SummaryPrevious studies evaluated the association between proton pump inhibitor (PPI) use and subsequent fracture risk, but they showed ambiguous results. Therefore, the objective was to evaluate this association in a different study population. Our findings show that there is probably no causal relationship between PPI use and hip fracture risk.IntroductionPrevious studies evaluated the association between PPI use and subsequent fracture risk, but they showed ambiguous results. To further test these conflicting results, the objective of this study was to evaluate the association between the use of PPIs and the risk of hip/femur fracture in a different study population.MethodsA case-control study was conducted using data from the Dutch PHARMO record linkage system. The study population included 6,763 cases aged 18 years and older with a first hip/femur fracture during enrolment and 26,341 age-, gender- and region-matched controls.ResultsCurrent users of PPIs had an increased risk of hip/femur fracture yielding an adjusted odds ratio (AOR) of 1.20 (95% CI 1.04–1.40). Fracture risk attenuated with increasing durations of use, resulting in AORs of 1.26 (95% CI 0.94–1.68) in the first 3 months, 1.31 (95% CI 0.97–1.75) between 3 and 12 months, 1.18 (95% CI 0.92–1.52) between 13 and 36 months and 1.09 (95% CI 0.81–1.47) for use longer than 36 months.ConclusionOur findings show that there is probably no causal relationship between PPI use and hip fracture risk. The observed association may be the result of unmeasured distortions: although current use of PPIs was associated with a 1.2-fold increased risk of hip/femur fracture, the positive association was attenuated with longer durations of continuous use. Our findings do not support that discontinuation of PPIs decreases risk of hip fracture in elderly patients.

Summary This case-control study showed that current use of conventional antipsychotics, but not atypical antipsychotics, seems to be associated with an increased risk of a hip/femur fracture, possibly related to the pharmacological properties of conventional antipsychotics. Furthermore, no evidence for a dose effect was found.

SummaryAnti-depressants are used largely, but have serious side effects. We show that both selective serotonin re-uptake inhibitors (SSRIs) and tricyclic anti-depressants (TCAs) increase the risk of hip/femur fracture and that this risk is time related and depends on the degree of serotonin transporter inhibition. This should be considered when prescribing anti-depressants to patients.IntroductionAnti-depressants are known to have serious side effects. We examined the association between the use of anti-depressants and the risk of hip/femur fractures with a special focus on the relation with the degree of 5-hydroxytryptamine transporter (5-HTT) inhibition and the duration of use.MethodsA case–control study was conducted within the Dutch PHARMO-RLS database. Cases (n = 6,763) were adult patients with a first hip/femur fracture during the study period. For each case, four controls (n = 26341) were matched by age, gender and geographic region.ResultsThe risk of hip/femur fracture increased with current use of SSRIs (adjusted odds ratio (ORadj) 2.35 [95% confidence interval (CI) 1.94–2.84]) and TCAs (ORadj 1.76 [95% CI 1.45–2.15]). The risk of hip/femur fracture declined rapidly after discontinuation of use. The risk of hip/femur fracture increased as the degree of 5-HTT inhibition of all anti-depressants increased from ORadj 1.64 [95% CI 1.14–2.35] for drugs with low 5-HTT inhibition to ORadj 2.31 [95% CI 1.94–2.76] for those with high 5-HTT inhibiting properties.ConclusionCurrent use of both SSRIs and TCAs increase hip/femur fracture risk. Further studies are needed to elucidate the mechanistic pathways and the relation with the underlying pathophysiology. Until then, the elevated fracture risk should be considered when prescribing anti-depressants.

Background and Purpose-Stroke increases the risk of hip/femur fracture, as seen in several studies, although the time course of this increased risk remains unclear. Therefore, our purpose is to evaluate this risk and investigate the time course of any elevated risk. Methods-We conducted a case-control study using the Dutch PHARMO Record Linkage System database. Cases (nϭ6763) were patients with a first hip/femur fracture; controls were matched by age, sex, and region. Odds ratio (OR) for the risk of hip/femur fracture was derived using conditional logistic regression analysis, adjusted for disease and drug history. Results-An increased risk of hip/femur fracture was observed in patients who experienced a stroke at any time before the index date (adjusted OR, 1.96; 95% CI, 1.65-2.33). The fracture risk was highest among patients who sustained a stroke within 3 months before the index date (adjusted OR, 3.35; 95% CI, 1.87-5.97) and among female patients (adjusted OR, 2.12; 95% CI, 1.73-2.59). The risk further increased among patients younger than 71 years (adjusted OR, 5.12; 95% CI, 3.00 -8.75). Patients who had experienced a hemorrhagic stroke tended to be at a higher hip/femur fracture risk compared with those who had experienced an ischemic stroke. Conclusions-Stroke is associated with a 2.0-fold increase in the risk of hip/femur fracture. The risk was highest among patients younger than 71 years, females, and those whose stroke was more recent. Fall prevention programs, bone mineral density measurements, and use of bisphosphonates may be necessary to reduce the occurrence of hip/femur fractures during and after stroke rehabilitation. Key Words: bone density Ⅲ fracture Ⅲ risk factors Ⅲ stroke S troke is a major cause of death and long-term disability in most industrialized populations. More than half of all strokes occur in people older than 75 years of age, and there is a trend toward increasing stroke incidence, especially in the elderly population, because the population is living longer. 1 Osteoporosis has been recognized as a serious complication after stroke. 2,3 Stroke has been associated with a 1.5-to 4-times higher risk of hip fractures, 4,5 and there is an increasing prevalence of hip/femur fractures among stroke survivors. 6 Several long-term, prospective studies investigated bone mineral density (BMD) after stroke. 2 Those studies reported nonuniform patterns of changes in BMD with significant bone loss on the paretic side, with a rapid onset after stroke, especially in patients with the most severe functional deficits.Information about the time course of increased risk of hip/femur fracture during the first year after stroke is scarce. Most studies, 4,6,7 but not all, 8 that investigated fracture risk in relation to time after stroke adjusted for a limited number of confounders (age and sex) and did not distinguish between hemorrhagic and ischemic stroke. The objective of this study, therefore, was to evaluate the association between stroke and the risk of hip/femur fracture, and to identify any ...