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Risk of fracture with thiazolidinediones: an individual patient data meta-analysis

Risk of fracture with thiazolidinediones: an individual patient data meta-analysis
Risk of fracture with thiazolidinediones: an individual patient data meta-analysis
Background
The use of thiazolidinediones (TZDs) has been associated with increased fracture risks. Our aim was to estimate the risk of fracture with TZDs in three different healthcare registries, using exactly the same study design, and to perform an individual patient data meta-analysis of these three studies.

Methods
Population-based cohort studies were performed utilizing the British General Practice Research Database (GPRD), the Dutch PHARMO Record Linkage System (RLS), and the Danish National Health Registers. In all three databases, the exposed cohort consisted of all patients (aged 18+) with at least one prescription of antidiabetic (AD) medication. Cox proportional hazards models were used to estimate hazard ratios (HRs) of fracture. The total period of follow-up for each patient was divided into periods of current exposure and past exposure, with patients moving between current and past use.

Results
In all three registries, the risk of fracture was increased for women who were exposed to TZDs: HR 1.48 (1.37-1.60) in GPRD, HR 1.35 (1.15-1.58) in PHARMO, and HR 1.22 (1.03-1.44) in Denmark. Combining the data in an individual patient data meta-analysis resulted, for women, in a 1.4-fold increased risk of any fracture for current TZD users versus other AD drug users [adj. HR 1.44 (1.35-1.53)]. For men, there was no increased fracture risk [adj. HR 1.05 (0.96-1.14)]. Risks were increased for fractures of the radius/ulna, humerus, tibia/fibula, ankle, and foot, but not for hip/femur or vertebral fractures. Current TZD users with more than 25 TZD prescriptions ever before had a 1.6-fold increased risk of fracture compared with other AD drug users [HR 1.59 (1.46-1.74)].

Conclusion
In this study, we consistently found a 1.2- to 1.5-fold increased risk of fractures for women using TZDs, but not for men, across three different healthcare registries. TZD users had an increased risk for fractures of the extremities, and risks further increased for prolonged users of TZDs.
1664-2392
11
Bazelier, Marloes T.
701385a8-2cb1-4258-88a4-249c3a7f07f5
de Vries, Frank
10245a32-6083-4feb-9d20-7e7db0f358b1
Vestergaard, Peter
3336d4f1-072c-4b02-935e-a5eca05858e2
Herings, Ron M.C.
686402e8-dfc1-4586-bdac-cbc952747322
Gallagher, Arlene M.
4a77b2c1-c628-47e0-a29c-f726ca3445bc
Leufkens, Hubert G.M.
299d1b54-3a02-48a9-9ffb-71ba2c3fa469
van Staa, Tjeerd-Pieter
f840d545-0e8d-40fe-9124-976826190cc3
Bazelier, Marloes T.
701385a8-2cb1-4258-88a4-249c3a7f07f5
de Vries, Frank
10245a32-6083-4feb-9d20-7e7db0f358b1
Vestergaard, Peter
3336d4f1-072c-4b02-935e-a5eca05858e2
Herings, Ron M.C.
686402e8-dfc1-4586-bdac-cbc952747322
Gallagher, Arlene M.
4a77b2c1-c628-47e0-a29c-f726ca3445bc
Leufkens, Hubert G.M.
299d1b54-3a02-48a9-9ffb-71ba2c3fa469
van Staa, Tjeerd-Pieter
f840d545-0e8d-40fe-9124-976826190cc3

Bazelier, Marloes T., de Vries, Frank, Vestergaard, Peter, Herings, Ron M.C., Gallagher, Arlene M., Leufkens, Hubert G.M. and van Staa, Tjeerd-Pieter (2013) Risk of fracture with thiazolidinediones: an individual patient data meta-analysis. Frontiers in Endocrinology, 4, 11. (doi:10.3389/fendo.2013.00011). (PMID:23549934)

Record type: Article

Abstract

Background
The use of thiazolidinediones (TZDs) has been associated with increased fracture risks. Our aim was to estimate the risk of fracture with TZDs in three different healthcare registries, using exactly the same study design, and to perform an individual patient data meta-analysis of these three studies.

Methods
Population-based cohort studies were performed utilizing the British General Practice Research Database (GPRD), the Dutch PHARMO Record Linkage System (RLS), and the Danish National Health Registers. In all three databases, the exposed cohort consisted of all patients (aged 18+) with at least one prescription of antidiabetic (AD) medication. Cox proportional hazards models were used to estimate hazard ratios (HRs) of fracture. The total period of follow-up for each patient was divided into periods of current exposure and past exposure, with patients moving between current and past use.

Results
In all three registries, the risk of fracture was increased for women who were exposed to TZDs: HR 1.48 (1.37-1.60) in GPRD, HR 1.35 (1.15-1.58) in PHARMO, and HR 1.22 (1.03-1.44) in Denmark. Combining the data in an individual patient data meta-analysis resulted, for women, in a 1.4-fold increased risk of any fracture for current TZD users versus other AD drug users [adj. HR 1.44 (1.35-1.53)]. For men, there was no increased fracture risk [adj. HR 1.05 (0.96-1.14)]. Risks were increased for fractures of the radius/ulna, humerus, tibia/fibula, ankle, and foot, but not for hip/femur or vertebral fractures. Current TZD users with more than 25 TZD prescriptions ever before had a 1.6-fold increased risk of fracture compared with other AD drug users [HR 1.59 (1.46-1.74)].

Conclusion
In this study, we consistently found a 1.2- to 1.5-fold increased risk of fractures for women using TZDs, but not for men, across three different healthcare registries. TZD users had an increased risk for fractures of the extremities, and risks further increased for prolonged users of TZDs.

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Published date: February 2013
Organisations: Faculty of Medicine

Identifiers

Local EPrints ID: 352415
URI: https://eprints.soton.ac.uk/id/eprint/352415
ISSN: 1664-2392
PURE UUID: 5e69dfb1-f175-47a4-9fd5-b1ad53fc6477

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Date deposited: 13 May 2013 13:07
Last modified: 16 Jul 2019 21:34

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Contributors

Author: Marloes T. Bazelier
Author: Frank de Vries
Author: Peter Vestergaard
Author: Ron M.C. Herings
Author: Arlene M. Gallagher
Author: Hubert G.M. Leufkens
Author: Tjeerd-Pieter van Staa

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