Repetitive stress fracture: a warning sign of genetic susceptibility to fracture? A case report of a heterozygous variant in SERPINF1

SUMMARY The occurrence of fractures in young individuals is frequently overlooked by physicians, especially when associated with exercise or trauma. Nevertheless, multiple fractures should always be investigated since underlying conditions can predispose to such events. We describe here the case of a young, healthy woman who sustained multiple fractures in the lower limbs, which were initially considered to be "stress fractures". Further investigation, including a panel of genes associated with osteogenesis imperfecta, revealed that the patient is a heterozygous carrier of a SERPINF1 variant. According to criteria recommended by the American College of Medical Genetics and Genomics and the Association for Molecular Pathology, this variant is classified as likely benign (PM2, PP3, PP4, BP1, and BP4). The patient's mother and brother were also asymptomatic carriers of the variant and had sustained previous minor fractures. The patient had normal biochemical profile and bone density. This condition has been rarely described and is not associated with low bone mineral density or altered bone turnover markers. This case highlights the importance of investigating multiple fractures in young patients who are otherwise healthy since these may be a warning sign of rare genetic conditions associated with fragility fractures.

Resultados de los concentrados plaquetarios en la regeneración ósea guiada / Results of platelet concentrates in guided bone regeneration

Los defectos óseos alrededor de los implantes dentales son considerados enfermedades que afectan el soporte y estabilidad del implante dental lo que limita la oseointegración. El tratamiento de estos defectos involucra procedimientos de regeneración ósea guiada que se define como la reproducción o reconstitución de una parte perdida o dañada del tejido óseo periimplantario con el fin de restaurar su arquitectura y función. El plasma rico en plaquetas y el plasma rico en fibrina son concentrados de plaquetas autólogos ampliamente usados en la regeneración periodontal y regeneración ósea guiada; sin embargo, sus resultados clínicos, histológicos y radiográficos son discutidos cuando se tratan defectos óseos alrededor de implantes dentales. En la presente revisión se realizó una búsqueda de la información mediante las bases de datos de diferentes buscadores (PubMed, SciELO, Redalyc y ScienceDirect) para encontrar artículos que traten sobre el uso de los concentrados plaquetarios (plasma rico en plaquetas y plasma rico en fibrina) en la terapia de la regeneración ósea guiada. Clínicamente, los concentrados plaquetarios otorgan resultados favorables en la reducción de la profundidad de sondaje y ganancia de nivel de inserción clínica en el tratamiento de defectos infraóseos periodontales. Histológicamente, los concentrados plaquetarios favorecen la neoformación ósea aumentando la velocidad de regeneración. Radiográficamente, los concentrados plaquetarios favorecen el aumento de densidad ósea, relleno óseo y tejido mineralizado. Con ello, se logra una reducción significativa del tamaño del defecto óseo(AU)

Bone defects around dental implants are considered to be diseases affecting the support and stability of the implant, thus limiting osseointegration. Treatment of these defects involves guided bone regeneration procedures, defined as the reproduction or reconstitution of a part lost or damaged of the peri-implant bone tissue with the purpose of restoring its architecture and function. Platelet-rich plasma and fibrin-rich plasma are autologous platelet concentrates widely used in guided bone regeneration and periodontal regeneration. However, their clinical, histological and radiographic results are debated when bone defects around dental implants are dealt with. The present review included a search for information in the databases of various search engines (PubMed, SciELO, Redalyc and ScienceDirect) to find papers about the use of platelet concentrates (platelet-rich plasma and fibrin-rich plasma) in guided bone regeneration therapy. Clinically, platelet concentrates yield favorable results in reducing probing depth and raising the level of clinical insertion in the treatment of periodontal intraosseous defects. Histologically, platelet concentrates enhance bone neoformation, speeding up regeneration. Radiographically, platelet concentrates lead to an increase in bone density, bone filler and mineralized tissue. A significant reduction is thus achieved in the size of the bone defect(AU)

Polimorfismos de los genes JAG1, MEF2C y BDNF asociados con la densidad mineral ósea en mujeres del norte de México / JAG1, MEF2C and BDNF polymorphisms associated with bone mineral density in women from Northern México

Resumen Introducción. La osteoporosis se caracteriza por una baja densidad mineral ósea; la composición genética es uno de los factores que más influyen en ella, pero hay pocos estudios de genes asociados con esta condición en la población mexicana. Objetivo. Investigar la posible asociación de ocho polimorfismos de un solo nucleótido (Single Nucleotide Polymorphism, SNP) de los genes JAG1, MEF2C y BDNF con la densidad mineral ósea en mujeres del norte de México. Materiales y métodos. Participaron 124 mujeres de 40 a 80 años, sin parentesco entre ellas. Su densidad mineral ósea se determinó mediante absorciometría dual de rayos X y la genotipificación se hizo utilizando discriminación alélica mediante PCR en tiempo real; se estudiaron cuatro de los SNP del gen JAG1 (rs6514116, rs2273061, rs2235811 y rs6040061), tres del MEF2C (rs1366594, rs12521522 y rs11951031) y uno del BDNF (rs6265). El análisis estadístico de los datos obtenidos se hizo por regresión lineal. Resultados. El SNP rs2235811 presentó asociación significativa con la densidad mineral ósea de todo el cuerpo bajo el modelo de herencia dominante (p=0,024) y, aunque los otros SNP no tuvieron relación significativa con esta densidad, en ninguno de los modelos de herencia estudiados, se observó una tendencia hacia esta asociación. Conclusión. Los resultados sugieren que el SNP rs2235811 del gen JAG1 podría contribuir a la variación en la densidad mineral ósea de las mujeres del norte de México.

Abstract Introduction: Osteoporosis is characterized by a low bone mineral density. Genetic composition is one of the most influential factors in determining bone mineral density (BMD). There are few studies on genes associated with BMD in the Mexican population. Objective: To investigate the association of eight single nucleotide polymorphisms (SNP) of JAG1, MEF2C and BDNF genes with BMD in women of Northern México. Materials and methods: This study involved 124 unrelated Mexican women between 40 and 80 years old. BMD was determined by dual X-ray absorptiometry. Genotyping was performed using allelic discrimination by real time PCR. We analyzed the SNP of JAG1 (rs6514116, rs2273061, rs2235811 and rs6040061), MEF2C (rs1366594, rs12521522 and rs11951031), and BDNF (rs6265) and the data using linear regression. Results: The JAG1 SNP rs2235811 was associated with the BMD of the total body under the dominant inheritance model (p=0,024). Although the other SNPs were not associated with BMD in any of the inheritance models studied, a trend was observed. Conclusion: Our results suggest that the SNP rs2235811 in the JAG1 gene might contribute to the variation in BMD in women from northern México.

Relationship between glycemic control and OPG gene polymorphisms with lower bone mineral density in patients with type 1 Diabetes mellitus

ABSTRACT The aim of the present study was to investigate the bone mineral density (BMD) of patients with type 1 Diabetes mellitus (T1DM). We also assessed the association between osteoprotegerin (OPG) genetic polymorphisms and BMD. Genotyping was performed for 1181G>C and 163A>G OPG polymorphisms by allelic discrimination in 119 patients with T1DM and 161 normoglycemic (NG) individuals, aged 6 to 20 years old. Glycemic control, serum parameters of bone metabolism and BMD were evaluated. T1DM patients showed low BMD, poor glycemic control and decreased total calcium values when compared to controls (p < 0.05). For all the polymorphisms studied, the genotype and allele frequencies in patients with T1DM were not significantly different from the controls. In patients with T1DM, carriers of OPG 1181CC showed higher concentrations of ionized calcium compared to patients with GG+GC genotypes. These results suggest that low BMD is associated with poor glycemic control in T1DM. Despite the lack of a detected association between OPG polymorphisms and BMD in these patients, the increased ionized calcium in those carrying OPG 1181CC suggests a possible increase in osteoclastogenesis, a conclusion that may be supported by the lower BMD observed in these subjects.

Genetics of osteoporosis: searching for candidate genes for bone fragility

ABSTRACT The pathogenesis of osteoporosis, a common disease with great morbidity and mortality, comprises environmental and genetic factors. As with other complex disorders, the genetic basis of osteoporosis has been difficult to identify. Nevertheless, several approaches have been undertaken in the past decades in order to identify candidate genes for bone fragility, including the study of rare monogenic syndromes with striking bone phenotypes (e.g. osteogenesis imperfecta and osteopetroses), the analysis of individuals or families with extreme osteoporotic phenotypes (e.g. idiopathic juvenile and pregnancy-related osteoporosis), and, chiefly, genome-wide association studies (GWAS) in large populations. Altogether, these efforts have greatly increased the understanding of molecular mechanisms behind bone remodelling, which has rapidly translated into the development of novel therapeutic strategies, exemplified by the tales of cathepsin K (CTSK) and sclerostin (SOST). Additional biological evidence of involvement in bone physiology still lacks for several candidate genes arisen from GWAS, opening an opportunity for the discovery of new mechanisms regulating bone strength, particularly with the advent of high-throughput genomic technologies. In this review, candidate genes for bone fragility will be presented in comprehensive tables and discussed with regard to how their association with osteoporosis emerged, highlighting key players such as LRP5, WNT1 and PLS3. Current limitations in our understanding of the genetic contribution to osteoporosis, such as yet unidentified genetic modifiers, may be overcome in the near future with better genotypic and phenotypic characterisation of large populations and the detailed study of candidate genes in informative individuals with marked phenotype.

Frequencies of interleukin-6, GST and progesterone receptor gene polymorphisms in postmenopausal women with low bone mineral density / Frequência do polimorfismo da interleucina-6, GST, e dos receptores de progesterona em mulheres na pós-menopausa com baixa densidade mineral óssea

CONTEXT AND OBJECTIVE: Osteoporosis is a skeletal disorder characterized by low bone mineral density (BMD). Studies have shown that some of the genetic components relating to lower BMD may be detected by polymorphisms. Our aim was to evaluate the frequencies of interleukin-6, GST and progesterone receptor gene polymorphisms in postmenopausal women with low BMD. DESIGN AND SETTING: Cross-sectional study, conducted in a public university in São Paulo, Brazil. METHODS : We evaluated interleukin-6 (IL-6), progesterone receptor gene (PROGINS) and glutathione S-transferase (GST) polymorphisms in 110 postmenopausal women with no previous use of hormone therapy. Tests were performed using DNA-PCR, from oral scrapings. We used Student's t-test and a logistic regression model for statistical analysis. RESULTS : Regarding IL-6 polymorphism, 58.2% of the patients were homozygotes (GG) and 41.8% had allele C (heterozygote or mutant homozygote + GC or CC). PROGINS genotype polymorphism was absent in 79% (wild homozygote or P1/P1) and present in 20.9% (heterozygote or P1/P2). Regarding GSTM1 polymorphism, the allele (1/1) was present in 72.7% of the patients and was absent in 27.3%. We found that IL-6 polymorphism had statistically significant correlations with the L2-L4 T-score (P = 0.032) and with BMD (P = 0.005). Women with IL-6 polymorphism were 2.3 times more likely to have a L2-L4 T-score of less than -1, compared with those not presenting this polymorphism. CONCLUSION: IL-6 gene polymorphism was correlated with low BMD, whereas the PROGINS and GSTM1 polymorphisms did not show any correlation. .

CONTEXTO E OBJETIVO: A osteoporose é uma desordem esquelética caracterizada por baixa densidade mineral óssea. Estudos têm demonstrado que alguns componentes genéticos relacionados com a menor densidade mineral óssea podem ser detectados por polimorfismos. Nosso objetivo foi avaliar a presença do polimorfismo de genes em mulheres pós-menopáusicas com baixa densidade mineral óssea. TIPO DE ESTUDO E LOCAL: Estudo transversal, conduzido em universidade pública em São Paulo, Brasil. MÉTODOS: Avaliamos os polimorfismos relacionados à interleucina-6 (IL-6), o gene receptor de progesterona (PROGINS) e glutationa S-transferase (GST) em 110 mulheres na pós-menopausa sem terapia hormonal prévia. Os testes foram realizados com DNA-PCR a partir de raspados orais. Foram utilizados teste t de Student e modelo de regressão logística para análise estatística. RESULTADOS: Em relação ao polimorfismo IL-6, 58,2% dos pacientes eram homozigotos (GG) e 41,8% tinham o alelo C (heterozigoto ou homozigoto mutante + GC ou CC). Nos genótipos do polimorfismo PROGINS, 79% estavam ausentes (homozigoto selvagem ou P1/P1) e 20,9% presentes (heterozigoto ou P1/P2). No polimorfismo do GSTM1, o alelo (1/1) estava presente em 72,7% dos pacientes e ausente em 27,3%. Encontramos significância estatística entre o polimorfismo genético da IL-6 com o T-score de L2-L4 (P = 0,032) e a densidade mineral óssea (P = 0,005). As mulheres com polimorfismo da IL-6 tiveram 2,3 vezes mais chance de ter menos de -1 na L2-L4 T-score, quando comparadas às não portadoras. CONCLUSÃO: O polimorfismo do gene da IL-6 está correlacionado com baixa densidade mineral óssea, enquanto os polimorfismos GSTM1 e PROGINS não mostraram correlação. .

effects of estrogen receptor gene-alpha polymorphism on bone mineral density and serum osteoprotegerin levels in postmenopausal Egyptian women

The gene coding for estrogen receptor-alpha [ER-a] is a potential candidate for the regulation of bone mineral density [BMD] in postmenopausal women. The present study was aimed at elucidating the role of two restriction fragment lengths Pvu II and Xba I polymorphisms of the ER-a gene as determinants of bone mineral density; special attention was paid to the correlation between serum osteoprotegerin [OPG] levels and BMD in different ER-a genotypes in postmenopausal [PM] Egyptian women. BMD was measured at the femur neck [FN-BMD]. ER-a gene polymorphisms were detected by PCR-RFLP. Serum OPG levels were measured by an enzyme linked immunosorbent assay. There were significant differences in BMD and OPG according to different genotypes of Pvu II Single-nucleotide polymorphism [SNP]. Carriers of the pp genotype were more likely to have lower BMD and lower OPG values than noncarriers. While there was no significant relationship between Xbal polymorphism and these variables. Postmenopausal [PM] women were stratified into; those with osteoporosis and those without osteoporosis. The difference in BMD and OPG among genotypes were significant in PM with osteoporosis. Further we confirmed that the frequency of p allele. and pp genotype of Pvu II polymorphism were significantly higher in PM with osteoporosis as compared to PMwithout osteoporosis. Xba I failed to show any significant difference in genotype and allele frequencies between the two groups. Genotypes modulate the relationships between BMD and OPG levels, in women with the PP [r=0.512, p<0.000l] and Pp [r=0.346, p<0.0009] genotypes but not in women with the other genotypes [p>0.05]. These results suggest that the Pvu II polymorphism of ER-a may be associated with the FN-BMD in PM Egyptian women. Further, P allele carriers supposed to protect against PM osteoporosis at least partly by increasing serum OPG

Osteogenesis Imperfecta Type VI with Severe Bony Deformities Caused by Novel Compound Heterozygous Mutations in SERPINF1

Osteogenesis imperfecta (OI) comprises a heterogeneous group of disorders characterized by bone fragility, frequent fractures, and low bone mass. Dominantly inherited COL1A1 or COL1A2 mutations appear to be causative in the majority of OI types, but rare recessively inherited genes have also been reported. Recently, SERPINF1 has been reported as another causative gene in OI type VI. To date, only eight SERPINF1 mutations have been reported and all are homozygous. Our patient showed no abnormalities at birth, frequent fractures, osteopenia, and poor response on pamidronate therapy. At the time of her most recent evaluation, she was 8 yr old, and could not walk independently due to frequent lower-extremity fractures, resulting in severe deformity. No clinical signs were seen of hearing impairment, blue sclera, or dentinogenesis imperfecta. In this study, we describe the clinical and radiological findings of one Korean patient with novel compound heterozygous mutations (c.77dupC and c.421dupC) of SERPINF1.

Association of ADIPOR1 polymorphisms with bone mineral density in postmenopausal Korean women

Adiponectin may affect bone through interactions with two known receptors, adiponectin receptors (ADIPOR) 1 and 2. We examined the association between polymorphisms of ADIPOR1 and ADIPOR2 and bone mineral density (BMD) in postmenopausal Korean women. Six polymorphisms in ADIPOR1 and four polymorphisms in ADIPOR2 were selected and genotyped in all study participants (n = 1,329). BMD at the lumbar spine and femur neck were measured using dual-energy X-ray absorptiometry. Lateral thoracolumbar (T4-L4) radiographs were obtained for vertebral fracture assessment and the occurrence of non-vertebral fractures examined using self-reported data. P values were adjusted for multiple testing using Bonferroni correction (Pcorr). ADIPOR1 rs16850799 and rs34010966 polymorphisms were significantly associated with femur neck BMD (Pcorr = 0.036 in the dominant model; Pcorr = 0.024 and Pcorr = 0.006 in the additive and dominant models, respectively). Subjects with the rare allele of each polymorphism had lower BMD, and association of rs34010966 with BMD showed a gene dosage effect. However, ADIPOR2 single nucleotide polymorphisms and haplotypes were not associated with BMD at any site. Our results suggest that ADIPOR1 polymorphisms present a useful genetic marker for BMD in postmenopausal Korean women.

El hueso en el síndrome de Turner / The bone in Turner syndrome

Las pacientes con síndrome de Turner presentan retardo en el crecimiento óseo, que determina una talla final muy inferior a la normal. Muestran anomalías óseas tales como metacarpianos cortos, cubitus valgus, genu valgum, deformidad de Madelung, micrognatia y paladar ojival, cuya etiología se atribuye a la deleción heterocigota del gen SHOX debido a la ausencia total o parcial del cromosoma X. Esta haploinsuficiencia de SHOX podría también contribuir, junto con otros genes, a la hipomineralización ósea predominantemente cortical que presentan estas niñas, la cual se agudiza en la adolescencia y en la vida adulta, etapa en la que se añade hipomineralización del hueso trabecular, producto de la deficiencia estrogénica crónica. Estas alteraciones conducen a un incremento en el riesgo de fracturas. La administración de hormona de crecimiento mejora sustancialmente la talla final, mientras que la terapia de reemplazo hormonal es fundamental para la adquisición y el mantenimiento de la densidad mineral ósea.

Hyperhomocysteinemia and bone mineral density: a case - control study

To find out whether homocysteine has a direct effect on bone or it is an innocent bystander? The study was designed to investigate probable role of homocysteine on bone mineral density [BMD]. This a case-control study wherein, 30 patients with at Least one densitometry criterion of osteoporosis in femoral neck or Lumbar spine were enrolled as the case group along with another 30 normal subjects with normal BMD, as the control group. The patients of the two groups were matched for their ages and sex. In all eligible patients BMD was measured by DEXA and fasting serum homocysteine level were measured by Enzyme Immunoassay Kit. The mean of serum level of homocysteine were 11.67 +/- 4.38 and 11.97 +/- 3.09 imol/l in control and case groups respectively. The difference between two groups was not significant [P=0.761]. Serum homocysteine level and BMC of various areas in case and control groups had no significant correlation [lumbar spine in control group [r= 0.025, p=0.9], lumbar spine in case group [r=0.071, p=0.716], femoral neck in control group [r=0.276, p=0.147], femoral neck in case group [r=0.001, p=0.998fl. Despite numerous studies about direct effect of homocysteine on increase of osteoporotic fracture risk, our study did not show a correlation between serum Level of homocysteine and BMD. Due to multiplicity of factors affecting bone density, final conclusions need extensive investigations with attention to other confounding factors

Correlation trends for bone mineral density in Mexican women: evidence of familiar predisposition: [review] / Tendencias de correlación para la densidad mineral ósea en mujeres mexicanas: pruebas de predisposición familiar: [revisión]

OBJECTIVE: Genetic factors determine bone mineral density (BMD) and peak bone density between 20 and 30 years of age, as well as bone mineral loss after menopause. BMD is a predictor of fractures due to osteoporosis and the impact of genetic factors on osteoporosis. The variation in BMD for each individual is determined by an underlying genetic structure, common genetic effects, particularly with respect to compact bones as compared to those that are primarily trabecular. This article presents the correlation of BMD by anatomical site among different samples of Mexican grandmothers, mothers and granddaughters of mixed race. MATERIAL AND METHODS: The present analysis was performed of healthy employees and their healthy relatives from three different health and academic institutions: the Instituto Mexicano del Seguro Social and the Instituto Nacional de Salud Pública, both located in Cuernavaca, Morelos, as well as the Universidad Autónoma del Estado de México. We selected family-related female participants in order to obtain pairs of mothers and daughters and, whenever possible, grandmother-mother-daughter groups. We were able to match 591 mother-daughter pairs for analysis. Additionally, we were able to include grandmothers to create grandmother-mother-daughter triads for further analysis. Bone density measurements were performed of the non-dominant proximal femur, the lumbar spine (L1-L4) and the whole body using a dual X-ray absorptiometry (DXA) Lunar DPX NT instrument. RESULTS: This study included 591 granddaughters, 591 mothers and 69 grandmothers; mean ages were 20, 47 and 72 years old, respectively. A close relationship existed with respect to body mass index (BMI) between mothers and grandmothers (27.9 vs. 27.3). The largest proportion of body fat mass was observed in the group of mothers (28.5 percent), but was also high in grandmothers (25.7 percent) and granddaughters (21.1 percent). The percentage of lean body mass was similar...

OBJETIVO: Factores genéticos determinan la densidad mineral ósea (DMO) y el pico máximo de masa ósea entre los 20 y 30 años de edad, así como la pérdida de densidad mineral ósea después de la menopausia. La DMO es un predictor de fracturas debido a osteoporosis y el impacto de factores genéticos sobre esta. La variación en DMO para cada individuo es determinada genéticamente, en particular en lo que concierne a huesos compactos en comparación con aquellos que son principalmente trabeculares. Este artículo presenta la correlación de DMO por sitio anatómico entre abuelas, madres y nietas mexicanas. MATERIAL Y MÉTODOS: El presente análisis fue realizado en empleados sanos y sus familiares sanos de tres diferentes instituciones de salud e instituciones académicas: el Instituto Mexicano del Seguro Social, Instituto Nacional de Salud Pública, ambos localizados en Cuernavaca, Morelos, así como la Universidad Autónoma del Estado de México. Seleccionamos a participantes femeninos relacionados para obtener los pares de madres e hijas y siempre que fuera posible a las abuelas. Nos fue posible recolectar 591 pares de madre-hija para el análisis. Además de incluir a abuelas para crear tríadas abuela-madre-hija para el análisis. Las medidas de densidad ósea fueron realizadas del fémur proximal no dominante, espina lumbar (L1-L4) y DMO total mediante el instrumento DPX DXA Lunar NT. RESULTADOS: Este estudio incluyó a 591 nietas, 591 madres y 69 abuelas; la edad promedio fue 20, 47 y 72 años. Hay una relalción entre el índice de masa corporal (BMI) entre madres y abuelas de 27.9 contra 27.3. La proporción mayor de masa grasa de cuerpo fue observada en el grupo de madres (el 28.5 por ciento), pero también se observó alto en abuelas (el 25.7 por ciento) y nietas (el 21.1 por ciento). El porcentaje de masa magra fue similar entre los tres grupos. La correlación mayor de DMO entre madres y abuelas fue para el DMO subtotal (0.44), y para caderas (0.39)...

Polimorfismos del gen del receptor de vitamina D y riesgo de fractura de cadera en la mujer adulta mayor de la Región del Bío Bío / Vitamin D receptor gene polymorphisms and risk of hip fracture in Chilean elderly women

Background: Osteoporotic hip fractures are devastating events in older women. There is a genetic modulation of bone phenotypic parameters including bone density (BMD) and bone fragility fractures. Vitamin D receptor (VDR) gene polymorphisms explain a small part of the genetic influence on BMD, whereas their effect on fractures remains uncertain. Aim: To examine the contributions of VDR genotypes to the susceptibility to hip fracture in elderly Chilean women. Patients and methods: We recruited 126 women (67 with fractures and 59 without) from Bio-Bio Region, Chile, aged 65 to 94 years. Genotyping for Bsm-l, Apa-1, Taq-1 and Fok-1 VDR polymorphisms was performed using polymerase chain reaction methods. All hip fractures were confirmed by X-ray. Results: The alíele frequencies were 0.49 for B, 0.57 for A, 0.60 for T and 0.65 for F in the Bsm-l, Apa-1, Taq-1 and Fok-1 polymorphisms respectively. The prevalence of these VDR gene polymorphisms in women with fractures were 16 percent BB, 69 percent Bb, 15 percent bb for Bsm-l; 30 percent AA, 46 percent Aa, 14 percent aa for Apa-1; 17 percent TT, 34 Tt, 8 percent tt for Taq-1 and 43 percentFF, 41 percent Ff, 16 percent ff for Fok-1. All VDR genotype frequencies did not differ from Hardy- Weinberg expectations. Alíele or genotype frequencies did not differ between women with or without fractures. These results did not change when analysis was adjusted by age weight, height or gynecologic history. Conclusions: The genotype frequencies of the VDR polymorphisms are in accordance with the frequencies of other Hispanic and Caucasian populations. Our results suggest that VDR polymorphisms are not associated with the risk of hip fracture in older women of this Region of Southern Chile.

Hip fracture risk and different gene polymorphisms in the turkish population

BACKGROUND: We aimed to discuss the risk assessments for both patients with hip fractures due to fall-related, low energy traumas and non-fractured control patients by examining bone mineral density and genetic data, two features associated with femoral strength and hip fracture risk. METHODS: Twenty-one osteoporotic patients with proximal femur fractures and non-fractured, osteoporotic, age- and gender-matched controls were included in the study. Bone mineral density measurements were performed with a Lunar DXA. The COL1A1, ESR, VDR, IL-6, and OPG genes were amplified, and labeling of specific gene sequences was performed in a multiplex polymerase chain reaction using the osteo/check PCR kit from the whole blood of all subjects. RESULTS: The bone mineral density (trochanteric and total bone mineral density values) of the fracture group was significantly decreased relative to the control group. We were not able to conduct statistical tests for the polymorphisms of the COL1A1, ESR, and VDR genes because our results were expressed in terms of frequency. Although they were not significant, we did examine differences in the IL-6 and OPG genes polymorphisms between the two groups. We concluded that increasing the number of cases will allow us to evaluate racial differences in femoral hip fracture risk by genotypes.

Genotypes of vitamin D and estrogen receptors in pre and perimenopausal women from Córdoba, Argentina

El propósito del estudio fue determinar la frecuencia de los genotipos de los receptores de vitamina D y de estrógeno y su relación con la densidad mineral ósea en mujeres sanas pre y perimenopáusicas de la ciudad de Córdoba y alrededores. Los genotipos se determinaron con la técnica de reacción en cadena de la polimerasa y análisis de los polimorfismos de longitud de fragmentos de restricción. Se usaron como restrictasas Bsm I y Fok I para el gen del receptor de vitamina D y Pvu II y Xba I para el gen del receptor de estrógeno. Se reclutaron y agruparon por edad doscientos diez mujeres pre y peri-menopáusicas. Sus niveles séricos de Ca y de hormona paratiroidea fueron similares, pero los de fósforo y b-Cross Laps disminuyeron con la edad. La densidad mineral ósea de cuello femoral disminuyó después de los 30 años. Las frecuencias genotípicas de ambos receptores fueron similares a aquéllas de otras mujeres caucásicas. No hubo asociación entre los genotipos de los receptores y la densidad mineral ósea. Los análisis de interacción entre ambos genes no evidenciaron influencia sobre la densidad mineral ósea, utilizándose edad, talla e índice de masa corporal como covariables. Los estilos de vida y hábitos de fumar y beber alcohol tampoco afectaron la densidad mineral ósea. En conclusión, estos datos no sostienen la hipótesis de que los genotipos de los receptores de vitamina D y de estrógeno influencian la densidad mineral ósea de columna lumbar y cuello femoral en mujeres sanas pre y perimenopáusicas de esta región de Argentina.

The aim of this study was to determine the frequency of vitamin D receptor and estrogen receptor genotypes and their relationship with the lumbar spine or femoral neck bone mineral density in healthy pre and perimenopausal women from Córdoba (Argentina) and adjacent areas. Genotypes were assessed by restriction fragment length polymorphism-polymerase chain reaction technique. Bsm I and Fok I for vitamin D receptor gene and XbaI and PvuII for estrogen receptor gene were used as restrictases. Two hundred and ten healthy pre and perimenopausal women were recruited and analyzed by age. Calcemia and serum parathyroid hormone did not change, but serum P and b-CrossLaps decreased with age. Femoral neck bone mineral density decreased significantly after 30 years old. Vitamin D receptor and estrogen receptor genotype frequencies were similar to those from other Caucasian women. No association between vitamin D receptor and estrogen receptor genotypes with the lumbar spine or femoral neck bone mineral density has been detected. Analysis of interaction between vitamin D receptor and estrogen receptor genes using covariates such as age, height and body mass index did not show any influence of the combination of those genotypes on bone mineral density. Lifestyle, smoking and alcohol intake had no effect on lumbar spine and femoral neck bone mineral density. To conclude, these data do not support the hypothesis that vitamin D receptor and estrogen receptor genotypes influence on lumbar spine and femoral neck bone mineral density in healthy pre and perimenopausal women from this area of Argentina.

Análisis del patrón óseo trabecular de mandíbulas maceradas en radiografías panorámicas digitales / Analysis of the trabecular bone pattern of dry human mandibles in digital panoramic radiographies

Nuestro propósito fue estudiar la sensibilidad de la metodología de esqueletonizacion en las alteraciones del patrón óseo trabecular, en radiografías panorámicas digitales. Con el fin de poder utilizar esta metodología a futuro para el análisis y la observación de los cambios de densidad ósea en la estructura trabecular, en pacientes con osteoporosis y sanos. El material examinado consistió en cinco mandíbulas adultas, maceradas. Los 4 sitios de interés de cada mandíbula fueron escogidos en cuerpo mandibular, debajo de los alvéolos dentarios: Sitio 1. Oral y anterior al foramen mentoniano derecho. Sitio 2. Oral y posterior al foramen mentoniano derecho. Sitio 3. Oral y anterior al foramen mentoniano izquierdo. Sitio 4. Oral y posterior al foramen mentoniano izquierdo. Se realizó la toma de radiografías panorámicas digitales. Posterior a la primera toma radiográfica, se recortaron las áreas delimitadas removiendo las tablas vestibulares, Se fracturó intencionalmente el trabeculado óseo y luego se reubicaron las tablas vestibulares y se realizó una segunda toma radiográfica, con el uso de un soporte confeccionado para el posicionamiento de las mandíbulas, manteniendo las líneas guía fijas,para cada especimen: Plano mediano, Línea canina y Plano de Frankfurt. Los sitios de interés fueron trabajados en software, siguiendo el método empleado por Watanabe (2003), las imágenes resultantes, que muestran los esqueletos de las trabéculas óseas fueron analizadas utilizando las siguientes herramientas: Histograma, Análisis de partículas, Dimensión fractal, Cantidad de Uniones o encuentro triple de trabéculas y Porcentaje de trabéculas por área. En el análisis estadístico según los datos obtenidos de las diferentes regiones, antes y después de la remoción/inserción, no se encontró una diferencia estadísticamente significativa. Las trabéculas vistas en la radiografía panorámica son formadas principalmente por inserciones en las corticales. El método de retirar la tabla óse...

Advances in the research of vitamin D receptor gene / 法医学杂志

The polymorphism of vitamin D receptor (VDR) gene may be associated with bone density, osteoporosis and body height. In this review, the authors summarize the association of the four VDR single nucleotide polymorphisms (SNPs) loci FokI, BsmI, ApaI, TaqI with bone density, osteoporosis and body height reported at home and abroad in recent years. And find that though each country's report may be different, its valuable in the field of genetics, clinical endocrinology and metabolism, especially in the research area of body height in forensic medicine.

Cytokine Production by Whole Blood Cells: Relationship to Interleukin Gene Polymorphism and Bone Mass

The aims of this study were to investigate the relationships between the production of interleukin-1 (IL-1), and IL-6 system by whole blood cells, and bone mineral density (BMD), and polymorphisms in IL-1 system and IL-6 gene in postmenopausal Korean women. The production of IL-1alpha, IL-1beta, IL-1 receptor antagonist (IL-1ra), IL-6, and soluble IL-6 receptor (sIL-6r) by lipopolysaccharide-stimulated whole blood cells was measured by ELISA in 110 subjects. Serum osteocalcin, C-telopeptide of type I collagen, and BMD at lumbar spine and proximal femur were measured. IL-1alphaC(-889)T polymorphism, IL-1beta C(-511)T polymorphism, 86-base pair variable number tandem repeat polymorphism in the IL-1ra gene, and IL-6 C(-634)G polymorphism were analyzed. The production of IL-1beta correlated positively with BMD at femoral neck, whereas the production of other ILs did not correlate with BMD at the skeletal sites examined. No significant differences in the production of ILs were observed among normal, osteopenic and osteoporotic postmenopausal women, and among the different IL system polymorphisms groups studied. No correlation between bone turnover markers and the production of ILs was noted. In conclusion IL-1beta may regulate bone metabolism at femoral neck, and the IL system polymorphism do not affect the production of ILs by whole blood cells.

Análisis de polimorfismos APO-E en mujeres colombianas con osteoporosis y correlación con variables clínicas y sociales de riesgo / Polymorphismsof APO-E in Colombian women with osteoporosis: correlation among clinical and s9ocial risk variables

Varios estudios han demostrado la asociación de los polimorfismos de la apolipoproteína E (APO-E) con la osteoporosis, especialmente, la APO-E 4. Para analizar los polimorfismos APOE e identificar la asociación con variables clínicas y sociales, se realizó un estudio descriptivo de 32 mujeres con osteoporosis, provenientes de diferentes regiones de Colombia, mediante metodologías PCR y RFLP. Se observaron en osteoporosis, osteopenia y osteoporosis combinada con osteopenia frecuencias para el genotipo épsilon3/épsilon3 en el 84,3% (n=27), y en el 15,6% para los genotipos con el alelo épsilon4 (épsilon3/épsilon4=12,5%, n=4; épsilon4/épsilon4=3,1%, n=1); la misma tendencia se observó en la distribución por edad de la menopausia, épsilon3/épsilon3 en el 83,3% (n=25), y genotipos con el alelo épsilon4 en el 16,6% (n=5) (épsilon3/épsilon4=13,3%, n=4; épsilon4/épsilon4=3,3%, n=1). No hubo asociación de APO-E4 con estrato socioeconómico, fracturas, enfermedades o consumo de lácteos. Aunque no hubo efecto del alelo épsilon4 en la densidad mineral ósea (DMO) de la columna lumbar: épsilon4+/-(épsilon3/épsilon4 0,960±0,144 g/cm2); épsilon4+/+ (épsilon4/épsilon4 0,873±0,00 g/cm2); épsilon4-/- (épsilon3/épsilon3 0,858±0,160 g/cm2); p=0,49, ni en cuello femoral: épsilon4+/-(épsilon3/épsilon4 0,841±0,026 g/cm2); épsilon4+/+ (épsilon4/épsilon4 0,842±0,00 g/cm2); épsilon4- /- (épsilon3/épsilon3 0,735±0,013 g/cm2), p=0,14, al explorar las diferencias de medias de DMO en el cuello femoral, se observó una diferencia significativa, t=4,17 p=0,05. Estos datos confirman una frecuencia del alelo épsilon4 similar a lo reportado en poblaciones caucásicas y japonesas; se sugiere realizar estudios a gran escala para esclarecer el impacto de la APO-E sobre la DMO y su relación dosis-efecto.

Several studies have reported an association between apolipoprotein E polymorphisms and osteoporosis, specially the genotype APO-E4. In order to analyze the APO-E polymorphisms and to identify their association with clinical and social variables, a descriptive study was undertaken that included 32 women with osteoporosis, from different regions of Colombia. The polymorphisms were detected by PCR and RFLP methods. In osteopenia and osteoporosis combined with osteopenia were observed the genotype epsilon3/epsilon3 in the 84% (n=27), and 16% (epsilon3/epsilon4=12,5%, n=4; epsilon4/epsilon4=3,1%, n=1) for the genotypes bearing the epsilon4 allele. The same tendency was observed by age of the menopause,epsilon3/epsilon3 in the 83% (n=25), and the genotypes bearing the epsilon4 allele in the 17% (n=5)(epsilon3/epsilon4=13,3%, n=4; epsilon4/epsilon4=3,3%, n=1). No association of APO-E4 was detected with socioeconomic stratum, fracture, illness, surgeries, and milk consumption. No significant differences were observed in the bone mineral density (BMD) of the lumbar column between the genotypes with or without the epsilon4 allele epsilon4+/- (epsilon3/epsilon4 0.96±0.14 g/cm2); epsilon4+/+ (epsilon4/epsilon4 0.87±0.0 g/cm2); epsilon4-/- (epsilon3/epsilon3 0.86±0.16 g/cm2); p=0.49, and femoral bone mineral density epsilon4+/- (epsilon3/epsilon4 0.84±0.03 g/cm2); epsilon4+/+ (epsilon4/epsilon4 0.84±0.0 g/cm2); epsilon4-/- (epsilon3/epsilon3 0.74±0.01 g/cm2); p=0.014. However, when exploring the differences of BMD in the femoral neck, a significant difference was observed (t=4.17, p=0.05). These results confirm epsilon4 allele frequencies similar to those reported for caucasian and Japanese, subjects. Larger studies are necessary to elucidate the effect of APO-E in bone marrow and the dose-effect relation.

Estudo do marcador genético de osteoporose COLI AI, atraves de diferentes enzimas de restrição, em mulheres climatericas brasileiras / Osteoporosis genetic markers study (COLI AI) with diferent restrictions enzimes, in Brazilian climateric women

Os objetivos do trabalho foram estudar o polimorfismo do gene do colageno tipo alfa 1 (COLI AI) como marcador genetico, comparado a densidade mineral...