Fracture Risk With Thiazolidinediones
Condition: Fractures, Bone; Type II Diabetes
MeSH terms: Diabetes Mellitus, Type 2; Fractures, Bone
Study type: Observational

Summary: 
      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.
    

Detailed description: 
      Patients were not recruited for nor enrolled in this study. This study is a retrospective
      observational study. Data from medical records or insurance claims databases are anonymised
      and used to develop a patient cohort. All diagnoses and treatment are recorded in the course
      of routine medical practice.
    

Intervention name(s): TZD only (RSG or PIO or troglitazone); TZD + spironolactone; TZD + amiloride
Intervention type(s): Drug; Drug; Drug
Intervention description(s): Drug exposure will be inferred from prescription claims. Subjects who have been exposed to TZD for at least 6 months or at least 12 months will be considered for inclusion.; Subjects who have been exposed to TZD for at least 6 months or at least 12 months will be considered for inclusion.
In order to be eligible for inclusion in this category, the prescription days supply for TZD and spirinolactone must overlap by at least 30 days.; Subjects who have been exposed to TZD for at least 6 months or at least 12 months will be considered for inclusion.
In order to be eligible for inclusion in this category, the prescription days supply for TZD and Amiloride must overlap by at least 30 days.
Intervention MeSH terms: Troglitazone; Amiloride; Spironolactone
Observational model: Case-Control
Time perspective: Retrospective
Sampling method: Non-Probability Sample
Study population: 
        The study population will consist of type 2 diabetes patients aged 18 -65 years old exposed
        to TZD for at least 6 months or at least 12 months. The study will use data from the US
        health claims database, the Ingenix Impact National Managed Care Database (Impact
        Database). The Impact Database system is a comprehensive, de-identified U.S. healthcare
        claims database that is representative of the non-elderly, insurance-carrying population.
        It includes 89.3 million lives from 1997 to 2008. Approximately 74 percent of all patients
        in the database have pharmacy benefits and, on average, 25 months of enrollment/claims
        information. The data are collected from over 46 different healthcare plans serving members
        across nine census regions.
      
Keywords: thiazolidinediones; rosiglitazone; amiloride; pioglitazone; fracture; Spironolactone