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Leif Mosekilde

Publications and source records attributed to Leif Mosekilde.

At least 19 recordsLinked to original sources
PubMed2007

[Oesteogenesis imperfecta--genetics, diagnosis and medical treatment].

The molecular background for osteogenesis imperfecta (OI) is mutations in one of the two genes (COL1A1 and COL1A2) encoding collagen I. The disease is characterised by varying degrees of fragile bones, retarded growth, bone deformities, tooth abnormalities, blue sclerae, and hearing loss. Treatment with bisphosphonates reduces the incidence of fractures in children with severe OI, while this still remains to be demonstrated in adults. Results from bone marrow transplantation and animal experiments may lead to alternative treatment in severe OI.

Adult↗
PubMed2006

Fracture risk in users of oral anticoagulants: a nationwide case-control study.

BACKGROUND: Vitamin K antagonists (VKA) are often used as oral anticoagulants in order to prevent thromboembolic diseases. In bone, vitamin K reduces bone resorption and functions as a cofactor in the posttranslational carboxylation of several bone proteins. Discrepant results have been reported on whether VKA affects bone mineral density and fracture risk. AIM: In a nationwide population-based pharmaco-epidemiological case-control study we assessed fracture risk in users of VKA. METHODS: We compared 124,655 cases that sustained a fracture during year 2000 with 373,962 age- and gender-matched controls. We used computerized registers to assess individual drug use and related these data to individual fracture data and information on confounders. RESULTS: VKA was used in 2.2% of the cases and in 1.6% of the controls (crude OR 1.34; 95% CI, 1.28-1.41). After confounder adjustment, current use of VKA was associated with an increased risk of any fracture (OR 1.10; 95%CI, 1.03-1.18). Fracture risk was not increased in former users. Dose-effect analysis showed that only those who had used a relatively low accumulated dose of VKA (less than 100 defined daily dosages) had an increased risk of any fracture (adj. OR 1.49; 95%CI, 1.31-1.69), as well as an increased risk of fractures at the hip (adj. OR 1.43; 95%CI, 1.09-1.87) and forearm (adj. OR 1.42; 95%CI, 1.02-1.97). CONCLUSION: Current use of small, accumulated amounts of VKA is associated with an increased fracture risk. This may be due to circumstances related to the disease necessitating therapy as well as due to a pharmacological effect.

Administration, Oral↗
PubMed2006

Oral contraceptive use and risk of fractures.

INTRODUCTION: Prior studies have suggested that oral contraceptives (OCs) may be associated with an increased fracture risk. However, the previous studies have only performed a limited adjustment for other potential risk factors. SUBJECTS AND METHODS: All women with a fracture (n=64,548) in the year 2000 in Denmark served as cases. For each case, three age-matched controls were randomly drawn from the general population (n=193,641). Exposure was use of OCs between January 1, 1996, and December 31, 2000. Adjustments were made for use of other drugs, pregnancy, prior fracture, other diseases and social variables. RESULTS: In the unadjusted analysis, use of OCs in low dose was associated with a small increase in overall fracture risk. However, upon adjustment, no increase in fracture risk could be demonstrated in any age or dose group. CONCLUSION: Oral contraceptives are not associated with an increase or a decrease in fracture risk. Any change in fracture risk may be due to confounders.

Adult↗
PubMed2006

Fracture reducing potential of hormone replacement therapy on a population level.

OBJECTIVES: To study the fracture reducing potential of hormone replacement therapy (HRT) at a population level, the effect of age on the fracture reducing potential of HRT, and to examine whether socio-economic factors confound the effects of HRT on fracture risk. SUBJECTS AND METHODS: Case-control study. All women who sustained any fracture during the year 2000 in Denmark served as cases (n=64,548). For each case, three age-matched controls were randomly drawn from the background population (n=193,641). The main exposure was the average daily dose of HRT (expressed as defined daily doses DDD/day). Adjustments were made for co-morbidity, socio-economic factors, and prior fracture. RESULTS: A fracture risk reduction was seen in women aged>or=50 years using >or=0.3 DDD/day. The risk reduction for any fracture was larger in women aged>or=60 years (0.3-0.99 DDD/day: odds ratio (OR)=0.77, 95% confidence intervals (CI): 0.73-0.82, >or=1 DDD/day: OR=0.61, 95% CI: 0.56-0.67) than in women aged 50-59 years (0.3-0.99 DDD/day: OR=0.92, 95% CI: 0.85-0.99, >or=1 DDD/day: OR=0.77, 95% CI: 0.70-0.84). Larger risk reductions were seen for Colles' fractures (age 50-59 years: OR=0.64 for 0.3-0.99 DDD/day, and OR=0.57 for >or=1 DDD/day, age>or=60 years: OR=0.52 for 0.3-0.99 DDD/day, and OR=0.40 for >or=1 DDD/day). Adjustment only changed the estimates little. No difference between oral and dermal preparations could be found. CONCLUSIONS: Hormonal replacement therapy possesses a fracture-reducing potential at population level even at dosages lower than usually recommended. The risk reduction was larger with advancing age for any fracture and Colles' fractures.

Case-Control Studies↗
PubMed2006

[Cinacalcet--a new drug for the treatment of secondary hyperparathyroidism in patients with uraemia, parathyroid cancer or primary hyperparathyroidism].

Cinacalcet is a new drug with antiparathyroid effects that belongs to the class of calcimimetics. It increases the sensitivity of the calcium-sensing receptor (CaSR) to calcium, thus inducing a decrease in plasma parathyroid (PTH) levels. In patients with uncontrolled secondary hyperparathyroidism due to uremia, cinacalcet has been shown to decrease the levels of PTH even in those optimally treated with calcium and 1-ahydroxylated vitamin D. Cinacalcet decreases plasma calcium and plasma PTH levels in patients with primary hyperparathyroidism or parathyroid cancer.

Calcium↗
PubMed2006

Socioeconomic aspects of fractures within universal public healthcare: a nationwide case-control study from Denmark.

AIMS: To investigate the effects of income and other socioeconomic variables on fracture risk adjusted for disease-related confounders as fractures are a major public health problem. METHODS: Case-control study where all subjects in Denmark with a fracture during the year 2000 (n = 124,655) served as cases. From the general population three age- and gender-matched subjects were selected as controls (n = 373,962). Adjustment were made for income, living with someone vs. living alone, having a job vs. being out of work, education, comorbidity (Charlson index), number of bed days in hospital, number of contacts with general practitioner, use of corticosteroids, prior fracture, and alcoholism. RESULTS: Income was not associated with fracture risk on adjustment for the other covariates. Living with someone was associated with a decreased risk of any fracture in all ages. A higher level of education was associated with a decreased fracture risk in the age groups<60 years, but an increased fracture risk among subjects>or=60 years. Being at work was associated with a decreased hip fracture risk among subjects>or=40 years. Alcoholism and a prior fracture were significant predictors of fracture in all age groups. CONCLUSIONS: Income does not predict fracture risk in Denmark after adjustment for other social and comorbidity variables. This may signal neutralization of the effect by socioeconomic compensation or that income was the product of underlying socioeconomic variables.

Adrenal Cortex Hormones↗
PubMed2006

Treatment with beta-blockers, ACE inhibitors, and calcium-channel blockers is associated with a reduced fracture risk: a nationwide case-control study.

BACKGROUND: Cardiovascular diseases are associated with disturbances in calcium metabolism, including increased urinary calcium, vitamin D insufficiency, and decreased bone mineral density. Antihypertensive drugs may increase the risk of falling. However, risk of fracture in patients treated with non-diuretic cardiovascular drugs is largely unknown. AIM: We investigated associations between fracture risk and treatment with commonly used cardiovascular drugs: beta-blockers, angiotensin-converting enzyme (ACE) inhibitors, and calcium-channel blockers. DESIGN: A population-based pharmaco-epidemiological case-control study with fracture in year 2000 as outcome and drug use during the previous 5 years as exposure. We used nationwide computerized registers to assess individual use of drugs and related these data to individual fracture records and information on socio-economic and health-related confounders. RESULTS: We included 124,655 cases that sustained a fracture and 373,962 age and gender-matched controls. After adjustment for potential confounders, risk of any fracture was reduced by 9% [odds ratio (OR) 0.91; 95% confidence interval (CI), 0.88-0.93] in users of beta-blockers, by 6% (OR, 0.94; 95%CI, 0.91-0.96) in users of calcium-channel blockers, and by 7% (OR, 0.93; 95%CI, 0.90-0.96) in users of ACE inhibitors. Moreover, risk of hip fractures was reduced significantly by 7-14% in users of the three groups of drugs. No major differences were found between men and women or in subjects younger or older than 70 years of age. Sub-analyses indicated differences between groups of calcium-channel blockers, as use of non-dihydropyridine drugs was associated with a larger risk reduction than use of dihydropyridine drugs. CONCLUSION: Treatment with beta-blockers, ACE inhibitors, and calcium-channel blockers is associated with a small but significantly reduced risk of fracture.

Adolescent↗
PubMed2006

Ten-year absolute risk of osteoporotic fractures according to BMD T score at menopause: the Danish Osteoporosis Prevention Study.

UNLABELLED: In the non-HRT arms of the DOPS study, 10-year fracture risk was higher at each level of T score than predicted by the Kanis algorithm. Under-reporting of fractures in registers and inclusion of HRT users are probable explanations for inappropriately low fracture risk estimates for younger women. INTRODUCTION: International recommendations highlight the importance of absolute fracture risk in establishing intervention thresholds. The available estimates of long-term risk have been derived by combining relative risks from meta-analyses with U.S. normative BMD data and Swedish fracture incidence records. We validated the 2001 Kanis risk algorithm using incident fractures observed in untreated women in the first 10 years of the Danish Osteoporosis Prevention Study (DOPS). Comparisons were also made with the relative risks derived from a recent meta-analysis of 12 cohort studies. MATERIALS AND METHODS: We analyzed DXA of the spine and hip from 872 women who were enrolled in the non-hormone replacement therapy (HRT) arms of the study and had not received HRT, bisphosphonates, or raloxifene. We collected verified reports of fractures at each visit. We focused on fractures of the hip, spine, shoulder, and forearm to provide risks comparable with the Kanis algorithm. Accordingly, asymptomatic radiographic vertebral fractures were not included. RESULTS: Seventy-eight women (9%) sustained relevant fractures. The risk of fracture increased by 1.32 (95% CI, 1.02; 1.70) for each unit decrease in femoral neck T score and by 1.30 (95% CI, 1.06; 1.58) for each unit decrease in lumbar spine T score at baseline. Absolute fracture risk was higher than expected from the Kanis algorithm at all T score levels. The difference was greatest for participants in the higher range of T scores. At T = -1, the observed risk was 10.9% as opposed to an expected risk of 5.7%. Relative risk gradients were similar to those of the recent meta-analysis. CONCLUSIONS: In healthy women, examined in the first year or two after menopause, 10-year fracture risk was higher at each level of BMD T score than expected from the model by Kanis et al. Inclusion of HRT users in the cohorts used may have led to higher BMD values and lower absolute fracture risk in the Kanis model. These longitudinal data can be used directly in estimating absolute fracture risk in untreated north European women from BMD at menopause.

Absorptiometry, Photon↗
PubMed2006

Decreased fracture risk in users of organic nitrates: a nationwide case-control study.

UNLABELLED: In a nationwide population-based pharmaco-epidemiological case-control study, including 124,655 subjects who had sustained a fracture during 2000 (cases) and 373,962 age- and sex-matched controls, we found an approximately 15% reduced risk of fractures in users of organic nitrates. Thus, organic nitrates may protect against osteoporosis. INTRODUCTION: Organic nitrates are widely used in the treatment of ischemic heart diseases. In addition, nitrates may affect bone. In vitro studies have shown that nitrates are able to inhibit bone resorption, and recent studies in humans have shown a positive effect on BMD and bone turnover. MATERIALS AND METHODS: We studied the effect of organic nitrates on risk of fracture. We performed a population-based pharmaco-epidemiological case-control study with fracture in 2000 as outcome and use of nitrates (isosorbide mononitrate, isosorbide dinitrate, and nitroglycerin) during the previous 5 years as exposure variable. We used nationwide computerized registers to assess individual use of nitrates and related these data to individual fracture data and information on potential confounders. In the study, we included 124,655 subjects who had sustained a fracture during 2000 (cases) and 373,962 age- and sex-matched controls. RESULTS: After confounder adjustment, use of nitrates was associated with an 11% reduced risk of any fracture (OR = 0.89; 95% CI, 0.86-0.92) and a 15% reduced risk of hip fracture (OR = 0.85; 95% CI, 0.79-0.92). Risk of any fracture was reduced in both men and women, but risk of hip fracture was only reduced in women. Hip fracture risk was reduced dose-dependently. Use of nitrates with a short duration of action was associated with lower risk estimates than use of slow release preparations. CONCLUSIONS: Treatment with nitrates is associated with a decreased risk of fracture. Further studies should determine whether a causal relationship exists.

Adolescent↗
PubMed2006

Body composition is distinctly altered in Turner syndrome: relations to glucose metabolism, circulating adipokines, and endothelial adhesion molecules.

BACKGROUND: Body composition in Turner syndrome (TS) is altered with final height of TS decreased; anthropometry and bone mass distinctly changed. AIM: To describe total and regional distribution of fat and muscle mass in TS and the relation to measures of glucose metabolism, sex hormones, IGFs, and markers of inflammation and vascular function. MATERIAL AND METHODS: Fifty-four women with TS (mean age, 42.5 +/- 9.7 years) and an age-matched group of controls (n = 55) were examined by dual-energy X-ray absorptiometry scans with determination of regional body composition and estimation of visceral fat and skeletal muscle mass. We determined maximal oxygen uptake and assessed physical activity using a questionnaire. We measured serum adiponectin, ghrelin, IGF-I, IGF-binding protein-3 (IGFBP-3), estradiol, testosterone, sex hormone-binding globulin (SHBG), insulin, glucose, cytokines, vascular cell adhesion molecule-I, and intercellular cell adhesion molecule-I. Insulin sensitivity was estimated. Multiple linear regression models were used to examine the relationships between variables. RESULTS: TS had lower total lean body mass (LBM), while body mass index (BMI) and total fat mass (FM) were increased. We found increased visceral FM, and decreased trunk LBM, appendicular LBM, and skeletal muscle mass. VO2max and physical activity were significantly lower in TS, as were most hormone levels, except increased leptin. In multiple linear regression models, status (i.e. TS or control) was a consistent contributing variable. CONCLUSION: Profound changes are present in body composition in TS, with increased FM, and decreased skeletal muscle mass. Circulating hormones, VO2max, and insulin sensitivity influence body composition. The accumulation of visceral fat would predict a higher risk of development of the insulin resistance syndrome.

Adipocytes↗
PubMed2006

The metabolic syndrome is frequent in Klinefelter's syndrome and is associated with abdominal obesity and hypogonadism.

OBJECTIVE: Klinefelter's syndrome is associated with an increased prevalence of diabetes, but the pathogenesis is unknown. Accordingly, the aim of this study was to investigate measures of insulin sensitivity, the metabolic syndrome, and sex hormones in patients with Klinefelter's syndrome and an age-matched control group. RESEARCH DESIGN AN METHODS: In a cross-sectional study, we examined 71 patients with Klinefelter's syndrome, of whom 35 received testosterone treatment, and 71 control subjects. Body composition was evaluated using dual-energy X-ray absorptiometry scans. Fasting blood samples were analyzed for sex hormones, plasma glucose, insulin, C-reactive protein (CRP), and adipocytokines. We analyzed differences between patients with untreated Klinefelter's syndrome and control subjects and subsequently analyzed differences between testosterone-treated and untreated Klinefelter's syndrome patients. RESULTS: Of the patients with Klinefelter's syndrome, 44% had metabolic syndrome (according to National Cholesterol Education Program/Adult Treatment Panel III criteria) compared with 10% of control subjects. Insulin sensitivity (assessed by homeostasis model assessment 2 modeling), androgen, and HDL cholesterol levels were significantly decreased, whereas total fat mass and LDL cholesterol, triglyceride, CRP, leptin, and fructosamine levels were significantly increased in untreated Klinefelter's syndrome patients. In treated Klinefelter's syndrome patients, LDL cholesterol and adiponectin were significantly decreased, whereas no difference in body composition was found in comparison with untreated Klinefelter's syndrome patients. Multivariate analyses showed that truncal fat was the major determinant of metabolic syndrome and insulin sensitivity. CONCLUSIONS: The prevalence of metabolic syndrome was greatly increased, whereas insulin sensitivity was decreased in Klinefelter's syndrome. Both correlated with truncal obesity. Hypogonadism in Klinefelter's syndrome may cause an unfavorable change in body composition, primarily through increased truncal fat and decreased muscle mass. Testosterone treatment in Klinefelter's syndrome only partly corrected the unfavorable changes observed in untreated Klinefelter's syndrome, perhaps due to insufficient testosterone doses.

Abdominal Fat↗
PubMed2005

Loop diuretics increase bone turnover and decrease BMD in osteopenic postmenopausal women: results from a randomized controlled study with bumetanide.

UNLABELLED: To study effects of loop diuretics on bone, 87 women were randomized to 1 year of treatment with bumetanide or placebo. Compared with placebo, bumetanide decreased BMD by 2% at the total hip and by 1.4% at the whole body. Levels of biochemical bone markers were lower in the placebo than in the bumetanide group. Thus, treatment with loop diuretics affects bone metabolism. INTRODUCTION: Loop diuretics may affect bone because they increase the renal calcium excretion and alters the diurnal rhythm of plasma PTH levels. We studied the effects of 1 year of treatment with the loop diuretic bumetanide on bone metabolism. MATERIALS AND METHODS: In a double-blinded design, 87 healthy postmenopausal women with osteopenia were randomized to 1-year bumetanide treatment 2 mg/day or placebo. BMD, plasma levels of calcitropic hormones, and biochemical bone markers were measured at baseline, after 1 year of treatment (week 52), and 6 months after withdrawal of treatment (week 78). Calcium (800 mg/day) and vitamin D (10 microg/day) were administered to all participants during the entire 1.5-year study period. RESULTS: Compared with placebo, urinary calcium (+17%) and plasma PTH levels (+9%) increased significantly in response to bumetanide. After 1 year of treatment, BMD in the bumetanide compared with the placebo group was significantly decreased by 2% at the total hip and ultradistal forearm and by 1.4% at the whole body. In addition, levels of biochemical markers of bone turnover differed significantly (approximately 20%) between groups, with lower levels in the placebo than in the bumetanide group. Six months after the end of treatment, the effects of bumetanide were weakening. CONCLUSIONS: Treatment with loop diuretics affects bone turnover and decreases BMD. Further studies may reveal whether loop diuretics should be considered as a risk factor for fracture.

Aged↗
PubMed2005

[Strontium ranelate: a new therapeutic principle for postmenopausal osteoporosis].

Strontium ranelate (SR) is a new drug for osteoporosis that has a unique effect profile, being antiresorptive as well as anabolic. In postmenopausal women with spinal osteoporosis pretreated with calcium and vitamin D, SR reduced the risk of new vertebral fractures after 1 year by 49% and after 3 years by 41% (NNT = 9). The numbers of clinical fractures were in the same periods reduced by 52% and 38%, respectively. The number of patients with more than one new spinal fracture was reduced by 36%. Height reduction was less among the patients so treated, and there was a tendency towards less lumbar pain. Measured lumbar BMD increased 14.4% over three years, corresponding to an increase of 6.8% after adjustment for bone strontium content, compared with a decrease in the placebo group of 1.3%. The risk of new non-vertebral fractures was reduced by 16%. Among elderly women with a hip T-score <-3, SR decreased the risk of hip fractures by 36% over three years (NNT = 48). In patients with osteopenia and at least one clinical risk factor, SR reduced the risk of first vertebral fracture by 72% over three years (NNT = 12). In patients over 80 years of age, the risk of new vertebral fractures was reduced by 32% (NNT = 14). There were few side effects. SR is thus suitable for reducing the risk of vertebral and hip fractures from postmenopausal osteoporosis, especially among patients with upper abdominal dyspepsia and the elderly.

Aged↗
PubMed2005

Ten-year prediction of osteoporosis from baseline bone mineral density: development of prognostic thresholds in healthy postmenopausal women. The Danish Osteoporosis Prevention Study.

Osteopenia is common in healthy women examined in the first year or two following menopause. Short-term fracture risk is low, but we lack algorithms to assess long-term risk of osteoporosis. Because bone loss proceeds at only a few percent per year, we speculated that baseline bone mineral density (BMD) would predict a large proportion of 10-year BMD and be useful for deriving predictive thresholds. We aimed to identify prognostic thresholds associated with less than 10% risk of osteoporosis by 10 years in the individual participant, in order to allow rational osteodensitometry and intervention. We analyzed dual energy X-ray absorptometry (DXA) of the lumbar spine (LS) and femoral neck (FN) from 872 women, who participated in the non-HRT arms of the Danish Osteoporosis Prevention Study and had remained on no HRT, bisphosphonates or raloxifene since inclusion 10 years ago. We defined development of a T -score below -2.5 at the LS and/or FN or incident fracture as end-point, and we derived prognostic thresholds for baseline BMD, defining 90% NPV (negative predictive value) and 90% sensitivity, respectively. Seventy-six percent of the variation in BMD of the LS at 10 years was predicted by baseline BMD. In an individual participant, a baseline BMD T -score above -1.4 (FN or LS, whichever was lower) was associated with a 10-year risk of less than 10% of developing osteoporotic BMD or fracture. This covered 69% of the population. By contrast, participants with T -scores below -1.4 had a 56% risk of fracture or low BMD within 10 years. At the population level, baseline T -score cutoffs below 0 at the LS (68% of the population), 0 at the FN (72%) or -0.6 (62%) at the lower of the two sites capture 90% of the population that developed osteoporosis during the following 10 years. A BMD measurement, performed in the first two years following menopause, is a strong long-term predictor of BMD in healthy women. The association is strong enough to provide robust prognostic thresholds, which can be used to divide the population into two prognostic classes at menopause.

Absorptiometry, Photon↗
PubMed2005

[Hyperthyroidism and risk of atrial fibrillation or flutter--secondary publication. A population-based study].

We identified all patients with an incident diagnosis of hyperthyroidism in the Danish National Patient Registry, and among those we identified subjects with a diagnosis of atrial fibrillation or flutter that occurred +/- 30 days from the date of the diagnosis of hyperthyroidism. Among 40,628 subjects with hyperthyroidism, 3,362 (8.3%) had a diagnosis of atrial fibrillation or flutter. Male sex, increasing age, ischemic heart disease, congestive heart failure and heart valve disease were associated with an increased risk of atrial fibrillation or flutter in patients with hyperthyroidism.

Adult↗
PubMed2005

Trends in incidence and mortality in the hospital diagnosis of atrial fibrillation or flutter in Denmark, 1980-1999.

BACKGROUND: The incidence of diagnosed atrial fibrillation is increasing in the USA, England, Wales, Scotland and Denmark, and the mortality rate in patients with diagnosed atrial fibrillation has been reported to be declining in Scotland and Denmark. We undertook this study to examine recent trends in incidence and mortality in subjects with a hospital diagnosis of atrial fibrillation or flutter in Denmark from 1980 to 1999 by sex, 10-year age group and conditions of comorbidity. METHODS: We identified all individuals, aged 40-89 years, with an incident hospital diagnosis of atrial fibrillation or flutter in the Danish National Registry of Patients, and subjects were followed in the Danish Civil Registration System. We used multivariate Cox proportional hazard models to estimate trends in mortality. RESULTS: Atrial fibrillation or flutter was diagnosed in 131,728 subjects (68,660 men and 63,068 women), and the incidence of a hospital diagnosis of atrial fibrillation or flutter more than doubled during the study period. The hazard ratios for mortality adjusted for 10-year age group, conditions of comorbidity and mortality trend in the Danish population in the last 5-year period compared to the first 5-year period were 0.80 (95% confidence interval 0.78-0.82) in men, and 0.82 (95% confidence interval 0.80-0.84) in women. CONCLUSIONS: The incidence of a hospital diagnosis of atrial fibrillation or flutter more than doubled, and the 10-year age group- and comorbidity- and general population-adjusted mortality decreased, equally, from the first to the last 5-year period by 20% in men and 18% in women.

Adult↗