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AIMS: The Beers criteria for prescribing in elderly are well known and used for many drug utilization studies. We investigated the clinical value of the Beers criteria for benzodiazepine use, notably the association between inappropriate use and risk of fracture. METHODS: We performed a nested case-control study within the Rotterdam Study, a population-based cohort study in 7983 elderly. The proportion of 'inappropriate' benzodiazepine use according to the Beers criteria was compared between fracture patients and controls. 'Inappropriate' use for elderly implies use of some long-acting benzodiazepines and some intermediate/short-acting ones exceeding a suggested maximum daily dose. Also, alternative criteria were applied to compare the risk of fracture. Cases were defined as persons with incident fracture between 1991 and 2002 who were current benzodiazepine users on the fracture date. Controls were matched on fracture date and were also current benzodiazepine users. RESULTS: The risk of fracture in 'inappropriate' benzodiazepine users according to the Beers criteria was not significantly different from 'appropriate' users [odds ratio (OR) 1.07, 95% confidence interval (CI) 0.72, 1.60]. However, a significantly higher risk of fracture was found in 'high dose' users and a longer duration of use (14-90 days), irrespective of the type of benzodiazepine (OR 3.45, 95% CI 1.38, 8.59). CONCLUSIONS: These findings suggest that inappropriate benzodiazepine use according to the Beers criteria is not associated with increased risk of fracture. Daily dose and longer duration of use (>14 days) is associated with higher risk of fracture, irrespective of the type of benzodiazepine prescribed.

In this thesis,we examine various associations between three important cardiovascular drugs and bone. Fractureincidenceisthemostclinicallyrelevantfeatureofosteoporosis.Theriskto fractureaboneisdeterminedbyseveralfactors:Bonemineraldensity(BMD),micro-architecture of bone,bone structure and risk of falling.In this thesis we investigate the association between use of thiazides,ß-blockers and statins and fracture risk,but also the association between medication use and (change in) BMD and the association between medication use and hip bone structure to gain more insight in the causal chain of the as-sociation between use of medication and its effects on bone. We performed all our studies in the cohort of the Rotterdam Study.This is a prospec-tive,population-basedcohortstudyondeterminantsandoccurrenceofdiseasesin the elderly.The study started in 1990 and included 7983 persons of 55 years and older. Detailed data on many potential confounders was available and since all pharmacies in theresearchneighborhoodarecomputerizedandlinkedtoonenetwork,wehavede-tailed exposure data on drug use for all participants.

BACKGROUND: Since most hip fractures are related to osteoporosis, treating accelerated bone loss can be an important strategy to prevent hip fractures. Thiazides have been associated with reduced age-related bone loss by decreasing urinary calcium excretion. OBJECTIVE: To examine the association between dose and duration of thiazide diuretic use and the risk for hip fracture and to study the consequences of discontinuing use. DESIGN: Prospective population-based cohort study. SETTING: The Rotterdam Study. PARTICIPANTS: 7891 individuals 55 years of age and older. MEASUREMENTS: Hip fractures were reported by the general practitioners and verified by trained research assistants. Details of all dispensed drugs were available on a day-to-day basis. Exposure to thiazides was divided into 7 mutually exclusive categories: never use, current use for 1 to 42 days, current use for 43 to 365 days, current use for more than 365 days, discontinuation of use since 1 to 60 days, discontinuation of use since 61