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3. A meta-analysis of previous falls and subsequent fracture risk in cohort studies

Author

Vandenput, Liesbeth, Johansson, Helena, McCloskey, Eugene V., Liu, Enwu, Schini, Marian, Åkesson, Kristina E., Anderson, Fred A., Azagra, Rafael, Bager, Cecilie L., Beaudart, Charlotte, Bischoff-Ferrari, Heike A., Biver, Emmanuel, Bruyère, Olivier, Cauley, Jane A., Center, Jacqueline R., Chapurlat, Roland, Christiansen, Claus, Cooper, Cyrus, Crandall, Carolyn J., Cummings, Steven R., da Silva, José A. P., Dawson-Hughes, Bess, Diez-Perez, Adolfo, Dufour, Alyssa B., Eisman, John A., Elders, Petra J. M., Ferrari, Serge, Fujita, Yuki, Fujiwara, Saeko, Glüer, Claus-Christian, Goldshtein, Inbal, Goltzman, David, Gudnason, Vilmundur, Hall, Jill, Hans, Didier, Hoff, Mari, Hollick, Rosemary J., Huisman, Martijn, Iki, Masayuki, Ish-Shalom, Sophia, Jones, Graeme, Karlsson, Magnus K., Khosla, Sundeep, Kiel, Douglas P., Koh, Woon-Puay, Koromani, Fjorda, Kotowicz, Mark A., Kröger, Heikki, Kwok, Timothy, Lamy, Olivier, Langhammer, Arnulf, Larijani, Bagher, Lippuner, Kurt, McGuigan, Fiona E. A., Mellström, Dan, Merlijn, Thomas, Nguyen, Tuan V., Nordström, Anna, Nordström, Peter, O’Neill, Terence W., Obermayer-Pietsch, Barbara, Ohlsson, Claes, Orwoll, Eric S., Pasco, Julie A., Rivadeneira, Fernando, Schott, Anne-Marie, Shiroma, Eric J., Siggeirsdottir, Kristin, Simonsick, Eleanor M., Sornay-Rendu, Elisabeth, Sund, Reijo, Swart, Karin M. A., Szulc, Pawel, Tamaki, Junko, Torgerson, David J., van Schoor, Natasja M., van Staa, Tjeerd P., Vila, Joan, Wareham, Nicholas J., Wright, Nicole C., Yoshimura, Noriko, Zillikens, MCarola, Zwart, Marta, Harvey, Nicholas C., Lorentzon, Mattias, Leslie, William D., and Kanis, John A.

Published
2024
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11. Multimorbidity clusters potentially superior to individual diseases for stratifying fracture risk in older people: a nationwide cohort study.

Author

Tran, Thach, Bliuc, Dana, Abrahamsen, Bo, Chen, Weiwen, Eisman, John A, Hansen, Louise, Vestergaard, Peter, Nguyen, Tuan V, Blank, Robert D, and Center, Jacqueline R

Subjects
RISK assessment, RESEARCH funding, HUMAN beings, STRUCTURAL equation modeling, DESCRIPTIVE statistics, BONE fractures, LONGITUDINAL method, COMORBIDITY, PROPORTIONAL hazards models, DISEASE risk factors, OLD age
Abstract

Rationale Comorbidities are common in fracture patients, but the interaction between fracture and comorbidities remains unclear. This study aimed to define specific multimorbidity clusters in older adults and quantify the association between the multimorbidity clusters and fracture risk. Methods This nationwide cohort study includes 1.7 million adults in Denmark aged ≥50 years who were followed from 2001 through 2014 for an incident low-trauma fracture. Chronic diseases and fractures were identified from the Danish National Hospital Discharge Register. Latent class analysis and Cox's regression were conducted to define the clusters and quantify fracture risk, respectively. Results The study included 793 815 men (age: 64 ± 10) and 873 524 women (65.5 ± 11), with a third having ≥1 chronic disease. The pre-existent chronic diseases grouped individuals into low-multimorbidity (80.3% in men, 83.6% in women), cardiovascular (12.5%, 10.6%), malignant (4.1%, 3.8%), diabetic (2.4%, 2.0%) and hepatic clusters (0.7%, men only). These clusters distinguished individuals with advanced, complex, or late-stage disease from those having earlier-stage disease. During a median follow-up of 14 years (IQR: 6.5, 14), 95 372 men and 212 498 women sustained an incident fracture. The presence of multimorbidity was associated with a significantly greater risk of fracture, independent of age and sex. Importantly, the multimorbidity clusters had the highest discriminative performance in assessing fracture risk, whereas the strength of their association with fracture risk equalled or exceeded that of both the individual chronic diseases most prevalent in each cluster and of counts-based comorbidity indices. Conclusions Future fracture prevention strategies should take comorbidities into account. Multimorbidity clusters may provide greater insight into fracture risk than individual diseases or counts-based comorbidity indices. [ABSTRACT FROM AUTHOR]

Published
2024
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13. Osteocyte transcriptome mapping identifies a molecular landscape controlling skeletal homeostasis and susceptibility to skeletal disease

Author

Youlten, Scott E., Kemp, John P., Logan, John G., Ghirardello, Elena J., Sergio, Claudio M., Dack, Michael R. G., Guilfoyle, Siobhan E., Leitch, Victoria D., Butterfield, Natalie C., Komla-Ebri, Davide, Chai, Ryan C., Corr, Alexander P., Smith, James T., Mohanty, Sindhu T., Morris, John A., McDonald, Michelle M., Quinn, Julian M. W., McGlade, Amelia R., Bartonicek, Nenad, Jansson, Matt, Hatzikotoulas, Konstantinos, Irving, Melita D., Beleza-Meireles, Ana, Rivadeneira, Fernando, Duncan, Emma, Richards, J. Brent, Adams, David J., Lelliott, Christopher J., Brink, Robert, Phan, Tri Giang, Eisman, John A., Evans, David M., Zeggini, Eleftheria, Baldock, Paul A., Bassett, J. H. Duncan, Williams, Graham R., and Croucher, Peter I.

Published
2021
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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

16. Genetic determinants of heel bone properties: genome-wide association meta-analysis and replication in the GEFOS/GENOMOS consortium.

Author

Moayyeri, Alireza, Hsu, Yi-Hsiang, Karasik, David, Estrada, Karol, Xiao, Su-Mei, Nielson, Carrie, Srikanth, Priya, Giroux, Sylvie, Wilson, Scott G, Zheng, Hou-Feng, Smith, Albert V, Pye, Stephen R, Leo, Paul J, Teumer, Alexander, Hwang, Joo-Yeon, Ohlsson, Claes, McGuigan, Fiona, Minster, Ryan L, Hayward, Caroline, Olmos, José M, Lyytikäinen, Leo-Pekka, Lewis, Joshua R, Swart, Karin MA, Masi, Laura, Oldmeadow, Chris, Holliday, Elizabeth G, Cheng, Sulin, van Schoor, Natasja M, Harvey, Nicholas C, Kruk, Marcin, del Greco M, Fabiola, Igl, Wilmar, Trummer, Olivia, Grigoriou, Efi, Luben, Robert, Liu, Ching-Ti, Zhou, Yanhua, Oei, Ling, Medina-Gomez, Carolina, Zmuda, Joseph, Tranah, Greg, Brown, Suzanne J, Williams, Frances M, Soranzo, Nicole, Jakobsdottir, Johanna, Siggeirsdottir, Kristin, Holliday, Kate L, Hannemann, Anke, Go, Min Jin, Garcia, Melissa, Polasek, Ozren, Laaksonen, Marika, Zhu, Kun, Enneman, Anke W, McEvoy, Mark, Peel, Roseanne, Sham, Pak Chung, Jaworski, Maciej, Johansson, Åsa, Hicks, Andrew A, Pludowski, Pawel, Scott, Rodney, Dhonukshe-Rutten, Rosalie AM, van der Velde, Nathalie, Kähönen, Mika, Viikari, Jorma S, Sievänen, Harri, Raitakari, Olli T, González-Macías, Jesús, Hernández, Jose L, Mellström, Dan, Ljunggren, Osten, Cho, Yoon Shin, Völker, Uwe, Nauck, Matthias, Homuth, Georg, Völzke, Henry, Haring, Robin, Brown, Matthew A, McCloskey, Eugene, Nicholson, Geoffrey C, Eastell, Richard, Eisman, John A, Jones, Graeme, Reid, Ian R, Dennison, Elaine M, Wark, John, Boonen, Steven, Vanderschueren, Dirk, Wu, Frederick CW, Aspelund, Thor, Richards, J Brent, Bauer, Doug, Hofman, Albert, Khaw, Kay-Tee, Dedoussis, George, Obermayer-Pietsch, Barbara, Gyllensten, Ulf, Pramstaller, Peter P, and Lorenc, Roman S

Subjects
Calcaneus, Humans, Osteoporosis, Genetic Predisposition to Disease, Ultrasonography, Cohort Studies, Bone Density, Polymorphism, Single Nucleotide, Adult, Aged, Aged, 80 and over, Middle Aged, Female, Male, Fractures, Bone, Genome-Wide Association Study, Young Adult, Human Genome, Genetics, Aging, 2.1 Biological and endogenous factors, Aetiology, Musculoskeletal, Biological Sciences, Medical and Health Sciences, Genetics & Heredity
Abstract

Quantitative ultrasound of the heel captures heel bone properties that independently predict fracture risk and, with bone mineral density (BMD) assessed by X-ray (DXA), may be convenient alternatives for evaluating osteoporosis and fracture risk. We performed a meta-analysis of genome-wide association (GWA) studies to assess the genetic determinants of heel broadband ultrasound attenuation (BUA; n = 14 260), velocity of sound (VOS; n = 15 514) and BMD (n = 4566) in 13 discovery cohorts. Independent replication involved seven cohorts with GWA data (in silico n = 11 452) and new genotyping in 15 cohorts (de novo n = 24 902). In combined random effects, meta-analysis of the discovery and replication cohorts, nine single nucleotide polymorphisms (SNPs) had genome-wide significant (P < 5 × 10(-8)) associations with heel bone properties. Alongside SNPs within or near previously identified osteoporosis susceptibility genes including ESR1 (6q25.1: rs4869739, rs3020331, rs2982552), SPTBN1 (2p16.2: rs11898505), RSPO3 (6q22.33: rs7741021), WNT16 (7q31.31: rs2908007), DKK1 (10q21.1: rs7902708) and GPATCH1 (19q13.11: rs10416265), we identified a new locus on chromosome 11q14.2 (rs597319 close to TMEM135, a gene recently linked to osteoblastogenesis and longevity) significantly associated with both BUA and VOS (P < 8.23 × 10(-14)). In meta-analyses involving 25 cohorts with up to 14 985 fracture cases, six of 10 SNPs associated with heel bone properties at P < 5 × 10(-6) also had the expected direction of association with any fracture (P < 0.05), including three SNPs with P < 0.005: 6q22.33 (rs7741021), 7q31.31 (rs2908007) and 10q21.1 (rs7902708). In conclusion, this GWA study reveals the effect of several genes common to central DXA-derived BMD and heel ultrasound/DXA measures and points to a new genetic locus with potential implications for better understanding of osteoporosis pathophysiology.

Published
2014

17. A meta-analysis of the association of fracture risk and body mass index in women.

Author

Johansson, Helena, Kanis, John A, Odén, Anders, McCloskey, Eugene, Chapurlat, Roland D, Christiansen, Claus, Cummings, Steve R, Diez-Perez, Adolfo, Eisman, John A, Fujiwara, Saeko, Glüer, Claus-C, Goltzman, David, Hans, Didier, Khaw, Kay-Tee, Krieg, Marc-Antoine, Kröger, Heikki, LaCroix, Andrea Z, Lau, Edith, Leslie, William D, Mellström, Dan, Melton, L Joseph, O'Neill, Terence W, Pasco, Julie A, Prior, Jerilynn C, Reid, David M, Rivadeneira, Fernando, van Staa, Tjerd, Yoshimura, Noriko, and Zillikens, M Carola

Subjects
Humans, Obesity, Body Mass Index, Risk, Cohort Studies, Bone Density, Adult, Aged, Aged, 80 and over, Middle Aged, Female, Fractures, Bone, Osteoporotic Fractures, BMI, FRACTURE RISK, OBESITY, POISSON REGRESSION MODEL, POPULATION STUDIES, WOMEN, and over, Fractures, Bone, Osteoporosis, Injury (total) Accidents/Adverse Effects, Clinical Research, Injuries and Accidents, Musculoskeletal, Anatomy & Morphology, Medical and Health Sciences, Biological Sciences, Engineering
Abstract

Several recent studies suggest that obesity may be a risk factor for fracture. The aim of this study was to investigate the association between body mass index (BMI) and future fracture risk at different skeletal sites. In prospective cohorts from more than 25 countries, baseline data on BMI were available in 398,610 women with an average age of 63 (range, 20-105) years and follow up of 2.2 million person-years during which 30,280 osteoporotic fractures (6457 hip fractures) occurred. Femoral neck BMD was measured in 108,267 of these women. Obesity (BMI ≥ 30 kg/m(2) ) was present in 22%. A majority of osteoporotic fractures (81%) and hip fractures (87%) arose in non-obese women. Compared to a BMI of 25 kg/m(2) , the hazard ratio (HR) for osteoporotic fracture at a BMI of 35 kg/m(2) was 0.87 (95% confidence interval [CI], 0.85-0.90). When adjusted for bone mineral density (BMD), however, the same comparison showed that the HR for osteoporotic fracture was increased (HR, 1.16; 95% CI, 1.09-1.23). Low BMI is a risk factor for hip and all osteoporotic fracture, but is a protective factor for lower leg fracture, whereas high BMI is a risk factor for upper arm (humerus and elbow) fracture. When adjusted for BMD, low BMI remained a risk factor for hip fracture but was protective for osteoporotic fracture, tibia and fibula fracture, distal forearm fracture, and upper arm fracture. When adjusted for BMD, high BMI remained a risk factor for upper arm fracture but was also a risk factor for all osteoporotic fractures. The association between BMI and fracture risk is complex, differs across skeletal sites, and is modified by the interaction between BMI and BMD. At a population level, high BMI remains a protective factor for most sites of fragility fracture. The contribution of increasing population rates of obesity to apparent decreases in fracture rates should be explored.

Published
2014

27. List of Contributors

Author

Adams, John S., primary, Adams, Judith E., additional, Alsalem, Jawaher A., additional, Anderson, Paul H., additional, Andreopoulou, Panagiota, additional, Angellotti, Edith, additional, Arnold, Leggy A., additional, Atkins, Gerald J., additional, Barbáchano, Antonio, additional, Bassuk, Shari S., additional, Beaudin, Sarah, additional, Belorusova, Anna Y., additional, Benkusky, Nancy A., additional, Bernal-Mizrachi, Carlos, additional, Bhan, Ishir, additional, Bhattoa, Harjit P., additional, Bikle, Daniel D., additional, Bilezikian, John P., additional, Binkley, Neil C., additional, Bischoff-Ferrari, Heike A., additional, Bishop, Charles W., additional, Boisen, Ida M., additional, Bonelli, Fabrizio, additional, Boskey, Adele L., additional, Boucher, Barbara J., additional, Bouillon, Roger, additional, Bouttier, Manuella, additional, Boyan, Barbara D., additional, Bruce, Danny, additional, Buburuzan, Laura, additional, Burghardt, Andrew J., additional, Burne, Thomas H.J., additional, Calvo, Mona S., additional, Camargo Jr., Carlos A., additional, Cannata-Andia, Jorge B., additional, Cantorna, Margherita T., additional, Carlberg, Carsten, additional, Carmeliet, Geert, additional, Carpenter, Thomas O., additional, Carter, Graham D., additional, Cashman, Kevin D., additional, Ceglia, Lisa, additional, Christakos, Sylvia, additional, Christopher, Kenneth B., additional, Chun, Rene F., additional, Coe, Fredric L., additional, Coffman, Frederick, additional, Compston, Juliet, additional, Cooper, Cyrus, additional, Curtis, Elizabeth M., additional, Cusano, Natalie E., additional, Danilenko, Michael, additional, David Roodman, G., additional, Dawson-Hughes, Bess, additional, De Clercq, Pierre, additional, DeLuca, Hector F., additional, Demaret, Julie, additional, Demay, Marie B., additional, Dempster, David W., additional, Dennison, Elaine M., additional, Dhawan, Puneet, additional, Dimitrov, Vassil, additional, Dixon, Katie M., additional, Doroudi, Maryam, additional, Doyle, Shevaun M., additional, Dusso, Adriana S., additional, Dvorzhinskiy, Aleksey, additional, Ebeling, Peter R., additional, Eisman, John A., additional, Emkey, Gregory R., additional, Epstein Jr., Ervin H., additional, Epstein, Sol, additional, Eyles, Darryl, additional, Favus, Murray J., additional, Feldman, David, additional, Ferrer-Mayorga, Gemma, additional, Findlay, David M., additional, Fleet, James C., additional, Foster, Brian L., additional, Franceschi, Renny T., additional, Fraser, David R., additional, Furst, Jessica M., additional, Gafni, Rachel I., additional, Giovannucci, Edward, additional, Girgis, Christian M., additional, Gleason, James L., additional, Glorieux, Francis H., additional, Gocek, Elzbieta, additional, Goltzman, David, additional, González-Sancho, José Manuel, additional, Graeff-Armas, Laura A., additional, Grant, William B., additional, Groves, Natalie J., additional, Gysemans, Conny, additional, Hansen, Lasse Bøllehuus, additional, Harvey, Nicholas C., additional, Hawrylowicz, Catherine M., additional, Hayes, Colleen E., additional, Heaney, Robert P., additional, Hendy, Geoffrey N., additional, Hershberger, Pamela A., additional, Hewison, Martin, additional, Holick, Michael F., additional, Hollis, Bruce W., additional, Hujoel, Philippe P., additional, Hyppönen, Elina, additional, Insogna, Karl L., additional, Jablonski, Nina G., additional, Jensen, Martin Blomberg, additional, Jolliffe, David A., additional, Jones, Glenville, additional, Jones, Kerry S., additional, Jüppner, Harald, additional, Kallay, Enikö, additional, Karaplis, Andrew C., additional, Kaufmann, Martin, additional, Kiely, Mairead, additional, Kim, Tiffany Y., additional, Konrad, Martin, additional, Kovacs, Christopher S., additional, Kremer, Richard, additional, Krug, Roland, additional, Kumar, Rajiv, additional, Kurihara, Noriyoshi, additional, Laing, Emma, additional, Lane, Joseph M., additional, Larner, Dean P., additional, Larriba, María Jesús, additional, Laverny, Gilles, additional, Le Roy, Nathalie, additional, Lee, Seong M., additional, Levine, Michael A., additional, Lewis, Richard, additional, Lips, Paul, additional, Lisse, Thomas S., additional, Liu, Eva S., additional, Liu, Philip T., additional, Li, Yan, additional, Li, Yan Chun, additional, MacKrell, James G., additional, Mady, Leila J., additional, Majumdar, Sharmila, additional, Makishima, Makoto, additional, Malloy, Peter J., additional, Mann, Elizabeth H., additional, Manson, JoAnn E., additional, Martineau, Adrian R., additional, Mason, Rebecca S., additional, Mathieu, Chantal, additional, Matsumoto, Toshio, additional, Matthews, Donald G., additional, McGrath, John J., additional, Metzger, Daniel, additional, Meyer, Mark B., additional, Miao, Denshun, additional, Mizwicki, Mathew T., additional, Moon, Rebecca J., additional, Morris, Howard A., additional, Mortensen, Li J., additional, Muñoz, Alberto, additional, Nakamichi, Yuko, additional, Narvaez, Carmen J., additional, Nashold, Faye E., additional, Naveh-Many, Tally, additional, Nielson, Carrie M., additional, Norman, Anthony W., additional, Nys, Yves, additional, Onal, Melda, additional, Pal, Lubna, additional, Patterson, Kristine Y., additional, Pauwels, Steven, additional, Pehrsson, Pamela R., additional, Petkovich, Martin, additional, Pettifor, John M., additional, Pfeffer, Paul E., additional, Phillips, Katherine M., additional, Pike, J. Wesley, additional, Pilz, Stefan, additional, Pittas, Anastassios G., additional, Pludowski, Pawel, additional, Prosser, David E., additional, Pullagura, Sri Ramulu N., additional, Quarles, L. Darryl, additional, Rajagopal, Rithwick, additional, Ransohoff, Katherine J., additional, Rauz, Saaeha, additional, Rebolledo, Brian J., additional, Reichrath, Jörg, additional, Rieger, Sandra, additional, Riek, Amy E., additional, Rochel, Natacha, additional, Roizen, Jeffrey D., additional, Roseland, Janet M., additional, Rosen, Cliff, additional, Rybchyn, Mark S., additional, Saitoh, Hiroshi, additional, Salehi-Tabar, Reyhaneh, additional, Schafer, Anne L., additional, Schlingmann, Karl P., additional, Schoenmakers, Inez, additional, Schwartz, Zvi, additional, Scott, Kayla, additional, Sempos, Christopher T., additional, Sepiashvili, Lusia, additional, Seshadri, Mukund, additional, Shane, Elizabeth, additional, Shaurova, Tatiana, additional, Shui, Irene, additional, Silver, Justin, additional, Singh, Ravinder J., additional, Skingle, Linda, additional, St-Arnaud, René, additional, Starr, Jessica, additional, Stayrook, Keith R., additional, Stein, Emily M., additional, Stites, Ryan E., additional, Studzinski, George P., additional, Suda, Tatsuo, additional, Takahashi, Fumiaki, additional, Takahashi, Naoyuki, additional, Tang, Jean Y., additional, Taylor, Christine L., additional, Taylor, Hugh S., additional, Tebben, Peter J., additional, Thacher, Thomas D., additional, Thadhani, Ravi, additional, Thandrayen, Kebashni, additional, Thys-Jacobs, Susan, additional, Tiosano, Dov, additional, Toni, Roberto, additional, Towler, Dwight A., additional, Trump, Donald L., additional, Udagawa, Nobuyuki, additional, Uitterlinden, André G., additional, Unnanuntana, Aasis, additional, van de Peppel, Jeroen, additional, van der Eerden, Bram C.J., additional, van Driel, Marjolein, additional, van Leeuwen, Johannes P.T.M., additional, van Schoor, Natasja, additional, Vanherwegen, An-Sofie, additional, Vazirnia, Aria, additional, Verlinden, Lieve, additional, Verstuyf, Annemieke, additional, Vieth, Reinhold, additional, Wagner, Carol L., additional, Wallace, Graham R., additional, Weaver, Connie, additional, Welsh, JoEllen, additional, White, John H., additional, Whiting, Susan J., additional, Whyte, Michael P., additional, Wysolmerski, John J., additional, Yamada, Sachiko, additional, Yu, Olivia B., additional, Zavala, Kathryn, additional, Zechner, Christoph, additional, Zeytinoglu, Meltem, additional, and Zhao, Hengguang, additional

Published
2018
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29. List of Contributors

Author

Ackert-Bicknell, Cheryl, primary, Agarwal, Sunita K., additional, Albagha, Omar M.E., additional, Allen, Robyn S., additional, Arnold, Andrew, additional, Bassett, J.H. Duncan, additional, Bateman, John F., additional, Bellido, Teresita, additional, Bonewald, Lynda, additional, Boudin, Eveline, additional, Bouxsein, Mary L., additional, Boyce, Brendan F., additional, Brewer, Niambi S., additional, Brewster, Stephanie J., additional, Briggs, Mike, additional, Brown, Edward M., additional, Brown, Matthew A., additional, Bushinsky, David A., additional, Cabral, Wayne A., additional, Collins, Michael T., additional, Convente, Michael R., additional, Costa-Guda, Jessica, additional, Deng, Hong-Wen, additional, Devuyst, Olivier, additional, Drezner, Marc K., additional, Duncan, Emma L., additional, Egbuna, Ogo I., additional, Eisman, John A., additional, Farber, Charles R., additional, Feldman, David, additional, Ferreira, Carlos R., additional, Gahl, William A., additional, Gorvin, Caroline M., additional, Grol, Matthew W., additional, Guo, Yan, additional, Guse, Kilian, additional, Hannan, Fadil M., additional, Hao, Ruo-Han, additional, Holm, Ingrid A., additional, Igarashi, Takashi, additional, Jacobsen, Christina, additional, Johannesdottir, Fjola, additional, Jüppner, Harald, additional, Kaplan, Frederick S., additional, Karsenty, Gerard, additional, Kovacs, Christopher S., additional, Kuiper, John J., additional, Lee, Brendan H., additional, Loots, Gabriela G., additional, Lories, Rik J., additional, Luyten, Frank P., additional, Malloy, Peter J., additional, Mannstadt, Michael, additional, Marini, Joan C., additional, John Martin, T., additional, Miller, Walter L., additional, Moe, Orson W., additional, Newey, Paul J., additional, Nguyen, Tuan V., additional, Okamoto, Kazuo, additional, Pajevic, Paola D., additional, Papasian, Christopher J., additional, Piret, Siân E., additional, Ralston, Stuart H., additional, Rivadeneira, Fernando, additional, Robey, Pamela G., additional, Rosen, Clifford J., additional, Ruan, Merry Z.C., additional, Scheinman, Steven J., additional, Schurman, Scott J., additional, Sebastian, Aimy, additional, Shen, Yiping, additional, Shore, Eileen M., additional, Silve, Caroline, additional, Sims, Natalie A., additional, Stanley, Alexandra K., additional, Stone, Adrianne, additional, Takayanagi, Hiroshi, additional, Thakker, Rajesh V., additional, Towler, O. Will, additional, Uitterlinden, André G., additional, Valdes, Ana M., additional, van der Eerden, Bram C.J., additional, Van Hul, Wim, additional, Wei, Jianwen, additional, Wein, Marc N., additional, Weinstein, Lee S., additional, Whyte, Michael P., additional, Williams, Graham R., additional, Xing, Lianping, additional, Yang, Tie-Lin, additional, Zankl, Andreas, additional, Ziegler, Shira G., additional, and Zuscik, Michael J., additional

Published
2018
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31. Publisher Correction: GWAS of bone size yields twelve loci that also affect height, BMD, osteoarthritis or fractures

Author

Styrkarsdottir, Unnur, Stefansson, Olafur A., Gunnarsdottir, Kristbjorg, Thorleifsson, Gudmar, Lund, Sigrun H., Stefansdottir, Lilja, Juliusson, Kristinn, Agustsdottir, Arna B., Zink, Florian, Halldorsson, Gisli H., Ivarsdottir, Erna V., Benonisdottir, Stefania, Jonsson, Hakon, Gylfason, Arnaldur, Norland, Kristjan, Trajanoska, Katerina, Boer, Cindy G., Southam, Lorraine, Leung, Jason C. S., Tang, Nelson L. S., Kwok, Timothy C. Y., Lee, Jenny S. W., Ho, Suzanne C., Byrjalsen, Inger, Center, Jacqueline R., Lee, Seung Hun, Koh, Jung-Min, Lohmander, L. Stefan, Ho-Pham, Lan T., Nguyen, Tuan V., Eisman, John A., Woo, Jean, Leung, Ping-C., Loughlin, John, Zeggini, Eleftheria, Christiansen, Claus, Rivadeneira, Fernando, van Meurs, Joyce, Uitterlinden, Andre G., Mogensen, Brynjolfur, Jonsson, Helgi, Ingvarsson, Thorvaldur, Sigurdsson, Gunnar, Benediktsson, Rafn, Sulem, Patrick, Jonsdottir, Ingileif, Masson, Gisli, Holm, Hilma, Norddahl, Gudmundur L., Thorsteinsdottir, Unnur, Gudbjartsson, Daniel F., and Stefansson, Kari

Published
2019
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32. GWAS of bone size yields twelve loci that also affect height, BMD, osteoarthritis or fractures

Author

Styrkarsdottir, Unnur, Stefansson, Olafur A., Gunnarsdottir, Kristbjorg, Thorleifsson, Gudmar, Lund, Sigrun H., Stefansdottir, Lilja, Juliusson, Kristinn, Agustsdottir, Arna B., Zink, Florian, Halldorsson, Gisli H., Ivarsdottir, Erna V., Benonisdottir, Stefania, Jonsson, Hakon, Gylfason, Arnaldur, Norland, Kristjan, Trajanoska, Katerina, Boer, Cindy G., Southam, Lorraine, Leung, Jason C. S., Tang, Nelson L. S., Kwok, Timothy C. Y., Lee, Jenny S. W., Ho, Suzanne C., Byrjalsen, Inger, Center, Jacqueline R., Lee, Seung Hun, Koh, Jung-Min, Lohmander, L. Stefan, Ho-Pham, Lan T., Nguyen, Tuan V., Eisman, John A., Woo, Jean, Leung, Ping-C., Loughlin, John, Zeggini, Eleftheria, Christiansen, Claus, Rivadeneira, Fernando, van Meurs, Joyce, Uitterlinden, Andre G., Mogensen, Brynjolfur, Jonsson, Helgi, Ingvarsson, Thorvaldur, Sigurdsson, Gunnar, Benediktsson, Rafn, Sulem, Patrick, Jonsdottir, Ingileif, Masson, Gisli, Holm, Hilma, Norddahl, Gudmundur L., Thorsteinsdottir, Unnur, Gudbjartsson, Daniel F., and Stefansson, Kari

Published
2019
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36. Association of Multimorbidity and Excess Mortality After Fractures Among Danish Adults

Author

Tran, Thach, primary, Bliuc, Dana, additional, Ho-Le, Thao, additional, Abrahamsen, Bo, additional, van den Bergh, Joop P., additional, Chen, Weiwen, additional, Eisman, John A., additional, Geusens, Piet, additional, Hansen, Louise, additional, Vestergaard, Peter, additional, Nguyen, Tuan V., additional, Blank, Robert D., additional, and Center, Jacqueline R., additional

Published
2022
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37. Decreased Mortality and Subsequent Fracture Risk in Patients With a Major and Hip Fracture After the Introduction of a Fracture Liaison Service: A 3‐Year Follow‐Up Survey

Author

Vranken, Lisanne, primary, de Bruin, Irma J.A., additional, Driessen, Annemariek H.M., additional, Geusens, Piet P.M., additional, Eisman, John A., additional, Center, Jacqueline R., additional, van der Velde, Robert Y., additional, Janzing, Heinrich M.J., additional, Kaarsemaker, Sjoerd, additional, van den Bergh, Joop P., additional, and Wyers, Caroline E., additional

Published
2022
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45. Association between incident falls and subsequent fractures in patients attending the fracture liaison service after an index fracture: a 3-year prospective observational cohort study

Author

Vranken, Lisanne, primary, Wyers, Caroline E, additional, Van der Velde, Robert Y, additional, Janzing, Heinrich M J, additional, Kaarsemakers, Sjoerd, additional, Driessen, Johanna, additional, Eisman, John, additional, Center, Jacqueline R, additional, Nguyen, Tuan V, additional, Tran, Thach, additional, Bliuc, Dana, additional, Geusens, Piet, additional, and van den Bergh, Joop P, additional

Published
2022
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48. Association of Multimorbidity and Excess Mortality After Fractures Among Danish Adults

Author

Tran, Thach, Bliuc, Dana, Ho-Le, Thao, Abrahamsen, Bo, van den Bergh, Joop P, Chen, Weiwen, Eisman, John A, Geusens, Piet, Hansen, Louise, Vestergaard, Peter, Nguyen, Tuan V, Blank, Robert D, Center, Jacqueline R, Tran, Thach, Bliuc, Dana, Ho-Le, Thao, Abrahamsen, Bo, van den Bergh, Joop P, Chen, Weiwen, Eisman, John A, Geusens, Piet, Hansen, Louise, Vestergaard, Peter, Nguyen, Tuan V, Blank, Robert D, and Center, Jacqueline R

Abstract

Importance: Limited knowledge about interactions among health disorders impedes optimal patient care. Because comorbidities are common among patients 50 years and older with fractures, these fractures provide a useful setting for studying interactions among disorders.Objective: To define multimorbidity clusters at the time of fracture and quantify the interaction between multimorbidity and fracture in association with postfracture excess mortality.Design, Setting, and Participants: This nationwide cohort study included 307 870 adults in Denmark born on or before January 1, 1951, who had an incident low-trauma fracture between January 1, 2001, and December 31, 2014, and were followed up through December 31, 2016. Data were analyzed from February 1 to March 31, 2022.Main Outcomes and Measures: Fracture and 32 predefined chronic diseases recorded within 5 years before the index fracture were identified from the Danish National Hospital Discharge Register. Death was ascertained from the Danish Register on Causes of Death. Latent class analysis was conducted to identify multimorbidity clusters. Relative survival analysis was used to quantify excess mortality associated with the combination of multimorbidity and fractures at specific sites.Results: Among the 307 870 participants identified with incident fractures, 95 372 were men (31.0%; mean [SD] age at fracture, 72.3 [11.2] years) and 212 498 were women (69.0%; mean [SD] age at fracture, 74.9 [11.2] years). During a median of 6.5 (IQR, 3.0-11.0) years of follow-up, 41 017 men (43.0%) and 81 727 women (38.5%) died. Almost half of patients with fractures (42.9%) had at least 2 comorbidities. Comorbidities at fracture were categorized as low-multimorbidity (60.5% in men and 66.5% in women), cardiovascular (23.7% in men and 23.5% in women), diabetic (5.6% in men and 5.0% in women), malignant (5.1% in men and 5.0% in women), and mixed hepatic and/or inflammatory (5.1% in men only) clusters. The

Published
2022

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