Biomedical subjects

L Mosekilde

Publications and source records attributed to L Mosekilde.

At least 37 records · Page 2Linked to original sources

PubMed2005

Plasma concentrations of 25-hydroxy-vitamin D and 1,25-dihydroxy-vitamin D are related to the phenotype of Gc (vitamin D-binding protein): a cross-sectional study on 595 early postmenopausal women.

The major transporter of vitamin D metabolites in the circulation is the multifunctional plasma protein Gc, also known as group-specific component, Gc globulin, vitamin D-binding protein, or DBP. There are several phenotypes of Gc, and we examined the influence of Gc phenotype and Gc concentration on vitamin D status. By using isoelectric focusing we identified the Gc phenotype of 595 caucasian recent postmenopausal women enrolled into the Danish Osteoporosis Prevention Study (DOPS). We measured plasma concentration of Gc by immunonephelometry (coefficient of variation [CV] < 5%), 25-hydroxy vitamin D (25OHD) by a competitive protein-binding assay (CV 10%), and 1,25-dihydroxy-vitamin D (1,25(OH)(2)D) by a radioimmunoassay (CV 6--14%), and calculated index as the molar ratio of vitamin concentration divided by Gc concentration. Plasma levels of Gc, 25OHD, 25OHD index, and 1,25(OH)(2)D, but not 1,25(OH)(2)D index, differed significantly between women with different Gc phenotype, being highest in Gc1-1, intermediate in Gc1-2, and lowest in Gc2-2. In multiple regression analysis, Gc concentration was an independent predictor of 1,25(OH)(2)D, whereas Gc phenotype was a significant predictor of 25OHD concentration, even after adjustment for the effects of season, sunbathing habits, skin thickness, use of vitamin supplements, smoking, and body mass index (BMI). Plasma parathyroid hormone (PTH) level did not differ between Gc phenotypes. Despite the fact that more than 60% of the women with Gc phenotype Gc2-2 had plasma 25OHD levels of less than 50 nmol/L none of them had plasma PTH higher than reference limits. Bone mineral content (BMC), Bone mineral density (BMD), and bone markers did not differ between Gc phenotypes. In conclusion, plasma 1,25(OH)(2)D, 25OHD, and 25OHD index are related to Gc phenotype, and we speculate that the thresholds for vitamin D sufficiency differ between Gc phenotypes.

Cross-Sectional Studies↗

PubMed2005

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↗

PubMed2005

Geometry of the proximal femur in relation to age and sex: a cross-sectional study in healthy adult Danes.

PURPOSE: To describe the natural variation in hip geometry in relation to Danish population characteristics, and to establish normal reference values. MATERIAL AND METHODS: We included 249 healthy individuals (94 M and 155 F, aged 19-79 years) and measured hip-axis-length (HAL), neck-width (NW), neck-shaft-angle (NSA), and femoral head-radius (HR) on dual-energy X-ray absorptiometry (DXA) screen images. RESULTS: HAL, NW, HR, and NSA were higher in men than in women (10.9 +/- 0.7 vs. 9.5 +/- 0.6 cm (P<0.001), 3.8 +/- 0.3 vs. 3.3 +/- 0.3 cm (P<0.01), 2.5 +/- 0.3 vs. 2.3 +/- 0.2 cm (P< 0.001), and 131 +/- 5 vs. 129 +/- 5 degrees (P< 0.01). NSA was higher in post-menopausal than in pre-menopausal women (130 +/- 4 vs. 128 +/- 5 degrees (P<0.001)). In multiple regression analysis, HAL, NW, and HR were positively related to body height in both sexes (R = 0.20 to 0.63, P<0.05 to P<0.001). In females, NSA was positively related to body height (R = 0.20, P<0.05) and negatively to body weight (R = -0.30, P<0.01). NW increased with age in men (R = 0.34, P<0.01) but not in women. CONCLUSION: Hip dimensions differ between genders in the Danish population. HAL, NW, and HR depend on body height. Finally, NW increases with age in men but not in women.

Absorptiometry, Photon↗

PubMed2005

Vitamin D status, seasonal variations, parathyroid adenoma weight and bone mineral density in primary hyperparathyroidism.

BACKGROUND: Primary hyperparathyroidism (PHPT) and vitamin D insufficiency are common conditions that can occur in combination. However, low plasma 25-hydroxyvitamin D (25OHD) may also enhance the risk of PHPT or modify disease severity. AIM: To compare the risk of vitamin D insufficiency and deficiency stratified by age, sex and season between PHPT patients and controls and to assess associations between plasma 25OHD and adenoma weight, biochemical variables, bone mineral density (BMD) and clinical complications. DESIGN: Cross-sectional study. MATERIAL: A total of 289 consecutive Caucasian patients with PHPT aged 65.9 (24-92) years, 289 sex-, age- and season-matched normocalcaemic controls and 187 healthy adult blood donors. PHPT diagnosis was confirmed in 214 by neck exploration. RESULTS: Vitamin D insufficiency (plasma 25OHD < 50 nmol/l) was observed in 81% of PHPT patients compared with 60% of sex- and age-matched controls (P < 0.001) and 35% of blood donors (P < 0.001). During summer, 77%vs. 53% (P < 0.001) and 4% (P < 0.001), respectively, had vitamin D insufficiency. Average plasma 25OHD was 41 (range 9-87) nmol/l among 27 PHPT patients compared with 87 (21-173) nmol/l (P < 0.001) among aged-matched blood donors. During winter, 86%vs. 66% (P < 0.001) and 71% (P < 0.05), respectively, had vitamin D insufficiency. Vitamin D deficiency (plasma 25OHD < 25 nmol/l) was observed in 33% of PHPT patients compared with 20% of age- and sex-matched controls (P < 0.001) and 13% of blood donors (P < 0.001). Both PHPT patients and controls showed seasonal variations in 25OHD related to the average number of sun hours, but values were lower in PHPT patients at all calendar months. In PHPT patients low plasma 25OHD was associated with higher plasma levels of calcium, PTH and alkaline phosphatase and with lower renal calcium excretion, femoral neck and forearm BMD. No association was found between plasma 25OHD and adenoma weight (total or divided into tertiles). There was a trend towards increased risk of osteoporotic fractures (P < 0.08) with low plasma 25OHD. CONCLUSION: Vitamin D insufficiency and deficiency are common findings in PHPT and occur more often than in a sex- and age-matched control group referred from general practice and in normal blood donors irrespective of season. Low plasma 25OHD levels are associated with an aggravated clinical presentation of PHPT but do not affect adenoma size.

Adenoma↗

PubMed2005

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↗

PubMed2005

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↗

PubMed2004

Performance of four clinical screening tools to select peri- and early postmenopausal women for dual X-ray absorptiometry.

Several methods to select postmenopausal women for dual X-ray absorptiometry (DXA) have been proposed. We decided to compare the performance of three clinical decision rules (SCORE, ORAI, OST) with the usual case-finding strategy based on the presence of a major risk factor for future fracture (CFMRF). The study subjects were 2009 healthy, white, peri- or early postmenopausal women participating in the Danish Osteoporosis Prevention Study (DOPS). DXA results expressed as T-scores and scores on SCORE, ORAI, OST and CFMRF were extracted from the DOPS database. First, we evaluated the screening tools as originally described by the developers. The resulting sensitivities and specificities ranged from 18% to 92% and from 66% to 85%, respectively. Only OST achieved a high sensitivity (92%) with respect to femoral neck T-score < or = -2.5; however, the sensitivity with respect to lumbar spine T-score < or = -2.5 was only 51%. Next, the performance of the screening tools was evaluated against T-score < or = -2.0 (and T-score < or = -2.5) in at least one of the regions: femoral neck, total hip or lumbar spine. Using ROC curve analysis, we determined cut-offs yielding sensitivities as close as possible to 90%. The CFMRF and the ORAI tool were too coarse to yield 90% sensitivity. The performances of OST and SCORE were equal from a clinical perspective in that the sensitivities and the specificities varied from 89% to 94% and from 23% to 28%, respectively. The performance of CFMRF was no better than could be expected by chance, yielding a sensitivity of 19% and a specificity of 85%. Applying SCORE or OST 75% of the women would have to be referred for densitometry to identify 90% of the women with T-score < or = -2.0 (or T-score < or = -2.5) in at least one region. In conclusion, our results question the utility of all the evaluated tools for screening peri- and early postmenopausal women for low BMD. However, if a decision on referral has to be made, it may be based on the simple OST rule, which performed as well as or better than any of the other tools.

Absorptiometry, Photon↗

PubMed2004

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↗

PubMed2004

Two single nucleotide polymorphisms in the CYP17 and COMT Genes--relation to bone mass and longitudinal bone changes in postmenopausal women with or without hormone replacement therapy. The Danish Osteoporosis Prevention Study.

Sex steroids are important physiologic regulators of bone mass, and genes regulating sex steroid production and metabolism are obvious as candidate genes for osteoporosis susceptibility. We present data from a study of 1795 recent postmenopausal women, assigned to either hormone replacement therapy (HRT) or no treatment and followed for 5 years. The association between bone mass measurements and two single nucleotide polymorphisms, a T (A1) to C (A2) transition in the 5'-UTR of the cytochrome P450c17alpha (CYP17) gene and a G (Val) to A (Met) transition in exon 4 of the catechol- O-methyltransferase (COMT) gene, was evaluated. Association with CYP17 genotype was modified by body mass index (BMI). In lean women, individuals homozygous for the CYP17 A2 allele were 1 cm shorter and had lower baseline BMD (bone mineral density), BMC, and CSA (cross sectional area) in the spine and femoral neck than did other women (BMD spine A2A2: 0.975 g/cm2 versus 1.011 g/cm2 in A1A1 + A1A2, P = 0.002). Conversely, an adverse association with A2A2 and bone loss over 5 years seemed present only in overweight women, but differences were small. Response to HRT was not dependent on CYP17 genotype. COMT genotype was not associated with bone mass at baseline, bone loss in untreated women, or response to HRT. In conclusion, the A2 allele of the CYP17 T(27)-C polymorphism is associated with reduced bone mass and bone size in lean perimenopausal women, whereas high BMI protects against this negative association. The COMT G(1947)-A polymorphism is not associated with bone parameters in this study.

5' Untranslated Regions↗

PubMed2004

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

In recent studies from Sweden and the United States, a high vitamin A intake has been associated with low bone mineral density (BMD) and increased fracture risk. In Sweden and the United States, food items such as milk and breakfast cereals are fortified with vitamin A, whereas in Denmark there is no mandatory fortification with vitamin A. In the present study, we investigated relations between vitamin A intake and BMD and fracture risk in a Danish population consuming mostly unfortified food items. Within a population-based cohort study in 2,016 perimenopausal women, associations between BMD and vitamin A intake were assessed at baseline and after 5-year follow-up. Moreover, associations between baseline vitamin A intake and 5-year changes in BMD were studied. Finally, fracture risk was assessed in relation to vitamin A intake. In our cohort, dietary retinol intake (0.53 mg/day) was lower than the intake reported in recent studies form Sweden (0.78 mg/day) and the United States (1.66 mg/day). Cross-sectional and longitudinal analyses showed no associations between intake of vitamin A and BMD of the femoral neck or lumbar spine. Neither did BMD differ between those 5% who had the highest, and those 5% who had the lowest, vitamin A intake. During the 5-year study period, 163 subjects sustained a fracture (cases). Compared to 978 controls, logistic regression analyses revealed no difference in vitamin A intake. Thus, in a Danish population, average vitamin A intake is lower than in Sweden and the United States and not associated with detrimental effects on bone.

Bone Density↗

PubMed2004

Parathyroid surgery is associated with a decreased risk of hip and upper arm fractures in primary hyperparathyroidism: a controlled cohort study.

OBJECTIVES: To study if parathyroid surgery reduced fracture risk in patients with primary hyperparathyroidism. DESIGN: Controlled cohort study. SETTING: All subjects diagnosed with primary hyperparathyroidism (ICD8 codes: 252.00, 252.01, 252.03, 252.04, 252.05, 252.08, 252.09, and ICD10 codes: E21.0, E21.2, E21.3) between 1980 and 1999 in Denmark were retrieved from the National Hospital Discharge System. SUBJECTS: A total of 3213 subjects (mean age at diagnosis 60.9 +/- 16.3 years) were identified of whom 1934 (60%) had parathyroid surgery whilst 1279 (40%) did not. Total follow-up time after diagnosis was 19.565 (median 6.1) years. MAIN OUTCOME MEASURE: Fracture occurrence after diagnosis was identified from the National Hospital Discharge System. RESULTS: Conservatively treated patients were older than surgically treated at diagnosis (64.2 +/- 17.4 years vs. 58.3 +/- 15.2 years, P < 0.01). The mean serum calcium was 2.95 mmol L-1 in surgically treated and 2.74 in conservatively treated in a subgroup from one centre, n = 687). At the time of diagnosis, 172 (9%) of the subsequently surgically treated had had any fracture whilst the same was the case for 176 (14%) of the conservatively treated (P < 0.05). Parathyroid surgery reduced the risk of hip (HR = 0.44, 95% CI: 0.32-0.62) and upper arm (HR = 0.44, 95% CI: 0.27-0.72) fractures after diagnosis whilst the occurrence of other fracture types remained unchanged. CONCLUSIONS: Parathyroid surgery reduces the occurrence of hip and upper arm fractures with approximately 50% in patients with primary hyperparathyroidism. This may advocate surgery in patients with primary hyperparathyroidism with serum calcium levels in the range presented here. Further studies in patients with mild disease are warranted.

Aged↗

PubMed2003

Vitamin D insufficiency in Greenlanders on a westernized fare: ethnic differences in calcitropic hormones between Greenlanders and Danes.

We studied the influence of age, gender, latitude, season, diet and ethnicity on plasma 25-hydroxyvitamin D 25 OHD, PTH, 1,25-dihydroxyvitamin D, vitamin D-binding protein, bone-specific alkaline phosphatase, and osteocalcin levels in 46 Greenlanders living in Nuuk (64 degrees N) on a traditional fare (group A), 45 Greenlanders living in Nuuk on a westernized fare (group B), 54 Greenlanders (group C), and 43 Danes (Group D) living in Denmark (55 degrees N) on a westernized fare. Blood specimens were drawn both summer and winter. Vitamin D insufficiency (plasma 25 OHD <40 nmol/l) was common in all four study groups during summer (23-74%) and winter (42-81%). Compared to groups A and D, vitamin D insufficiency was significantly more frequent in groups B and C. In all groups, summer levels of 25 OHD were above winter levels. Multiple regression analysis revealed a significant effect of ethnicity. Compared to Danes, Greenlanders had higher 1,25-dihydroxyvitamin D levels, but lower 25 OHD and PTH levels despite relatively low plasma calcium concentrations. In addition to ethnicity, 25(OH)D levels were influenced by age, season (summer > winter), and diet (a traditional Inuit diet>westernized diet). Ethnic differences exist between Greenlanders and Danes. Our results suggest that Greenlanders may have an inherent lower "set-point" for calcium-regulated PTH release or an enhanced renal 1,25(OH)(2)D production. In addition to ethnicity, age, season, and diet were important determinants of vitamin D status. Changes from a traditional to a westernized fare are associated with a reduced vitamin D status in Greenlanders. Vitamin D supplementation should be considered.

Adult↗

PubMed2003

Polymorphisms in the CYP19 and AR genes--relation to bone mass and longitudinal bone changes in postmenopausal women with or without hormone replacement therapy: The Danish Osteoporosis Prevention Study.

Polymorphisms in the androgen receptor ( AR) gene and genes encoding enzymes involved in synthesis of sex steroids (e.g., the CYP19 gene encoding aromatase) have recently received attention in osteoporosis research. In the Danish Osteoporosis Prevention Study, recent postmenopausal women were allocated to either hormone replacement therapy (HRT) or no treatment. We genotyped 1792 women for the CYP19 (TTTA)(n) repeat [short (TTTA)(n 7)] the CYP19 C(1558)-T, and the AR (CAG)(n) repeat polymorphism [short (CAG)(n < 22), long (CAG)(n >or= 22)], and investigated associations with bone mineral density (BMD) and 5-year change in BMD. The CYP19 polymorphisms were in strong linkage disequilibrium. Perimenopausal bone mass or bone loss in untreated women was not associated with the CYP19 polymorphisms. In hormone-treated women, BMD increase in the femoral neck was highest (+0.3%/year) for long CYP19 alleles, lowest (-0.09%/year) for short alleles, and intermediate (-0.002%/year) in heterozygous women, P = 0.015. Differences were also significant in the lumbar spine, total hip, and ultradistal forearm. The C(1558)-T T-allele was associated with a more pronounced response to HRT ( P = 0.04, total hip). AR genotype was not related to BMD, but a modifying effect of sex hormone-binding globulin (SHBG) was present. In the highest SHBG quartile (SHBG > 95 nmol/1, n = 222), AR genotype was associated with baseline BMD (femoral neck: P < 0.001, total hip: P = 0.008), but without a clear gene dosage effect. We have demonstrated that polymorphisms in the CYP19 gene are associated with the magnitude of bone gain in response to HRT and that the (CAG)(n) repeat polymorphism in the AR gene is associated with bone mass in women with high levels of SHBG. These findings emphasize the complexity of the genetics of bone mass and bone loss.

Alleles↗

PubMed2003

Dose-effect relations of loop- and thiazide-diuretics on calcium homeostasis: a randomized, double-blinded Latin-square multiple cross-over study in postmenopausal osteopenic women.

BACKGROUND: Thiazide diuretics (TDs) reduce whereas loop diuretics (LDs) increase urinary calcium. We studied the effects of different doses of a TD and LD on electrolytes, calcitropic hormones and biochemical bone markers. SUBJECTS AND METHODS: In a five-period crossover study, comparing four active doses with placebo, 40 postmenopausal women with osteopenia were treated with different doses of LD bumetanide (n = 20, 0.5-2.0 mg per day) or TD bendroflumethiazide (n = 20, 2.5-10 mg per day). Each treatment period lasted 1 week. RESULTS: Urinary calcium decreased dose-dependently in response to the bendroflumethiazide. The best hypocalciuric effect was achieved by 5 mg day-1 of bendroflumethiazide. Total plasma calcium levels increased, whereas ionised calcium at ambient pH-values decreased because of increased pH-values in response to the bendroflumethiazide. Plasma PTH levels did not change, whereas a slight dose-dependent increase occurred in plasma 1,25(OH)2D levels. As a marker of bone formation, plasma osteocalcin levels increased. Conversely, bumetanide dose-dependently increased renal calcium losses with a concomitant increase in plasma PTH and 1,25(OH)2D levels. Plasma osteocalcin levels increased and bone-specific alkaline phosphatase levels decreased dose-dependently. CONCLUSION: Whether a LD or TD is chosen as diuretic therapy affects calcium homeostasis. The effects of LDs are potentially harmful to bone. Further studies are needed to evaluate whether long-term treatment with LDs causes osteoporosis. Until then, we suggest using, if possible, a TD rather than a LD as diuretic therapy in order not to risk deleterious effects on bone metabolism.

Alkaline Phosphatase↗

PubMed2003

Corticosteroid use and risk of hip fracture: a population-based case-control study in Denmark.

OBJECTIVE: To examine the association between cumulative CS dose and risk of hip fracture. DESIGN: Population-based case-control design. SUBJECTS AND METHODS: A total of 6660 subjects with hip fracture and 33,272 age-matched population controls were identified using the County Hospital Discharge Registry in North Jutland County, Denmark and the Danish Central Personal Registry, respectively. Data on redeemed prescriptions for CS within the last 5 years before the index date were retrieved from a population-based prescription database, and recalculated to prednisolone equivalents. Cases and controls were categorized according to cumulative CS dose: (i) no use; (ii) <130 mg (e.g. equivalent to 30 mg of prednisolone for 4 days given for an acute exacerbation of asthma); (iii) 130-499 mg (e.g. equivalent to a short course of prednisolone of 450 mg for acute asthma); (iv) 500-1499 mg (e.g. equivalent to 7.5 mg prednisolone daily for 6 months or 800 microg day(-1) of inhaled budesonide for 1 year); and (v) > or =1500 mg (e.g. equivalent to >4.1 mg day(-1) for 1 year, a long-term high dose). Data were analysed using conditional logistic regression adjusted for potential confounders including gender, redeemed prescriptions for hormone replacement therapy, antiosteoporotic, anxiolytic, antipsychotic and antidepressant drugs. RESULTS: Compared with never users, an increased risk of hip fracture was found for CS users, with increasing cumulative doses of any type of CS use during the preceding 5 years [adjusted odds ratio (OR)=0.96, 95% confidence interval (CI)=0.89-1.04] for <130 mg prednisolone; OR=1.17 (CI=1.01-1.35) for 130-499 mg; OR=1.36 (CI=1.19-1.56) for 500-1499 mg; and OR=1.65 (CI=1.43-1.92) for > or =1500 mg. An increased risk was also found when the study population was stratified according to gender, age and type of CS (systemic or topical). CONCLUSIONS: Even a limited daily dose of CS (more than an average dose of approximately 71 microg prednisolone per day) was associated with an increased risk of hip fracture.

Adolescent↗

PubMed2003

Skeletal growth and long-term bone turnover after enterocystoplasty in a chronic rat model.

OBJECTIVE: To investigate skeletal growth and bone metabolism in a chronic animal model of urinary diversion. MATERIALS AND METHODS: Young male Wistar rats (120) were allocated randomly to four groups undergoing: ileocystoplasty, ileocystoplasty and resection of the ileocaecal segment, colocystoplasty, and controls. All animals received antibiotics for 1 week after surgery; half of each group remained on oral antibiotics. Bone-related biochemistry was measured in serum and urine. Dual-energy X-ray absorptiometry and peripheral quantitative computed tomography (pQCT) were used to determine bone mass ex vivo. RESULTS: Most (90%) of the rats survived the study period (8 months); six rats died from bowel obstruction at the level of the entero-anastomosis and four had to be killed because of persistent severe diarrhoea. Vital intestinal mucosa was found in all augmented bladders. There were no differences in bone length and volume. Loss of bone mass was almost exclusively in rats with ileocystoplasty and resection of the ileocaecal segment (-37.5%, pQCT, P < 0.01). There was no hyperchloraemic metabolic acidosis or gross impairment of renal function. Hypomagnesaemia, hypocalcaemia and decreased insulin-like growth factor-binding protein 3 were the only significant findings on blood analysis. Deoxypyridinoline crosslinks in urine were higher in rats with an enterocystoplasty than in controls. CONCLUSIONS: Enterocystoplasty in rats neither impairs skeletal growth nor bone quantity, but leads to significant loss of bone mass when combined with resection of the ileocaecal segment. Rarefaction of the trabecular network is confined to the metabolically highly active cancellous compartment, most likely as a consequence of intestinal malabsorption.

Absorptiometry, Photon↗

PubMed2003

Effect of long-term hormone replacement therapy on tissue factor pathway inhibitor and thrombin activatable fibrinolysis inhibitor in healthy postmenopausal women: a randomized controlled study.

It was recently reported from the Women's Health Initiative that healthy women using combined hormone replacement therapy (HRT) for 5 years have an increased cardiovascular risk. We hypothesize that the increased risk is confined to subgroups of atherosclerotic women. Such women may have higher arterial tissue factor expression and higher thrombin formation, and changes in tissue factor pathway coagulation inhibitor (TFPI) and thrombin activatable fibrinolysis inhibitor (TAFI) may be deleterious. Healthy postmenopausal women (n = 719) were randomized to hormone therapy [n = 357; opposed (n = 290) and unopposed (n = 67)] or no treatment (n = 362). Plasma TFPI and TAFI and the TFPI -287T/C and TAFI -438G/A polymorphisms were measured 5-6 years after randomization. Concentrations of TFPI were significantly lower in the hormone group than in the control group (P < 0.001) and in all genotypes of the TFPI polymorphism. Overall, concentrations of TAFI did not differ between the two groups but were reduced by hormone therapy in homozygotes for the rare TAFI -438 A allele (P < 0.05). The hormone effects on TFPI and TAFI were similar in smokers and non-smokers and in women using unopposed and opposed therapy. The observed decrease in TFPI may contribute to the increased cardiovascular risk associated with HRT.

Arteriosclerosis↗

PubMed2003

Fracture risk associated with smoking: a meta-analysis.

OBJECTIVES: To assess fracture risk associated with smoking. DESIGN: Systematic review. DATA SOURCES: Cohort, case-control, and cross-sectional studies identified by searching PubMed and EMBASE, and by recursive screening of reference lists. SUBJECTS: Fifty studies including 512 399 subjects were included. MAIN OUTCOME MEASURE: Fracture occurrence in current, previous, and never smokers. RESULTS: Fracture risk was significantly increased in current smokers for all fracture types combined (pooled relative risk 1.26, 95% CI 1.12-1.42) and for hip (1.39, 95% CI 1.23-1.58) and spine fractures (1.76, 95% CI 1.10-2.82), but not for wrist fractures (0.86, 95% CI 0.46-1.60). In previous smokers the estimate was significantly lower for as well all types of fractures (1.02, 95% CI 0.85-1.22, P = 0.03 compared with current smokers), as for hip fractures (1.19, 95% CI 1.06-1.34, P = 0.04). There was a trend towards higher risk estimates in previous smokers for hip fractures in case-control studies than in cohort studies. A similar difference between case-control and cohort studies was not present for current smokers. There was a geographical heterogeneity: the risk of hip fractures associated with current smoking increased with latitude, i.e. the risk was higher in Northern Europe and the USA than in Southern Europe and countries close to the equator. CONCLUSIONS: Smoking is associated with an increased overall fracture risk, an increased risk of hip and spine but not wrist fractures. Cessation of smoking seems associated with a decrease in fracture risk. The impact of smoking varied geographically with an increase with latitude.

Adult↗