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Risk of venous thromboembolism among different anti-osteoporosis drugs: a population-based cohort analysis including over 200,000 participants from Spain and the UK

Risk of venous thromboembolism among different anti-osteoporosis drugs: a population-based cohort analysis including over 200,000 participants from Spain and the UK
Risk of venous thromboembolism among different anti-osteoporosis drugs: a population-based cohort analysis including over 200,000 participants from Spain and the UK
Summary:

The venous thromboembolism risk among anti-osteoporotics is unknown. In this primary care study, the risk with other bisphosphonates [1.05 (0.94–1.18) and 0.96 (0.78–1.18)], strontium [0.90 (0.61–1.34) and 1.19 (0.82–1.74)], in the UK and Spain respectively, and denosumab [1.77 (0.25–12.66)] and teriparatide [1.27 (0.59–2.71)] in Spain, did not differ versus alendronate.

Introduction:

Most of the known adverse drug reactions described for anti-osteoporosis medication (AOM) have been described in studies comparing AOM users to non-users. We aimed to compare the risk of venous thromboembolism (VTE) among incident users of different AOM compared to alendronate (first line therapy).

Methods:

Two cohort studies were performed using data from the UK (CPRD) and Spain (BIFAP) primary care records separately. All patients aged ≥ 50 years with at least 1 year of data available and a new prescription or dispensation of AOM (date for therapy initiation) during 2000–2014 (CPRD) or 2001–2013 (BIFAP) were included. Users of raloxifene/bazedoxifene were excluded from both databases. Five exposure cohorts were identified according to first treatment: (1) alendronate, (2) other bisphosphonates, (3) strontium ranelate, (4) denosumab, and (5) teriparatide. Participants were followed from the day after therapy initiation to the earliest of a treated VTE (cases), end of AOM treatment (defined by a refill gap of 180 days), switching to an alternative AOM, drop-out, death, or end of study period. Incidence rates of VTE were estimated by cohort. Adjusted hazard ratios (HR 95%CI) were estimated according to drug used.

Results:

Overall, 2035/159,209 (1.28%) in CPRD and 401/83,334 (0.48%) in BIFAP had VTE. Compared to alendronate, adjusted HR of VTE were 1.05 (0.94–1.18) and 0.96 (0.78–1.18) for other bisphosphonates, and 0.90 (0.61–1.34) and 1.19 (0.82–1.74) for strontium in CPRD and BIFAP, respectively; 1.77 (0.25–12.66) for denosumab and 1.27 (0.59–2.71) for teriparatide in BIFAP.

Conclusions:

VTE risk during AO therapy did not differ by AOM drug use. Our data does not support an increased risk of VTE associated with strontium ranelate use in the community.
0937-941X
1-12
Martin-Merino, E.
b539c4b3-858a-4e36-b515-be81735b20a5
Petersen, I.
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Hawley, S.
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Alverez-Gutierrez, A.
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Khalid, S.
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Llorente-Garcia, A.
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Delmestri, A.
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Javaid, M. K.
8841650b-9deb-4d23-933b-6be97763ba65
Van Staa, T. P.
c7951548-8377-4909-9dc2-eb29456f9da9
Judge, A.
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Cooper, C.
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Prieto-Alhambra, D.
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Martin-Merino, E.
b539c4b3-858a-4e36-b515-be81735b20a5
Petersen, I.
12390ec9-c76d-4225-8444-a74853a54a39
Hawley, S.
665700ff-33b4-44b9-8d37-a8e474e7c131
Alverez-Gutierrez, A.
53383693-9381-4bd2-b90d-36c1470694d7
Khalid, S.
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Llorente-Garcia, A.
678d75f6-fcd6-4035-bd6b-e16b4f005718
Delmestri, A.
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Javaid, M. K.
8841650b-9deb-4d23-933b-6be97763ba65
Van Staa, T. P.
c7951548-8377-4909-9dc2-eb29456f9da9
Judge, A.
c6a83964-1d7c-4aa8-b2bf-9c264d1e487d
Cooper, C.
e05f5612-b493-4273-9b71-9e0ce32bdad6
Prieto-Alhambra, D.
051113cd-2da1-4e0d-aa4b-d7b1fe63cd12

Martin-Merino, E., Petersen, I., Hawley, S., Alverez-Gutierrez, A., Khalid, S., Llorente-Garcia, A., Delmestri, A., Javaid, M. K., Van Staa, T. P., Judge, A., Cooper, C. and Prieto-Alhambra, D. (2017) Risk of venous thromboembolism among different anti-osteoporosis drugs: a population-based cohort analysis including over 200,000 participants from Spain and the UK. Osteoporosis International, 1-12. (doi:10.1007/s00198-017-4308-5).

Record type: Article

Abstract

Summary:

The venous thromboembolism risk among anti-osteoporotics is unknown. In this primary care study, the risk with other bisphosphonates [1.05 (0.94–1.18) and 0.96 (0.78–1.18)], strontium [0.90 (0.61–1.34) and 1.19 (0.82–1.74)], in the UK and Spain respectively, and denosumab [1.77 (0.25–12.66)] and teriparatide [1.27 (0.59–2.71)] in Spain, did not differ versus alendronate.

Introduction:

Most of the known adverse drug reactions described for anti-osteoporosis medication (AOM) have been described in studies comparing AOM users to non-users. We aimed to compare the risk of venous thromboembolism (VTE) among incident users of different AOM compared to alendronate (first line therapy).

Methods:

Two cohort studies were performed using data from the UK (CPRD) and Spain (BIFAP) primary care records separately. All patients aged ≥ 50 years with at least 1 year of data available and a new prescription or dispensation of AOM (date for therapy initiation) during 2000–2014 (CPRD) or 2001–2013 (BIFAP) were included. Users of raloxifene/bazedoxifene were excluded from both databases. Five exposure cohorts were identified according to first treatment: (1) alendronate, (2) other bisphosphonates, (3) strontium ranelate, (4) denosumab, and (5) teriparatide. Participants were followed from the day after therapy initiation to the earliest of a treated VTE (cases), end of AOM treatment (defined by a refill gap of 180 days), switching to an alternative AOM, drop-out, death, or end of study period. Incidence rates of VTE were estimated by cohort. Adjusted hazard ratios (HR 95%CI) were estimated according to drug used.

Results:

Overall, 2035/159,209 (1.28%) in CPRD and 401/83,334 (0.48%) in BIFAP had VTE. Compared to alendronate, adjusted HR of VTE were 1.05 (0.94–1.18) and 0.96 (0.78–1.18) for other bisphosphonates, and 0.90 (0.61–1.34) and 1.19 (0.82–1.74) for strontium in CPRD and BIFAP, respectively; 1.77 (0.25–12.66) for denosumab and 1.27 (0.59–2.71) for teriparatide in BIFAP.

Conclusions:

VTE risk during AO therapy did not differ by AOM drug use. Our data does not support an increased risk of VTE associated with strontium ranelate use in the community.

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More information

Accepted/In Press date: 7 November 2017
e-pub ahead of print date: 3 December 2017

Identifiers

Local EPrints ID: 416921
URI: http://eprints.soton.ac.uk/id/eprint/416921
ISSN: 0937-941X
PURE UUID: e71c1baa-45f7-4d01-90e1-d57b30fe22e4
ORCID for C. Cooper: ORCID iD orcid.org/0000-0003-3510-0709

Catalogue record

Date deposited: 15 Jan 2018 17:30
Last modified: 26 Nov 2021 02:39

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Contributors

Author: E. Martin-Merino
Author: I. Petersen
Author: S. Hawley
Author: A. Alverez-Gutierrez
Author: S. Khalid
Author: A. Llorente-Garcia
Author: A. Delmestri
Author: M. K. Javaid
Author: T. P. Van Staa
Author: A. Judge
Author: C. Cooper ORCID iD
Author: D. Prieto-Alhambra

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