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2. Patients’ preferences for fracture risk communication: the Risk Communication in Osteoporosis (RICO) study

Author

Beaudart, Charlotte, Sharma, Mitali, Clark, Patricia, Fujiwara, Saeko, Adachi, Jonathan D., Messina, Osvaldo D., Morin, Suzanne N., Kohlmeier, Lynn A., Sangan, Caroline B., Nogues, Xavier, Cruz-Priego, Griselda Adriana, Cavallo, Andrea, Cooper, Fiona, Grier, Jamie, Leckie, Carolyn, Montiel-Ojeda, Diana, Papaioannou, Alexandra, Raskin, Nele, Yurquina, Leonardo, Wall, Michelle, Bruyère, Olivier, Boonen, Annelies, Dennison, Elaine, Harvey, Nicholas C., Kanis, John A., Kaux, Jean-François, Lewiecki, E. Michael, Lopez-Borbon, Oscar, Paskins, Zoé, Reginster, Jean-Yves, Silverman, Stuart, and Hiligsmann, Mickaël

Published
2024
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10. Spanish National Registry of Major Osteoporotic Fractures (REFRA) seen at Fracture Liaison Services (FLS): objectives and quality standards

Author

Montoya-Garcia, Maria Jose, Carbonell-Abella, Cristina, Cancio-Trujillo, Jose Manuel, Moro-Álvarez, Maria Jesus, Mora-Fernández, Jesus, Izquierdo-Avino, Rafael, Nogues, Xavier, Mesa-Ramos, Manuel, San Segundo-Mozo, Rosa Maria, Calero-Muñoz, Elena, Naves-Diaz, Manuel, Olmo-Montes, F. Jesus, and Duaso, Enric

Published
2022
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12. Genetic characteristics involved in COVID‐19 severity. The CARGENCORS case‐control study and meta‐analysis

Author

Camps‐Vilaró, Anna, primary, Pinsach‐Abuin, Mel·lina, additional, Degano, Irene R., additional, Ramos, Rafel, additional, Martí‐Lluch, Ruth, additional, Elosua, Roberto, additional, Subirana, Isaac, additional, Solà‐Richarte, Clàudia, additional, Puigmulé, Marta, additional, Pérez, Alexandra, additional, Vilaró, Ingrid, additional, Cruz, Raquel, additional, Diz‐de Almeida, Silvia, additional, Nogues, Xavier, additional, Masclans, Joan R., additional, Güerri‐Fernández, Roberto, additional, Marin, Judith, additional, Tizon‐Marcos, Helena, additional, Vaquerizo, Beatriz, additional, Brugada, Ramon, additional, and Marrugat, Jaume, additional

Published
2024
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13. Patients’ preferences for fracture risk communication: the Risk Communication in Osteoporosis (RICO) study

Author

Beaudart, Charlotte, primary, Sharma, Mitali, additional, Clark, Patricia, additional, Fujiwara, Saeko, additional, Adachi, Jonathan D., additional, Messina, Osvaldo D., additional, Morin, Suzanne N., additional, Kohlmeier, Lynn A., additional, Sangan, Caroline B., additional, Nogues, Xavier, additional, Cruz-Priego, Griselda Adriana, additional, Cavallo, Andrea, additional, Cooper, Fiona, additional, Grier, Jamie, additional, Leckie, Carolyn, additional, Montiel-Ojeda, Diana, additional, Papaioannou, Alexandra, additional, Raskin, Nele, additional, Yurquina, Leonardo, additional, Wall, Michelle, additional, Bruyère, Olivier, additional, Boonen, Annelies, additional, Dennison, Elaine, additional, Harvey, Nicholas C., additional, Kanis, John A., additional, Kaux, Jean-François, additional, Lewiecki, E. Michael, additional, Lopez-Borbon, Oscar, additional, Paskins, Zoé, additional, Reginster, Jean-Yves, additional, Silverman, Stuart, additional, and Hiligsmann, Mickaël, additional

Published
2023
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14. Whole‐genome sequencing identifies EN1 as a determinant of bone density and fracture

Author

Zheng, Hou‐Feng, Forgetta, Vincenzo, Hsu, Yi‐Hsiang, Estrada, Karol, Rosello‐Diez, Alberto, Leo, Paul J, Dahia, Chitra L, Park‐Min, Kyung Hyun, Tobias, Jonathan H, Kooperberg, Charles, Kleinman, Aaron, Styrkarsdottir, Unnur, Liu, Ching‐Ti, Uggla, Charlotta, Evans, Daniel S, Nielson, Carrie M, Walter, Klaudia, Pettersson‐Kymmer, Ulrika, McCarthy, Shane, Eriksson, Joel, Kwan, Tony, Jhamai, Mila, Trajanoska, Katerina, Memari, Yasin, Min, Josine, Huang, Jie, Danecek, Petr, Wilmot, Beth, Li, Rui, Chou, Wen‐Chi, Mokry, Lauren E, Moayyeri, Alireza, Claussnitzer, Melina, Cheng, Chia‐Ho, Cheung, Warren, Medina‐Gómez, Carolina, Ge, Bing, Chen, Shu‐Huang, Choi, Kwangbom, Oei, Ling, Fraser, James, Kraaij, Robert, Hibbs, Matthew A, Gregson, Celia L, Paquette, Denis, Hofman, Albert, Wibom, Carl, Tranah, Gregory J, Marshall, Mhairi, Gardiner, Brooke B, Cremin, Katie, Auer, Paul, Hsu, Li, Ring, Sue, Tung, Joyce Y, Thorleifsson, Gudmar, Enneman, Anke W, van Schoor, Natasja M, de Groot, Lisette CPGM, van der Velde, Nathalie, Melin, Beatrice, Kemp, John P, Christiansen, Claus, Sayers, Adrian, Zhou, Yanhua, Calderari, Sophie, van Rooij, Jeroen, Carlson, Chris, Peters, Ulrike, Berlivet, Soizik, Dostie, Josée, Uitterlinden, Andre G, Williams, Stephen R, Farber, Charles, Grinberg, Daniel, LaCroix, Andrea Z, Haessler, Jeff, Chasman, Daniel I, Giulianini, Franco, Rose, Lynda M, Ridker, Paul M, Eisman, John A, Nguyen, Tuan V, Center, Jacqueline R, Nogues, Xavier, Garcia‐Giralt, Natalia, Launer, Lenore L, Gudnason, Vilmunder, Mellström, Dan, Vandenput, Liesbeth, Amin, Najaf, van Duijn, Cornelia M, Karlsson, Magnus K, Ljunggren, Östen, Svensson, Olle, Hallmans, Göran, Rousseau, François, Giroux, Sylvie, Bussière, Johanne, and Arp, Pascal P

Subjects
Biological Sciences, Biomedical and Clinical Sciences, Clinical Sciences, Genetics, Human Genome, Biotechnology, Osteoporosis, Stem Cell Research, 2.1 Biological and endogenous factors, 1.1 Normal biological development and functioning, Aetiology, Underpinning research, Musculoskeletal, Injuries and accidents, Animals, Bone Density, Bone and Bones, Disease Models, Animal, Europe, Exome, Female, Fractures, Bone, Gene Frequency, Genetic Predisposition to Disease, Genetic Variation, Genome, Human, Genomics, Genotype, Homeodomain Proteins, Humans, Mice, Sequence Analysis, DNA, White People, Wnt Proteins, AOGC Consortium, UK10K Consortium, General Science & Technology
Abstract

The extent to which low-frequency (minor allele frequency (MAF) between 1-5%) and rare (MAF ≤ 1%) variants contribute to complex traits and disease in the general population is mainly unknown. Bone mineral density (BMD) is highly heritable, a major predictor of osteoporotic fractures, and has been previously associated with common genetic variants, as well as rare, population-specific, coding variants. Here we identify novel non-coding genetic variants with large effects on BMD (ntotal = 53,236) and fracture (ntotal = 508,253) in individuals of European ancestry from the general population. Associations for BMD were derived from whole-genome sequencing (n = 2,882 from UK10K (ref. 10); a population-based genome sequencing consortium), whole-exome sequencing (n = 3,549), deep imputation of genotyped samples using a combined UK10K/1000 Genomes reference panel (n = 26,534), and de novo replication genotyping (n = 20,271). We identified a low-frequency non-coding variant near a novel locus, EN1, with an effect size fourfold larger than the mean of previously reported common variants for lumbar spine BMD (rs11692564(T), MAF = 1.6%, replication effect size = +0.20 s.d., Pmeta = 2 × 10(-14)), which was also associated with a decreased risk of fracture (odds ratio = 0.85; P = 2 × 10(-11); ncases = 98,742 and ncontrols = 409,511). Using an En1(cre/flox) mouse model, we observed that conditional loss of En1 results in low bone mass, probably as a consequence of high bone turnover. We also identified a novel low-frequency non-coding variant with large effects on BMD near WNT16 (rs148771817(T), MAF = 1.2%, replication effect size = +0.41 s.d., Pmeta = 1 × 10(-11)). In general, there was an excess of association signals arising from deleterious coding and conserved non-coding variants. These findings provide evidence that low-frequency non-coding variants have large effects on BMD and fracture, thereby providing rationale for whole-genome sequencing and improved imputation reference panels to study the genetic architecture of complex traits and disease in the general population.

Published
2015

18. Applications of a New Handheld Reference Point Indentation Instrument Measuring Bone Material Strength

Author

Randall, Connor, Bridges, Daniel, Guerri, Roberto, Nogues, Xavier, Puig, Lluis, Torres, Elisa, Mellibovsky, Leonardo, Hoffseth, Kevin, Stalbaum, Tyler, Srikanth, Ananya, Weaver, James C, Rosen, Sasha, Barnard, Heather, Brimer, Davis, Proctor, Alex, Candy, James, Saldana, Christopher, Chandrasekar, Srinivasan, Lescun, Timothy, Nielson, Carrie M, Orwoll, Eric, Herthel, Doug, Kopeikin, Hal, Yang, Henry TY, Farr, Joshua N, McCready, Louise, Khosla, Sundeep, Diez-Perez, Adolfo, and Hansma, Paul K

Subjects
Musculoskeletal, bone, bone fracture, bone mechanical properties, bone material properties, Biomedical Engineering, Clinical Sciences
Abstract

A novel, hand-held Reference Point Indentation (RPI) instrument, measures how well the bone of living patients and large animals resists indentation. The results presented here are reported in terms of Bone Material Strength, which is a normalized measure of how well the bone resists indentation, and is inversely related to the indentation distance into the bone. We present examples of the instrument's use in: (1) laboratory experiments on bone, including experiments through a layer of soft tissue, (2) three human clinical trials, two ongoing in Barcelona and at the Mayo Clinic, and one completed in Portland, OR, and (3) two ongoing horse clinical trials, one at Purdue University and another at Alamo Pintado Stables in California. The instrument is capable of measuring consistent values when testing through soft tissue such as skin and periosteum, and does so handheld, an improvement over previous Reference Point Indentation instruments. Measurements conducted on horses showed reproducible results when testing the horse through tissue or on bare bone. In the human clinical trials, reasonable and consistent values were obtained, suggesting the Osteoprobe® is capable of measuring Bone Material Strength in vivo, but larger studies are needed to determine the efficacy of the instrument's use in medical diagnosis.

Published
2013

20. Factors associated with poor anticoagulation control with vitamin K antagonists among outpatients attended in Internal Medicine and Neurology. The ALADIN study

Author

Pose, Antonio, Díaz, José Antonio, Rodríguez, Manuel, Pena, Marta, Arias, Susana, Larrosa, Davinia, González, Álvaro, Rodríguez, Elisa, González, Montserrat, Fernández, Dolores, Barbagelata, Cristina, Raña, Natividad, Freire, Santiago, Cerqueiro, J. Manuel, Guerrero, Héctor, Ramos, Laura, Álvarez, Leticia, de Lis, José M., Caro, Carmen, Seijo, Manuel, Mederer, Susana, de Zarraga, Miguel Alberto, Ferreiro, José, Terrero, José M., Arias, Mónica, Pérez, Roberto, Sánchez, Joaquín, Maciñeiras, José, Fernández, Julián, Jaén, Fernando, Esteva, David, Zamora, Mónica, Navarrete, Nuria, García, Javier, Mérida, Luis, Corrales, Miguel Ángel, Quirós, Raúl, Cantero, Jesús, Barrero, Francisco Javier, Villegas, Inmaculada, Castro, José, Foronda, Jesús, Carrillo, Dionisio, Vega, Jesús, Trujillo, José Antonio, Montero, Manuel, Jurado, Ana, Sánchez, Carlos, Agüera-Morales, Eduardo, Sánchez, María, Durán, Purificación, Fernández de la Puerta, Rafael, Pérez de la Blanca, María, Martínez, María Paz, Fernández, Óscar, Tamayo, José Antonio, Bustamante, Rafael, Serrano, Pedro Jesús, Arjona, Antonio, Fernández, Javier, Payan, Manuel, Gómez, Ricardo, Peña, Daniel, Cabrerizo, Enrique, Salgado, Fernando, Ivanova Georgieva, Radka, Gil-Núñez, Antonio, Bello, Elena, Díaz, Fernando, Medina, Antonio, Castellano, Ana, Miranda, Yesica, Fabre, Óscar, García Polo, Iluminada, Ibáñez, Patricia, Sainz, Clara, Sierra, Fernando, Aragón, Esther, Díaz, Jaime, Aguilar, Fernando, Ortega, María Ángeles, Egido, José Antonio, Pontes, José Carlos, García, Miguel Ángel, Cabrera, Francisco, Batalla, Blanca, Culla, Alex, Molina, Carlos, Flores, Alan, Seró, Laia, Muchada, Marian, Meler, Pilar, Boned-Riera, Sandra, Cánovas, David, Estela, Jordi, Font, Juli, Purroy, Francisco, Benabdelhak, Ikram, Sanahuja, Jordi, Roquer, Jaume, Rodríguez, Ana, Ois, Ángel, Cuadrado, Elisa, Jiménez, Jordi, Nogués, Xavier, Kuprinski, Jerzy, German, Antoni, Irigoyen, Daniel, Cara, Juan José, Font, Maria Àngels, Huertas, Sonia, Martínez-Domeño, Alejandro, Arroyo, Juan Antonio, Delgado-Mederos, Raquel, Gómez-Choco, Manuel Jesús, Mengual, Juan José, García, Sonia M., Castellanos, M. del Mar, van Eedenburg, Cecile, Cañas, Imma, Espinosa, Jordi, Montull, Santiago, Quesada, Helena, Ustrell, Xavier, Homedes, Christian, Navalpotro, Irene, Casanova, Jordi, Lago, Aida Pilar, Morata, Carmen, Gorriz, David, Moreno, Iván, Tembl, José, Ponz, Alejandro, Fonseca, M. José, Chamarro, Raquel, Gil, Rosario, Oliver, Vicente, Pampliega, Ana, Artero, Arturo, Puchades, Francesc, Landete, Lamberto, Vilar, Carlos, Jiménez, Carmen, Vives, Bárbara, Moragues, M. Dolores, Díaz, Rosa, Tur, Silvia, Escribano, José Bernardo, Lucas, César, Martínez, Francisco, Pons, José Miguel, Romero, Amparo, García, David, Pérez, José, Villaverde, Ramón, Martínez, Salvadora, Rodríguez, Aida, Tejero, Carlos, Pérez, Cristina, Mostacero, Enrique, Fernández, Covadonga, Luna, Alain, Pérez, Tomás, González, Félix, de Arce, Ana, Martínez, Maite, Díez, Noemí, Gállego, Jaime, Zandio, Beatriz, Herrera, María, Aymerich, Nuria, Muñoz, Roberto, Marta, Javier, Artal, Jorge, Errea, José M., Timiraos, Juan José, Moreno, M. Pilar, Freijo, Mar, García, Juan Manuel, Gil, M. Carmen, Revilla, M. Ángeles, Palacio, Enrique, Vázquez, José Luis, Bestué, María, Latorre, Ana, Calvo, Eva, Ballester, Laura, Serrano, Marta, Juega, Jesús M., López, M. Ángeles, Irimia, Pablo, Imaz, Laura, Fuentes, Blanca, Sanz, Borja Enrique, Beltrán, Luis, Ruiz, Gerardo, Martínez, Patricia, Sánchez, Demetrio, Barroso, Emilio, Molina, Igor, Budiño, Marco Antonio, Masjuan, Jaime, de Felipe, Alicia, Matute, Consuelo, Tejada, Javier, Morán, Alberto, Fernández, Esther, Riveira, M. del Carmen, Carnedo, Joaquín, Manquillo, Antonio, González, Raquel, Fernández, José Carlos, Guillan, Marta, Yebra, Miguel, Trejo, José M., Saiz, Jesús, Martínez-Acitores, Juan Carlos, Bravo, Yolanda, Arenillas, Juan Francisco, Calleja, Ana, Cortijo, Elisa, Reyes, Javier, López, Luis, Muñoz, Pedro Luis, Fidalgo, M. Ángeles, Hernández, Jacinto, Gómez, José Carlos, Morán, José Carlos, Gonzalo, Sonia, Marrero, Jorge, Satué, José Ángel, Belinchón, Juan Carlos, Moniche, Francisco, Calderón, Enrique, Escudero, Irene, de la Torre, Javier, Casado, Ignacio, Antón, Joaquín, Portilla, Juan Carlos, Luengo, Juan, Rosal, Joan, Calzado, Elena, Anglada, Juan Carlos, Girón, Juan, Ramírez, José M., Pijierro, Agustín, Roa, Ana, Romero, Jorge, Aguayo, Mariano, Borrachero, Cristina, Sanz, Gema, Gómez, M. José, Rico, Miguel Ángel, Cayon, Antonio, Carmona, Eduardo, Cerro, Román, López, Rafael, Aguirre, Alfonso, Lozano, Francisco, Rivera, José M., Contreras Muruaga, M.M., Reig, G., Vivancos, J., González, A., Cardona, P., Ramírez-Moreno, J.M., Martí-Fábregas, J., and Suárez Fernández, C.

Published
2018
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21. Factores asociados al mal control de la anticoagulación con antivitamina K en pacientes con fibrilación auricular no valvular atendidos en consultas de Medicina Interna y Neurología. Estudio ALADIN

Author

Pose, Antonio, Díaz, José Antonio, Rodríguez, Manuel, Pena, Marta, Arias, Susana, Larrosa, Davinia, González, Álvaro, Rodríguez, Elisa, González, Montserrat, Fernández, Dolores, Barbagelata, Cristina, Raña, Natividad, Freire, Santiago, Cerqueiro, J. Manuel, Guerrero, Héctor, Ramos, Laura, Álvarez, Leticia, de Lis, José M., Caro, Carmen, Seijo, Manuel, Mederer, Susana, de Zarraga, Miguel Alberto, Ferreiro, José, Terrero, José M., Arias, Mónica, Pérez, Roberto, Sánchez, Joaquín, Maciñeiras, José, Fernández, Julián, Jaén, Fernando, Esteva, David, Zamora, Mónica, Navarrete, Nuria, García, Javier, Mérida, Luis, Corrales, Miguel Ángel, Quirós, Raúl, Cantero, Jesús, Barrero, Francisco Javier, Villegas, Inmaculada, Castro, José, Foronda, Jesús, Carrillo, Dionisio, Vega, Jesús, Trujillo, José Antonio, Montero, Manuel, Jurado, Ana, Sánchez, Carlos, Agüera-Morales, Eduardo, Sánchez, María, Durán, Purificación, Fernández de la Puerta, Rafael, Pérez de la Blanca, María, Martínez, María Paz, Fernández, Óscar, Tamayo, José Antonio, Bustamante, Rafael, Serrano, Pedro Jesús, Arjona, Antonio, Fernández, Javier, Payan, Manuel, Gómez, Ricardo, Peña, Daniel, Cabrerizo, Enrique, Salgado, Fernando, Ivanova Georgieva, Radka, Gil-Núñez, Antonio, Bello, Elena, Díaz, Fernando, Medina, Antonio, Castellano, Ana, Miranda, Yesica, Fabre, Óscar, García Polo, Iluminada, Ibáñez, Patricia, Sainz, Clara, Sierra, Fernando, Aragón, Esther, Díaz, Jaime, Aguilar, Fernando, Ortega, María Ángeles, Egido, José Antonio, Pontes, José Carlos, García, Miguel Ángel, Cabrera, Francisco, Batalla, Blanca, Culla, Alex, Molina, Carlos, Flores, Alan, Seró, Laia, Muchada, Marian, Meler, Pilar, Boned-Riera, Sandra, Cánovas, David, Estela, Jordi, Font, Juli, Purroy, Francisco, Benabdelhak, Ikram, Sanahuja, Jordi, Roquer, Jaume, Rodríguez, Ana, Ois, Ángel, Cuadrado, Elisa, Jiménez, Jordi, Nogués, Xavier, Kuprinski, Jerzy, German, Antoni, Irigoyen, Daniel, Cara, Juan José, Font, Maria Àngels, Huertas, Sonia, Martínez-Domeño, Alejandro, Arroyo, Juan Antonio, Delgado-Mederos, Raquel, Gómez-Choco, Manuel Jesús, Mengual, Juan José, García, Sonia M., Castellanos, M. del Mar, van Eedenburg, Cecile, Cañas, Imma, Espinosa, Jordi, Montull, Santiago, Quesada, Helena, Ustrell, Xavier, Homedes, Christian, Navalpotro, Irene, Casanova, Jordi, Lago, Aida Pilar, Morata, Carmen, Gorriz, David, Moreno, Iván, Tembl, José, Ponz, Alejandro, Fonseca, M. José, Chamarro, Raquel, Gil, Rosario, Oliver, Vicente, Pampliega, Ana, Artero, Arturo, Puchades, Francesc, Landete, Lamberto, Vilar, Carlos, Jiménez, Carmen, Vives, Bárbara, Moragues, M. Dolores, Díaz, Rosa, Tur, Silvia, Escribano, José Bernardo, Lucas, César, Martínez, Francisco, Pons, José Miguel, Romero, Amparo, García, David, Pérez, José, Villaverde, Ramón, Martínez, Salvadora, Rodríguez, Aida, Tejero, Carlos, Pérez, Cristina, Mostacero, Enrique, Fernández, Covadonga, Luna, Alain, Pérez, Tomás, González, Félix, de Arce, Ana, Martínez, Maite, Díez, Noemí, Gállego, Jaime, Zandio, Beatriz, Herrera, María, Aymerich, Nuria, Muñoz, Roberto, Marta, Javier, Artal, Jorge, Errea, José M., Timiraos, Juan José, Moreno, M. Pilar, Freijo, Mar, García, Juan Manuel, Gil, M. Carmen, Revilla, M. Ángeles, Palacio, Enrique, Vázquez, José Luis, Bestué, María, Latorre, Ana, Calvo, Eva, Ballester, Laura, Serrano, Marta, Juega, Jesús M., López, M. Ángeles, Irimia, Pablo, Imaz, Laura, Fuentes, Blanca, Sanz, Borja Enrique, Beltrán, Luis, Ruiz, Gerardo, Martínez, Patricia, Sánchez, Demetrio, Barroso, Emilio, Molina, Igor, Budiño, Marco Antonio, Masjuan, Jaime, de Felipe, Alicia, Matute, Consuelo, Tejada, Javier, Morán, Alberto, Fernández, Esther, Riveira, M. del Carmen, Carnedo, Joaquín, Manquillo, Antonio, González, Raquel, Fernández, José Carlos, Guillan, Marta, Yebra, Miguel, Trejo, José M., Saiz, Jesús, Martínez-Acitores, Juan Carlos, Bravo, Yolanda, Arenillas, Juan Francisco, Calleja, Ana, Cortijo, Elisa, Reyes, Javier, López, Luis, Muñoz, Pedro Luis, Fidalgo, M. Ángeles, Hernández, Jacinto, Gómez, José Carlos, Morán, José Carlos, Gonzalo, Sonia, Marrero, Jorge, Satué, José Ángel, Belinchón, Juan Carlos, Moniche, Francisco, Calderón, Enrique, Escudero, Irene, de la Torre, Javier, Casado, Ignacio, Antón, Joaquín, Portilla, Juan Carlos, Luengo, Juan, Rosal, Joan, Calzado, Elena, Anglada, Juan Carlos, Girón, Juan, Ramírez, José M., Pijierro, Agustín, Roa, Ana, Romero, Jorge, Aguayo, Mariano, Borrachero, Cristina, Sanz, Gema, Gómez, M. José, Rico, Miguel Ángel, Cayon, Antonio, Carmona, Eduardo, Cerro, Román, López, Rafael, Aguirre, Alfonso, Lozano, Francisco, Rivera., José M., Contreras Muruaga, M.M., Reig, G., Vivancos, J., González, A., Cardona, P., Ramírez-Moreno, J.M., Martí-Fábregas, J., and Suárez Fernández, C.

Published
2018
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22. Microindentation for in vivo measurement of bone tissue mechanical properties in humans.

Author

Diez-Perez, Adolfo, Güerri, Roberto, Nogues, Xavier, Cáceres, Enric, Peña, Maria Jesus, Mellibovsky, Leonardo, Randall, Connor, Bridges, Daniel, Weaver, James C, Proctor, Alexander, Brimer, Davis, Koester, Kurt J, Ritchie, Robert O, and Hansma, Paul K

Subjects
Bone and Bones, Humans, Osteoporosis, Cadaver, ROC Curve, Orthopedics, Tissue Donors, Female, Fractures, Bone, Biomechanical Phenomena, BONE, FRACTURE, BONE QUALITY, INSTRUMENT, CLINICAL TRIALS, Fractures, Bone, Anatomy & Morphology, Biological Sciences, Engineering, Medical and Health Sciences
Abstract

Bone tissue mechanical properties are deemed a key component of bone strength, but their assessment requires invasive procedures. Here we validate a new instrument, a reference point indentation (RPI) instrument, for measuring these tissue properties in vivo. The RPI instrument performs bone microindentation testing (BMT) by inserting a probe assembly through the skin covering the tibia and, after displacing periosteum, applying 20 indentation cycles at 2 Hz each with a maximum force of 11 N. We assessed 27 women with osteoporosis-related fractures and 8 controls of comparable ages. Measured total indentation distance (46.0 +/- 14 versus 31.7 +/- 3.3 microm, p = .008) and indentation distance increase (18.1 +/- 5.6 versus 12.3 +/- 2.9 microm, p = .008) were significantly greater in fracture patients than in controls. Areas under the receiver operating characteristic (ROC) curve for the two measurements were 93.1% (95% confidence interval [CI] 83.1-100) and 90.3% (95% CI 73.2-100), respectively. Interobserver coefficient of variation ranged from 8.7% to 15.5%, and the procedure was well tolerated. In a separate study of cadaveric human bone samples (n = 5), crack growth toughness and indentation distance increase correlated (r = -0.9036, p = .018), and scanning electron microscope images of cracks induced by indentation and by experimental fractures were similar. We conclude that BMT, by inducing microscopic fractures, directly measures bone mechanical properties at the tissue level. The technique is feasible for use in clinics with good reproducibility. It discriminates precisely between patients with and without fragility fracture and may provide clinicians and researchers with a direct in vivo measurement of bone tissue resistance to fracture.

Published
2010

23. Fracture risk reduction and safety by osteoporosis treatment compared with placebo or active comparator in postmenopausal women: systematic review, network meta-analysis, and meta-regression analysis of randomised clinical trials

Author

Händel, Mina Nicole, primary, Cardoso, Isabel, additional, von Bülow, Cecilie, additional, Rohde, Jeanett Friis, additional, Ussing, Anja, additional, Nielsen, Sabrina Mai, additional, Christensen, Robin, additional, Body, Jean-Jacques, additional, Brandi, Maria Luisa, additional, Diez-Perez, Adolfo, additional, Hadji, Peyman, additional, Javaid, Muhammad Kassim, additional, Lems, Willem Frederik, additional, Nogues, Xavier, additional, Roux, Christian, additional, Minisola, Salvatore, additional, Kurth, Andreas, additional, Thomas, Thierry, additional, Prieto-Alhambra, Daniel, additional, Ferrari, Serge Livio, additional, Langdahl, Bente, additional, and Abrahamsen, Bo, additional

Published
2023
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25. Management of Aromatase Inhibitor-Associated Bone Loss (AIBL) in postmenopausal women with hormone sensitive breast cancer: Joint position statement of the IOF, CABS, ECTS, IEG, ESCEO, IMS, and SIOG

Author

Hadji, Peyman, Aapro, Matti S., Body, Jean-Jacques, Gnant, Michael, Brandi, Maria Luisa, Reginster, Jean Yves, Zillikens, M. Carola, Glüer, Claus-C., de Villiers, Tobie, Baber, Rod, Roodman, G. David, Cooper, Cyrus, Langdahl, Bente, Palacios, Santiago, Kanis, John, Al-Daghri, Nasser, Nogues, Xavier, Eriksen, Erik Fink, Kurth, Andreas, Rizzoli, Rene, and Coleman, Robert E.

Published
2017
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27. Fracture risk reduction and safety by osteoporosis treatment compared with placebo or active comparator in postmenopausal women:systematic review, network meta-analysis, and meta-regression analysis of randomised clinical trials

Author

Händel, Mina Nicole, Cardoso, Isabel, Von Bülow, Cecilie, Rohde, Jeanett Friis, Ussing, Anja, Nielsen, Sabrina Mai, Christensen, Robin, Body, Jean Jacques, Brandi, Maria Luisa, Diez-Perez, Adolfo, Hadji, Peyman, Javaid, Muhammad Kassim, Lems, Willem Frederik, Nogues, Xavier, Roux, Christian, Minisola, Salvatore, Kurth, Andreas, Thomas, Thierry, Prieto-Alhambra, Daniel, Ferrari, Serge Livio, Langdahl, Bente, Abrahamsen, Bo, Händel, Mina Nicole, Cardoso, Isabel, Von Bülow, Cecilie, Rohde, Jeanett Friis, Ussing, Anja, Nielsen, Sabrina Mai, Christensen, Robin, Body, Jean Jacques, Brandi, Maria Luisa, Diez-Perez, Adolfo, Hadji, Peyman, Javaid, Muhammad Kassim, Lems, Willem Frederik, Nogues, Xavier, Roux, Christian, Minisola, Salvatore, Kurth, Andreas, Thomas, Thierry, Prieto-Alhambra, Daniel, Ferrari, Serge Livio, Langdahl, Bente, and Abrahamsen, Bo

Abstract

Objective: To review the comparative effectiveness of osteoporosis treatments, including the bone anabolic agents, abaloparatide and romosozumab, on reducing the risk of fractures in postmenopausal women, and to characterise the effect of antiosteoporosis drug treatments on the risk of fractures according to baseline risk factors. Design: Systematic review, network meta-analysis, and meta-regression analysis of randomised clinical trials. Data sources: Medline, Embase, and Cochrane Library to identify randomised controlled trials published between 1 January 1996 and 24 November 2021 that examined the effect of bisphosphonates, denosumab, selective oestrogen receptor modulators, parathyroid hormone receptor agonists, and romosozumab compared with placebo or active comparator. Eligibility criteria for selecting studies: Randomised controlled trials that included non-Asian postmenopausal women with no restriction on age, when interventions looked at bone quality in a broad perspective. The primary outcome was clinical fractures. Secondary outcomes were vertebral, non-vertebral, hip, and major osteoporotic fractures, all cause mortality, adverse events, and serious cardiovascular adverse events. Results: The results were based on 69 trials (>80 000 patients). For clinical fractures, synthesis of the results showed a protective effect of bisphosphonates, parathyroid hormone receptor agonists, and romosozumab compared with placebo. Compared with parathyroid hormone receptor agonists, bisphosphonates were less effective in reducing clinical fractures (odds ratio 1.49, 95% confidence interval 1.12 to 2.00). Compared with parathyroid hormone receptor agonists and romosozumab, denosumab was less effective in reducing clinical fractures (odds ratio 1.85, 1.18 to 2.92 for denosumab v parathyroid hormone receptor agonists and 1.56, 1.02 to 2.39 for denosumab v romosozumab). An effect of all treatments on vertebral fractures compared with placebo was found. In the active tr

Published
2023

28. Fracture risk reduction and safety by osteoporosis treatment compared with placebo or active comparator in postmenopausal women: systematic review, network meta-analysis, and meta-regression analysis of randomised clinical trials

Author

Händel, Mina Nicole, Cardoso, Isabel, Von Bülow, Cecilie, Rohde, Jeanett Friis, Ussing, Anja, Nielsen, Sabrina Mai, Christensen, Robin, Body, Jean-Jacques, Brandi, Maria Luisa, Diez-Perez, Adolfo Diez A., Hadji, Peyman, Javaid, Muhammad Kassim, Lems, Willem Frederik, Nogues, Xavier, Roux, Christian, Minisola, S., Kurth, Andreas, Thomas, Thierry Y.P.Y., Prieto-Alhambra, Daniel, Ferrari, Serge Livio Ivio S.L., Langdahl, Bente, Abrahamsen, Bo, Händel, Mina Nicole, Cardoso, Isabel, Von Bülow, Cecilie, Rohde, Jeanett Friis, Ussing, Anja, Nielsen, Sabrina Mai, Christensen, Robin, Body, Jean-Jacques, Brandi, Maria Luisa, Diez-Perez, Adolfo Diez A., Hadji, Peyman, Javaid, Muhammad Kassim, Lems, Willem Frederik, Nogues, Xavier, Roux, Christian, Minisola, S., Kurth, Andreas, Thomas, Thierry Y.P.Y., Prieto-Alhambra, Daniel, Ferrari, Serge Livio Ivio S.L., Langdahl, Bente, and Abrahamsen, Bo

Abstract

Objective: To review the comparative effectiveness of osteoporosis treatments, including the bone anabolic agents, abaloparatide and romosozumab, on reducing the risk of fractures in postmenopausal women, and to characterise the effect of antiosteoporosis drug treatments on the risk of fractures according to baseline risk factors. Design: Systematic review, network meta-analysis, and meta-regression analysis of randomised clinical trials. Data sources: Medline, Embase, and Cochrane Library to identify randomised controlled trials published between 1 January 1996 and 24 November 2021 that examined the effect of bisphosphonates, denosumab, selective oestrogen receptor modulators, parathyroid hormone receptor agonists, and romosozumab compared with placebo or active comparator. Eligibility criteria for selecting studies: Randomised controlled trials that included non-Asian postmenopausal women with no restriction on age, when interventions looked at bone quality in a broad perspective. The primary outcome was clinical fractures. Secondary outcomes were vertebral, non-vertebral, hip, and major osteoporotic fractures, all cause mortality, adverse events, and serious cardiovascular adverse events. Results: The results were based on 69 trials (>80 000 patients). For clinical fractures, synthesis of the results showed a protective effect of bisphosphonates, parathyroid hormone receptor agonists, and romosozumab compared with placebo. Compared with parathyroid hormone receptor agonists, bisphosphonates were less effective in reducing clinical fractures (odds ratio 1.49, 95% confidence interval 1.12 to 2.00). Compared with parathyroid hormone receptor agonists and romosozumab, denosumab was less effective in reducing clinical fractures (odds ratio 1.85, 1.18 to 2.92 for denosumab v parathyroid hormone receptor agonists and 1.56, 1.02 to 2.39 for denosumab v romosozumab). An effect of all treatments on vertebral fractures compared with placebo was found. In the active treatmen, SCOPUS: ar.j, info:eu-repo/semantics/published

Published
2023

32. Early biomarkers of Williams-Beuren syndrome: a preclinical study in the CD mouse model

Author

Giannoccaro, Silvia, Ferraguto, Celeste, Petroni, Valeria, Marcelly, Coline, Nogues, Xavier, Campuzano Uceda, María Victoria, and Pietropaolo, Susanna

Subjects
Ratolins (Animals de laboratori), Williams syndrome, Biochemical markers, Behavior disorders, Producció de sons pels animals, Adolescència, Adolescence, Mice (Laboratory animals), Mental illness, Síndrome de Williams, Marcadors bioquímics, Malalties mentals, Trastorns de la conducta, Sound production by animals
Abstract

Williams-Beuren syndrome (WBS) is a neurodevelopmental disorder caused by a chromosomic microdeletion (7q11.23). WBS has been modeled by a mouse line having a complete deletion (CD) of the equivalent mouse locus. This model has been largely used to investigate the etiopathological mechanisms of WBS, although pharmacological therapies have not been identified yet. Surprisingly, CD mice were so far mainly tested in adulthood, despite the developmental nature of WBS and the critical relevance of early timing for potential treatments. Here we provide for the first time a phenotypic characterization of CD mice of both sexes during infancy and adolescence, i.e., between birth and 7 weeks of age. CD pups of both sexes showed reduced body growth, delayed sensory development, and altered patterns of ultrasonic vocalizations and exploratory behaviors. Adolescent CD mice showed reduced locomotion and acoustic startle response, and altered social interaction and communication, the latter being more pronounced in female mice. Juvenile CD mutants of both sexes also displayed reduced brain weight, cortical and hippocampal dendritic length, and spine density. Our findings highlight the critical relevance of early neurobehavioral alterations as biomarkers of WBS pathology, underlying the importance of adolescence for identifying novel therapeutic targets for this neurological disorder.

Published
2023

36. Spanish National Registry of Major Osteoporotic Fractures (REFRA) seen at Fracture Liaison Services (FLS): objectives and quality standards

Author

Universidad de Sevilla. Departamento de Citología e Histología Normal y Patológica, Universidad de Sevilla. Departamento de Medicina, Montoya García, María José, Carbonell Abella, Cristina, Cancio Trujillo, José Manuel, Moro Álvarez, María Jesús, Izquierdo Avino, Rafael, Nogues, Xavier, Giner García, Mercedes, Universidad de Sevilla. Departamento de Citología e Histología Normal y Patológica, Universidad de Sevilla. Departamento de Medicina, Montoya García, María José, Carbonell Abella, Cristina, Cancio Trujillo, José Manuel, Moro Álvarez, María Jesús, Izquierdo Avino, Rafael, Nogues, Xavier, and Giner García, Mercedes

Abstract

Summary REFRA-FLS is a new registry in Spain aimed at identifying individuals over 50 years of age with a fragility fracture. Using this registry, we found hip fracture is the most prevalent fracture. Treatment for osteoporosis was 87.7%, with 65.3% adherence. REFRA-FLS provides fundamental data in the study of fragility fractures. Purpose Fragility fractures are a growing public health concern in modern-aged societies. Fracture Liaison Services (FLS) have been shown to successfully lower rates of secondary fractures. A new registry (REFRA-FLS) has been created to moni tor quality indicators of FLS units in Spain and to explore the occurrence and characteristic of fragility fractures identifed by these centers. Methods We conducted a prospective cohort study based on fragility fractures recorded in the REFRA-FLS registry. Par ticipants were individuals 50 years or above who sufered a low energy fragility fracture identifed by the 10 participating FLS units during the study period. The type of FLS unit, the characteristics of the individuals at baseline, along with patient outcomes as quality indicators among those who completed 1 year of follow-up were analyzed. Results A total of 2965 patients and 3067 fragility fractures were identifed, and the most frequent locations were hip (n=1709, 55.7%) and spine (n=492, 16.0%). A total of 43 refractures (4.5%) and 46 deaths (4.9%) were observed among 948 individuals in the follow-up analyses. Time from fracture to evaluation was less than 3 months in 76.7% of individuals. Osteoporosis treatment was prescribed in 87.7%, and adherence was 65.3% in Morisky–Green test. Conclusion Our results provide a comprehensive picture of fragility fractures identifed in FLS units from Spain. Overall, quality indicators are satisfactory although a much higher use of DXA would be desirable. As the registry grows with the incorporation of new FLS units and longer follow-up, incoming analyses will provide valuable insight.

Published
2022

44. Romosozumab improves lumbar spine bone mass and bone strength parameters relative to alendronate in postmenopausal women: results from the Active-Controlled Fracture Study in Postmenopausal Women With Osteoporosis at High Risk (ARCH) trial

Author

Brown, Jacques P., primary, Engelke, Klaus, additional, Keaveny, Tony M., additional, Chines, Arkadi, additional, Chapurlat, Roland, additional, Foldes, A. Joseph, additional, Nogues, Xavier, additional, Civitelli, Roberto, additional, De Villiers, Tobias, additional, Massari, Fabio, additional, Zerbini, Cristiano A.F., additional, Wang, Zhenxun, additional, Oates, Mary K., additional, Recknor, Christopher, additional, and Libanati, Cesar, additional

Published
2021
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49. Association of Tramadol vs Codeine Prescription Dispensation With Mortality and Other Adverse Clinical Outcomes

Author

Xie, Junqing, primary, Strauss, Victoria Y., additional, Martinez-Laguna, Daniel, additional, Carbonell-Abella, Cristina, additional, Diez-Perez, Adolfo, additional, Nogues, Xavier, additional, Collins, Gary S., additional, Khalid, Sara, additional, Delmestri, Antonella, additional, Turkiewicz, Aleksandra, additional, Englund, Martin, additional, Tadrous, Mina, additional, Reyes, Carlen, additional, and Prieto-Alhambra, Daniel, additional

Published
2021
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