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

Author

Vandenput, L, Johansson, H, McCloskey, EV, Liu, E, Schini, M, Åkesson, KE, Anderson, FA, Azagra, R, Bager, CL, Beaudart, C, Bischoff-Ferrari, HA, Biver, E, Bruyère, O, Cauley, JA, Center, JR, Chapurlat, R, Christiansen, C, Cooper, C, Crandall, CJ, Cummings, SR, da Silva, JAP, Dawson-Hughes, B, Diez-Perez, A, Dufour, AB, Eisman, JA, Elders, PJM, Ferrari, S, Fujita, Y, Fujiwara, S, Glüer, C-C, Goldshtein, I, Goltzman, D, Gudnason, V, Hall, J, Hans, D, Hoff, M, Hollick, RJ, Huisman, M, Iki, M, Ish-Shalom, S, Jones, G, Karlsson, MK, Khosla, S, Kiel, DP, Koh, W-P, Koromani, F, Kotowicz, MA, Kröger, H, Kwok, T, Lamy, O, Langhammer, A, Larijani, B, Lippuner, K, McGuigan, FEA, Mellström, D, Merlijn, T, Nguyen, TV, Nordström, A, Nordström, P, O'Neill, TW, Obermayer-Pietsch, B, Ohlsson, C, Orwoll, ES, Pasco, JA, Rivadeneira, F, Schott, A-M, Shiroma, EJ, Siggeirsdottir, K, Simonsick, EM, Sornay-Rendu, E, Sund, R, Swart, KMA, Szulc, P, Tamaki, J, Torgerson, DJ, van Schoor, NM, van Staa, TP, Vila, J, Wareham, NJ, Wright, NC, Yoshimura, N, Zillikens, M, Zwart, M, Harvey, NC, Lorentzon, M, Leslie, WD, Kanis, JA, Vandenput, L, Johansson, H, McCloskey, EV, Liu, E, Schini, M, Åkesson, KE, Anderson, FA, Azagra, R, Bager, CL, Beaudart, C, Bischoff-Ferrari, HA, Biver, E, Bruyère, O, Cauley, JA, Center, JR, Chapurlat, R, Christiansen, C, Cooper, C, Crandall, CJ, Cummings, SR, da Silva, JAP, Dawson-Hughes, B, Diez-Perez, A, Dufour, AB, Eisman, JA, Elders, PJM, Ferrari, S, Fujita, Y, Fujiwara, S, Glüer, C-C, Goldshtein, I, Goltzman, D, Gudnason, V, Hall, J, Hans, D, Hoff, M, Hollick, RJ, Huisman, M, Iki, M, Ish-Shalom, S, Jones, G, Karlsson, MK, Khosla, S, Kiel, DP, Koh, W-P, Koromani, F, Kotowicz, MA, Kröger, H, Kwok, T, Lamy, O, Langhammer, A, Larijani, B, Lippuner, K, McGuigan, FEA, Mellström, D, Merlijn, T, Nguyen, TV, Nordström, A, Nordström, P, O'Neill, TW, Obermayer-Pietsch, B, Ohlsson, C, Orwoll, ES, Pasco, JA, Rivadeneira, F, Schott, A-M, Shiroma, EJ, Siggeirsdottir, K, Simonsick, EM, Sornay-Rendu, E, Sund, R, Swart, KMA, Szulc, P, Tamaki, J, Torgerson, DJ, van Schoor, NM, van Staa, TP, Vila, J, Wareham, NJ, Wright, NC, Yoshimura, N, Zillikens, M, Zwart, M, Harvey, NC, Lorentzon, M, Leslie, WD, and Kanis, JA

Abstract

UNLABELLED: The relationship between self-reported falls and fracture risk was estimated in an international meta-analysis of individual-level data from 46 prospective cohorts. Previous falls were associated with an increased fracture risk in women and men and should be considered as an additional risk factor in the FRAX® algorithm. INTRODUCTION: Previous falls are a well-documented risk factor for subsequent fracture but have not yet been incorporated into the FRAX algorithm. The aim of this study was to evaluate, in an international meta-analysis, the association between previous falls and subsequent fracture risk and its relation to sex, age, duration of follow-up, and bone mineral density (BMD). METHODS: The resource comprised 906,359 women and men (66.9% female) from 46 prospective cohorts. Previous falls were uniformly defined as any fall occurring during the previous year in 43 cohorts; the remaining three cohorts had a different question construct. The association between previous falls and fracture risk (any clinical fracture, osteoporotic fracture, major osteoporotic fracture, and hip fracture) was examined using an extension of the Poisson regression model in each cohort and each sex, followed by random-effects meta-analyses of the weighted beta coefficients. RESULTS: Falls in the past year were reported in 21.4% of individuals. During a follow-up of 9,102,207 person-years, 87,352 fractures occurred of which 19,509 were hip fractures. A previous fall was associated with a significantly increased risk of any clinical fracture both in women (hazard ratio (HR) 1.42, 95% confidence interval (CI) 1.33-1.51) and men (HR 1.53, 95% CI 1.41-1.67). The HRs were of similar magnitude for osteoporotic, major osteoporotic fracture, and hip fracture. Sex significantly modified the association between previous fall and fracture risk, with predictive values being higher in men than in women (e.g., for major osteoporotic fracture, HR 1.53 (95% CI 1.27-1.84) in men vs. HR 1

Published
2024

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

Author

Vandenput, L., Johansson, H., McCloskey, E. V., Liu, E., Schini, M., Åkesson, K.E., Anderson, F. A., Azagra, R., Bager, C. L., Beaudart, C., Bischoff-Ferrari, H. A., Biver, E., Bruyère, O., Cauley, J. A., Center, J. R., Chapurlat, R., Christiansen, C., Cooper, C., Crandall, C. J., Cummings, S. R., da Silva, J. A. P., Dawson-Hughes, B., Diez-Perez, A., Dufour, A. B., Eisman, J. A., Elders, P. J. M., Ferrari, S., Fujita, Y., Fujiwara, S., Glüer, C. -C, Goldshtein, I., Goltzman, D., Gudnason, V., Hall, J., Hans, D., Hoff, M., Hollick, R. J., Huisman, M., Iki, M., Ish-Shalom, S., Jones, G., Karlsson, M. K., Khosla, S., Kiel, D. P., Koh, W. -P, Koromani, F., Kotowicz, M. A., Kröger, H., Kwok, T., Lamy, O., Langhammer, A., Larijani, B., Lippuner, K., McGuigan, F. E. A., Mellström, D., Merlijn, T., Nguyen, T. V., Nordström, Anna, Nordström, P., O’Neill, T. W., Obermayer-Pietsch, B., Ohlsson, C., Orwoll, E. S., Pasco, J. A., Rivadeneira, F., Schott, A. -M, Shiroma, E. J., Siggeirsdottir, K., Simonsick, E. M., Sornay-Rendu, E., Sund, R., Swart, K. M. A., Szulc, P., Tamaki, J., Torgerson, D. J., van Schoor, N. M., van Staa, T. P., Vila, J., Wareham, N. J., Wright, N. C., Yoshimura, N., Zillikens, M. C., Zwart, M., Harvey, N. C., Lorentzon, M., Leslie, W. D., Kanis, J. A., Vandenput, L., Johansson, H., McCloskey, E. V., Liu, E., Schini, M., Åkesson, K.E., Anderson, F. A., Azagra, R., Bager, C. L., Beaudart, C., Bischoff-Ferrari, H. A., Biver, E., Bruyère, O., Cauley, J. A., Center, J. R., Chapurlat, R., Christiansen, C., Cooper, C., Crandall, C. J., Cummings, S. R., da Silva, J. A. P., Dawson-Hughes, B., Diez-Perez, A., Dufour, A. B., Eisman, J. A., Elders, P. J. M., Ferrari, S., Fujita, Y., Fujiwara, S., Glüer, C. -C, Goldshtein, I., Goltzman, D., Gudnason, V., Hall, J., Hans, D., Hoff, M., Hollick, R. J., Huisman, M., Iki, M., Ish-Shalom, S., Jones, G., Karlsson, M. K., Khosla, S., Kiel, D. P., Koh, W. -P, Koromani, F., Kotowicz, M. A., Kröger, H., Kwok, T., Lamy, O., Langhammer, A., Larijani, B., Lippuner, K., McGuigan, F. E. A., Mellström, D., Merlijn, T., Nguyen, T. V., Nordström, Anna, Nordström, P., O’Neill, T. W., Obermayer-Pietsch, B., Ohlsson, C., Orwoll, E. S., Pasco, J. A., Rivadeneira, F., Schott, A. -M, Shiroma, E. J., Siggeirsdottir, K., Simonsick, E. M., Sornay-Rendu, E., Sund, R., Swart, K. M. A., Szulc, P., Tamaki, J., Torgerson, D. J., van Schoor, N. M., van Staa, T. P., Vila, J., Wareham, N. J., Wright, N. C., Yoshimura, N., Zillikens, M. C., Zwart, M., Harvey, N. C., Lorentzon, M., Leslie, W. D., and Kanis, J. A.

Abstract

Summary: The relationship between self-reported falls and fracture risk was estimated in an international meta-analysis of individual-level data from 46 prospective cohorts. Previous falls were associated with an increased fracture risk in women and men and should be considered as an additional risk factor in the FRAX® algorithm. Introduction: Previous falls are a well-documented risk factor for subsequent fracture but have not yet been incorporated into the FRAX algorithm. The aim of this study was to evaluate, in an international meta-analysis, the association between previous falls and subsequent fracture risk and its relation to sex, age, duration of follow-up, and bone mineral density (BMD). Methods: The resource comprised 906,359 women and men (66.9% female) from 46 prospective cohorts. Previous falls were uniformly defined as any fall occurring during the previous year in 43 cohorts; the remaining three cohorts had a different question construct. The association between previous falls and fracture risk (any clinical fracture, osteoporotic fracture, major osteoporotic fracture, and hip fracture) was examined using an extension of the Poisson regression model in each cohort and each sex, followed by random-effects meta-analyses of the weighted beta coefficients. Results: Falls in the past year were reported in 21.4% of individuals. During a follow-up of 9,102,207 person-years, 87,352 fractures occurred of which 19,509 were hip fractures. A previous fall was associated with a significantly increased risk of any clinical fracture both in women (hazard ratio (HR) 1.42, 95% confidence interval (CI) 1.33–1.51) and men (HR 1.53, 95% CI 1.41–1.67). The HRs were of similar magnitude for osteoporotic, major osteoporotic fracture, and hip fracture. Sex significantly modified the association between previous fall and fracture risk, with predictive values being higher in men than in women (e.g., for major osteoporotic fracture, HR 1.53 (95% CI 1.27–1.84) in men vs. HR 1.32

Published
2024
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3. Previous fracture and subsequent fracture risk : a meta-analysis to update FRAX

Author

Kanis, J. A., Johansson, H., McCloskey, E. , V, Liu, E., Akesson, K. E., Anderson, F. A., Azagra, R., Bager, C. L., Beaudart, C., Bischoff-Ferrari, H. A., Biver, E., Bruyere, O., Cauley, J. A., Center, J. R., Chapurlat, R., Christiansen, C., Cooper, C., Crandall, C. J., Cummings, S. R., da Silva, J. A. P., Dawson-Hughes, B., Diez-Perez, A., Dufour, A. B., Eisman, J. A., Elders, P. J. M., Ferrari, S., Fujita, Y., Fujiwara, S., Glueer, C. -c., Goldshtein, I., Goltzman, D., Gudnason, V., Hall, J., Hans, D., Hoff, M., Hollick, R. J., Huisman, M., Iki, M., Ish-Shalom, S., Jones, G., Karlsson, M. K., Khosla, S., Kiel, D. P., Koh, W. -p., Koromani, F., Kotowicz, M. A., Kroger, H., Kwok, T., Lamy, O., Langhammer, A., Larijani, B., Lippuner, K., Mellstrom, D., Merlijn, T., Nordström, Anna, Nordström, Peter, O'Neill, T. W., Obermayer-Pietsch, B., Ohlsson, C., Orwoll, E. S., Pasco, J. A., Rivadeneira, F., Schott, A. -M, Shiroma, E. J., Siggeirsdottir, K., Simonsick, E. M., Sornay-Rendu, E., Sund, R., Swart, K. M. A., Szulc, P., Tamaki, J., Torgerson, D. J., van Schoor, N. M., van Staa, T. P., Vila, J., Wareham, N. J., Wright, N. C., Yoshimura, N., Zillikens, M. C., Zwart, M., Vandenput, L., Harvey, N. C., Lorentzon, M., Leslie, W. D., Kanis, J. A., Johansson, H., McCloskey, E. , V, Liu, E., Akesson, K. E., Anderson, F. A., Azagra, R., Bager, C. L., Beaudart, C., Bischoff-Ferrari, H. A., Biver, E., Bruyere, O., Cauley, J. A., Center, J. R., Chapurlat, R., Christiansen, C., Cooper, C., Crandall, C. J., Cummings, S. R., da Silva, J. A. P., Dawson-Hughes, B., Diez-Perez, A., Dufour, A. B., Eisman, J. A., Elders, P. J. M., Ferrari, S., Fujita, Y., Fujiwara, S., Glueer, C. -c., Goldshtein, I., Goltzman, D., Gudnason, V., Hall, J., Hans, D., Hoff, M., Hollick, R. J., Huisman, M., Iki, M., Ish-Shalom, S., Jones, G., Karlsson, M. K., Khosla, S., Kiel, D. P., Koh, W. -p., Koromani, F., Kotowicz, M. A., Kroger, H., Kwok, T., Lamy, O., Langhammer, A., Larijani, B., Lippuner, K., Mellstrom, D., Merlijn, T., Nordström, Anna, Nordström, Peter, O'Neill, T. W., Obermayer-Pietsch, B., Ohlsson, C., Orwoll, E. S., Pasco, J. A., Rivadeneira, F., Schott, A. -M, Shiroma, E. J., Siggeirsdottir, K., Simonsick, E. M., Sornay-Rendu, E., Sund, R., Swart, K. M. A., Szulc, P., Tamaki, J., Torgerson, D. J., van Schoor, N. M., van Staa, T. P., Vila, J., Wareham, N. J., Wright, N. C., Yoshimura, N., Zillikens, M. C., Zwart, M., Vandenput, L., Harvey, N. C., Lorentzon, M., and Leslie, W. D.

Abstract

A large international meta-analysis using primary data from 64 cohorts has quantified the increased risk of fracture associated with a previous history of fracture for future use in FRAX.IntroductionThe aim of this study was to quantify the fracture risk associated with a prior fracture on an international basis and to explore the relationship of this risk with age, sex, time since baseline and bone mineral density (BMD).MethodsWe studied 665,971 men and 1,438,535 women from 64 cohorts in 32 countries followed for a total of 19.5 million person-years. The effect of a prior history of fracture on the risk of any clinical fracture, any osteoporotic fracture, major osteoporotic fracture, and hip fracture alone was examined using an extended Poisson model in each cohort. Covariates examined were age, sex, BMD, and duration of follow-up. The results of the different studies were merged by using the weighted & beta;-coefficients.ResultsA previous fracture history, compared with individuals without a prior fracture, was associated with a significantly increased risk of any clinical fracture (hazard ratio, HR = 1.88; 95% CI = 1.72-2.07). The risk ratio was similar for the outcome of osteoporotic fracture (HR = 1.87; 95% CI = 1.69-2.07), major osteoporotic fracture (HR = 1.83; 95% CI = 1.63-2.06), or for hip fracture (HR = 1.82; 95% CI = 1.62-2.06). There was no significant difference in risk ratio between men and women. Subsequent fracture risk was marginally downward adjusted when account was taken of BMD. Low BMD explained a minority of the risk for any clinical fracture (14%), osteoporotic fracture (17%), and for hip fracture (33%). The risk ratio for all fracture outcomes related to prior fracture decreased significantly with adjustment for age and time since baseline examination.ConclusionA previous history of fracture confers an increased risk of fracture of substantial importance beyond that explained by BMD. The effect is similar in men and women. Its quantitati

Published
2023
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4. Update of the fracture risk prediction tool FRAX : a systematic review of potential cohorts and analysis plan

Author

Vandenput, L., Johansson, H., McCloskey, E.V., Liu, E., Åkesson, K.E., Anderson, F.A., Azagra, R., Bager, C.L., Beaudart, C., Bischoff-Ferrari, H.A., Biver, E., Bruyère, O., Cauley, J.A., Center, J.R., Chapurlat, R., Christiansen, C., Cooper, C., Crandall, C.J., Cummings, S.R., da Silva, J.A.P., Dawson-Hughes, B., Diez-Perez, A., Dufour, A.B., Eisman, J.A., Elders, P.J.M., Ferrari, S., Fujita, Y., Fujiwara, S., Glüer, C.-C., Goldshtein, I., Goltzman, D., Gudnason, V., Hall, J., Hans, D., Hoff, M., Hollick, R.J., Huisman, M., Iki, M., Ish-Shalom, S., Jones, G., Karlsson, M.K., Khosla, S., Kiel, D.P., Koh, W.-P., Koromani, F., Kotowicz, M.A., Kröger, H., Kwok, T., Lamy, O., Langhammer, A., Larijani, B., Lippuner, K., Mellström, D., Merlijn, T., Nordström, Annika, Nordström, Peter, O’Neill, T.W., Obermayer-Pietsch, B., Ohlsson, C., Orwoll, E.S., Pasco, J.A., Rivadeneira, F., Schei, B., Schott, A.-M., Shiroma, E.J., Siggeirsdottir, K., Simonsick, E.M., Sornay-Rendu, E., Sund, R., Swart, K.M.A., Szulc, P., Tamaki, J., Torgerson, D.J., van Schoor, N.M., van Staa, T.P., Vila, J., Wareham, N.J., Wright, N.C., Yoshimura, N., Zillikens, M.C., Zwart, M., Harvey, N.C., Lorentzon, M., Leslie, W.D., Kanis, J.A., Vandenput, L., Johansson, H., McCloskey, E.V., Liu, E., Åkesson, K.E., Anderson, F.A., Azagra, R., Bager, C.L., Beaudart, C., Bischoff-Ferrari, H.A., Biver, E., Bruyère, O., Cauley, J.A., Center, J.R., Chapurlat, R., Christiansen, C., Cooper, C., Crandall, C.J., Cummings, S.R., da Silva, J.A.P., Dawson-Hughes, B., Diez-Perez, A., Dufour, A.B., Eisman, J.A., Elders, P.J.M., Ferrari, S., Fujita, Y., Fujiwara, S., Glüer, C.-C., Goldshtein, I., Goltzman, D., Gudnason, V., Hall, J., Hans, D., Hoff, M., Hollick, R.J., Huisman, M., Iki, M., Ish-Shalom, S., Jones, G., Karlsson, M.K., Khosla, S., Kiel, D.P., Koh, W.-P., Koromani, F., Kotowicz, M.A., Kröger, H., Kwok, T., Lamy, O., Langhammer, A., Larijani, B., Lippuner, K., Mellström, D., Merlijn, T., Nordström, Annika, Nordström, Peter, O’Neill, T.W., Obermayer-Pietsch, B., Ohlsson, C., Orwoll, E.S., Pasco, J.A., Rivadeneira, F., Schei, B., Schott, A.-M., Shiroma, E.J., Siggeirsdottir, K., Simonsick, E.M., Sornay-Rendu, E., Sund, R., Swart, K.M.A., Szulc, P., Tamaki, J., Torgerson, D.J., van Schoor, N.M., van Staa, T.P., Vila, J., Wareham, N.J., Wright, N.C., Yoshimura, N., Zillikens, M.C., Zwart, M., Harvey, N.C., Lorentzon, M., Leslie, W.D., and Kanis, J.A.

Abstract

Summary: We describe the collection of cohorts together with the analysis plan for an update of the fracture risk prediction tool FRAX with respect to current and novel risk factors. The resource comprises 2,138,428 participants with a follow-up of approximately 20 million person-years and 116,117 documented incident major osteoporotic fractures. Introduction: The availability of the fracture risk assessment tool FRAX® has substantially enhanced the targeting of treatment to those at high risk of fracture with FRAX now incorporated into more than 100 clinical osteoporosis guidelines worldwide. The aim of this study is to determine whether the current algorithms can be further optimised with respect to current and novel risk factors. Methods: A computerised literature search was performed in PubMed from inception until May 17, 2019, to identify eligible cohorts for updating the FRAX coefficients. Additionally, we searched the abstracts of conference proceedings of the American Society for Bone and Mineral Research, European Calcified Tissue Society and World Congress of Osteoporosis. Prospective cohort studies with data on baseline clinical risk factors and incident fractures were eligible. Results: Of the 836 records retrieved, 53 were selected for full-text assessment after screening on title and abstract. Twelve cohorts were deemed eligible and of these, 4 novel cohorts were identified. These cohorts, together with 60 previously identified cohorts, will provide the resource for constructing an updated version of FRAX comprising 2,138,428 participants with a follow-up of approximately 20 million person-years and 116,117 documented incident major osteoporotic fractures. For each known and candidate risk factor, multivariate hazard functions for hip fracture, major osteoporotic fracture and death will be tested using extended Poisson regression. Sex- and/or ethnicity-specific differences in the weights of the risk factors will be investigated. After meta-analyses of

Published
2022
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5. Design of the SALT Osteoporosis Study: a randomised pragmatic trial, to study a primary care screening and treatment program for the prevention of fractures in women aged 65 years or older

Author

Elders, P. J. M., primary, Merlijn, T., additional, Swart, K. M. A., additional, van Hout, W., additional, van der Zwaard, B. C., additional, Niemeijer, C., additional, Heymans, M. W., additional, van der Heijden, A. A., additional, Rutters, F., additional, van der Horst, H. E., additional, Lips, P., additional, Netelenbos, J. C., additional, and van Schoor, N. M., additional

Published
2017
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6. A Meta-Analysis of Trabecular Bone Score in Fracture Risk Prediction and Its Relationship to FRAX

Author

McCloskey, E.V., Oden, A., Harvey, N.C., Leslie, W.D., Hans, D., Johansson, H., Barkmann, R., Boutroy, S., Brown, J., Chapurlat, R., Elders, P. J. M., Fujita, Yuki, Gluer, C. C., Goltzman, D., Iki, M., Karlsson, M., Kindmark, A., Kotowicz, M., Kurumatani, N., Kwok, Terry, Lamy, O., Leung, J., Lippuner, K., Ljunggren, O., Lorentzon, M., Mellstrom, D., Merlijn, T., Oei, L., Ohlsson, C., Pasco, J. A., Rivadeneira, F., Rosengren, B., Sornay-Rendu, E., Szulc, P., Tamaki, J., Kanis, John A., Epidemiology, Internal Medicine, General practice, and EMGO - Musculoskeletal health

Subjects
Male, Lumbar Vertebrae, Hip Fractures, Models, Biological, frax, meta-analysis, trabecular bone structure, fracture, Bone Density, Risk Factors, Humans, Osteoporosis, Spinal Fractures, tbs, Female, Prospective Studies, risk
Abstract

Trabecular bone score (TBS) is a gray-level textural index of bone microarchitecture derived from lumbar spine dual-energy X-ray absorptiometry (DXA) images. TBS is a bone mineral density (BMD)-independent predictor of fracture risk. The objective of this meta-analysis was to determine whether TBS predicted fracture risk independently of FRAX probability and to examine their combined performance by adjusting the FRAX probability for TBS. We utilized individual-level data from 17,809 men and women in 14 prospective population-based cohorts. Baseline evaluation included TBS and the FRAX risk variables, and outcomes during follow-up (mean 6.7 years) comprised major osteoporotic fractures. The association between TBS, FRAX probabilities, and the risk of fracture was examined using an extension of the Poisson regression model in each cohort and for each sex and expressed as the gradient of risk (GR; hazard ratio per 1 SD change in risk variable in direction of increased risk). FRAX probabilities were adjusted for TBS using an adjustment factor derived from an independent cohort (the Manitoba Bone Density Cohort). Overall, the GR of TBS for major osteoporotic fracture was 1.44 (95% confidence interval [CI] 1.35-1.53) when adjusted for age and time since baseline and was similar in men and women (p > 0.10). When additionally adjusted for FRAX 10-year probability of major osteoporotic fracture, TBS remained a significant, independent predictor for fracture (GR = 1.32, 95% CI 1.24-1.41). The adjustment of FRAX probability for TBS resulted in a small increase in the GR (1.76, 95% CI 1.65-1.87 versus 1.70, 95% CI 1.60-1.81). A smaller change in GR for hip fracture was observed (FRAX hip fracture probability GR 2.25 vs. 2.22). TBS is a significant predictor of fracture risk independently of FRAX. The findings support the use of TBS as a potential adjustment for FRAX probability, though the impact of the adjustment remains to be determined in the context of clinical assessment guidelines. (C) 2015 American Society for Bone and Mineral Research.

Published
2015
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7. A Meta-Analysis Of Trabecular Bone Score In Fracture Risk Prediction And Its Interaction With Frax

Author

Kanis, J. A., Oden, A., Harvey, N. C., Leslie, W. D., Hans, D., Johansson, H., Barkmann, R., Boutroy, S., Brown, J. P., Chapurlat, R. D., Elders, P., Fujita, Y., Glueer, C. C., Goltzman, D., Iki, M., Karlsson, M. K., Kindmark, Andreas, Kurtunatani, N., Kwok, A., Leung, J., Lippuner, K., Ljunggren, Östen, Lorentzon, M., Mellstrom, D., Merlijn, T., Oei, L., Ohlsson, C., Pasco, J. A., Rivadeneira, F., Rosengren, B., Sornay-Rendu, E., Szulc, P., Tamaki, J., McCloskey, E. V., Kanis, J. A., Oden, A., Harvey, N. C., Leslie, W. D., Hans, D., Johansson, H., Barkmann, R., Boutroy, S., Brown, J. P., Chapurlat, R. D., Elders, P., Fujita, Y., Glueer, C. C., Goltzman, D., Iki, M., Karlsson, M. K., Kindmark, Andreas, Kurtunatani, N., Kwok, A., Leung, J., Lippuner, K., Ljunggren, Östen, Lorentzon, M., Mellstrom, D., Merlijn, T., Oei, L., Ohlsson, C., Pasco, J. A., Rivadeneira, F., Rosengren, B., Sornay-Rendu, E., Szulc, P., Tamaki, J., and McCloskey, E. V.

Published
2015

8. The Effect of a Screening and Treatment Program for the Prevention of Fractures in Older Women: A Randomized Pragmatic Trial.

Author

Merlijn T, Swart KM, van Schoor NM, Heymans MW, van der Zwaard BC, van der Heijden AA, Rutters F, Lips P, van der Horst HE, Niemeijer C, Netelenbos JC, and Elders PJ

Subjects
Aged, Aged, 80 and over, Female, Follow-Up Studies, Humans, Hip Fractures epidemiology, Hip Fractures prevention & control, Mass Screening, Osteoporosis diagnosis, Osteoporosis drug therapy, Osteoporosis epidemiology, Osteoporotic Fractures epidemiology, Osteoporotic Fractures prevention & control, Surveys and Questionnaires
Abstract

Population screening for fracture risk may reduce the fracture incidence. In this randomized pragmatic trial, the SALT Osteoporosis Study (SOS), we studied whether screening for fracture risk and subsequent treatment in primary care can reduce fractures compared with usual care. A total of 11,032 women aged 65 to 90 years with ≥1 clinical risk factor for fractures were individually randomized to screening (n = 5575) or usual care (n = 5457). Participants in the screening group underwent a screening program, including bone densitometry and vertebral fracture assessment. Participants with a high 10-year fracture probability (FRAX) or a vertebral fracture were offered treatment with anti-osteoporosis medication by their general practitioner. Incident fractures as reported by questionnaires were verified with medical records. Follow-up was completed by 94% of the participants (mean follow-up = 3.7 years). Of the 5575 participants in the screening group, 1417 (25.4%) had an indication for anti-osteoporosis medication. Screening and subsequent treatment had no statistically significant effect on the primary outcome fracture (hazard ratio [HR] = 0.97; 95% confidence interval [CI] 0.87-1.08), nor on the secondary outcomes osteoporotic fractures (HR = 0.91; 95% CI 0.81-1.03), major osteoporotic fractures (HR = 0.91; 95% CI 0.80-1.04), hip fractures (HR = 0.91; 95% CI 0.71-1.15), falls (odds ratio [OR] = 0.91; 95% CI 0.72-1.15), or mortality (HR = 1.03; 95% CI 0.91-1.17). Post hoc explorative finding suggested that screening might be most effective after a recent fracture (HR = 0.65; 95% CI 0.44-0.96 for major osteoporotic fractures and HR = 0.38; 95% CI 0.18-0.79 for hip fractures). The results of this study might have been compromised by nonparticipation and medication nonadherence in the screening group. Overall, this study does not provide sufficient indications to consider screening for fracture prevention. However, we cannot exclude its clinical relevance to reduce (major) osteoporotic fractures and hip fractures because of the relatively small number of women with a treatment indication in the intervention group. © 2019 The Authors. Journal of Bone and Mineral Research Published by Wiley Periodicals, Inc., (© 2019 The Authors. Journal of Bone and Mineral Research Published by Wiley Periodicals, Inc.)

Published
2019
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9. A Meta-Analysis of Trabecular Bone Score in Fracture Risk Prediction and Its Relationship to FRAX.

Author

McCloskey EV, Odén A, Harvey NC, Leslie WD, Hans D, Johansson H, Barkmann R, Boutroy S, Brown J, Chapurlat R, Elders PJM, Fujita Y, Glüer CC, Goltzman D, Iki M, Karlsson M, Kindmark A, Kotowicz M, Kurumatani N, Kwok T, Lamy O, Leung J, Lippuner K, Ljunggren Ö, Lorentzon M, Mellström D, Merlijn T, Oei L, Ohlsson C, Pasco JA, Rivadeneira F, Rosengren B, Sornay-Rendu E, Szulc P, Tamaki J, and Kanis JA

Subjects
Female, Humans, Male, Prospective Studies, Risk Factors, Bone Density, Hip Fractures diagnostic imaging, Hip Fractures etiology, Hip Fractures metabolism, Lumbar Vertebrae diagnostic imaging, Lumbar Vertebrae metabolism, Models, Biological, Osteoporosis complications, Osteoporosis diagnostic imaging, Osteoporosis metabolism, Spinal Fractures diagnostic imaging, Spinal Fractures etiology, Spinal Fractures metabolism
Abstract

Trabecular bone score (TBS) is a gray-level textural index of bone microarchitecture derived from lumbar spine dual-energy X-ray absorptiometry (DXA) images. TBS is a bone mineral density (BMD)-independent predictor of fracture risk. The objective of this meta-analysis was to determine whether TBS predicted fracture risk independently of FRAX probability and to examine their combined performance by adjusting the FRAX probability for TBS. We utilized individual-level data from 17,809 men and women in 14 prospective population-based cohorts. Baseline evaluation included TBS and the FRAX risk variables, and outcomes during follow-up (mean 6.7 years) comprised major osteoporotic fractures. The association between TBS, FRAX probabilities, and the risk of fracture was examined using an extension of the Poisson regression model in each cohort and for each sex and expressed as the gradient of risk (GR; hazard ratio per 1 SD change in risk variable in direction of increased risk). FRAX probabilities were adjusted for TBS using an adjustment factor derived from an independent cohort (the Manitoba Bone Density Cohort). Overall, the GR of TBS for major osteoporotic fracture was 1.44 (95% confidence interval [CI] 1.35-1.53) when adjusted for age and time since baseline and was similar in men and women (p > 0.10). When additionally adjusted for FRAX 10-year probability of major osteoporotic fracture, TBS remained a significant, independent predictor for fracture (GR = 1.32, 95% CI 1.24-1.41). The adjustment of FRAX probability for TBS resulted in a small increase in the GR (1.76, 95% CI 1.65-1.87 versus 1.70, 95% CI 1.60-1.81). A smaller change in GR for hip fracture was observed (FRAX hip fracture probability GR 2.25 vs. 2.22). TBS is a significant predictor of fracture risk independently of FRAX. The findings support the use of TBS as a potential adjustment for FRAX probability, though the impact of the adjustment remains to be determined in the context of clinical assessment guidelines. © 2015 American Society for Bone and Mineral Research., (© 2015 American Society for Bone and Mineral Research.)

Published
2016
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10. Prediction of vitamin D deficiency by simple patient characteristics.

Author

Sohl E, Heymans MW, de Jongh RT, den Heijer M, Visser M, Merlijn T, Lips P, and van Schoor NM

Subjects
Aged, Aged, 80 and over, Bayes Theorem, Female, Humans, Logistic Models, Longitudinal Studies, Male, Middle Aged, Netherlands, Prevalence, Risk Factors, Vitamin D Deficiency blood, Vitamin D blood, Vitamin D Deficiency diagnosis, Vitamin D Deficiency epidemiology
Abstract

Background: Vitamin D status is currently diagnosed by measuring serum 25-hydroxyvitamin D [25(OH)D]., Objective: This study aimed to develop a risk profile that can be used to easily identify older individuals at high risk of vitamin D deficiency., Design: This study was performed within the Longitudinal Aging Study Amsterdam, an ongoing cohort study in a representative sample of the Dutch older population (n = 1509 for the development sample and n = 1100 for the validation sample). Prediction models for serum 25(OH)D concentrations <50 and <30 nmol/L were developed by using backward logistic regression. Risk scores were calculated by dividing the individual regression coefficients by the regression coefficient with the lowest β to create simple scores., Results: Serum 25(OH)D concentrations <50 and <30 nmol/L were present in 46.2% and 17.5% of participants, respectively. The model for the prediction of concentrations <50 nmol/L consisted of 13 easily assessable predictors, whereas the model for concentrations <30 nmol/L contained 10 predictors. The resulting areas under the curve (AUCs) were 0.78 and 0.80, respectively. The AUC in the external validation data set was 0.71 for the <50-nmol/L model. At a cutoff of 58 in total risk score (range: 8-97), the model predicted concentrations <50 nmol/L with a sensitivity of 61% and a specificity of 82%, whereas these values were 61% and 84%, respectively, at a cutoff of 110 in the total risk score (range: 6-204) in the model for concentrations <30 nmol/L., Conclusions: Two total risk scores, including 13 or 10 predictors that can easily be assessed, were developed and are able to predict serum 25(OH)D concentrations <50 and <30 nmol/L accurately. These risk scores may be useful in clinical practice to identify persons at risk of vitamin D deficiency.

Published
2014
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11. Physiological concentrations of insulin induce endothelin-mediated vasoconstriction during inhibition of NOS or PI3-kinase in skeletal muscle arterioles.

Author

Eringa EC, Stehouwer CD, Merlijn T, Westerhof N, and Sipkema P

Subjects
Animals, Arterioles drug effects, Arterioles physiology, Culture Techniques, Dose-Response Relationship, Drug, Insulin physiology, Male, Microcirculation drug effects, Nitric Oxide physiology, Nitric Oxide Synthase antagonists & inhibitors, Phosphatidylinositol 3-Kinases physiology, Phosphoinositide-3 Kinase Inhibitors, Rats, Rats, Wistar, Signal Transduction, Vasoconstriction physiology, Endothelin-1 physiology, Insulin pharmacology, Muscle, Skeletal blood supply, Nitric Oxide Synthase physiology, Vasoconstriction drug effects
Abstract

Objective: To determine the roles of nitric oxide, endothelin-1 and phosphatidylinositol 3-kinase (PI3-kinase) in acute responses of isolated rat skeletal muscle arterioles to insulin., Methods: Rat cremaster first order arterioles were separated from surrounding tissue, cannulated in a pressure myograph and responses to insulin (4 microU/ml-3.4 mU/ml) were studied without intraluminal blood or flow., Results: Insulin alone did not significantly affect arteriolar diameter. Non-selective antagonism of endothelin receptors, with PD-142893, uncovered insulin-induced vasodilatation (25+/-8% from baseline at 3.4 mU/ml), which was abolished by inhibition of NO synthesis with N(G)-nitro-L-arginine (L-NA). Inhibition of NO synthesis alone uncovered insulin-induced vasoconstriction at physiological concentrations (21+/-5% from baseline diameter at 34 microU/ml), which was abolished by PD-142893. The NO donor, S-nitroso-N-acetyl-penicillamine (SNAP) inhibited insulin-induced vasoconstriction during NOS inhibition, even at a concentration that did not elicit vasodilatation itself. Inhibition of PI3-kinase, an intracellular mediator of insulin-induced NO production, with wortmannin, also uncovered insulin-induced vasoconstriction (13+/-3% from baseline at 34 microU/ml) that was abolished by PD-142893., Conclusions: Insulin induces both nitric oxide and endothelin-1 activity in rat cremaster first-order arterioles. This study demonstrates for the first time that vasoconstrictive effects of physiological concentrations of insulin during inhibition of NOS activity are mediated by endothelin and that insulin induces endothelin-1-mediated vasoconstriction in isolated skeletal muscle arterioles during inhibition of PI3-kinase. These findings support the hypothesis of altered microvascular reactivity to insulin in conditions of diminished PI3-kinase activity, a prominent feature of insulin resistance.

Published
2002
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