Dysregulated expression of miR-92a-3p in senile osteoporosis and its diagnostic value in hip fragility fractures / 中华内分泌外科杂志

Objective:To investigate the expression of miR-92a-3p in senile osteoporosis (OP) and its diagnostic value in hip fragility fractures.Methods:With the help of the National Center for Biotechnology Information (NCBI) website, the data sets related to OP and miRNA were retrieved and analyzed and screened to obtain the target miRNA. Serum samples were collectedfrom 53 OP patients and 24 healthy people, and the OP patients were divided into hip fragility fracture group (OP_F; n=30) and no hip fragility fracture group (OP_WF; n=23). The subjects' bone mineral density and serum bone metabolism markers were measured: calcium, phosphorus, parathyroid hormone, 25-hydroxyvitamin D, bone alkaline phosphatase, serum C-terminal peptide. The expression levels of target miRNAs in serum samples were detected by qRT-PCR. Chi-square test, t test, Spearman rank correlation and receiver operating characteristic curve (ROC curve) were used to analyze the potential relationship between the expression level of miR-92a-3p and the clinical characteristics of patients.Results:According to the analysis of NCBI website, the expression of miR-92a-3p in OP patients was higher ( t=3.41, P=0.007) than that in healthy people, and the expression level of miR-1304-5p was lower ( t=5.13, P<0.001). qRT-PCR experiments confirmed the above results, and further found that the expression of miR-92a-3p in the OP_F group was significantly higher than that in the OP_WF group (t=3.01, P=0.004), but there was no significant difference in miR-1304-5p between the two groups (t=0.71, P=0.480). Compared with the healthy control group, the BMI ( t=2.71, P=0.008), bone mineral density score ( t=29.02, P<0.001), calcium ( t=61.20, P<0.001), phosphorus ( t=2.54, P=0.013), 25-hydroxyvitamin D (t=3.01, P=0.004) ,bone alkaline phosphatase ( t=12.56, P<0.001), and serum C-terminal peptide ( t=7.52, P<0.001) levels were statistically different between the OP patient group and the healthy control group. Compared with the OP_WF group, the bone mineral density score ( t=2.08, P=0.042), calcium ( t=15.75, P<0.001), bone alkaline phosphatase ( t=2.02, P=0.049) and serum C-terminal peptide ( t=3.39, P=0.001) levels were statistically different between the OP_F group and the OP_WF group. Bone mineral density score and bone alkaline phosphatase concentration were related to the expression of miR-92a-3p and were negatively and positively correlated ( r=0.416, P=0.022), respectively ( r=-0.403, P=0.027). The area under the ROC curve was 0.723, and the level of miR-92a-3p had potential significance in the diagnosis of hip fragility fractures ( P=0.006) . Conclusion:miR-92a-3p is highly expressed in OP and has biological significance for the diagnosis of hip fragility fractures.

Caso clínico: hipofosfatasia de la niñez. Seguimiento clínico / Clinical case: childhood hypophosphatasia. Clinical follow-up

La hipofosfatasia (HP) es una enfermedad congénita, causada por mutaciones con pérdida de función en el gen ALPL que codifica la isoenzima no específica de tejido de la fosfatasa alcalina (TNSALP). Su expresión clínica es muy variable, desde casos de muerte intraútero por alteración grave de la mineralización ósea, hasta casos solo con caída prematura de la dentición. Se presenta el caso clínico de un varón al que se le diagnosticó odontohipofosfatasia a los 30 meses por pérdida temprana de piezas dentarias y niveles anormalmente bajos de fosfatasa alcalina, sin signos de raquitismo ni deformidades óseas. Durante su seguimiento, hasta los 13 años, presentó síntomas compatibles con HP infantil leve, como cansancio al caminar, incoordinación en la marcha y dolor en miembros inferiores que aumentaban con la actividad física. Ante la aparición de edema bimaleolar y poca respuesta al tratamiento con calcitonina y antiinflamatorios, se descartaron patologías infecciosas o reumáticas o ambas y se diagnosticó, por biopsia de tibia y peroné, periostitis sin detección de cristales de pirofosfato. Los controles radiológicos durante su evolución mostraron ensanchamiento metafisario en muñeca, falta de remodelado de metacarpianos, hojaldrado perióstico en tibia y peroné e hipomineralización en metáfisis tibiales, con "lenguas radiolúcidas" características de HP. Como conclusión, la hipofosfatasia debe considerarse como una entidad clínica para descartar en niños que presentan pérdida temprana de dientes. La presencia de este cuadro clínico es en general suficiente para realizar el diagnóstico de HP de la niñez. (AU)

Hypophosphatasia (HP) is a congenital disease, caused by mutations with loss of function in the gene ALPL that encodes the non-specific tissue isoenzyme of alkaline phosphatase (TNSALP). Its clinical expression displays considerable variability, from cases of intrauterine death due to severe alteration of bone mineralization, to cases with only early loss of teeth. We report the case of a male, diagnosed as odontohypophosphatasia at 30 months of age due to early loss of teeth and abnormally low levels of alkaline phosphatase, without signs of rickets or bone deformities. During follow-up, up to 13 years of age, he presented symptoms consistent with mild infantile HP such as tiredness when walking, lack of gait coordination, and pain in lower limbs, especially after physical activity. Due to the appearance of bimalleolar edema and poor response to treatment with calcitonin and anti-inflammatory drugs, infectious and / or rheumatic pathologies were ruled out. Periostitis without pyrophosphate crystal detection was diagnosed by tibial and fibular biopsy. Radiological controls during follow up showed metaphyseal wrist enlargement, lack of remodeling of metacarpals, periosteal flaking in the tibia and fibula and hypomineralization in the tibial metaphysis, with "radiolucent tongues"; characteristic of HP. In conclusion, hypophosphatasia should be considered as a clinical entity in children who present early loss of teeth. The presentation of this clinical case is generally sufficient to make the diagnosis of childhood HP. (AU)

Fosfatasa alcalina ósea sérica elevada no mediada por metástasis en un paciente con cáncer renal / Elevated bone alkaline phosphatase not mediated by metastasis in a patient with renal cancer

Presentamos un paciente de 63 años con cáncer renal y aumento de fosfatasa alcalina sérica de tipo óseo de acuerdo con su reactividad con anticuerpos monoclonales específicos. Se descartaron las causas conocidas de aumento de la isoenzima, incluyendo metástasis óseas. Los niveles enzimáticos cayeron abruptamente con la remoción del tumor, por lo que consideramos a este último como su origen. Diversas isoenzimas de fosfatasa alcalina pueden ser producidas y secretadas por tumores como manifestación paraneoplásica. El conocimiento de esto puede, en ocasiones, orientarnos hacia la presencia de una neoplasia oculta. Además, los cambios en los niveles séricos de esas isoenzimas pueden ser indicadores de respuesta al tratamiento o de recidiva tumoral. (AU)

A 63-year old man was seen in the outpatient clinic because of renal cancer and elevation in bone alkaline phosphatase measured by monoclonal antibodies assay. Known causes of bone isoenzyme augmentation, including bone metastases, were ruled out. The tumoral origin of the isoenzyme was diagnosed because after removal of the tumor the enzymatic levels fell sharply. Several alkaline phosphatase isoenzymes can be produced and secreted by tumors as a paraneoplasic manifestation and their elevation could be a manifestation of an occult neoplasia. Furthermore the monitoring of their blood levels can be useful means of treatment response and a tool to monitoring recurrence if a sharp decrease after removal of the tumor is observed. (AU)

Relationship between vitamin D level and related indicators in breastfeeding infants in People's Hospital of Longhua New District in Shenzhen City / 中华临床营养杂志

Objective To investigate the changes of vitamin D level and its relationship with bone alkaline phosphatase(BAP)and parathyroid hormone(PTH)in infants fed with breast milk and vitamin D supplementation for 0-8 months in People`s Hospital of Longhua New District in Shenzhen city.MethodsTotally 67 newborns in the Department of Obstetrics and Gynecology of People`s Hospital of Longhua New District were selected.These newborns were breastfed and began to supplement vitamin D 400 U/d in the 15th day after birth.The serum 25-(OH)D3 and BAP and PTH levels were measured in newborns and 4-/8-month-old infants,and the correlations of serum 25-(OH)D3 with BAP and PTH were analyzed by Pearson correlation analysis.ResultsCompared with the newborns,the serum 25-(OH)D3 [(78.47±36.41)nmol/L,(75.26±34.73)nmol/L],BAP[(231.43±78.81)μg/L,(205.97±71.64)μg/L],PTH[(31.76±11.54)pg/ml,and(32.94±13.82)pg/ml] levels of 4-and 8-month-old infants were significantly higher,and the difference were statistically significant(t4 months=7.823,12.568,11.852,t8 months=7.364,9.473,11.947;all P=0.000).There was a negative correlation between serum 25-(OH)D3 and BAP in newborns and 4-/8-monthold infants(r=-0.372,-0.463,-0.309;P=0.008,0.016,0.021),the serum BAP was positively correlated with PTH in infants aged 4 months and 8 months(r=0.487,0.338;P=0.005,0.032),and the serum 25-(OH)D3 was negatively correlated with PTH in infants aged 4 months(r=-0.297,P=0.041).Conclusions Infants at birth are prone to vitamin D deficiency in Shenzhen City.After 4 months of breastfeeding and vitamin D400U/d supplementation,the vitamin D levels in most infants become normal.25-(OH)D3 is correlated with BAP and PTH in different months.

Study on levels of serum phosphorus, bone alkaline phosphatase and 25-hydroxyvitamin D in preterm infants with very low birth weight / 中华流行病学杂志

Objective To compare the levels of serum phosphorus,bone alkaline phosphatase and 25-hydroxyvitamin D3 in preterm infants with very low birth weight, and provide evidence for early screening, prevention of metabolic bone disease in preterm infants.Methods A total of 110 newborns who met the inclusion criteria were selected in pediatric ward in our hospital.The case group included 60 preterm infants with very low birth weight and control group included 50 full term infants.Fasting blood were taken from the subjects at week 1, 4, and 12 respectively, and ELISA was conducted to quantitatively detect the serum levels of phosphorus, bone alkaline phosphatase and 25-hydroxyvitamin D.Results The increase of serum 25-hydroxyvitamin D3 in case group was smaller than that in control group;the levels of serum phosphorus had no significant difference between two groups.In case group, the level of bone alkaline phosphatase increased at week 1,4, and 12, and the 25-hydroxyvitamin D3 level had significant difference at week 12 (P＜0.05).The abnormal rate of 25-hydroxyvitamin D3 level was 26.7％ for case group and 0％ for control group.Conclusion There were significant differences between case group and control group in levels of bone alkaline phosphatase and 25-hydroxyvitamin D3, suggesting that detecting the serum levels of bone alkaline phosphatase and 25-hydroxyvitamin D3 would facilitate the early diagnosis of metabolic bone disease in preterm infants.

Analysis of detection results of bone alkaline phosphatase in 2 184 children in Baoji area / 国际检验医学杂志

Objective To evaluate the clinical value of bone alkaline phosphatase in early diagnosis and treatment effect of chil-dren′rickets and to understand the incidence rate of rickets in children in the local region by the detection of neonatal bone alkaline phosphatase(NBAP).Methods 2 184 children with physical examination in our hospital from January to December 2013 were se-lected and divided into the infants,young children,preschool and school-age children groups according to age.The finger blood was collected for detecting the bone alkaline phosphatase in the peripheral blood by the bone alkaline phosphatase reagent kit provided by Beijing Jinyu diagnosis technology Co.,Ltd.Results Among detected 2 184 children,the detection rate of clinical rickets(NBAP>250 U/L)was 10.1 %,moreover the smaller the age,the higher the detection rate;the detection rate of subclinical rickets(NBAP 200~250 U/L)was 65.5%,indicating that most children in Baoji region were in sub-health state;the detection rate in spring and winter was higher than that in summer and autumn;the detection rate of NBAP had no gender difference.Conclusion Children are in the rapid growth and development period,easy to suffer from vitamin D deficiency,the activity detection of NBAP has important clinical value in the early diagnosis of rickets caused by vitamin D deficiency.Prevention should begin from perinatal period and NBAP should be timely detected in order to conduct early diagnosis and early treatment.

A hospital based study of biochemical markers of bone turnovers & bone mineral density in north Indian women.

Background & objectives: The osteoporotic risk for women increases soon after menopause. Bone turnover markers are known to be associated with bone loss and fracture risk. This study was aimed to assess bone turnover using bone markers and their correlation with bone mineral density (BMD) in pre- and post-menopausal women. Methods: A total of 255 healthy women (160 pre- and 95 post-menopausal) were enrolled. Serum bone alkaline phosphatase (sBAP) and serum N-terminal telopeptide of type I collagen (NTX) were measured to evaluate the bone formation and resorption, respectively. Bone mineral density was determined at lumbar spine (L2-L4) anteroposteriorly, femoral neck and Ward’s triangle using Prodigy dual-energy X-ray absorptiometry (DXA) system. The comparison of years since menopause with respect to BMD and bone markers was also evaluated. Results: NTX and sBAP showed significant negative correlation with BMD of femur neck and Ward’s triangle in postmenopausal women. BMD of all three sides were significant variables for NTX and BMD of femur neck and Ward’s triangle for sBAP in postmenopausal women. BMD lumbar spine was a significant variable for sBAP in premenopausal women. The mean values of NTX increased significantly with increase in the duration of years since menopause. The BMD of all three sides decreased significantly with increase in the duration of years since menopause. Interpretation & conclusions: Serum NTX and sBAP were inversely correlated to BMD of femur neck and Ward’s triangle in post-menopausal women. Simultaneous measurements of NTX and BMD in the north Indian women, suggest that bone resorption in women with low BMD remains high after menopause.

The effect of high voltage alternating electric field therapy on fracture healing / 中华物理医学与康复杂志

Objective To explore the effect of high voltage alternating electric field therapy on fracture healing in rats. Methods An animal model of cortical bone defect was successfully established in the unilateral proximal tibia of 41 rats.They were then randomized into an experimental group (21 rats) and a control group (20 rats).The animals in the experimentsl group were given high voltage alternating electric field therapy for 30 minutes daily,while those in the control group only had sham exposure to the high voltage alternating electric field therapy.Rats in each group were sacrificed at days 7,14,21 and 28 post-operation.After blood collection,the operated tibias of the rats were resected with muscle and other soft tissue removed.Bone mineral density (BMD) of the callus at the fracture point was measured using dual energy X-ray absorptiometry (DEXA).The calluses were then cut down and fixed,decalcificated and sliced for histological observation.At the same time serum osteocalcin ( OC ) and bone alkaline phosphatase (RAP) were also detected by ABC-ELISA. Results The BMD examination showed that callus BMD in the experimental group was significantly higher than in the control group at days 14 and 28.Serum OC and RAP in the experimental group were also higher at days 14 day 21,and OC was still significantly higher in the experimental group at day 28.Histological examination showed that in the early stages of bone healing hematoma absorption and organization appeared earlier in the experimental group than in the control group,with remarkable osteoblast and chondroblast proliferation.While at the later stage,bone trabeculas connection and mineralization also appeared earlier in the experimental group than in the control group. Conclusions High voltage alternating electric field therapy may promote fracture healing by accelerating hematoma absorption and organization,elevating osteoblast proliferation and differentiation as well as promoting extracellular matrix secretion and mineralization.The underlying therapeutic mechanism might be related to the increased expression of OC and RAP caused by exposure to the high voltage alternating electric field.

The diagnostic application value of bone alkaline phosphates in breast cancer postoperative bone metastases / 中国医师进修杂志

ObjectiveTo study the diagnostic application value of bone alkaline phosphates (AKP-3) in breast cancer postoperative bone metastases.Methods Fifty cases with breast cancer postoperative bone metastases were selected.The relationship between the serum levels of AKP-3 and bone metastases was analyzed,and the diagnostic application value of AKP-3 in breast cancer postoperative bone metastases was studied.ResultsAccording to the degree of the bone imaging,among 50 cases,9 cases in the degree M0,the constituent ratio was 18.0％(9/50); 14 cases in the degree M1,the constituent ratio was 28.0％( 14/50); 20 cases in the degree M2,the constituent ratio was 40.0％(20/50); 7 cases in the degree M3,the constituent ratio was 14.0％ (7/50); the constituent ratios were not statistically significant (P ＞0.05 ).The serum levels of AKP-3 in the degree M0,M 1,M2,M3 were(20.3 ± 6.1 ),(42.4 ± 7.4),(54.1 ±8.9),(86.8 ± 9.2) U/L,the differences were statistically significant (P＜ 0.05).ConclusionThe detection and dynamic observations of AKP-3 help in the early diagnosis and prognostic evaluation of breast cancer postoperative bone metastases.

Diagnóstico clínico e laboratorial do hiperparatiroidismo secundário / Clinical and laboratory diagnoses of secondary hyperparathyroidism

O hiperparatiroidismo secundário (HPTS), observado nos doentes urémicos, apesar de se instalar desde estadios precoces da insuficiência renal,apresenta manifestações clínicas pouco específicas e frequentemente tardias. Para além da promissora técnica de avaliação da arquitectura trabecularóssea por tomografia quantitativa microcomputorizada os métodos imagiológicos são de escassa utilidade no diagnóstico das alterações ósseasassociadas ao HPTS. Ao longo dos últimos anos foram avaliados diversos marcadores bioquímicos da remodelação óssea e a respectiva utilidade nodiagnóstico não invasivo da osteodistrofia renal. Finalmente, é ainda discutido o eventual papel de factores locais (citoquinas e factores de crescimento) na modulação da remodelação óssea.

Secondary hyperparathyroidism represents one extreme of the spectrum of the bone and endocrine changes observed in uraemic patients, and may develop since early stages of renal failure. The clinical symptoms and signs are non-specific and the contribution of image evaluation in the diagnosis of secondary hyperparathyroidism is, frequently, misleading. In this review, in addition to the classic modulators of bone remodeling, like parathyroid hormone (and PTHfragments), calcitriol and calcitonin, the role of others local factors involved in osteoblast and osteoclast activation, like cytokines and growth factors, is alsodiscussed.

Study on the activity of serum bone alkaline phosphatase and its relations to the heritability among prepuberty Twins / 中华流行病学杂志

Objective To evaluate calcium deficiency and demand in pre-puberty twins and to analyze the heritability of serum bone alkaline phosphatase(BALP).Methods A total of 73 pairs of twins aged 9-16 years were examined by BALP test.Microsatellite polymorphism Was used To diagnose the zygosity of twins,while both intraclass correlation coefficient method and Christian formula were perfortled to investigate heritability of serum BALP.Results The results of zygosity diagnosis displayed that 34 pairs of twins were monozygotic(MZ)twins and 39 pairs were dizygotic(DZ)twins.97.9％of the subjects appeared unusual in the activity of BALP,with activity of BALP>250 U/L in 43.1％of subjects and 200-250 U/L in 54.8％of the subjects.The intake of calcium Was unsatisfied in 48.4％of the boys and 39.0％in girls.Less than 10.0％ of the Sllbiects were satisfied with the intake of calcium in each age group while over 45.0％of the snbjects in 10-13 age group were deficient in calcium.Differences between the means of BALP in different sex groups(t=1.633,P=0.105)and different age groups(F=0.323,P=0.924)were not statistically significant.Heritability analysis displayed that intra-class variation.Inter-class variation.Intra-class correlation coefficient were 191.54,1462.22,0.77 in MZ twins,and those were 491.03,1475.57,0.50 in DZ twins respectively with the heritability of BALP activity as 0.54.Conclusion Calcium deficiency Is commonplace in pre-puberty twins.Our data showed that the BALP activity was influenced both by genetic(54％)and environmental(46％)factors.