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Six hundred and nine patients with hip fractures in Malmö, Sweden, were compared with a sex- and age-matched control group (609). The comparison showed that patients with hip fractures were more often institutionalized, had more home aid, walking aids, poorer eyesight and were slender. Furthermore, the hip-fracture group more often showed signs of changes in mental status and concomitant illnesses.

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.

The incidence of fragility fractures begins to increase in middle age. We investigated prospectively risk factors for low-energy fractures in men and women, and specifically for forearm, proximal humerus, vertebral, and ankle fractures. The population-based Malmo Preventive Project consists of 22,444 men and 10,902 women, mean age 44 and 50 years, respectively, at inclusion. Baseline assessment included multiple examinations and lifestyle information. Mean follow-up was 19 and 15 years for men and women, respectively, regarding incident fractures. Fractures were ascertained from radiographic files. At least one low-energy fracture occurred in 1,262 men and 1,257 women. In men, the risk factors most strongly associated with low-energy fractures were diabetes [relative risk (RR) 2.38, confidence interval (CI) 95% 1.65-3.42] and hospitalization for mental health problems (RR 1.92, CI 95% 1.47-2.51). Factors associated with mental health and lifestyle significantly increased the fracture risk in most of the specific fracture groups: hospitalizations for mental health problems (RR 2.28-3.38), poor appetite (RR 3.05-3.43), sleep disturbances (RR 1.72-2.95), poor self-rated health (RR 1.80-1.83), and smoking (RR 1.70-2.72). In women, the risk factors most strongly associated with low-energy fractures were diabetes (RR 1.87, CI 95% 1.26-2.79) and previous fracture (RR 2.00, CI 95% 1.56-2.58). High body mass index (BMI) significantly increased the risk of proximal humerus and ankle fractures (RR 1.21-1.33) while, by contrast, lowering the risk of forearm fractures (RR 0.88, CI 95% 0.81-0.96). Risk factors for fracture in middle-aged men and women are similar but with gender differences for forearm, vertebral, proximal humerus, and hip fracture whereas risk factors for ankle fractures differ to a certain extent. The risk-factor pattern indicates a generally impaired health status, with mental health problems as a major contributor to fracture risk, particularly in men. Keywords Diabetes * Fragility fractures * Mental health * Risk factors

Introduction: Risedronate, a bisphosphonate for treatment and prevention of osteoporosis, has been shown in several clinical trials to reduce the risk of fractures in postmenopausal women with osteoporosis. The cost-effectiveness of risedronate treatment has previously been evaluated within different country settings using different model and analysis approaches. The objective of this study was to assess the cost-effectiveness of risedronate in postmenopausal women in four European countries--Sweden, Finland, Spain, and Belgium--by making use of the same modelling framework and analysis setup. Methods: A previously developed Markov cohort model for the evaluation of osteoporosis treatments was used to estimate the cost-effectiveness of risedronate treatment. For each country, the model was populated with local mortality, fracture incidence, and cost data. Hip fractures, clinical vertebral fractures, and wrist fractures were included in the model. Results: The incremental cost per quality-adjusted life years (QALY) gained from a 5-year intervention with risedronate compared to 'no intervention' in 70-year-old women at the threshold of osteoporosis [T-score = -2.5 based on National Health and Nutrition Examination Survey (NHANES) III data] and previous vertebral fracture was estimated to be 860 [euro], 19,532 [euro], 11,782 [euro], and 32,515 [euro] in Sweden, Finland, Belgium, and Spain, respectively. Among 70-year-old women at the threshold of osteoporosis without previous fracture the estimated cost per QALY gained ranged from 21,148 [euro] (Sweden) to 80,100 [euro] (Spain). The differences in cost-effectiveness between countries are mainly explained by different costs (fracture and treatment costs), fracture risks, and discount rates. Based on cost per QALY gained threshold values found in the literature, the study results indicated risedronate to be cost effective in the treatment of elderly women with established osteoporosis in all the included countries. Conclusions: At a hypothetical threshold value of 40,000 [euro] per QALY gained, the results in this study indicate that risedronate is a cost-effective treatment in elderly women at the threshold of osteoporosis (i.e., a T-score of -2.5) with prevalent vertebral fractures in Sweden, Finland, Belgium, and Spain. Keywords Belgium * Cost-effectiveness * Finland * Fracture * Osteoporosis * Postmenopausal women * Risedronate * Spain * Sweden

Byline: J. A. Kanis (1), F. Borgstrom (2), O. Johnell (3), B. Jonsson (4) Keywords: Cost-effectiveness; Meta-analysis; Osteoporosis; Postmenopausal women; Risedronate; UK; Vertebral fracture Abstract: Randomized, double-blind, controlled studies have shown that treatment with risedronate reduces the risk of vertebral fracture in postmenopausal women with established vertebral osteoporosis. They also show that the drug decreases the risk of non-vertebral fractures in women with osteoporosis. The aim of this study was to investigate the cost-effectiveness of risedronate in postmenopausal women with osteoporosis. A Markov model was applied to a UK setting. Treatment effects were computed by meta-analysis of randomized, controlled trials and given over 5 years to subjects aged between 60 and 80 years. Quality-adjusted life years (QALYs) and life years gained were used as outcome measures. Intervention with risedronate was cost-effective in women aged 60 years and older. Cost savings were also found for postmenopausal women aged 70 years and older with established vertebral osteoporosis (a prior spine fracture and BMD T-score a$?-2.5 SD). This treatment was cost-effective for women aged 65 years and older who had a prior vertebral fracture and a BMD T-score at the threshold of osteoporosis (T-score=-2.5 SD), and in women with a T-scorea$?-2.5 SD, but without a prior vertebral fracture. In women aged 60--80 years and at the threshold of osteoporosis (T-score=-2.5 SD) but without a prior vertebral fracture, treatment exceeded the threshold for cost-effectiveness. However, if an additional, independent risk factor was assumed (e.g., corticosteroid use) treatment became cost-effective. Author Affiliation: (1) WHO Collaborating Centre for Metabolic Bone Diseases, University of Sheffield Medical School, Beech Hill Road, , Sheffield, S10 2RX, UK (2) Stockholm Health Economics, Stockholm, Sweden (3) Department of Orthopaedics, Malmo General Hospital, Malmo, Sweden (4) Department of Economics, Stockholm School of Economics, Stockholm, Sweden Article History: Registration Date: 31/03/2004 Received Date: 14/01/2004 Accepted Date: 31/03/2004 Online Date: 03/06/2004

Byline: O. Johnell (1), J. A. Kanis (2) Keywords: Disability; Hip fracture; Mortality; Prevalence Abstract: The aim of this study was to quantify the global burden of osteoporosis as judged by hip fracture and the burden in different socio-economic regions of the world. The population mortality in 1990 and the incidence of hip fracture in different regions were identified, where possible in 1990. Excess mortality from hip fracture used data for Sweden, and disability weights were assigned to survivors from hip fracture. In 1990 there were an estimated 1.31 million new hip fractures, and the prevalence of hip fractures with disability was 4.48 million. There were 740,000 deaths estimated to be associated with hip fracture. There were 1.75 million disability adjusted life-years lost, representing 0.1% of the global burden of disease world-wide and 1.4% of the burden amongst women from the established market economies. We conclude that hip fracture is a significant cause of morbidity and mortality worldwide. Author Affiliation: (1) Department of Orthopaedics, Malmo General Hospital, Malmo, Sweden (2) WHO Collaborating Centre for Metabolic Bone Diseases, University of Sheffield Medical School, Beech Hill Road, Sheffield, S10 2RX, UK Article History: Registration Date: 09/03/2004 Received Date: 17/12/2003 Accepted Date: 08/03/2004 Online Date: 04/05/2004

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: S. Boonen (1), R. Rizzoli (2), P. J. Meunier (3), M. Stone (4), G. Nuki (5), U. Syversen (6), M. Lehtonen-Veromaa (7), P. Lips (8), O. Johnell (9), J.-Y. Reginster (10) Keywords: Calcium; Fracture prevention; Osteoporosis drugs; Vitamin D Abstract: A European Union (EU) directive on vitamins and minerals used as ingredients of food supplements with a nutritional or physiological effect (2002/46/EC) was introduced in 2003. Its implications for the use of oral supplements of calcium and vitamin D in the prevention and treatment of osteoporosis were discussed at a meeting organized with the help of the World Health Organization (WHO) Collaborating Center for Public Health Aspects of Rheumatic Diseases (Liege, Belgium) and the support of the WHO Collaborating Center for Osteoporosis Prevention (Geneva, Switzerland). The following issues were addressed: Is osteoporosis a physiological or a medical condition? What is the evidence for the efficacy of calcium and vitamin D in the management of postmenopausal osteoporosis? What are the risks of self-management by patients in osteoporosis? From their discussions, the panel concluded that: (1) osteoporosis is a disease that requires continuing medical attention to ensure optimal therapeutic benefits (2) when given in appropriate doses, calcium and vitamin D have been shown to be pharmacologically active (particularly in patients with dietary deficiencies), safe, and effective for the prevention and treatment of osteoporotic fractures (3) calcium and vitamin D are an essential, but not sufficient, component of an integrated management strategy for the prevention and treatment of osteoporosis in patients with dietary insufficiencies, although maximal benefit in terms of fracture prevention requires the addition of antiresorptive therapy (4) calcium and vitamin D are a cost-effective medication in the prevention and treatment of osteoporosis (5) it is apparent that awareness of the efficacy of calcium and vitamin D in osteoporosis is still low and further work needs to be done to increase awareness among physicians, patients, and women at risk and (6) in order that calcium and vitamin D continues to be manufactured to Good Manufacturing Practice standards and physicians and other health care professionals continue to provide guidance for the optimal use of these agents, they should continue to be classified as medicinal products. Author Affiliation: (1) Leuven University Centre for Metabolic Bone Diseases &amp Division of Geriatric Medicine, University Hospital Leuven, Herestraat 49, B-3000, Leuven, Belgium (2) University Hospital, Geneva, Switzerland (3) Hopital Edouard Herriot, Lyon, France (4) Llandough Hospital, Penarth, UK (5) University of Edinburgh, Edinburgh, UK (6) St Olavs Hospital HF, Trondheim, Norway (7) University of Turku, Turku, Finland (8) VU Medical Centre, Amsterdam, The Netherlands (9) Malmo Hospital, University of Malmo, Malmo, Sweden (10) Unite d'Exploration de l'Os et du Cartilage, Liege, Belgium Article History: Registration Date: 05/03/2004 Received Date: 03/10/2003 Accepted Date: 24/02/2004 Online Date: 07/04/2004

Byline: O. Johnell (1), J. A. Kanis (2), A. Oden (3), I. Sernbo (1), I. Redlund-Johnell (1), C. Petterson (1), C. Laet (4), B. Jonsson (5) Keywords: Fracture risk; Forearm; Hip; Osteoporosis; Spine Abstract: The aim of this study was to examine the pattern of fracture risk following a prior fracture at the spine, shoulder or hip. We studied 1918 patients with fractures at these sites identified from the Department of Radiology in Malmo who were followed for 5 years. Poisson regression was used to compute fracture rates immediately after the initial fracture and at 5 years thereafter in men and women aged 60 or 80 years. Immediate fracture risk was higher than that of the general population, more markedly so at the age of 60 than at 80 years. At the age of 60 years, the risk of hip, forearm and spine fractures were significantly increased following a prior spine, hip or shoulder fracture in men. A similar pattern was seen in women, except that the increase in risk of forearm fracture following a spine or hip fracture was not statistically significant. The incidence of further fractures at the shoulder, spine or hip fell with time after the first fracture, a fall that was significant for all fractures after a shoulder fracture, hip fracture after a spine fracture, and hip and spine fractures after a hip fracture. We conclude that the risk of a subsequent fracture immediately after an osteoporotic fracture is highest immediately after the event. This provides a rationale for very early intervention immediately after fractures to avoid recurrent fractures. Author Affiliation: (1) Department of Orthopaedics, Malmo University Hospital, Malmo, Sweden (2) WHO Collaborating Centre for Metabolic Bone Diseases, University of Sheffield Medical School, Sheffield, UK (3) Gothenburg, Sweden (4) Institute for Public Health, University Medical Center, Rotterdam, The Netherlands (5) Department of Economics, Stockholm School of Economics, Stockholm, Sweden Article History: Registration Date: 01/01/2003 Received Date: 07/04/2003 Accepted Date: 22/09/2003 Online Date: 23/12/2003

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: J. A. Kanis (1), O. Johnell (2), A. Oden (3), F. Borgstrom (4), N. Zethraeus (4), C. Laet (5), B. Jonsson (4) Keywords: Burden of fracture; Osteoporotic fracture; Utility; Vertebral fracture Abstract: The aim of this study was to determine the risk and burden of vertebral fractures judged as those coming to clinical attention and as morphometric fractures. Incidence and utility loss were computed from data from Malmo, Sweden. Clinical fractures accounted for 23% of all vertebral deformities in women and for 42% in men. The average 10-year fracture probability for morphometric fractures increased with age in men from 2.9% at the age of 50 years (7.2% in women) to 8.4 at the age of 85 years (26.7% in women). As expected, probabilities increased with decreasing T-score for hip BMD. Cumulative utility loss from a clinical vertebral fracture was substantial and was 50--62% of that due to a hip fracture depending on age. When incidence of fractures in the population was weighted by disutility, all spine fractures accounted for more morbidity than hip fracture up to the age of 75 years. We conclude that vertebral fractures have a major personal and societal impact that needs to be recognised in algorithms for assessment of risk and in health economic strategies for osteoporosis. Author Affiliation: (1) Centre for Metabolic Bone Diseases (WHO Collaborating Centre), University of Sheffield Medical School, Beech Hill Road, Sheffield, S10 2RX, UK (2) Department of Orthopaedics, Malmo General Hospital, Malmo, Sweden (3) Consulting Statistician, Gothenburg, Sweden (4) Department of Economics, Stockholm School of Economics, Stockholm, Sweden (5) Department of Public Health, Erasmus Medical Center, 3000 DR, Rotterdam, The Netherlands Article History: Received Date: 11/03/2003 Accepted Date: 23/05/2003 Online Date: 31/10/2003

Byline: M. Sundberg (1,2), P. Gardsell (1), O. Johnell (1), E. Ornstein (2), M. K. Karlsson (1), I. Sernbo (1) Keywords: Adolescents; Bone mineral density; Growth; Longitudinal Abstract: Fragility fractures are correlated to reduced bone size and/or reduced volumetric bone density (vBMD). These region-specific deficits may originate from reduced mineral accrual and/or reduced skeletal growth during the first 2 decades of life. Before pathological development can be defined, normal skeletal growth must be described. To evaluate growth of bone size, accrual of bone mineral content (BMC), areal bone mineral density (aBMD) and vBMD in a population-based cohort, 44 boys and 42 girls were followed by annual measurements from the age of 12 to 16 (attendance rates 90--100%). Segmental bone length, bone width, BMC, aBMD and vBMD were measured by dual-energy X-ray absorptiometry (DXA). Data were compared with predicted adult peak, as determined in 36 men aged 27.7+-4.6 years and 44 women aged 26.8+-4.9 years. Growth in width of the femoral neck precedes accrual of BMC in the femoral neck in both genders up to age 15. The girls were at all ages closer to their predicted adult peak in both bone width and BMC compared with the boys except in the femoral neck. As femoral neck vBMD had reached its predicted adult peak already at 12 years in both genders, the increase in femoral neck BMC and femoral neck aBMD from age 12 to 16 was most likely to be explained by the increase in bone size. In boys the peak velocity growth was recorded at ~14 years for BMC, height, width and lean mass. Growth from the age of 12 to 16 seems to build a bigger but not a denser skeleton in the femoral neck. Author Affiliation: (1) Department of Orthopedics, Malmo University Hospital, SE-205 02, Malmo, Sweden (2) Department of Orthopedics, Hassleholm-Kristianstad Hospital, Kristianstad, Sweden Article History: Received Date: 16/05/2002 Accepted Date: 12/02/2003 Online Date: 29/04/2003

Byline: L. J. Melton (1,5), S. E. Gabriel (1), C. S. Crowson (1), A. N. A. Tosteson (2), O. Johnell (3), J. A. Kanis (4) Keywords: Cost analysis; Epidemiology; Forearm fracture; Hip fracture; Osteoporosis; Vertebral fracture Abstract: Methods Among 985 Olmsted County, Minnesota, residents who experienced an osteoporotic fracture (distal forearm, humerus, clavicle/scapula/sternum, ribs, vertebrae, pelvis, hip, other femur or tibia/fibula [the latter in women only]), we estimated the incremental cost of direct medical care in the following year compared with age- and sex-matched controls without a fracture randomly sampled from the same community. Results The overall median incremental (case minus control) cost in the succeeding year was $2390, with a particularly high incremental cost for hip fractures ($11,241). There was fair concordance between the incremental cost of the different fractures, relative to hip fracture alone, and the previously published disutility associated with each fracture type relative to hip fracture. Overall, the incremental cost for all osteoporotic fractures combined was 46% greater than that for hip fractures alone in women and 47% greater in men. This is consistent with the earlier report that overall morbidity from all osteoporotic fractures combined is 47% and 39% greater in women and men, respectively, than the morbidity attributable solely to hip fractures. Conclusion These data lend support to the notion that other osteoporotic fractures can be quantified relative to hip fracture on the basis of their cost, as well as their morbidity and mortality. This may simplify health economic analyses by allowing all fracture outcomes to be modeled relative to hip fractures (i.e., hip fracture 'equivalents') and will provide a more comprehensive assessment of osteoporosis outcomes than is possible by focusing only on hip fractures. Author Affiliation: (1) Department of Health Sciences Research, Mayo Clinic and Mayo Foundation, Rochester, MN 55905, USA (2) Center for Evaluative Clinical Sciences, Dartmouth Medical School, Hanover, NH, USA (3) Department of Orthopaedics, Malmo General Hospital, Malmo, Sweden (4) WHO Collaborating Centre for Metabolic Bone Diseases, University of Sheffield Medical School, Sheffield, UK (5) Division of Epidemiology, Mayo Clinic, 200 First Street SW, Rochester, MN 55905, USA Article History: Received Date: 01/08/2002 Accepted Date: 30/12/2002 Online Date: 01/04/2003 Article note: Supported in part by grants AG12262, AG04875, and AR30582 from the National Institutes of Health, US Public Health Service.

Byline: R. Hasserius (1), M.K. Karlsson (1), B.E. Nilsson (1), I. (1), O. Johnell (2) Keywords: KeywordsaFractures; Fragility fractures; Mortality; Osteoporosis; Prediction; Vertebral deformity Abstract: aThe aim of this study was to evaluate whether a prevalent vertebral deformity predicts mortality and fractures in both men and women. In the city of Malmo, 598 individuals (298 men, 300 women age 50--80 years) were selected from the city's population and were included in the Swedish part of the European Vertebral Osteoporosis Study (EVOS). At baseline the participants answered a questionnaire and lateral spine radiographs were performed. The prevalence of subjects with vertebral deformity was assessed using a morphometric method. The mortality during a 10-year follow-up period was determined through the register of the National Swedish Board of Health and Welfare. Eighty-five men and 43 women died during the study period. The subsequent fracture incidence during the follow-up period was ascertained by postal questionnaires, telephone interviews and by a survey of the archives of the Department of Radiology in the city hospital. Thirty-seven men and 69 women sustained a fracture during the study period. Data are presented as hazard ratios (HR) with 95% confidence interval (95% CI) within brackets. Prevalent vertebral deformity, defined as a reduction by more than 3 standard deviations (SD) in vertebral height ratio, predicted mortality during the forthcoming decade in both men [age-adjusted HR 2.4 (95% CI 1.6--3.9)] and women [age-adjusted HR 2.3 (95% CI 1.3--4.3)]. In men there was an increased mortality due to cardiovascular and pulmonary diseases and in women due to cancer. Prevalent vertebral deformity predicted an increased risk of any fracture during the forthcoming decade in both men [age-adjusted HR 2.7 (95% CI 1.4--5.3)] and women [age-adjusted HR 1.8 (95% CI 1.1--2.9)]. Prevalent vertebral deformity predicted an increased risk of any subsequent fragility fracture in women [age-adjusted HR 2.0 (95% CI 1.1--3.5)] however, in men the increased risk was nonsignificant [age-adjusted HR 1.9 (95% CI 0.7--5.1)]. In summary, a prevalent vertebral deformity can predict both increased mortality and increased fracture incidence during the following decade in both men and women. We conclude that prevalent vertebral deformity could be used as a risk factor in both genders for mortality and future fracture. Author Affiliation: (1) Department of Orthopaedics, Malmo University Hospital, SE-205 02 Malmo, Sweden Tel: +46 40 331000 Fax: +46 40 336200 e-mail: Ralph.Hasserius@skane.se, SE (2) Department of Diagnostic Radiology, Malmo University Hospital, SE-205 02 Malmo, Sweden, SE Article note: Received: 22 March 2002 / Accepted: 27 August 2002 AcknowledgementaFinancial support was received from the Swedish Medical Research Council K2001-73GX-14080-01 and K2001-73P-14088-01A, the Swedish Society of Medicine, the Swedish Society of Medical Research and the Greta and Johan Kock Foundation.

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: N. Zethraeus (1), W. Ben Sedrine (2), F. Caulin (3), S. Corcaud (4), H. J. Gathon (5), M. Haim (6), O. Johnell (7), B. Jonsson (1), J. A. Kanis (8), Y. Tsouderos (9), J.-Y. Reginster (2) Keywords: Key words: Abstract: Author Affiliation: (1) Centre for Health Economics, Stockholm School of Economics, BE (2) WHO Collaborating Center for Public Health Aspects of Rheumatic Disorders Liege, Belgium, BE (3) FC Consulting, Paris, France, FR (4) Groupe de Recherche Servier, Neuilly-sur-Seine, France, FR (5) Department of Economics, University of Liege, Belgium, BE (6) Merck Sharp &amp Dohme S.A., Paris, France, FR (7) Department of Orthopaedics, Malmo General Hospital, SE 20202, Malmo, Sweden, SE (8) Centre for Metabolic Bone Diseases (WHO Collaborating Centre), University of Sheffield, Sheffield, UK, GB (9) Institut de Recherches Internationales Servier, Courbevoie Cedex, France, FR Article note: Received: 6 May 2002 / Accepted: 7 May 2002 Correspondence and offprint requests to: Niklas Zethraeus, Centre for Health Economics, Stockholm School of Economics, PO Box 6501, S-113 83 Stockholm, Sweden. Tel: +46 8 7369640. Fax: +46 8 302115. e-mail: henz@hhs.se

Byline: J. A. Kanis (1), D. Black (2), C. Cooper (3), P. Dargent (4), B. Dawson-Hughes (5), C. De Laet (6), P. Delmas (7), J. Eisman (8), O. Johnell (9), B. Jonsson (10), L. Melton (11), A. Oden (12), S. Papapoulos (13), H. Pols (14), R. Rizzoli (15), A. Silman (16), A. Tenenhouse , on behalf of the International Osteoporosis Foundation and the National Osteoporosis Foundation, USA (17) Keywords: Key words: Abstract: Author Affiliation: (1) WHO Centre for Metabolic Bone Diseases, University of Sheffield, UK, GB (2) Division of Clinical Epidemiology, University of California at San Francisco, USA, GB (3) MRC Environmental Epidemiology Unit, University of Southampton, UK, GB (4) INSERM, Paris, France, FR (5) USDA Human Research Center, Tufts University, Boston, USA (President, NOF), US (6) Institute for Public Health, Erasmus MC, Rotterdam, The Netherlands, NL (7) INSERM Research Unit, Hopital Edouard Herriot, Lyon, France (President, IOF), FR (8) Garvan Institute of Medical Research, St Vincent's Hospital, Australia, AU (9) Department of Orthopaedics, Malmo General Hospital, Sweden, SE (10) Dept Economics, Stockholm School of Economics, Sweden, SE (11) Section of Clinical Epidemiology, Mayo Clinic, Rochester, USA, US (12) Consulting Statistician, Gothenburg, Sweden, SE (13) Department of Endocrinology, Leiden University Medical Center, The Netherlands, NL (14) Ziekenhuis Dijkzigt, Rotterdam, The Netherlands, NL (15) Division of Bone Diseases, University Hospital, Geneva, Switzerland, CH (16) ARC Epidemiology Research Unit, University of Manchester, UK , GB (17) Division of Bone Metabolism, The Montreal General Hospital, Canada, CA Article note: Received: 18 February 2002 / Accepted: 22 February 2002

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: O. Johnell (1), A. Oden (2), C. De Laet (3), P. Garnero (4), P. D. Delmas (4), J. A. Kanis (5) Keywords: Key words: Abstract: Author Affiliation: (1) Department of Orthopaedics, Malmo General Hospital, Malmo, Sweden, SE (2) Consulting Statistician, Gothernberg, Sweden, SE (3) Institute for Public Health, Erasmus MC, Rotterdam, The Netherlands, NL (4) INSERM Research Unit 403, Hopital E. Herriot, Lyon, France , FR (5) WHO Collaborating Centre for Metabolic Bone Diseases, University of Sheffield Medical School, Sheffield, UK, GB Article note: Received: 18 July 2001 / Accepted: 20 December 2001

Byline: J. A. Kanis (1), A. Oden (2), O. Johnell (3), F. Caulin (4), H. Bone (5), J.-M. Alexandre (6), E. Abadie (7), F. Lekkerkerker (8) Keywords: Key words:Comparator studies -- Drug treatment -- Fracture -- Medical ethics -- Placebo-controlled trials Abstract: The advent of effective agents for the treatment of osteoporosis has led to the view that placebo-controlled trials to test new agents for efficacy are no longer appropriate since proven treatments are available. In this review we argue that, if new agents are to be developed, there is still a place for the placebo-controlled trial. A move to studies of equivalence or non-inferiority raises more problems than it resolves. Author Affiliation: (1) WHO Collaborating Centre for Metabolic Bone Diseases, University of Sheffield Medical School, Sheffield, UK, GB (2) Solberg, Romelanda, Sweden, SE (3) Department of Orthopaedics, MalmoA' General Hospital, Sweden, SE (4) FC Consulting SA, Paris, France, FR (5) Michigan Bone &amp Mineral Clinic, Detroit, Michigan, USA, US (6) Ho^pital EuropeA'en George Pompidou, Paris, France, FR (7) AFFSAPS, 143 bd Anatole France, St Denis, France , FR (8) Medicines Evaluation Board, The Netherlands, NL Article note: Received: 19 December 2001 / Accepted: 11 March 2002

Byline: J. A. Kanis (1), O. Johnell (2), A. Oden (3), A. Dawson (4), C. De Laet (5), B. Jonsson (6) Keywords: Key words:Absolute risk -- Colles' fracture -- Hip fracture -- Humeral fracture -- Intervention thresholds -- Osteoporotic fracture -- Vertebral fracture Abstract: The objectives of the present study were to estimate 10 year probabilities of osteoporotic fractures in men and women according to age and bone mineral density (BMD) at the femoral neck. Risks were computed from the incidence of a first hip, distal forearm, proximal humerus and symptomatic vertebral fracture from patient records in MalmoA', Sweden and future mortality rates for each year of age from Poisson models using the Swedish patient register and statistical year book. Fracture probability was computed using the Swedish population and cut-off values for T-scores based on the NHANES III female population. We assumed that the risk of fracture increased with decreasing BMD as assessed by meta-analysis in independent studies. The 10-year probability of any fracture was determined from the proportion of individuals fracture-free from the age of 45 years. With the exception of forearm fractures in men, 10 year probabilities increased with age and T-score. In the case of hip and spine fractures, fracture probabilities for any age with low BMD were similar between men and women. The effect of age on risk independently of BMD suggests that intervention thresholds should not be at a fixed T-score but vary according to absolute probabilities. Intervention thresholds based on hip BMD T-scores are similar between sexes. Author Affiliation: (1) WHO Collaborating Centre for Metabolic Bone Diseases, University of Sheffield Medical School, Sheffield, UK, GB (2) Department of Orthopaedics, MalmoA' General Hospital, MalmoA', SE (3) Consulting Statistician, Gothenberg, Sweden, SE (4) Lilly Research Centre Ltd, Windlesham, UK, GB (5) Institute for Medical Technology Assessment, Rotterdam, The Netherlands , NL (6) Department of Economics, Stockholm School of Economics, Stockholm, Sweden, SE Article note: Received: 14 December 2000 / Accepted: 2 July 2001

Byline: M. Lunt (1), W. Gowin (2), O. Johnell (3), G. Armbrecht (2), D. Felsenberg (2), J. Reeve (1) Keywords: Key words:Epidemiology -- Magnification correction -- Robust estimation -- Vertebral morphometry Abstract: Incident vertebral deformities are commonly defined by observed changes in height between measurements on two consecutive radiographs. However, conventional radiographs are subject to magnification, and this magnification may differ between films, leading to artifactual changes in height. In order to minimize this effect, it is common practice to record the spine--film and film--focus distances, and from this to calculate a magnification factor for each film. We present a simple statistical method for correcting for differences in magnification between two films if the spine--film and film--focus distances are unknown. This method is shown to reduce the variance of the magnification differences in vertebral heights by 14%, considerably more than is possible using the spine--film distance. Using the statistical method, the number of vertebrae that showed not only a reduction in one or more height of 15%, but were also judged clinically to be free from any incident deformity by an expert radiologist, was reduced from 100 to 46. The number showing a reduction of 20% that were judged fracture-free was reduced from 15 to 9. In the subset of subjects for whom the spine--film distance was known, the reduction in false positives was similar, whichever method was used to correct for magnification. There was no difference in the number of confirmed incident fractures detected when magnification correction by either method was employed. It is concluded that correcting for magnification differences using the statistical method outlined here reduces the number of false positive deformities very substantially and by a similar extent as correcting the magnification using reliable, measured spine--film and film--focus distances. A further advantage of this method is that it can be used retrospectively. Author Affiliation: (1) Strangeways Research Laboratory, Cambridge, UK, GB (2) Abteilung Radiologie und Nuklearmedizin, UniversitaA'tsklinikum Benjamin Franklin, FU Berlin, Berlin, Germany , DE (3) Department of Orthopaedics, MalmoA' General Hospital, MalmoA', Sweden., SE Article note: Received: 26 May 1999 / Accepted: 9 May 2001

Byline: D. M. Black (1), M. Steinbuch (2), L. Palermo (1), P. Dargent-Molina (3), R. Lindsay (4), M. S. Hoseyni (2), O. Johnell (5) Keywords: Key words:Bone mineral density -- Fracture risk -- Hip fracture -- Osteoporosis -- Postmenopausal women -- Risk assessment Abstract: Due to the magnitude of the morbidity and mortality associated with untreated osteoporosis, it is essential that high-risk individuals be identified so that they can receive appropriate evaluation and treatment. The objective of this investigation was to develop a simple clinical assessment tool based on a small number of risk factors that could be used by women or their clinicians to assess their risk of fractures. Using data from the Study of Osteoporotic Fractures (SOF), a total of 7782 women age 65 years and older with bone mineral density (BMD) measurements and baseline risk factors were included in the analysis. A model with and without BMD T-scores was developed by identifying variables that could be easily assessed in either clinical practice or by self-administration. The assessment tool, called the FRACTURE Index, is comprised of a set of seven variables that include age, BMD T-score, fracture after age 50 years, maternal hip fracture after age 50, weight less than or equal to 125 pounds (57 kg), smoking status, and use of arms to stand up from a chair. The FRACTURE Index was shown to be predictive of hip fracture, as well as vertebral and nonvertebral fractures. In addition, this index was validated using the EPIDOS fracture study. The FRACTURE Index can be used either with or without BMD testing by older postmenopausal women or their clinicians to assess the 5-year risk of hip and other osteoporotic fractures, and could be useful in helping to determine the need for further evaluation and treatment of these women. Author Affiliation: (1) University of California, San Francisco, CA, USA, US (2) Procter &amp Gamble Pharmaceuticals, Cincinnati, OH, USA, US (3) INSERM Unit 149, Villejuif Cedex, France, FR (4) Helen Hayes Hospital, Regional Bone Center, West Haverstraw, NY, USA, US (5) Department of Orthopaedics, Malmo General Hospital, Malmo, Sweden, SE Article note: Received: 7 November 2000 / Accepted: 23 May 2001

Byline: J. A. Kanis (1), A. Oden (2), O. Johnell (3), B. Jonsson (4), C. de Laet (5), A. Dawson (6) Keywords: Key words:Absolute risk -- Hip fracture equivalents -- Intervention thresholds -- Quality of life -- Osteoporotic fracture Abstract: The aim of this study was to assess the relationship between morbidity from hip fracture and that from other osteoporotic fractures by age and sex based on the population of Sweden. Osteoporotic fractures were designated as those associated with low bone mineral density (BMD) and those that increased in incidence with age after the age of 50 years. Severity of fractures was weighted according to their morbidity using utility values based on those derived by the National Osteoporosis Foundation. Morbidity from fractures other than hip fracture was converted to hip fracture equivalents according to their disutility weights. Excess morbidity was 3.34 and 4.75 in men and women at the age of 50 years, i.e. the morbidity associated with osteoporotic fractures was 3--5 times that accounted for by hip fracture. Excess moribidity decreased with age to approximately 1.25 between the ages of 85 and 89 years. On the assumption that the age- and sex-specific pattern of fractures due to osteoporosis is similar in different communities, the computation of excess morbidity can be utilized to determine the total morbidity from osteoporotic fractures from knowledge of hip fracture rates alone. Such data can be used to weight probabilities of hip fracture in different countries in order to take into account the morbidity from fractures other than hip fracture, and to modify intervention thresholds based on hip fracture risk alone. If, for example, a 10-year probability of hip fracture of 10% was considered an intervention threshold, this would be exceeded in women with osteoporosis aged 65 years and more, but when weighted for other osteoporotic fractures would be exceeded in all women (and men) with osteoporosis. Author Affiliation: (1) WHO Collaborating Centre for Metabolic Bone Diseases, University of Sheffield Medical School, Sheffield, UK, GB (2) Consulting statistician, Gothenberg, Sweden, SE (3) Department of Orthopedics, Malmo General Hospital, Malmo, Sweden, SE (4) Department of Economics, Stockholm School of Economics, Stockholm, Sweden, SE (5) Institute for Medical Technology Assessment, The Netherlands, NL (6) Lilly Research Centre Ltd, Windlesham, UK, GB Article note: Received: 1 May 2000 / Accepted: 1 December 2000

Byline: J. A. Kanis (1), A. Dawson (2), A. Oden (3), O. Johnell (4), C. de Laet (5), B. Jonsson (6) Keywords: Key words:Cost-effectiveness -- Global strategy -- Hip fracture -- Screening Abstract: The aims of this study were to determine whether treatments that reduce the incidence of hip fracture might be used in the general female population rather than screening or case-finding strategies. Cost-effectiveness, measured as cost per quality-adjusted life-year (QALY) gained using threshold values for cost-effectiveness of $20.000 or $30.000/QALY gained, was assessed during and after treatment using a computer simulation model applied to the female population of Sweden. The base case assumed a 5-year intervention that reduced the risk of hip fracture by 35% during the treatment period, and an effect that reversed to the pretreatment risk during the next 5 years. Sensitivity analyses included the effects of age, different treatment costs and effectiveness. Cost-effectiveness was critically dependent upon the age and costs of intervention. Reasonable cost-effectiveness was shown even with relatively high intervention costs for women at average risk at the age of 84 years or more. For the cheapest interventions ($63/year) cost-effectiveness could be found from the age of 53 years. Variations in effectiveness (15--50% risk reduction) had marked effects on the age that treatment was worthwhile. We conclude that segments of the apparently healthy population could be advantaged by treatment if efficacy were supported by randomized controlled studies. Author Affiliation: (1) Centre for Metabolic Bone Diseases (WHO Collaborating Centre), University of Sheffield Medical School, Sheffield, UK, GB (2) Lilly Research Centre, Windlesham, Surrey, UK, GB (3) Solberg 8414, S-442 92 Romelanda, Sweden, SE (4) Department of Orthopaedics, MalmoA' General Hospital, Sweden, SE (5) Institute for Medical Technology Assessment, The Netherlands , NL (6) Department of Economics, Stockholm School of Economics, Stockholm, Sweden, SE Article note: Received: May 2000 / Accepted: November 2000

Byline: M. Sundberg (1), P. GaA'rdsell (2), O. Johnell (2), M. K. Karlsson (2), E. Ornstein (1), B. Sandstedt (1), I. Sernbo (2) Keywords: Key words:Adolescents -- Bone mineral density -- Intervention -- Moderate exercise -- Population-based Abstract: On the basis of cross-sectional studies in elite athletes and longitudinal studies, physical activity in growing children has been suggested to enhance bone mineral acquisition and prevent osteoporosis later in life. The level of exercise in most of these studies is not applicable in a population on a day-to-day basis. The aim of this study was to determine whether moderate increased exercise within the school curriculum from age 12 to 16 years would have anabolic bone effects. In a population-based setting of 40 boys and 40 girls the school curriculum was enhanced to physical education 4 times per week for 3--4 years. Controls were 82 boys and 66 girls who had had physical education twice a week over a corresponding period. Both cases and controls were measured at age 16 years. Bone mineral content (BMC), areal bone mineral density (aBMD), bone size (femoral neck width) and volumetric BMD (vBMD) were measured in total body, spine and femoral neck (FN) by dual-energy X-ray absorptiometry. Data are presented as mean +- SD. BMC (8 +- 15%, p= 0.04), aBMD (9 +- 13%, p= 0.002) and vBMD (9 +- 15%, p= 0.001) were all higher in FN in the male intervention group compared with controls. FN bone size was no higher in the intervention group than in the controls. In girls, no differences were found when comparing the intervention group with controls. The results remained after adjusting for confounding factors such as weight, height, milk intake and activity after school. In summary, we report that increased bone mass can be achieved in a population-based cohort of boys (but not in girls) by moderate increased physical activity within the school curriculum from age 12 to 16 years. We speculate that the same results can be seen in girls if intervention starts at an earlier age. We conclude that increasing the physical education content of the Swedish school curriculum may improve bone mass in at least peripubertal boys. Author Affiliation: (1) Department of Orthopedic Surgery, Hassleholm-Kristianstad, SE (2) Department of Orthopedic Surgery, Malmo University Hospital, Sweden, SE Article note: Received: 20 April 2000 / Accepted: 17 October 2000

Byline: O. Johnell (1), A. Oden (2), F. Caulin (3), J. A. Kanis (4) Keywords: Key words:Hip fracture -- Osteoporotic fractures -- Vertebral fracture Abstract: The aims of this study were to determine the magnitude of the increase in risk of further fracture following hospitalization for vertebral fracture, and in particular to determine the time course of this risk. The records of the Swedish Patient Register were examined from 1987 to 1994 to identify all patients who were admitted to hospital for thoracic or lumbar vertebral fractures. Vertebral fractures were characterized as due to high- or low-energy trauma. Patients were followed for subsequent hospitalizations for hip fracture, and for all fractures combined. A Poisson model was used to determine the absolute risk of subsequent nonvertebral fracture and compared with that of the general population. We analyzed 13.4 million hospital admissions from which 28.869 individuals with vertebral fracture were identified, of which 60% were associated with low-energy trauma. There was a marked increase in subsequent incidence of hip and all fractures within the first year following hospitalization for vertebral fracture in both men and women. Thereafter, fracture incidence declined toward, but did not attain, baseline risk. Increased risks were particularly marked in the young. The increase in fracture risk was more marked following low-energy vertebral fracture than in the case of high-eneergy trauma. We conclude that the high incidence of new fractures within a year of hospitalization for vertebral fractures, irrespective of the degree of trauma involved, indicates that such patients should be preferentially targeted for treatment. It is speculated that short courses of treatment at the time of first vertebral fracture could provide important therapeutic dividends. Author Affiliation: (1) Department of Orthopaedics, MalmoA' General Hospital, MalmoA', Sweden, SE (2) Solberg, Romelanda, Sweden, SE (3) FC Consulting SA, Paris, France , FR (4) Centre for Metabolic Bone Diseases, University of Sheffield Medical School, Sheffield, UK, GB Article note: Received: 6 June 2000 / Accepted: 28 September 2000

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: G. Maalouf (1), S. Salem (1), M. Sandid (2), P. Attallah (1), J. Eid (3), N. Saliba (4), I. Nehme (5), O. Johnell (6) Keywords: Key words: Bone mineral density -- Lebanese Abstract: We determined the bone mineral density (BMD) of normal Lebanese subjects and compared results with US/European reference data. The investigation was conducted at one center, and included 858 women and 165 men aged 20--79 years. Spine, femoral and radial BMD measurements were made using dual-energy X-ray absorptiometry. Age-related changes in BMD were similar in form to those of US/European reference data. However, BMD values of Lebanese were generally lower than US/European values. Spine BMD of Lebanese women was about 8% lower than US/European values between ages 20 and 59 years, and 5--6% lower for ages 60--79 years. Femoral neck BMD values for Lebanese women were 8% lower in the young adult years (age 20--39 years), but only 2--3% lower in the postmenopausal years, compared with US/European women. There were smaller postmenopausal decreases in femoral and radial BMD in Lebanese women compared with US/European women, which led to a convergence of BMD after age 70 years. The BMD of Lebanese men was 5--8% lower than US/European values throughout the age range (20--79 years). The effect of weight on BMD ranged from 0.2% to 0.4% per kilogram. Height was not significantly associated with BMD when both height and weight were entered in multiple regression analyses. The prevalence of osteoporosis appeared to be overestimated if the US/European reference data, rather than Lebanese reference data, were used to calculate T-scores. Author Affiliation: (1) Saint George Hospital, Beirut, Lebanon, LB (2) Lebanese Association for Diabetes, Saint George Hospital, Beirut, Lebanon, LB (3) Clinical Fellowship, Saint George Hospital, Beirut, Lebanon, LB (4) Lebanese Hospital, Jeitawi, Lebanon, LB (5) CHU Rangueil, Toulouse, France , FR (6) Malmo University Hospital, Malmo, Sweden, SE Article note: Received: 25 February 1999 / Accepted: 9 March 2000

Byline: J. A. Kanis (1), O. Johnell (2), A. Oden (3), I. Sernbo (2), I. Redlund-Johnell (2), A. Dawson (4), C. De Laet (5), B. Jonsson (6) Keywords: Key words: Absolute risk -- Colles' fracture -- Hip fracture -- Lifetime risk -- Osteoporotic fracture -- Shoulder fracture -- Vertebral fracture Abstract: The objectives of the present study were to estimate long-term risks of osteoporotic fractures. The incidence of hip, distal forearm, proximal humerus and vertebral fracture were obtained from patient records in MalmoA', Sweden. Vertebral fractures were confined to those coming to clinical attention, either as an inpatient or an outpatient case. Patient records were examined to exclude individuals with prior fractures at the same site. Future mortality rates were computed for each year of age from Poisson models using the Swedish Patient Register and the Statistical Year Book. The incidence and lifetime risk of any fracture were determined from the proportion of individuals fracture-free from the age of 45 years. Lifetime risk of shoulder, forearm, hip and spine fracture were 13.3%, 21.5%, 23.3% and 15.4% respectively in women at the age of 45 years. Corresponding values for men at the age of 45 years were 4.4%, 5.2%, 11.2% and 8.6%. The risk of any of these fractures was 47.3% and 23.8% in women and men respectively. Remaining lifetime risk was stable with age for hip fracture, but decreased by 20--30% by the age of 70 years in the case of other fractures. Ten and 15 year risks for all types of fractures increased with age until the age of 80 years, when they approached lifetime risks because of the competing probabilities of fracture and death. We conclude that fractures of the hip and spine carry higher risks than fractures at other sites, and that lifetime risks of fracture of the hip in particular have been underestimated. Author Affiliation: (1) WHO Collaborating Centre for Metabolic Bone Diseases, University of Sheffield Medical School, Sheffield, UK, GB (2) Department of Orthopaedics, Malmo General Hospital, Malmo, Sweden, SE (3) Consulting Statistician, Gothenberg, Sweden, SE (4) Lilly Research Centre Ltd, Windlesham, Surrey, UK, GB (5) Institute for Medical Technology Assessment, Rotterdam, The Netherlands , NL (6) Department of Economics, Stockholm School of Economics, Stockholm, Sweden, SE Article note: Received: 9 November 1999 / Accepted: 2 February 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: J. A. Kanis (1), O. Johnell (2), A. Oden (3), B. Jonsson (4), A. Dawson (5), W. Dere (6) Keywords: Key words:Absolute risk -- Hip fracture -- Relative risk -- Risk factors Abstract: Bone mineral density measurements are widely used to estimate the relative risk of hip fracture. In addition, many other risk factors have been identified, some of which are known to add to the risk independently of other risk factors, including bone mineral density measurements. In this paper we develop an algorithm that converts relative risks for hip fracture to absolute (15 years and lifetime) risks, modeled on the population of Sweden. Lifetime risks increased as expected with increments in relative risk. Average lifetime risk in women at the age of 50 years was 22.7%, which increased to 64.9% when the relative risk was 6.0. In men the risk increased from 11.1% to 41.3%. The identification of high-risk groups had little effect on the specificity of assessments but increased the sensitivity over a wide range of assumptions. The increment in lifetime risk was relatively stable across all ages, reducing the complexity of computing lifetime risks from relative risk. The derivation of absolute risk from relative risk permits the optimization of selection of individuals or populations either for further risk assessment or for treatment. Author Affiliation: (1) WHO Collaborating Centre for Metabolic Bone Diseases, University of Sheffield Medical School, Sheffield, UK, GB (2) Department of Orthopaedics, Malmo General Hospital, Malmo, Sweden, SE (3) Statistical Consultant, Romelanda, Sweden, SE (4) Department of Economics, Stockholm School of Economics, Stockholm Sweden, SE (5) Lilly Research Centre Ltd, Surrey, UK , GB (6) Lilly Research Laboratories and Indiana University School of Medicine, Indianapolis, USA, US Article note: Received: 21 December 1999 / Accepted: 2 July 1999

Byline: B. Jonsson (1), J. Kanis (2), A. Dawson (3), A. Oden (4), O. Johnell (5) Keywords: Key words:Cost-effectiveness -- Hip fracture -- Offset time -- Quality of life year gained Abstract: We investigated the cost-effectiveness of treatments that reduce the risk of hip fracture using a computer simulation model. Cost-effectiveness was measured as cost per quality-adjusted life-year (QALY) gained using a threshold value for cost-effectiveness of $30.000/QALY gained. The baseline simulations assumed a 5-year intervention that reduced the risk of hip fracture by 50% during the intervention period, and an effect which reversed to the pretreatment risk during the next 5 years. Sensitivity analyses inlcuded the effects of age, different fracture risks, and different treatment costs and duration of therapeutic effect once treatment was stopped. Cost-effectiveness was critically dependent upon absolute risk determined by the age and the relative risk of hip fracture at any given age. Reasonable cost-effectiveness was shown even with relatively high intervention costs for women with a risk about twice the average at the age of 70 or more years. Cost-effectiveness was critically dependent upon the assumptions made concerning offset of effect of intervention after the end of treatment. Where no residual effect was assumed, it was difficult to show cost-effectiveness from any intervention except for the most effective and least expensive. Conversely, cost-effectiveness improved considerably where effectiveness persisted for a longer time. These studies support the view that intervention in the elderly with agents affecting skeletal metabolism alone may be preferred to such interventions at the time of the menopause, and that offset time, hitherto poorly characterized, is a critical component of cost-effectiveness, particularly in younger women. Author Affiliation: (1) Department of Economics, Stockholm School of Economics, Stockholm, Sweden, SE (2) Centre for Metabolic Bone Diseases (WHO Collaborating Centre), University of Sheffield Medical School, Sheffield, UK, GB (3) Lilly Research Centre Ltd, Surrey, UK, GB (4) Solberg 8414, Romelanda, Sweden, SE (5) Department of Orthopaedics, MalmoA' General Hospital, Sweden, SE Article note: Received: 26 May 1998 / Accepted: 8 February 1999

Byline: J. Kanis (1), O. Johnell (2), B. Gullberg (2), E. Allander (3), L. Elffors (3), J. Ranstam (4), J. Dequeker (5), G. Dilsen (6), C. Gennari (7), A. Lopes Vaz (8), G. Lyritis (9), G. Mazzuoli (10), L. Miravet (11), M. Passeri (12), R. Perez Cano (13), A. Rapado (14), C. Ribot (15) Keywords: Key words:Body mass index -- Calcium intake -- Hip fracture -- Men -- Physical activity -- Tea Abstract: The aims of this study were to identify risk factors for hip fracture in men aged 50 years or more. We identified 730 men with hip fracture from 14 centers from Portugal, Spain, France, Italy, Greece and Turkey during the course of a prospective study of hip fracture incidence and 1132 age-stratified controls selected from the neighborhood or population registers. The questionnaire examined aspects of work, physical activity past and present, diseases and drugs, height, weight, indices of co-morbidity and consumption of tobacco, alcohol, calcium, coffee and tea. Significant risk factors identified by univariate analysis included low body mass index (BMI), low sunlight exposure, a low degree of recreational physical activity, low consumption of milk and cheese, and a poor mental score. Co-morbidity including sleep disturbances, loss of weight, impaired mental status and poor appetite were also significant risk factors. Previous stroke with hemiplegia, prior fragility fractures, senile dementia, alcoholism and gastrectomy were associated with significant risk, whereas osteoarthrosis, nephrolithiasis and myocardial infarction were associated with lower risks. Taking medications was not associated with a difference in risk apart from a protective effect with the use of analgesics independent of co-existing osteoarthrosis and an increased risk with the use of anti-epileptic agents. Of the potentially 'reversible' risk factors, BMI, leisure exercise, exposure to sunlight and consumption of tea and alcohol and tobacco remained independent risk factors after multivariate analysis, accounting for 54% of hip fractures. Excluding BMI, 46% of fractures could be explained on the basis of the risk factors sought. Of the remaining factors low exposure to sunlight and decreased physical activity accounted for the highest attributable risks (14% and 9% respectively). The use of risk factors to predict hip fractures had relatively low sensitivity and specificity (59.6% and 61.0% respectively). We conclude that lifestyle factors are associated with significant differences in the risk of hip fracture. Potentially remediable factors including a low degree of physical exercise and a low BMI account for a large component of the total risk. Author Affiliation: (1) WHO Collaborating Centre for Metabolic Bone Diseases, University of Sheffield Medical School, Sheffield, UK, GB (2) Department of Orthopaedics and Community Health Sciences, MalmoA' General Hospital, MalmoA', Sweden, SE (3) WHO Collaborating Centre for the Epidemiology of Rheumatic Conditions, Huddinge University Hospital, Huddinge, Sweden, SE (4) Department of Community Health Sciences, Lund University, MalmoA', Sweden, SE (5) Afdeling Rheumatologie, Academisch Ziekenhuis, Pellenberg, Belgium, BE (6) Istanbul Universitesi, Istanbul Tip Fakultesi, Fiziksel Tip ve Rehabilitasyon, Istanbul, Turkey, TR (7) Institute of Medical Pathology, University of Siena, Siena, Italy, IT (8) Rua Gaspar Correia 87, Porto, Portugal, PT (9) Th. Garofalidis Research Center, Accident Hospital, Kifissia, Greece, GR (10) Policlinico Umberto I, II Clinica Medica, Rome, Italy, IT (11) Centre Viggo Petersen, Ho^pital Lariboisiere, Paris, France, FR (12) Instituto di Clinica Medica Generale, e Terapia Medica, Parma, Italy, IT (13) Department of Medicine, University Hospital of Seville, Seville, Spain, ES (14) Departmento de Medicina Interna, Fundacion Jimenez Diaz, Madrid, Spain, ES (15) Service d'Endocrinologie, CHU Toulouse Purpan, Toulouse Cedex, France, FR Article note: Received: 15 May 1997 / Accepted: 27 April 1998

Byline: A. Oden (1), A. Dawson (2), W. Dere (3), O. Johnell (4), B. Jonsson (5), J. A. Kanis (6) Keywords: Key words:Hip fracture -- Lifetime risk -- Mortality . Abstract: Estimates of lifetime risk of osteoporotic fracture have assumed that mortality rates do not change. Since mortality in the elderly is decreasing in all regions of the world we assessed the effect of this on lifetime risks for hip fracture using Sweden as a reference country. Lifetime risks of hip fracture at the age of 50 years were 4.6% and 13.9% in men and women respectively, assuming all survive to current average life expectancy. Estimates increased to 8.1% and 19.5% when based on present mortality and to 11.1% and 22.7% respectively based on predicted mortality. We conclude that lifetime risks of hip fracture have been considerably underestimated. Author Affiliation: (1) Consulting Statistician, Gothenburg, Sweden, SE (2) Lilly Research Centre Ltd, Windlesham, Surrey, UK, GB (3) Indiana University School of Medicine and Lilly Research Laboratories, Indianapolis, Indiana, USA, US (4) Department of Orthopaedics, MalmoA' General Hospital, MalmoA', Sweden, SE (5) Department of Economics, Stockholm School of Economics, Stockholm, Sweden , SE (6) WHO Collaborating Centre for Metabolic Bone Diseases, Sheffield, UK, GB Article note: Received: 15 September 1997 / Revised: 17 March 1998

Byline: K. MichaA< Keywords: Key words:Estrogen -- Hip fracture -- Hormone replacement therapy -- Interaction -- Physical activity -- Weight Abstract: Use of postmenopausal hormone replacement therapy (HRT) has been associated with a reduced risk of osteoporotic fractures. However, it is uncertain whether this risk reduction is modified by other risk factors for hip fracture. In a population-based case--control study in Sweden, we investigated the association between HRT and hip fracture risk within categories of age, body measures and lifestyle factors in postmenopausal women, 50--81 years of age. Mailed questionnaires and telephone interviews were used to collect data. Of those eligible, 1328 incident cases with hip fracture (82.5%) and 3312 randomly selected controls (81.6%) answered the questionnaire. Ever use of HRT in women less than 75 years old was associated with an odds ratio (OR) of 0.66 (95% confidence interval: 95% CI 0.50--0.87) for hip fracture compared with OR 0.40 (95% CI 0.21--0.77) in women 75 years or older. We found a significant interaction between HRT and both weight and physical activity (p&lt 0.05). The protective effect of HRT was particularly pronounced in lean women: compared with never HRT users, ever users weighing under 60 kg had an OR of 0.44 (95% CI 0.30--0.66) whereas women weighing more than 70 kg had an OR of 0.91 (95% CI 0.53-1.-56). Women with low recent leisure physical activity (less than 1 h/week) similarly benefited more from HRT for hip fracture prevention than women with a higher degree of recreational physical activity. The observed interactions with weight and physical activity suggest that HRT has the best protective effect against hip fracture among high-risk women. Author Affiliation: (1) Department of Orthopaedics, University Hospital, Uppsala, Sweden, SE (2) Departments of Medicine and Community &amp Family Medicine, Dartmouth Medical School, Hanover, New Hampshire, USA, US (3) Department of Medical Epidemiology, Karolinska Institute, Stockholm, Sweden, SE (4) Department of Orthopaedics, MalmA<< General Hospital, MalmA< (5) Department of Internal Medicine, University Hospital, Uppsala, Sweden, SE Article note: Received: 7 October 1997 / Revised: 21 January 1998

Byline: M. Sundberg (1), P. Gardsell (2), O. Johnell (2), E. Ornstein (1), I. Sernbo (2) Keywords: Key words:Bone mineral density -- Children -- DXA -- SXA -- Quantitative ultrasound Abstract: We performed ultrasound measurements (QUS) of the calcaneus in a population-based setting on 280 healthy children, aged 11--16 years, from a small urban area in southern Sweden. The results are compared with dual-energy X-ray absorptiometry (DXA) measurements in the total body, the lumbar spine and the hip, as well as single-energy X-ray absorptiometry (SXA) of the forearm. Normative data and correlations between the three different techniques were determined. We found significant correlations between QUS and age (r= 0.34--0.54), height (r= 0.13--0.56) and weight (r= 0.30--0.60), and between QUS and bone mineral density (BMD) measurements (r= 0.44--0.70). Boys increased all their bone mineral variables with age, whereas girls showed a decreasing trend from age 15 years. QUS had a significantly higher increase in standardized value with age than Ward's triangle BMD, but a significantly lower increase in standardized value with age than distal radius (cortical site) BMD. At other BMD sites we did not find any significant differences compared with QUS regarding changes with age. The measurements obtained by QUS, DXA and SXA, respectively, were divided into quartiles. Of all subjects in the lowest quartile for QUS measurements, only 34--50% were also in the lowest quartiles for DXA and SXA measurements. In conclusion, QUS measurements of the calcaneus in children show similar results as for adult regarding the correlation with DXA and SXA they also have a significant correlation with anthropometric data. QUS did not identify the same individuals with low bone mass as the X-ray techniques. Author Affiliation: (1) Department of Orthropaedics, Hassleholm-Kristianstad, SE (2) Department of Orthopaedics, Malmo University Hospital, Sweden, SE Article note: Received: 23 June 1997 / Accepted: 21 January 1998