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Performance of FRAX in women with breast cancer initiating aromatase inhibitor therapy: A Registry-Based Cohort Study

Performance of FRAX in women with breast cancer initiating aromatase inhibitor therapy: A Registry-Based Cohort Study
Performance of FRAX in women with breast cancer initiating aromatase inhibitor therapy: A Registry-Based Cohort Study

FRAX was developed to predict 10-year probability of major osteoporotic fracture (MOF) and hip fracture in the general population. Aromatase inhibitors (AI) used in breast cancer induce loss in bone mineral density (BMD) and are reported to increase fracture risk. AI exposure is not a direct input to FRAX but is captured under “secondary osteoporosis”. To inform use of FRAX in women treated with AI, we used a population-based registry for the Province of Manitoba, Canada, to identify women aged ≥40 years initiating AI for breast cancer with at least 12 months’ AI exposure (n = 1775), women with breast cancer not receiving AI (n = 1016), and women from the general population (n = 34,205). Among AI users, fracture probability estimated without BMD (AI use coded as secondary osteoporosis) significantly overestimated risk (10-year observed/predicted ratio 0.56, 95% confidence interval [CI] 0.45–0.68; 10-year hip fracture observed/predicted ratio 0.33, 95% CI 0.18–0.49). However, when BMD was included in the fracture probability, there was no significant difference between observed and predicted fracture risk. In Cox proportional hazards models, FRAX stratified risk of MOF, hip, and any fracture equally well in all subgroups (p-interaction >0.1). When adjusted for FRAX score without BMD, with AI use coded as secondary osteoporosis, AI users were at significantly lower risk for MOF (hazard ratio [HR] = 0.78, 95% CI 0.64–0.95), hip fracture (HR = 0.46, 95% CI 0.29–0.73) and any fracture (HR = 0.75, 95% CI 0.63–0.89). AI use was no longer significantly associated with fractures when AI use was not entered as secondary osteoporosis in FRAX without BMD or when BMD was included in the FRAX calculation. In conclusion, FRAX scores stratify fracture risk equally well in women receiving AI therapy as in non-users, but including secondary osteoporosis as a risk factor for AI users overestimates fracture risk. Our results call this practice into question.

AROMATASE INHIBITORS, BONE DENSITOMETRY, BREAST CANCER, FRACTURE RISK, FRAX, OSTEOPOROSIS
0884-0431
1-8
Leslie, William D.
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Morin, Suzanne N.
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Lix, Lisa M.
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Niraula, Saroj
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McCloskey, Eugene V.
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Johansson, Helena
04f12338-4dd1-437b-b9bc-e0884130c215
Harvey, Nicholas C.
ce487fb4-d360-4aac-9d17-9466d6cba145
Kanis, John A.
f1621d8d-8afb-4d97-9679-2165d88a344d
Leslie, William D.
5b2dd5d6-4569-40a3-a9b1-95152d11e4f1
Morin, Suzanne N.
68489af8-f604-4f28-88e0-60add9fde4ae
Lix, Lisa M.
2fb61783-047d-4a4b-a45d-e09ac0763a7b
Niraula, Saroj
06711258-9723-4a9b-bf1d-706e06d44cb2
McCloskey, Eugene V.
2f057a16-3d4e-4597-80c7-6ce47f969c78
Johansson, Helena
04f12338-4dd1-437b-b9bc-e0884130c215
Harvey, Nicholas C.
ce487fb4-d360-4aac-9d17-9466d6cba145
Kanis, John A.
f1621d8d-8afb-4d97-9679-2165d88a344d

Leslie, William D., Morin, Suzanne N., Lix, Lisa M., Niraula, Saroj, McCloskey, Eugene V., Johansson, Helena, Harvey, Nicholas C. and Kanis, John A. (2019) Performance of FRAX in women with breast cancer initiating aromatase inhibitor therapy: A Registry-Based Cohort Study. Journal of Bone and Mineral Research, 1-8. (doi:10.1002/jbmr.3726).

Record type: Article

Abstract

FRAX was developed to predict 10-year probability of major osteoporotic fracture (MOF) and hip fracture in the general population. Aromatase inhibitors (AI) used in breast cancer induce loss in bone mineral density (BMD) and are reported to increase fracture risk. AI exposure is not a direct input to FRAX but is captured under “secondary osteoporosis”. To inform use of FRAX in women treated with AI, we used a population-based registry for the Province of Manitoba, Canada, to identify women aged ≥40 years initiating AI for breast cancer with at least 12 months’ AI exposure (n = 1775), women with breast cancer not receiving AI (n = 1016), and women from the general population (n = 34,205). Among AI users, fracture probability estimated without BMD (AI use coded as secondary osteoporosis) significantly overestimated risk (10-year observed/predicted ratio 0.56, 95% confidence interval [CI] 0.45–0.68; 10-year hip fracture observed/predicted ratio 0.33, 95% CI 0.18–0.49). However, when BMD was included in the fracture probability, there was no significant difference between observed and predicted fracture risk. In Cox proportional hazards models, FRAX stratified risk of MOF, hip, and any fracture equally well in all subgroups (p-interaction >0.1). When adjusted for FRAX score without BMD, with AI use coded as secondary osteoporosis, AI users were at significantly lower risk for MOF (hazard ratio [HR] = 0.78, 95% CI 0.64–0.95), hip fracture (HR = 0.46, 95% CI 0.29–0.73) and any fracture (HR = 0.75, 95% CI 0.63–0.89). AI use was no longer significantly associated with fractures when AI use was not entered as secondary osteoporosis in FRAX without BMD or when BMD was included in the FRAX calculation. In conclusion, FRAX scores stratify fracture risk equally well in women receiving AI therapy as in non-users, but including secondary osteoporosis as a risk factor for AI users overestimates fracture risk. Our results call this practice into question.

Full text not available from this repository.

More information

Accepted/In Press date: 10 March 2019
e-pub ahead of print date: 9 May 2019
Keywords: AROMATASE INHIBITORS, BONE DENSITOMETRY, BREAST CANCER, FRACTURE RISK, FRAX, OSTEOPOROSIS

Identifiers

Local EPrints ID: 431263
URI: http://eprints.soton.ac.uk/id/eprint/431263
ISSN: 0884-0431
PURE UUID: 6f6d0dcc-81c1-4bb8-bf75-8e273018ee18
ORCID for Nicholas C. Harvey: ORCID iD orcid.org/0000-0002-8194-2512

Catalogue record

Date deposited: 29 May 2019 16:30
Last modified: 07 Oct 2020 01:49

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