Datenbankbasierte epidemiologische retrospektive Untersuchung zu Risikofaktoren für Frakturen

The aim of this work was (i) to compare the risk of bone fracture in women using hormonal contraception with that in women who have never used hormonal contraception in UK and (ii) to analyze the impact of dipeptidyl peptidase-4 inhibitor (DPP4i) use on the risk of bone fracture in patients diagnosed with type 2 diabetes mellitus (T2DM) in Germany. This dissertation is based upon two articles published in Osteoporosis International. The oral hormonal contraceptive is the most common method of contraception used by women, with 28 % of women aged 16–49 in the UK using it in 1015. Oral contraception (OC) is one of the safest, most easy-to-use contraceptives and is used not only to prevent unwanted pregnancy but also for treating skin disorders such as acne or gynecological diseases such as endometriosis. Existing studies have provided differing results when evaluating the impact of hormonal contraception. These include possible effects on bone mineral density (BMD), including a higher risk of osteoporosis and consequently fracture exposure. Diabetes is one of the most frequently occurring chronic disorders in the world, and more than 8% of the global population is affected by this condition. In Germany, the prevalence of diabetes in adults is estimated at around 10.6%, the number of related deaths at approximately 55,000, and the cost per person at $5,300. Therefore, diabetes has an important impact on both the health and the economy of this European country. Type 2 diabetes mellitus (T2DM) is known to be associated with an increase in the risk of developing bone fractures. This association may be explained by the fact that diabetes related comorbidities (i.e., retinopathy and neuropathy) lead to the occurrence of recurrent falls while hyperglycemia leads to an important alteration of bone tissues, indirectly resulting in increased bone fragility and osteoporosis. Evidence concerning bone changes associated with contraceptive use and the influence of diabetes treatment on fracture risk is still ambiguous. Further research is clearly still needed in this highly interesting and relevant medical area. Both analysis were performed on the IMS Disease Analyzer® database (DA IMS Health), which provides diagnoses, prescribed treatments, laboratory values, and demographic data obtained directly and in anonymous form from the computer systems used daily in the offices of participating doctors. The value of the data is monitored by means of numerous quality criteria that ensure that the database provides valuable information on diagnoses (ICD-10), prescriptions (Anatomical Therapeutic Chemical classification system (ATC)), and other medical records. Finally, this database has already been used in several studies focusing on fractures. The first study - a retrospective case-control analysis – compared 6,485 women with fractures and 6,485 women without fractures from 135 general practitioner offices in the UK. Women without bone fractures were statistically more likely to have been exposed to oral contraception (OR 0.81), depending on their age and therapy duration. This effect was strongest in the age groups 18–25 and 26–35 and in patients with an OC treatment duration of more than 1 year. The second work discovered, that in type 2 diabetes patients treated in German primary care practices, the use of dipeptidyl peptidase-4 inhibitor (DPP4i) in combination with metformin was associated with a significant decrease in the risk of developing bone fractures compared to metformin monotherapy. Within five years of the index date, 6.4% of users and 8.3% of non-users developed bone fractures (log-rank p-value < 0.001). Finally, as a conclusion, this work was able to identify two important impact factors, which are associated with a decrease in the risk of bone fracture.