RESUMO
Schimke immuno-osseous dysplasia is a rare multisystemic disorder caused by biallelic loss of function of the SMARCAL1 gene that plays a pivotal role in replication fork stabilization and thus DNA repair. Individuals affected from this disease suffer from disproportionate growth failure, steroid resistant nephrotic syndrome leading to renal failure and primary immunodeficiency mediated by T cell lymphopenia. With infectious complications being the leading cause of death in this disease, researching the nature of the immunodeficiency is crucial, particularly as the state is exacerbated by loss of antibodies due to nephrotic syndrome or immunosuppressive treatment. Building on previous findings that identified the loss of IL-7 receptor expression as a possible cause of the immunodeficiency and increased sensitivity to radiation-induced damage, we have employed spectral cytometry and multiplex RNA-sequencing to assess the phenotype and function of T cells ex-vivo and to study changes induced by in-vitro UV irradiation and reaction of cells to the presence of IL-7. Our findings highlight the mature phenotype of T cells with proinflammatory Th1 skew and signs of exhaustion and lack of response to IL-7. UV light irradiation caused a severe increase in the apoptosis of T cells, however the expression of the genes related to immune response and regulation remained surprisingly similar to healthy cells. Due to the disease's rarity, more studies will be necessary for complete understanding of this unique immunodeficiency.
Assuntos
Reparo do DNA , Osteocondrodisplasias , Doenças da Imunodeficiência Primária , Humanos , Doenças da Imunodeficiência Primária/genética , Doenças da Imunodeficiência Primária/diagnóstico , Doenças da Imunodeficiência Primária/imunologia , Osteocondrodisplasias/genética , Osteocondrodisplasias/imunologia , Reparo do DNA/genética , DNA Helicases/genética , Síndrome Nefrótica/etiologia , Síndrome Nefrótica/genética , Linfócitos T/imunologia , Arteriosclerose/genética , Arteriosclerose/etiologia , Arteriosclerose/imunologia , Masculino , Feminino , Embolia Pulmonar/genética , Embolia Pulmonar/etiologia , Doenças Ósseas Metabólicas/etiologia , Doenças Ósseas Metabólicas/genética , Transtornos do Crescimento/genética , Transtornos do Crescimento/etiologia , Raios Ultravioleta/efeitos adversos , Criança , Apoptose/genética , Síndromes de Imunodeficiência/genética , Síndromes de Imunodeficiência/imunologiaRESUMO
BACKGROUND: Complications of prolonged continuous kidney replacement therapy (CKRT) have not been well described. Our objective was to describe mineral metabolism and bone findings in children who required prolonged CKRT. METHODS: In this single center prospective observational study, we enrolled 37 patients who required CKRT for ≥ 28 days with regional citrate anticoagulation. Exposure was duration on CKRT and outcomes were 25-hydroxy vitamin D and osteopenia and/or fractures. RESULTS: The prevalence of vitamin D deficiency and insufficiency was 17.2% and 69.0%, respectively. 29.7% of patients had radiographic findings of osteopenia and/or fractures. There was no association between vitamin D deficiency or insufficiency with age or ethnicity. Time on CKRT and intact PTH levels were not predictive of vitamin D levels. Children with chronic liver disease were more likely to have osteopenia and/or fractures compared children with other primary diagnoses, odds ratio (3.99 (95%CI, 1.58-2.91), p = 0.003) after adjusting for age and time on CKRT. CONCLUSION: Vitamin D deficiency and/or insufficiency, and osteopenia and/or fractures are prevalent among children who require CKRT for a prolonged period. The risk for MBD may be higher with chronic liver disease. Higher doses of vitamin D may be required to maintain normal levels while on CKRT.
Assuntos
Doenças Ósseas Metabólicas , Terapia de Substituição Renal Contínua , Deficiência de Vitamina D , Vitamina D , Humanos , Feminino , Masculino , Doenças Ósseas Metabólicas/epidemiologia , Doenças Ósseas Metabólicas/etiologia , Estudos Prospectivos , Deficiência de Vitamina D/epidemiologia , Deficiência de Vitamina D/complicações , Deficiência de Vitamina D/sangue , Deficiência de Vitamina D/tratamento farmacológico , Criança , Vitamina D/sangue , Vitamina D/análogos & derivados , Vitamina D/uso terapêutico , Pré-Escolar , Adolescente , Fraturas Ósseas/epidemiologia , Fraturas Ósseas/etiologia , PrevalênciaRESUMO
Pyruvate kinase (PK) deficiency, a rare, congenital haemolytic anaemia caused by mutations in the PKLR gene, is associated with many clinical manifestations, but the full disease burden has yet to be characterised. The Peak Registry (NCT03481738) is an observational, longitudinal registry of adult and paediatric patients with PK deficiency. Here, we described comorbidities and complications in these patients by age at most recent visit and PKLR genotype. As of 13 May 2022, 241 patients were included in the analysis. In total, 48.3% had undergone splenectomy and 50.5% had received chelation therapy. History of iron overload (before enrolment/during follow-up) was common (52.5%), even in never-transfused patients (20.7%). Neonatal complications and symptoms included jaundice, splenomegaly and hepatomegaly, with treatment interventions required in 41.5%. Among adults, osteopenia/osteoporosis occurred in 19.0% and pulmonary hypertension in 6.7%, with median onset ages of 37, 33 and 22 years, respectively. Biliary events and bone health problems were common across PKLR genotypes. Among 11 patients who had thromboembolic events, eight had undergone prior splenectomy. Patients with PK deficiency may have many complications, which can occur early in and throughout life. Awareness of their high disease burden may help clinicians better provide appropriate monitoring and management of these patients.
Assuntos
Anemia Hemolítica Congênita não Esferocítica , Piruvato Quinase , Erros Inatos do Metabolismo dos Piruvatos , Sistema de Registros , Humanos , Piruvato Quinase/deficiência , Piruvato Quinase/genética , Masculino , Feminino , Adulto , Criança , Anemia Hemolítica Congênita não Esferocítica/genética , Anemia Hemolítica Congênita não Esferocítica/epidemiologia , Erros Inatos do Metabolismo dos Piruvatos/genética , Erros Inatos do Metabolismo dos Piruvatos/epidemiologia , Adolescente , Pré-Escolar , Lactente , Comorbidade , Pessoa de Meia-Idade , Esplenectomia , Adulto Jovem , Hipertensão Pulmonar/etiologia , Hipertensão Pulmonar/genética , Hipertensão Pulmonar/epidemiologia , Sobrecarga de Ferro/etiologia , Sobrecarga de Ferro/epidemiologia , Doenças Ósseas Metabólicas/etiologia , Doenças Ósseas Metabólicas/epidemiologia , Recém-NascidoRESUMO
PURPOSE: Metabolic bone disease of prematurity (MBDP) remains a significant cause of morbidity in extremely premature newborns. In high-risk patients, suspected diagnosis and subsequent treatment modifications, with limitations in terms of sensitivity and specificity, rely on low phosphorus levels and/or high levels of alkaline phosphatase (ALP). We investigated the potential of fibroblast growth factor-23 (FGF23) as an early marker for MBDP when measured at 3-4 weeks of life in at-risk patients. METHODS: A single-center prospective observational non-interventional study including preterm newborns of both sexes, with a gestational age of less than 32 weeks and/or a birth weight of less than 1500 g. In the standard biochemical screening for MBDP performed between 3 and 4 weeks of life within a nutritional profile, the determination of FGF23 was included along with other clinical and metabolic studies. The study was conducted at Marqués de Valdecilla University Hospital in Santander, Spain, from April 2020 to March 2021. Participants provided informed consent. Biochemical analyses were conducted using various platforms, and follow-up evaluations were performed at the discretion of neonatologists. Patients at high risk for MBDP received modifications in treatment accordingly. The sample was descriptively analyzed, presenting measures of central tendency and dispersion for continuous variables, and absolute numbers/percentages for categorical ones. Tests used included t-tests, MannâWhitney U tests, chi-square tests, logistic regressions, Pearson correlation, and ROC curve analysis (IBM SPSS Statistics version 19). Significance level: P < 0.05. RESULTS: In the study involving 25 at-risk premature newborns, it was found that 20% (n = 5) were diagnosed with MBDP. Three of these patients (60%) were identified as high-risk based on standard biochemical evaluation at 3-4 weeks of age, while the other two patients (40%) were diagnosed in subsequent weeks. However, in all 5 patients, measurement of FGF23 levels would allow for early identification and optimization of treatment before other markers become altered. Low levels of FGF23 at 3-4 weeks, even with normal phosphorus and ALP levels, indicate the need for modifications in nutritional supplementation. CONCLUSIONS: MBDP remains a significant concern in extremely premature newborns. Current diagnostic methods rely on limited biochemical markers. Early detection of low FGF23 levels enables timely interventions, potentially averting demineralization.
Assuntos
Biomarcadores , Doenças Ósseas Metabólicas , Fator de Crescimento de Fibroblastos 23 , Fatores de Crescimento de Fibroblastos , Humanos , Recém-Nascido , Feminino , Fatores de Crescimento de Fibroblastos/sangue , Biomarcadores/sangue , Estudos Prospectivos , Masculino , Doenças Ósseas Metabólicas/sangue , Doenças Ósseas Metabólicas/diagnóstico , Doenças Ósseas Metabólicas/etiologia , Doenças do Prematuro/diagnóstico , Doenças do Prematuro/sangue , Recém-Nascido PrematuroRESUMO
Patients with inflammatory bowel disease (IBD) are prone to reduced bone mineral density and elevated overall fracture risk. Osteopenia affects up to 40% of patients with IBD (high regional variability). Besides disease activity, IBD specialists must consider possible side effects of medication and the presence of associated diseases and extraintestinal manifestations. Osteopenia and osteoporosis remain frequent problems in patients with IBD and are often underestimated because of widely differing screening and treatment practices. Malnutrition, chronic intestinal inflammation and corticosteroid intake are the major pathophysiological factors contributing to osteoporosis. Patients with IBD are screened for osteoporosis using dual-energy X-ray absorptiometry (DXA), which is recommended for all patients with a prolonged disease course of more than three months, with repeated corticosteroid administration, aged >40 years with a high FRAX risk score or aged <40 years with multiple risk factors. From a therapeutic perspective, besides good disease control, vitamin D supplementation and glucocorticoid sparing, several specific osteological options are available: bisphosphonates, receptor activator of nuclear factor kappa-B ligand (RANKL) inhibitors (denosumab), parathyroid hormone (PTH) analogues and selective estrogen receptor modulators. This review provides an overview of the pathophysiology, diagnosis, prevention and treatment of IBD-associated bone loss.
Assuntos
Absorciometria de Fóton , Densidade Óssea , Doenças Ósseas Metabólicas , Doenças Inflamatórias Intestinais , Osteoporose , Humanos , Doenças Inflamatórias Intestinais/complicações , Doenças Inflamatórias Intestinais/fisiopatologia , Osteoporose/etiologia , Doenças Ósseas Metabólicas/etiologia , Fatores de Risco , Vitamina D/uso terapêutico , Conservadores da Densidade Óssea/uso terapêutico , Difosfonatos/uso terapêuticoRESUMO
BACKGROUND: Osteopenia reflects frailty and has been shown to be associated with outcomes in cancer patients. This study was undertaken to examine whether osteopenia is an independent prognostic factor in patients with esophageal cancer after resection. METHODS: A total of 214 patients who underwent surgery for esophageal cancer were analyzed retrospectively. Bone mineral density (BMD) of the 11th thoracic vertebra was measured by computed tomography scan, and patients classified into osteopenia and normal BMD groups with BMD <160 Hounsfield units as the cutoff. Clinicopathological data and prognosis were analyzed. RESULTS: The 5-year survival rate was 55.4% for the osteopenia group and 74.7% for the normal BMD group with a significantly worse prognosis in the osteopenia group (p = 0.0080). In multivariable analysis, osteopenia was a significant independent risk factor associated with overall survival (hazard ratio [HR] 1.90, 95% confidence interval [CI] 1.27-3.34, and p = 0.0151) along with R1/2 resection (HR 3.02, 95% CI 1.71-5.18, and p = 0.0002). CONCLUSION: In patients with esophageal cancer undergoing resection, osteopenia may be a surrogate marker for frailty and an independent predictor of prognosis.
Assuntos
Doenças Ósseas Metabólicas , Neoplasias Esofágicas , Esofagectomia , Humanos , Neoplasias Esofágicas/cirurgia , Neoplasias Esofágicas/mortalidade , Neoplasias Esofágicas/complicações , Neoplasias Esofágicas/patologia , Masculino , Feminino , Doenças Ósseas Metabólicas/etiologia , Doenças Ósseas Metabólicas/diagnóstico , Estudos Retrospectivos , Pessoa de Meia-Idade , Idoso , Prognóstico , Densidade Óssea , Fatores de Risco , Taxa de Sobrevida , Período Pré-Operatório , Tomografia Computadorizada por Raios X , Idoso de 80 Anos ou maisRESUMO
Introduction: Musculoskeletal disorders could be associated with metabolic disorders that are common after kidney transplantation, which could reduce the quality of life of patients. The aim of this study was to assess the prevalence of both musculoskeletal and metabolic disorders in kidney transplant patients. Methods: MEDLINE, CINAHL, Cochrane Library, EMBASE and Web of Science were searched from their inception up to June 2023. DerSimonian and Laird random-effects method was used to calculate pooled prevalence estimates and their 95% confidence intervals (CIs). Results: 21,879 kidney transplant recipients from 38 studies were analysed. The overall proportion of kidney transplant patients with musculoskeletal disorders was 27.2% (95% CI: 18.4-36.0), with low muscle strength (64.5%; 95% CI: 43.1-81.3) being the most common disorder. Otherwise, the overall proportion of kidney transplant patients with metabolic disorders was 37.6% (95% CI: 21.9-53.2), with hypovitaminosis D (81.8%; 95% CI: 67.2-90.8) being the most prevalent disorder. Conclusion: The most common musculoskeletal disorders were low muscle strength, femoral osteopenia, and low muscle mass. Hypovitaminosis D, hyperparathyroidism, and hyperuricemia were also the most common metabolic disorders. These disorders could be associated with poorer quality of life in kidney transplant recipients. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/, identifier [CRD42023449171].
Assuntos
Transplante de Rim , Doenças Metabólicas , Doenças Musculoesqueléticas , Humanos , Transplante de Rim/efeitos adversos , Prevalência , Doenças Musculoesqueléticas/epidemiologia , Doenças Musculoesqueléticas/etiologia , Doenças Metabólicas/epidemiologia , Qualidade de Vida , Força Muscular , Transplantados , Deficiência de Vitamina D/epidemiologia , Deficiência de Vitamina D/complicações , Doenças Ósseas Metabólicas/epidemiologia , Doenças Ósseas Metabólicas/etiologia , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologiaRESUMO
Fragility fractures as a result of osteoporosis, osteopenia, or vitamin D deficiency are some of the most common injuries encountered in orthopedics and require careful consideration when determining the appropriate management and treatment options. A thorough perioperative evaluation can identify causes of low bone mineral density allowing for initiation of appropriate therapy. Surgical treatment of these fractures can be difficult, and techniques should be employed to ensure stable fixation. It is important to understand the potential pitfalls associated with treatment of fragility fractures to prevent avoidable complications. Postoperative management is key to preventing future injuries in this unique patient population.
Assuntos
Doenças Ósseas Metabólicas , Osteoporose , Deficiência de Vitamina D , Humanos , Deficiência de Vitamina D/complicações , Doenças Ósseas Metabólicas/etiologia , Doenças Ósseas Metabólicas/prevenção & controle , Osteoporose/complicações , Extremidade Superior/cirurgia , Extremidade Superior/lesões , Fraturas por Osteoporose/cirurgia , Fraturas por Osteoporose/prevenção & controle , Fraturas por Osteoporose/etiologia , Densidade ÓsseaRESUMO
The objectives were to examine if there is a causal relationship between osteosarcopenic adiposity (OSA) syndrome (coexistence of osteopenia/osteoporosis, sarcopenia, and excess adiposity) and cardiometabolic disorders or if these disorders initiate the development of OSA and its worsening. The search was conducted in PubMed, Scopus, and Web of Science to include articles up to the end of 2023. Of n=539 articles retrieved, n=15 met the eligibility criteria. Only studies conducted in adults and with all three body composition compartments (bone, muscle/lean, adipose) measured were considered. The results revealed that several cardiometabolic disorders, namely, hypertension, dyslipidemia (elevated total and LDL-cholesterol, lower HDL-cholesterol), insulin resistance, hyperglycemia, lower serum vitamin D, and some inflammatory markers were accompanied by OSA. In most cases, the OSA phenotype was associated with worse outcomes than cases with healthy or less impaired body composition. Our initial questions about the reciprocal cause-and-effect relationships could be surmised with more certainty for the OSA and some cardiovascular risks (hypertension, dyslipidemia) and some metabolic abnormalities (several inflammatory markers). The results of this review underscore the importance of body composition in health and from a clinical perspective, all three body composition compartments should be measured by standardized technologies using regulated diagnostic criteria to identify OSA. Randomized trials and prospective studies in diverse groups of older and younger individuals are necessary to determine if the relationships between OSA and clinical endpoints are causal and reversible through intervention and to uncover the mechanisms.
Assuntos
Adiposidade , Fenótipo , Sarcopenia , Humanos , Doenças Cardiovasculares , Composição Corporal/fisiologia , Osteoporose/etiologia , Doenças Ósseas Metabólicas/etiologia , Doenças Ósseas Metabólicas/metabolismo , Fatores de Risco CardiometabólicoRESUMO
BACKGROUND: Osteoporosis is one of the risk factors for screw loosening after lumbar fusion. However, the probability of preoperative osteoporosis screening in patients with lumbar degenerative disease is low. Therefore, the aim of this study was to investigate whether a simplified vertebral bone quality (VBQ) score based on T12 T1-MRI could opportunistically predict osteoporosis in patients with degenerative lumbar spine diseases. METHODS: We retrospectively analyzed cases treated for lumbar degenerative diseases at a single institution between August 2021 and June 2022. The patients were divided into three groups by the lowest T-score: osteoporosis group, osteopenia group, and normal bone mineral density (BMD) group. The signal intensity based on the T12 vertebral body divided by the signal intensity of the cerebrospinal fluid was calculated to obtain the simplified VBQ score, as well as the CT-based T12HU value and the traditional L1-4VBQ score. Various statistical analyses were used to compare VBQ, HU and DEXA, and the optimal T12VBQ threshold for predicting osteoporosis was obtained by plotting the receiver operating curve (ROC) analysis. RESULTS: Total of 166 patients were included in this study. There was a statistically significant difference in T12VBQ scores between the three groups (p < 0.001). Pearson correlation showed that there was a moderate correlation between T12VBQ and T-score (r=-0.406, p < 0.001). The AUC value of T12VBQ, which distinguishes between normal and low BMD, was 0.756, and the optimal diagnostic threshold was 2.94. The AUC value of T12VBQ, which distinguishes osteoporosis from non-osteoporosis, was 0.634, and the optimal diagnostic threshold was 3.18. CONCLUSION: T12VBQ can be used as an effective opportunistic screening method for osteoporosis in patients with lumbar degenerative diseases. It can be used as a supplement to the evaluation of DEXA and preoperative evaluation. TRIAL REGISTRATION: retrospectively registered number:1502-009-644; retrospectively registered number date:27 oct 2022.
Assuntos
Densidade Óssea , Vértebras Lombares , Osteoporose , Humanos , Osteoporose/diagnóstico por imagem , Feminino , Masculino , Vértebras Lombares/diagnóstico por imagem , Estudos Retrospectivos , Pessoa de Meia-Idade , Idoso , Imageamento por Ressonância Magnética/métodos , Valor Preditivo dos Testes , Vértebras Torácicas/diagnóstico por imagem , Degeneração do Disco Intervertebral/diagnóstico por imagem , Absorciometria de Fóton , Doenças Ósseas Metabólicas/diagnóstico por imagem , Doenças Ósseas Metabólicas/etiologia , AdultoRESUMO
OBJECTIVE: Increasing research suggests that paraspinal muscle fat infiltration may be a potential biological marker for the assessment of osteoporosis. Our aim was to investigate the relationship between lumbar paraspinal muscle properties on MRI and volumetric bone mineral density (vBMD) based on QCT in patients with lumbar disc herniation (LDH). METHODS: A total of 383 patients (aged 24-76 years, 193 females) with clinically and radiologically diagnosed LDH were enrolled in this retrospective study. The muscle cross-sectional area (CSA) and the proton density fat fraction (PDFF) were measured for the multifidus (MF), erector spinae (ES) and psoas major (PS) at the central level of L3/4, L4/5 and L5/S1 on lumbar MRI. QCT was used to measure the vBMD of two vertebral bodies at L1 and L2 levels. Patients were divided into three groups based on their vBMD values: normal bone density group (> 120 mg/cm3), osteopenia group (80 to 120 mg/cm3) and osteoporosis group (< 80 mg/cm3). The differences in paraspinal muscle properties among three vBMD groups were tested by one-way ANOVA with post hoc analysis. The relationships between paraspinal muscle properties and vBMD were analyzed using Pearson correlation coefficients. Furthermore, the association between vBMD and paraspinal muscle properties was further evaluated using multiple linear regression analysis, with age and sex also included as predictors. RESULTS: Among the 383 LDH patients, 191 had normal bone density, 129 had osteopenia and 63 had osteoporosis. In LDH patients, compared to normal and osteopenia group, paraspinal muscle PDFF was significantly greater in osteoporosis group, while paraspinal muscle CSA was lower (p < 0.001). After adjusting for age and sex, it was found that MF PDFF and PS CSA were found to be independent factors influencing vBMD (p < 0.05). CONCLUSION: In patients with LDH, paraspinal muscle properties measured by IDEAL-IQ sequence and lumbar MR scan were found to be related to vBMD. There was a correlation between the degree of paraspinal muscle PDFF and decreasing vBMD, as well as a decrease paraspinal muscle CSA with decreasing vBMD. These findings suggest that clinical management should consider offering tailored treatment options for patients with LDH based on these associations.
Assuntos
Densidade Óssea , Deslocamento do Disco Intervertebral , Vértebras Lombares , Imageamento por Ressonância Magnética , Osteoporose , Músculos Paraespinais , Humanos , Pessoa de Meia-Idade , Feminino , Masculino , Músculos Paraespinais/diagnóstico por imagem , Músculos Paraespinais/patologia , Músculos Paraespinais/fisiopatologia , Adulto , Densidade Óssea/fisiologia , Vértebras Lombares/diagnóstico por imagem , Deslocamento do Disco Intervertebral/diagnóstico por imagem , Deslocamento do Disco Intervertebral/fisiopatologia , Estudos Retrospectivos , Idoso , Osteoporose/diagnóstico por imagem , Tomografia Computadorizada por Raios X , Adulto Jovem , Doenças Ósseas Metabólicas/diagnóstico por imagem , Doenças Ósseas Metabólicas/etiologiaRESUMO
BACKGROUND: Activin A has been shown to enhance osteoclast activity and its inhibition results in bone growth. The potential role of activin A as a marker of chronic kidney disease-mineral bone disease (CKD-MBD) and its relationship with other markers has not been studied in children with CKD. METHODS: A cross sectional study was conducted among 40 children aged 2 to 18 years with CKD (Stage 2 to 5; 10 in each stage) and 40 matched controls. Activin A, cathepsin K, FGF-23, PTH, serum calcium, phosphorous and alkaline phosphatase in both groups were measured and compared. The correlation of activin A and markers of CKD-MBD was studied. A p value of < 0.05 was considered significant. RESULTS: The mean age of children with CKD was 9.30 ± 3.64 years. Mean levels of activin A in cases were 485.55 pg/ml compared to 76.19 pg/ml in controls (p < 0.001). FGF-23 levels in cases were 133.18 pg/ml while in controls it was 6.93 pg/ml (p < 0.001). Mean levels of cathepsin K were also significantly higher in cases as compared to controls. There was a progressive increase in activin A and cathepsin K levels with increasing stage of CKD. Activin A had a significant positive correlation with serum creatinine (r = 0.51; p < 0.001). CONCLUSIONS: Activin A levels progressively rise with advancing CKD stage. These findings suggest that activin A can be a potential early marker of CKD-MBD in children.
Assuntos
Ativinas , Biomarcadores , Fator de Crescimento de Fibroblastos 23 , Fatores de Crescimento de Fibroblastos , Insuficiência Renal Crônica , Humanos , Criança , Ativinas/sangue , Fator de Crescimento de Fibroblastos 23/sangue , Biomarcadores/sangue , Feminino , Estudos Transversais , Masculino , Adolescente , Pré-Escolar , Insuficiência Renal Crônica/sangue , Insuficiência Renal Crônica/complicações , Fatores de Crescimento de Fibroblastos/sangue , Catepsina K/sangue , Distúrbio Mineral e Ósseo na Doença Renal Crônica/sangue , Distúrbio Mineral e Ósseo na Doença Renal Crônica/diagnóstico , Distúrbio Mineral e Ósseo na Doença Renal Crônica/etiologia , Estudos de Casos e Controles , Hormônio Paratireóideo/sangue , Cálcio/sangue , Fosfatase Alcalina/sangue , Doenças Ósseas Metabólicas/sangue , Doenças Ósseas Metabólicas/etiologia , Doenças Ósseas Metabólicas/diagnósticoRESUMO
OBJECTIVE: To identify patients with type 2 diabetes mellitus (T2DM) with no history of fracture or osteoporosis treatment who are at risk of bone complications through the assessment of bone quality and quantity. METHODS: Of the outpatients attending our clinic during 2021 to 2022, we retrospectively enrolled 137 (men/women: 85/52, median age: 65 years) consecutive patients aged ≥40 years who had T2DM but no history of fracture or osteoporosis treatment. The lumbar spine and femoral neck bone mineral density and the trabecular bone score were determined using dual-energy X-ray absorptiometry. Independent factors associated with bone disease were identified using logistic regression analysis, and odds ratios (ORs) were calculated. RESULTS: Age and female sex were significantly associated with high ORs for development of bone disease. The integrated risk of bone complications was nearly 40-fold higher in older (≥65 years) women than in younger (<65 years) men. This difference remained after adjustment for the duration of T2DM, body mass index, and HbA1c level. CONCLUSIONS: Older women have the highest risk of osteopenia and osteoporosis among patients with T2DM who have no history of fracture or osteoporosis treatment. These patients should undergo intensive monitoring for bone fragility from an early stage of their disease.
Assuntos
Absorciometria de Fóton , Densidade Óssea , Diabetes Mellitus Tipo 2 , Osteoporose , Humanos , Diabetes Mellitus Tipo 2/complicações , Masculino , Feminino , Idoso , Pessoa de Meia-Idade , Osteoporose/complicações , Osteoporose/etiologia , Fatores Sexuais , Estudos Retrospectivos , Fatores Etários , Fatores de Risco , Fraturas por Osteoporose/epidemiologia , Fraturas por Osteoporose/etiologia , Doenças Ósseas Metabólicas/etiologia , Doenças Ósseas Metabólicas/complicações , Doenças Ósseas Metabólicas/epidemiologia , Vértebras Lombares/diagnóstico por imagem , Colo do Fêmur/diagnóstico por imagem , Colo do Fêmur/patologia , Índice de Massa CorporalRESUMO
BACKGROUND/AIM: Osteopenia, the loss of bone mineral density (BMD), was recently reported as a prognostic factor in various cancers. However, the prognostic significance of preoperative osteopenia in breast cancer remains unclear. This study aimed to clarify the clinical significance of preoperative osteopenia in breast cancer. PATIENTS AND METHODS: We retrospectively analyzed the relationship between osteopenia and clinical factors and prognosis in 532 patients with pathological Stage I-III primary breast cancer between 2009 and 2017. Osteopenia was assessed by measuring the average pixel density (Hounsfield unit) in the midvertebral core of the 11th thoracic vertebra on enhanced preoperative computed tomography. RESULTS: Osteopenia was diagnosed in 186 (35.0%) patients. The recurrence-free survival (RFS) rate was significantly worse in the osteopenia group than in the non-osteopenia group (p=0.0275), but there was no significant difference in overall survival (OS) between the two groups. When evaluated by menopausal status, RFS and OS were significantly worse in the osteopenia group than in the non-osteopenia group (p=0.0094 and p=0.0264, respectively) in premenopausal patients. However, there were no significant differences in RFS and OS between the two groups among postmenopausal patients. In premenopausal patients, osteopenia was an independent prognostic factor for RFS in a multivariate analysis (p=0.0266). CONCLUSION: Preoperative osteopenia was independently associated with recurrence of breast cancer.
Assuntos
Doenças Ósseas Metabólicas , Neoplasias da Mama , Humanos , Neoplasias da Mama/cirurgia , Neoplasias da Mama/complicações , Neoplasias da Mama/patologia , Neoplasias da Mama/mortalidade , Feminino , Doenças Ósseas Metabólicas/complicações , Doenças Ósseas Metabólicas/patologia , Doenças Ósseas Metabólicas/etiologia , Pessoa de Meia-Idade , Prognóstico , Adulto , Idoso , Estudos Retrospectivos , Densidade Óssea , Período Pré-Operatório , Idoso de 80 Anos ou mais , Intervalo Livre de DoençaRESUMO
Chronic pancreatitis (CP) is a progressive inflammatory disease with an increasing global prevalence. In recent years, a strong association between CP and metabolic bone diseases (MBDs), especially osteoporosis, has been identified, attracting significant attention in the research field. Epidemiological data suggest a rising trend in the incidence of MBDs among CP patients. Notably, recent studies have highlighted a profound interplay between CP and altered nutritional and immune profiles, offering insights into its linkage with MBDs. At the molecular level, CP introduces a series of biochemical disturbances that compromise bone homeostasis. One critical observation is the disrupted metabolism of vitamin D and vitamin K, both essential micronutrients for maintaining bone integrity, in CP patients. In this review, we provide physio-pathological perspectives on the development and mechanisms of CP-related MBDs. We also outline some of the latest therapeutic strategies for treating patients with CP-associated MBDs, including stem cell transplantation, monoclonal antibodies, and probiotic therapy. In summary, CP-associated MBDs represent a rising medical challenge, involving multiple tissues and organs, complex disease mechanisms, and diverse treatment approaches. More in-depth studies are required to understand the complex interplay between CP and MBDs to facilitate the development of more specific and effective therapeutic approaches.
Assuntos
Doenças Ósseas Metabólicas , Pancreatite Crônica , Humanos , Pancreatite Crônica/epidemiologia , Pancreatite Crônica/metabolismo , Pancreatite Crônica/complicações , Doenças Ósseas Metabólicas/epidemiologia , Doenças Ósseas Metabólicas/etiologia , Doenças Ósseas Metabólicas/metabolismo , Vitamina D/metabolismo , Vitamina D/uso terapêutico , Vitamina K/metabolismo , AnimaisRESUMO
PURPOSE: Sarcopenia is a prognostic predictor in emergency surgery. However, there are no reports on the relationship between osteopenia and in-hospital mortality. This study clarified the effect of preoperative osteosarcopenia on patients with gastrointestinal perforation after emergency surgery. METHODS: We included 216 patients with gastrointestinal perforations who underwent emergency surgery between January 2013 and December 2022. Osteopenia was evaluated by measuring the pixel density in the mid-vertebral core of the 11th thoracic vertebra. Sarcopenia was evaluated by measuring the area of the psoas muscle at the level of the third lumbar vertebra. Osteosarcopenia is defined as the combination of osteopenia and sarcopenia. RESULTS: Osteosarcomas were identified in 42 patients. Among patients with osteosarcopenia, older and female patients and those with an American Society of Anesthesiologists Physical Status of ≥ 3 were significantly more common, and the body mass index, hemoglobin value, and albumin level were significantly lower in these patients than in patients without osteosarcopenia. Furthermore, the osteosarcopenia group presented with more postoperative complications than patients without osteosarcopenia (P < 0.01). In the multivariate analysis, age ≥ 74 years old (P = 0.04) and osteosarcopenia (P = 0.04) were independent and significant predictors of in-hospital mortality. CONCLUSION: Preoperative osteosarcopenia is a risk factor of in-hospital mortality in patients with gastrointestinal perforation after emergency surgery.
Assuntos
Doenças Ósseas Metabólicas , Mortalidade Hospitalar , Perfuração Intestinal , Complicações Pós-Operatórias , Sarcopenia , Humanos , Sarcopenia/complicações , Sarcopenia/etiologia , Sarcopenia/diagnóstico , Feminino , Masculino , Idoso , Prognóstico , Perfuração Intestinal/cirurgia , Perfuração Intestinal/etiologia , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/epidemiologia , Pessoa de Meia-Idade , Doenças Ósseas Metabólicas/etiologia , Doenças Ósseas Metabólicas/complicações , Período Pré-Operatório , Idoso de 80 Anos ou mais , Emergências , Resultado do Tratamento , Fatores Etários , Tratamento de Emergência , Fatores Sexuais , Procedimentos Cirúrgicos do Sistema DigestórioRESUMO
BACKGROUND: Endocrine regulation of bone metabolisms is the focus of the "Skeletal Endocrinology" series of meetings. AIMS: To report on the outcome of the discussion on the role of vitamin D/PTH axis in endocrine osteopathies held during the 10th Skeletal Endocrinology Meeting which took place in Stresa (Italy) in March 2023. OUTCOMES: Vitamin D/PTH axis has relevant influence on several outcomes in the general population and in patients affected by endocrinopathies such as hypoparathyroidism and secreting pituitary adenomas. CONCLUSIONS: Assessing the status of the vitamin D/PTH axis and using vitamin D and PTH as therapeutic agents is mandatory in several endocrine-related bone metabolic conditions.
Assuntos
Doenças Ósseas Metabólicas , Hormônio Paratireóideo , Vitamina D , Humanos , Doenças Ósseas Metabólicas/metabolismo , Doenças Ósseas Metabólicas/etiologia , Doenças do Sistema Endócrino/metabolismo , Hipoparatireoidismo/metabolismo , Hormônio Paratireóideo/sangue , Hormônio Paratireóideo/metabolismo , Neoplasias Hipofisárias/metabolismo , Vitamina D/metabolismo , Vitamina D/sangueRESUMO
Phenolic acids, such as hippuric acid (HA) and 3-(3-hydroxyphenyl) propionic acid (3-3-PPA), can be produced from microbiome digestion of polyphenols. Previously it was found that HA and 3-3-PPA facilitate bone formation and suppress bone resorption. However, the mechanism of action by which HA and 3-3-PPA protect bone from degeneration is currently unknown. In this report, we present that HA and 3-3-PPA suppression of bone resorption is able to ameliorate bone loss in an ovariectomy (OVX) osteopenic mouse model though not to the extent of Zoledronic acid (ZA). HA and 3-3-PPA treatments were shown to significantly decrease bone marrow adipocyte-like cell formation and inhibited gene expression of key adipogenesis regulator peroxisome proliferator activated receptor gamma (PPARγ) and lipoprotein lipase (Lpl) in bone from OVX mice. In addition, ChIP experiments showed that the association between PPARγ and Lpl promoter region in preadipocyte-like cells was significantly suppressed following HA or 3-3-PPA treatment. Contrasting HA and 3-3-PPA, ZA significantly increased TRAP activity in the area close to growth plate and significantly suppressed bone cell proliferation. These data suggest that phenolics acids such as HA or 3-3-PPA may prevent bone degeneration after OVX through suppression of inflammatory milieu in the bone.
Assuntos
Doenças Ósseas Metabólicas , Reabsorção Óssea , Hidroxibenzoatos , Fenóis , Propionatos , Feminino , Camundongos , Animais , Humanos , Adipogenia , Medula Óssea , PPAR gama/genética , PPAR gama/metabolismo , Doenças Ósseas Metabólicas/tratamento farmacológico , Doenças Ósseas Metabólicas/etiologia , Doenças Ósseas Metabólicas/prevenção & controle , Ácido Zoledrônico , Esteroides , OvariectomiaRESUMO
AIMS: The aim was to analyse the use and safety of bisphosphonate treatment for metabolic bone complications in paediatric cancer patients. METHODS: We retrospectively describe our experience with bisphosphonate treatment in 25 childhood cancer patients (aged <18 years) in a single tertiary hospital between 1999 and 2020. RESULTS: The most common primary diagnosis was acute lymphoblastic leukaemia (n = 16) and Hodgkin lymphoma (n = 3). Eleven patients (44%) had received allogeneic stem cell transplantation and two patients autologous stem cell transplantation. Sixteen patients (64%) had been treated with radiotherapy, either total-body (n = 11) or local (n = 5). The main indication for bisphosphonates was osteoporosis with vertebral compression fractures in 13/25, osteonecrosis in 6/25 and hypercalcaemia in 2/25. The bisphosphonate treatment was started on average 13 (range 0-76) months after the diagnosis of the bone complication. Bisphosphonate treatment lasted between weeks (hypercalcaemia) to 5 years (severe osteoporosis). Mild, non-symptomatic hypophosphatemia (n = 8), hypocalcaemia (n = 6) and moderate, transient pain (n = 6) were the most common adverse effects. No severe side effects were observed even when bisphosphonates were administered concomitantly with chemotherapy. Bone mineral density significantly improved with the bisphosphonate treatment (mean lumbar spine Z-score -1.17 vs. -0.07, p < 0.001). CONCLUSION: Bisphosphonate treatment was well tolerated in this paediatric patient cohort.