshold for severe CS (-4.77 vs -1.38). CONCLUSIONS: OLIF combined with PSRF can effectively avoid foraminal height loss and prevent severe CS, which may be more suitable for patients with osteoporosis or osteopenia and improve clinical outcomes.


Assuntos
Vértebras Lombares/cirurgia , Osteoporose/cirurgia , Parafusos Pediculares , Fusão Vertebral/instrumentação , Fusão Vertebral/métodos , Densidade Óssea , Feminino , Humanos , Modelos Lineares , Masculino , Pessoa de Meia-Idade , Osteoporose/diagnóstico por imagem , Osteoporose/fisiopatologia , Período Pós-Operatório , Radiografia , Estudos Retrospectivos , Resultado do Tratamento
20.
Orthop Surg ; 13(4): 1262-1268, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33951328

RESUMO

OBJECTIVE: To evaluate the effects of different intervention measures to prevent falls in elderly osteoporotic patients. METHODS: A randomized controlled trial was conducted in our outpatient ward from August 2014 to September 2015. A total of 420 patients over 60 years of age were assigned to four groups. NA VitD group took 800 mg calcium and 800 IU non-active vitamin D. P-NA VitD group took 800 mg calcium, 800 IU non-active vitamin D, and received physical exercise. A VitD group took 800 mg calcium and 0.5 µg active vitamin D. P-A VitD took 800 mg calcium, 0.5 µg active vitamin D, and received physical exercise. Physical exercise includes guidance in improving muscle strength and balance ability. Short physical performance battery (SPPB), grip strength, modified falls efficacy scale (MFES), blood calcium, and 25-hydroxyl vitamin D were measured before interventions and at 3, 6, and 12 months after interventions. Bone mineral density (BMD) was detected before interventions and at 12 months after interventions. The incidence of falls and fractures, adverse events, and drug reactions were recorded for 12 months. RESULTS: A total of 420 patients were allocated in the four groups: 98 cases into the NA VitD group (11 males, 87 females), 97 cases into the P-NA VitD group (13 males, 84 females), 99 cases in the A VitD group (15 males, 84 females), and 98 cases into the P-A VitD group (11 males, 87 females). At 6 months after interventions, the SPPB of A VitD group significantly increased from 6.9 ± 1.9 to 8.0 ± 2.4 (P < 0.05), and the SPPB of A VitD group significantly increased from 7.2 ± 2.1 to 8.6 ± 1.7 (P < 0.05). At 6 months after interventions, MFES of P-NA VitD group 7.0 ± 1.6 to 7.6 ± 1.6 (P < 0.05), and MFES of P-A VitD group significantly increased from 6.7 ± 1.6 to 7.5 ± 1.6 (P < 0.05). At 12 months after interventions, SPPB of all groups, grip strength, and MFES of P-NA VitD group, A VitD group, P-A VitD group were significantly improved (P < 0.05). The BMD of lumbar vertebrae of A VitD group significantly increased from 0.742 ± 0.042 to 0.776 ± 0.039, and P-A VitD group significantly increased from 0.743 ± 0.048 to 0.783 ± 0.042 (P < 0.05). No serious adverse events occurred during the 12 months of follow-up. CONCLUSION: Active vitamin D is better than non-active vitamin D to improve physical ability and the BMD of lumbar vertebrae and reduce the risk of falls.


Assuntos
Acidentes por Quedas/prevenção & controle , Cálcio/administração & dosagem , Terapia por Exercício/métodos , Osteoporose/prevenção & controle , Vitamina D/administração & dosagem , Idoso , Densidade Óssea/fisiologia , Terapia Combinada , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Força Muscular/fisiologia , Osteoporose/fisiopatologia , Equilíbrio Postural/fisiologia
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