F. de Vries

Use of anti-depressants and the risk of fracture of the hip or femur

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 (nu2009=u20096,763) were adult patients with a first hip/femur fracture during the study period. For each case, four controls (nu2009=u200926341) 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.

Fracture risk in patients receiving acid-suppressant medication alone and in combination with bisphosphonates

SummaryPrevious studies have found an association between acid suppressants and fracture risk. We assessed fracture risk in patients taking concomitant acid suppressant and bisphosphonates. Positive associations were observed for any hip and vertebral fracture. The effect size was modest; however, the significance lies in the widespread prescribing of acid suppressants.IntroductionPrevious studies have found that acid-suppressive medication (ASM) is associated with an increased risk of fracture. Bisphosphonates can cause upper gastrointestinal problems, and patients may be prescribed ASM to minimise these effects.MethodsA retrospective cohort study using the GPRD was conducted in patients aged 40xa0years and older starting proton pump inhibitors (PPI, Nu2009=u2009234,144), H2 receptor antagonists (H2RA, Nu2009=u2009166,798) or bisphosphonates (Nu2009=u200967,309). Fracture risk in current versus past use of ASM and concomitant use of bisphosphonate plus ASM versus bisphosphonate alone was compared using time-dependent Cox regression.ResultsIn the 6xa0months before initiating bisphosphonate therapy, 20.1% of patients received a PPI and 7.5% an H2RA. Current PPI use was associated with an increased risk of any (adjusted relative rate (ARR) 1.15, 95% CI 1.10–1.20), hip (ARR 1.22, 95% CI 1.10–1.37), and vertebral fracture (ARR 1.40, 95% CI 1.11–1.78); and concomitant bisphosphonates and PPIs with an increased risk of any (ARR 1.08, 95% CI 1.01–1.16) and hip fracture (ARR 1.24, 95% CI 1.08–1.42).ConclusionsASM is associated with an increased risk of fracture when taken alone or in combination with bisphosphonates. Given the frequency of coprescription of ASM and bisphosphonates, this issue requires further investigation.

The Netherlands Chlamydia cohort study (NECCST) protocol to assess the risk of late complications following Chlamydia trachomatis infection in women

BackgroundChlamydia trachomatis (CT), the most common bacterial sexually transmitted infection (STI) among young women, can result in serious sequelae. Although the course of infection is often asymptomatic, CT may cause pelvic inflammatory disease (PID), leading to severe complications, such as prolonged time to pregnancy, ectopic pregnancy, and tubal factor subfertility. The risk of and risk factors for complications following CT-infection have not been assessed in a long-term prospective cohort study, the preferred design to define infections and complications adequately.MethodsIn the Netherlands Chlamydia Cohort Study (NECCST), a cohort of women of reproductive age with and without a history of CT-infection is followed over a minimum of ten years to investigate (CT-related) reproductive tract complications. This study is a follow-up of the Chlamydia Screening Implementation (CSI) study, executed between 2008 and 2011 in the Netherlands. For NECCST, female CSI participants who consented to be approached for follow-up studies (nxa0=xa014,685) are invited, and prospectively followed until 2022. Four data collection moments are foreseen every two consecutive years. Questionnaire data and blood samples for CT-Immunoglobulin G (IgG) measurement are obtained as well as host DNA to determine specific genetic biomarkers related to susceptibility and severity of infection. CT-history will be based on CSI test outcomes, self-reported infections and CT-IgG presence. Information on (time to) pregnancies and the potential long-term complications (i.e. PID, ectopic pregnancy and (tubal factor) subfertility), will be acquired by questionnaires. Reported subfertility will be verified in medical registers. Occurrence of these late complications and prolonged time to pregnancy, as a proxy for reduced fertility due to a previous CT-infection, or other risk factors, will be investigated using longitudinal statistical procedures.DiscussionIn the proposed study, the occurrence of late complications following CT-infection and its risk factors will be assessed. Ultimately, provided reliable risk factors and/or markers can be identified for such late complications. This will contribute to the development of a prognostic tool to estimate the risk of CT-related complications at an early time point, enabling targeted prevention and care towards women at risk for late complications.Trial registrationDutch Trial Register NTR-5597. Retrospectively registered 14 February 2016.

Incidence of subsequent fractures in the UK between 1990 and 2012 among individuals 50 years or older.

SummaryWe studied the incidence of subsequent fractures in persons of 50+u2009years from 1990 to 2012 and the relative risk (RR) of subsequent fractures after an index femur/hip fracture, stratified per 5-year age band. Patients suffering a fracture have a high incidence of a subsequent fracture; the RR of subsequent fracture after a femur/hip fracture ranged from 2 to 7.IntroductionRecent information on the risk of subsequent fractures after a broad range of index fractures in the UK population is scarce. We therefore studied the rates of subsequent fractures of the femur/hip, humerus, radius/ulna, vertebrae, rib, or pelvis after fractures at one of these sites from 1990 to 2012 in 3,156,347 UK men and women aged 50xa0years or over.MethodsWe undertook a retrospective observational study using the UK Clinical Practice Research Datalink (CPRD). The incidence of subsequent fractures at a specific site was calculated by dividing the observed number of fractures by the number of person-years (py) at risk. The relative risk (RR) of subsequent fractures after a femur/hip fracture, by 5-year age band, was calculated by dividing the incidence of a specific subsequent fracture type by the incidence of first fractures at the same site in the same age group.ResultsThe highest subsequent fracture incidence after a femur/hip fracture was for humerus fracture in men (59.5/10.000xa0py) and radius/ulna fracture in women (117.2/10.000xa0py). After an index fracture of the radius/ulna, humerus fracture in men (59.3/10.000xa0py) and femur/hip fracture in women (82.4 per 10.000xa0py) were most frequent. The RR of fractures after a femur/hip fracture ranged from 2 to 7 and were highest in men and younger age groups.ConclusionPatients suffering a fracture have a high incidence of a subsequent fracture. Our findings demonstrate the importance of fracture prevention in patients with a history of a fracture by adequate medical diagnosis and treatment.

Association between use of antidepressants or benzodiazepines and the risk of subsequent fracture among those aged 65+ in the Netherlands

SummaryThis is the first study to examine the association between antidepressant and benzodiazepine use following a MOF and risk of subsequent fracture in those 65+. Using national data, drug use following MOF showed that the 1-year fully adjusted risk of subsequent MOF in those on antidepressants was more than doubled.IntroductionWe evaluated the association between the use of antidepressants or benzodiazepines and the risk of a subsequent major osteoporotic fracture.MethodsA cohort study was performed using the Dutch PHARMO Database Network. Between 2002 and 2011, a total of 4854 patients sustained a first major osteoporotic fracture after the age of 65xa0years, of which 1766 sustained a hip fracture. Incidence rates and adjusted hazard ratios were calculated using Cox proportional hazards models.ResultsWithin 1xa0year following a major osteoporotic fracture, 15% (95% CI 13.7–15.7) and 31% (95% CI 30.1–32.8) of patients were dispensed an antidepressant or benzodiazepine, respectively. Current use of antidepressants in the first year following a major osteoporotic fracture was associated with subsequent fracture (adjusted HR 2.17 (95% CI 1.37–3.43)). Recent and past use of antidepressants were also associated with an increased risk of subsequent fracture. When the complete follow-up period was included, only the current use of antidepressants was associated with subsequent fracture following a major osteoporotic fracture (adjusted HR 1.48; 95% CI 1.06–2.06). Current benzodiazepine use was not associated with an increased risk of fracture within 1xa0year following a major osteoporotic fracture (adjusted HR 1.18; 95% CI 0.76–1.81) or during the complete follow-up period (adjusted HR 1.18; 95% CI 0.90–1.55).ConclusionThis study provides evidence that antidepressants should be used with caution following a major osteoporotic fracture. It provides needed insights that can be used to inform clinicians when assessing subsequent fracture risk in patients.

Association of type 2 diabetes mellitus with self-reported knee pain and clinical knee osteoarthritis: The Maastricht Study

Diabetes & Metabolism - In Press.Proof corrected by the author Available online since mercredi 28 fevrier 2018