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Biomedical subjects

Lars Rejnmark

Publications and source records attributed to Lars Rejnmark.

18 recordsLinked to original sources
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

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

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↗
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

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↗
PubMed2004

Fracture risk in perimenopausal women treated with beta-blockers.

beta2-Adrenergic receptors have been identified on human osteoblastic and osteoclastic cells, raising the question of a sympathetic regulation of bone metabolism. We investigated effects of treatment with beta-adrenergic receptor antagonists (beta-blockers) on bone turnover, bone mineral density (BMD), and fracture risk. Within the Danish Osteoporosis Prevention Study (DOPS) a population based, comprehensive cohort study of 2016 perimenopausal women, associations between treatment with beta-blockers and bone turnover and BMD were assessed in a cross-sectional design at the start of study. Moreover, in a nested case-control design, fracture risk during the subsequent 5 years was assessed in relation to treatment with beta-blockers at baseline. Multiple regression- and logistic regression-analyses were performed. Treatment with beta-blockers was associated with a threefold increased fracture risk (OR(adj) 3.3; 95% CI: 1.1-9.4). Analyses on duration of treatment showed that women who had been treated for more than 8 years had a higher fracture risk (OR(adj) 5.3; 95% CI: 1.1-26.3) than those treated for less than 8 years (OR(adj) 2.4; 95% CI: 0.6-9.5). In addition, cross-sectional data showed 20% lower serum osteocalcin levels (an osteoblastic marker of bone formation) in women treated with beta-blockers compared to untreated women (P < 0.001), whereas BMD at the lumbar spine and femoral neck did not differ between groups. beta-Blockers may decrease the activity of bone-forming cells and thereby increase fracture risk. However, confirmative studies and studies exploring mechanisms of action are needed.

Adrenergic beta-Antagonists↗
PubMed2004

Osteoporosis is markedly underdiagnosed: a nationwide study from Denmark.

AIM: To compare the number of patients diagnosed with osteoporosis and osteoporotic fractures in Denmark, with the number of subjects expected to have osteoporosis. SUBJECTS AND METHODS: From the National Hospital Discharge Register, records for all patients diagnosed with osteoporosis and/or with osteoporotic fractures between 1995 and 1999 were retrieved. Based on normal Danish values for BMD, the expected number of subjects aged 50 years or more with osteoporosis according to the WHO definition was calculated. RESULTS: The estimated prevalence of osteoporosis was 40.8% of women aged >or=50 years and 17.7% among men. The expected annual incidence was 58,658/million inhabitants in women >or=50 years of age and 23,648/million in men >or=50 years. However, the observed incidence was only 4,823 and 862/million per year, respectively (8.2% and 3.6% of the expected). In 1999, a total of 34,691 hip, spine, and forearm fractures were reported in subjects >or=50 years, and of these, 18,566 were potentially attributable to osteoporosis (14,240 fractures in women and 4,326 in men equaling 14,976 and 5,297/million per year). Only 0.3% of men >or=50 years were receiving a bisphosphonate, while 2.2% of women received a bisphosphonate or raloxifene. Among women >or=50 years, 27.7% received hormone replacement therapy. CONCLUSIONS: Osteoporotic fractures of the hip, spine, and forearm are rather frequent in Denmark, but the diagnosis of osteoporosis is rarely used. It seems that osteoporosis is markedly underdiagnosed and undertreated in Denmark as probably also elsewhere. This may have significant implications for the prevention of osteoporotic fractures.

Adult↗
PubMed2004

Hip fracture risk in statin users--a population-based Danish case-control study.

Based on animal studies, statins (3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors) have been suggested as potential agents in the treatment of osteoporosis. In some epidemiological studies, statins have been associated with a reduced fracture risk. Our objective was to examine associations between statin treatment and risk of hip fracture in a population-based case-control study. A total of 6660 subjects with hip fracture and 33,274 gender- and age-matched population controls were identified from 1 January 1994 to 31 December 2001 using the Hospital Patient Register in North Jutland County, Denmark, and the Danish Central Personal Registry, respectively. Data on redeemed prescriptions for statins within the last 5 years before the index date were retrieved from a population-based prescription database. We used conditional logistic regression to estimate odds ratios (OR) for hip fracture according to use of statin prescriptions adjusted for potential confounding factors, i.e. gender, other diseases, and use of other drugs known to affect bone metabolism and fracture risk. After adjustment for potential confounders, statin treatment was associated with a reduced risk of hip fracture (OR=0.68; 95% confidence interval: 0.50-0.93) for those who had redeemed more than three prescriptions for a statin drug. We found that risk of hip fracture decreased with the number of statin prescriptions. Stratified analyses on gender and age did not reveal any major differences between men and women or among different age groups on the estimates between use of statins and hip fracture risk. Our findings support an association between statin treatment and a reduced hip fracture risk. However, it is unclear whether this association is causal.

Adolescent↗
PubMed2004

Effects of simvastatin on bone turnover and BMD: a 1-year randomized controlled trial in postmenopausal osteopenic women.

UNLABELLED: To study effects of statins on human bone, 82 postmenopausal women were randomized to 1-year treatment with simvastatin 40 mg/day or placebo. The study showed no effect of simvastatin on biochemical bone markers or on BMD at the hip or spine. Thus, our results do not support a general beneficial effect of simvastatin on bone. INTRODUCTION: Statins have been reported to cause bone anabolic as well as antiresorptive effects, and therefore statins have been suggested as potential agents in treatment of osteoporosis. MATERIALS AND METHODS: In a double-blinded design, 82 healthy postmenopausal women with osteopenia were randomized to 1-year simvastatin treatment 40 mg/day or placebo. BMD and plasma levels of cholesterol, parathyroid hormone (PTH), and biochemical bone markers were measured at baseline, after 1 year of treatment (week 52), and 26 weeks after withdrawal of treatment (week 78). Calcium supplements (400 mg/day) were administrated during the entire 1.5-year study period. RESULTS: Seventy-eight women completed the 1-year treatment. After 1 year, simvastatin but not placebo caused reduced plasma cholesterol (-27% versus +1%, p < 0.001) and low-density lipoprotein (LDL) levels (-43% versus +1%, p < 0.001). After withdrawal of treatment, cholesterol and LDL levels returned to baseline levels and no longer differed from the placebo group. However, plasma levels of PTH and biochemical bone markers did not differ between groups at week 52 or 78. Compared with placebo, simvastatin caused no changes in BMD at the lumbar spine, total hip, femoral neck, or whole body at week 52 or 78. However, a significant increase in BMD was found in response to simvastatin at the forearm. Within the simvastatin group, changes in cholesterol levels did not correlate to BMD changes at any site. CONCLUSIONS: Our results do not support a general beneficial effect of simvastatin on bone.

Aged↗
PubMed2004

Fracture risk associated with use of antiepileptic drugs.

PURPOSE: To assess fracture risk associated with different antiepileptic drugs (AEDs). An increased fracture risk has been reported in patients with epilepsy. Classical AEDs have been associated with decreased bone mineral density. The effects of newer AEDs are unknown. METHODS: We undertook a population-based pharmacoepidemiologic case-control study with any fracture as outcome and use of AEDs as exposure variables (124,655 fracture cases and 373,962 controls). RESULTS: All AEDs were associated with an increased fracture risk in an unadjusted analysis. After adjustment for prior fracture, use (ever) of corticosteroids, comorbidity, social variables, and diagnosis of epilepsy, carbamazepine [CBZ; odds ratio (OR), 1.18; 95% confidence interval (CI), 1.10-1.26], [and oxcarbazepine (OXC; 1.14, 1.03-1.26)], clonazepam (CZP; 1.27, 1.15-1.41), phenobarbital (PB; 1.79, 1.64-1.95), and valproate (VPA; 1.15, 1.05-1.26) were statistically significantly associated with risk of any fracture. Ethosuximide (0.75, 0.37-1.52), lamotrigine (1.04, 0.91-1.19), phenytoin (1.20, 1.00-1.43), primidone (1.18, 0.95-1.48), tiagabine (0.75, 0.40-1.41), topiramate (1.39, 0.99-1.96), and vigabatrin (0.93, 0.70-1.22) were not statistically significantly associated with fracture risk after adjustment for confounders. The relative increase was modest and in the same range for the significant and nonsignificant results. CBZ, PB, OXC, and VPA displayed a dose-response relation. Fracture risk was more increased by liver-inducing AEDs (OR, 1.38; 95% CI, 1.31-1.45) than by noninducing AEDs (1.19; 95% CI, 1.11-1.27). CONCLUSIONS: A very limited increased fracture risk is present in users of CBZ, CZP, OXC, PB, and VPA. A limited significant increase cannot be excluded for the other AEDs because of the statistical power.

Adult↗
PubMed2002

Fracture risk is increased in patients with GH deficiency or untreated prolactinomas--a case-control study.

OBJECTIVE: The pituitary secretes many hormones of significance to bone turnover and thus skeletal integrity. The aim of this study was to examine fracture risk in patients with pituitary disorders with special reference to GH deficiency and hyperprolactinaemia. DESIGN: Case-control study. MEASUREMENTS: Fracture occurrence. PATIENTS: A self-administered questionnaire was issued to 537 consecutive patients with pituitary disorders excluding Cushing's disease. A total of 426 (79%) returned the questionnaire and 422 of these could be analysed. Each respondent was compared to three age- and gender-matched control respondents to the same questionnaire drawn randomly from the background population. RESULTS: The patients had a mean age of 51.4 +/- 14.8 years. One hundred and eight patients had acromegaly, 86 had prolactinomas, 136 had non-functioning pituitary adenomas (NFPA), 23 had craniopharyngiomas, and 73 had other types of pituitary disorders. For the total group the fracture risk was not elevated either before or after confirmed diagnosis compared to controls. However, among the patients with prolactinomas, the fracture risk was significantly increased before (relative risk, RR = 1.6, 95% CI: 1.1--2.3) but not after diagnosis. In patients with NFPA, fracture risk was borderline significantly elevated following diagnosis (RR = 1.6, 95% CI: 1.0--2.6). Patients with subnormal stimulated peak GH values suggestive of GH deficiency had a significantly higher risk of fractures after diagnosis than patients who had normal stimulated peak GH values (odds ratio, OR = 4.90, 95% CI: 1.10--21.88). CONCLUSIONS: Untreated prolactinomas were associated with a significant increase in fracture risk. Growth hormone deficiency was also associated with a higher fracture risk.

Adenoma↗
PubMed2002

Smoking as a risk factor for Graves' disease, toxic nodular goiter, and autoimmune hypothyroidism.

To study the association between smoking and thyroid disease (Graves' disease [E05.0], nodular toxic goiter [E05.2], and autoimmune hypothyroidism [E03.9]) in a low-iodine intake area a case-control study was undertaken. A self-administered questionnaire was issued to 864 consecutive patients with hyperthyroidism and 628 patients with autoimmune hypothyroidism treated at five university or regional endocrinologic clinics in Denmark between January 1, 1990 and December 31, 1998. Each respondent was compared to an age- (+/- 5 years) and gender-matched normal control person randomly drawn from the background population. A total of 621 patients with hyperthyroidism (72%) and 411 patients with autoimmune hypothyroidism (66%) responded. Of these, 617 (542 females) and 408 (364 females) could be analyzed, respectively. There was an increased risk of both Graves' disease (odds ratio [OR] = 2.5, 95% confidence interval [CI]: 1.8-3.5), toxic nodular goiter (OR = 1.7, 95% CI: 1.1-2.5), and autoimmune hypothyroidism (OR = 1.5, 95% CI: 1.1-2.1) with ever smoking compared to never smoking in women, but not in men. With the high proportion of ever-smokers among women (56%), the attributable risk of smoking in women was 45% in Graves' disease, 28% in toxic nodular goiter, and 23% in autoimmune hypothyroidism. Ever use of oral contraceptives was associated with a slightly lower risk of Graves' disease in women, but not of toxic nodular goiter or autoimmune hypothyroidism. In conclusion, smoking is a powerful risk factor for thyroid disease, especially in populations with a high smoking frequency. Oral contraceptive use is associated with a slightly lower frequency of Graves' disease.

Adult↗
PubMed2002

Increased risk of osteoporotic fractures in patients with Cushing's syndrome.

OBJECTIVE: To evaluate if fracture risk was increased in patients with Cushing's syndrome due to the increased endogenous cortisol production. DESIGN: Cohort. METHODS: A self-administered questionnaire was mailed to 125 patients with Cushing's syndrome diagnosed between 1985 and 1999 in Denmark. The response of each patient was compared with that of three age- and gender-matched control subjects randomly drawn among respondents to the same questionnaire from the background population. RESULTS: One hundred and four patients (83%) responded. The median age of the patients was 48 years (range 19-85 years). Sixty-eight had pituitary disease, 28 had adrenal disease, four had had both pituitary and adrenal surgery while four had not undergone surgery at the time of the study. The median time from diagnosis to surgery was 0.2 (range 0-3) years. Eighty-six percent were cured following surgery. There was an increased fracture risk within the last 2 years prior to diagnosis (incidence rate ratio 6.0, 95% confidence intervals (CI): 2.1-17.2). More than 2 years prior to diagnosis and following diagnosis there was no difference in fracture risk between patients and controls. The patients had more low-energy fractures than the controls (relative risk 5.4, 95% CI: 1.4-20.1). There was no difference in fracture risk between patients with adrenal or pituitary disease. CONCLUSIONS: Patients with Cushing's syndrome had an increased fracture risk in a narrow time interval before diagnosis, while no increase in fracture risk could be demonstrated after diagnosis and treatment.

Adrenal Glands↗
PubMed2002

Diurnal rhythm of plasma 1,25-dihydroxyvitamin D and vitamin D-binding protein in postmenopausal women: relationship to plasma parathyroid hormone and calcium and phosphate metabolism.

OBJECTIVE: Diurnal variations in plasma levels of 1,25-dihydroxyvitamin D (1,25(OH)(2)D) have previously only been investigated in young individuals, and these studies have failed to demonstrate a diurnal rhythm. We have studied whether plasma levels of 1,25(OH)(2)D and vitamin D-binding protein (DBP) vary in a diurnal rhythm in postmenopausal women. METHODS: Blood and urine were sampled with 2- and 4-h intervals in order to assess diurnal variations in plasma levels of 1,25(OH)(2)D, DBP and parathyroid hormone (PTH), as well as in plasma levels and urinary excretion rates of calcium and phosphate. Additionally, the free 1,25(OH)(2)D index was calculated (the molar ratio of 1,25(OH)(2)D to DBP). RESULTS: Plasma 1,25(OH)(2)D exhibited a diurnal rhythm (P<0.01) with a nadir in the morning (99+/-12 pmol/l), followed by a rapid increase to a plateau during the day (113+/-13 pmol/l, i.e. 14% above nadir level; P=0.005). A similar pattern of variation was found in plasma levels of DBP with peak levels 15% above nadir levels (P<0.01). The free 1,25(OH)(2)D index did not vary in a diurnal rhythm. PTH and plasma levels and urinary excretions of calcium and phosphate exhibited a diurnal pattern of variation. The diurnal rhythm of DBP was correlated with the rhythm of 1,25(OH)(2)D (r=0.47, P<0.01) and plasma albumin (r=0.76, P<0.01). Moreover, the rhythm of plasma calcium and PTH varied inversely (r=-0.36, P=0.02). CONCLUSIONS: With the disclosure of a diurnal rhythm of total plasma 1,25(OH)(2)D, all major hormones and minerals related to calcium homeostasis have now been shown to exhibit diurnal variations. In clinical studies, the diurnal variations of 1,25(OH)(2)D and DBP must be considered, i.e. blood sampling must be standardised according to the time of day.

Aged↗