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Byline: S. Kaptoge (1,32), G. Armbrecht (2), D. Felsenberg (2), M. Lunt (3), K. Weber (4), S. Boonen (5), I. Jajic (6), J. J. Stepan (7), D. Banzer (8), W. Reisinger (9), J. Janott (10), G. Kragl (11), C. Scheidt-Nave (12), B. Felsch (13), C. Matthis (14), H. H. Raspe (14), G. Lyritis (15), G Poor (16), R. Nuti (17), T. Miazgowski (18), K. Hoszowski (19), J. Bruges Armas (20), A. Lopes Vaz (21), L. I. Benevolenskaya (22), P. Masaryk (23), J. B. Cannata (24), O. Johnell (25), D. M. Reid (26), A. Bhalla (27), A. D. Woolf (28), C. J. Todd (29), C. Cooper (30), R. Eastell (31), J. A. Kanis (31), T. W. O'Neill (3), A. J. Silman (3), J. Reeve (1) Keywords: Algorithm; Osteoporosis diagnosis; Osteoporosis treatment; Radiograph; Spine X-ray; Vertebral fracture Abstract: Introduction Vertebral fracture is a strong risk factor for future spine and hip fractures yet recent data suggest that only 5--20% of subjects with a spine fracture are identified in primary care. We aimed to develop easily applicable algorithms predicting a high risk of future spine fracture in men and women over 50 years of age. Methods Data was analysed from 5,561 men and women aged 50+ years participating in the European Prospective Osteoporosis Study (EPOS). Lateral thoracic and lumbar spine radiographs were taken at baseline and at an average of 3.8 years later. These were evaluated by an experienced radiologist. The risk of a new (incident) vertebral fracture was modelled as a function of age, number of prevalent vertebral fractures, height loss, sex and other fracture history reported by the subject, including limb fractures occurring between X-rays. Receiver Operating Characteristic (ROC) curves were used to compare the predictive ability of models. Results In a negative binomial regression model without baseline X-ray data, the risk of incident vertebral fracture significantly increased with age [RR 1.74, 95% CI (1.44, 2.10) per decade], height loss [1.08 (1.04, 1.12) per cm decrease], female sex [1.48 (1.05, 2.09)], and recalled fracture history [1.65 (1.15, 2.38) to 3.03 (1.66, 5.54)] according to fracture site. Baseline radiological assessment of prevalent vertebral fracture significantly improved the areas subtended by ROC curves from 0.71 (0.67, 0.74) to 0.74 (0.70, 0.77) P=0.013 for predicting 1+ incident fracture and from 0.74 (0.67, 0.81) to 0.83 (0.76, 0.90) P=0.001 for 2+ incident fractures. Age, sex and height loss remained independently predictive. The relative risk of a new vertebral fracture increased with the number of prevalent vertebral fractures present from 3.08 (2.10, 4.52) for 1 fracture to 9.36 (5.72, 15.32) for 3+. At a specificity of 90%, the model including X-ray data improved the sensitivity for predicting 2+ and 1+ incident fractures by 6 and 4 fold respectively compared with random guessing. At 75% specificity the improvements were 3.2 and 2.4 fold respectively. With the modelling restricted to the subjects who had BMD measurements (n=2,409), the AUC for predicting 1+ vs. 0 incident vertebral fractures improved from 0.72 (0.66, 0.79) to 0.76 (0.71, 0.82) upon adding femoral neck BMD (P=0.010). Conclusion We conclude that for those with existing vertebral fractures, an accurately read spine X-ray will form a central component in future algorithms for targeting treatment, especially to the most vulnerable. The sensitivity of this approach to identifying vertebral fracture cases requiring anti-osteoporosis treatment, even when X-rays are ordered highly selectively, exceeds by a large margin the current standard of practice as recorded anywhere in the world. Author Affiliation: (1) Department of Medicine & Institute of Public Health, University of Cambridge, Cambridge, UK (2) Department of Radiology Charite, University Medicine Berlin Campus Benjamin Franklin, Berlin, Germany (3) ARC Epidemiology Unit, University of Manchester, Manchester, UK (4) University Hospital, Graz, Austria (5) University Hospital, Leuven, Belgium (6) Clinical Hospital, Zagreb, Croatia (7) Charles University, Prague, Czech-Republic (8) Behring Hospital, Berlin, Germany (9) Humboldt University, Berlin, Germany (10) Ruhr University, Bochum, Germany (11) Medical Academy, Erfurt, Germany (12) University of Heidelberg, Heidelberg, Germany (13) Clinic for Internal Medicine, Jena, Germany (14) Institute of Social Medicine, Lubeck, Germany (15) University of Athens, Athens, Greece (16) National Institute of Rheumatology and Physiotherapy, Budapest, Hungary (17) University of Siena, Siena, Italy (18) University School of Medicine, Szczecin, Poland (19) PKP Hospital, Warsaw, Poland (20) Hospital de Angra do Herismo, SEEBMO, Azores, Portugal (21) Hospital de San Joao, Oporto, Portugal (22) Institute of Rheumatology, Moscow, Russia (23) Institute of Rheumatic Diseases, Piestany, Slovakia (24) Asturia General Hospital, Oviedo, Spain (25) Lund University, Malmo, Sweden (26) University of Aberdeen, Aberdeen, UK (27) Royal National Hospital for Rheumatic Diseases, Bath, UK (28) Royal Cornwall Hospital, Truro, UK (29) School of Nursing, Midwifery and Social Work, University of Manchester, Manchester, UK (30) University of Southampton, Southampton, UK (31) University of Sheffield, Sheffield, UK (32) Strangeways Research Laboratory, Worts Causeway, Cambridge, CB1 8RN, UK Article History: Registration Date: 23/12/2005 Received Date: 18/07/2005 Accepted Date: 22/12/2005 Online Date: 05/07/2006 Article note: This work was presented in part at the 30th European Symposium on Calcified Tissues, 8--12 May 2003, Rome, Italy. A.J. Silman and J. Reeve are the EU Grant holders and Project Leaders.

Byline: T. W. O'Neill (1), W. Cockerill (1), C. Matthis (2), H. H. Raspe (2), M. Lunt (1), C. Cooper (3), D. Banzer (4), J. B. Cannata (5), M. Naves (5), B. Felsch (6), D. Felsenberg (7), J. Janott (8), O. Johnell (9), J. A. Kanis (10), G. Kragl (11), A. Lopes Vaz (12), G. Lyritis (13), P. Masaryk (14), G. Poor (15), D. M. Reid (16), W. Reisinger (17), C. Scheidt-Nave (18), J. J. Stepan (19), C. J. Todd (20), A. D. Woolf (21), J. Reeve (22), A. J. Silman (1) Keywords: Back pain; Disability; Prospective study; Vertebral fracture Abstract: Vertebral fractures are associated with back pain and disability. There are, however, few prospective data looking at back pain and disability following identification of radiographic vertebral fracture. The aim of this analysis was to determine the impact of radiographically identified vertebral fracture on the subsequent occurrence of back pain and disability. Women aged 50 years and over were recruited from population registers in 18 European centers for participation in the European Prospective Osteoporosis Study. Participants completed an interviewer-administered questionnaire which included questions about back pain in the past year and various activities of daily living, and they had lateral spine radiographs performed. Participants in these centers were followed prospectively and had repeat spine radiographs performed a mean of 3.7 years later. In addition they completed a questionnaire with the same baseline questions concerning back pain and activities of daily living. The presence of prevalent and incident vertebral fracture was defined using established morphometric criteria. The data were analyzed using logistic regression with back pain or disability (present or absent) at follow-up as the outcome variable with adjustment made for the baseline value of the variable. The study included 2,260 women, mean age 62.2 years. The mean time between baseline and follow-up survey was 5.0 years. Two hundred and forty participants had prevalent fractures at the baseline survey, and 85 developed incident fractures during follow-up. After adjustment for age, center, and the baseline level of disability, compared with those without baseline prevalent fracture, those with a prevalent fracture (odds ratio [OR]=1.4 95% confidence interval [CI] 1.0 to 2.0) or an incident fracture (OR=1.7 95% CI, 0.9 to 3.2) were more likely to report disability at follow-up, though the confidence intervals embraced unity. Those with both a prevalent and incident fracture, however, were significantly more likely to report disability at follow-up (OR=3.1 95% CI, 1.4 to 7.0). After adjustment for age, center, and frequency of back pain at baseline, compared with those without baseline vertebral fracture, those with a prevalent fracture were no more likely to report back pain at follow-up (OR=1.2 95%CI, 0.8 to 1.7). There was a small increased risk among those with a preexisting fracture who had sustained an incident fracture during follow-up (OR=1.6 95%CI, 0.6 to 4.1) though the confidence intervals embraced unity. In conclusion, although there was no significant increase in the level of back pain an average of 5 years following identification of radiographic vertebral fracture, women who suffered a further fracture during follow-up experienced substantial levels of disability with impairment in key physical functions of independent living. Author Affiliation: (1) ARC Epidemiology Research Unit, University of Manchester, Manchester, M13 9PT, UK (2) Institute for Social Medicine, Medical University of Lubeck, Lubeck, Germany (3) MRC Environmental Epidemiology Unit, Southampton General Hospital, Southampton, UK (4) Department of Radiology, Behring Hospital, Berlin, Germany (5) Asturia General Hospital, Oviedo, Spain (6) Clinic for Internal Medicine, Jena, Germany (7) Department of Radiology and Nuclear Medicine, Free University, Berlin, Germany (8) Ruhr University, Bochum, Germany (9) Department of Orthopedics, Lund University, Malmo, Sweden (10) Centre for Metabolic Bone Disease, Sheffield, UK (11) Medical Academy, Erfurt, Germany (12) Hospital de San Joao, Oporto, Portugal (13) Laboratory for the Research of Musculoskeletal System, University of Athens, Athens, Greece (14) Institute of Rheumatic Diseases, Piestany, Slovakia (15) National Institute of Rheumatology and Physiotherapy, Budapest, Hungary (16) Department of Medicine and Therapeutics, University of Aberdeen, Aberdeen, UK (17) Institute for Diagnostic Radiology, Humboldt University, Berlin, Germany (18) Department of General Practice, University of Goettingen, Goettingen, Germany (19) Department of Medicine, Charles University, Prague, Czech Republic (20) School of Nursing, Midwifery and Health Visiting, University of Manchester, Manchester, UK (21) Department of Rheumatology, Royal Cornwall Hospital, Truro, UK (22) University Department of Medicine and Institute of Public Health, Cambridge, UK Article History: Registration Date: 12/02/2004 Received Date: 27/11/2003 Accepted Date: 11/02/2004 Online Date: 12/05/2004

Byline: W. Cockerill (1), M. Lunt (1), A. J. Silman (1), C. Cooper (2), P. Lips (3), A. K. Bhalla (4), J. B. Cannata (5), R. Eastell (6), D. Felsenberg (7), C. Gennari (8), O. Johnell (9), J. A. Kanis (10), C. Kiss (11), P. Masaryk (12), M. Naves (5), G. Poor (11), H. Raspe (13), D. M. Reid (14), J. Reeve (15), J. Stepan (16), C. Todd (17), A. D. Woolf (18), T. W. O'Neill (1) Keywords: Health impact; Osteoporosis; Quality of life; Vertebral fracture Abstract: Background: Vertebral fractures are associated with back pain and disability however, relatively little is known about the impact of radiographic vertebral fractures on quality of life in population samples. The aim of this study was to determine the impact of a recent radiographic vertebral fracture on health-related quality of life (HRQoL). Methods: Men and women aged 50 years and over were recruited from population registers in 12 European centers. Subjects completed an interviewer-administered questionnaire and had lateral spine radiographs performed. Subjects in these centers were followed prospectively and had repeat spinal radiographs performed a mean of 3.8 years later. Prevalent deformities were defined using established morphometric criteria, and incident vertebral fractures by both morphometric criteria and qualitative assessment. For each incident fracture case, three controls matched for age, gender, and center were selected: one with a prevalent deformity (at baseline) and two without prevalent deformities. All subjects were interviewed or completed a postal questionnaire instrument which included Short Form 12 (SF-12), the EQ-5D (former EuroQol), and the quality of life questionnaire of the International Osteoporosis Foundation (QUALEFFO). The median time from the second spinal radiograph until the quality of life survey was 1.9 years. Comparison between cases and their matched controls was undertaken using the signed rank test. Results: 73 subjects with incident vertebral fracture (cases), mean age 64.8 years (of whom 23 had a baseline deformity), and 196 controls, mean age 63.9 years (of whom 60 had a baseline deformity), were studied. There were strong correlations between the domain scores for each of the three instruments. There was no statistically significant difference in any of the domain scores between cases and those controls with a prevalent deformity. However, compared with the controls without a prevalent deformity the cases had significantly impaired quality of life as determined using the total QUALEFFO score (38.2 vs 33.7), the physical component score of the SF-12 (39.9 vs 43.7) and the health status score of the EQ-5D (62.3 vs 69.9). When the analysis was repeated after stratification of the cases by baseline deformity status (i.e., cases with and without a prevalent deformity at baseline), cases with a prevalent deformity had impaired quality of life compared with their matched controls, both with and without a prevalent deformity. In contrast there was no significant difference in quality of life among the cases without a prevalent deformity and either control group. Conclusion: In this population-based study a recent vertebral fracture was associated with impairment in quality of life, though this was mainly among those who had sustained a previous vertebral deformity. Author Affiliation: (1) ARC Epidemiology Research Unit, University of Manchester, Stopford Building, Manchester, M13 9PT, UK (2) MRC Environmental Epidemiology Unit, Southampton General Hospital, Southampton, UK (3) Department of Endocrinology, Academic Hospital, Vrije Universiteit, Amsterdam, The Netherlands (4) Royal National Hospital for Rheumatic Diseases, Bath, UK (5) Asturia General Hospital, Oviedo, Spain (6) Bone Metabolism Group, Northern General Hospital, Sheffield, UK (7) Department of Radiology and Nuclear Medicine, Free University, Berlin, Germany (8) Institute of Clinical Medicine, University of Siena, Siena, Italy (9) Department of Orthopedics, Lund University, Malmo, Sweden (10) Centre for Metabolic Bone Disease, Sheffield, UK (11) National Institute of Rheumatology and Physiotherapy, Budapest, Hungary (12) Institute of Rheumatic Diseases, Piestany, Slovakia (13) Institute of Social Medicine, Lubeck, Germany (14) Department of Medicine and Therapeutics, University of Aberdeen, Aberdeen, UK (15) Institute of Public Health, Cambridge, UK (16) Institute of Rheumatology, Charles University, Prague, Czech Republic (17) Department of Nursing, Midwifery and Health Visiting, University of Manchester, Manchester, UK (18) Department of Rheumatology, Royal Cornwall Hospital, Truro, UK Article History: Registration Date: 16/10/2003 Received Date: 26/08/2002 Accepted Date: 15/10/2003 Online Date: 13/11/2003

Byline: M. Naves (1), J. B. Diaz-Lopez (1), C. Gomez (1), A. Rodriguez-Rebollar (1), M. Rodriguez-Garcia (1), J. B. Cannata-Andia (1) Keywords: Incidence; Mortality; Osteoporosis; Prevalence; Vertebral fracture Abstract: There is little data concerning the morbidity, mortality, and epidemiology of vertebral fracture. The aim of this study was to evaluate the effect of prevalent and incident vertebral fractures as risk factors for further osteoporotic fractures and mortality. The study was performed on a cohort of 316 women and 308 men older than 50 belonging to the EVOS study, randomly selected from our city register. At the beginning of the study and 4 years later, lateral dorsal and lumbar X-rays were performed. In addition, evaluation of the incidence of osteoporotic nonvertebral fractures was performed throughout 8 years. The incidence of all osteoporotic fractures was higher in women than in men (two-fold increase in vertebral fracture incidence and five-fold increase in Colles' and femur incidence). Vertebral fracture was a strong risk factor for a new vertebral fracture [RR=4.7 (1.8--11.9)], hip fracture [RR=6.7 (2.0--22.7)] and Colles' fracture [RR=3.0 (1.1--7.8)]. Prevalent and incident vertebral fractures were associated with a higher risk of having a hip fracture [RR=10.0 (2.0--50.2)] and Colles' fracture [RR=5.5 (1.3--23.4)]. In addition, in women, the vertebral fracture was associated with a higher mortality. By contrast, no association was found in men. These results demonstrate the association between a previous vertebral fracture with increments in the incidence of osteoporotic fractures of any type. In addition, we found a significantly higher mortality rate in women having vertebral fractures. These findings support the necessity of preventing the occurrence of vertebral fractures to limit their strong negative impact on mortality. Author Affiliation: (1) Bone and Mineral Research Unit, Instituto Reina Sofia de Investigacion, Hospital Universitario Central de Asturias, Universidad de Oviedo, 33006, Oviedo , Spain Article History: Received Date: 18/10/2002 Accepted Date: 12/02/2003 Online Date: 25/04/2003

Byline: D.K. Roy (2), T.W. O'Neill (2), J.D. Finn (2), M. Lunt (2), A.J. Silman (2), D. Felsenberg (3), G. Armbrecht (3), D. Banzer (4), L.I. Benevolenskaya (5), A. Bhalla (6), J. Bruges Armas (7), J.B. Cannata (8), C. Cooper (9), J. Dequeker (10), M.N. Diaz (8), R. Eastell (11), O.B. Yershova (12), B. Felsch (13), W. Gowin (3), S. Havelka (14), K. Hoszowski (15), A.A. Ismail (2), I. Jajic (16), I. Janott (17), O. Johnell (18), J.A. Kanis (19), G. Kragl (20), A. Lopez Vaz (21), R. Lorenc (22), G. Lyritis (23), P. Masaryk (24), C. Matthis (25), T. Miazgowski (26), C. Gennari (27), H.A.P. Pols (28), G. Poor (29), H.H. Raspe (25), D.M. Reid (30), W. Reisinger (31), C. Scheidt-Nave (32), J.J. Stepan (14), C.J. Todd (33), K. Weber (34), A.D. Woolf (35), J. Reeve (36) Keywords: KeywordsaIncident vertebral fracture; Osteoporosis; Prospective study; Risk factors Abstract: aThe 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. Author Affiliation: (1) ARC Epidemiology Unit, Stopford Building, University of Manchester, Manchester, M13 9PT, UK Tel: +44 (0)161 2755040 Fax: +44 (0)161 2755043 e-mail: Terry@fs1.ser.man.ac.uk, GB (2) ARC Epidemiology Unit, University of Manchester, Manchester, UK, GB (3) Department of Radiology and Nuclear Medicine, Free University, Berlin, Germany, DE (4) Behring Hospital, Berlin, Germany, DE (5) Institute of Rheumatology, Moscow, Russia, RU (6) Royal National Hospital for Rheumatic Diseases, Bath, UK, GB (7) Hospital de Angra do Herismo, Azores, Portugal, PT (8) Asturia General Hospital, Oviedo, Spain, ES (9) University of Southampton, Southampton General Hospital, Southampton, UK, GB (10) University Hospital, Leuven, Belgium, BE (11) Bone Metabolism Group, Northern General Hospital, Sheffield, UK, GB (12) Medical Institute, Yaroslavl, Russia, RU (13) Clinic for Internal Medicine, Jena, Germany, DE (14) Department of Internal Medicine, Charles University, Prague, Czech Republic, CZ (15) Medical Centre, Wilenska 18, Warsaw, Poland, PL (16) Clinical Hospital, Zagreb, Croatia, HR (17) Ruhr University, Bochum, Germany, DE (18) Lund University, Malmo, Sweden, SE (19) Centre for Metabolic Bone Disease, University of Sheffield, UK, GB (20) Medical Academy, Erfurt, Germany, DE (21) Hospital de San Joao, Oporto, Portugal, PT (22) The Children's Memorial Health Institute, Warsaw Poland, PL (23) Laboratory for the Research of Musculoskeletal System, University of Athens, Athens, Greece, GR (24) Institute of Rheumatic Diseases, Piestany, Slovakia, SK (25) Institute of Social Medicine, Lubeck, Germany, DE (26) Academy of Medicine, Szczecin, Poland, PL (27) Institute of Clinical Medicine, University of Siena, Siena, Italy, IT (28) Department of Epidemiology and Internal Medicine, Erasmus University, Rotterdam, The Netherlands, NL (29) National Institute of Rheumatology and Physiotherapy, Budapest, Hungary, HU (30) Department of Medicine and Therapeutics, University of Aberdeen, UK, GB (31) Institute for Diagnostic Radiology, Humboldt University, Berlin, Germany, DE (32) Department of General Practice, University of Goettingen, Germany, DE (33) School of Nursing, Midwifery and Health Visiting, University of Manchester, Manchester, UK, GB (34) Department of Medicine, University Hospital, Graz, Austria, AT (35) Royal Cornwall Hospital, Truro, UK, GB (36) Institute of Public Health, Cambridge, UK, GB Article note: Received: 24 May 2002 / Accepted: 27 August 2002 RID='*' ID='*' For full listing of participants, please see appendix RID='*' ID='*' Project co-ordinators AcknowledgementaThe study was financially supported by a European Union Concerted Action Grant under Biomed-1 (BMH1CT920182), and also EU grants C1PDCT925102, ERBC1PDCT 930105 &amp 940229. The central coordination was also supported by the UK Arthritis Research Campaign, the Medical Research Council (G9321536), and the European Foundation for Osteoporosis and Bone Disease. The EU's PECO program linked to BIOMED 1 funded in part the participation of the Budapest, Warsaw, Prague, Piestany, Szczecin and Moscow centers. Data collection from Croatia was supported by a grant from the Wellcome Trust. The central X-ray evaluation was generously sponsored by the Bundesministerium fur Forschung and Technologie, Germany. Individual centers acknowledge the receipt of locally acquired support for their data collection. We would like to thank the following individuals: Aberdeen, UK: Rita Smith Cambridge &amp Harrow, UK: Anna Martin, Judith Walton Truro, UK: Mrs Joanna Parsons Oviedo, Spain : J Bernardino Diaz Lopez, Ana Rodriguez Rebollar.

Byline: A. A. Ismail (1), S. R. Pye (1), W. C. Cockerill (1), M. Lunt (1), A. J. Silman* (1), J. Reeve* (2), D. Banzer (3), L. I. Benevolenskaya (4), A. Bhalla (5), J. Bruges Armas (6), J. B. Cannata (7), C. Cooper (8), P. D. Delmas (9), J. Dequeker (10), G. Dilsen (11), J. A. Falch (12), B. Felsch (13), D. Felsenberg (14), J. D. Finn (1), C. Gennari (15), K. Hoszowski (16), I. Jajic (17), J. Janott (18), O. Johnell (19), J. A. Kanis (20), G. Kragl (21), A. Lopez Vaz (22), R. Lorenc (23), G. Lyritis (24), F. Marchand (25), P. Masaryk (26), C. Matthis (27), T. Miazgowski (28), M. Naves-Diaz (7), H. A. P. Pols (29), G. Poor (30), A. Rapado (31), H. H. Raspe (27), D. M. Reid (32), W. Reisinger (33), C. Scheidt-Nave (34), J. Stepan (35), C. Todd (36), K. Weber (37), A. D. Woolf (38), T. W. O'Neill (1) Keywords: Key words:Epidemiology -- Europe -- Incidence -- Limb fracture -- Osteoporosis 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. Author Affiliation: (1) ARC Epidemiology Unit, University of Manchester, Manchester, UK, GB (2) Strangeways Research Laboratories, Cambridge, UK, GB (3) Behring Hospital, Berlin, Germany, DE (4) Institute of Rheumatology, Moscow, Russia, RU (5) Royal National Hospital for Rheumatic Diseases, Bath, UK, GB (6) Hospital de Angra do Heroismo, Azores, Portugal, PT (7) Asturia General Hospital, Oviedo, Spain, ES (8) University of Southampton, Southampton General Hospital, Southampton, UK, GB (9) U. INSERM 403, Lyon, France, FR (10) University Hospital, Leuven, Belgium, BE (11) Medical Faculty, University of Istanbul, Istanbul, Turkey, TR (12) Aker Hospital, Oslo, Norway, NO (13) Clinic for Internal Medicine, Jena, Germany, DE (14) Department of Radiology and Nuclear Medicine, Free University, Berlin, Germany, DE (15) Institute of Clinical Medicine, University of Siena, Siena, Italy, IT (16) Medical Centre, Warsaw, Poland, PL (17) Clinical Hospital, Zagreb, Croatia, YU (18) Ruhr University, Bochum, Germany, DE (19) Lund University, MalmoA', Sweden, SE (20) Centre for Metabolic Bone Disease, Sheffield, UK, GB (21) Medical Academy, Erfurt, Germany, DE (22) Hospital de San Joao, Oporto, Portugal, PT (23) The Children Memorial Health Institute, Warsaw, Poland, PL (24) Laboratory for the Research of Musculoskeletal System, University of Athens, Athens, Greece, GR (25) Centre de Medecine SpecialiseA'e, Montceau-les-Mines, France, FR (26) Institute of Rheumatic Diseases, Piestany, Slovakia, CS (27) Institute of Social Medicine, Lubeck, Germany, DE (28) Academy of Medicine, Szczecin, Poland, PL (29) Department of Epidemiology and Department of Internal Medicine, Erasmus University, Rotterdam, The Netherlands, NL (30) National Institute of Rheumatology and Physiotherapy, Budapest, Hungary, HU (31) Faculty of Medicine, University of Madrid, Madrid, Spain, ES (32) Department of Medicine and Therapeutics, University of Aberdeen, Aberdeen, UK, GB (33) Institute for Diagnostic Radiology, Humboldt University, Berlin, Germany, DE (34) Institute of Social Medicine, University of Heidelberg, Heidelberg, Germany, DE (35) Department of Internal Medicine, Charles University, Prague, Czech Republic, CS (36) School of Nursing, Midwifery and Health Visiting, University of Manchester, Manchester, UK, GB (37) Department of Medicine, University Hospital, Graz, Austria, AT (38) Department of Rheumatology, Royal Cornwall Hospital, Truro, UK, GB Article note: Received: 23 October 2001 / Accepted: 31 January 2002

Byline: M. Lunt (1), P. Masaryk (2), C. Scheidt-Nave (3), J. Nijs (4), G. Poor (5), H. Pols (6), J. A. Falch (7), G. Hammermeister (8), D. M. Reid (9), L. Benevolenskaya (10), K. Weber (11), J. Cannata (12), T. W. O'Neill (13), D. Felsenberg (8), A. J. Silman (13), J. Reeve (1) Keywords: Key words: Bone density -- Diet calcium -- Epidemiology -- Osteoporosis -- Physical activity -- Smoking Abstract: The risk of low and moderate energy fracture is related to bone mineral density (BMD). Yet it is uncertain whether the epidemiologic determinants of fracture risk are the same as for low bone density. The European Vertebral Osteoporosis Study was a population-based prevalence study of vertebral deformity in 36 age-stratified population samples aged 50--80 years. In nearly 4000 subjects (13 centers), BMD measurements were also made at the spine, femoral neck and femoral trochanter. To investigate whether effects of reported physical activity on spine deformity risk were mediated through BMD, we modeled these and other risk factor data with BMD as the dependent variate after adjusting for age, center, sex and body mass index (BMI). The significant determinants of vertebral deformity risk were also entered into logistic models of deformity risk that included BMD measurements as covariates. Both current and lifetime physical activity were positively associated with BMD. This effect was stronger with hip BMD than with spine BMD. Lifetime smoking exposure was associated with reduced BMD. Type 2 diabetes mellitus was associated with increased BMD. Weak positive associations were found between consumption of dairy products and BMD at the three measured sites and these were strengthened by an interaction with measures of physical activity in men. Physical activity in women had the largest beneficial effect in lean women and in women exposed to hormone replacement therapy. When fracture risk was modeled with BMD as a covariate, the lifestyle and dietary determinants became less strongly related to vertebral deformity risk, suggesting that BMD may have acted as an intermediary variable. However, heavy physical activity in men still increased spine deformity risk after adjusting for BMD. It is concluded that physical activity in both genders and milk consumption in young women might protect against vertebral deformities in later life through their effects on bone density. The adverse effect of smoking on BMD was confirmed. Heavy physical activity in men might increase spine deformity risk even when BMD is normal. Author Affiliation: (1) Institute of Public Health, Cambridge, UK, GB (2) Research Institute for Rheumatic Diseases, Piestany, Slovakia, SK (3) Medizinische Klinik &amp Poliklinik, Heidelberg, Germany, DE (4) Afdeling Reumatologie, Universitaire Ziekenhuizen K U, Leuven, Belgium, BE (5) National Institute of Rheumatology, Budapest, Hungary, HU (6) Erasmus University Medical School, Rotterdam, The Netherlands, HL (7) Aker Hospital, Oslo, Norway, NO (8) Freie Universitat Berlin -- Benjamin Franklin Medical School, Berlin, Germany, DE (9) Rheumatology Department, Aberdeen Royal Infirmary, UK, GB (10) Institute of Rheumatology of R.A.M.S, Moscow, Russia, RU (11) Medizinische Universitatsklinik, Graz, Austria, AT (12) Hospital Central de Asturias, Oviedo, Spain , ES (13) ARC Epidemiology Research Unit, University of Manchester, UK, GB Article note: Received: 29 June 2000 / Accepted: 5 January 2001

Byline: A. A. Ismail (1), W. Cockerill (1), C. Cooper (2), J. D. Finn (1), K. Abendroth (3), G. Parisi (4), D. Banzer (5), L. I. Benevolenskaya (6), A. K. Bhalla (7), J. Bruges Armas (8), J. B. Cannata (9), P. D. Delmas (10), J. Dequeker (11), G. Dilsen (12), R. Eastell (13), O. Ershova (14), J. A. Falch (15), B. Felsch (3), S. Havelka (16), K. Hoszowski (17), I. Jajic (18), U. Kragl (19), O. Johnell (20), A. Lopez Vaz (21), R. Lorenc (17), G. Lyritis (22), F. Marchand (23), P. Masaryk (24), C. Matthis (25), T. Miazgowski (26), H. A. P. Pols (27), G. Poor (28), A. Rapado (29), H. H. Raspe (25), D. M. Reid (30), W. Reisinger (31), J. Janott (32), C. Scheidt-Nave (33), J Stepan (34), C. Todd (35), K. Weber (36), A. D. Woolf (37), G. Ambrecht (38), W. Gowin (38), D. Felsenberg (38), M. Lunt (1), J. A. Kanis (39), J. Reeve (35), A. J. Silman (1), T. W. O'Neill (1) Keywords: Key words: Incidence -- Limb fracture -- Osteoporosis -- Vertebral deformity -- Vertebral osteoporosis Abstract: The presence of a vertebral deformity increases the risk of subsequent spinal deformities. The aim of this analysis was to determine whether the presence of vertebral deformity predicts incident hip and other limb fractures. Six thousand three hundred and forty-four men and 6788 women aged 50 years and over were recruited from population registers in 31 European centers and followed prospectively for a median of 3 years. All subjects had radiographs performed at baseline and the presence of vertebral deformity was assessed using established morphometric methods. Incident limb fractures which occurred during the follow- up period were ascertained by annual postal questionnaire and confirmed by radiographs, review of medical records and personal interview. During a total of 40348 person-years of follow-up, 138 men and 391 women sustained a limb fracture. Amongst the women, after adjustment for age, prevalent vertebral deformity was a strong predictor of incident hip fracture, (rate ratio (RR) = 4.5 95% CI 2.1--9.4) and a weak predictor of 'other' limb fractures (RR = 1.6 95% CI 1.1--2.4), though not distal forearm fracture (RR = 1.0 95% CI 0.6--1.6). The predictive risk increased with increasing number of prevalent deformities, particularly for subsequent hip fracture: for two or more deformities, RR = 7.2 (95% CI 3.0--17.3). Amongst men, vertebral deformity was not associated with an increased risk of incident limb fracture though there was a nonsignificant trend toward an increased risk of hip fracture with increasing number of deformities. In summary, prevalent radiographic vertebral deformities in women are a strong predictor of hip fracture, and to a lesser extent humerus and 'other' limb fractures however, they do not predict distal forearm fractures. Author Affiliation: (1) ARC Epidemiology Unit, University of Manchester, Manchester, UK, GB (2) University of Southampton, Southampton General Hospital, Southampton, UK, GB (3) Clinic for Internal Medicine, Jena, Germany, DE (4) Institute of Clinical Medicine, University of Siena, Siena, Italy, IT (5) Behring Hospital, Berlin, Germany, DE (6) Institute of Rheumatology, Moscow, Russia, RU (7) Royal National Hospital for Rheumatic Diseases, Bath, UK, GB (8) Hospital de Angra do Heroismo, Azores, Portugal, PT (9) Asturia General Hospital, Oviedo, Spain, ES (10) Ho^pital Edouard Herriot, Lyon, France, FR (11) Rheumatology Unit, University Hospital, Leuven, Belgium, BE (12) Medical Faculty, University of Istanbul, Istanbul, Turkey, TR (13) Bone Metabolism Group, Northern General Hospital, Sheffield, UK, GB (14) Medical Institute, Yaroslavl, Russia, RU (15) Aker Hospital, Oslo, Norway, NO (16) Institute of Rheumatology, Prague, Czech Republic, CS (17) PKP Hospital, Warsaw, Poland, PL (18) Clinical Hospital, Zagreb, Croatia, YU (19) Medical Academy, Erfurt, Germany, DE (20) MalmoA' University Hospital, MalmoA', Sweden, SE (21) Hospital de San Joao, Oporto, Portugal, PT (22) Laboratory for the Research of Musculoskeletal System, University of Athens, Athens, Greece, GR (23) Centre de Medecine SpecialiseA'e, Montceau-les-Mines, France, FR (24) Institute of Rheumatic Diseases, Piestany, Slovakia, YU (25) Institute of Social Medicine, Lubeck, Germany, DE (26) Academy of Medicine, Szczecin, Poland, PL (27) Department of Epidemiology and Department of Internal Medicine, Erasmus University, Rotterdam, Netherlands, NL (28) National Institute of Rheumatology and Physiotherapy, Budapest, Hungary, HU (29) Faculty of Medicine, University of Madrid, Madrid, Spain, ES (30) Department of Medicine and Therapeutics, University of Aberdeen, UK, UK (31) Institute for Diagnostic Radiology, Humboldt University, Berlin, Germany, DE (32) Department of Clinical Medicine, Ruhr University, Bochum, Germany, DE (33) Department of Endocrinology, University of Heidelberg, Heidelberg, Germany, DE (34) Department of Internal Medicine, Charles University, Prague, Czech Republic, CZ (35) Institute of Public Health, Cambridge, UK, GB (36) Department of Medicine, University Hospital, Graz, Austria, AT (37) Royal Cornwall Hospital, Truro, UK, GB (38) Department of Radiology and Nuclear Medicine, Free University, Berlin, Germany, DE (39) Centre for Metabolic Bone Disease, Sheffield, UK, GB Article note: Received: 23 February 2000 / Accepted: 11 August 2000

Byline: A. A. Ismail (1), T. W. O'Neill (1), W. Cockerill (1), J. D. Finn (1), J. B. Cannata (1), K. Hoszowski (1), O. Johnell (1), C. Matthis (1), H. Raspe (1), A. Raspe (1), J. Reeve (1), A. J. Silman (1) Keywords: Key words:Fracture -- Manikin -- Osteoporosis -- Questionnaire -- Validation Abstract: In population-based studies of osteoporosis, ascertainment of fractures is typically based on self-report, with subsequent verification by medical records. The aim of this analysis was to assess the validity of self-report of incident nonspine fractures using a postal questionnaire. The degree of overreporting of fracture (false positives) was assessed by comparing self-reports of new fracture from respondents in the multicenter European Prospective Osteoporosis Study with data from other sources including radiographs and medical records. In the analysis, 563 subjects reported nonspine fractures. Verification of the presence of fracture was possible in 510 subjects. Of these, fractures were not confirmed in 11% (false positives). The percentage of false positives was greater in men than in women (15% vs 9%, p=0.04), and less for fractures of the distal forearm and hip than for fractures at other sites. In a separate study, the degree of underreporting (false negatives) was assessed by follow-up of 251 individuals with confirmed fracture ascertained from the records of fracture clinics in three European centers (Lubeck, Oviedo, Warsaw). Questionnaire responses were received from 174 (69%) subjects. Of these, 12 (7%) did not recall sustaining a fracture (false negatives). The percentage of false negatives was lower for hip and distal forearm fractures with only 3 of 90 (3%) such fractures not recalled. Using the combined data from both studies, of those who reported a 'date' of fracture on the questionnaire, 91% of subjects were correct to within 1 month of the actual date of the fracture. A postal questionnaire is a relatively simple and accurate method for obtaining information about the occurrence of hip and distal forearm fractures, including their timing. Accuracy of ascertainment of fractures at other sites is less good and where possible self-reported fractures at such sites should be verified from other sources. Author Affiliation: (1) ARC Epidemiology Unit, Manchester, UK, GB Article note: Received: 22 March 1999 / Accepted: 20 August 1999

Byline: C. Gomez (1), M. L. Naves (1), Y. Barrios (2), J. B. Diaz (1), J. L. Fernandez (1), E. Salido (2), A. Torres (2), J. B. Cannata (1) Keywords: Key words:Bone mass -- Genetic -- Osteoporosis -- Polymorphisms -- Vertebral fractures -- Vitamin D receptor gene Abstract: Bone mineral density (BMD), the major determinant of fracture risk, is under strong genetic control. Although polymorphisms of the vitamin D receptor (VDR) gene have been suggested to account for some of the genetic variation in bone mass, the influence of VDR genotypes on osteoporosis remains controversial. Previous published studies have focused mainly on women, but the pattern of response in men has not been determined. Using the BsmI restriction enzyme, we studied the influence of the different VDR genotypes on bone mass, bone loss and the prevalence of vertebral fractures in a population-based sample of both sexes (n=326). BMD was measured at the lumbar spine and femoral neck, with a 4-year interval, using dual-energy X-ray absorptiometry. Vertebral fractures were assessed by two lateral radiographs at the beginning and end of the study. The prevalence of the three possible VDR genotypes was similar to those in other Caucasian populations and no differences were found between men and women. Women with the favorable bb genotype showed significantly higher BMD values at the lumbar spine and femoral neck, and a positive rate of BMD change at the femoral neck compared with women with the BB and Bb genotypes. Moreover, women with the bb genotype showed a trend toward a lower prevalence and incidence of vertebral fractures (p= 0.07). We have not found any differences between VDR genotypes in men. In conclusion, VDR gene polymorphisms are related to bone mass and bone loss in women also a trend in the prevalence of vertebral fractures was observed in postmenopausal women but not in men. Author Affiliation: (1) Bone and Mineral Research Unit, Instituto Reina Sofia de Investigacion, Hospital Central de Asturias, Oviedo, ES (2) Unidad de Investigacion, Hospital Universitario de Canarias, Tenerife, Spain, ES Article note: Received: 8 June 1998 / Accepted: 7 December 1998

The European Renal Association–European Dialysis and Transplant Association (ERA-EDTA) CKD-MBD working group, in collaboration with the Committee of Scientific Advisors of the International Osteoporosis Foundation, published a position paper for the diagnosis and management of osteoporosis in patients with CKD stages 4–5D (eGFR < 30 ml/min 1.73 m2). The present article reports and summarizes the main recommendations included in this 2021 document. The following areas are reviewed: diagnosis of osteoporosis; risk factors for fragility fractures; fracture risk assessment; intervention thresholds for pharmacological intervention; general and pharmacological management of osteoporosis; monitoring of treatment, and systems of care, all in patients with CKD stages 4–5D. Guidance is provided for clinicians caring for CKD stages 4–5D patients with osteoporosis, allowing for a pragmatic individualized diagnostic and therapeutic approach as an alternative to current variations in care and treatment nihilism. [ABSTRACT FROM AUTHOR]

Autologous and allogeneic hematopoietic stem cell transplantation (HSCT) is the treatment of choice for patients with some malignant and non-malignant hematological diseases. Advances in transplantation techniques and supportive care measures have substantially increased the number of long-term HSCT survivors. This has led to an increasing patient population suffering from the late effects of HSCT, of which, bone loss and its consequent fragility fractures lead to substantial morbidity. Altered bone health, with consequent fragility fractures, and chronic graft-versus-host disease (GVHD) are factors affecting long-term quality of life after HSCT. Hypogonadism, HSCT preparative regimens, nutritional factors, and glucocorticoids all contribute to accelerated bone loss and increased fracture risk. Management strategies should include bone mineral density examination, evaluation of clinical risk factors, and general dietary and physical activity measures. Evidence has accumulated permitting recommendations for more attentiveness to evaluation and monitoring of bone health, with appropriate application of osteoporosis pharmacotherapies to patients at increased risk of bone loss and fracture. [ABSTRACT FROM AUTHOR]

Summary: Osteoporosis represents a significant and increasing healthcare burden in Europe, but most patients at increased risk of fracture do not receive medication, resulting in a large treatment gap. Identification of patients who are at particularly high risk will help clinicians target appropriate treatment more precisely and cost-effectively, and should be the focus of future research. Introduction: The purpose of the study was to review data on the identification and treatment of patients with osteoporosis at increased risk of fracture. Methods: A working group convened by the European Society for Clinical and Economic Aspects of Osteoporosis and Osteoarthritis met to review current data on the epidemiology and burden of osteoporosis and the patterns of medical management throughout Europe. Results: In Europe in 2010, the cost of managing osteoporosis was estimated at €37 billion and notably the costs of treatment and long-term care of patients with fractures were considerably higher than the costs for pharmacological prevention. Despite the availability of effective treatments, the uptake of osteoporosis therapy is low and declining, in particular for secondary fracture prevention where the risk of a subsequent fracture following a first fracture is high. Consequently, there is a significant treatment gap between those who would benefit from treatment and those who receive it, which urgently needs to be addressed so that the burden of disease can be reduced. Conclusions: Implementation of global fracture prevention strategies is a critical need. Future research should focus on identifying specific risk factors for imminent fractures, periods of high fracture risk, patients who are at increased risk of fracture and therapies that are most suited to such high-risk patients and optimal implementation strategies in primary, secondary and tertiary care. [ABSTRACT FROM AUTHOR]

Summary: In 27 centres across Europe, the prevalence of deforming spinal Scheuermann's disease in age-stratified population-based samples of over 10,000 men and women aged 50+ averaged 8 % in each sex, but was highly variable between centres. Low DXA BMD was un-associated with Scheuermann's, helping the differential diagnosis from osteoporosis. Introduction: This study aims to assess the prevalence of Scheuermann's disease of the spine across Europe in men and women over 50 years of age, to quantitate its association with bone mineral density (BMD) and to assess its role as a confounder for the radiographic diagnosis of osteoporotic fracture. Methods: In 27 centres participating in the population-based European Vertebral Osteoporosis Study (EVOS), standardised lateral radiographs of the lumbar and of the thoracic spine from T4 to L4 were assessed in all those of adequate quality. The presence of Scheuermann's disease, a confounder for prevalent fracture in later life, was defined by the presence of at least one Schmorl's node or irregular endplate together with kyphosis (sagittal Cobb angle >40° between T4 and T12) or a wedged-shaped vertebral body. Alternatively, the (rare) Edgren-Vaino sign was taken as diagnostic. The 6-point-per-vertebral-body (13 vertebrae) method was used to assess osteoporotic vertebral shape and fracture caseness. DXA BMD of the L2-L4 and femoral neck regions was measured in subsets. We also assessed the presence of Scheuermann's by alternative published algorithms when these used the radiographic signs we assessed. Results: Vertebral radiographic images from 4486 men and 5655 women passed all quality checks. Prevalence of Scheuermann's varied considerably between centres, and based on random effect modelling, the overall European prevalence using our method was 8 % with no significant difference between sexes. The highest prevalences were seen in Germany, Sweden, the UK and France and low prevalences were seen in Hungary, Poland and Slovakia. Centre-level prevalences in men and women were highly correlated. Scheuermann's was not associated with BMD of the spine or hip. Conclusions: Since most of the variation in population impact of Scheuermann's was unaccounted for by the radiological and anthropometric data, the search for new genetic and environmental determinants of this disease is encouraged. [ABSTRACT FROM AUTHOR]

Summary: Two matrix Gla protein (MGP) polymorphisms were associated with progression of aortic calcification and femoral neck bone loss in men. All these findings were also functionally corroborated in two vascular and bone in vitro systems indicating that MGP genetic variations can be partly responsible of higher risk of bone loss and vascular calcification. Introduction: MGP plays an important role in bone and vascular mineralization as confirmed by MGP-deficient murine model. We therefore aimed to find a genetic association among -138T>C, -7G>A, and Thr83Ala MGP single-nucleotide polymorphisms (SNPs), bone loss, and progression of aortic calcification in a randomly selected general population of 296 individuals who participated in the European Vertebral Osteoporosis Study. Methods: To evaluate the rate of change in bone mineral density (BMD) and the progression of aortic calcification, dual X-ray absorptiometry and lateral spine X-rays were performed at baseline and after 4 years of follow-up. Genotyping for the three polymorphisms was carried out using polymerase chain reaction and restriction fragment length analysis. In addition, functional studies of MGP-7G>A and Thr83Ala SNPs were performed on transiently transfected osteoblast-like UMR-106 and vascular smooth muscle A7r5 cells. Results: The proportion of men who had lost BMD in the femoral neck was higher among homozygous -7AA and 83Ala-Ala ( p = 0.039 and p = 0.009, respectively), and also featured a higher risk of progression of aortic calcifications (OR = 5.6, 95 % CI = 1.2-27.8 and OR = 6.8, 95 % CI = 1.4-32.3, respectively). No effect was observed in women. The MGP-7A allele produced a reduction in luciferase activity compared to MGP-7G: 47 % less in vascular cells and 34 % less in bone cells ( p = 0.001 and 0.012, respectively). In vascular cells under calcifying conditions, the MGP 83Thr allele showed a slightly higher, although not significant, inhibition than the MGP 83 Ala allele in calcium content suggesting functional differences between both variants. Conclusion: These results suggest that MGP genetic variations could predict a higher risk of bone loss and progression of vascular calcification in men. [ABSTRACT FROM AUTHOR]

Summary: Postmenopausal estrogen decline is implicated in several age-related physical and psychological changes in women, including decreases in perceived quality of life. The phytoestrogen genistein at a dose of 54 mg daily in osteopenic postmenopausal women after 2 years implies an improvement on quality of life and depression symptoms. Introduction: Postmenopausal estrogen decline is implicated in several age-related physical and psychological changes in women, including decreases in perceived quality of life (QoL). A number of trials with hormone therapy showed beneficial effects of the intervention on quality of life parameters. However, because of known or suspected serious side effects of conventional hormone therapy, there is a need for alternatives. Methods: We conducted a double-blind randomized placebo-controlled trial using the isoflavone genistein, 54 mg, or placebo for 2 years. In this trial, we recruited 262 postmenopausal women aged 49 to 67 years. Results: At baseline, after 1 year, and at final visit, participants filled in the Short Form of 36 questions (SF-36) and the Zung Self-rating Depression Scale (ZSDS). For the placebo group, scores on all dimensions of the SF-36 decreased after 1 and 2 years. The genistein group showed increases on all dimensions of the SF-36 at the end of the study. There were, however, statistically significant differences in changes of scores between the two intervention groups. For the ZSDS, similarly, significant differences were found between groups. Conclusion: In conclusion, the findings of this randomized trial showed that genistein improves quality of life (health status, life satisfaction, and depression) in osteopenic postmenopausal women. [ABSTRACT FROM AUTHOR]

Bone is commonly affected in cancer. Cancer-induced bone disease results from the primary disease, or from therapies against the primary condition, causing bone fragility. Bone-modifying agents, such as bisphosphonates and denosumab, are efficacious in preventing and delaying cancer-related bone disease. With evidence-based care pathways, guidelines assist physicians in clinical decision-making. Of the 57 million deaths in 2008 worldwide, almost two thirds were due to non-communicable diseases, led by cardiovascular diseases and cancers. Bone is a commonly affected organ in cancer, and although the incidence of metastatic bone disease is not well defined, it is estimated that around half of patients who die from cancer in the USA each year have bone involvement. Furthermore, cancer-induced bone disease can result from the primary disease itself, either due to circulating bone resorbing substances or metastatic bone disease, such as commonly occurs with breast, lung and prostate cancer, or from therapies administered to treat the primary condition thus causing bone loss and fractures. Treatment-induced osteoporosis may occur in the setting of glucocorticoid therapy or oestrogen deprivation therapy, chemotherapy-induced ovarian failure and androgen deprivation therapy. Tumour skeletal-related events include pathologic fractures, spinal cord compression, surgery and radiotherapy to bone and may or may not include hypercalcaemia of malignancy while skeletal complication refers to pain and other symptoms. Some evidence demonstrates the efficacy of various interventions including bone-modifying agents, such as bisphosphonates and denosumab, in preventing or delaying cancer-related bone disease. The latter includes treatment of patients with metastatic skeletal lesions in general, adjuvant treatment of breast and prostate cancer in particular, and the prevention of cancer-associated bone disease. This has led to the development of guidelines by several societies and working groups to assist physicians in clinical decision making, providing them with evidence-based care pathways to prevent skeletal-related events and bone loss. The goal of this paper is to put forth an IOF position paper addressing bone diseases and cancer and summarizing the position papers of other organizations. [ABSTRACT FROM AUTHOR]

Summary: In this observational study, we found a positive relationship between low calcidiol levels and the risk of aortic calcification progression. A 10-ng/mL increase of calcidiol was associated with a decrease in the risk of progression by 44%. This figure was higher than that observed if we increased age by 10 years. Introduction: The aim of this study was to investigate the relationship between serum calcidiol levels and the onset and progression of aortic calcifications in a community-based sample of ambulatory subjects. Methods: Three hundred two men and women aged 50 and over underwent two lateral X-rays and were followed up for 4 years. Abdominal aortic calcifications were classified as absent, mild-moderate, and severe. The biochemical measurements of serum calcium, phosphorus, parathyroid hormone, total alkaline phosphatase, tartrate-resistant acid phosphatase, creatinine, calcidiol, calcitriol, and osteocalcin were determined. Subjects who had received anti-osteoporotic treatments were excluded from the analysis. Results: Subjects with progression of aortic calcifications had significantly lower serum calcidiol levels than those without progression. In the multivariate analysis, using the agreed upon serum levels for calcidiol (>30 ng/mL) as the reference, those subjects with calcidiol levels between 10 and 20 ng/mL showed a higher risk of progression of aortic calcification (odds ratio (OR) = 3.95; 95% confidence interval (CI) = 1.16 to 13.40). An even higher OR was observed in subjects with calcidiol values <10 ng/mL (OR = 4.10; 95% CI = 1.12 to 14.99). In addition, an increase by 1 ng/mL in osteocalcin levels was associated with a 17% reduction of the risk of aortic calcification progression. Conclusions: An increase by 10 ng/mL of calcidiol was associated with a decrease in the risk of aortic calcifications progression by 44%. This figure was even higher than that observed if we increased age by 10 years. Levels of calcidiol higher than 30 ng/mL seem to be desirable to reduce the progression of aortic calcification and to maintain bone turnover. [ABSTRACT FROM AUTHOR]

Abstract There is little data concerning the morbidity, mortality, and epidemiology of vertebral fracture. The aim of this study was to evaluate the effect of prevalent and incident vertebral fractures as risk factors for further osteoporotic fractures and mortality. The study was performed on a cohort of 316 women and 308 men older than 50 belonging to the EVOS study, randomly selected from our city register. At the beginning of the study and 4 years later, lateral dorsal and lumbar X-rays were performed. In addition, evaluation of the incidence of osteoporotic nonvertebral fractures was performed throughout 8 years. The incidence of all osteoporotic fractures was higher in women than in men (two-fold increase in vertebral fracture incidence and five-fold increase in Colles' and femur incidence). Vertebral fracture was a strong risk factor for a new vertebral fracture [RR=4.7 (1.8-11.9)], hip fracture [RR=6.7 (2.0-22.7)] and Colles' fracture [RR=3.0 (1.1-7.8)]. Prevalent and incident vertebral fractures were associated with a higher risk of having a hip fracture [RR=10.0 (2.0-50.2)] and Colles' fracture [RR=5.5 (1.3-23.4)]. In addition, in women, the vertebral fracture was associated with a higher mortality. By contrast, no association was found in men. These results demonstrate the association between a previous vertebral fracture with increments in the incidence of osteoporotic fractures of any type. In addition, we found a significantly higher mortality rate in women having vertebral fractures. These findings support the necessity of preventing the occurrence of vertebral fractures to limit their strong negative impact on mortality. [ABSTRACT FROM AUTHOR]

A correction is presented to the article "Identification and management of patients at increased risk of osteoporotic fracture: outcomes of an ESCEO expert consensus meeting" published in the perodical.