Expression of CircRNA_0048211 and its correlation with bone metabolic markers in patients with postmenopausal osteoporosis / 中华骨科杂志

Objective:To investigate the diagnostic value of serum CircRNA_0048211 expression level in postmenopausal osteoporosis (PMOP) and its correlation with bone-specific alkaline phosphatase (BALP), osteopontin (OPN), procollagen type I N-terminal propeptide (PINP) and β-crosslaps (β-CTX). Methods:Data of postmenopausal women who underwent physical examination in our hospital from January 2019 to December 2021 were collected. All subjects were measured bone mineral density (BMD) by dual-energy X-ray absorptiometry and divided into PMOP group, decreased bone mass group and normal bone mass group according to BMD level. The serum CircRNA_0048211, BALP, OPN, PINP and β-CTX levels were compared in each group. Binary logistic regression was used to analyze the risk factors of PMOP, the receiver operating characteristic curve (ROC) was drawn to analyze the diagnostic value of CircRNA_0048211, BALP, OPN, PINP and β-CTX on PMOP. The correlation between CircRNA_0048211 expression level and BALP, OPN, PINP and β-CTX was analyzed by Pearson correlation analysis. Results:A total of 218 patients were included in this study. Age is 60.52±6.83 years (range, 47-76 years), body mass index is 24.27±2.28 kg/m 2 (range, 22.18-25.73 kg/m 2) and menopausal time is 10.16±4.25 years (range, 2.30-21.80 years). There were 40 cases in PMOP group, 97 cases in osteopenia group and 81 cases in normal bone mass group. The serum CircRNA_ 0048211, BALP, OPN, PINP and β-CTX was significantly different between PMOP group, osteopenia group and normal group ( F=21.15, P<0.001; F=12.52, P<0.001; F=17.86, P<0.001; F=14.32, P<0.001; F=15.52, P<0.001). The serum CircRNA_0048211 level in PMOP group (0.37±0.08) were significantly lower than that of osteopenia group (1.05±0.46) and normal bone mass group (1.73±0.81), the difference was statistically significant ( P<0.05). The levels of BALP (28.42±7.35 μg/L), OPN (17.28±7.30 ng/ml), PINP (58.40±14.37 ng/ml) and β-CTX (1.52±0.28 μg/L) in PMOP group were significantly higher than those in osteopenia group (22.61±5.93 μg/L, 11.95±5.64 ng/ml, 49.16±11.24 ng/ml, 0.81±0.17 μg/L) and normal bone mass group (16.30±4.18 μg/L, 7.62±3.25 ng/ml, 35.48±7.12 ng/ml, 0.37±0.10 μg/L), the difference was statistically significant ( P<0.05). Binary logistic regression analysis showed that decreased CircRNA_0048211 expression level [ OR=3.53, 95% CI (2.73, 10.32)] was a risk factor for the occurrence of PMOP ( P<0.001). ROC curve showed that CircRNA_0048211≤0.76 has a diagnostic significance on PMOP, and its combination of BALP, OPN, PINP and β-CTX has the highest AUC [0.95, 95% CI (0.89, 1.00)] in diagnosing PMOP. Correlation analysis showed that CircRNA_0048211 expression level were negatively correlated with BALP, OPN, PINP and β-CTX ( r=-0.46, P<0.001; r=-0.80, P<0.001; r=-0.81, P<0.001; r=-0.69, P<0.001). Conclusion:The CircRNA_0048211 showed low expression in PMOP, which was negatively correlated with BALP, OPN, PINP and β-CTX. The combination of these five factors has certain clinical value in the diagnosis of PMOP.

Importancia de la biopsia de hueso en el diagnóstico de las enfermedades metabólicas óseas / Importance of bone biopsy in the diagnose on the bone metabolic diseases

RESUMEN Objetivo. Evaluar la importancia de las biopsias óseas en el diagnóstico de las enfermedades óseas metabólicas, su relación con la densitometría ósea (DMO) y los biomarcadores. Métodos. Estudio transversal, descriptivo. Se efectuaron biopsias de la cresta pelviana a 38 personas, 36 mujeres (34 menopáusicas y 2 premenopáusicas) y 2 varones. DMO en columna vertebral, cadera y/o antebrazo por absorciometría dual de rayos X. Se determinó calcio, fósforo, osteocalcina, fosfatasa alcalina, vitamina D, parathormona, hemoglobina, transaminasas, proteínas totales y fracciones en sangre y en orina, N-telopéptido de enlaces de colágeno tipo I, calcio y fósforo por métodos convencionales. Resultados. La edad promedio de 34 mujeres postmenopáusicas fue 58 ± 7,79 y el tiempo de la menopausia 11,48 ± 8,76 años; la DMO promedio en columna, cadera y antebrazo fue de -2,88 ± 1,16, -2,13 ± 0,82, y -5,14 ± 1,76, respectivamente; la biopsia demostró osteoporosis en 33 y enfermedad de Paget en 1. Dos varones de 48 y 63 años, con DMO en antebrazo de -3,2 y -4,9, y osteoporosis en la biopsia. Mujer de 34 años con DMO -3 y osteoporosis en biopsia; y una mujer de 29 años con DMO -3 y osteomalacia en biopsia. Hubo correlación negativa entre la edad y duración de la menopausia con la disminución de la DMO. Conclusiones. Hubo correlación entre la edad y tiempo de menopausia con la disminución de la DMO. Una DMO baja no siempre es osteoporosis, puede tratarse de otra enfermedad ósea metabólica como osteomalacia o enfermedad de Paget. La biopsia ósea es el procedimiento más confiable para el diagnóstico de estas enfermedades.

ABSTRACT Objective. To evaluate the importance of bone biopsy in the diagnose of the bone metabolic diseases, its relationship with bone densitometry (BMD) and biomarkers. Methods. In a descriptive, transversal study, 38 biopsies of pelvic bone were made, 36 in female (34 postmenopausal and 2 premenopausal) and 2 in male. All had BMD in spine, hip and/or forearm measured by dual x-ray absorptiometry. Calcium, phosphorus, parathormone, vitamin D, alkaline phosphatase, osteocalcin, hemoglobin, transaminases, total protein and fractions were measured in blood and N-telopeptide of collagen type I, calcium and phosphorus in urine by conventional methods. Results. The mean age of 34 menopausal women was 58 ± 7,79 and menopause time was 11,48 ± 8,76 years; mean BMD in spine, hip and forearm were -2,88 ± 1,16, -2,13 ± 0,82, y - 5,14 ± 1,76, respectively; bone biopsy demonstrated osteoporosis in 33 y Paget´s disease in one. Male persons 48 and 63 years old had BMD in forearm -3,2 and -4,9, and osteoporosis in biopsy. A woman 34 years old had a BMD of -3 and osteoporosis en bone biopsy, a woman 29 years old with BMD -3 presented osteomalacia in biopsy. There was a negative correlatión between age and time of menopause with BMD decrease. Conclusions. A negative correlation between the age and time of menopause with BMD decrease was found. A low BMD not always is osteoporosis, it might be other bone metabolic disease like osteomalacia or Paget´s disease. Bone biopsy is a more trustworthy procedure for the diagnose of these diseases.

Does the use of dynamic surgical guidance assist accurate pedicle screw placement in patients with osteoporosis or osteopenia? / O uso do guia cirúrgico dinâmico auxilia a acurácia do posicionamento dos parafusos pediculares em pacientes com osteoporose ou osteopenia? / ¿el uso de guía quirúrgica dinámica ayuda a colocar con precisión los tornillos pediculares en pacientes con osteoporosis u osteopenia?

ABSTRACT Objective To compare the use of a dynamic surgical guide (PediGuard®) and pilot hole preparation, with the use of a probe and the aid of fluoroscopy in osteoporotic or osteopenic patients undergoing pedicular fixation of the thoracic or lumbar spine. Methods One hundred and eight patients were randomized. A pilot hole was prepared with the dynamic surgical guide (PediGuard®), or with a probe with the aid of fluoroscopy. A total of 657 vertebral pedicles (120 thoracic and 180 lumbar) were included in the study. The parameters used for the comparison were: accuracy of the pedicular screw, number of fluoroscopic shots, and change in intraoperative trajectory of the perforation after detecting pedicle wall rupture. Results In the group with use of the dynamic surgical guide, malpositioning of the pedicle screws was observed in 8 (2.6%) patients and intraoperative change of perforation trajectory in 12 (4%) patients, and there were 52 fluoroscopic shots. In the group without use of the dynamic surgical guide (PediGuard®), misplacement of the pedicle screws was observed in 33 (11%) patients and intraoperative change of perforation trajectory in 47 (13.2%) patients, and there were 136 fluoroscopic shots. Conclusion The use of the dynamic surgical guide (PediGuard®) in patients with osteoporosis or osteopenia enabled more accurate placement of pedicular screws, with less change in the intraoperative course of the perforation and less intraoperative radiation. Level of Evidence II; Randomized clinical trial of lesser quality.

RESUMO Objetivo Comparar o uso de um guia cirúrgico dinâmico (PediGuard®) e o preparo de orifício piloto com uma sonda e o auxílio de fluoroscopia em pacientes com osteopenia ou osteoporose submetidos à fixação pedicular da coluna torácica ou lombar. Métodos Cento e oito pacientes foram randomizados. Um orifício piloto foi preparado com o guia cirúrgico dinâmico (PediGuard®) ou com uma sonda com auxílio de fluoroscopia. Foram incluídos no estudo 657 pedículos vertebrais (120 torácicos e 180 lombares). Os parâmetros usados para a comparação foram: acurácia da colocação do parafuso pedicular, número de disparos fluoroscópicos e mudança da trajetória intraoperatória da perfuração depois da detecção de ruptura da parede do pedículo. Resultados No grupo de pacientes em que se usou o guia cirúrgico dinâmico, observou-se mau posicionamento dos parafusos pediculares em oito (2,6%) pacientes e alteração da trajetória intraoperatória da perfuração em 12 (4%) pacientes, com 52 disparos fluoroscópicos. No grupo de pacientes em que o guia cirúrgico dinâmico (PediGuard®) não foi usado o mau posicionamento dos parafusos pediculares foi observado em 33 (11%) pacientes, a mudança intraoperatória da trajetória da perfuração foi vista em 47 (13,2%) pacientes, com 136 disparos fluoroscópicos. Conclusão O uso do guia cirúrgico dinâmico (PediGuard®) em pacientes com osteoporose ou osteopenia permitiu a colocação de parafusos pediculares com maior acurácia, com menor alteração da trajetória intraoperatória da perfuração e menor dose de radiação intraoperatória. Nível de Evidência II; Estudo clínico randomizado de menor qualidade.

RESUMEN Objetivo Comparar el uso de una guía quirúrgica dinámica (PediGuard®) y la preparación del orificio piloto con una sonda y la ayuda de fluoroscopia en pacientes con osteopenia u osteoporosis sometidos a fijación pedicular de la columna torácica o lumbar. Métodos Ciento ocho pacientes fueron asignados aleatoriamente. Se preparó un orificio piloto preparado con la guía quirúrgica dinámica (PediGuard®) o con una sonda con ayuda de fluoroscopia. Se incluyeron en el estudio 657 pedículos vertebrales (120 torácicos y 180 lumbares). Los parámetros utilizados para la comparación fueron: precisión de la colocación del tornillo pedicular, número de disparos del dispositivo de fluoroscopia y cambio en la trayectoria intraoperatoria de la perforación después de la detección de ruptura de la pared del pedículo. Resultados En el grupo de pacientes en el que se utilizó la guía quirúrgica dinámica, se observó mal posicionamiento de los tornillos pediculares en 8 (2,6%) pacientes y cambios de la trayectoria intraoperatoria de la perforación en 12 (4%) pacientes, con 52 disparos del aparato de fluoroscopia. En el grupo de pacientes en los que no se utilizó la guía quirúrgica dinámica (PediGuard®), se observó un mal posicionamiento de los tornillos pediculares en 33 (11%) pacientes, el cambio intraoperatorio de la trayectoria de perforación se observó en 47 (13,2%) pacientes, con 136 disparos fluoroscópicos. Conclusión El uso de la guía quirúrgica dinámica (PediGuard®) en pacientes con osteoporosis u osteopenia permitió la colocación de tornillos pediculares con mayor precisión, menos cambios en la trayectoria intraoperatoria de la perforación y dosis más baja de radiación intraoperatoria. Nivel de Evidencia II; Ensayo clínico aleatorizado de menor calidad.

The enigma of aluminum deposition in bone tissue from a patient with chronic kidney disease: a case report / O enigma da deposição de alumínio no tecido ósseo de um paciente com doença renal crônica: relato de caso

ABSTRACT About four decades ago, the relationship between dialysis-dementia and aluminum (Al) began to be established. The restriction of drugs containing Al and improvements on water quality used for dialysis resulted in the clinical disappearance of Al intoxication. However, high prevalence of Al deposition in bone tissue from Brazilian dialysis patients is still being detected. Through the case report of a patient on hemodialysis (HD) for one year, presenting significant Al deposition in bone tissue, we speculated if this problem is not being underestimated. We used extensive investigation to identify potential sources of Al exposure with a careful review of medication history and water quality controls. Al concentration was measured by different methods, including mass spectrometry, in poly-electrolyte concentrate solutions and solution for peritoneal dialysis, in an attempt to elucidate the possible sources of contamination. The objective of this case report is to alert the medical community about a potential high prevalence of Al deposition in bone tissue and to discuss the possible sources of contamination in patients with chronic kidney disease (CKD).

RESUMO Cerca de quatro décadas atrás, a relação entre demência relacionada à diálise e alumínio (Al) começou a ser estabelecida. A restrição de medicamentos contendo Al e melhorias na qualidade da água utilizada na diálise resultaram no desaparecimento clínico da intoxicação por Al. Contudo, no Brasil continua a ser identificada uma elevada prevalência de deposição de Al no tecido ósseo de pacientes em diálise. O presente relato de caso de um paciente em hemodiálise (HD) há um ano com deposição significativa de Al no tecido ósseo nos leva a especular se esse problema não tem sido subestimado. Realizamos uma ampla investigação para identificar possíveis fontes de exposição ao Al, com uma revisão cuidadosa do histórico de medicação e dos controles de qualidade da água. A concentração de Al foi medida por diferentes métodos, incluindo espectrometria de massa, nos concentrados polieletrolíticos para hemodiálise e soluções de diálise peritoneal, na tentativa de elucidar as possíveis fontes de contaminação. O objetivo do presente relato de caso é alertar a comunidade médica sobre uma possível elevada prevalência de deposição de Al no tecido ósseo e discutir as possíveis fontes de contaminação nos pacientes com doença renal crônica (DRC).

Association of Severity of Coronary Lesions with Bone Mineral Density in Postmenopausal Women / Associação entre Gravidade das Lesões Coronarianas e Densidade Mineral Óssea em Mulheres Pós-Menopausa

Abstract Background: Coronary artery disease (CAD) and osteoporosis (OP) are common diseases in postmenopausal women. In both cross-sectional and longitudinal epidemiologic studies, low bone mass has been related to increased frequency of CAD. However, available data on the relationship between bone mineral density (BMD) and severity of coronary lesions is limited. Objective: To investigate association between the BMD and severity of coronary lesions assessed by Gensini score in postmenopausal women. Methods: This study included 122 postmenopausal women who were diagnosed with CAD. These patients were divided into two groups according to the severity of coronary lesions assessed by the Gensini score - patients with mild coronary lesions (Gensini score < 25) and patients with severe coronary lesions (Gensini score ≥ 25). Femoral neck mineral density was measured with dual energy X-ray absorptiometry (DXA). Results: The study included postmenopausal women aged 64.31 ± 4.71 years, 85 of whom (69.7%) exhibited severe coronary lesions. Participants with severe coronary lesions had a significantly higher T score than did those with mild coronary lesions at the femoral neck (p < 0.05). The mean T-score was −0.84 ± 1.01 in mild coronary lesions group, −1.42 ± 1.39 in severe coronary lesions group (p < 0.05). Multivariable logistic regression analysis showed that osteopenia-osteoporosis at the Femoral neck (odds ratio 2.73; 95% confidence interval 1.06 to 6.13) was associated with an increased risk of developing severe coronary lesions. The multiple regression model showed that T-scores (b = −0.407, SE = 0.151, p=0.007) were the independent predictors of Gensini score. Conclusion: The relationship between severity of coronary lesions and BMD was significant in postmenopausal women. BMD, a low-cost technique involving minimal radiation exposure, widely used for osteoporosis screening, is a promising marker of severity of coronary lesions.

Resumo Fundamento: A doença arterial coronariana (DAC) e a osteoporose são doenças comuns em mulheres pós-menopausa. Tanto em estudos transversais como em estudos epidemiológicos longitudinais, a massa óssea diminuída foi relacionada à frequência aumentada de DAC. No entanto, dados disponíveis sobre a relação entre densidade mineral óssea (DMO) e gravidade das lesões coronarianas são limitados. Objetivo: Investigar a associação entre DMO e gravidade das lesões coronarianas avaliadas pelo escore de Gensini em mulheres pós-menopausa. Métodos: Este estudo incluiu 122 mulheres pós-menopausa diagnosticadas com DAC. As pacientes foram divididas em dois grupos de acordo com a gravidade das lesões coronarianas avaliada pelo escore de Gensini - pacientes com lesões coronarianas leves (escore de Gensini < 25) e pacientes com lesões coronarianas graves (escore de Gensini ≥ 25). A densidade mineral do colo femoral foi medida por absorção de raios-X de dupla energia (DXA). Resultados: O estudo incluiu mulheres pós-menopausa com idade de 64,31 ± 4,71 anos, 85 delas (69,7%) com lesões coronarianas graves. Pacientes com lesões coronarianas graves apresentaram um escore T mais elevado que aquelas com lesões coronarianas leves no colo femoral (p < 0,05). O escore T médio foi -0,84 ± 1,01 no grupo com lesões leves, e -1,42 ± 1,39 no grupo com lesões graves (p < 0,05). A análise de regressão logística multivariada mostrou que a osteopenia-osteoporose no colo femoral (odds ratio 2,73; intervalo de confiança de 95% 1,06 - 6,13) esteve associada com um risco aumentado de se desenvolver lesões coronarianas graves. O modelo de regressão múltipla mostrou que os escores T (b = -0,407; EP= 0,151; p = 0,007) foram preditores independentes do escore de Gensini. Conclusão: Encontrou-se uma relação significativa entre a gravidade das lesões coronarianas e a DMO em mulheres pós-menopausa. DMO, uma técnica de baixo custo que envolve mínima exposição à radiação, e amplamente utilizada no rastreamento de osteoporose, é um marcador promissor da gravidade de lesões coronarianas graves.

Clinical Implication of Sarcopenia in Patients with Inflammatory Bowel Disease / 대한소화기학회지

Recent studies have shown that inflammatory bowel disease (IBD) patients are affected by altered body composition, especially low muscle mass or sarcopenia. Detection of sarcopenia is important, as it can independently predict osteopenia, sarcopenic obesity, and poor disease outcomes during IBD progress. The challenges are needed to identify diagnostic and managing strategies for sarcopenia in IBD to improve disease outcomes and increase the quality of life in patients with IBD.

Relationship between mineral and bone metabolic disorders and prognosis in patients with chronic renal disease / 中国医师杂志

Objective To investigate the relationship between mineral and bone metabolic disorders and prognosis in patients with chronic renal disease (CKD).Methods 200 patients with CKD admitted to our hospital from October 2015 to October 2017 were included.The prognosis of the patients was analyzed and grouped according to their prognosis.The follow-up was 6 months.They were divided into good prognosis group (no event survival) and poor prognosis group (complication and death).The clinical characteristics of the two groups were compared,and ROC curves were drawn to analyze the predictive value of mineral and bone metabolic indexes for poor prognosis,including serum calcium (Ca),phosphorus (P),calcium × phosphorus (Ca × P),bone alkaline phosphatase (BSALP),25 hydroxyvitamin D3 [25 (OH) D3],osteocalcin (OC),total parathyroid hormone (iPTH).Logistic regression analysis was used to determine the independent risk factors of poor prognosis in patients with chronic kidney disease.Results Of the 200 patients,164 (82％) had a good prognosis,and 36 (18％) had poor prognosis.The ratio of CKD4,CKD5,poor blood glucose control and poor blood pressure control in the poor prognosis group were 27.78％,16.67％,47.22％,41.67％,respectively,better than the prognosis group (4.27％,1.22％,18.29％,15.85％).The levels of Ca × P,BSALP and OC in the poor prognosis group were (3.46 ±0.21) mmol2/ L2,(98.64 ± 12.67) U/L,(71.19 ±58.73) μg/L,higher than the good prognosis group [(3.34 ±0.28) mmol2/L2,(85.43 ± 15.58) U/L,(36.57 ± 23.65) μg/L];The 25 (OH) D3 level in the poor prognosis group was (11.39 ±6.56) μg/L,which was lower than that in the good prognosis group (19.64 ±8.65) μg/L;with statistically significant difference (P ＜0.05).The area under the curve of Ca × P,BSALP,25 (OH) D3 and OC was 0.782,0.806,0.815 and 0.857,respectively,to predict the poor prognosis of CKD.The logistic regression analysis showed that CKD stage (stage 4-5),poor glycemic control,poor control of blood pressure,Ca × P≥3.393 mmol2/L2,BSAL≥92.932 U/L,25 (OH) D3 ≤ 14.016 μg/L,OC ≥86.339 μg/L were independent risk factors of poor prognosis of CKD (P ＜ 0.05).Conclusions Serum Ca × P,BSALP,25 (OH) D3 and OC levels have certain predictive value for the poor prognosis of CKD.The more serious the mineral and bone metabolism disorders are,the greater the risk of poor prognosis.

Prevalence of osteoporosis and hypovitaminosis d at siriraj metabolic bone disease clinic / Prevalência de osteoporose e hipovitaminose d na siriraj metabolic bone disease clinic

ABSTRACT Objective: To identify the prevalence of osteoporosis and hypovitaminosis D among patients at the Siriraj Metabolic Bone Disease (MBD) Clinic, and to compare initial vitamin D levels in patients with and without a history of fragility fractures. Methods: Medical records of patients who attended our MBD clinic between 2012 and 2015 were retrospectively reviewed. Patient baseline demographic, clinical, bone mineral density (BMD), and laboratory data were collected and analyzed. Osteoporosis was diagnosed when patients had a BMD T-score <-2.5 or presented with fragility fractures. Results: There were 761 patients included in this study. Of these, 627 patients (82.4%) were diagnosed with osteoporosis and 508 patients (66.8%) had fragility fractures. Baseline serum 25-hydroxyvitamin D (25(OH)D) levels were available in 685 patients. Of these, 391 patients (57.1%) were diagnosed with hypovitaminosis D. When evaluated only in patients with fragility fractures, the average initial 25(OH)D level was 28.2±11.6 ng/mL, and the prevalence of hypovitaminosis D was 57.6%. Conclusion: A high prevalence of osteoporosis and hypovitaminosis D was found among patients at our clinic; two-thirds of patients had a history of fragility fractures, and no difference in initial 25(OH)D levels was seen between patients with and without fragility fractures. Level of Evidence III, Retrospective Study .

RESUMO Objetivo: Identificar a prevalência de osteoporose e hipovitaminose D entre os pacientes na Siriraj Metabolic Bone Disease (MBD) Clinic e comparar o nível inicial de vitamina D em pacientes com e sem história de fratura por fragilidade óssea. Métodos: Os prontuários de pacientes atendidos em nossa clínica MBD durante o período de 2012 a 2015 foram analisados retrospectivamente. Os dados demográficos, clínicos, densidade mineral óssea (DMO) e os dados laboratoriais basais foram coletados e analisados. A osteoporose foi diagnosticada quando os pacientes tinham DMO com escore T≤ -2,5 ou fraturas por fragilidade óssea. Resultados: Foram incluídos 761 pacientes dos quais, 627 pacientes (82,4%) foram diagnosticados com osteoporose e 508 (66,8%) tinham fraturas por fragilidade. O nível sérico basal de 25-hidroxivitamina D (25(OH)D) estava disponível para 685 pacientes. Desses, 391 pacientes (57,1%) foram diagnosticados com hipovitaminose D. Quando avaliado apenas em pacientes com fratura por fragilidade óssea, o nível inicial médio de 25(OH)D foi de 28,2 ± 11,6 ng/ml e a prevalência de hipovitaminose D foi de 57,6%. Conclusão: Encontrou-se alta prevalência de osteoporose e hipovitaminose D entre os pacientes de nossa clínica, sendo que dois terços deles tinham história de fratura por fragilidade óssea e nenhuma diferença no nível basal de 25(OH)D entre pacientes com e sem fratura por fragilidade. Nível de Evidência III, Estudo Retrospectivo

Phosphaturic mesenchymal tumor (PMT): exceptionally rare disease, yet crucial not to miss

Phosphaturic mesenchymal tumors (PMTs) are very rare tumors which are frequently associated with Tumor Induced Osteomalacia (TIO), a paraneoplastic syndrome that manifests as renal phosphate wasting. The tumor cells produce a peptide hormone-like substance known as fibroblast growth factor 23 (FGF23), a physiologic regulator of phosphate levels. FGF23 decreases proximal tubule reabsorption of phosphates and inhibits 1-α-hydroxylase, which reduces levels of 1-α, 25-dihydroxyvitamine D3. Thus, overexpression of FGF23 by the tumor cells leads to increased excretion of phosphate in the urine, mobilization of calcium and phosphate from bones, and the reduction of osteoblastic activity, ultimately resulting in widespread osteomalacia. Patients typically present with gradual muscular weakness and diffuse bone pain from pathologic fractures. The diagnosis is often delayed due to the non-specific nature of the symptoms and lack of clinical suspicion. While serum phosphorus and FGF23 testing can assist in making a clinical diagnosis of PMT, the responsible tumor is often difficult to locate. The pathologic diagnosis is often missed due to the rarity of PMTs and histologic overlap with other mesenchymal neoplasms. While patients can experience severe disabilities without treatment, excision is typically curative and results in a dramatic reversal of symptoms. Histologically, PMT has a variable appearance and can resemble other low grade mesenchymal tumors. Even though very few cases of PMT have been reported in the world literature, it is very important to consider this diagnosis in all patients with hypophosphatemic osteomalacia. Here we present a patient who suffered for almost 5 years without a diagnosis. Ultimately, the PMT was located on a 68Ga-DOTA TATE PET/CT scan and subsequently confirmed by histologic and immunohistologic study. Interestingly, strong positivity for FGFR1 by IHC might be related to the recently described FN1-FGFR1 fusion. Upon surgical removal, the patient's phosphate and FGF23 levels returned to normal and the patient's symptoms resolved.

High-impact drop exercise alters mechanical properties in osteopenic bone / Exercício de queda altera as propriedades mecânicas em osso osteopênico / El ejercicio de caída altera las propiedades mecánicas en hueso osteopénico

ABSTRACT Introduction: Osteopenia is a reversible condition and precedes osteoporosis. Physical activity and mechanical loading appear to play an important role in the regulation of bone homeostasis, without the side effects of targeted drug therapy. However, there is controversy as to which type of stimulus promotes more effective adaptations with respect to mechanical properties of bones. Objective: To investigate the effects of high-impact drop training on bone structure after ovariectomy-induced osteopenia in 40 10-week-old female Wistar rats. Methods: Twenty female rats (prevention program) were randomly assigned into two groups (n=10): Ovariectomized sedentary (OVXs), and OVX trained (OVX+Dropt). OVX+Dropt animals began training 3 days after surgery. Another twenty female rats (treatment program) were randomly assigned to two other groups (n=10): Ovariectomized sedentary (OVXs), and OVX trained (OVX+Dropt). OVX+Dropt animals began training 60 days after surgery. The rats in the trained groups were dropped from 40 cm height 20 times/day, 5 days/week over a period of 12 weeks period. At the end, the biomechanical tests were analyzed. Results: The final load and stiffness of the left tibia in the trained groups were higher than in the sedentary groups (p<0.05). Conclusions: Dropping exercise induced favorable changes in bone mechanical properties. High-impact drop exercise is effective to prevent bone loss after ovariectomy even when osteopenia is already established.

RESUMO Introdução: A osteopenia é uma doença reversível e precede a osteoporose. A atividade física e a carga mecânica parecem desempenhar um papel importante na regulação da homeostase óssea, sem os efeitos colaterais da terapia medicamentosa direcionada. No entanto, é controverso qual tipo de estímulo promove adaptações mais eficazes com relação às propriedades mecânicas dos ossos. Objetivo: Investigar os efeitos do treinamento de queda com impacto sobre a estrutura óssea depois de osteopenia induzida por ovariectomia em 40 ratas Wistar com 10 semanas de idade. Métodos: Vinte ratas (programa de prevenção) foram distribuídas aleatoriamente em dois grupos (n = 10): Ovariectomizadas sedentárias (OVXs) e OVX treinadas (OVX + Dropt). Os animais OVX + Dropt começaram a treinar três dias após a cirurgia. Outras vinte ratas (programa de tratamento) foram alocadas aleatoriamente em outros dois grupos (n = 10): Ovariectomizadas sedentários (OVXs) e OVX exercitadas (OVX + Dropt). Os animais OVX + Dropt iniciaram o treinamento 60 dias após a cirurgia. As ratas nos grupos treinados foram deixadas cair 20 vezes/dia, 5 dias/semana, de altura de 40 cm durante um período de 12 semanas. Ao final, foram analisados os testes biomecânicos. Resultados: A carga final e a rigidez da tíbia esquerda nos grupos treinados foram maiores do que nos grupos sedentários (p < 0,05). Conclusões: O exercício de queda provocou alterações favoráveis nas propriedades mecânicas dos ossos. O exercício de queda com impacto é eficaz para prevenir a perda óssea após ovariectomia, mesmo quando a osteopenia já está estabelecida

RESUMEN Introducción: La osteopenia es una enfermedad reversible y precede a la osteoporosis. La actividad física y la carga mecánica parecen desempeñar un papel importante en la regulación de la homeostasis ósea, sin los efectos secundarios de la terapia farmacológica dirigida. Sin embargo, es controvertido qué tipo de estímulo promueve adaptaciones más eficaces con respecto a las propiedades mecánicas de los huesos. Objetivo: Investigar los efectos del entrenamiento de caída con alto impacto sobre la estructura ósea después de osteopenia inducida por ovariectomía en 40 ratas Wistar hembras de diez semanas de edad. Métodos: Se asignaron aleatoriamente veinte ratas (programa de prevención) en dos grupos (n = 10): Ovariectomizadas sedentarios (OVXs) y OVX entrenadas (OVX + Drope). Los animales OVX + Drope comenzaron a entrenar tres días después de la cirugía. Otras veinte ratas hembras (programa de tratamiento) fueron asignadas aleatoriamente a otros dos grupos (n = 10): Ovariectomizadas sedentarias (OVXs) y OVX entrenadas (OVX + Drope). Los animales OVX + Drope iniciaron el entrenamiento 60 días después de la cirugía. Las ratas en los grupos entrenados se dejaron caer de una altura de 40 cm 20 veces/día, 5 días/semana durante un período de 12 semanas. Al final, se analizaron las pruebas biomecánicas. Resultados: La carga y rigidez de la tibia izquierda en los grupos entrenados fueron mayores que en los grupos sedentarios (p < 0,05). Conclusiones: El ejercicio de caída provocó cambios favorables en las propiedades de los huesos. El ejercicio de caída con impacto es eficaz para prevenir la pérdida ósea después de la ovariectomía, incluso cuando la osteopenia ya está establecida.

Avaliação do potencial osteogênico de células estromais da medula óssea de pacientes com escoliose / Evaluation of the osteogenic potential of bone marrow stromal cells isolated from scoliotic patients

Apesar de descrita há muitos anos em pacientes com escoliose idiopática do adolescente (EIA), a relação entre osteopenia e escoliose ainda é pouco compreendida. Mais recentemente, redução da densidade mineral óssea também foi relatada em associação com a escoliose congênita (EC). Estudos in vitro demonstraram que células estromais da medula óssea (BMSC) de pacientes com EIA apresentam diminuição na capacidade de diferenciação osteogênica e essa pode ser uma das razões pelas quais esses pacientes desenvolvem osteopenia e osteoporose. Apesar do relato da diminuição da massa óssea em pacientes com escoliose congênita (EC), não existem dados na literatura sobre a capacidade de diferenciação de BMSC desses pacientes. Assim, o objetivo deste estudo foi avaliar o potencial de formação óssea das BMSC de pacientes com EIA e EC, analisar sua frequência na medula óssea, sua capacidade proliferativa e o potencial de diferenciação in vitro e in vivo. BMSC foram isoladas de amostras ósseas de pacientes com EC e EIA, coletadas durante a cirurgia para correção da curvatura da coluna vertebral, e de indivíduos sem escoliose submetidos ao tratamento cirúrgico de fraturas esqueléticas. O teste de eficiência de formação de colônias mostrou frequência reduzida de BMSC isoladas de pacientes com EIA e também maior tempo de duplicação celular em relação às BMSC de pacientes com EC e controles sem escoliose. A avaliação dos marcadores de superfície CD34, CD45, CD73, CD90 e CD146 por citometria de fluxo demonstrou perfil fenotípico similar entre as BMSC dos três grupos (EC, EIA e controle). Quanto ao potencial de diferenciação in vitro, BMSC dos três grupos foram capazes de originar células das linhagens osteogênica, adipogênica e condrogênica. Os ensaios funcionais para avaliar o potencial de formação de tecido ósseo in vivo mostraram que as BMSC de EIA e as BMSC do grupo controle reproduziram a microarquitetura do tecido ósseo, recapitulando o microambiente da medula óssea. Embora os mecanismos celulares e moleculares que contribuem para a perda de massa óssea na EIA e EC ainda não estejam totalmente definidos, nossos resultados favorecem a hipótese de que deficiências quantitativas e qualitativas da população de BMSC possam estar implicadas, respectivamente, com a patogenia da EIA e da EC

Although reported for many years in patients with adolescent idiopathic scoliosis (AIS), the relationship between osteopenia e scoliosis is still poorly understood. Recently, decreased bone mineral density has also been described in congenital scoliosis (CS) patients. In vitro studies have shown that bone marrow stromal cells (BMSC) isolated from patients with EIA present reduced osteogenic differentiation capacity, which may be related to osteopenia. Despite reports of decreased bone mass in patients with congenital scoliosis (CS), there are no data in the literature on the differentiation potential of BMSC of those patients. Thus, the aim of this study was to evaluate the bone forming potential of BMSC of patients with AIS e CS, to analyze their frequency in the bone marrow, its proliferative capacity e the potential for differentiation in vitro e in vivo. BMSC were isolated from EC e EIA bone samples harvested during surgery for spine curvature correction, e from individuals without scoliosis submitted surgical treatment of skeletal trauma. Colony forming efficiency assay showed reduced frequency of BMSC isolated from patients with EIA e also a longer time of cell duplication compared to BMSC of patients with CS e control without scoliosis. The evaluation of the surface markers CD34, CD45, CD73, CD90, e CD146 by flow cytometry demonstrated similar phenotypic profile for BMSC from the three groups (EC, EIA e control). In relation to the potential to differentiate in vitro, BMSC from the three groups differentiated into osteogenic, chondrogenic e adipogenic lineages. Functional assays to evaluate the potential for bone tissue formation in vivo showed that BMSC from AIS e BMSC from control group reproduced the microarchitecture of bone tissue, recapitulating the microenvironment of the bone marrow. Although the cellular e molecular mechanisms contributing to bone mass loss in AIS e CS have not yet been fully established, our results favor the hypothesis that quantitative e qualitative impairment of BMSC population may be, respectively, implicated in the pathogenesis of osteopenia associated with AIS e CS

Transient hyperphosphatemia: a benign laboratory disorder in a boy with Gitelman syndrome / Hiperfosfatemia transitória: uma alteração laboratorial benigna em um menino com síndrome de Gitelman

Abstract Transient hyperphosphatasemia of infancy and early childhood (THI) is characterized by transiently increased activity of serum alkaline phosphatase (S-ALP), predominantly its bone or liver isoform, in children under five years of age. There are no signs of metabolic bone disease or hepatopathy corresponding with the increased S-ALP. THI is benign disorder, rather laboratory than clinical disorder, which is usually accidentally detected in both healthy and sick children. When encountered in a child with either chronic bone, liver or kidney disease, it might concern the physician. We present a three year old boy with genetically confirmed Gitelman syndrome where THI was detected accidentally during periodic check-up. S-ALP peaked to 41.8 µkat/L, there were neither laboratory or clinical signs of liver or bone disease; the S-ALP dropped to normal value of 4 µkat/L 60 days later. Therefore, the patient fulfilled the criteria for THI. There were no further increases in S-ALP.

Resumo A hiperfosfatasemia transitória benigna da infância (HTBI) é caracterizada por elevação transitória da atividade da fosfatase alcalina sérica (S-ALP), predominantemente em sua isoforma óssea ou hepática, em crianças com menos de cinco anos de idade. Não há sinais de patologia óssea metabólica ou hepatopatia correspondentes ao aumento da S-ALP. A HTBI é um distúrbio benigno, mais laboratorial que clínico, normalmente detectado acidentalmente em crianças saudáveis e acometidas por alguma patologia. Quando encontrada em crianças com doença crônica óssea, hepática ou renal, maiores preocupações são justificadas. O presente relato descreve o caso de um menino de três anos de idade com síndrome de Gitelman geneticamente confirmada, em que a HTBI foi detectada acidentalmente durante um exame periódico. A S-ALP atingiu o pico de 41,8 µkat/L, sem sinais laboratoriais ou clínicos de doença hepática ou óssea. O valor de S-ALP caiu para o nível normal de 4 µkat/L 60 dias mais tarde. Portanto, o paciente satisfazia os critérios para HTBI. Não houve outros aumentos na S-ALP.

Psoriasis: new comorbidities

Abstract Psoriasis is a chronic inflammatory disease associated with several comorbidities. A few decades ago, it was considered an exclusive skin disease but today it is considered a multisystem disease. It is believed that 73% of psoriasis patients have at least one comorbidity. Studies have demonstrated the association of psoriasis with inflammatory bowel disease, uveitis, psychiatric disorders, metabolic syndrome and its components and cardiovascular diseases. The systemic inflammatory state seems to be the common denominator for all these comorbidities. This work aims at presenting a review of the current literature on some new comorbidities that are associated with psoriasis as osteoporosis, obstructive sleep apnea and chronic obstructive pulmonary disease. While there is still controversy, many studies already point to a possible bone involvement in patients with psoriasis, especially in the male group, generally less affected by osteoporosis. Psoriasis and chronic obstructive pulmonary disease present some risk factors in common as obesity, smoking and physical inactivity. Besides, both diseases are associated with the metabolic syndrome. These factors could be potential confounders in the association of the two diseases. Further prospective studies with control of those potential confounders should be developed in an attempt to establish causality. Existing data in the literature suggest that there is an association between obstructive sleep apnea and psoriasis, but studies performed until now have involved few patients and had a short follow-up period. It is, therefore, premature to assert that there is indeed a correlation between these two diseases.

Fracture in a Young Male Patient Leading to the Diagnosis of Wilson's Disease: A Case Report

Wilson's disease is a rare genetic disorder that has abnormal copper metabolism. Although the disease's main problems are found in liver and brain, some studies revealed manifestation of various musculoskeletal problems in the patients. In this report, we encountered a young patient who had fracture in the forearm bone. Initially, exception to a previous history of fracture from a motorcycle accident, the patient did not have any medical or drug use history, and laboratory work-ups were insignificant. However, with suspicion on his bone's integrity, bone densitometry was recommended and revealed osteopenic change. To disclose a cause for the change, questions were made to recall any particular history or event, and his complaint of recent vision loss led to ophthalmologic consultation where under slit-lamp test found Kayser-Fleischer ring. Further laboratory work-up found low levels of serum copper and ceruloplasmin and high copper level in 24-hr urine sample that led to the diagnosis of Wilson's disease. Although Wilson's disease has been frequently noticed with considerable musculoskeletal manifestation, it rarity makes the diagnosis illusive to a physician. Hence, despite of its rarity, it is imperative to remember the disease's bony manifestation, and it should be suspected in young patients with demineralized bone when the reason for brittle bone cannot be answered with other better known conditions.

Variability and clinical application of metabolic markers of bone / 天津医药

Metabolic markers were released in the process of bone resorption and formation during bone remodelling. These markers have been extensively studied in trials of osteoporosis and other metabolic bone disorders during the past de?cades. Bone metabolic markers can replenish bone mineral density in the management of osteoporosis, but their use in clini?cal practice is challenged by their variability. Recently, there are many great progress in research of bone metabolic markers application in non metabolic bone disorders.

Semaphorins play an important role in bone homeostasis and metabolic bone disease / 中国组织工程研究

BACKGROUND:Bone formation is a dynamic process, and osteoclasts and osteoblasts are involved in this dynamic process. Semaphorins were found first as axonal growth cone guidance molecules, which express in many different tissues and regulate many physiological processes. Recently, Semaphorins are confirmed to play an important role in the regulation of osteoclasts and osteoblasts. OBJECTIVE:To summarize the role of Semaphorins in bone homeostasis. METHODS: A computer-based search of PubMed and Web of Science was performed for articles related to the effect of Semaphorins in regulation of bone metabolism published from June 1993 to January 2014 using the keywords of “semaphorin, sema”. Irrelevant articles or duplicate content articles were excluded, and finaly 48 articles were reviewed. RESULTS AND CONCLUSION:Semaphorins act as a new class of regulatory molecules in the aspect of bone cytobiology. Studies have show semaphorins are actively involved in bone remodeling through some special mechanisms, and semaphorin proteins are crucial for bone homeostasis, which provides a new method and therapeutic target for the treatment of osteoporosis, bone sclerosis, osteolysis adjacent to joint prosthesis and other bone diseases.

Effect and mechanism of leptin on bone metabolism in postmenopausal women / 中华骨科杂志

Objective To investigate the effects of Leptin on the base of anthropometry,densitometry,and biochemistry and reveal the role of Leptin in bone metabolism in postmenopausal women with osteoporosis (OP).Methods From January 2008 to January 2014,data of 82 postmenopausal females with or without OP were analyzed.They were randomized into two groups:OP (n=40) and conditional control group (CON) (n=42).The expression of Leptin receptors in osteoblasts was observed by immunohistochemistry.1 × 10 ng/ml,1 × 102 ng/ml,1 × 103 ng/ml,1× 104 ng/ml of Leptin were added respectively.Then the proliferation,differentiation and mineralization of osteoblasts were measure at 24 h,48 h and 96 h.The gene expressions of bone marrow mesenchymal stem cells (BMSCs) derived osteoblasts and adipocytes treated with Leptin were examined by quantitative analysis of Real time-PCR.Results The expression of Leptin receptors in osteoblasts was observed on plasma membranes and cytoplasm in the normal group and osteoporosis group.In osteoporosis group,different concentrations of Leptin enhanced cell proliferation,cell differentiation and cell mineralization.The growth rate of MTT and the concentration of ALP in the serum of were significantly increased with the effects of 1×10 ng/ml,1×102 ng/ml and 1×103 ng/ml of Leptin,and the action of 1×102 ng/ml Leptin was the most powerful with time dependence.Within 96 hours,the growth rate of osteoblasts increased gradually,and the concentration of ALP increased gradually in 3 weeks.The expression of RANKL/OPG in bone marrow BMSCs derived osteoblasts treated with Leptin were significantly increased.Conclusion Leptin receptor is present in osteoblasts,and Leptin affects biological behaviors of osteoblasts through receptors.The direct effect of Leptin may relate the expression of RANKL/OPG.Then,the balance between bone resorption and bone formation was broken and finally osteoporosis occurred.Lepin may promote osteogenesis and inhibit bone resorption in the differentiation of BMSCs.

Distúrbio mineral ósseo e calcificação vascular em pacientes renais crônicos / Mineral and bone disorder and vascular calcification in patients with chronic kidney disease

Calcificações vasculares têm sido associadas aos distúrbios minerais e ósseos. As alterações nas concentrações séricas de cálcio e fosfato são fatores importantes implicados no processo da calcificação arterial na doença renal crônica. A patogênese da calcificação vascular é um mecanismo complexo e não completamente claro, podendo corresponder a um processo ativo de transformação celular e ossificação heterotópica. Além da hipercalcemia e hiperfosfatemia, estão envolvidos neste processo alterações no metabolismo de substâncias inibidoras e promotoras de calcificação como a fetuína A, osteopontina, osteoprotegerina e proteína de matriz gla. Para o diagnóstico da lesão arterial calcificada, estão disponíveis diversos métodos, um método de estimativa do risco cardiovascular baseado em radiografias simples de coluna lombar e outro método baseado em radiografias simples da pelve e das mãos. Apresentamos, a seguir, uma revisão abordando a relação entre calcificações vasculares e os distúrbios minerais.

Vascular calcifications has been associated with bone and mineral disorders. The alterations in the serum level of calcium concentrations and phosphate are importants factors implicated in the arterial calcification in chronic kidney disease. The pathogenesis of vascular calcification is a complex mechanism and not completely clear, being able to correspond to an active process of cellular transformation and heterotopic ossification. Beyond the hypercalcemia and hyperphosphatemia, they are involved in this process changes in the metabolism of inhibitors and promoters of calcification such as fetuin A, osteopontin, osteoprotegerin, and matrix gla protein. For the diagnosis of the calcified arterial injury are available several complementary methods, a method of estimate of the cardiovascular risk based on plain radiographs of the lumbar column and another method based on simple x-rays of the pelvis and hands. Below, we will present a review approching the link between vascular calcifications and mineral disorders.

Exercise and bone metabolism：evaluation based on bone mineral density, bone biomechanics and biochemical indicators / 中国组织工程研究

BACKGROUND:Based on the blood and urine biochemical changes in different intensities and types of exercise, this research describes the impact of exercise on bone metabolism. Meantime, these biochemical indexes also show a method of marking physiological differences of certain individuals, and also reflect the impact of exercise on bone. These can be regarded as a monitoring index of bone growth and metabolism. OBJECTIVE:To study exercise effect from the biochemical indicators in bone metebolism, and make a further discussion about its influence on bone formation and bone resorption. METHODS:Databases of CNKI and PubMed were retrieved by computer with key words of “exercise; bone metabolism; biochemical indicators” in Chinese and English, respectively, by screening titles and abstracts to search papers related to exercise effects on the blood and urine biochemical indicators. Totaly 236 papers were initialy found, and only 38 papers were included in result analysis. RESULTS AND CONCLUSION: Low-intensity exercise shows less effect on the bone, but excessive exercise is harmful to the bone that can cause stress fractures. What’s worse, it causes a lack of female hormone and reduce bone mass. Exercise can alter the blood and urine biochemical indicators in aspects of types of exercise and intensities. Only the exercise at appropriate intensity makes positive effects on bone formation and resorption, and assists bone mineral density and bone biomechanical indicators to develop exercise prescription and arrange rehabilitation exercises. MechanismS of bone turnover need further discussion at the celular level.