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Predicting imminent fractures in patients with a recent fracture or starting oral bisphosphonate therapy: development and international validation of prognostic models

Predicting imminent fractures in patients with a recent fracture or starting oral bisphosphonate therapy: development and international validation of prognostic models
Predicting imminent fractures in patients with a recent fracture or starting oral bisphosphonate therapy: development and international validation of prognostic models
The availability of anti-osteoporosis medications with rapid onset and high potency requires tools to identify patients at high imminent fracture risk (IFR). There are few tools that predict a patient's IFR. We aimed to develop and validate tools for target patients with a recent fracture or initiating oral bisphosphonate therapy. Models for two separate cohorts, those with incident fragility fracture (IFx) and with incident oral bisphosphonate prescription (OBP), were developed in primary care records from Spain (SIDIAP database), UK (Clinical Practice Research Datalink GOLD), and Denmark (Danish Health Registries). Separate models were developed for hip, major, and any fracture outcomes. Only variables present in all databases were included in Lasso regression models for the development and logistic regression models for external validation. Discrimination was tested using area under curve (AUC) and calibration was assessed using observed vs predicted risk plots stratified by age, sex, and previous fracture history. The development analyses included 35,526 individuals in the IFx and 41,401 in OBP cohorts, with 671,094 in IFx and 330,256 in OBP for the validation analyses. Both the IFx and OBP models demonstrated similarly good performance for hip fracture at 1 year (with AUCs of 0.79 (95% CI 0.75 to 0.82) and 0.87 (0.83 to 0.91) in Spain, 0.71 (0.71 to 0.72) and 0.73 (0.72 to 0.74) in the UK, and 0.70 (0.70 to 0.70) and 0.69 (0.68 to 0.70) in Denmark), and lower discrimination for major osteoporotic and any fracture sites. Calibration was good across all three countries with similar discrimination and calibration for the 2-year models. The proposed IFR prediction models could be used to identify more precisely patients at high imminent risk of fracture and inform anti-osteoporosis treatment selection. The freely available model parameters permit local validation and implementation.
ANTIRESORPTIVE, FRACTURE PREVENTION, FRACTURE RISK ASSESSMENT, OSTEOPOROSIS, PROGNOSTIC MODEL
0884-0431
Khalid, Sara
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Moncusi, Marta Pineda
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El-Hussein, Leena
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Delmestri, Antonella
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Ernst, Martin
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Smith, Christopher
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Libanati, Cesar
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Toth, Emese
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Javaid, Muhammad K.
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Cooper, Cyrus
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Abrahamsen, Bo
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Prieto-Alhambra, Daniel
e596722a-2f01-4201-bd9d-be3e180e76a9
Khalid, Sara
e86b1286-c1a9-40c1-aa80-c62ceb4c92d9
Moncusi, Marta Pineda
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El-Hussein, Leena
17ff3968-566d-405d-bd32-2b849d455de5
Delmestri, Antonella
d6087fde-5a65-41de-9b5e-bcefc4379ceb
Ernst, Martin
c8bb4e9a-c97f-4bf5-898d-436776695444
Smith, Christopher
969cad82-7677-470b-8997-c9a8c3cb0e13
Libanati, Cesar
4e3b711d-453b-4f15-b175-3975d566b9c9
Toth, Emese
bdefc477-9f08-428c-9132-23f8a8685fa9
Javaid, Muhammad K.
96dface0-b6e3-47f0-8365-7f22f33a2022
Cooper, Cyrus
e05f5612-b493-4273-9b71-9e0ce32bdad6
Abrahamsen, Bo
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Prieto-Alhambra, Daniel
e596722a-2f01-4201-bd9d-be3e180e76a9

Khalid, Sara, Moncusi, Marta Pineda, El-Hussein, Leena, Delmestri, Antonella, Ernst, Martin, Smith, Christopher, Libanati, Cesar, Toth, Emese, Javaid, Muhammad K., Cooper, Cyrus, Abrahamsen, Bo and Prieto-Alhambra, Daniel (2021) Predicting imminent fractures in patients with a recent fracture or starting oral bisphosphonate therapy: development and international validation of prognostic models. Journal of Bone and Mineral Research. (doi:10.1002/jbmr.4414).

Record type: Article

Abstract

The availability of anti-osteoporosis medications with rapid onset and high potency requires tools to identify patients at high imminent fracture risk (IFR). There are few tools that predict a patient's IFR. We aimed to develop and validate tools for target patients with a recent fracture or initiating oral bisphosphonate therapy. Models for two separate cohorts, those with incident fragility fracture (IFx) and with incident oral bisphosphonate prescription (OBP), were developed in primary care records from Spain (SIDIAP database), UK (Clinical Practice Research Datalink GOLD), and Denmark (Danish Health Registries). Separate models were developed for hip, major, and any fracture outcomes. Only variables present in all databases were included in Lasso regression models for the development and logistic regression models for external validation. Discrimination was tested using area under curve (AUC) and calibration was assessed using observed vs predicted risk plots stratified by age, sex, and previous fracture history. The development analyses included 35,526 individuals in the IFx and 41,401 in OBP cohorts, with 671,094 in IFx and 330,256 in OBP for the validation analyses. Both the IFx and OBP models demonstrated similarly good performance for hip fracture at 1 year (with AUCs of 0.79 (95% CI 0.75 to 0.82) and 0.87 (0.83 to 0.91) in Spain, 0.71 (0.71 to 0.72) and 0.73 (0.72 to 0.74) in the UK, and 0.70 (0.70 to 0.70) and 0.69 (0.68 to 0.70) in Denmark), and lower discrimination for major osteoporotic and any fracture sites. Calibration was good across all three countries with similar discrimination and calibration for the 2-year models. The proposed IFR prediction models could be used to identify more precisely patients at high imminent risk of fracture and inform anti-osteoporosis treatment selection. The freely available model parameters permit local validation and implementation.

Text
Khalid JBMR - Accepted Manuscript
Restricted to Repository staff only until 30 September 2022.
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More information

Accepted/In Press date: 1 August 2021
Published date: 3 August 2021
Keywords: ANTIRESORPTIVE, FRACTURE PREVENTION, FRACTURE RISK ASSESSMENT, OSTEOPOROSIS, PROGNOSTIC MODEL

Identifiers

Local EPrints ID: 450790
URI: http://eprints.soton.ac.uk/id/eprint/450790
ISSN: 0884-0431
PURE UUID: e6eb7b0a-9f42-4944-b8f4-6e5baf346ea7
ORCID for Cyrus Cooper: ORCID iD orcid.org/0000-0003-3510-0709

Catalogue record

Date deposited: 11 Aug 2021 16:32
Last modified: 08 Sep 2021 01:37

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Contributors

Author: Sara Khalid
Author: Marta Pineda Moncusi
Author: Leena El-Hussein
Author: Antonella Delmestri
Author: Martin Ernst
Author: Christopher Smith
Author: Cesar Libanati
Author: Emese Toth
Author: Muhammad K. Javaid
Author: Cyrus Cooper ORCID iD
Author: Bo Abrahamsen
Author: Daniel Prieto-Alhambra

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