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A review of the methods used to define glucocorticoid exposure and risk attribution when investigating the risk of fracture in a rheumatoid arthritis population

A review of the methods used to define glucocorticoid exposure and risk attribution when investigating the risk of fracture in a rheumatoid arthritis population
A review of the methods used to define glucocorticoid exposure and risk attribution when investigating the risk of fracture in a rheumatoid arthritis population
Background: Glucocorticoid therapy is used widely in patients with rheumatoid arthritis (RA) with good efficacy but concerns about safety including fractures. Estimates of fracture risk for any given patient are complicated by the dynamic pattern of glucocorticoid use, where patients vary in their dose, duration and timing of glucocorticoid use.

Objective: To investigate which methods are currently used to attribute fractures to glucocorticoid exposure and investigate whether such methods can consider individual treatment patterns.

Results: Thirty-eight studies used five common definitions of risk attribution to glucocorticoid exposure: “current use”, “ever use”, “daily dose”, “cumulative dose” and “time variant”. One study attempted to combine multiple definitions where “cumulative dose” was nested within “daily dose”, covering the effects of dose and duration but not timing. The majority of results demonstrated an equivocal or increased risk of fracture with increased exposure, although there was wide variation, with odds ratios, hazard ratios and relative risks ranging from 0.16 to 8.16. Within definitions there was also variability in the results with the smallest range for “time variant”, 1.07 to 2.8, and the largest for “cumulative dose”, ranging from risk estimates of 0.88 to 8.12.

Conclusion: Many studies have looked into the effect of glucocorticoids on fracture risk in patients with RA. Despite this, there is no clear consensus about the magnitude of risk. This is a consequence of the varied analysis models and their different assumptions. Moreover, no current analysis method allows consideration of dose, duration and timing of glucocorticoid therapy, preventing a clear understanding of fracture risk for patients and their individual treatment patterns.
8756-3282
1-31
Robinson, D.E.
a89b4176-6b64-4be4-bbca-6b3c630f5570
Dennison, E.M.
ee647287-edb4-4392-8361-e59fd505b1d1
Cooper, C.
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van Staa, T.P.
31b8bfb4-4e1b-4a48-a5a6-90ca601b94af
Dixon, W.G.
5dddafc1-ae5f-466e-8517-8369ee750cbc
Robinson, D.E.
a89b4176-6b64-4be4-bbca-6b3c630f5570
Dennison, E.M.
ee647287-edb4-4392-8361-e59fd505b1d1
Cooper, C.
e05f5612-b493-4273-9b71-9e0ce32bdad6
van Staa, T.P.
31b8bfb4-4e1b-4a48-a5a6-90ca601b94af
Dixon, W.G.
5dddafc1-ae5f-466e-8517-8369ee750cbc

Robinson, D.E., Dennison, E.M., Cooper, C., van Staa, T.P. and Dixon, W.G. (2016) A review of the methods used to define glucocorticoid exposure and risk attribution when investigating the risk of fracture in a rheumatoid arthritis population. Bone, 1-31. (doi:10.1016/j.bone.2016.06.001). (PMID:27268854)

Record type: Article

Abstract

Background: Glucocorticoid therapy is used widely in patients with rheumatoid arthritis (RA) with good efficacy but concerns about safety including fractures. Estimates of fracture risk for any given patient are complicated by the dynamic pattern of glucocorticoid use, where patients vary in their dose, duration and timing of glucocorticoid use.

Objective: To investigate which methods are currently used to attribute fractures to glucocorticoid exposure and investigate whether such methods can consider individual treatment patterns.

Results: Thirty-eight studies used five common definitions of risk attribution to glucocorticoid exposure: “current use”, “ever use”, “daily dose”, “cumulative dose” and “time variant”. One study attempted to combine multiple definitions where “cumulative dose” was nested within “daily dose”, covering the effects of dose and duration but not timing. The majority of results demonstrated an equivocal or increased risk of fracture with increased exposure, although there was wide variation, with odds ratios, hazard ratios and relative risks ranging from 0.16 to 8.16. Within definitions there was also variability in the results with the smallest range for “time variant”, 1.07 to 2.8, and the largest for “cumulative dose”, ranging from risk estimates of 0.88 to 8.12.

Conclusion: Many studies have looked into the effect of glucocorticoids on fracture risk in patients with RA. Despite this, there is no clear consensus about the magnitude of risk. This is a consequence of the varied analysis models and their different assumptions. Moreover, no current analysis method allows consideration of dose, duration and timing of glucocorticoid therapy, preventing a clear understanding of fracture risk for patients and their individual treatment patterns.

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Accepted/In Press date: 1 June 2016
e-pub ahead of print date: 3 June 2016
Organisations: Faculty of Medicine

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Local EPrints ID: 396513
URI: http://eprints.soton.ac.uk/id/eprint/396513
ISSN: 8756-3282
PURE UUID: a45d5859-8fb7-43fb-9119-1b0ffa232728
ORCID for E.M. Dennison: ORCID iD orcid.org/0000-0002-3048-4961
ORCID for C. Cooper: ORCID iD orcid.org/0000-0003-3510-0709

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Date deposited: 10 Jun 2016 09:24
Last modified: 18 Feb 2021 16:48

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Contributors

Author: D.E. Robinson
Author: E.M. Dennison ORCID iD
Author: C. Cooper ORCID iD
Author: T.P. van Staa
Author: W.G. Dixon

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