Treatment with thiazolidinediones (TZD) has recently been reported to possibly increase the
risk of fractures in a randomized trial exploring the efficacy of rosiglitazone (RSG),
metformin, or glyburide encompassing 4360 patients with type 2 diabetes.
It is hypothesized that spironolactone, a diuretic that is broadly used for the treatment of
fluid retention and edema associated with TZD, has a potential protective effect against bone
fractures. However, to our knowledge, this has not been tested in diabetic patients treated
with TZD. Amiloride is another diuretic that shares with spironolactone the anti
mineralocorticoid ion gated channels activity and will be analysed in this study with regard
to possible protective effect against bone fracture in combination with TZD.
This study is a nested case-control study conducted among type 2 diabetes subjects exposed to
TZD. The study aims to explore if the risk of fracture is reduced among type 2 diabetic
subjects exposed to spironolactone and TZD. The study will compare the odds of any low impact
fracture, and hand, foot, upper arm, wrist, and hip fracture incidence in subjects treated
with TZD+spironolactone and TZD+amiloride compared to subjects treated with TZD only.
The study population will consist of type 2 diabetes patients aged 18 -65 years old exposed
to TZD. To be eligible for the study, a subject must have had at least one International
Classification of Disease (ICD)-9 code for type 2 diabetes and have at least 6 months or at
least 12 months of exposure to TZD (rosiglitazone [RSG], pioglitazone [PIO] or troglitazone)
during their follow-up time available in the database.