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Biomedical subjects

L Rejnmark

Publications and source records attributed to L Rejnmark.

At least 19 recordsLinked to original sources

Fracture risk in patients treated with amiodarone or digoxin for cardiac arrhythmias: a nation-wide case-control study.

BACKGROUND: Cardiac arrhythmias and osteoporotic fractures are common in the elderly. AIM: We studied whether tachyarrhythmia and/or the drugs used to treat arrhythmias affect risk of fracture. METHODS: In a population-based nation-wide pharmaco-epidemiological case-control design, we compared 124,655 patients that sustained a fracture during 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: Risk of any fracture was increased in patients with atrial fibrillation [Odds ratio (OR): 1.14; 95% confidence interval (95%CI): 1.08-1.21] and in patients currently treated with amiodarone (OR: 1.47; 95%CI: 1.21-1.78). Conversely, current use of digoxin decreased fracture risk (OR: 0.75; 95%CI: 0.71-0.79). Subanalysis showed similar effects in men and in women, but drug treatment only affected fracture risk in subjects older than 65 years of age. In current users of digoxin, risk of any fracture and risk of hip and forearm fracture decreased dose-dependently with increased dose. The use of other antiarrhythmics did not affect fracture risk. CONCLUSION: Special attention should be paid to patients on treatment with amiodarone and/or a diagnosis of atrial fibrillation as they may have an increased risk of fracture. Conversely, treatment with digoxin may reduce fracture risk.

Adult↗

Fracture risk associated with use of nonsteroidal anti-inflammatory drugs, acetylsalicylic acid, and acetaminophen and the effects of rheumatoid arthritis and osteoarthritis.

We studied the effects of various nonmorphine pain medications as well as rheumatoid arthritis and osteoarthritis on fracture risk in a nationwide case-control study. Cases were all subjects with any fracture sustained during the year 2000 (n = 124,655) in Denmark. For each case, three controls (n = 373,962) matched on age and gender were randomly drawn from the background population. The primary exposure variables were use of acetaminophen, nonsteroidal anti-inflammatory drugs (NSAIDs), or acetylsalicylic acid (ASA). Adjustments were made for several confounders. The effect of dose was examined by stratifying for cumulated dose (defined daily dose, DDD). For acetaminophen, a small increase in overall fracture risk was observed with use within the last year (odds ratio [OR] = 1.45, 95% confidence interval [CI] 1.41-1.49). For ASA, no increase in overall fracture risk was present with recent use. Significant heterogeneity was present for the NSAIDs; e.g., ibuprofen was associated with an increased overall fracture risk (OR = 2.09, 95% CI 2.00-2.18 for <20 DDD), while celecoxib was not (OR = 0.76, 95% CI 0.51-1.13 for <20 DDD, 2P < 0.01 for comparison). Osteoarthritis was associated with a decreased risk of any fracture if the diagnosis had been made more than 1 year ago (OR = 0.70, 95% CI 0.67-0.72). Rheumatoid arthritis was associated with an increase in overall fracture risk if the diagnosis had been made within the last year (OR = 1.86, 95% CI 1.68-2.07). Weak analgesics may be associated with fracture risk in a varying way. The effects in most cases were small. Falls may be one reason for the increase in fracture risk with some NSAIDs.

Acetaminophen↗

Proton pump inhibitors, histamine H2 receptor antagonists, and other antacid medications and the risk of fracture.

We studied the effect of proton pump inhibitors, histamine H(2) receptor antagonists, and other types of antacid drugs on fracture risk. All cases were subjects with any fracture sustained during the year 2000 (n = 124,655). For each case, three controls (n = 373,962) matched on age and gender were randomly drawn from the background population. The primary exposure variables were use of proton pump inhibitors, histamine H(2) antagonists, and other antacid drugs. Adjustments were made for several confounders, including diagnosis of an ulcer, nonsteroidal anti-inflammatory drug use, use of histamine H(1) antagonists, stomach resection, previous fracture, and use of corticosteroids. The effect of dose was examined by stratifying for cumulated dose (defined daily dose). Use of proton pump inhibitors was associated with an increase in fracture risk for use within the last year [odds ratio (OR) = 1.18, 95% confidence interval (CI) 1.12-1.43 for overall fracture risk; OR = 1.45, 95% CI 1.28-1.65 for hip fractures; and OR = 1.60, 95% CI 1.25-2.04 for spine fractures). Histamine H(2) antagonists were associated with a decreased fracture risk if they had been used within the last year (OR = 0.88, 95% CI 0.82-0.95 for any fracture, OR = 0.69, 95% CI 0.57-0.84 for hip fractures). Other antacids were not associated with overall fracture risk but were associated with hip and spine fractures. Proton pump inhibitors appeared to be associated with a limited increase in fracture risk, in contrast to histamine H( 2 ) antagonists, which seemed to be associated with a small decrease in fracture risk. In all cases, the changes in risk estimates were small and the clinical significance was limited.

Adrenal Cortex Hormones↗

Methotrexate, azathioprine, cyclosporine, and risk of fracture.

We studied the fracture risk associated with use of methotrexate, azathioprine, and cyclosporine. The study was designed as a case-control study. All patients with a fracture (n = 124,655) in the year 2000 in Denmark served as cases. Information on fractures and confounders was retrieved from the National Hospital Discharge Register and a number of other national registers. For each case, three age- and gender-matched controls were randomly drawn from the general population (n = 373,962). Exposure was use of the drugs and a number of covariates including other immunosuppressive drugs, corticosteroids, any cancer, Crohn's disease, ulcerative colitis, rheumatoid arthritis, psoriasis, liver and kidney disease, prior fracture, and alcoholism. Azathioprine was associated with an increase in overall fracture risk, but besides this, none of the drugs was significantly associated with overall fracture risk or risk of hip, spine, or forearm fracture. Liver [odds ratio (OR) = 1.55, 95% confidence interval (CI) 1.42-1.69] and kidney (OR = 1.26, 95% CI 1.16-1.37) diseases were significantly associated with increased risk of fractures. Azathioprine was associated with an increase in overall fracture risk but not in the risk of spine, hip, or forearm fractures. Methotrexate and cyclosporine were not associated with fracture risk. It thus seems that the underlying disease for which the treatment is administered may be responsible for much of the increase in fracture risk rather than the drugs used to treat the disorder in question.

Adult↗

Statin but not non-statin lipid-lowering drugs decrease fracture risk: a nation-wide case-control study.

INTRODUCTION: Discrepant results have been reported on association between treatment with lipid lowering drugs and fracture risk. Several studies have failed to demonstrate an effect of statins on bone mineral density. Therefore, the epidemiological findings of a reduced fracture risk may be due to selections bias, e.g. a healthy drug user effect. If so, the reduced fracture risk is most likely independent of type of lipid lowering drug. AIM: We assessed fracture risk in users of various lipid-lowering drugs. METHODS: In a case-control design, we compared 124,655 fracture cases 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 potential confounders. RESULTS: Use of statins was associated with a reduced risk of any fracture (adj. OR 0.87; 95% CI, 0.83-0.92) and hip fractures (adj. OR 0.57; 95% CI, 0.48-0.69). Risk of hip fracture decreased with increased accumulated dose of statins. This was true in men and in women and in subjects younger and older than 65 years of age. However, fracture risk was not reduced in patients treated with pravastatin (adj. OR 1.02; 95% CI, 0.89-1.17) or non-statin lipid lowering drugs (adj. OR 0.99; 95% CI, 0.86-1.15). CONCLUSIONS: The reduced fracture risk in users of lipid lowering drugs is apparently specifically related to users of non-pravastatin statins. Our findings do not support the hypothesis of a healthy drug user effect as an explanation for the reduced fracture risk in users of statins.

Adolescent↗

Postpartum vitamin D insufficiency and secondary hyperparathyroidism in healthy Danish women.

OBJECTIVE: To examine vitamin D status and parathyroid function in normal Danish women postpartum. DESIGN: Three cross-sectional measures during follow-up of 89 women postpartum. SUBJECTS AND INTERVENTION: We assessed vitamin D status by measuring plasma 25-hydroxyvitamin D (P-25OHD) and the degree of secondary hyperparathyroidism by measuring plasma parathyroid hormone (P-PTH) in 89 Caucasian women at three consecutive visits: (mean (range)) 23 (10-37) days (spring), 117 (95-140) days (late summer) and 274 (254-323) days (winter) postpartum. RESULTS: P-25OHD showed seasonal variations with higher values in late summer than in the other periods (P < 0.001). At the first visit, 65% received vitamin D supplements. At the following visits, almost 50% were supplemented. Vitamin D insufficiency (P-25OHD < 50 nmol/l) occurred more often during winter (28%) than in spring (14%) (Fisher's exact test, P = 0.02) or late summer (7%) (P = 0.0001). Irrespective of season, vitamin D insufficiency occurred most frequent in women who did not take vitamin D supplements (Fisher's exact test, P < 0.02). Frank vitamin D deficiency (P-25OHD < 25 nmol/l) was observed during winter in 6%. At all three periods, P-25OHD correlated inversely with P-PTH indicating secondary hyperparathyroidism at deficient vitamin D status. During spring, late summer and winter three, one and four females, respectively, had elevated plasma PTH. CONCLUSION: Vitamin D insufficiency with secondary hyperparathyroidism is a frequent finding in healthy Danish women postpartum and especially during winter. Vitamin D supplements reduced the risk of vitamin D insufficiency, especially during winter. Our results support the importance of increased alertness regarding information of pregnant and lactating women about vitamin D supplements. Furthermore, it has to be studied whether the present recommendations of an intake of 5-10 microg vitamin D/day are sufficient, especially during winter months.

Adult↗

No effect of vitamin K1 intake on bone mineral density and fracture risk in perimenopausal women.

INTRODUCTION: Vitamin K functions as a co-factor in the post-translational carboxylation of several bone proteins, including osteocalcin. AIM: The aim of this study was to investigate the relationship between vitamin K(1) intake and bone mineral density (BMD) and fracture risk in a perimenopausal Danish population. DESIGN: The study was performed within the Danish Osteoporosis Prevention Study (DOPS), including a population-based cohort of 2,016 perimenopausal women. During the study approximately 50% of the women received hormone replacement therapy (HRT). Associations between vitamin K(1) intake and BMD were assessed at baseline and after 5-years of follow-up (cross-sectional design). Moreover, associations between vitamin K(1) intake and 5-year and 10-year changes in BMD were studied (follow-up design). Finally, fracture risk was assessed in relation to vitamin K(1) intake (nested case-control design). RESULTS: In our cohort, dietary vitamin K(1) intake (60 mug/day) was close to the daily intake recommended by the Food and Agriculture Organization (FAO). Cross-sectional and longitudinal analyses showed no associations between intake of vitamin K(1) and BMD of the femoral neck or lumbar spine. Neither did BMD differ between those 5% that had the highest vitamin K(1) intake and those 5% that had the lowest. During the 10-years of follow-up, 360 subjects sustained a fracture (cases). In a comparison between the cases and 1,440 controls, logistic regression analyses revealed no difference in vitamin K(1) intake between cases and controls. CONCLUSION: In a group of perimenopausal and early postmenopausal women, vitamin K(1) intake was not associated with effects on BMD or fracture risk.

Adult↗

Anxiolytics, sedatives, antidepressants, neuroleptics and the risk of fracture.

INTRODUCTION: Our objective was to study the association between fracture risk and the use of anxiolytics and sedatives (benzodiazepines, etc.), neuroleptics and antidepressants. SUBJECTS AND METHODS: This was a case control study. All cases consisted of subjects who had sustained a fracture during the year 2000 (n=124,655). For each case, three controls (n=373,962) matched for age and gender were randomly drawn from the background population. Exposure was defined as the use of neuroleptics, antidepressants and anxiolytics/sedatives, psychiatric disease (manic depressive states, schizophrenia, other psychoses), and other confounders. The effect of dose was examined as a defined daily dose per day (DDD/day). The values referred to are confounder-adjusted. RESULTS: For anxiolytics and sedatives, there was a small increase in overall fracture risk (OR: around 1.1) even with limited doses (<0.1 DDD/day). No dose-response relationship was observed for anxiolytics and sedatives. For neuroleptics, a limited increase in overall fracture risk was observed (OR: around 1.2 from <0.05 DDD/day with no dose-response relationship). For antidepressants, a dose-response relationship was observed for fracture risk (OR: increasing from 1.15, 95% CI: 1.11-1.19 at <0.15 DDD/day to 1.40, 95% CI: 1.35-1.46 for >or=0.75 DDD/day). The risk of fracture was higher with selective serotonin re-uptake inhibitors than with tricyclic antidepressants. CONCLUSIONS: Small increases in fracture risk were seen with the use of anxiolytics and sedatives and neuroleptics without a dose-response relationship. The increase may be linked to an increased risk of falls. For antidepressants, a dose-response relationship was found, with a higher fracture risk for selective serotonin re-uptake inhibitors.

Adolescent↗

Vitamin D and its binding protein Gc: long-term variability in peri- and postmenopausal women with and without hormone replacement therapy.

OBJECTIVE: Measurement of plasma 25-hydroxyvitamin D (25OHD) level is often used to evaluate a patient's vitamin D status. The purpose of this study was to investigate the variability in individual plasma 25OHD- and vitamin D-binding protein- (Gc) levels over a 5-year period in postmenopausal women with and without hormone replacement therapy (HRT). MATERIAL AND METHODS: A total of 187 women were followed-up for 5 years. At baseline, 89 women were allocated to treatment with HRT, given orally. Measurements were performed at baseline and after 1, 2 and 5 years of follow-up. RESULTS: At baseline, 25OHD levels were positively associated with sunbathing and use of vitamin D supplements, and inversely associated with smoking. HRT therapy increased plasma levels of Gc (+8 %) but did not affect 25OHD levels or the free 25OHD index (molar ratio of 25OHD- to Gc levels). Among those classified in the lowest 25OHD tertile at baseline, 40 % remained in the lowest tertile during all subsequent measurement time-points. Similarly, 32 % of those classified in the highest baseline tertile remained in the highest tertile during all subsequent measurements. Use of the free 25OHD index showed similar results. No independent predictors of changes in vitamin D tertiles during follow-up were identified, which suggests that the observed variation was caused by the intra-individual variation in measured parameters. For all participants, the within-patient variability in 25OHD measurements was between 13 % and 19 %. CONCLUSIONS: In healthy postmenopausal women, HRT increases Gc levels. Owing to the high intra-individual variation in plasma 25OHD, it seems questionable to use a single estimate as a predictor of individual vitamin D status.

Analysis of Variance↗

Fracture risk in patients treated with loop diuretics.

BACKGROUND: Loop diuretics (LD) increase renal calcium excretion. Discrepant results on associations between LD and fracture risk have been reported. OBJECTIVE: To assess the fracture risk in users of LD. DESIGN AND SUBJECTS: A population-based pharmaco-epidemiological case-control design with fracture in year 2000 as outcome and use of LD during the previous 5 years as exposure variable. We used nationwide computerized registers to assess individual use of LD and related these data to individual fracture data and information on potential confounders. We compared 64,699 cases aged 40 years or more who sustained a fracture during year 2000 with 194,111 age- and gender-matched controls. RESULTS: A total of 44,001 subjects used LD. Ever use of LD was associated with a crude 51% (OR 1.51; 95% CI 1.48-1.55) increased risk of any fracture and a 72% (OR 1.72; 95% CI 1.64-1.81) increased risk of hip fracture. The risk estimates were reduced after confounder adjustment, i.e. adjusted risk of any fracture was increased by 4% (OR 1.04; 95% CI 1.01-1.07) and risk of hip fracture by 16% (OR 1.16; 95% CI 1.10-1.23). In current users, a tendency towards a decreased fracture risk with increased dose was observed, whereas in former users risk of fracture increased with increased dose. Use of furosemide was associated with higher risk estimates than use of bumetanide. CONCLUSION: Treatment with LD affects fracture risk. Special attention should be paid to patients in whom treatment with LD is initiated or stopped, as they may be at an increased risk of fracture.

Aged↗

Fracture risk associated with the use of morphine and opiates.

OBJECTIVES: To study the effect of morphine and opiates on fracture risk. DESIGN: Case-control study. SETTING: Nationwide register-based study. SUBJECTS: Cases were all subjects with any fracture sustained during the year 2000 (n = 124,655). For each case, three controls (n = 373,962) matched on age and gender were randomly drawn from the background population. The primary exposure variables were use of morphine and opiates. Morphine and other opiates had been used by 10 015 (8.0%) of the case subjects and 12 108 (3.2%) of the controls. Adjustments were made for several confounders including prior fracture, and use of weak analgesics [nonsteroidal anti-inflammatory drugs, acetylsalicylic acid (ASA) and acetaminophene]. The effect of dose was examined by stratifying for cumulated dose (defined daily dose). MAIN OUTCOME MEASURE: Fracture. RESULTS: Morphine (1.47, 95% CI 1.37-1.58), fentanyl (2.23, 95% CI 1.89-2.64), methadone (1.39, 95% CI 1.05-1.83), oxycodone (1.36, 95% CI 1.08-1.69), nicomorphine (1.57, 95% CI 1.38-1.78), ketobemidone (1.07, 95% CI 1.02-1.13), tramadol (1.54, 95% CI 1.49-1.58) and codeine (1.16, 95% CI 1.12-1.20) were all associated with an increase in overall fracture risk. No increase was present for buprenorphine (0.86, 95% CI 0.79-0.95), pethidine (0.98, 95% CI 0.89-1.08), dextropropoxiphene (1.02, 95% CI 0.90-1.16), and combinations of ASA and codeine (0.94, 95% CI 0.88-1.01). CONCLUSIONS: An increased fracture risk is seen in users of morphine and opiates. The reason for this may be related to the risk of falls due to central nervous system effects such as dizziness.

Accidental Falls↗

Influence of hyper- and hypothyroidism, and the effects of treatment with antithyroid drugs and levothyroxine on fracture risk.

The purpose of this study was to assess alterations in fracture risk in patients with hyper- and hypothyroidism, and the effects of antithyroid drugs and levothyroxine on fracture risk. The study was designed as a case-control study. All patients with a fracture (n = 124,655) in the year 2000 in Denmark served as cases. For each case, three age- and gender-matched controls were randomly drawn from the general population (n = 373,962). Exposure variables were a diagnosis of hyperthyroidism, hypothyroidism, ever use of antithyroid drugs, and ever use of levothyroxine. Adjustments were made for time since diagnosis, surgery for hyperthyroidism, thyroid cancer, prior fracture, alcoholism, and corticosteroid use. There was an increase in the risk of any fracture within the first 5 years after a diagnosis of hyperthyroidism, and the first 10 years after a diagnosis of hypothyroidism. Use of antithyroid drugs was associated with a significantly reduced fracture risk independently of the dose used (odds ratio [OR] 0.79-0.84, 2P < 0.05). No effect of levothyroxine on fracture risk was present. Thyroid surgery for hyperthyroidism and thyroid cancer were not associated with fracture risk. A prior fracture, alcoholism, and corticosteroid use were significant risk factors for fractures. Fracture risk is increased at the time of diagnosis of both hyper- and hypothyroidism, and this increase seems reversible. Low-dose levothyroxine was not associated with fracture risk. The effect of antithyroid drugs may be caused by the reduction in thyroid hormone levels.

Adult↗

Reduced relative risk of fractures among users of lithium.

Lithium has been shown to inhibit bone resorption and to interact with W nt signaling, potentially pointing to bone anabolic properties. We, therefore, studied the effects of lithium on fracture risk using a case-control study design. Cases were all subjects including children with any fracture sustained during the year 2000 (n=124,655). For each case, three controls (n=373,962) matched according to age and gender was randomly drawn from the background population. Adjustments were made for use of other psychotropic drugs (neuroleptics, antidepressants, and anxiolytics/sedatives), psychiatric disease (manic depressive states, schizophrenia, and other psychoses), and other confounders. The effect of dose was examined by stratifying for cumulated dose (DDD, defined daily dose). In the crude analysis, there was a decreasing relative risk of any fracture with increasing accumulated dose of lithium. After adjustment for psychotropic drug use, the risk of any fracture was decreased (odds ratio [OR] 0.74, 95% confidence interval [CI] 0.60--0.92 for 250--849 DDD, and OR 0.67, 95% CI 0.55--0.81 for >or= 850 DDD of lithium). For Colles' fractures and spine fractures, a significant decrease was seen with >or= 850 DDD (OR 0.57, 95% CI 0.35--0.94 for Colles' fracture and OR 0.32, 95% CI 0.11--0.95 for spine fractures). For hip fractures, a nonsignificant trend toward a decrease was seen; however, without a dose-response relationship. Adjustment for further confounders did not change the results. Lithium treatment was associated with a decreased risk of fractures potentially pointing at bone anabolic properties.

Adolescent↗

Relative fracture risk in patients with diabetes mellitus, and the impact of insulin and oral antidiabetic medication on relative fracture risk.

AIMS/HYPOTHESIS: We studied the association between fractures and type 1 and type 2 diabetes mellitus. METHODS: In this case-control study, all subjects diagnosed with a fracture (n=124,655) in Denmark served as cases, and for each case three control subjects (n=373,962) matched for sex and age were retrieved from the general population. RESULTS: Type 1 and type 2 diabetes were associated with an increased risk (1) of any fracture (odds ratio [OR]=1.3, 95% CI: 1.2-1.5 for type 1 diabetes and 1.2, 95% CI: 1.1-1.3 for type 2 diabetes after adjustment for confounders) and (2) of hip fractures (OR=1.7, 95% CI: 1.3-2.2 for type 1 diabetes, and 1.4, 95% CI: 1.2-1.6 for type 2 diabetes). Furthermore, type 2 diabetes was associated with a significant increase in forearm fractures (OR=1.2, 95% CI: 1.0-1.5), and type 1 diabetes was associated with an increased risk of spine fractures (OR=2.5, 95% CI: 1.3-4.6), whereas type 2 diabetes was not. Use of metformin and sulphonylureas was associated with a significantly decreased risk of any fracture, whereas a non-significant trend towards decreased risk of any fracture was associated with the use of insulin. Except for a decrease in hip fractures with use of sulphonylureas, no change in fracture risk in the hip, spine or forearm was associated with the use of insulin or oral antidiabetic drugs. CONCLUSIONS/INTERPRETATION: Type 1 and type 2 diabetes are associated with an increased risk of any fracture and hip fractures. The use of drugs to control diabetes may reduce the association between diabetes and fractures.

Administration, Oral↗

Reduced fracture risk in users of thiazide diuretics.

Thiazide diuretics (TD) reduce renal calcium excretion and may increase bone mineral density. A reduced fracture risk has been reported in some but not all studies. The aim of this study was to assess fracture risk in users of TD. The study design was nationwide population-based pharmacoepidemiological case-control study with fracture in year 2000 as outcome and use of TD during the previous 5 years as the exposure variable. Individual use of TD was derived from the Danish National Pharmacological Database and related to fracture data from the National Hospital Discharge Register. These data were combined with information on use of other drugs, social status, working status, income, educational status, contacts with general practitioners and practicing specialists, and comorbidity. A total of 64,699 patients (age = 40 years) who sustained a fracture during the year 2000 were compared to 194,111 age- and gender-matched controls. After adjustment for potential confounders, current use of TD was associated with a 10% (95% confidence interval [CI], 7% to 12%) reduced risk of any fracture and a 17% (95% CI 11% to 23%) reduced risk of forearm fractures. In former TD users, the risk reduction was slightly less pronounced. Similar results were found in men and women, and in subjects younger or > or = 65 years of age. Dose-effect analysis revealed a decreased risk of any fracture and fractures at the forearm and hip with an increased number of redeemed defined daily dosages (DDDs) of TD. Therefore, use of more than 2000 DDD was associated with a 19% (95% CI 10% to 27%) decreased hip fracture risk. We conclude that use of TD is associated with a significantly reduced fracture risk.

Aged↗

Effects of long-term treatment with loop diuretics on bone mineral density, calcitropic hormones and bone turnover.

BACKGROUND: Loop diuretics (LD) are widely used in the treatment of cardiovascular diseases and disorders with fluid accumulation. LD are known to increase renal calcium losses and may thereby affect calcium homeostasis and bone metabolism. OBJECTIVE: We studied to what extent long-term treatment with LD affects calcium homeostasis and bone metabolism. DESIGN AND SUBJECTS: In a cross-sectional design we compared 140 postmenopausal women treated with a LD for more than 2 years with 140 age-matched women not in diuretic therapy. RESULTS: Treatment with LD was associated with significantly increased urinary calcium, plasma parathyroid hormone (PTH) and 1,25-dihydroxyvitamin D levels. Per 40 mg day(-1) of furosemide, urinary calcium was increased by 17% (P < 0.05) and plasma PTH levels were increased by 28% (P = 0.04). Users of LD had a 17% higher body weight (P < 0.001) compared with nonusers. This was due to a 32% higher fat mass (P < 0.001) and a 6% higher lean tissue mass (P < 0.001). Moreover, users of LD had a higher bone mineral density (BMD) at the spine (+7.5%, P < 0.001), hip (+4.8%, P = 0.004), forearm (+3.7%, P = 0.01) and whole body (+2.5%, P = 0.06). However, after adjustment for body weight differences, BMD did not differ between groups. Nevertheless, duration of LD treatment was positively associated with BMD at the spine (P = 0.03) and whole body (P < 0.05). BMD at the spine increases by 0.3% per 1 year of treatment. CONCLUSIONS: The increased renal calcium losses in users of LD are compensated for by a PTH-dependent increase in 1,25(OH)(2)D levels. Thereby calcium balance remains neutral without major effects on bone metabolism.

Aged↗

Fracture risk associated with systemic and topical corticosteroids.

OBJECTIVES: To study the fracture risk associated with the use of corticosteroids in any formulation and administration. DESIGN: Case-control study. SETTING: Community-based study in Denmark. Subjects. Cases were all subjects with any fracture sustained during the year 2000 (n = 124,655). For each case, three controls (n = 373,962) matched on age and gender were randomly drawn from the background population. Adjustments were made for concurrent diseases (lung diseases, rheumatic disorders), use of other drugs (inhaled bronchodilators), contacts to hospitals and general practitioners, and social variables. RESULTS: An increased risk of any fracture, hip, spine, and forearm fractures was present with use of more than 2.5 mg of prednisolone or equivalent orally per day. For inhaled corticosteroids a limited increase in the risk of any fracture was present in users of more than 7.5 mg prednisolone equivalents per day (equivalent to 1875 mug of budesonide per day). However, no increase in the risk of hip, spine or forearm fractures was present in users of inhaled corticosteroids. For other topical corticosteroids (dermal, rectal, nasal, local application in the mouth, the eyes or the ears) no increase in fracture risk could be demonstrated even at high doses after adjustment for confounders. CONCLUSIONS: Ingestion of more than 2.5 mg of oral prednisolone equivalents per day is associated with an increase in fracture risk. No increase is associated with inhaled corticosteroids except at daily dosages above 7.5 mg of prednisolone equivalents. No increase in fracture risk is associated with other forms of topical corticosteroids.

Administration, Inhalation↗

Response rates to oestrogen treatment in perimenopausal women: 5-year data from the Danish Osteoporosis Prevention Study (DOPS).

OBJECTIVE: To characterise women with no response or with a good response to hormone replacement therapy (HRT), evaluated by change in bone mineral density (BMD). DESIGN: Nested case-control study within a comprehensive cohort study. SUBJECTS AND METHODS: In the Danish Osteoporosis Prevention Study (DOPS), perimenopausal women were allocated to either HRT or no HRT. In the present study, we included 466 women who had been treated with HRT for 5 years and 466 untreated women from the same cohort. Non-responders were women in the treatment group, who decreased in BMD more than the mean decrease observed in the untreated group. Good responders were women with a larger increase in BMD than the upper 95% percentile of untreated women. Baseline characteristics were evaluated as predictors of response to HRT. RESULTS: 8.4 and 5.6% were classified as non-responders, whereas 25 and 57% were good responders according to changes in BMD of the femoral neck and lumbar spine, respectively. Combining measuring sites, 2.6% were non-responders and 20% were good responders. Non-responders at the femoral neck were more often smokers and had a lower spine BMD. Good responders were older, had a higher body weight, and higher alcohol consumption. In addition, good responders at both measurements sites had a lower BMD at the total hip. CONCLUSION: A favourable BMD response to HRT can be expected in most post-menopausal women especially if they are non-smokers with a moderate--as opposed to low--alcohol intake, a high body mass and a low initial hip BMD.

Absorptiometry, Photon↗