Joan Bentzen

Childhood body mass index and multiple sclerosis risk: a long-term cohort study.

Background: Obesity in late adolescence has been associated with an increased risk of multiple sclerosis (MS); however, it is not known if body size in childhood is associated with MS risk. Methods: Using a prospective design we examined whether body mass index (BMI) at ages 7–13 years was associated with MS risk among 302,043 individuals in the Copenhagen School Health Records Register (CSHRR). Linking the CSHRR with the Danish MS registry yielded 774 MS cases (501 girls, 273 boys). We used Cox proportional hazards models to estimate the hazard ratios (HRs) and 95% confidence intervals (CIs). Results: Among girls, at each age 7–13 years, a one-unit increase in BMI z-score was associated with an increased risk of MS (HRage 7=1.20, 95% CI: 1.10–1.30; HRage 13=1.18, 95% CI: 1.08–1.28). Girls who were ≥95th percentile for BMI had a 1.61–1.95-fold increased risk of MS as compared to girls <85th percentile. The associations were attenuated in boys. The pooled HR for a one-unit increase in BMI z-score at age 7 years was 1.17 (95% CI: 1.09–1.26) and at age 13 years was 1.15 (95% CI: 1.07–1.24). Conclusion: Having a high BMI in early life is a risk factor for MS, but the mechanisms underlying the association remain to be elucidated.

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.

Prevalence of multiple sclerosis in Denmark 1950—2005

Multiple sclerosis is an inflammatory disease of the central nervous system of unknown aetiology. Its prevalence varies by ethnicity and place: persons of northern European descent are at increased risk while persons living at lower latitudes appear to be protected against the disease. The Danish Multiple Sclerosis Registry is a national registry established in 1956 after a population-based survey which receives information from numerous sources. It is considered to be more than 90% complete, with a validity of 94%. Using data from the Registry, we calculated prevalences per 100,000 inhabitants. The standardized prevalence of multiple sclerosis increased from 58.8 (95% confidence interval: 54.9—62.7) in 1950 to 154.5 per 100,000 (95% confidence interval: 148.8—160.2) in 2005, and the female to male ratio increased from 1.31 in 1950 to 2.02 in 2005. The increase in prevalence is due to both increased survival of multiple sclerosis patients and an increased incidence rate. The rise in prevalence in the past 50 years is probably due more to environmental factors than to genetic changes in the Danish population. Among women, environmental changes could include older age at first birth, use of oral contraceptives, or changes in sun behaviour and/or vitamin D status.

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.

The risk of fracture in incident multiple sclerosis patients: The Danish National Health Registers

Background: Patients with multiple sclerosis (MS) may be at increased risk of fractures owing to osteoporosis and falling. Objective: To evaluate the risk of fracture in incident MS patients drawn from a dedicated MS registry compared with population-based controls. Methods: We conducted a population-based cohort study (1996–2007) utilising the Danish National Health Registers that were linked to the Danish MS Registry and the Danish MS Treatment Registry. Incident MS patients (2963 cases) were 1:6 matched by year of birth, gender, calendar time and region to persons without MS (controls). Cox proportional hazards models and logistic regression were used to estimate the risk of fracture in MS. Time-dependent adjustments were made for age, history of diseases and drug use. Results: Compared with controls, patients with MS had no overall increased risk of fracture (adjusted hazard ratio (adj. HR): 1.0, 95% CI: 0.9–1.2). However, the risk of femur/hip fracture (adj. HR: 1.9, 95% CI: 1.1–3.4) was significantly increased compared to controls. As compared with unexposed patients, MS patients who had been exposed to a short course of methylprednisolone in the prior year had no significantly increased risk of osteoporotic fracture (adj. HR: 1.2, 95% CI: 0.5–2.9). Disabled MS patients with Expanded Disability Status Scale [EDSS] scores between 6 and 10, had a 2.6-fold increased risk of osteoporotic fracture (adjusted odds ratio (adj. OR): 2.6, 95% CI: 1.0–6.6) compared to patients with an EDSS score between 0 and 3. Conclusion: Patients with MS had a higher risk of femur/hip fracture than controls. Disability status is probably more important than glucocorticoid use in the aetiology of MS and osteoporotic fracture.

A simple score for estimating the long-term risk of fracture in patients with multiple sclerosis

Objective: To derive a simple score for estimating the long-term risk of osteoporotic and hip fracture in individual patients with MS. Methods: Using the UK General Practice Research Database linked to the National Hospital Registry (1997–2008), we identified patients with incident MS (n = 5,494). They were matched 1:6 by year of birth, sex, and practice with patients without MS (control subjects). Cox proportional hazards models were used to calculate the long-term risk of osteoporotic and hip fracture. We fitted the regression model with general and specific risk factors, and the final Cox model was converted into integer risk scores. Results: In comparison with the FRAX calculator, our risk score contains several new risk factors that have been linked with fracture, which include MS, use of antidepressants, use of anticonvulsants, history of falling, and history of fatigue. We estimated the 5- and 10-year risks of osteoporotic and hip fracture in relation to the risk score. The C-statistic was moderate (0.67) for the prediction of osteoporotic fracture and excellent (0.89) for the prediction of hip fracture. Conclusion: This is the first clinical risk score for fracture risk estimation involving MS as a risk factor.

Costs of illness for melanoma and nonmelanoma skin cancer in Denmark.

Incidences of melanoma and nonmelanoma skin cancer are high and increasing in many countries including Denmark. The diseases are highly preventable. We have estimated the healthcare costs of these cancers by comparing costs for cohorts of patients and matched controls in a national register-based study in Denmark. All incident patients with a diagnosis of melanoma, basal cell carcinoma, or squamous cell carcinoma in the period 2004–2008 were included. Four control individuals for each case were matched in terms of sex, age, and area of residence. Healthcare costs and productivity loss for patients and controls were estimated using Danish health and social registries 3 years before and 3 years after diagnosis. The healthcare costs of melanoma and nonmelanoma skin cancer were &OV0556;33.3 million in the 3-year period after diagnosis, with male patients inducing the highest costs for all three cancers and costs increasing with age. The diagnoses of basal cell carcinoma and melanoma had almost the same healthcare costs, but per patient average healthcare costs were higher for melanoma. The costs of melanoma and nonmelanoma skin cancers, which can be prevented by sensible sun habits, exceed the costs of the preventive measures of the Danish SunSmart campaign manifold. Costs of melanoma and nonmelanoma skin cancer are expected to increase in the future with populations aging in the western world. The analyses provide a strong argument for the societal rationale of skin cancer prevention in Denmark.

Feasibility of smartphone diaries and personal dosimeters to quantitatively study exposure to ultraviolet radiation in a small national sample

In 2007, a national skin cancer prevention campaign was launched to reduce the UV exposure of the Danish population. To improve campaign evaluation a questionnaire validation using UV‐dosimeters was initiated.

Short and long term variation in ultraviolet radiation and multiple sclerosis

We examined the role of ultraviolet radiation (UVR) in persons diagnosed with multiple sclerosis (MS) in four different populations, Italians, Danish, White and African Americans. We tested whether variation in UVR as determined by seasons (short term variation) and solar cycles (long term variation) is related to MS birth month and to survival as measured by lifespan. Cases were selected from three Italian MS Case Registries (2,737); from the United States National Center for Health Statistics (56,020); and from the Danish Multiple Sclerosis registry (15,900). Chi-square tests were used to study the pattern of month of birth distribution in patients with MS comparing with general population data. T-tests were employed to study solar cycles association with lifespan. A surplus of births was observed in June for White Americans. A decrease of births in October and November, though not significant after multiple testing correction, was observed in the three populations. In White American with MS overall, males and females, we found that solar cycle is associated with lifespan. We found that season and solar cycles have some role in MS susceptibility and life duration. However, this is an exploratory analysis and further work is needed to discern the association.

Determinants of sunbed use in a population of Danish adolescents.

In Denmark, melanoma is the most common type of cancer in individuals aged 15–34 years. Ultraviolet radiation from sunbeds is a risk factor for melanoma. Knowledge of the characteristics of sunbed users is important in the development and implementation of prevention strategies of sunbed use. The objective of this study was to examine sunbed use and its association with smoking, parental socioeconomic status (SES), friends’ attitudes towards artificial tanning, and school environment among adolescents aged 14–18 years at continuation schools in Denmark. We conducted a survey among adolescents in Danish continuation schools in 2011. We examined sunbed use and its association with age, smoking, friends’ attitudes towards artificial tanning, parental SES, and shared environment of the continuation school, using logistic regression. Within the past 12 months, 38% of the pupils had used a sunbed (70% girls and 28% boys). There was no difference in sunbed use according to age. Smoking and friends’ positive attitudes towards, and higher use of sunbeds were associated with increased use of sunbeds. High SES of mothers’ was associated with lower odds for sunbed use among girls. The association of school environment with sunbed use was modest compared with the other variables. Adolescents in continuation schools report a higher use of sunbeds than Danish adolescents as such. Educational interventions should be targeted at preteens, as sunbed use is common in 14-year-olds. Special educational tools are tested in the continuation school environment and may prove effective in this population.