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      Predicting risk of osteoporotic fracture in men and women in England and Wales: prospective derivation and validation of QFractureScores

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      BMJ : British Medical Journal
      BMJ Publishing Group Ltd.

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          Abstract

          Objective To develop and validate two new fracture risk algorithms (QFractureScores) for estimating the individual risk of osteoporotic fracture or hip fracture over 10 years.

          Design Prospective open cohort study with routinely collected data from 357 general practices to develop the scores and from 178 practices to validate the scores.

          Setting General practices in England and Wales.

          Participants 1 183 663 women and 1 174 232 men aged 30-85 in the derivation cohort, who contributed 7 898 208 and 8 049 306 person years of observation, respectively. There were 24 350 incident diagnoses of osteoporotic fracture in women and 7934 in men, and 9302 incident diagnoses of hip fracture in women and 5424 in men.

          Main outcome measures First (incident) diagnosis of osteoporotic fracture (vertebral, distal radius, or hip) and incident hip fracture recorded in general practice records.

          Results Use of hormone replacement therapy (HRT), age, body mass index (BMI), smoking status, recorded alcohol use, parental history of osteoporosis, rheumatoid arthritis, cardiovascular disease, type 2 diabetes, asthma, tricyclic antidepressants, corticosteroids, history of falls, menopausal symptoms, chronic liver disease, gastrointestinal malabsorption, and other endocrine disorders were significantly and independently associated with risk of osteoporotic fracture in women. Some variables were significantly associated with risk of osteoporotic fracture but not with risk of hip fracture. The predictors for men for osteoporotic and hip fracture were age, BMI, smoking status, recorded alcohol use, rheumatoid arthritis, cardiovascular disease, type 2 diabetes, asthma, tricyclic antidepressants, corticosteroids, history of falls, and liver disease. The hip fracture algorithm had the best performance among men and women. It explained 63.94% of the variation in women and 63.19% of the variation in men. The D statistic values for discrimination were highest for hip fracture in women (2.73) and men (2.68) and were over twice the magnitude of the corresponding values for osteoporotic fracture. The ROC statistics for hip fracture were also high: 0.89 in women and 0.86 for men versus 0.79 and 0.69, respectively, for the osteoporotic fracture outcome. The algorithms were well calibrated with predicted risks closely matching observed risks. The QFractureScore for hip fracture also had good performance for discrimination and calibration compared with the FRAX (fracture risk assessment) algorithm.

          Conclusions These new algorithms can predict risk of fracture in primary care populations in the UK without laboratory measurements and are therefore suitable for use in both clinical settings and for self assessment (www.qfracture.org). QFractureScores could be used to identify patients at high risk of fracture who might benefit from interventions to reduce their risk.

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          Most cited references31

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          Missing data: our view of the state of the art.

          Statistical procedures for missing data have vastly improved, yet misconception and unsound practice still abound. The authors frame the missing-data problem, review methods, offer advice, and raise issues that remain unresolved. They clear up common misunderstandings regarding the missing at random (MAR) concept. They summarize the evidence against older procedures and, with few exceptions, discourage their use. They present, in both technical and practical language, 2 general approaches that come highly recommended: maximum likelihood (ML) and Bayesian multiple imputation (MI). Newer developments are discussed, including some for dealing with missing data that are not MAR. Although not yet in the mainstream, these procedures may eventually extend the ML and MI methods that currently represent the state of the art.
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            Active smoking and the risk of type 2 diabetes: a systematic review and meta-analysis.

            Observational studies have suggested an association between active smoking and the incidence of type 2 diabetes. To conduct a systematic review with meta-analysis of studies assessing the association between active smoking and incidence of type 2 diabetes. A search of MEDLINE (1966 to May 2007) and EMBASE (1980 to May 2007) databases was supplemented by manual searches of bibliographies of key retrieved articles, reviews of abstracts from scientific meetings, and contact with experts. Studies were included if they reported risk of impaired fasting glucose, impaired glucose tolerance, or type 2 diabetes in relationship to smoking status at baseline; had a cohort design; and excluded persons with diabetes at baseline. Two authors independently extracted the data, including the presence or absence of active smoking at baseline, the risk of diabetes, methods used to detect diabetes, and key criteria of study quality. Relative risks (RRs) were pooled using a random-effects model. Associations were tested in subgroups representing different patient characteristics and study quality criteria. The search yielded 25 prospective cohort studies (N = 1.2 million participants) that reported 45 844 incident cases of diabetes during a study follow-up period ranging from 5 to 30 years. Of the 25 studies, 24 reported adjusted RRs greater than 1 (range for all studies, 0.82-3.74). The pooled adjusted RR was 1.44 (95% confidence interval [CI], 1.31-1.58). Results were consistent and statistically significant in all subgroups. The risk of diabetes was greater for heavy smokers (> or =20 cigarettes/day; RR, 1.61; 95% CI, 1.43-1.80) than for lighter smokers (RR,1.29; 95% CI, 1.13-1.48) and lower for former smokers (RR, 1.23; 95% CI, 1.14-1.33) compared with active smokers, consistent with a dose-response phenomenon. Active smoking is associated with an increased risk of type 2 diabetes. Future research should attempt to establish whether this association is causal and to clarify its mechanisms.
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              Vitamin D3 and calcium to prevent hip fractures in the elderly women.

              Hypovitaminosis D and a low calcium intake contribute to increased parathyroid function in elderly persons. Calcium and vitamin D supplements reduce this secondary hyperparathyroidism, but whether such supplements reduce the risk of hip fractures among elderly people is not known. We studied the effects of supplementation with vitamin D3 (cholecalciferol) and calcium on the frequency of hip fractures and other nonvertebral fractures, identified radiologically, in 3270 healthy ambulatory women (mean [+/- SD] age, 84 +/- 6 years). Each day for 18 months, 1634 women received tricalcium phosphate (containing 1.2 g of elemental calcium) and 20 micrograms (800 IU) of vitamin D3, and 1636 women received a double placebo. We measured serial serum parathyroid hormone and 25-hydroxyvitamin D (25(OH)D) concentrations in 142 women and determined the femoral bone mineral density at base line and after 18 months in 56 women. Among the women who completed the 18-month study, the number of hip fractures was 43 percent lower (P = 0.043) and the total number of nonvertebral fractures was 32 percent lower (P = 0.015) among the women treated with vitamin D3 and calcium than among those who received placebo. The results of analyses according to active treatment and according to intention to treat were similar. In the vitamin D3-calcium group, the mean serum parathyroid hormone concentration had decreased by 44 percent from the base-line value at 18 months (P < 0.001) and the serum 25(OH)D concentration had increased by 162 percent over the base-line value (P < 0.001). The bone density of the proximal femur increased 2.7 percent in the vitamin D3-calcium group and decreased 4.6 percent in the placebo group (P < 0.001). Supplementation with vitamin D3 and calcium reduces the risk of hip fractures and other nonvertebral fractures among elderly women.
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                Author and article information

                Contributors
                Role: professor of clinical epidemiology and general practice
                Role: associate professor in medical statistics
                Journal
                BMJ
                bmj
                BMJ : British Medical Journal
                BMJ Publishing Group Ltd.
                0959-8138
                1468-5833
                2009
                2009
                19 November 2009
                : 339
                : b4229
                Affiliations
                [1 ]Division of Primary Care, Tower Building, University Park, Nottingham NG2 7RD
                Author notes
                Correspondence to: J Hippisley-Cox Julia.hippisley-cox@ 123456nltworld.com
                Article
                hipj633099
                10.1136/bmj.b4229
                2779855
                19926696
                53346deb-995f-4f08-9a0a-3485c8094ad6

                This is an open-access article distributed under the terms of the Creative Commons Attribution Non-commercial License, which permits use, distribution, and reproduction in any medium, provided the original work is properly cited, the use is non commercial and is otherwise in compliance with the license. See: http://creativecommons.org/licenses/by-nc/2.0/ and http://creativecommons.org/licenses/by-nc/2.0/legalcode.

                History
                : 8 July 2009
                Categories
                Research
                Liver disease
                Smoking and tobacco
                Epidemiologic studies
                General practice / family medicine
                Immunology (including allergy)
                Drugs: cardiovascular system
                Menopause (including HRT)
                Asthma
                Connective tissue disease
                Degenerative joint disease
                Drugs: musculoskeletal and joint diseases
                Musculoskeletal syndromes
                Osteoporosis
                Rheumatoid arthritis
                Trauma
                Calcium and bone
                Diabetes
                Metabolic disorders
                Health education
                Injury
                Health promotion
                Smoking

                Medicine
                Medicine

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