Utrecht Institute for Pharmaceutical Sciences Use of thiazolidinediones and risk of osteoporotic fracture: disease or drugs? Frank de Vries, PharmD,PhD.

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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


Conflict of Interest

This work was funded by a grant from the European Calcified Tissue Society, and the Dutch Organisation for Scientific Research


Introduction

• Glitazones• Antidiabetic treatment• Linked with low bone density and

fracture


Are glitazones useless?


Introduction

• Type 2 diabetes mellitus is a risk factor for osteoporotic fracture

• Epidemiological studies have not been clear about confounding by disease severity


Objective

• To study the association between thiazolidinedione use, severity of diabetes mellitus and fracture risk


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


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%


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)


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)


Limitations

• No data on BMI, alcohol or smoking• Insulin use may have anabolic effects

on bone


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


Thank you very much for your attention• www.pharm.uu.nl/epithera• [email protected]

Utrecht Institute for Pharmaceutical Sciences Use of thiazolidinediones and risk of osteoporotic fracture: disease or drugs? Frank de Vries, PharmD,PhD.

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