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376 results on '"Lorenc, R."'

1. Is it time to consider population screening for fracture risk in postmenopausal women? A position paper from the International Osteoporosis Foundation Epidemiology/Quality of Life Working Group

Author

Chotiyarnwong, P., McCloskey, E. V., Harvey, N. C., Lorentzon, M., Prieto-Alhambra, D., Abrahamsen, B., Adachi, J. D., Borgström, F., Bruyere, O., Carey, J. J., Clark, P., Cooper, C., Curtis, E. M., Dennison, E., Diaz-Curiel, M., Dimai, H. P., Grigorie, D., Hiligsmann, M., Khashayar, P., Lewiecki, E. M., Lips, P., Lorenc, R. S., Ortolani, S., Papaioannou, A., Silverman, S., Sosa, M., Szulc, P., Ward, K. A., Yoshimura, N., and Kanis, J. A.

Published
2022
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2. An appendix to the 2012 IOF–ECTS guidelines for the management of glucocorticoid-induced osteoporosis

Author

Lekamwasam, S., Adachi, J. D., Agnusdei, D., Bilezikian, J., Boonen, S., Borgström, F., Cooper, C., Perez, A. Diez, Eastell, R., Hofbauer, L. C., Kanis, J. A., Langdahl, B. L., Lesnyak, O., Lorenc, R., McCloskey, E., Messina, O. D., Napoli, N., Obermayer-Pietsch, B., Ralston, S. H., Sambrook, P. N., Silverman, S., Sosa, M., Stepan, J., Suppan, G., Wahl, D. A., Compston, J. E., and for the Joint IOF–ECTS GIO Guidelines Working Group

Published
2012
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3. A framework for the development of guidelines for the management of glucocorticoid-induced osteoporosis

Author

Lekamwasam, S., Adachi, J. D., Agnusdei, D., Bilezikian, J., Boonen, S., Borgström, F., Cooper, C., Diez Perez, A., Eastell, R., Hofbauer, L. C., Kanis, J. A., Langdahl, B. L., Lesnyak, O., Lorenc, R., McCloskey, E., Messina, O. D., Napoli, N., Obermayer-Pietsch, B., Ralston, S. H., Sambrook, P. N., Silverman, S., Sosa, M., Stepan, J., Suppan, G., Wahl, D. A., Compston, J. E., and Joint IOF-ECTS GIO Guidelines Working Group

Published
2012
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7. Determinants of incident vertebral fracture in men and women: results from the European Prospective Osteoporosis Study (EPOS)

Author

Roy, D.K., O'Neill, T.W., Finn, J.D., Lunt, M., Silman, A.J., Felsenberg, D., Armbrecht, G., Banzer, D., Benevolenskaya, L.I., Bhalla, A., Bruges Armas, J., Cannata, J.B., Cooper, C., Dequeker, J., Diaz, M.N., Eastell, R., Yershova, O.B., Felsch, B., Gowin, W., Havelka, S., Hoszowski, K., Ismail, A.A., Jajic, I., Janott, I., Johnell, O., Kanis, J.A., Kragl, G., Lopez Vaz, A., Lorenc, R., Lyritis, G., Masaryk, P., Matthis, C., Miazgowski, T., Gennari, C., Pols, H.A.P., Poor, G., Raspe, H.H., Reid, D.M., Reisinger, W., Scheidt-Nave, C., Stepan, J.J., Todd, C.J., Weber, K., Woolf, A.D., and Reeve, J.

Published
2003
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8. Incidence of Limb Fracture across Europe: Results from the European Prospective Osteoporosis Study (EPOS)

Author

Ismail, A. A., Pye, S. R., Cockerill, W. C., Lunt, M., Silman*, A. J., Reeve*, J., Banzer, D., Benevolenskaya, L. I., Bhalla, A., Bruges Armas, J., Cannata, J. B., Cooper, C., Delmas, P. D., Dequeker, J., Dilsen, G., Falch, J. A., Felsch, B., Felsenberg, D., Finn, J. D., Gennari, C., Hoszowski, K., Jajic, I., Janott, J., Johnell, O., Kanis, J. A., Kragl, G., Lopez Vaz, A., Lorenc, R., Lyritis, G., Marchand, F., Masaryk, P., Matthis, C., Miazgowski, T., Naves-Diaz, M., Pols, H. A. P., Poor, G., Rapado, A., Raspe, H. H., Reid, D. M., Reisinger, W., Scheidt-Nave, C., Stepan, J., Todd, C., Weber, K., Woolf, A. D., and O’Neill, T. W.

Published
2002
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10. Prevalent Vertebral Deformity Predicts Incident Hip though not distal Forearm Fracture: Results from the European Prospective Osteoporosis Study

Author

Ismail, A. A., Cockerill, W., Cooper, C., Finn, J. D., Abendroth, K., Parisi, G., Banzer, D., Benevolenskaya, L. I., Bhalla, A. K., Bruges Armas, J., Cannata, J. B., Delmas, P. D., Dequeker, J., Dilsen, G., Eastell, R., Ershova, O., Falch, J. A., Felsch, B., Havelka, S., Hoszowski, K., Jajic, I., Kragl, U., Johnell, O., Lopez Vaz, A., Lorenc, R., Lyritis, G., Marchand, F., Masaryk, P., Matthis, C., Miazgowski, T., Pols, H. A. P., Poor, G., Rapado, A., Raspe, H. H., Reid, D. M., Reisinger, W., Janott, J., Scheidt-Nave, C., Stepan, J, Todd, C., Weber, K., Woolf, A. D., Ambrecht, G., Gowin, W., Felsenberg, D., Lunt, M., Kanis, J. A., Reeve, J., Silman, A. J., and O’Neill, T. W.

Published
2001
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13. Is the predictive power of previous fractures for new spine and non-spine fractures associated with biochemical evidence of altered bone remodelling? The EPOS study

Author

Vergnaud, P, Lunt, M, Scheidt-Nave, C, Poor, G, Gennari, C, Hoszowski, K, Lopes Vaz, A, Reid, D.M, Benevolenskaya, L, Grazio, S, Weber, K, Miazgowski, T, Stepan, J.J, Masaryk, P, Galan, F, Bruges Armas, J, Lorenc, R, Havelka, S, Perez Cano, R, Seibel, M, Armbrecht, G, Kaptoge, S, O'Neill, T.W, Silman, A.J, Felsenberg, D, Reeve, J, and Delmas, P.D

Published
2002
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17. Large-scale analysis of association between LRP5 and LRP6 variants and osteoporosis

Author

van Meurs, J, Trikalinos, T, Ralston, S, Balcells, S, Brandi, M, Brixen, K, Kiel, D, Langdahl, B, Lips, P, Ljunggren, O, Lorenc, R, Obermayer-Pietsch, B, Ohlsson, C, Pettersson, U, Reid, D, Rousseau, F, Scollen, S, Van Hul, W, Agueda, L, Akesson, K, Benevolenskaya, L, Ferrari, S, Hallmans, G, Hofman, A, and Husted, L

Abstract

CONTEXT: Mutations in the low-density lipoprotein receptor-related protein 5 (LRP5) gene cause rare syndromes characterized by altered bone mineral density (BMD). More common LRP5 variants may affect osteoporosis risk in the general population. OBJECTIVE: To generate large-scale evidence on whether 2 common variants of LRP5 (Val667Met, Ala1330Val) and 1 variant of LRP6 (Ile1062Val) are associated with BMD and fracture risk. DESIGN AND SETTING: Prospective, multicenter, collaborative study of individual-level data on 37,534 individuals from 18 participating teams in Europe and North America. Data were collected between September 2004 and January 2007; analysis of the collected data was performed between February and May 2007. Bone mineral density was assessed by dual-energy x-ray absorptiometry. Fractures were identified via questionnaire, medical records, or radiographic documentation; incident fracture data were available for some cohorts, ascertained via routine surveillance methods, including radiographic examination for vertebral fractures. MAIN OUTCOME MEASURES: Bone mineral density of the lumbar spine and femoral neck; prevalence of all fractures and vertebral fractures. RESULTS: The Met667 allele of LRP5 was associated with reduced lumbar spine BMD (n = 25,052 [number of participants with available data]; 20-mg/cm2 lower BMD per Met667 allele copy; P = 3.3 x 10(-8)), as was the Val1330 allele (n = 24,812; 14-mg/cm2 lower BMD per Val1330 copy; P = 2.6 x 10(-9)). Similar effects were observed for femoral neck BMD, with a decrease of 11 mg/cm2 (P = 3.8 x 10(-5)) and 8 mg/cm2 (P = 5.0 x 10(-6)) for the Met667 and Val1330 alleles, respectively (n = 25 193). Findings were consistent across studies for both LRP5 alleles. Both alleles were associated with vertebral fractures (odds ratio [OR], 1.26; 95% confidence interval [CI], 1.08-1.47 for Met667 [2001 fractures among 20 488 individuals] and OR, 1.12; 95% CI, 1.01-1.24 for Val1330 [1988 fractures among 20,096 individuals]). Risk of all fractures was also increased with Met667 (OR, 1.14; 95% CI, 1.05-1.24 per allele [7876 fractures among 31,435 individuals)]) and Val1330 (OR, 1.06; 95% CI, 1.01-1.12 per allele [7802 fractures among 31 199 individuals]). Effects were similar when adjustments were made for age, weight, height, menopausal status, and use of hormone therapy. Fracture risks were partly attenuated by adjustment for BMD. Haplotype analysis indicated that Met667 and Val1330 variants both independently affected BMD. The LRP6 Ile1062Val polymorphism was not associated with any osteoporosis phenotype. All aforementioned associations except that between Val1330 and all fractures and vertebral fractures remained significant after multiple-comparison adjustments. CONCLUSIONS: Common LRP5 variants are consistently associated with BMD and fracture risk across different white populations. The magnitude of the effect is modest. LRP5 may be the first gene to reach a genome-wide significance level (a conservative level of significance [herein, unadjusted P < 10(-7)] that accounts for the many possible comparisons in the human genome) for a phenotype related to osteoporosis.

Published
2016

19. Is the predictive power of previous fractures for new spine and non-spine fractures associated with biochemical evidence of altered bone remodelling? The EPOS study. European Prospective Osteoporosis Study

Author

Vergnaud, P, Lunt, M, Scheidt-Nave, C, Poor, G, Gennari, C, Hoszowski, K, Vaz, A, Reid, D, Benevolenskaya, L, Grazio, S, Weber, K, Miazgowski, T, Stepan, J, Masaryk, P, Galan, F, Armas, J, Lorenc, R, Havelka, S, Perez Cano, R, Seibel, M, Armbrecht, G, Kaptoge, S, O'Neill, T, Silman, A, and Felsenberg, D

Abstract

BACKGROUND: In the European Prospective Osteoporosis Study (EPOS), a past spine fracture increased risk of an incident fracture 3.6 - 12-fold even after adjusting for BMD. We examined the possibility that biochemical marker levels were associated with this unexplained BMD-independent element of fracture risk. METHODS: Each of 182 cases in EPOS of spine or non-spine fracture that occurred in 3.8 years of follow-up was matched by age, sex and study centre with two randomly assigned never-fractured controls and one case of past fracture. Analytes measured blind were: osteocalcin, bone-specific alkaline phosphatase, total alkaline phosphatase, serum creatinine, calcium, phosphate and albumin, together with the collagen cross-links degradation products serum CTS and urine CTX. Most subjects also had bone density measured by DXA. RESULTS: Cases who had recent fractures did not differ in marker levels from cases who had their last fracture more than 3 years previously. No statistically significant effect of recent fracture was found for any marker except osteocalcin, which was 17.6% lower in recent peripheral cases compared to unfractured controls (p

Published
2016

20. Determinants of the size of incident vertebral deformities in European men and women in the sixth to ninth decades of age: the European Prospective Osteoporosis Study (EPOS)

Author

Reeve, J., Lunt, M., Felsenberg, D., Silman, A.J., Scheidt-Nave, C., Poor, G., Gennari, C., Weber, K., Lorenc, R., Masaryk, P., Cannata, J.B., Dequeker, J., Reid, D.M., Pols, H.A., Benevolenskaya, L.I., Stepan, J.J., Miazgowski, T., Bhalla, A., Bruges, Armas J., Eastell, R., Lopes-Vaz, A., Lyritis, G., Jajić, Ivo, Woolf, A.D., Banzer, D., Reisinger, W., Todd, C.J., Felsch, B., Havelka, S., Hoszowski, K., Janott, J., Johnell, O., Raspe, H.H., Yershova, O.B., Kanis, J.A., Armbrecht, G., Finn, J.D., Gowin, W., and O'Neill, T.W.

Subjects
Male, medicine.medical_specialty, Bone density, Endocrinology, Diabetes and Metabolism, Osteoporosis, osteoporosis, vertebral fractures, cohort study, radiological morphometry, fracture risk, macromolecular substances, Bone Density, medicine, Deformity, Humans, Orthopedics and Sports Medicine, Prospective Studies, Prospective cohort study, Osteoporosis, Postmenopausal, Aged, Aged, 80 and over, Orthodontics, business.industry, musculoskeletal, neural, and ocular physiology, Middle Aged, Prognosis, medicine.disease, Height loss, Spine, Surgery, Vertebra, Europe, medicine.anatomical_structure, nervous system, Fracture (geology), Spinal Fractures, Female, medicine.symptom, business, Cohort study
Abstract

More severe vertebral fractures have more personal impact. In the European Prospective Osteoporosis Study, more severe vertebral collapse was predictable from prior fracture characteristics. Subjects with bi-concave or crush fractures at baseline had a 2-fold increase in incident fracture size and thus increased risk of a disabling future fracture. Introduction: According to Euler's buckling theory, loss of horizontal trabeculae in vertebrae increases the risk of fracture and suggests that the extent of vertebral collapse will be increased in proportion. We tested the hypothesis that the characteristics of a baseline deformity would influence the size of a subsequent deformity. Methods: In 207 subjects participating in the European Prospective Osteoporosis Study who suffered an incident spine fracture in a previously normal vertebra, we estimated loss of volume (fracture size) from plane film images of all vertebral bodies that were classified as having a new fracture. The sum of the three vertebral heights (anterior, mid-body, and posterior) obtained at follow-up was subtracted from the sum of the same measures at baseline. Each of the summed height loss for vertebrae with a McCloskey-Kanis deformity on the second film was expressed as a percentage. Results and Conclusions: In univariate models, the numbers of baseline deformities and the clinical category of the most severe baseline deformity were each significantly associated with the size of the most severe incident fracture and with the cumulated sum of all vertebral height losses. In multivariate modeling, age and the clinical category of the baseline deformity (crush > bi-concave > uni-concave > wedge) were the strongest determinants of both more severe and cumulative height loss. Baseline biconcave and crush fractures were associated at follow-up with new fractures that were approximately twice as large as those seen with other types of deformity or who previously had undeformed spines. In conclusion, the characteristics of a baseline vertebral deformity determines statistically the magnitude of vertebral body volume lost when a subsequent fracture occurs. Because severity of fracture and number of fractures are determinants of impact, the results should improve prediction of the future personal impact of osteoporosis once a baseline prevalent deformity has been identified.

Published
2016

22. Letter

Author

Reeve, J., Lunt, M., Kalender, W., Dequeker, J., Jajic, I., Lorenc, R., Pols, H., Poor, G., and Stepan, J.

Published
1996
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23. The association between common vitamin D receptor gene variations and osteoporosis

Author

Uitterlinden, A. G., Ralston, S. H., Brandi, M. L., Carey, A. H., Grinberg, D., Langdahl, B. L., Lips, P., Lorenc, R., Obermayer-Pietsxch, B., Reeve, J., Reid, D. M., Amedei, A., Bassiti, A., Bustamante, M., Husted, L. B., Diez-Perez, A., Dobnig, H., Dunning, A. M., Enjuanes, A., Fahrleitner-Pammer, A., Fang, Y., Karczmarewicz, E., Kruk, M., Johannes van Leeuwen, Mavilia, C., Meurs, J. B. J., Mangion, J., Mcguigan, F. E. A., Pols, H. A. P., Renner, W., Rivadeneira, F., Schoor, N. M., Scollen, S., Sherlock, R. E., Ioannidis, J. P. A., Parsons, C., Bear, S., Farmer, R., Lukaszkiewicz, J., Bilinski, P., Czerwinski, E., Lewinski, A., Marcinowska-Suchowierska, E., Milewicz, A., Spaczynski, M., Jaworski, M., Nuti, R., Grazio, S., Miazgowski, T., Boonen, R., Masaryk, P., Stepan, J. J., Lopes Vaz, A., Cannata, J., Weber, K., Benevolenskaya, L. I., Todd, C., Khaw, K. -T, Da Silva, J., Bhalla, A., Poor, G., Bruges Armas, J., Lyritis, G., O Neill, T. W., Lunt, M., Compston, J., Cooper, C., Duncan, E., Keen, R., Mclellan, A., Wass, J., Dekema, E., Essen, H., Pluijm, S., Bravenboer, N., Hofman, A., Duijn, C. M., Jong, P. J., Breteler, M. M., Stricker, B. H., Witteman, J. C., Internal medicine, VU University medical center, and Internal Medicine

Subjects
Male, Bone density, Osteoporosis, Osteoporosis/*genetics, Fractures, Bone/genetics, Calcitriol receptor, Fractures, Bone, chemistry.chemical_compound, Bone Density, Receptors, Calcitriol/*genetics, CDX2 Transcription Factor, Prospective Studies, Deoxyribonucleases, Type II Site-Specific, Promoter Regions, Genetic, education.field_of_study, biology, General Medicine, Middle Aged, FokI, Vitamin D3 Receptor, Female, musculoskeletal diseases, Adult, Bone Density/*genetics, congenital, hereditary, and neonatal diseases and abnormalities, medicine.medical_specialty, TaqI, Genotype, Population, Polymorphism, Genetic, Homeodomain Proteins/*genetics, Internal medicine, Internal Medicine, medicine, Vitamin D and neurology, Humans, education, Aged, Homeodomain Proteins, business.industry, medicine.disease, Endocrinology, chemistry, Haplotypes, biology.protein, Receptors, Calcitriol, business
Abstract

Background: Polymorphisms of the vitamin D receptor (VDR) gene have been implicated in the genetic regulation of bone mineral density (BMD). However, the clinical impact of these variants remains unclear. Objective: To evaluate the relation between VDR polymorphisms, BMD, and fractures. Design: Prospective multicenter large-scale association study. Setting: The Genetic Markers for Osteoporosis consortium, involving 9 European research teams. Participants: 26 242 participants (18 405 women). Measurements: Cdx2 promoter, FokI, BsmI, ApaI, and TaqI polymorphisms; BMD at the femoral neck and the lumbar spine by dual x-ray absorptiometry; and fractures. Results: Comparisons of BMD at the lumbar spine and femoral neck showed nonsignificant differences less than 0.011 g/cm2 for any genotype with or without adjustments. A total of 6067 participants reported a history of fracture, and 2088 had vertebral fractures. For all VDR alleles, odds ratios for fractures were very close to 1.00 (range, 0.98 to 1.02) and collectively the 95% CIs ranged from 0.94 (lowest) to 1.07 (highest). For vertebral fractures, we observed a 9% (95% CI, 0% to 18%; P = 0.039) risk reduction for the Cdx2 A-allele (13% risk reduction in a dominant model). Limitations: The authors analyzed only selected VDR polymorphisms. Heterogeneity was detected in some analyses and may reflect some differences in collection of fracture data across cohorts. Not all fractures were related to osteoporosis. Conclusions: The FokI, BsmI, ApaI, and TaqI VDR polymorphisms are not associated with BMD or with fractures, but the Cdx2 polymorphism may be associated with risk for vertebral fractures.

Published
2006

27. Genetic sharing with cardiovascular disease risk factors and diabetes reveals novel bone mineral density loci

Author

Reppe, S. (Sjur), Wang, Y. (Yunpeng), Thompson, W.K. (Wesley K.), McEvoy, L.K. (Linda K.), Schork, N.J. (Nicholas), Zuber, V. (Verena), Leblanc, M. (Marissa), Bettella, F. (Francesco), Mills, I.G. (Ian G.), Desikan, R.S. (Rahul S.), Djurovic, S. (Srdjan), Gautvik, K.M. (Kaare), Dale, A.M. (Anders), Andreassen, O.A. (Ole), Estrada Gil, K. (Karol), Styrkarsdottir, U. (Unnur), Evangelou, E. (Evangelos), Hsu, Y.-H. (Yi-Hsiang), Duncan, E.L. (Emma), Ntzani, E.E. (Evangelia), Oei, L. (Ling), Albagha, O.M.E. (Omar M.), Amin, N. (Najaf), Kemp, J.P. (John), Koller, D.L. (Daniel), Li, G. (Guo), Liu, C.-T. (Ching-Ti), Minster, R.L. (Ryan), Moayyeri, A. (Alireza), Vandenput, L. (Liesbeth), Willner, D. (Dana), Xiao, S.-M. (Su-Mei), Yerges-Armstrong, L.M. (Laura), Zheng, H.-F. (Hou-Feng), Alonso, N. (Nerea), Eriksson, J. (Joel), Kammerer, C.M. (Candace), Kaptoge, S. (Stephen), Leo, P.J. (Paul), Thorleifsson, G. (Gudmar), Wilson, S.G. (Scott), Wilson, J.F. (James F), Aalto, V. (Ville), Alen, M. (Markku), Aragaki, A.K. (Aaron), Aspelund, T. (Thor), Center, J.R. (Jacqueline), Dailiana, Z. (Zoe), Duggan, C., Garcia, M. (Melissa), Garcia-Giralt, N. (Natàlia), Giroux, S. (Sylvie), Hallmans, G. (Göran), Hocking, L.J. (Lynne), Husted, L.B. (Lise Bjerre), Jameson, K. (Karen), Khusainova, R. (Rita), Kim, G.S. (Ghi Su), Kooperberg, C. (Charles), Koromila, T. (Theodora), Kruk, M. (Marcin), Laaksonen, M. (Marika), Lacroix, A.Z. (Andrea Z.), Lee, S.H. (Seung Hun), Leung, P.C. (Ping C.), Lewis, J.R. (Joshua), Masi, L. (Laura), Mencej-Bedrac, S. (Simona), Nguyen, T.V. (Tuan), Nogues, X. (Xavier), Patel, M.S. (Millan), Prezelj, J. (Janez), Rose, L.M. (Lynda), Scollen, S. (Serena), Siggeirsdottir, K. (Kristin), Smith, A.V. (Davey), Svensson, O. (Olle), Trompet, S. (Stella), Trummer, O. (Olivia), Schoor, N.M. (Natasja) van, Woo, J. (Jean), Zhu, K. (Kun), Balcells, S. (Susana), Brandi, M.L., Buckley, B.M. (Brendan M.), Cheng, S. (Sulin), Christiansen, C., Cooper, C. (Charles), Dedoussis, G.V. (George), Ford, I. (Ian), Frost, M. (Morten), Goltzman, D. (David), González-Macías, J. (Jesús), Kähönen, M. (Mika), Karlsson, M. (Magnus), Khusnutdinova, E.K. (Elza), Koh, J.-M. (Jung-Min), Kollia, P. (Panagoula), Langdahl, B.L. (Bente), Leslie, W.D. (William D.), Lips, P. (Paul), Ljunggren, O. (Östen), Lorenc, R. (Roman), Marc, J. (Janja), Mellström, D. (Dan), Obermayer-Pietsch, B. (Barbara), Olmos, D. (David), Pettersson-Kymmer, U. (Ulrika), Reid, D.M. (David), Riancho, J.A. (José), Ridker, P.M. (Paul), Rousseau, M.F. (Francois), Slagboom, P.E. (Eline), Tang, N.L.S. (Nelson L.S.), Urreizti, R. (Roser), Van Hul, W. (Wim), Viikari, J. (Jorma), Zarrabeitia, M.T. (María), Aulchenko, Y.S. (Yurii), Castaño Betancourt, M.C. (Martha), Grundberg, E. (Elin), Herrera, L. (Lizbeth), Ingvarsson, T. (Torvaldur), Johannsdottir, H. (Hrefna), Kwan, T. (Tony), Li, R. (Rui), Luben, R.N. (Robert), Medina-Gomez, M.C. (Carolina), Palsson, S.T. (Stefan Th), Rotter, J.I. (Jerome I.), Sigurdsson, G. (Gunnar), Meurs, J.B.J. (Joyce) van, Verlaan, D.J. (Dominique), Williams, F.M. (Frances), Wood, A.R. (Andrew), Zhou, Y. (Yanhua), Pastinen, T. (Tomi), Raychaudhuri, S. (Soumya), Cauley, J.A. (Jane), Chasman, D.I. (Daniel), Clark, G.R. (Graeme), Cummings, S.R. (Steven R.), Danoy, P. (Patrick), Dennison, E.M. (Elaine), Eastell, R. (Richard), Eisman, J.A. (John), Gudnason, V. (Vilmundur), Hofman, A. (Albert), Jackson, R.D. (Rebecca), Jones, G. (Graeme), Jukema, J.W. (Jan Wouter), Khaw, K.T., Lehtimäki, T. (Terho), Liu, Y. (YongMei), Lorentzon, M. (Mattias), McCloskey, E.V. (Eugene), Mitchell, B.D. (Braxton), Nandakumar, K. (Kannabiran), Nicholson, G.C. (Geoffrey), Oostra, B.A. (Ben), Peacock, M. (Munro), Pols, H.A.P. (Huib), Prince, R.L. (Richard), Raitakari, O. (Olli), Reid, I.R. (Ian), Robbins, J. (John), Sambrook, P.N. (Philip), Sham, P.C. (Pak Chung), Shuldiner, A.R. (Alan), Tylavsky, F.A. (Frances), Duijn, C.M. (Cornelia) van, Wareham, N.J. (Nicholas J.), Cupples, L.A. (Adrienne), Econs, M.J. (Michael), Evans, D.M. (David), Harris, T.B. (Tamara B.), Kung, A.W.C. (Annie Wai Chee), Psaty, B.M. (Bruce), Reeve, J. (Jonathan), Spector, T.D. (Timothy), Streeten, E.A. (Elizabeth), Zillikens, M.C. (Carola), Thorsteinsdottir, U. (Unnur), Ohlsson, C. (Claes), Karasik, D. (David), Richards, J.B. (Brent), Brown, M.A. (Matthew), Zwart, J-A. (John-Anker), Uitterlinden, A.G. (André), Ralston, S.H. (Stuart), Ioannidis, J.P.A. (John P.A.), Kiel, D.P. (Douglas P.), Rivadeneira Ramirez, F. (Fernando), Reppe, S. (Sjur), Wang, Y. (Yunpeng), Thompson, W.K. (Wesley K.), McEvoy, L.K. (Linda K.), Schork, N.J. (Nicholas), Zuber, V. (Verena), Leblanc, M. (Marissa), Bettella, F. (Francesco), Mills, I.G. (Ian G.), Desikan, R.S. (Rahul S.), Djurovic, S. (Srdjan), Gautvik, K.M. (Kaare), Dale, A.M. (Anders), Andreassen, O.A. (Ole), Estrada Gil, K. (Karol), Styrkarsdottir, U. (Unnur), Evangelou, E. (Evangelos), Hsu, Y.-H. (Yi-Hsiang), Duncan, E.L. (Emma), Ntzani, E.E. 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(John P.A.), Kiel, D.P. (Douglas P.), and Rivadeneira Ramirez, F. (Fernando)

Abstract

Bone Mineral Density (BMD) is a highly heritable trait, but genome-wide association studies have identified few genetic risk factors. Epidemiological studies suggest associations between BMD and several traits and diseases, but the nature of the suggestive comorbidity is still unknown. We used a novel genetic pleiotropy-informed conditional False Discovery Rate (FDR) method to identify single nucleotide polymorphisms (SNPs) associated with BMD by leveraging cardiovascular disease (CVD) associated disorders and metabolic traits. By conditioning on SNPs associated with the CVD-related phenotypes, type 1 diabetes, type 2 diabetes, systolic blood pressure, diastolic blood pressure, high density lipoprotein, low density lipoprotein, triglycerides and waist hip ratio, we identified 65 novel independent BMD loci (26 with femoral neck BMD and 47 with lumbar spine BMD) at conditional FDR < 0.01. Many of the loci were confirmed in genetic expression studies. Genes validated at the mRNA levels were characteristic for the osteoblast/osteocyte lineage, Wnt signaling pathway and bone metabolism. The results provide new insight into genetic mechanisms of variability in BMD, and a better understanding of the genetic underpinnings of clinical comorbidity.

Published
2015
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28. New genetic loci link adipose and insulin biology to body fat distribution

Author

Shungin, D, Winkler, T, Croteau Chonka, D, Ferreira, T, Locke, A, Mägi, R, Strawbridge, R, Pers, T, Fischer, K, Justice, A, Workalemahu, T, Wu, J, Buchkovich, M, Heard Costa, N, Roman, T, Drong, A, Song, C, Gustafsson, S, Day, F, Esko, T, Fall, T, Kutalik, Z, Luan, J, Randall, J, Scherag, A, Vedantam, S, Wood, A, Chen, J, Fehrmann, R, Karjalainen, J, Kahali, B, Liu, C, Schmidt, E, Absher, D, Amin, N, Anderson, D, Beekman, M, Bragg Gresham, J, Buyske, S, Demirkan, A, Ehret, G, Feitosa, M, Goel, A, Jackson, A, Johnson, T, Kleber, M, Kristiansson, K, Mangino, M, Leach, I, Medina Gomez, C, Palmer, C, Pasko, D, Pechlivanis, S, Peters, M, Prokopenko, I, Stanca'Kova', A, Sung, Y, Tanaka, T, Teumer, A, Van Vliet Ostaptchouk, J, Yengo, L, Zhang, W, Albrecht, E, Ärnlöv, J, Arscott, G, Bandinelli, S, Barrett, A, Bellis, C, Bennett, A, Berne, C, Blüher, M, Böhringer, S, Bonnet, F, Böttcher, Y, Bruinenberg, M, Carba, D, Caspersen, I, Clarke, R, Daw, E, Deelen, J, Deelman, E, Delgado, G, Doney, A, 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Jr, Mosley TH, Seshadri S, Shrine NR, Wain LV, Morken MA, Laitinen J, Zitting P, Cooper JA, van Gilst WH, Janipalli CS, Mani K, Yajnik CS, Mattace Raso FU, Lakatta EG, Orru M, Scuteri A, Ala Korpela M, Kangas AJ, Soininen P, Tukiainen T, Würtz P, Ong RT, Dörr M, Galan P, Hercberg S, Lathrop M, Zelenika D, Zhai G, Meschia JF, Nalls MA, Sharma P, Terzic J, Kumar M, Denniff M, Zukowska Szczechowska E, Wagenknecht LE, Fowkes F, Charchar FJ, Rotimi C, Bots ML, Brand E, Talmud PJ, Nyberg F, Laan M, Palmer LJ, van der Schouw YT, Casas JP, Vineis P, Ganesh SK, Wong TY, Tai ES, Rao DC, Morris RW, Dominiczak AF, Marmot MG, Miki T, Chandak GR, Zhu X, Gyllensten UB, Elosua R, Soranzo N, Sijbrands EJ, Uda M, Vasan RS, Larson MG, Caulfield MJ, Anderson CA, Gordon S, Guo Q, Henders A, Lambert A, Kraft P, Kennedy SH, Macgregor S, Missmer SA, Montgomery GW, Nyholt DR, Painter JN, Roseman F, Treloar SA, Visscher PM, Wallace L, Zondervan KT, Alizadeh B, de Boer RA, Boezen HM, Bruinenberg M, Franke L, Hillege HL, van der Klauw MM, Ormel J, Postma DS, Rosmalen JG, Slaets JP, Stolk RP, Lagou V, Welch RP, Wheeler E, Rehnberg E, Yengo L, Lecoeur C, Johnson PC, Mahajan A, Verweij N, Hottenga JJ, Sennblad B, Salo P, Timpson NJ, Hui J, Bielak LF, Zhao W, Horikoshi M, Navarro P, Fall T, Chen H, Robertson N, Rybin D, Chines PS, Song K, An P, Marullo L, Jansen H, Oldehinkel AJ, North KE, Forouhi NG, Edkins S, Varga TV, Oksa H, Antonella M, Kong A, Herder C, Antti J, Miljkovic I, Atalay M, Kiess W, James AL, Smit JH, Campbell S, Fowkes GR, Basart HV, Rathmann W, Maerz W, Province MA, Watanabe RM, de Geus EJ, Penninx BW, Oostra B, Toenjes A, Peyser PA, Körner A, Keinanen Kiukaanniemi SM, Saaristo TE, Boomsma D, Cucca F, Balkau B, Froguel P, Jarvelin MR, Bouatia Naji N, Ahmadi KR, Ainali C, Barrett A, Bataille V, Bell JT, Buil A, Dermitzakis ET, Dimas AS, Durbin R, Glass D, Hassanali N, Hedman ÅK, Ingle C, Keildson S, Knowles D, Krestyaninova M, Lowe CE, Meduri E, di Meglio P, Min JL, Montgomery SB, Nestle FO, Nica AC, Nisbet J, O'Rahilly S, Parts L, Potter S, Sekowska M, Shin SY, Small KS, Surdulescu G, Travers ME, Tsaprouni L, Tsoka S, Wilk A, Matise T, Buyske S, Higashio J, Williams R, Nato A, Ambite JL, Deelman E, Manolio T, Hindorff L, Heiss G, Taylor K, Avery C, Graff M, Lin D, Quibrera M, Cochran B, Kao L, Umans J, Cole S, MacCluer J, Person S, Pankow J, Gross M, Fornage M, Durda P, Jenny N, Patsy B, Arnold A, Buzkova P, Crawford D, Haines J, Murdock D, Glenn K, Brown Gentry K, Thornton Wells T, Dumitrescu L, Jeff J, Bush WS, Mitchell SL, Goodloe R, Wilson S, Boston J, Malinowski J, Restrepo N, Oetjens M, Fowke J, Zheng W, Spencer K, Ritchie M, Pendergrass S, Le Marchand L, Wilkens L, Park L, Tiirikainen M, Kolonel L, Lim U, Cheng I, Wang H, Shohet R, Haiman C, Stram D, Henderson B, Monroe K, Schumacher F, Peters U, Anderson G, Carlson C, Prentice R, LaCroix A, Wu C, Carty C, Gong J, Rosse S, Young A, Haessler J, Kocarnik J, Lin Y, Jackson R, Duggan D, Kuller L, Stolk L, He C, Sulem P, Barbalic M, Broer L, Byrne EM, Gudbjartsson DF, McArdle PF, Porcu E, van Wingerden S, Zhuang W, Albrecht E, Alizadeh BZ, Lauc LB, Broekmans FJ, Burri A, Chanock SJ, Chen C, Corre T, Coviello AD, d'Adamo P, Davies G, Deary IJ, Ebrahim S, Fauser BC, Ferreli L, Folsom AR, Garcia ME, Hall P, Haller T, Hankinson SE, Hass M, Heath AC, Janssens AC, Keyzer J, Lahti J, Lai S, Laisk T, Laven JS, Liu J, Lopez LM, Louwers YV, Marongiu M, Klaric IM, Masciullo C, McKnight B, Medland SE, Melzer D, Newman AB, Paré G, Peeters PH, Plump AS, Pop VJ, Räikkönen K, Salumets A, Smith JA, Stacey SN, Starr JM, Stathopoulou MG, Tenesa A, Thorand B, Tryggvadottir L, Tsui K, van Dam RM, van Gils CH, van Nierop P, Vink JM, Voorhuis M, Wallaschofski H, Widen E, Wijnands van Gent CJ, Zgaga L, Zygmunt M, Arnold AM, Buring JE, Crisponi L, Demerath EW, Hunter DJ, Schlessinger D, Murray A, Murabito JM, Visser JA, Lunetta KL, Elks CE, Cousminer DL, Feenstra B, Lin P, van Wingerden SW, Smith EN, Warrington NM, Alavere H, Berenson GS, Blackburn H, Busonero F, Chen W, Couper D, Easton DF, Foroud T, Geller F, Hernandez DG, Kilpeläinen TO, Li S, Melbye M, Murray JC, Murray SS, Nelis M, Ness AR, Northstone K, Pennell CE, Pharoah P, Rafnar T, Rice JP, Ring SM, Schork NJ, Segrè AV, Sovio U, Srinivasan SR, Tammesoo ML, Tyrer J, Weedon MN, Wichmann H, Young L, Zhuang WV, Bierut LJ, Boyd HA, and Murray A.

Abstract

Body fat distribution is a heritable trait and a well-established predictor of adverse metabolic outcomes, independent of overall adiposity. To increase our understanding of the genetic basis of body fat distribution and its molecular links to cardiometabolic traits, we conducted genome-wide association meta-analyses of waist and hip circumference-related traits in up to 224,459 individuals. We identified 49 loci (33 new) associated with waist-to-hip ratio adjusted for body mass index (WHRadjBMI) and an additional 19 loci newly associated with related waist and hip circumference measures (P<5×10-8). Twenty of the 49 WHRadjBMI loci showed significant sexual dimorphism, 19 of which displayed a stronger effect in women. The identified loci were enriched for genes expressed in adipose tissue and for putative regulatory elements in adipocytes. Pathway analyses implicated adipogenesis, angiogenesis, transcriptional regulation, and insulin resistance as processes affecting fat distribution, providing insight into potential pathophysiological mechanisms.

Published
2015

29. Risk factors for Colles' fracture in men and women: results from the European Prospective Osteoporosis Study

Author

Reeve, J (Reeve, J), Silman, AJ (Silman, AJ), O'Neill, TW (O'Neill, TW), Finn, JD (Finn, JD), Pye, SR(Pye, SR), Cockerill, WC (Cockerill, WC), Ismail, AA (Ismail, AA), Roy, DK (Roy, DK), Banzer, D (Banzer, D), Benevolenskaya, LI (Benevolenskaya, LI), Bhalla, A (Bhalla, A), Armas, JB (Armas, JB), Cannata, JB(Cannata, JB), Delmas, P (Delmas, P), Dilsen, G (Dilsen, G), Dequeker, J (Dequeker, J), Falch, J (Falch, J), Felsch, B (Felsch, B), Felsenberg, D (Felsenberg, D), Gennari, C (Gennari, C), Hoszowski, K (Hoszowski, K), Jajic, I (Jajic, Ivo), Janot, J (Janot, J), Johnell, O (Johnell, O), Kragl, G (Kragl, G), Vaz, AL (Vaz, AL), Lorenc, R(Lorenc, R), Lyritis, G (Lyritis, G), Marchand, F (Marchand, F), Masaryk, P (Masaryk, P), Matthis, C (Matthis, C), Miazgowski, T (Miazgowski, T), Diaz, MN (Diaz, MN), Pols, HAP (Pols, HAP), Poor, G (Poor, G), Rapado, A (Rapado, A), Raspe, HH (Raspe, HH), Reid, DM (Reid, DM), Reisinger, W (Reisinger, W), Scheidt-Nave, C (Scheidt-Nave, C), Stepan, J (Stepan, J), Todd, C (Todd, C), Weber, K (Weber, K), Woolf, AD (Woolf, AD), Pye, SR (Pye, SR), Lunt, M (Lunt, M), Kanis, JA (Kanis, JA), and Cooper, C (Cooper, C)

Subjects
Risk factors for Colles' fracture in men and women: results from the European Prospective Osteoporosis Study
Abstract

Risk factors for Colles' fracture in men and women: results from the European Prospective Osteoporosis Study

Published
2004

30. Once-yearly zoledronic acid and days of disability, bed rest, and back pain: Randomized, controlled HORIZON Pivotal Fracture Trial

Author

Cauley, J. a., Dennis, Black, Steven, Boonen, Cummings, Steven R., Peter, Mesenbrink, Lisa, Palermo, Zulema, Man, Peyman, Hadji, Horizon Pivotal Fracture Group Horowitz, Reid Ir Z., Orloff, J., Black, D., Cummings, S., Delmas, P., Eastell, R., Reid, Ian R., Boonen, S., Cauley, J., Cosman, F., Lakatos, P., Leung, P. c., Man, Z., Lau, E., Jasqui, S., Mautalen, C., Rosario Jansen, T., Caminis, J., Eriksen, E. f., Mesenbrink, P., Raisz, L., Bauer, P., Compston, J., Demets, D., Hirschberg, R., Johnell, O., Ralston, S., Wallace, R., Farkough, M., Flood, M., Bauer, D., Palermo, L., Lang, T., Kerzberg, E., Ridruejo, M., Tate, G., Velasco, J., Hooper, M., Kotowicz, M., Nash, P., Prince, R., Roberts, A., Sambrook, P., Dobnig, H., Finkenstedt, G., Hoefle, G., Klaushofer, K., Pecherstorfer, M., Peichl, P., Body, J., Devogelaer, J. p., Geusens, P., Kaufman, J., Brenol, J., Kochen, J., Lederman, R., Radominski, S., Szejnfeld, V., Zerbini, C., Adachi, J., Brown, J., Choquette, D., Hanley, D., Josse, R., Kendler, D., Kremer, R., Morin, F., Olszynski, W., Papaioannou, A., Kinyuen, C., Chen, B., Lin, S., Casas, N., Chalem, M., Jaller, J., Molina, J., Aro, H., Heikkinen, J., Kroger, H., Makinen, L., Saltevo, J., Salmi, J., Valimaki, M., Benhamou, C. l., Fardellone, P., Werhya, G., Allolio, B., Felsenberg, D., Happ, J., Hartard, M., Hensen, J., Kaps, P., Kekow, J., Moericke, R., Ortloff, B., Schneider, P., Wassenberg, S., Balogh, A., Gomor, B., Hidvegi, T., Koranyi, L., Poor, G., Tulassay, Z., Pollak, R. d., Eshed, V., Foldes, A. j., Ish Shalom, S., Vered, I., Weiss, M., Adami, S., Barone, A., Bianchi, G., Giannini, S., Isaia, G. c., Luisetto, G., Minisola, Salvatore, Molea, N., Nuti, R., Ortolani, S., Passeri, M., Rubinacci, A., Seriolo, B., Sinigaglia, L., Choi, W. h., Kang, M. i., Kim, G. s., Kim, H. s., Kim, Y. k., Lim, S. k., Son, H. y., Yoon, H. k., Abud, C., Garcia, P., Ochoa, L., Orozco, J., Santos, J., Reid, I., Elle, S., Halse, J., Høiseth, A., Olav, H., Røed, H. i., Skag, A., Stakkestad, J., Syversen, U., Badurski, J., Czerwinski, E., Lorenc, R., Marcinowska Suchowierska, E., Sawicki, A., Supronik, J., Ailamazyan, E., Benevolenskaya, L., Dreval, A., Dvoretsky, L., Dyomina, R., Mazurov, V., Melnichenko, G., Mkrtoumyan, A., Orlov Morozov, A., Ostroumova, O., Pikhlak, E., Shemerovskaya, T., Shostak, N., Skripnikova, I., Smetnik, V., Tsyrlina, E., Usova, G., Zalevskaya, A., Zazerskaya, I., Zotkin, E., Ljunggren, O., Lofgren, J., Palmer, M., Saaf, M., Stenstrom, M., Hasler, P., Lamy, O., Lippuner, K., Merlin, C., Rizzoli, R., Theiler, R., Tyndall, A., Uebelhart, D., Chen, J. f., Chen, P. q., Chin, L. s., Hwang, J. s., Yang, T. s., Jirapinyo, M., Sattaya, R., Sriussadaporn, S., Supasin, S., Taechakraichana, N., Wilawan, K., Donnachie, H., Fraser, W., Mclellan, A., Reid, D., Abruzzo, J., Ackerman, R., Adler, R., Aloia, J., Birbara, C., Bode, B., Bone, H., Brandon, D., Dionne, D., Jr Downs, R., Dreyfus, J., Elinoff, V., Emkey, R., Fanciullo, J., Fiske, D., Genaro, P., Gollapudi, M., Gordon, R., Hennessey, J., Howard, P., Johnson, K., Johnston, C., Kagan, R., Kafka, S., Kaine, J., Klein, T., Koltun, W., Leboff, M., Levine, B., Lewiecki, E. m., Lewis, C. e., Licata, A., Lillestol, M., Lubin, B., Malamet, R., Mangione, A., Matkovic, V., Mehta, D., Miller, P., Miller, S., Murphy, F. t., Nattrass, S., Podlecki, D., Recknor, C., Rosen, C., Rowe, D., Rude, R., Schnitzer, T., Sherrer, Y., Silverman, S., Stephenson, K., Troupin, B., Tucci, J., Villareal, R., Watts, N., Weinstein, R., Weitz, M., and White, R.

Subjects
medicine.medical_specialty, Endocrinology, Diabetes and Metabolism, medicine.medical_treatment, Osteoporosis, Bed rest, Placebo, Drug Administration Schedule, Article, law.invention, postmenopausal osteoporosis, zoledronic acid, Randomized controlled trial, Risk Factors, law, Back pain, disability, fracture, Internal medicine, Prevalence, Humans, Medicine, Disabled Persons, Orthopedics and Sports Medicine, Probability, Bone Density Conservation Agents, Diphosphonates, business.industry, Imidazoles, medicine.disease, Back Pain, Female, Multivariate Analysis, Spinal Fractures, Bed Rest, Low back pain, Surgery, Zoledronic acid, Relative risk, medicine.symptom, business, medicine.drug
Abstract

The objective of this study was to determine the effect of once-yearly zoledronic acid on the number of days of back pain and the number of days of disability (ie, limited activity and bed rest) owing to back pain or fracture in postmenopausal women with osteoporosis. This was a multicenter, randomized, double-blind, placebo-controlled trial in 240 clinical centers in 27 countries. Participants included 7736 postmenopausal women with osteoporosis. Patients were randomized to receive either a single 15-minute intravenous infusion of zoledronic acid (5 mg) or placebo at baseline, 12 months, and 24 months. The main outcome measures were self-reported number of days with back pain and the number of days of limited activity and bed rest owing to back pain or a fracture, and this was assessed every 3 months over a 3-year period. Our results show that although the incidence of back pain was high in both randomized groups, women randomized to zoledronic acid experienced, on average, 18 fewer days of back pain compared with placebo over the course of the trial (p = .0092). The back pain among women randomized to zoledronic acid versus placebo resulted in 11 fewer days of limited activity (p = .0017). In Cox proportional-hazards models, women randomized to zoledronic acid were about 6% less likely to experience 7 or more days of back pain [relative risk (RR) = 0.94, 95% confidence interval (CI) 0.90–0.99] or limited activity owing to back pain (RR = 0.94, 95% CI 0.87–1.00). Women randomized to zoledronic acid were significantly less likely to experience 7 or more bed-rest days owing to a fracture (RR = 0.58, 95% CI 0.47–0.72) and 7 or more limited-activity days owing to a fracture (RR = 0.67, 95% CI 0.58–0.78). Reductions in back pain with zoledronic acid were independent of incident fracture. Our conclusion is that in women with postmenopausal osteoporosis, a once-yearly infusion with zoledronic acid over a 3-year period significantly reduced the number of days that patients reported back pain, limited activity owing to back pain, and limited activity and bed rest owing to a fracture.

Published
2011

31. A genome-wide copy number association study of osteoporotic fractures points to the 6p25.1 locus

Author

Oei, L. (Ling), Hsu, Y.-H. (Yi-Hsiang), Styrkarsdottir, U. (Unnur), Eussen, H.J.F.M.M. (Bert), Klein, J.E.M.M. (Annelies) de, Peters, M.J. (Marjolein), Halldorsson, B.V. (Bjarni), Liu, C.-T. (Ching-Ti), Alonso, N. (Nerea), Kaptoge, S. (Stephen), Thorleifsson, G. (Gudmar), Hallmans, G. (Göran), Hocking, L.J. (Lynne), Husted, L.B. (Lise Bjerre), Jameson, K. (Karen), Kingdom, M.K. (Marcin KrUnited), Lewis, J.R. (Joshua), Patel, M.S. (Millan), Scollen, S. (Serena), Svensson, O. (Olle), Trompet, S. (Stella), Schoor, N.M. (Natasja) van, Zhu, K. (Kun), Buckley, B.M. (Brendan M.), Cooper, C. (Charles), Ford, I. (Ian), Goltzman, D. (David), González-Macías, J. (Jesús), Langdahl, B.L. (Bente), Leslie, W.D. (William), Lips, P. (Paul), Lorenc, R. (Roman), Olmos, D. (David), Pettersson-Kymmer, U. (Ulrika), Reid, D.M. (David), Riancho, J.A. (José), Slagboom, P.E. (Eline), Garcia-Ibarbia, C. (Carmen), Ingvarsson, T. (Torvaldur), Johannsdottir, H. (Hrefna), Luben, R.N. (Robert), Medina-Gomez, M.C. (Carolina), Arp, P.P. (Pascal), Nandakumar, K. (Kannabiran), Palsson, S.T. (Stefan Th), Sigurdsson, G. (Gunnar), Meurs, J.B.J. (Joyce) van, Zhou, Y. (Yanhua), Hofman, A. (Albert), Jukeme, J.W. (J. Wouter), Pols, H.A.P. (Huib), Prince, R.L. (Richard), Cupples, L.A. (Adrienne), Marshall, C.R. (Christian), Pinto, D. (Duane), Sato, D.K. (DaisUnited Kingdome), Scherer, S.W. (Stephen), Reeve, J. (Jonathan), Thorsteinsdottir, U. (Unnur), Karasik, D. (David), Richards, J.B. (Brent), Zwart, J-A. (John-Anker), Uitterlinden, A.G. (André), Ralston, S.H. (Stuart), Ioannidis, J.P.A. (John), Kiel, D.P. (Douglas), Rivadeneira Ramirez, F. (Fernando), Estrada Gil, K. (Karol), Oei, L. (Ling), Hsu, Y.-H. (Yi-Hsiang), Styrkarsdottir, U. (Unnur), Eussen, H.J.F.M.M. (Bert), Klein, J.E.M.M. (Annelies) de, Peters, M.J. (Marjolein), Halldorsson, B.V. (Bjarni), Liu, C.-T. (Ching-Ti), Alonso, N. (Nerea), Kaptoge, S. (Stephen), Thorleifsson, G. (Gudmar), Hallmans, G. (Göran), Hocking, L.J. (Lynne), Husted, L.B. (Lise Bjerre), Jameson, K. (Karen), Kingdom, M.K. (Marcin KrUnited), Lewis, J.R. (Joshua), Patel, M.S. (Millan), Scollen, S. (Serena), Svensson, O. (Olle), Trompet, S. (Stella), Schoor, N.M. (Natasja) van, Zhu, K. (Kun), Buckley, B.M. (Brendan M.), Cooper, C. (Charles), Ford, I. (Ian), Goltzman, D. (David), González-Macías, J. (Jesús), Langdahl, B.L. (Bente), Leslie, W.D. (William), Lips, P. (Paul), Lorenc, R. (Roman), Olmos, D. (David), Pettersson-Kymmer, U. (Ulrika), Reid, D.M. (David), Riancho, J.A. (José), Slagboom, P.E. (Eline), Garcia-Ibarbia, C. (Carmen), Ingvarsson, T. (Torvaldur), Johannsdottir, H. (Hrefna), Luben, R.N. (Robert), Medina-Gomez, M.C. (Carolina), Arp, P.P. (Pascal), Nandakumar, K. (Kannabiran), Palsson, S.T. (Stefan Th), Sigurdsson, G. (Gunnar), Meurs, J.B.J. (Joyce) van, Zhou, Y. (Yanhua), Hofman, A. (Albert), Jukeme, J.W. (J. Wouter), Pols, H.A.P. (Huib), Prince, R.L. (Richard), Cupples, L.A. (Adrienne), Marshall, C.R. (Christian), Pinto, D. (Duane), Sato, D.K. (DaisUnited Kingdome), Scherer, S.W. (Stephen), Reeve, J. (Jonathan), Thorsteinsdottir, U. (Unnur), Karasik, D. (David), Richards, J.B. (Brent), Zwart, J-A. (John-Anker), Uitterlinden, A.G. (André), Ralston, S.H. (Stuart), Ioannidis, J.P.A. (John), Kiel, D.P. (Douglas), Rivadeneira Ramirez, F. (Fernando), and Estrada Gil, K. (Karol)

Abstract

Background Osteoporosis is a systemic skeletal disease characterised by reduced bone mineral density and increased susceptibility to fracture; these traits are highly heritable. Both common and rare copy number variants (CNVs) potentially affect the function of genes and may influence disease risk. Aim To identify CNVs associated with osteoporotic bone fracture risk. Method We performed a genome-wide CNV association study in 5178 individuals from a prospective cohort in the Netherlands, including 809 osteoporotic fracture cases, and performed in silico lookups and de novo genotyping to replicate in several independent studies. Results A rare (population prevalence 0.14%, 95% CI 0.03% to 0.24%) 210 kb deletion located on chromosome 6p25.1 was associated with the risk of fracture (OR 32.58, 95% CI 3.95 to 1488.89; p=8.69×10−5). We performed an in silico meta-analysis in four studies with CNV microarray data and the association with fracture risk was replicated (OR 3.11, 95% CI 1.01 to 8.22; p=0.02). The prevalence of this deletion showed geographic diversity, being absent in additional samples from Australia, Canada, Poland, Iceland, Denmark, and Sweden, but present in the Netherlands (0.34%), Spain (0.33%), USA (0.23%), England (0.15%), Scotland (0.10%), and Ireland (0.06%), with insufficient evidence for association with fracture risk. Conclusions These results suggest that deletions in the 6p25.1 locus may predispose to higher risk of fracture in a subset of populations of European origin; larger and geographically restricted studies will be needed to confirm this regional association. This is a first step towards the evaluation of the role of rare CNVs in osteoporosis.

Published
2014
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32. Childhood fractures do not predict future fractures: results from the European Prospective Osteoporosis Study

Author

Pye, SR, Tobias, J, Silman, AJ, Reeve, J, O'Neill, TW, Weber, K, Dequeker, J, Jajić, Ivo, Havelka, S, Stephan, J, Masaryk, P, Delmas, PD, Marchand, F, Felsenberg, D, Banzer, D, Reisinger, Bochum W, Schatz, Erfurt H, Kragl, G, Scheidt-Nave, Jena C, Abendroth, K, Felsch, B, Raspe, H, Matthis, C, Lyritis Heraklion G, Dretakis, E, Poor, G, Gennari, C, Lips, P, Pols, HA, Falch, JA, Miazgowski, T, Hoszowski, K, Lorenc, R, Bruges Armas, J, Lopez, Vaz A, Benevolenskaya, Yaroslavl LI, Ershova, O, Rapado, A, Perez Cano, R, Galan, F, Cannata, JB, Johnell, O, Kröger, H, Dilsen, G, Reid, DM, Bhalla, AK, Todd, C, and Woolf, AD

Subjects
childhood fracture, prevalent vertebral fracture, incident limb fracture, epidemiology, prospective study
Abstract

Childhood fractures are common. Their clinical relevance to osteoporosis and fractures in later life is unclear. The aim of this study was to determine the predictive risk of childhood fracture on the risk of fracture in later life. Men and women ≥50 yr of age were recruited from population registers for participation in the European Prospective Osteoporosis Study (EPOS). Subjects completed an interviewer administered questionnaire that included questions about previous fractures and the age at which the first of these fractures occurred. Lateral spine radiographs were performed to ascertain prevalent vertebral deformities. Subjects were followed prospectively by postal questionnaire to determine the occurrence of clinical fractures. A subsample of subjects had BMD measurements performed. Cox proportional hazards model was used to determine the predictive risk of childhood fracture between the ages of 8 and 18 yr on the risk of future limb fracture and logistic regression was used to determine the association between reported childhood fractures and prevalent vertebral deformity. A total of 6451 men (mean age, 63.8 yr) and 6936 women (mean age, 63.1 yr) were included in the analysis. Mean follow-up time was 3 yr. Of these, 574 (8.9%) men and 313 (4.5%) women reported a first fracture (any site) between the ages of 8 and 18 yr. A recalled history of any childhood fracture or forearm fracture was not associated with an increased risk of future limb fracture or prevalent vertebral deformity in either men or women. Among the 4807 subjects who had DXA measurements, there was no difference in bone mass among those subjects who had reported a childhood fracture and those who did not. Our data suggest that self-reported previous childhood fracture is not associated with an increased risk of future fracture in men or women.

Published
2009

33. Large-scale analysis of association between polymorphisms in the transfonning growth factor beta 1 gene (TGFB1) and osteoporosis: The GENOMOS study

Author

Bl, Langdahl, Uitterlinden, André G., Sh, Ralston, Ta, Trikalinos, Balcells, S., Ml, Brandi, Scollen, S., Lips, P., Lorenc, R., Obermayer-Pietsch, B., Dm, Reid, Jb, Armas, Pascal Arp, Bassiti, A., Bustamante, M., Lb, Husted, Ah, Carey, Rp, Cano, Dobnig, H., Am, Dunning, Fahrleitner-Pammer, A., Falchetti, A., Karczmarewicz, E., Kruk, M., Johannes van Leeuwen, Masi, L., Joyce van Meurs, Mangion, J., Fea, Mcguigan, Mellibovsky, L., Mosekilde, L., Nogues, X., Huib Pols, Reeve, J., Renner, W., Fernando Rivadeneira, Nm, Schoor, Jpa, Ioannidis, and Internal Medicine

Abstract

Introduction: The TGFBI gene which encodes transforming growth factor beta 1, is a strong candidate for susceptibility to osteoporosis and several studies have reported associations between bone mineral density (BMD), osteoporotic fractures and polymorphisms of TGFBI, although these studies have yielded conflicting results. Methods: We investigated associations between TGFBI polymorphisms and BMD and fracture in the GENOMOS study: a prospective multicenter Study involving 10 European research studies including a total of 28,924 participants. Genotyping was conducted for known TGFBI polymorphisms at the following sites: G(-1639) -A (G(-800) -A, rs1800468), C-1348-T (C-509-T, rs1800469), T-29-C (Leu10Pro, rs1982073), G(74)-C (Arg25Pro, rs1800471) and C-788-T (Thr263Ile, rs1800472). These polymorphisms were genotyped prospectively and methodology was standardized across research centers. Genotypes and haplotypes were related to BMD at the lumbar sine and femoral neck and fractures. Results: There were no significant differences in either women or men at either skeletal site for any of the examined polymorphisms with the possible exception of a weak association with reduced BNID (- 12 mg/m(2)) in men with the T-1348 allele (p < 0.05). Nine of the haplotypes was associated with BMD and none of the polymorphisms or haplotypes significantly affected overall risk of fractures, however, the odds ratio for incident vertebral fracture in carriers of the rare T-788 allele was 1.64 (95% CI: 1.09-2.64), p < 0.05. Conclusions: This study indicates that polymorphic variation in the TGFBI gene does not play a major role in regulating BMD or susceptibility to fractures. The weak associations we observed between the C-1348-T and lumbar spine BMD in men and between C-788-T and risk of incident vertebral fractures are of interest but could be chance findings and will need replication in future studies. (c) 2007 Elsevier Inc. All rights reserved.

Published
2008

34. Cтронция ранелат (Бивалос) снижает риск переломов позвоночника при любых исходных уровнях маркеров перестройки костной ткани р305

Author

Collette, J., Reginster, J., Bruyère, O., Roux, C., Lorenc, R., Felsenberg, D., and Spector, T.

Abstract

Цель. Исходная скорость ремоделирования костной ткани может оказывать влияние на эффективность препаратов для лечения остеопороза в отношении профилактики переломов. Для того чтобы выбрать оптимальную индивидуальную стратегию лечения пациентов, была изучена эффективность стронция ранелата по профилактике переломов в зависимости от исходных уровней маркёров костного метаболизма. Материалы и методы. Проведено 2 двойных слепых плацебо-контролируемых исследования, в которых приняли участие женщины с постменопаузальным остеопорозом. Исследование SOTI (n=1649) было сконцентрировано на эффективности по предотвращению переломов позвоночника, а TROPOS (n=5091) на эффективности по предотвращению переломов других локализаций, случайные переломы позвоночника были определены вторичной конечной точкой у пациентов с выполненными рентгенограммами позвоночника (n=3640). В группе у 5082 женщин с повторными рентгеновскими снимками позвоночника и исходными показателями костной щелочной фосфатазы (КЩФ) и сывороточного С-телопептида (CTX), совмещенных из исследований SOTI и TROPOS и стратифицированных по квартилям в зависимости от исходного показателя минеральной плотности костной ткани, сравнивался риск новых переломов. Результаты. В исследуемых группах исходные характеристики были сходными (возраст 74,0±6,2 года Т-показатель минеральной плотности костной ткани поясничного отдела позвоночника -3,0±1,6 Т-показатель минеральной плотности костной ткани шейки бедра -3,0±0,7). Через три года лечения в группе стронция ранелата риск новых переломов позвоночника был достоверно ниже по сравнению с группой плацебо вне зависимости от рассматриваемого класса минеральной плотности костной ткани. Снижение риска новых переломов позвоночника по сравнению с плацебо составило 32% (р=0,040) в наименьшей квартили КЩФ (КЩФ14,5 нг/мл). При оценке СТх снижение риска новых переломов позвоночника по сравнению с плацебо составило 36% (р=0,001) в первой квартили (СТх5338 пмоль/л). Эффективность лечения не различалась между квартилями (тест взаимосвязи: р=0,349 для КЩФ и р=0,129 для СТх). Результаты были подтверждены при анализе снижения риска новых переломов у пациентов со значениями как КЩФ, так и СТх в нижней квартили или в высшей квартили по сравнению с плацебо, что составило 33% (р=0,042) и 42% (р=0,007) соответственно. Заключение. Эффективность стронция ранелата по достоверному снижению частоты случайных переломов позвоночника в значительной степени не зависит от исходных уровней биохимических маркёров костного метаболизма, что позволяет предположить, что стронция ранелат является эффективным у женщин с различными уровнями показателей костного обмена и тяжести заболевания.

Published
2007

38. Large-scale evidence for the effect of the COLIA1 Sp1 polymorphism on osteoporosis outcomes: The GENOMOS study (vol 3, pg 223, 2006)

Author

Ralston, SH, Uitterlinden, André, Brandi, ML, Balcells, S, Langdahl, BL, Lips, P, Lorenc, R, Obermayer-Pietsch, B, Scollen, S, Bustamante, M, Husted, LB, Carey, AH, Diez-Perez, A, Dunning, AM, Falchetti, A, Karczmarewicz, E, Kruk, M, van Leeuwen, Hans, van Meurs, Joyce, Mangion, J, McGuigan, FEA, Mellibovsky, L, del Monte, F, Pols, Huib, Reeve, J, Reid, DM, Renner, W, Rivadeneira, Fernando, van Schoor, NM, Sherlock, RE, Ioannidis, JPA, and Internal Medicine

Published
2006

39. Association between TGF-beta and LRP 5 & 6 genetic polymorphisms with fracture risk and bone mineral density in the EPOS study

Author

Kaptoge, S, Scollen, S, Boonen, S, Lyritis, G, Poor, G, Nuti, R, Vaz, AL, Bhalla, A, Benevolenskaya, LI, Jajic, Ivo, Todd, CJ, Cano, RP, Khaw, KT, Armas, JB, Da Silva, JA, Kruk, M, Lorenc, R, Dunning, A, and Reeve, J

Subjects
Association between TGF-beta and LRP 5 & 6 genetic polymorphisms with fracture risk and bone mineral density in the EPOS study, lipids (amino acids, peptides, and proteins)
Abstract

Association between TGF-beta and LRP 5 & 6 genetic polymorphisms with fracture risk and bone mineral density in the EPOS study

Published
2006

41. Low BMD is less predictive than reported falls for future limb fractures in women across Europe: results from the European Prospective Osteoporosis Study

Author

Kaptoge, S Benevolenskaya, LI Bhalla, AK Cannata, JB and Boonen, S Falch, JA Felsenberg, D Finn, JD Nuti, R and Hoszowski, K Lorenc, R Miazgowski, T Jajic, I Lyritis, G and Masaryk, P Naves-Diaz, M Poor, G Reid, DM and Scheidt-Nave, C Stepan, JJ Todd, CJ Weber, K Woolf, AD and Roy, DK Lunt, M Pye, SR O'Neill, TW Silman, AJ and Reeve, J

Abstract

We have previously shown that center- and sex-specific fall rates explained one-third of between-center variation in upper limb fractures across Europe. In this current analysis, our aim was to determine bow much of the between-center variation in fractures could be attributed to repeated falling, bone mineral density (BMD), and other risk factors in individuals, and to compare the relative contributions of centerspecific BMD vs. center-specific fall rates. A clinical history of fracture was assessed prospectively in 2451 men and 2919 women aged 5080 from 20 centers participating in the European Prospective Osteoporosis Study (EPOS) using standardized questionnaires (mean follow-up = 3 years). Bone mineral density (BMD, femoral neck, trochanter, and/or spine) was measured in 2103 men and 2565 women at these centers. Cox regression was used to model the risk of incident fracture as a function of the person-specific covariates: age, BMD, personal fracture history (PFH), family hip fracture history (FAMHIP), time spent walking/cycling, number of ‘all falls’ and falls not causing fracture fracture-free’) during follow-up, alcohol consumption, and body mass index. Center effects were modeled by inclusion of multiplicative gamma-distributed random effects, termed center-shared frailty (CSF), with mean 1 and finite variance theta (theta) acting on the hazard rate. The relative contributions of center-specific fall risk and center-specific BMD on the incidence of limb fractures were evaluated as components of CSF. In women, the risk of any incident nonspine fracture (n = 190) increased with age, PFH, FAMHIP, >= 1 h/day walking/cycling, and number of ‘all falls’ during follow-up (all P < 0.074). ‘Fracture-free’ falls (P = 0.726) and femoral neck BMD did not have a significant effect at the individual level, but there was a significant center-shared frailty effect (theta = 0.271, P - 0.001) that was reduced by 4% after adjusting for mean center BMD and reduced by 19% when adjusted for mean center fall rate. Femoral trochanter BMD was a significant determinant of lower limb fractures (n = 53, P = 0.014) and the center-shared frailty effect was significant for upper limb fractures (theta = 0.27 1, P = 0.011). This upper limb fracture center effect was unchanged after adjusting for mean center BMD but was reduced by 36% after adjusting for center mean fall rates. In men, risk of any nonspine fracture (n = 75) increased with PFH, fall during follow-up (P < 0.026), and with a decrease in trochanteric BMD [RR 1.38 (1.08, 1.79) per 1 SD decrease]. There was no center effect evident (theta = 0.081, P = 0.096). We conclude that BMD alone cannot be validly used to discriminate between the risk of upper limb fractures across populations without taking account of population-specific variations in fall risk and other factors. These variations might reflect shared environmental or possibly genetic factors that contribute quite substantially to the risk of upper limb fractures in women. (c) 2004 Elsevier Inc. All rights reserved.

Published
2005

43. Characteristics of a prevalent vertebral deformity predict subsequent vertebral fracture: results from the European Prospective Osteoporosis Study (EPOS)

Author

Lunt, Mark, O'Neill, Terence W., Felsenberg, Dieter, Reeve, Jonathan, Kanis, John A., Cooper, Cyrus, Silman, Alan J., Armbrecht, G., Gowin, W., Cockerill, W., Finn, J. D., Pye, S., Matthis, C., Raspe, H. H., Banzer, D., Benevolenskaya, L. I., Bhalla, A., Cannata, J. B., Dequeker, J., Eastell, R., Felsch, B., Franke, J., Gennari, C., Havelka, S., Hoszowski, K., Jajic, I., Janott, J., Johnell, O., Lopes Vaz, A., Lorenc, R., Lyritis, G., Masaryk, P., Miazgowski, T., Pols, H. A P, Poor, G., Reid, D. M., Reisinger, W., Scheidt-Nave, C., Stepan, J. J., Todd, C. J., Weber, K., and Woolf, A. D.

Subjects
Male, medicine.medical_specialty, Histology, Physiology, Endocrinology, Diabetes and Metabolism, Osteoporosis, Population, Dentistry, Vertebral deformity, Models, Biological, Sex Factors, Risk Factors, Deformity, Medicine, Humans, Prospective Studies, Prospective study, Risk factor, education, Prospective cohort study, Aged, education.field_of_study, business.industry, Age Factors, Middle Aged, medicine.disease, Incident vertebral fracture, Confidence interval, Surgery, Vertebra, Europe, medicine.anatomical_structure, Relative risk, Spinal Fractures, Female, medicine.symptom, Prediction, business, Population study
Abstract

The presence of a prevalent vertebral deformity increases the risk of a future vertebral fracture. The aim of this study was to determine whether certain characteristics of the prevalent deformity, including its shape and location in the spine, influenced this effect. The 3100 men and 3500 women who took part in this analysis were recruited from population registers for participation in the European Prospective Osteoporosis Study (EPOS). Subjects had lateral thoracic and lumbar spine x-rays at baseline, and again after a mean interval of 3.8 years. Prevalent morphometric vertebral deformities on the baseline film were identified by the McCloskey-Kanis method. Incident fractures were defined as vertebrae that also satisfied the McCloskey-Kanis criterion for prevalent deformities on the follow-up film, and in addition had at least one height (anterior, mid, or posterior) which had reduced by at least 20% between films. Poisson regression was used to assess the association between various characteristics of the prevalent deformity and the risk of an incident vertebral fracture, with generalised estimating equations used to allow for the fact that each subject contributed several vertebrae to the analysis. The risk of an incident fracture increased with the number of prevalent deformities: relative risk (RR) for one prevalent deformity 3.2 (95% confidence interval (CI); 2.1, 4.8); 9.8 (95% CI;6.1, 15.8) for 2; and 23.3 (95% CI;15.3, 35.4) for 3 or more. Relative risks differed significantly according to the shape of the prevalent deformity, ranging from 5.9 (95% CI; 4.1, 8.6) if the anterior and mid heights were reduced to 1.6 (95% CI;0.8, 3.2) if the posterior and mid heights were reduced. Risks varied also according to the severity of the deformity. There were fivefold differences in relative risk of incident fracture depending on the location of the prevalent deformity within the spine. Compared to vertebrae in subjects with no deformities at baseline, the relative risk of an incident fracture within three vertebrae of a prevalent deformity was greater (7.7 (95% CI;5.6, 10.5)) than the risk in more distant vertebrae (4.0 (95% CI;2.6, 6.0)). In summary, the risk of a subsequent vertebral fracture in individuals with preexisting deformities is importantly influenced by the characteristics of these deformities. © 2003 Elsevier Inc. All rights reserved.

Published
2003

44. Determinants of incident vertebral fracture in men and women: Results from the European Prospective Osteoporosis Study (EPOS)

Author

Roy, D.K. O'Neill, T.W. Finn, J.D. Lunt, M. Silman, A.J. Felsenberg, D. Armbrecht, G. Banzer, D. Benevolenskaya, L.I. Bhalla, A. Armas, J.B. Cannata, J.B. Cooper, C. Dequeker, J. Diaz, M.N. Eastell, R. Yershova, O.B. Felsch, B. Gowin, W. Havelka, S. Hoszowski, K. Ismail, A.A. Jajic, I. Janott, I. Johnell, O. Kanis, J.A. Kragl, G. Vaz, A.L. Lorenc, R. Lyritis, G. Masaryk, P. Matthis, C. Miazgowski, T. Gennari, C. Pols, H.A.P. Poor, G. Raspe, H.H. Reid, D.M. Reisinger, W. Scheidt-Nave, C. Stepan, J.J. Todd, C.J. Weber, K. Woolf, A.D. Reeve, J.

Abstract

The aim of this analysis was to determine the influence of lifestyle, anthropometric and reproductive factors on the subsequent risk of incident vertebral fracture in men and women aged 50-79 years. Subjects were recruited from population registers from 28 centers across Europe. At baseline, they completed an interviewer-administered questionnaire and had lateral thoraco-lumbar spine radiographs performed. Repeat spinal radiographs were performed a mean of 3.8 years later. Incident vertebral fractures were defined morphometrically and also qualitatively by an experienced radiologist. Poisson regression was used to determine the influence of the baseline risk factor variables on the occurrence of incident vertebral fracture. A total of 3173 men (mean age 63.1 years) and 3402 women (mean age 62.2 years) contributed data to the analysis. In total there were 193 incident morphometric and 224 qualitative fractures. In women, an age at menarche 16 years or older was associated with an increased risk of vertebral fracture (RR = 1.80; 95%CI 1.24, 2.63), whilst use of hormonal replacement was protective (RR=0.58; 95%CI 0.34, 0.99). None of the lifestyle factors studied including smoking, alcohol intake, physical activity or milk consumption showed any consistent associations with incident vertebral fracture. In men and women, increasing body weight and body mass index were associated with a reduced risk of vertebral fracture though, apart from body mass index in men, the confidence intervals embraced unity. For most variables the strengths of the associations observed were similar using the qualitative and morphometric approaches to fracture definition. In conclusion our data suggest that modification of other lifestyle risk factors is unlikely to have a major impact on the population occurrence of vertebral fractures. The important biological mechanisms underlying vertebral fracture risk need to be explored using new investigational strategies.

Published
2003

45. Improving risk assessment: Hip geometry, bone mineral distribution and bone strength in hip fracture cases and controls. The EPOS study

Author

Crabtree, NJ Kroger, H Martin, A Pols, HAP Lorenc, R and Nijs, J Stepan, JJ Falch, JA Miazgowski, T Grazio, S and Raptou, P Adams, J Collings, A Khaw, KT Rushton, N and Lunt, M Dixon, AK Reeve, J

Subjects
musculoskeletal diseases
Abstract

Hip geometry and bone mineral density (BMD) have previously been shown to relate independently to hip fracture risk. Our objective was to determine by how much hip geometric data improved the identification of hip fracture. Lunar pencil beam scans of the proximal femur were obtained. Geometric and densitometric values from 800 female controls aged 60 years or more (from population samples which were participants in the European Prospective Osteoporosis Study. EPOS) were compared with data from 68 female hip fracture patients aged over 60 years who were scanned within 4 weeks of a contralateral hip fracture. We used Lunar DPX ‘beta’ versions of hip strength analysis (HSA) and hip axis length (HAL) applied to DPX(L) data. Compressive stress (Cstress), calculated by the HSA software to occur as a result of a typical fall on the greater trochanter. HAL, body mass index (BMI: weight/(height)) and age were considered alongside femoral neck BMD (FN-BMD, g/cm(2)) as potential predictors of fracture. Logistic regression was used to generate predictors of fracture initially from FN-BMD. Next age, Cstress (as the most discriminating HSA-derived parameter), HAL and BMI were added to the model as potentially independent predictors. It was not necessary to include both HAL and Cstress in the logistic models. so the entire data set was examined without excluding the subjects missing HAL measurements. Cstress combined with age and BMI provided significantly better prediction of fracture than FN-BMD used alone as is current practice, judged by comparing areas under receiver operating characteristic (ROC) curves (p

Published
2002

46. The relationship between bone density and incident vertebral fracture in men and women

Author

O'Neill T.W., Cooper C., Lunt, M., Silman, A.J., Felsenberg, D., Benevolenskaya, L.I., Bhalla, A.K., Cannata, J.B., Crabtree, N., Dequeker, J., Hoszowski, K., Jajic, Ivo, Kanis, J.A., Kragl, G., Lopes, Vaz A., Lorenc, R., Lyritis, G., Masaryk, P., Miazgowski, T., Parisi, G., Pols, H.A.P., Poor, G., Reid, D.M., Scheidt-Nave, C., Stepan, J., Todd, C., Weber, K., Woolf, A.D. and Reeve, and J. EPOS Study Group.

Subjects
The relationship between bone density and incident vertebral fracture in men and women
Abstract

The relationship between bone density and incident vertebral fracture in men and women

Published
2002

47. Incidence of limb fracture across Europe: Results from the European Prospective Osteoporosis Study (EPOS)

Author

Ismail, AA Pye, SR Cockerill, WC Lunt, M Silman, AJ and Reeve, J Banzer, D Benevolenskaya, LI Bhalla, A Armas, JB Cannata, JB Cooper, C Delmas, PD Dequeker, J and Dilsen, G Falch, JA Felsch, B Felsenberg, D Finn, JD and Gennari, C Hoszowski, K Jajic, I Janott, J Johnell, O and Kanis, JA Kragl, G Vaz, AL Lorenc, R Lyritis, G and Marchand, F Masaryk, P Matthis, C Miazgowski, T and Naves-Diaz, M Pols, HAP Poor, G Rapado, A Raspe, HH and Reid, DM Reisinger, W Scheidt-Nave, C Stepan, J Todd, C and Weber, K Woolf, AD O'Neill, TW

Abstract

The aim of this population-based prospective study was to determine the incidence of limb fracture by site and gender in different regions of Europe. Men and women aged 50-79 years were recruited from population registers in 31 European centers. Subjects were invited to attend for an interviewer-administered questionnaire and lateral spinal radiographs. Subjects were subsequently followed up using an annual postal questionnaire which included questions concerning the occurrence of new fractures. Self-reported fractures were confirmed where possible by radiograph, attending physician or subject interview. There were 6451 men and 6936 women followed for a median of 3.0 years. During this time there were 140 incident limb fractures in men and 391 in women. The age-adjusted incidence of any limb fracture was 7,3/1000 person-years [pyrs] in men and 19 per 1000 pyrs in women, equivalent to a 2,5 times excess in women. Among women, the incidence of hip, humerus and distal forearm fracture, though not ‘other’ limb fracture, increased with age, while in men only the incidence of hip and humerus fracture increased with age. Among women, there was evidence of significant variation in the occurrence of hip, distal forearm and humerus fractures across Europe, with incidence rates higher in Scandinavia than in other European regions. though for distal forearm fracture the incidence in east Europe was similar to that observed in Scandinavia. Among men, there was no evidence of significant geographic variation in the occurrence of these fractures. This is the first large population-based study to characterize the incidence of limb fracture in men and women over 50 years of age across Europe. There are substantial differences in the descriptive epidemiology of limb fracture by region and gender.

Published
2002

48. Genome-wide meta-analysis identifies 56 bone mineral density loci and reveals 14 loci associated with risk of fracture

Author

Estrada Gil, K. (Karol), Styrkarsdottir, U. (Unnur), Evangelou, E. (Evangelos), Hsu, Y.-H. (Yi-Hsiang), Duncan, E.L. (Emma), Ntzani, E.E. (Evangelia), Oei, L. (Ling), Albagha, O.M.E. (Omar M.), Amin, N. (Najaf), Kemp, J.P. (John), Koller, D.L. (Daniel), Li, G. (Guo), Liu, C.-T. (Ching-Ti), Minster, R.L. (Ryan), Moayyeri, A. (Alireza), Vandenput, L. (Liesbeth), Willner, D. (Dana), Xiao, S.-M. (Su-Mei), Yerges-Armstrong, L.M. (Laura), Zheng, H.-F. (Hou-Feng), Alonso, N. (Nerea), Eriksson, J. (Joel), Kammerer, C.M. (Candace), Kaptoge, S. (Stephen), Leo, P.J. (Paul), Thorleifsson, G. (Gudmar), Wilson, S.G. (Scott), Wilson, J.F. (James), Aalto, V. (Ville), Alen, T.A. (Theo) van, Aragaki, A.K. (Aaron), Aspelund, T. (Thor), Center, J.R. (Jacqueline), Dailiana, Z. (Zoe), Duggan, C., Garcia, M. (Melissa), Garcia-Giralt, N. (Natàlia), Giroux, S. (Sylvie), Hallmans, G. (Göran), Hocking, L.J. (Lynne), Husted, L.B. (Lise Bjerre), Jameson, K. (Karen), Khusainova, R. (Rita), Kim, G.S. (Ghi Su), Kooperberg, C. (Charles), Koromila, T. (Theodora), Kruk, M. (Marcin), Laaksonen, M. (Marika), LaCroix, A.Z. (Andrea), Lee, S.U. (Seung), Leung, P.C. (Ping), Lewis, J.R. (Joshua), Masi, L. (Laura), Mencej-Bedrac, S. (Simona), Nguyen, T.V. (Tuan), Nogues, X. (Xavier), Patel, M.S. (Millan), Prezelj, J. (Janez), Rose, L.M. (Lynda), Scollen, S. (Serena), Siggeirsdottir, K. (Kristin), Smith, A.V. (Davey), Svensson, O. (Olle), Trompet, S. (Stella), Trummer, O. (Olivia), Schoor, N.M. (Natasja) van, Woo, M.M. (Margaret M.), Zhu, K. (Kun), Balcells, S. (Susana), Brandi, M.L., Buckley, B.M. (Brendan M.), Cheng, S. (Sulin), Christiansen, C., Cooper, C. (Charles), Dedoussis, G.V. (George), Ford, I. (Ian), Frost, M. (Morten), Goltzman, D. (David), González-Macías, J. (Jesús), Kähönen, M. (Mika), Karlsson, M. (Magnus), Khusnutdinova, E.K. (Elza), Koh, J.-M. (Jung-Min), Kollia, P. (Panagoula), Langdahl, B.L. (Bente), Leslie, W.D. (William), Lips, P. (Paul), Ljunggren, O. (Östen), Lorenc, R. (Roman), Marc, J. (Janja), Mellström, D. (Dan), Obermayer-Pietsch, B. (Barbara), Olmos, D. (David), Pettersson-Kymmer, U. (Ulrika), Reid, D.M. (David), Riancho, J.A. (José), Ridker, P.M. (Paul), Rousseau, M.F. (Francois), Slagboom, P.E. (Eline), Tang, N.L.S. (Nelson L.), Urreizti, R. (Roser), Van Hul, W. (Wim), Viikari, J. (Jorma), Zarrabeitia, M.T. (María), Aulchenko, Y.S. (Yurii), Castaño Betancourt, M.C. (Martha), Grundberg, E. (Elin), Herrera, L. (Lizbeth), Ingvarsson, T. (Torvaldur), Johannsdottir, H. (Hrefna), Kwan, T. (Tony), Li, R. (Rui), Luben, R.N. (Robert), Medina-Gomez, M.C. (Carolina), Palsson, S.T. (Stefan), Reppe, S. (Sjur), Rotter, J.I. (Jerome), Sigurdsson, G. (Gunnar), Meurs, J.B.J. (Joyce) van, Verlaan, D.J. (Dominique), Williams, F.M. (Frances), Wood, A.R. (Andrew), Zhou, Y. (Yanhua), Gautvik, K.M. (Kaare), Pastinen, T. (Tomi), Raychaudhuri, S. (Soumya), Cauley, J.A. (Jane), Chasman, D.I. (Daniel), Clark, G.R. (Graeme), Cummings, S., Danoy, P. (Patrick), Dennison, E.M. (Elaine), Eastell, R. (Richard), Eisman, J.A. (John), Gudnason, V. (Vilmundur), Hofman, A. (Albert), Jackson, R.D. (Rebecca), Jones, G. (Graeme), Jukema, J.W. (Jan Wouter), Khaw, K-T. (Kay-Tee), Lehtimäki, T. (Terho), Liu, Y. (YongMei), Lorentzon, M. (Mattias), McCloskey, E.V. (Eugene), Mitchell, B.D. (Braxton), Nandakumar, K. (Kannabiran), Nicholson, G.C. (Geoffrey), Oostra, B.A. (Ben), Peacock, M. (Munro), Pols, H.A.P. (Huib), Prince, R.L. (Richard), Raitakari, O. (Olli), Reid, I.R. (Ian), Robbins, J. (John), Sambrook, P.N. (Philip), Sham, P.C. (Pak), Shuldiner, A.R. (Alan), Tylavsky, F.A. (Frances), Duijn, C.M. (Cornelia) van, Wareham, N.J. (Nick), Cupples, L.A. (Adrienne), Econs, M.J. (Michael), Evans, D.M. (David), Harris, T.B. (Tamara), Kung, A.W.C. (Annie), Psaty, B.M. (Bruce), Reeve, J. (Jonathan), Spector, T.D. (Timothy), Streeten, E.A. (Elizabeth), Zillikens, M.C. (Carola), Thorsteinsdottir, U. (Unnur), Ohlsson, C. (Claes), Karasik, D. (David), Richards, J.B. (Brent), Brown, M.A. (Matthew), Zwart, J-A. (John-Anker), Uitterlinden, A.G. (André), Ralston, S.H. (Stuart), Ioannidis, J.P.A. (John), Kiel, D.P. (Douglas), Rivadeneira Ramirez, F. (Fernando), Estrada Gil, K. (Karol), Styrkarsdottir, U. (Unnur), Evangelou, E. (Evangelos), Hsu, Y.-H. (Yi-Hsiang), Duncan, E.L. (Emma), Ntzani, E.E. (Evangelia), Oei, L. (Ling), Albagha, O.M.E. (Omar M.), Amin, N. (Najaf), Kemp, J.P. (John), Koller, D.L. (Daniel), Li, G. (Guo), Liu, C.-T. (Ching-Ti), Minster, R.L. (Ryan), Moayyeri, A. (Alireza), Vandenput, L. (Liesbeth), Willner, D. (Dana), Xiao, S.-M. (Su-Mei), Yerges-Armstrong, L.M. (Laura), Zheng, H.-F. (Hou-Feng), Alonso, N. (Nerea), Eriksson, J. (Joel), Kammerer, C.M. (Candace), Kaptoge, S. (Stephen), Leo, P.J. (Paul), Thorleifsson, G. (Gudmar), Wilson, S.G. (Scott), Wilson, J.F. (James), Aalto, V. (Ville), Alen, T.A. (Theo) van, Aragaki, A.K. (Aaron), Aspelund, T. (Thor), Center, J.R. (Jacqueline), Dailiana, Z. (Zoe), Duggan, C., Garcia, M. (Melissa), Garcia-Giralt, N. (Natàlia), Giroux, S. (Sylvie), Hallmans, G. (Göran), Hocking, L.J. (Lynne), Husted, L.B. (Lise Bjerre), Jameson, K. (Karen), Khusainova, R. (Rita), Kim, G.S. (Ghi Su), Kooperberg, C. (Charles), Koromila, T. (Theodora), Kruk, M. (Marcin), Laaksonen, M. (Marika), LaCroix, A.Z. (Andrea), Lee, S.U. (Seung), Leung, P.C. (Ping), Lewis, J.R. (Joshua), Masi, L. (Laura), Mencej-Bedrac, S. (Simona), Nguyen, T.V. (Tuan), Nogues, X. (Xavier), Patel, M.S. (Millan), Prezelj, J. (Janez), Rose, L.M. (Lynda), Scollen, S. (Serena), Siggeirsdottir, K. (Kristin), Smith, A.V. (Davey), Svensson, O. (Olle), Trompet, S. (Stella), Trummer, O. (Olivia), Schoor, N.M. (Natasja) van, Woo, M.M. (Margaret M.), Zhu, K. (Kun), Balcells, S. (Susana), Brandi, M.L., Buckley, B.M. (Brendan M.), Cheng, S. (Sulin), Christiansen, C., Cooper, C. (Charles), Dedoussis, G.V. (George), Ford, I. (Ian), Frost, M. (Morten), Goltzman, D. (David), González-Macías, J. (Jesús), Kähönen, M. (Mika), Karlsson, M. (Magnus), Khusnutdinova, E.K. (Elza), Koh, J.-M. (Jung-Min), Kollia, P. (Panagoula), Langdahl, B.L. (Bente), Leslie, W.D. (William), Lips, P. (Paul), Ljunggren, O. (Östen), Lorenc, R. (Roman), Marc, J. (Janja), Mellström, D. (Dan), Obermayer-Pietsch, B. (Barbara), Olmos, D. (David), Pettersson-Kymmer, U. (Ulrika), Reid, D.M. (David), Riancho, J.A. (José), Ridker, P.M. (Paul), Rousseau, M.F. (Francois), Slagboom, P.E. (Eline), Tang, N.L.S. (Nelson L.), Urreizti, R. (Roser), Van Hul, W. (Wim), Viikari, J. (Jorma), Zarrabeitia, M.T. (María), Aulchenko, Y.S. (Yurii), Castaño Betancourt, M.C. (Martha), Grundberg, E. (Elin), Herrera, L. (Lizbeth), Ingvarsson, T. (Torvaldur), Johannsdottir, H. (Hrefna), Kwan, T. (Tony), Li, R. (Rui), Luben, R.N. (Robert), Medina-Gomez, M.C. (Carolina), Palsson, S.T. (Stefan), Reppe, S. (Sjur), Rotter, J.I. (Jerome), Sigurdsson, G. (Gunnar), Meurs, J.B.J. (Joyce) van, Verlaan, D.J. (Dominique), Williams, F.M. (Frances), Wood, A.R. (Andrew), Zhou, Y. (Yanhua), Gautvik, K.M. (Kaare), Pastinen, T. (Tomi), Raychaudhuri, S. (Soumya), Cauley, J.A. (Jane), Chasman, D.I. (Daniel), Clark, G.R. (Graeme), Cummings, S., Danoy, P. (Patrick), Dennison, E.M. (Elaine), Eastell, R. (Richard), Eisman, J.A. (John), Gudnason, V. (Vilmundur), Hofman, A. (Albert), Jackson, R.D. (Rebecca), Jones, G. (Graeme), Jukema, J.W. (Jan Wouter), Khaw, K-T. (Kay-Tee), Lehtimäki, T. (Terho), Liu, Y. (YongMei), Lorentzon, M. (Mattias), McCloskey, E.V. (Eugene), Mitchell, B.D. (Braxton), Nandakumar, K. (Kannabiran), Nicholson, G.C. (Geoffrey), Oostra, B.A. (Ben), Peacock, M. (Munro), Pols, H.A.P. (Huib), Prince, R.L. (Richard), Raitakari, O. (Olli), Reid, I.R. (Ian), Robbins, J. (John), Sambrook, P.N. (Philip), Sham, P.C. (Pak), Shuldiner, A.R. (Alan), Tylavsky, F.A. (Frances), Duijn, C.M. (Cornelia) van, Wareham, N.J. (Nick), Cupples, L.A. (Adrienne), Econs, M.J. (Michael), Evans, D.M. (David), Harris, T.B. (Tamara), Kung, A.W.C. (Annie), Psaty, B.M. (Bruce), Reeve, J. (Jonathan), Spector, T.D. (Timothy), Streeten, E.A. (Elizabeth), Zillikens, M.C. (Carola), Thorsteinsdottir, U. (Unnur), Ohlsson, C. (Claes), Karasik, D. (David), Richards, J.B. (Brent), Brown, M.A. (Matthew), Zwart, J-A. (John-Anker), Uitterlinden, A.G. (André), Ralston, S.H. (Stuart), Ioannidis, J.P.A. (John), Kiel, D.P. (Douglas), and Rivadeneira Ramirez, F. (Fernando)

Abstract

Bone mineral density (BMD) is the most widely used predictor of fracture risk. We performed the largest meta-analysis to date on lumbar spine and femoral neck BMD, including 17 genome-wide association studies and 32,961 individuals of European and east Asian ancestry. We tested the top BMD-associated markers for replication in 50,933 independent subjects and for association with risk of low-trauma fracture in 31,016 individuals with a history of fracture (cases) and 102,444 controls. We identified 56 loci (32 new) associated with BMD at genome-wide significance (P < 5 × 10 -8). Several of these factors cluster within the RANK-RANKL-OPG, mesenchymal stem cell differentiation, endochondral ossification and Wnt signaling pathways. However, we also discovered loci that were localized to genes not known to have a role in bone biology. Fourteen BMD-associated loci were also associated with fracture risk (P < 5 × 10 -4, Bonferroni corrected), of which six reached P < 5 × 10 -8, including at 18p11.21 (FAM210A), 7q21.3 (SLC25A13), 11q13.2 (LRP5), 4q22.1 (MEPE), 2p16.2 (SPTBN1) and 10q21.1 (DKK1). These findings shed light on the genetic architecture and pathophysiological mechanisms underlying BMD variation and fracture susceptibility.

Published
2012
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49. Does location of vertebral deformity within the spine influence back pain and disability?

Author

Cockerill, W., Ismail, A. A., Cooper, C., Matthis, C., Raspe, H., Silman, A. J., O'Neill, T. W., Agnusdei, D., Bergmann, K., Dequeker, J., Felsenberg, D., Kanis, J. A., Kruskemper, G., Weiland, E., Kaldis, L., Mews, J., Finn, D., Lauermann, T., Weber, K., Geusens, P., Jajic, I., Havelka, S., Vavrincova, P., Letkovska, A., Masaryk, P., Delmas, P. D., Marchand, F., Banzer, D., Kirschner, S., Reisinger, W., Janott, J., Schatz, H., Franke, J., Scheidt-Nave, C., Zeigler, R., Abendroth, K., Felsch, B., Antoniou, A., Lyritis, G., Kiss, C., Poor, G., Gennari, C., Ortolani, S., Hofman, A., Pols, H. A P, Falch, J. A., Meyer, H. E., Czekalski, S., Miazgowski, T., Hoszowski, K., Lorenc, R. S., Aroso, A., Lopez Vaz, A., Benevolenskaya, L. I., Mikhailov, E. E., Roig Escofet, D., Ruiz Martin, M., Sosa, M., Diaz Curiel, M., Rapado, A., Cannata Andia, J. B., Diaz Lopez, J. B., Johnell, O., Nilsson, B., Dilsen, G., Reid, D. M., Bhalla, A. K., Ring, F., Todd, C., Williams, R., Reeve, J., Eastell, R., and Woolf, A. D.

Subjects
Male, medicine.medical_specialty, vertebral deformity, back pain, Population, Immunology, Lumbar vertebrae, General Biochemistry, Genetics and Molecular Biology, Thoracic Vertebrae, Lumbar, Sex Factors, Rheumatology, medicine, Deformity, Back pain, Immunology and Allergy, Humans, Functional ability, education, Aged, education.field_of_study, Lumbar Vertebrae, business.industry, Middle Aged, Low back pain, Extended Report, medicine.anatomical_structure, Back Pain, Thoracic vertebrae, Physical therapy, Osteoporosis, Female, Spinal Diseases, medicine.symptom, business
Abstract

Objective - Vertebral deformity is associated with back pain and disability. The aim of tiffs analysis was to determine whether location within the spine influences the strength of association between vertebral deformity, back pain and disability. Methods - Men and women aged 50 years and over were recruited from population registers in 30 European centres. Subjects were invited for an interviewer administered questionnaire, and for lateral spinal radiographs. The questionnaire included questions about back pain, general health and functional ability. The spinal radiographs were evaluated morphometrically and vertebral deformity defined according to the McGloskey-Kanis method. Results - 756 (11.7%) men and 885 (11.8%) women had evidence of one or more vertebral deformities. Among women with a single deformity, after adjusting for age and centre, those with a lumbar deformity were more likely than those with a thoracic deformity to report back pain, both currently (OR = 1.4; 95% CI 1.0, 2.0) and in the past year (OR = 1.5; 95% CI 1.0, 2.3). No association was observed in men. Among women with two deformities, those with adjacent deformities were more likely than those with non-adjacent deformities to report poor general health (OR = 2.2; 95%CI 0.9, 5.6), impaired functional ability (OR = 1.9; 95%CI 0.8, 4.7) and current back pain (OR = 2.1; 95%CI 0.9, 4.9), though none of these associations were statistically significant. By contrast, among men, non-adjacent deformities were associated with impaired functional ability compared with those with adjacent deformities. Conclusions - Location within the spine influences the strength of association between self reported health factors and vertebral deformity.

Published
2000

50. Alendronate treatment of osteoporosis in men

Author

Orwoll, E., Ettinger, M., Weiss, M., Miller, P., Kendler, D., Graham, J., Adami, Silvano, Weber, K., Lorenc, R., Pietschmann, P., Silverman, S., Felsemberg, D., Vandormael, K., Daifotis, A., and Lombardi, A.

Published
2000

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