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

Authors: VANDENPUT, L - Australian Catholic University; JOHANSSON, H - Australian Catholic University; MCCLOSKEY, EUGENE - University Of Sheffield; LIU, E - Australian Catholic University; AKESSON, K - Lund University; ANDERSON, F - University Of Massachusetts; AZAGRA, R - Autonomous University Of Barcelona; BAGER, C - Nordic Bioscience As; BEAUDART, C - University Of Liege; BISCHOFF-FERRARI, HEIKE - University Hospital Zurich; BIVER, E - University Of Geneva; BRUYERE, OLIVIER - University Of Liege; CAULEY, J - University Of Pittsburgh; CENTER, J - Garvan Institute Of Medical Research; CHAPURLAT, R - University Of Lyon; CHRISTIANSEN, C - Nordic Bioscience As; COOPER, CYRUS - University Of Southampton; CRANDALL, C - Geffen School Of Medicine; CUMMINGS, STEVEN - University Of California San Francisco (UCSF); DA SILVA, J - University Of Coimbra; DAWSON-HUGHES, BESS - Jean Mayer Human Nutrition Research Center On Aging At Tufts University; DIEZ-PEREZ, A - Autonomous University Of Barcelona; DUFOUR, A - Marcus Institute For Aging Research; EISMAN, J - University Of New South Wales; ELDERS, P - Amsterdam Public Health Research Institute; FERRARI, S - University Of Geneva; FUJITA, Y - Kindai University; FUJIWARA, S - Yasuda Women'S University; GLUER, C - University Of Kiel; GOLDSTEIN, I - Maccabi Healthcare Services; GOLTZMAN, D - McGill University - Canada; GUDNASON, V - Icelandic Heart Association; HALL, J - University Of Edinburgh; HANS, D - Lausanne University Hospital; HOFF, M - Norwegian University Of Science And Technology; HOLLICK, R - University Of Aberdeen; HUISMAN, M - Vu University Medical Center; IKI, M - Kindai University; ISH-SHALOM, S - Elisha Hospital; JONES, G - University Of Tasmania; KARLSSON, M - Lund University; KHOSLA, S - Mayo Clinic; KIEL, D - Marcus Institute For Aging Research; KOH, W - National University Of Singapore; KOROMANI, F - Erasmus Medical Center; KOTOWICZ, M - Deakin University; KROGER, H - Kuopio University Hospital; KWOK, T - The Chinese University Of Hong Kong (CUHK); LAMY, OLIVIER - Lausanne University Hospital; LANGHAMMER, A - Norwegian University Of Science And Technology; LARIJANI, B - Tehran University; LIPPUNER, K - University Of Bern; MELLSTROM, D - University Of Gothenburg; MERLIJN, T - Amsterdam Public Health Research Institute; NORDSTROM, A - University Of Umea; NORDSTROM, P - University Of Umea; O'NEILL, T - Manchester Academic Health Science Centre; OBERMAYER-PIETSCH, B - Medical University Of Graz; OHLSSON, C - University Of Gothenburg; ORWOLL, E - Oregon Health & Science University; PASCO, J - Deakin University; RIVADENEIRA, F - Erasmus Medical Center; SCHEI, B - Norwegian University Of Science And Technology; SCHOTT, A - University Of Lyon; SHIROMA, E - National Institute On Aging (NIA, NIH); SIGGEIRSDOTTIR, K - Icelandic Heart Association; SIMONSICK, E - National Institute On Aging (NIA, NIH); SORNAY-RENDU, E - Institut National De La Sante Et De La Recherche Medicale (INSERM); SUND, R - University Of Eastern Finland; SWART, K - Amsterdam Public Health Research Institute; SZULC, P - University Of Lyon; TAMAKI, J - Osaka Medical College; TORGENSON, D - University Of York; VAN SCHOOR, N - Vu University Medical Center; VAN STAA, T - University Of Manchester; VILA, J - Hospital Del Mar Medical Research Institute; WAREHAM, N - University Of Cambridge; WRIGHT, N - University Of Alabama At Birmingham; YOSHIMURA, N - University Of Tokyo; ZILLIKENS, M - Erasmus Medical Center; ZWART, M - Catalan Institute Of Health; HARVEY, NICHOLAS - University Of Southampton; LORENTZON, M - Australian Catholic University; LESLIE, W - University Of Manitoba; KANIS, JOHN - University Of Sheffield

Submitted to: Osteoporosis International
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 5/18/2022
Publication Date: 5/31/2022
Citation: Vandenput, L., 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., Dawson-Hughes, B., Diez-Perez, A., Dufour, A.B., Eisman, J.A., Elders, P.J., Ferrari, S., Fujita, Y., Fujiwara, S., Gluer, C.C., Goldstein, 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., Nordstrom, A., Nordstrom, P., 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., Szulc, P., Tamaki, J., Torgenson, 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. 2022. Update of the fracture risk prediction tool FRAX: a systematic review of potential cohorts and analysis plan. Osteoporosis International. 33:3103-2136. https://doi.org/10.1007/s00198-022-06435-6.
DOI: https://doi.org/10.1007/s00198-022-06435-6

Interpretive Summary: The online fracture risk assessment tool, FRAX, has substantially enhanced the targeting of treatment to those at high risk of fracture. The FRAX algorithm has been incorporated into the US Clinical Practice Guidelines and into more than 100 other clinical osteoporosis guidelines worldwide. The aim of this study was to determine whether the current algorithm can be further improved with respect to current and novel risk factors. Data from the Boston STOP IT trial conducted at the HNRCA are included in the new updated database of 2,138,428 participants that will be used to assess risk factors for fracture. This paper describes the included cohorts and the analysis plan for the next updated version of the FRAX algorithm.

Technical 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 the cohort-specific beta coefficients for each risk factor, models comprising 10-year probability of hip and major osteoporotic fracture, with or without femoral neck bone mineral density, will be computed. Conclusions These assembled cohorts and described models will provide the framework for an updated FRAX tool enabling enhanced assessment of fracture risk (PROSPERO (CRD42021227266)).