Identification of core pathogenic genes and pathways in elderly osteoporosis based on bioinformatics analysis / 中华预防医学杂志

Objective: Using bioinformatics methods to analyze the core pathogenic genes and related pathways in elderly osteoporosis. Methods: From November 2020 and August 2021, eight elderly osteoporosis patients who received treatment and five healthy participants who underwent physical examinations in Beijing Jishuitan Hospital were selected as subjects. The expression level of RNA in the peripheral blood of eight elderly osteoporosis patients and five healthy participants was collected for high-throughput transcriptome sequencing and analysis. The gene ontology (GO) analysis Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis was performed for the differentially expressed genes (DEGs). The protein-protein interaction (PPI) network was constructed using the STRING website and Cytoscape software, and the most significant modules and hub genes were screened out. Results: Among the eight elderly osteoporosis patients, there were seven females and one male, with an average age of 72.4 years (SD=4.2). Among the five healthy participants, there were four females and one male, with an average age of 68.2 years (SD=5.7). A total of 1 635 DEGs (847 up-regulated and 788 down-regulated) were identified. GO analysis revealed that the molecular functions of DEGs were mainly enriched in structural constituents of the ribosome, protein dimerization activity, and cellular components were mainly enriched in the nucleosome, DNA packaging complex, cytosolic part, protein-DNA complex and the cytosolic ribosome. KEGG pathway analysis showed that DEGs were mainly enriched in systemic lupus erythematosus and ribosome. Gene UBA52, UBB, RPS27A, RPS15, RPS12, RPL13A, RPL23A, RPL10A, RPS25 and RPS6 were selected and seven of them could encode ribosome proteins. Conclusion: The pathogenesis of elderly osteoporosis may be associated with ribosome-related genes and pathways.

miR-877-3p causes osteoporosis in mice by inhibiting MCP-1 secretion from mouse bone marrow mesenchymal stem cells and the migration and apoptosis of T lymphocytes / 细胞与分子免疫学杂志

Objective To investigate the effects of miR-877-3p on migration and apoptotic T lymphocytes of bone mesenchymal stem cells (BMSCs). Methods The model of osteoporosis induced by bilateral ovariectomy (OVX) and sham operation was established. At 8 weeks after operation, the bone parameters of the two groups were detected by micro-CT. The levels of monocyte chemotactic protein 1(MCP-1) in BMSCs were detected by ELISA. BMSC in OVX group and sham group were co-cultured with T lymphocytes, respectively. The migration ability of T lymphocytes in the two groups was observed by TranswellTM assay with PKH26 staining and apoptosis of T lymphocytes were detected by flow cytometry. Reverse transcription PCR was used to detect the expression of miR-877-3p in BMSCs. miR-877-3p was overexpressed or down-regulated by cell transfection. The level of MCP-1 secreted by BMSCs in each group was detected by ELISA. The migration and apoptosis of T lymphocytes were detected by the above methods. Results The number of trabecular bone and bone mineral density in OVX group were lower than those in sham group. The levels of MCP-1 secretion, chemotactic and apoptotic T lymphocyte ability of BMSCs in OVX group were also lower than those in sham group. The expression level of miR-877-3p in BMSC in OVX group was higher than that in sham group. After overexpression of BMSC miR-877-3p, the levels of MCP-1 secreted from BMSCs, and apoptotic T lymphocytes decreased, while the results were opposite after down-regulation of miR-877-3p. Conclusion miR-877-3p may be one of the causes of osteoporosis by inhibiting MCP-1 secretion of BMSCs and the migration and apoptosis of T lymphocytes.

Advances on pentraxin 3 in osteoporosis and fracture healing / 中国骨伤

Pentaxin 3 (PTX3), as a multifunctional glycoprotein, plays an important role in regulating inflammatory response, promoting tissue repair, inducing ectopic calcification and maintaining bone homeostasis. The effect of PTX3 on bone mineral density (BMD) may be affected by many factors. In PTX3 knockout mice and osteoporosis (OP) patients, the deletion of PTX3 will lead to decrease of BMD. In Korean community "Dong-gu study", it was found that plasma PTX3 was negatively correlated with BMD of femoral neck in male elderly patients. In terms of bone related cells, PTX3 plays an important role in maintaining the phenotype and function of osteoblasts (OB) in OP state;for osteoclast (OC), PTX3 in inflammatory state could stimulate nuclear factor κ receptor activator of nuclear factor-κB ligand (RANKL) production and its combination with TNF-stimulated gene 6(TSG-6) could improve activity of osteoclasts and promote bone resorption;for mesenchymal stem cells (MSCs), PTX3 could promote osteogenic differentiation of MSCs through PI3K/Akt signaling pathway. In recent years, the role of PTX3 as a new bone metabolism regulator in OP and fracture healing has been gradually concerned by scholars. In OP patients, PTX3 regulates bone mass mainly by promoting bone regeneration. In the process of fracture healing, PTX3 promotes fracture healing by coordinating bone regeneration and bone resorption to maintain bone homeostasis. In view of the above biological characteristics, PTX3 is expected to become a new target for the diagnosis and treatment of OP and other age-related bone diseases and fracture healing.

Pathogenesis of glucocorticoid-induced osteoporosis based on label-free mass proteomics / 中国骨伤

OBJECTIVE@#To explore pathogenesis of glucocortocoid-induced osteoporosis(GIOP) based on label-free mass proteomics.@*METHODS@#Twevle female Sprague-Dawley(SD) rats were randomly divided into two groups, named as sham group and GIOP group. After one-week adaptive feeding, the rats of GIOP group were administered with dexamethasone via intramuscular injection according to 2.5 mg/kg weighting, while the rats of sham group were administered with the same amount of saline, twice a week. The tibias of each group were collected after 8-week modeling and made pathological sections to confirm the success of modeling. Three samples of each group were picked up to perform label-free mass proteomics. After quality control, differentially expressed proteins were identified according to qualitative and quantitative analyses. Then gene ontology(GO) and Kyoto encyclopedia of genes and genomes (KEGG) enrichment analysis, cluster analysis as well as protein-protein interaction analysis were performed using bioinformatics analysis.@*RESULTS@#Compared with sham group, the structure of bone trabecular in GIOP group showed abnormal arrangement, uneven distribution and obvious fragmentation, which could demonstrate successful modeling. A total of 47 differentially expressed proteins (DEPs) were identified including 20 up-regulated and 27 down-regulated proteins. The expression of protein nucleophosmin 1(NPM1), adipocyte plasma membrane associated protein (APMAP), cytochromec oxidase subunit 6A1 (COX6A1) and tartrate-resistant acid phosphatase (ACP5) showed a significant difference between two groups. KEGG results showed DEPs were enriched on metabolism-related pathways, immune-related pathways and AMP-activated kinase (AMPK) signaling pathway.@*CONCLUSION@#Protein NPM1, APMAP, COX6A1 and ACP5 showed a close relationship with pathogenesis of GIOP, which could serve as potential biomarkers of GIOP. AMPK signaling pathway played an important role in the occurrence and development of GIOP, which could be regarded as potential signaling pathway to treatment GIOP.

Co-regulation of circadian clock genes and microRNAs in bone metabolism / 浙江大学学报（英文版）（B辑：生物医学和生物技术）

Mammalian bone is constantly metabolized from the embryonic stage, and the maintenance of bone health depends on the dynamic balance between bone resorption and bone formation, mediated by osteoclasts and osteoblasts. It is widely recognized that circadian clock genes can regulate bone metabolism. In recent years, the regulation of bone metabolism by non-coding RNAs has become a hotspot of research. MicroRNAs can participate in bone catabolism and anabolism by targeting key factors related to bone metabolism, including circadian clock genes. However, research in this field has been conducted only in recent years and the mechanisms involved are not yet well established. Recent studies have focused on how to target circadian clock genes to treat some diseases, such as autoimmune diseases, but few have focused on the co-regulation of circadian clock genes and microRNAs in bone metabolic diseases. Therefore, in this paper we review the progress of research on the co-regulation of bone metabolism by circadian clock genes and microRNAs, aiming to provide new ideas for the prevention and treatment of bone metabolic diseases such as osteoporosis.

Role of ATP6V1H gene in bone metabolism / 中国骨伤

Osteoporosis is one of the common clinical orthopedic diseases, which can lead to a variety of complications. There are many pathogenic factors in this disease. The latest research found that ATP6V1H is a new gene leading to the occurrence of osteoporosis, and it is likely to become a new target for the future drug treatment of osteoporosis.This paper introduces the biological structure and characteristics of H subunit, summed up the human body caused by loss of ATP6V1H and animal models such as zebrafish, mice bone loss and osteoporosis symptom such as related research reports of the loss, from osteoclast, osteoblast and marrow stromal cell level and the connection between the various subunits further expounds the H subunit regulate bone dynamic balance of mechanism, to explore ATP6V1H in bone developmentand bone related diseases has laid a solid foundation, also provide new ideas for clinical treatment of osteoporosis.

Osteoporosis affects functional activity and gene expression of osteoblastic cells derived from rat alveolar bone

Abstract Recent studies suggest that osteoporosis, in addition to the damage caused in long bones, may cause deterioration in the jaws, especially in alveolar bone sites, with effects in the progress of periodontal disease as well as in bone healing. The aim of this study was to evaluate the effect of osteoporosis in the metabolism of rat alveolar bone osteoblasts. There were used 10 female rats divided in two experimental groups (Sham and OVX), which were ovariectomized and after 8 weeks euthanized to collect mandibular bone samples in order to isolate osteoblastic cells. The cells were cultured in 24-well plates to perform the in vitro experiments. After 7, 10 and 14 days, there were evaluated cell proliferation by MTT assay, in situ detection of alkaline phosphatase (ALP) as well as mineralized nodules and expression of genes associated to bone remodeling. Results showed that at 7, 10 and 14 days cell proliferation was lower for OVX group. In situ detection of ALP was higher at 7 days and lower at 10 and 14 days in OVX group. At 17 and 21 days, OVX group had a significative decrease of mineralization nodules. There was a downregulation in the expression of Alp, Bglap and Runx2 genes and an upregulation of Opg in OVX group, whereas Opn and Rankl modulation was similar between the evaluated groups. Our results suggest that osteoporosis has a deleterious effect on alveolar bone cells from ovariectomized rats, which might affect the treatment of diseases associated to the jaw bones.

Resumo Estudos recentes sugerem que a osteoporose, além dos danos provocados em ossos longos, pode causar deterioração dos ossos maxilares, especialmente na região do osso alveolar, com efeitos na progressão da doença periodontal assim como no reparo ósseo. O objetivo deste estudo foi avaliar o efeito da osteoporose no metabolismo de osteoblastos do osso alveolar mandibular de ratos. Foram utilizadas 10 ratas fêmeas divididas em dois grupos experimentais (Sham e OVX), que foram ovariectomizadas e após 8 semanas, eutanasiadas para coletar amostras do osso mandibular e isolar as células osteoblásticas. As células foram cultivadas em placas de cultura de 24 poços para serem realizados os experimentos in vitro. Após 7, 10 e 14 dias foram avaliados a proliferação celular pelo ensaio de MTT, detecção in situ de fosfatase alcalina (ALP) assim como de nódulos mineralizados e expressão quantitativa de genes associados à remodelação óssea. Os resultados mostraram que aos 7, 10 e 14 dias a proliferação celular foi menor para o grupo OVX. A detecção in situ de ALP foi maior aos 7 dias e menor aos 10 e 14 dias no grupo OVX. Aos 17 e 21 dias o grupo OVX apresentou uma diminuição dos nódulos mineralizados. Houve uma repressão na expressão dos genes Alp, Bglap e Runx2 e uma indução do gene Opg no grupo OVX, enquanto que a modulação dos genes Opn e Rankl foi similar entre os grupos experimentais. Nossos resultados sugerem que a osteoporose tem um efeito deletério no metabolismo de células do osso alveolar em ratas ovariectomizadas, o que pode afetar o tratamento de doenças associadas aos ossos maxilares

The roles of miRNA, lncRNA and circRNA in the development of osteoporosis

Osteoporosis is a common metabolic bone disease, influenced by genetic and environmental factors, that increases bone fragility and fracture risk and, therefore, has a serious adverse effect on the quality of life of patients. However, epigenetic mechanisms involved in the development of osteoporosis remain unclear. There is accumulating evidence that epigenetic modifications may represent mechanisms underlying the links of genetic and environmental factors with increased risk of osteoporosis and bone fracture. Some RNAs, such as microRNAs (miRNAs), long noncoding RNAs (lncRNAs), and circular RNAs (circRNAs), have been shown to be epigenetic regulators with significant involvement in the control of gene expression, affecting multiple biological processes, including bone metabolism. This review summarizes the results of recent studies on the mechanisms of miRNA-, lncRNA-, and circRNA-mediated osteoporosis associated with osteoblasts and osteoclasts. Deeper insights into the roles of these three classes of RNA in osteoporosis could provide unique opportunities for developing novel diagnostic and therapeutic approaches to this disease.

Osteopetrosis infantil maligna / Malignant Infantile osteopetrosis

INTRODUCCIÓN: Osteopetrosis Infantil Maligna (OIM) es un grave e inusual desorden genético debi do a una actividad osteoclástica anormal. OBJETIVO: Reportar lactante en quien se documentó una Osteopetrosis Infantil Maligna, revisando aspectos diagnósticos y terapéuticos más relevantes. CASO CLÍNICO: Reportamos un lactante de 10 meses de sexo masculino en quien se confirmó OIM tras presentar plaquetopenia y visceromegalias. En su historial destacó ser primer hijo de padres no consanguíneos, y entre sus hallazgos presentó hepatoesplenomegalia, plaquetopenia y anemia graves, compromiso sensorial visual y auditivo e infecciones a repetición. El diagnóstico fue confirmado mediante estudio genético, el cual identificó 2 mutaciones heterocigotas en el gen TCIRG1. Se rea lizó trasplante de precursores hematopoyéticos, sin haber presentado recuperación hematológica, falleciendo por enfermedad veno oclusiva. DISCUSIÓN: La OIM es una enfermedad inusual, grave y de inicio temprano, siendo necesario un elevado índice de sospecha ante hepatoesplenomegalia y falla medular. El diagnóstico temprano y el trasplante de precursores hematopoyéticos son las únicas intervenciones potencialmente curativas de esta entidad letal.

INTRODUCCIÓN: Malignant Infantile Osteopetrosis (MIOP) is a rare and severe genetic disorder due to abnormal osteoclast activity. OBJECTIVE: To report an infant who presented Malignant Infantile Osteopetrosis, reviewing the most relevant diagnostic and therapeutic aspects. CLINICAL CASE: A ten- month-old male infant with diagnosis of MIOP confirmed after presenting thrombocytopenia and visceromegaly. He was the first child of non-consanguineous parents, and among the findings, he presented severe hepatosplenomegaly, thrombocytopenia, and anemia; visual and hearing impairment, and repeated infections. The diagnosis was confirmed by genetic study, which identified two heterozygous mutations in the TCIRG1 gene. Hematopoietic stem cells were transplanted without hematological recovery. The patient died due to occlusive venous disease. DISCUSSION: MIOP is a rare, severe, and early-onset disease, with a high rate of suspicion necessary in the presence of hepatosplenomegaly and bone marrow failure. Early diagnosis and hematopoietic stem cells transplanta tion are the only potentially therapeutic interventions of this lethal entity.

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.

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.

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.

Osteoporose: visão do ortopedista / Osteoporosis: an orthopaedic standpoint

A osteoporose é o resultado da redução da massa mineral do osso e da deterioração da microarquitetura orgânica, com conseqüente enfraquecimento e predisposição a fraturas. A incidência de fraturas por osteoporose cresce pari passu com a longevidade populacional, que está em ascensão. O objetivo do tratamento da osteoporose é o de quebrar essa sincronia, reduzindo a incidência de fraturas. As fraturas do colo do fêmur constituem o problema maior, pois, em cada cinco vitimas, uma não sobrevive além de um ano; e somente metade das pacientes consegue recuperar seu nível de atividade pré-fratura. A profilaxia da osteoporose deve ser iniciada na puberdade, época da formação da massa óssea. A prática de esportes vigorosos, com alimentação sadia, rica em proteína e cálcio, deve ser incrementada. Um esqueleto bem formado no período de crescimento será mais resistente na velhice. A perda da massa óssea afeta, em maior ou menor grau, todos os indivíduos, independentemente do sexo ou etnia. Indivíduosincluídos nos grupos de risco devem ser advertidos pelos seus médicos quanto à maior vulnerabilidade às fraturas. A ocorrência de fratura do terço proximal do fêmur, epífise distal do rádio, colo do úmero, maleolares ou achatamento do corpo vertebral por traumatismo de baixa energia impõe a avaliação da densidade óssea. Nesse grupo aprofilaxia deve ser feita precocemente, com exercícios de média ou alta intensidade e complemento de cálcio e vitamina D. O tratamento medicamentoso estará indicado para homens e mulheres baseado no T-score

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.

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.

Análisis del polimorfismo Bsm I del gen receptor de la vitamina D (VDR) en pacientes venezolanas residentes del estado Zulia con osteoporosis

Resumen. Dentro de los genes implicados en el estudio de la genética de la osteoporosis, el más conocido es el gen receptor de la vitamina D (VDR), estudiado a través de la caracterización del polimorfismo Bsm I. En tal sentido, esta investigación tuvo como objetivo principal analizar el polimorfismo Bsm I del gen de VDR en una muestra de 133 mujeres posmenopáusicas distribuidas en tres grupos: 54 afectadas con osteoporosis, 24 con osteopenia y 55 controles normales para la enfermedad. De las mujeres con osteoporosis 28 presentaron el genotipo BB, asociado en otros países con disminución de la densidad mineral ósea, 20 presentaron el genotipo Bb y 6 el genotipo bb. Del grupo control sólo 11 mujeres presentaron el genotipo BB, 36 mostraron el genotipo heterocigoto Bb y 8 el genotipo bb. La frecuencia de los alelos B y b en la población general analizada resultó de 0,6 y 0,4, respectivamente. El genotipo BB se encontró en un 52% del grupo con osteoporosis y en un 20% en el grupo control normal, siendo estos hallazgos significativos estadísticamente, lo cual sugiere una asociación entre el genotipo BB y la osteoporosis.

Abstract. Among genes implied on the osteoporosis genetics, the most studied gene worldwide is the receptor gene of D vitamin (VDR), through the characterization of Bsm I polymorphism. The main objective of this research was to analyze the Bsm I polymorphism of the VDR gene in a sample of 133 postmenopausal women distributed in three groups: 54 with osteoporosis, 24 with osteopenia and 55 normal controls for the disease. 28 of the women with osteoporosis presented the BB genotype, which is related in others countries to bone mineral density decrease, 20 had the Bb genotype, and 6 the bb genotype. Of the control group only 11 women presented the BB genotype, 36 showed the heterozygote genotype and 8 the bb genotype. The frequencies of the B and b alleles in the analyzed population were 0.6 and 0.4 respectively. The BB genotype was found in 52% of the group with osteoporosis, and in 20% of the control group, these findings are statistically significant, which suggest an association between the BB genotype and osteoporosis.

Relationship between glucocorticoid-induced osteoporosis and vitamin D receptor genotypes / 华中科技大学学报（医学）（英德文版）

By means of polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) assay, the association between vitamin D receptor (VDR) genotypes and bone mineral density (BMD) in the patients receiving long-term glucocorticoid therapy was studied. The clinical data and blood of 71 patients with rheumatosis who received long-term glucocorticoid therapy were collected. BMD was measured by dual-energy X-ray absorptimometry. VDR gene fragment (about 185 bp) was amplified by PCR from the extracted genomic DNA, then digested with restriction endonuclease Bsm I. The genotypes were evaluated based on the fragment length following endonuclease digestion and the association between genotypes and BMD or Z-score values was analyzed. Among the 71 cases, the detected genotypes were Bb and bb with the distribution frequency being 11.3% and 88.7% respectively. The distribution frequency of the alleles was in agreement with the Hardy-Weinberg equilibrium. There was no significant difference between the two genotypes in age, gender, body mass index (BMI), disease duration, disease types, time of glucocorticoid administration and cumulative dosage (P > 0.05). Osteoporosis rate of the patients with Bb or bb genotype was 37.5% and 33.3% respectively, with the difference being not significant (chi 2 = 0.05, P = 0.8). The BMD and Z-score values at lumbar spine and femur in two genotypes were not similar, but the difference had no significant (P > 0.05). The distribution frequency of bb type of VDR genotypes in Han populations of China was more prevalent, followed by Bb and bb types in turn. In the patients receiving long-term glucocorticoid therapy, there was no significant difference in BMD between Bb and bb genotypes. The data suggest that the VDR genotypes may not be means of identifying patients at greater risk of glucocorticoid-induced osteoporosis, which await to be further confirmed by a large sample size.

Osteoporosis en todas las hijas jovenes de una madre con multiples fracturas osteoporóticas: un caso de osteoporosis familiar / Osteoporosis in all young daughters of a mother with multiple osteoporotic fractures: a case of familiar osteoporosis

Se describe una familia, en la cual todos sus miembros mujeres, madre postmenopáusica (caso índice) y sus tres hijas premenopáusicas presentan osteoporosis. La madre (60 años) presentó fracturas axiales y periféricas, con una densidad mineral ósea (DMO) muy baja para su edad. Su abuela había sufrido una fractura de cadera. La hija mayor (30 años) sufrió múltiples fracturas vertebrales durante el embarazo y lactancia asociadas a una DMO muy baja. En consecuencia se estudiaron las dos hijas menores (29 y 27 años). En ellas se observó que la DMO estaba severamente disminuida (valores densitométricos de osteoporosis según la definición de la OMS) pero sin antecedentes de fracturas óseas. Es probable que la alta heredabilidad de la masa ósea sea la causa de la severa disminución de la DMO observada en todas las mujeres de esta familia, y responsable de fracturas óseas en dos de ellas. No hemos encontrado en la literatura descripciones de una familia similar, que muestre la importancia del estudio de la masa ósea de los descendientes de un individuo con osteoporosis severa, permitiendo la detección de familiares con baja masa ósea y alto riesgo de desarrollo de fracturas óseas

Fractures of the proximal femur: correlation with vitamin D receptor gene polymorphism

Fractures are the feared consequences of osteoporosis and fractures of the proximal femur (FPF) are those that involve the highest morbidity and mortality. Thus far, evaluation of bone mineral density (BMD) is the best way to determine the risk of fracture. Genetic inheritance, in turn, is one of the major determinants of BMD. A correlation between different genotypes of the vitamin D receptor (VDR) and BMD has been recently reported. On this basis, we decided to determine the importance of the determination of VDR genotype in the presence of an osteoporotic FPF in a Brazilian population. We studied three groups: group I consisted of 73 elderly subjects older than 65 years (78.5 + 7.2 years) hospitalized for nonpathological FPF; group II consisted of 50 individuals older than 65 years (72.9 + 5.2 years) without FPF and group III consisted of 98 young normal Brazilian individuals aged 32.6 + 6.6 years (mean+SD). Analysis of VDR gene polymorphism by restriction fragment lenght polymorphism (RFLP) was performed by PCR amplification followed by BsmI digestion of DNA isolated from peripheral leukocytes. The genotype distribution in group I was 20.5 percent BB, 42.5 percent and 37 percent bb did not differ significantly from the values obtained for group II (16 percent BB, 36 percent Bb and 48 percent bb) or for group III (10.2 percent BB, 47.6 percent Bb and 41.8 percent bb). No differences in genotype distribution were observed between sexes or between the young and elderly groups. We conclude that determination of VDR polymorphism is of no practical use for the prediction of FPF. Other nongenetic factors probably start to affect bone mass, the risk to fall and consequently the occurence of osteoporotic fractures with advancing age.