Marloes T. Bazelier

Risk of fracture after bariatric surgery in the United Kingdom: population based, retrospective cohort study

Objectives To estimate fracture risk in patients receiving bariatric surgery versus matched controls. Design Population based, retrospective cohort study. Setting Use of records from the United Kingdom General Practice Research Database, now known as the Clinical Practice Research Datalink (from January 1987 to December 2010). Participants Patients with a body mass index of at least 30, with a record of bariatric surgery (n=2079), and matched controls without a record (n=10 442). Each bariatric surgery patient was matched to up to six controls by age, sex, practice, year, and body mass index. Patients were followed from the date of bariatric surgery for the occurrence of any fracture. We used time dependent Cox regression to calculate relative rates of fracture, adjusted for disease and previous drug treatment, and time-interaction terms to evaluate fracture timing patterns. Main outcome measure Relative rates of any, osteoporotic, and non-osteoporotic fractures. Results Mean follow-up time was 2.2 years. Overall, there was no significantly increased risk of fracture in patients who underwent bariatric surgery, compared with controls (8.8 v 8.2 per 1000 person years; adjusted relative risk 0.89, 95% confidence interval 0.60 to 1.33). Bariatric surgery also did not affect risk of osteoporotic and non-osteoporotic fractures. However, we saw a trend towards an increased fracture risk after three to five years following surgery, as well as in patients who had a greater decrease in body mass index after surgery, but this was not significant. Conclusion Bariatric surgery does not have a significant effect on the risk of fracture. For the first few years after surgery, these results are reassuring for patients undergoing such operations, but do not exclude a more protracted adverse influence on skeletal health in the longer term.

The Risk of Fracture in Patients With Multiple Sclerosis: The UK General Practice Research Database

Patients with multiple sclerosis (MS) may be at an increased risk of fracture owing to a greater risk of falling and decreased bone mineral density when compared with the general population. This study was designed to estimate the relative and absolute risk of fracture in patients with MS. We conducted a population‐based cohort study using data from the UK General Practice Research Database linked to the National Hospital Registry (1997–2008). Incident MS patients (n = 5565) were matched 1:6 by year of birth, sex, and practice with patients without MS (controls). Cox proportional‐hazards models were used to derive adjusted hazard ratios (HRs) for fracture associated with MS. Time‐dependent adjustments were made for age, comorbidity, and drug use. Absolute 5‐ and 10‐year risks of fracture were estimated for MS patients as a function of age. Compared with controls, MS patients had an almost threefold increased risk of hip fracture [HR = 2.79, 95% confidence interval (CI) 1.83–4.26] and a risk of osteoporotic fracture that was increased 1.4‐fold (HR = 1.35, 95% CI 1.13–1.62). Risk was greater in patients who had been prescribed oral/intravenous glucocorticoids (GCs; HR = 1.85, 95% CI 1.14–2.98) or antidepressants (HR = 1.79, 95% CI 1.37–2.35) in the previous 6 months. Absolute fracture risks were low in younger MS patients but became substantial when patients were older than 60 years of age. It is concluded that MS is associated with an increased risk of fracture. Fracture risk assessment may be indicated in patients with MS, especially those prescribed GCs or antidepressants.

Causes of death in patients with multiple sclerosis and matched referent subjects: a population-based cohort study

Background and purpose:  Multiple sclerosis (MS) has been associated with increased mortality rates. However, influence of lifestyle parameters remains unknown, and inconsistencies exist regarding findings for causes of death.

HIV infection and its association with an excess risk of clinical fractures: a nationwide case-control study.

Background:Different studies have reported an association between HIV infection, antiretroviral therapies, and impaired bone metabolism, but data on their impact on fracture risk are scarce. We studied the association between a clinical diagnosis of HIV infection and fracture risk. Methods:We conducted a case–control study using data from the Danish National Health Service registries, including 124,655 fracture cases and 373,962 age- and gender-matched controls. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using conditional logistic regression. Results:A total of 50 (0.40/1000) patients in the fracture group and 52 (0.14/1000) controls had an HIV diagnosis. The risk of any fracture was thus significantly increased among HIV-infected patients (age- and gender-matched OR = 2.89, 95% CI: 1.99 to 4.18). Similarly, significant increases in the risk of hip (OR = 8.99, 95% CI: 1.39 to 58.0), forearm (OR = 3.50, 95% CI: 1.26 to 9.72), and spine fractures (OR = 9.00, 95% CI: 1.39 to 58.1) were observed. Conclusions:HIV infection is associated with an almost 3-fold increase in fracture risk compared with that of age- and gender-matched uninfected patients. HIV patients are also at an almost 9-fold higher risk of hip fracture.

Use of insulin and insulin analogs and risk of cancer - systematic review and meta-analysis of observational studies

Background: An association of insulin use and risk of cancer has been reported but evidence is conflicting and methodological issues have been identified. Objective: To summarize results regarding insulin use and cancer risk by a systematic review and meta-analysis of cohort and case-control studies examining risk of cancer associated with insulin use in patients with diabetes. Data Sources: Systematic literature search in 5 databases: PubMed, Embase, Web of Science, Scopus and Cochrane Library. Study Eligibility Criteria (PICOS): Population: diabetes patients. Exposure: Users of any exogenous insulin. Comparison: Diabetes patients with or without use of antidiabetic drugs. Outcome: Any incident cancer. Study Design: Cohort and case-control studies. Results: 42 eligible studies examined risk of any cancer and 27 site-specific cancers. Results of individual studies were heterogeneous. Meta-analyses were significant for: Insulin vs No Insulin: Increased risk for pancreas, liver, kidney, stomach and respiratory cancer, decreased risk for prostate cancer. Insulin vs Non-Insulin Antidiabetics: Increased risk for any, pancreatic and colorectal cancer. Glargine vs Non-Glargine Insulin: Increased risk for breast cancer, decreased risk for colon cancer. Limitations: Few studies available for most cancer sites and exposure contrasts, and few assess effect of dose and duration of exposure. Methodological issues in several studies. Availability of confounders. Conclusions: Insulin use was associated with risk of cancer at several sites. Cautious interpretation of results is warranted as methodological issues and limitations in several of the included studies have been identified. Choice of study design may have a profound effect on estimated cancer risk.

Risk of fractures in patients with multiple sclerosis: A population-based cohort study

Objective: To examine the risk of fracture in patients with multiple sclerosis (MS) compared with population-based controls. Methods: A population-based cohort study was performed in the Dutch PHARMO Record Linkage System (1998–2008). Patients with MS (n = 2,415) were matched by year of birth, sex, and practice to up to 6 patients without MS (controls). We used Cox proportional hazards models to estimate the hazard ratio (HR) of fracture in MS. Time-dependent adjustments were made for age, history of disease, and drug use. Results: During follow-up, there were 59 fractures among patients with MS (2.4%) and 227 fractures among controls (1.8%). Patients with MS had a 1.7-fold increased risk of osteoporotic fracture (HR 1.73 [95% confidence interval (CI) 1.18–2.53]) and a 4-fold increased risk of hip fracture (HR 4.08 [95% CI 2.21–7.56]). The risk of osteoporotic fracture was significantly greater for patients with MS who had been prescribed antidepressants (HR 3.25 [95% CI 1.77–5.97]) or hypnotics/anxiolytics (HR 3.40 [95% CI 2.06–5.63]) in the previous 6 months, compared with controls. Conclusions: Increased awareness of the risk of hip fracture is warranted in patients with MS, especially in those who have recently been prescribed antidepressants or hypnotics/anxiolytics.

The risk of colorectal cancer in patients with type 2 diabetes: associations with treatment stage and obesity.

OBJECTIVE To assess the risk of colorectal cancer associated with type 2 diabetes, as compared with a nondiabetic reference population, and to study additional associations between treatment stage and duration of obesity and colorectal cancer risk. RESEARCH DESIGN AND METHODS We conducted an observational population-based cohort study within the Clinical Practice Research Datalink (1987–2012). All patients (≥18 years) with at least one prescription for an antidiabetic drug (n = 300,039) were matched (1:1) by birth year, sex, and practice to a comparison cohort without diabetes. Cox proportional hazards models were used to derive adjusted hazard ratios (HRs) for colorectal cancer associated with type 2 diabetes. Within the diabetic cohort, associations of colorectal cancer with treatment stages and duration of obesity (BMI ≥30 kg/m2) were studied. RESULTS After a median follow-up of 4.5 years, 2,759 cases of colorectal cancer were observed among the diabetic study population. Type 2 diabetes was associated with a 1.3-fold increased risk of colorectal cancer (HR 1.26 [95% CI 1.18–1.33]). Among diabetic patients, no association was found with treatment stages. A trend of increased colorectal cancer risk was observed with longer duration of obesity. Risk of colorectal cancer was significantly increased for patients with recorded duration of obesity of 4–8 years (HR 1.19 [1.06–1.34]) and >8 years (1.28 [1.11–1.49]). CONCLUSIONS Type 2 diabetes is associated with a moderately increased risk of colorectal cancer. Among diabetic patients, an increased risk was observed for patients who suffered from obesity for a total duration of 4 years or more.

The epidemiology of extra-articular manifestations in ankylosing spondylitis: a population-based matched cohort study

Objective To assess the incidence and risks of common extra-articular manifestations (EAMs), that is, acute anterior uveitis (AAU), psoriasis and inflammatory bowel disease (IBD), in patients with ankylosing spondylitis (AS) compared with population-based controls. Methods All incident patients with AS (n=4101) from the UK Clinical Practice Research Datalink (1987–2012) were matched with up to seven control subjects without AS by year of birth, sex and practice (n=28 591). Incidence rates, cumulative incidence rates and adjusted (adj) HRs for the development of EAMs were calculated, with time-dependent adjustments for age, sex, comorbidity and medication use. Results At diagnosis of AS, the proportion of patients with an EAM was 11.4% for AAU, 4.4% for psoriasis and 3.7% for IBD. Incidence rates of EAMs were 8.9/1000 person-years for AAU, 3.4/1000 person-years for psoriasis and 2.4 /1000 person-years for IBD in AS. The 20-year cumulative incidence was 24.5%, 10.1% and 7.5%, respectively. Risks of EAMs were 1.5-fold to 16-fold increased versus controls, with an adj HR of 15.5 (95% CI 11.6 to 20.7) for AAU, adj HR of 1.5 (95% CI 1.1 to 1.9) for psoriasis and adj HR of 3.3 (95% CI 2.3 to 4.8) for IBD. For psoriasis and IBD, the highest risks were found in the 1st years after diagnosis, while developing AAU continued to be increased also 10 years after diagnosis of AS. Conclusions The risk of, in particular AAU, but also of psoriasis and IBD, is significantly increased in patients with AS compared with controls. Hazard patterns are different for each of the EAMs.

Ankylosing spondylitis and risk of ischaemic heart disease: a population-based cohort study

Objective To investigate the incidence and risk of ischaemic heart disease (IHD) and acute myocardial infarction (AMI), including the role of non-steroidal anti-inflammatory drugs (NSAID), in patients with ankylosing spondylitis (AS) compared with population controls. Methods All patients with newly diagnosed AS (n=3809) from the British Clinical Practice Research Datalink (1987–2012) were matched with up to seven persons without AS by year of birth, gender and practice (n=26 197). Incidence rate ratios (IRR) and HRs for development of IHD and AMI were calculated. Stepwise analyses were performed adjusting for age, gender, comorbidity and drug use, including NSAIDs. Results At baseline, 4.3% of the patients had IHD and 1.8% had AMI compared with 3.4% and 1.4% of the controls, respectively. After exclusion of pre-existing IHD or AMI, the IRRs were 1.18 (95% CI 0.96 to 1.46) and 0.91 (95% CI 0.65 to 1.27) for IHD and AMI, respectively. Compared with controls, the age-gender adjusted HR for developing IHD was 1.20 (95% CI 0.97 to 1.48), and for AMI 0.91 (95% CI 0.65 to 1.28). In female patients, the risk of developing IHD was increased (HR 1.88, 95% CI 1.22 to 2.90), but after adjustment for all possible risk factors only a non-significant trend was found (HR 1.31, 95% CI 0.83 to 2.08). In particular, NSAID use explained this change (HR IHD adjusted for age-gender-NSAID use 1.57, 95% CI 0.99 to 2.48). Conclusions Female patients with AS had an increased age-adjusted risk of developing IHD, but after adjustment for NSAID use only a non-significant trend towards increased risk was found.

Incidence of fractures in patients with multiple sclerosis: the Danish National Health Registers

Background: Patients with multiple sclerosis (MS) are potentially at high risk of fracture due to falls and osteoporosis. Objective: To estimate incidence rates of fractures in MS patients, stratified by fracture type, sex and age, and to compare these rates with controls. Methods: The case population consisted of all patients with an accepted diagnosis of MS in the Danish MS Registry (1949–2007). Data were linked to the National Hospital Discharge Register (1977–2007). Patients with MS (n = 11,157) were 1:6 matched by year of birth, gender, calendar time and region to persons without MS (controls). Incidence rates of fracture were estimated as the number of fractures per 1000 person-years. Incidence rate ratios (IRRs) were calculated by dividing fracture rates in MS patients by fracture rates in controls. Results: Among patients with MS, the incidence rate of any fracture yielded 22.8 per 1000 person-years. The IRR of any fracture between MS patients and controls was 1.40 (95% CI 1.33–1.46). In particular, IRRs of tibia fracture (3.36 [2.75–4.11]), femur fracture (6.66 [5.06–8.76]) and hip fracture (3.20 [2.83–3.62]) were elevated in MS patients versus controls. Conclusion: Fractures occurred more often in patients with MS, especially fractures of the tibia, hip and femur.