Is periostin useful as a biomarker for fibrous dysplasia? / ¿Es útil periostina como biomarcador de displasia fibrosa?

Fibrous dysplasia (FD) is an infrequent non-hereditary bone disease caused by a somatic mutation of the GNAS gene. Periostin is a novel marker that increases during tissue healing and fibrous or inflammatory diseases. We conducted an exploratory case-control study to evaluate sensitivity of periostin as a biomarker of FD. The study comprised 15 patients with FD, and healthy age- and sex-matched subjects (controls). Serum periostin levels were assessed and comparisons were established between FD patients and controls, and between patients with the monostotic and the polyostotic form of FD. No statistically significant differences in serum periostin levels were observed between the cohort of FD patients studied here and the control group (FD: 51.1±10ng/ml vs. control: 44.2±15ng/ml; p=0.15), or between the clinical forms of FD (polyostotic: 51.8±9.1ng/ml vs. monostotic: 49.6±13 ng/ml; p=0.66). A sub-analysis performed to compare serum levels of periostin in FD patients with and without a history of fractures showed no statistically significant differences [fracture patients (n=4): 41.2±17ng/ml vs. non-fracture patients (n=11): 49.9±11 ng/ml; p=0.47].Lastly, sensitivity of periostin as a biomarker of FD was analyzed, and was found to have low sensitivity to estimate disease activity [ROC curve; cut-off points: 39.625(0.867-0.467)]. To conclude, in the cohort of FD patients studied here, periostin serum levels did not differ significantly from those of the control group or between the two forms of the disease, and showed low sensitivity as a biomarker of the disease. (AU)

La displasia fibrosa (DF) es una enfermedad infrecuente del hueso, no hereditaria producida por una mutación somática del gen GNAS. Periostina (Postn) es un novedoso marcador, cuyos niveles séricos se encuentran elevados en los procesos de reparación tisular, enfermedades fibrosas o inflamatorias. Llevamos a cabo un estudio exploratorio caso-control para evaluar la sensibilidad de Postn como biomarcador de DF. Se incluyeron en el estudio 15 pacientes con DF apareados por edad y género con sujetos sanos (controles) en los cuales se evaluó los niveles séricos de Postn en pacientes con DF y controles y según forma de presentación clínica. No observamos diferencias estadísticamente significativas en los niveles séricos de Postn y el grupo control (DF: 51.1±10ng/ml vs. control: 44.2±15ng/ml; p=0.15) como así tampoco por forma clínica de DF (poliostótica: 51.8±9.1ng/ml vs. monos-tótica: 49.6±13 ng/ml; p=0.66). Posteriormente realizamos un sub-análisis para evaluar los niveles séricos de Postn en los pacientes con DF y antecedentes de fracturas no observan-do diferencias estadísticamente significativas [fracturados (n=4): 41.2±17ng/ml vs. no frac-turados (n=11): 49.9±11 ng/ml; p=0.47]. Por último analizamos la sensibilidad Postn como biomarcador de DF, mostrando este poseer escasa sensibilidad para estimar actividad de la enfermedad [curva ROC; puntos de corte: 39.625 (0.867-0.467)]. En conclusión, los ni-veles séricos de Postn en nuestra cohorte de pacientes con DF no mostraron diferencias estadísticamente significativas comparadas con el grupo control o por forma clínica de presentación, mostrando una baja sensibilidad como biomarcador de enfermedad. (AU)

Hyponatremia in elderly patients with fragility fractures of the proximal femur: a cross-sectional study / Hiponatremia em pacientes idosos com fratura proximal de fêmur por fragilidade: um estudo transversal

ABSTRACT Introduction: Proximal femur fractures affect the mortality and morbidity of elderly individuals. Recent studies have shown an association between fragility fractures and hyponatremia, a common fluid and electrolyte balance disorder. Objectives: This study aimed to investigate the occurrence of hyponatremia in patients with fragility fractures of the proximal femur. Methods: The authors looked into the data from the medical records of patients admitted to the emergency unit of the Real Hospital Português for fragility fractures of the proximal femur from 2014 to 2017. The study included patients with serum sodium levels recorded in their charts. Results: Fourteen of 69 (20.3%) patients with proximal femur fractures had hyponatremia. The main factors linked to hyponatremia were lung disease, and prescription of amiodarone and/or antidepressants. Conclusion: In elderly individuals, fragility fractures of the proximal femur may correlate with hyponatremia, particularly among patients on amiodarone or antidepressants.

RESUMO Introdução: Fratura de fêmur proximal tem impacto na mortalidade e morbidade de idosos. Estudos recentes vêm demonstrando associação entre fratura por fragilidade e hiponatremia, um distúrbio hidroeletrolítico comum na prática médica. Objetivos: Investigar a ocorrência de hiponatremia em pacientes com fratura proximal de fêmur por fragilidade. Metodologia: Foram coletados dados a partir de prontuários de pacientes admitidos na emergência do Real Hospital Português devido à fratura proximal de fêmur por fragilidade, entre 2014 e 2017, e aqueles com natremia disponível no prontuário eletrônico foram incluídos no estudo. Resultado: Dentre os 69 pacientes com fratura de fêmur proximal, houve uma ocorrência de 14 pacientes com hiponatremia, o que corresponde a 20,3%. Os principais fatores associados à hiponatremia no estudo foram doença pulmonar, uso de amiodarona e antidepressivos. Conclusão: Em idosos, a fratura de fêmur proximal por fragilidade pode estar correlacionada com hiponatremia, principalmente quando estão sob uso de amiodarona ou antidepressivos.

MicroRNA-221 promotes cell proliferation, migration, and differentiation by regulation of ZFPM2 in osteoblasts

Bone fracture is a common medical condition, which may occur due to traumatic injury or disease-related conditions. Evidence suggests that microRNAs (miRNAs) can regulate osteoblast differentiation and function. In this study, we explored the effects and mechanism of miR-221 on the growth and migration of osteoblasts using MC3T3-E1 cells. The expression levels of miR-221 in the different groups were measured by qRT-PCR. Then, miR-221 mimic and inhibitor were transfected into MC3T3-E1 cells, and cell viability and migration were measured using the CCK-8 assay and the Transwell migration assay. Additionally, the expression levels of differentiation-related factors (Runx2 and Ocn) and ZFPM2 were measured by qRT-PCR. Western blot was used to measure the expression of cell cycle-related proteins, epithelial-mesenchymal transition (EMT)-related proteins, ZFPM2, and Wnt/Notch, and Smad signaling pathway proteins. miR-221 was significantly up-regulated in the patients with lumbar compression fracture (LCM) and trochanteric fracture (TF). miR-221 promoted ALP, Runx2, and OPN expressions in MC3T3-E1 cells. miR-221 overexpression significantly increased cell proliferation, migration, differentiation, and matrix mineralization, whereas suppression of miR-221 reversed these effects. Additionally, the results displayed that ZFPM2 was a direct target gene of miR-221, and overexpression of ZFPM2 reversed the promoting effects of miR-221 overexpression on osteoblasts. Mechanistic study revealed that overexpression of miR-221 inactivated the Wnt/Notch and Smad signaling pathways by regulating ZFPM2 expression. We drew the conclusions that miR-221 overexpression promoted osteoblast proliferation, migration, and differentiation by regulation of ZFPM2 expression and deactivating the Wnt/Notch and Smad signaling pathways.

Níveis séricos de homocisteína em crianças e adolescentes com comprometimento da saúde óssea / Serum homocysteine levels in children and adolescents with impaired bone health

INTRODUÇÃO: Foi documentada uma associação entre níveis séricos elevados de homocisteína (S-Hci) e baixa densidade mineral óssea (DMO) e aumento do risco de fratura em mulheres na pós-menopausa. São escassos os dados concernentes à S-Hci e à saúde óssea em crianças. OBJETIVO: Avaliar S-Hci em crianças e adolescentes com comprometimento da saúde óssea e procurar por relações com dados clínicos e laboratoriais. PACIENTES E MÉTODOS: Avaliamos os níveis de S-Hci em 37 crianças e adolescentes (22 meninos e 15 meninas; média de idade, 13,9 ± 3,5 anos) com fraturas prevalentes por trauma de baixa energia (média 3,3 ± 2,3 por paciente) e/ou baixa DMO espinhal/L1-L4 (escore Z abaixo de -2 DP; DXA Lunar GE). Também avaliamos S-ALP, CrossLaps sérico (S-Hci-CrossLaps), osteocalcina (S-OC), altura, peso corporal, índice de massa corporal (IMC) e níveis séricos de folato e vitamina B12. Por ocasião da avaliação, as crianças não estavam tomando qualquer medicação que sabidamente influenciasse o metabolismo ósseo. Os parâmetros dependentes de idade foram expressos como escores Z ± DP. RESULTADOS: O escore Z para S-Hci foi significativamente mais alto (1,3 ± 1,5; P < 0,0001) e o escore Z de para DMO/L1-L4 foi significativamente mais baixo (-1,7 ± 1,3; P < 0,0001), respectivamente, em comparação com os valores de referência. S-ALP não diferiu dos valores de referência (P = 0,88), enquanto S-CrossLaps e S-osteocalcina foram mais elevados (1,2 ± 1,8 e 0,4 ± 0,5; P = 0,0001 e P = 0,001, respectivamente). S-Hci estava inversamente correlacionada com DMO/L1-L4 (r = -0,33; P = 0,05) e S-ALP (r = -0,36; P = 0,04) não tendo relação com o número de fraturas prevalentes (r = 0,01), S-osteocalcina (r = -0,22) ou S-CrossLaps (r = 0,003). CONCLUSÃO: Esses resultados sugerem aumento na remodelação óssea e uma influência negativa da S-Hci elevada na formação óssea e na DMO em crianças e adolescentes com fraturas recorrentes.

INTRODUCTION: Association between high serum homocysteine (S-Hcy) levels and low bone mineral density (BMD) and increased fracture risk in postmenopausal women has been documented. Data concerning S-Hcy and bone health in children are scarce. OBJECTIVE: Our aim was to evaluate S-Hcy in children and adolescents with impaired bone health and look for correlations with clinical and laboratory data. PATIENTS AND METHODS: We assessed S-Hcy levels in 37 children and adolescents (22 boys and 15 girls; mean age 13.9 ± 3.5 years) with prevalent low-energy trauma fractures (mean 3.3 ± 2.3 per patient) and/or low spinal L1-L4 BMD (below -2SD Z-score; DXA Lunar GE). We also evaluated S-ALP, serum CrossLaps, osteocalcin (S-OC), body height, weight, body mass index (BMI) and serum levels of folate and vitamin B12. At the time of assessment, the children were not taking any drugs known to influence bone metabolism. The age-dependent parameters were expressed as Z-scores ± SD. RESULTS: S-Hcy Z-score was significantly higher (1.3 ± 1.5; P < 0.0001) and L1-L4 BMD Z-score was significantly lower (-1.7 ± 1.3; P < 0.0001), respectively, in comparison with reference values. S-ALP did not differ from reference values (P = 0.88), while S-CrossLaps and S-osteocalcin were higher (1.2 ± 1.8 and 0.4 ± 0.5; P = 0.0001 and P = 0.001, respectively). S-Hcy was inversely correlated to L1-L4 BMD (r = -0.33; P = 0.05) and S-ALP (r = -0.36; P = 0.04) and not related to number of prevalent fractures (r = 0.01), S-osteocalcin (r = -0.22) or S-CrossLaps (r = 0.003). CONCLUSION: These results suggest increased bone turnover and negative influence of elevated S-Hcy on bone formation and BMD in children and adolescents with recurrent fractures.

Variations in plasma trace-elements concentration during fracture healing in dogs.

The study was conducted on healthy Mongrel dogs. Fracture of Radius Ulna was inflicted with wire-saw. Subsequently repair was carried out using bone plates. Plasma Zinc concentrations decreased significantly from control values of 317.71 to 294.92 micrograms/dl at day one post-operatively and the values reached basal levels by 21st day. The concentrations of plasma Copper, Cobalt and Iron continued to decrease during the post-operative period. However, Manganese concentration increased significantly during the corresponding post operative period. Results indicate withdrawal of minerals from body reserves during bone repair.