utrecht institute for pharmaceutical sciences use of thiazolidinediones and risk of osteoporotic...
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![Page 1: Utrecht Institute for Pharmaceutical Sciences Use of thiazolidinediones and risk of osteoporotic fracture: disease or drugs? Frank de Vries, PharmD,PhD](https://reader030.vdocuments.net/reader030/viewer/2022032806/56649efc5503460f94c0f53c/html5/thumbnails/1.jpg)
Utrecht Institute for Pharmaceutical Sciences
Use of thiazolidinediones and risk of osteoporotic fracture: disease or drugs?
• Frank de Vries, PharmD,PhD• Marloes Bazelier MSc
– Universiteit Utrecht, NL– University of Southampton, UK
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Utrecht Institute for Pharmaceutical Sciences
Conflict of Interest
This work was funded by a grant from the European Calcified Tissue Society, and the Dutch Organisation for Scientific Research
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Utrecht Institute for Pharmaceutical Sciences
Introduction
• Glitazones• Antidiabetic treatment• Linked with low bone density and
fracture
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Utrecht Institute for Pharmaceutical Sciences
Are glitazones useless?
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Utrecht Institute for Pharmaceutical Sciences
Introduction
• Type 2 diabetes mellitus is a risk factor for osteoporotic fracture
• Epidemiological studies have not been clear about confounding by disease severity
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Utrecht Institute for Pharmaceutical Sciences
Objective
• To study the association between thiazolidinedione use, severity of diabetes mellitus and fracture risk
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Utrecht Institute for Pharmaceutical Sciences
Methods
• Dutch PHARMO database• 1998 – 2008• Hospitalisations linked to longitudinal drug
prescribing• 3 million patients• Population-based cohort study• Index date: first antidiabetic drug prescription• Cox Regression analysis
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Utrecht Institute for Pharmaceutical Sciences
Results: baseline characteristics Diabetes patients
Non-diabetes patients
N=123,452 N=451,388
Duration of follow-up, mean
4.5 yrs 4.0 yrs
Females 53% 53%
Mean age, yrs 64.0 64.0
History of fracture
1.4% 2.0%
Use of oral steroids
13.7% 14.3%
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Utrecht Institute for Pharmaceutical Sciences
Results: risk of fracture in glitazone users Fractures (n) Fully adjusted
Hazard ratio (95% CI)
Unexposed to antidiabetics
10,882 referent
Glitazone exposed
Any fracture 215 1.5 (1.4-1.8)
Osteoporotic 160 1.6 (1.4-1.9)
Hip 86 1.5 (1.2-1.8)
Vertebral 17 2.1 (1.3-3.4)
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Utrecht Institute for Pharmaceutical Sciences
Risk of osteoporotic fracture by disease stage Fully adjusted Hazard ratio (95% CI)
Unexposed to antidiabetics
referent
Diabetes severity stage
1. Metformin or sulphonurea
1.1 (1.0-1.2)
2. Metformin and sulphonurea
1.0 (1.0-1.1)
3. Glitazone 1.6 (1.3-1.8)
4. Insulin 1.2 (1.1-1.3)
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Utrecht Institute for Pharmaceutical Sciences
Limitations
• No data on BMI, alcohol or smoking• Insulin use may have anabolic effects
on bone
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Utrecht Institute for Pharmaceutical Sciences
Conclusion
• Risk of fracture is 1.5-fold increased in users of glitazones
• Severity of the underlying disease plays a minor role
• Fracture risk assessment may be considered in patients taking pioglitazone
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Utrecht Institute for Pharmaceutical Sciences
Thank you very much for your attention• www.pharm.uu.nl/epithera• [email protected]