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We leverage two unique natural experiments to show that, in public drug insurance for the low-income elderly in the U.S., defaults have large and persistent effects on plan enrollment and beneficiary drug utilization. We estimate that when a beneficiary’s default is exogenously changed from one year to the next, over 90% of beneficiaries follow that default. We then develop a general framework for choice under costly cognition that allows for the possibility that either paternalistic defaults that steer consumers to plans that suit them (Thaler and Sunstein 2008) or ‘shocking’ defaults that trigger consumers to make active choices (Carroll et al. 2009) could be optimal. We show that optimal default design depends on a previously-overlooked parameter: The elasticity of active choice propensity with respect to the value of the default. Leveraging variation in the match value of randomly-assigned default plans, we estimate an elasticity close to zero: There is little difference in the probability of active choice between beneficiaries assigned a well-matched default versus beneficiaries assigned a poorly-matched default. We also show that this passivity has real consequences, with beneficiaries assigned poorly-matched defaults experiencing large declines in drug consumption relative to those assigned well-matched defaults. This suggests that any potential welfare gains from an active choice response induced by a poorly-matched default are likely to be small and outweighed by the welfare losses due to reductions in drug consumption among beneficiaries who follow the poorly-matched default. Using a third natural experiment and a structural model of attention, we find that the little active choice that is present in this market appears to be largely random, with two-thirds of the variation in active choice coming from within-beneficiary transitory shocks to attention. Our results show that default rules are an integral part of insurance market design and that beneficiaries are likely to benefit from paternalistic defaults rather than be hurt by them.

Measuring consumer responsiveness to medical care prices is a central issue in health economics and a key ingredient in the optimal design and regulation of health insurance markets. We study consumer responsiveness to medical care prices, leveraging a natural experiment that occurred at a large self-insured firm which required all of its employees to switch from an insurance plan that provided free health care to a non-linear, high deductible plan. The switch caused a spending reduction between 11.79%-13.80% of total firm-wide health spending. We decompose this spending reduction into the components of (i) consumer price shopping (ii) quantity reductions and (iii) quantity substitutions, finding that spending reductions are entirely due to outright reductions in quantity. We find no evidence of consumers learning to price shop after two years in high-deductible coverage. Consumers reduce quantities across the spectrum of health care services, including potentially valuable care (e.g. preventive services) and potentially wasteful care (e.g. imaging services). We then leverage the unique data environment to study how consumers respond to the complex structure of the high-deductible contract. We find that consumers respond heavily to spot prices at the time of care, and reduce their spending by 42% when under the deductible, conditional on their true expected end-of-year shadow price and their prior year end-of-year marginal price. In the first-year post plan change, 90% of all spending reductions occur in months that consumers began under the deductible, with 49% of all reductions coming for the ex ante sickest half of consumers under the deductible, despite the fact that these consumers have quite low shadow prices. There is no evidence of learning to respond to the true shadow price in the second year post-switch.

The aim of the present study was to describe vitamin D status and seasonal variation in the general Danish population. In this study, 3092 persons aged 2 to 69 years (2565 adults, 527 children) had blood drawn twice (spring and autumn) between 2012 and 2014. A sub-sample of participants had blood samples taken monthly over a year. Serum 25-hydroxyvitamin D (25(OH)D) concentrations were measured by liquid chromatography mass spectrometry, and information on supplement use was assessed from questionnaires. Seasonal variations in 25(OH)D concentrations were evaluated graphically and descriptively, and status according to age, sex, and supplement use was described. It was found that 86% of both adults and children were vitamin D-sufficient in either spring and or/autumn, however, many had a spring concentration below 50 nmol/L. A wide range of 25(OH)D concentrations were found in spring and autumn, with very low and very high values in both seasons. Among adults, women in general had higher median 25(OH)D concentrations than men. Furthermore, vitamin D supplement use was substantial and affected the median concentrations markedly, more so during spring than autumn. Seasonal variation was thus found to be substantial, and bi-seasonal measurements are vital in order to capture the sizable fluctuations in vitamin D status in this Nordic population.

Little is known on how vitamin D status is affected by adherence to UVB-limiting sun exposure guidelines. Our aim was to investigate the relationship between adherence to the Danish sun exposure guidelines and vitamin D status. In total, 3194 Danes (2625 adults, 569 children) were recruited among the general population, and more than 92% had blood samples taken both autumn and spring. Using linear regression, we associated serum vitamin D concentrations to questionnaire responses on: seeking shade, wearing a sunhat, wearing protective clothing or using sunscreen. The odds ratio (OR) of either low (

The importance of cigarette smoking in relation to bone mass remains uncertain, especially in younger women. In a recent meta-analysis including 10 studies in premenopausal women no effect was seen in this age group. We used baseline data from a large national cohort study (Danish Osteoporosis Prevention Study [DOPS]) to study the cumulated effect of pre- and perimenopausal smoking on bone mineral density (BMD) measured shortly after the cessation of cyclic bleedings. Baseline observations on 2015 recently menopausal women were available. Eight hundred thirty-two women were current smokers and 285 were exsmokers. Significant negative associations of cigarette smoking coded as current, ex-, or never smoking were seen on bone mass in the lumbar spine (P = 0.012), femoral neck (P < 0.001), and total body (P < 0.001). Quantitatively, the differences between current smokers and never smokers were limited to 1.6, 2.9, and 1.9%, respectively. A statistical interaction was found between smoking and fat mass, indicating that women in the highest tertile of fat mass were unaffected by cigarette smoking. Serum vitamin D levels and osteocalcin were inversely related to the number of cigarettes smoked per day (r = 0.11 and P < 0.001; r = 0.17 and P = 0.04), respectively. Bone alkaline phosphatase (BALP) and urinary hydroxyproline (U-OHP) were unaffected by current smoking. The average cumulated effect of premenopausal smoking on bone is small but biologically significant. Reduced body mass in smokers explains part of the negative effect on the skeleton and a complex interaction between smoking and fat mass on the skeleton is indicated. Serum levels of 25-hydroxyvitamin D (25-OHD) and osteocalcin are lower in smokers, which may effect rate of bone loss.

Potential long-term negative effects of increased vitamin D consumption are not thoroughly examined. The aim of this study was to investigate possible negative effects of vitamin D supplementation on serum lipids and lipoproteins. A 1-year long randomised double-blinded placebo-controlled intervention study with two doses of vitamin D3 (10 and 20 microg/day) was carried out among 89 women (18-53 years of age) and 84 men (18-64 years of age) of Pakistani origin living in Denmark with low vitamin D status. This study did not find changes in total cholesterol, LDL-cholesterol, HDL-cholesterol, LDL-cholesterol/HDL-cholesterol ratio, VLDL-cholesterol and triacylglycerol after daily supplementation with 10 or 20 microg vitamin D for 1 year. In conclusion, increasing the vitamin D intake by 10-20 microg per day for 1 year is safe for Pakistani immigrants with regards to serum lipids and lipoproteins.

Severe vitamin D deficiency is common among Muslim immigrants. The dose necessary to correct the deficiency and its consequence for bone health are not known for immigrants. The aim was to assess the effect of relatively low dosages of supplemental vitamin D on vitamin D and bone status in Pakistani immigrants. This 1-year-long randomised double-blinded placebo-controlled intervention with vitamin D3 (10 and 20mg/d) included girls (10·1 – 14·7 years), women (18·1 – 52·7 years) and men (17·9 – 63·5 years) of Pakistani origin living in Denmark. The main endpoints were serum 25-hydroxyvitamin D (S-25OHD), parathyroid hormone, bone turnover markers and bone mass. The study showed that supplementation with 10 and 20mg vitamin D3 per d increased S-25OHD concentrations similarly in vitamin D-deficient Pakistani women (4-fold), and that 10mg increased S-25OHD concentrations 2-fold and 20mg 3-fold in Pakistani men. S-25OHD concentrations increased at 6 months and were stable thereafter. Baseline S-25OHD concentrations tended to be lower in girls and women than in men; females achieved about 46 nmol/l and men 55 nmol/l after supplementation. Serum intact parathyroid hormone concentrations decreased at 6 months, but there was no significant effect of the intervention on bone turnover markers and dual-energy X-ray absorptiometry measurements of the whole body and lumbar spine. Randomised controlled trials: Vitamin D intervention: Pakistani immigrants: Bone turnover: Bone mass

Udgivelsesdato: 2008-Jul BACKGROUND: Vitamin D insufficiency is very common and is known to cause secondary hyperparathyroidism (SHPT). However, in some subjects the PTH response to low vitamin D levels is blunted, which has been termed functional hypoparathyroidism (FHPT). AIM: We compared indices of calcium homeostasis, bone metabolism and body composition in subjects with differential PTH responses to low vitamin D levels. DESIGN: Cross-sectional study. In 405 recent postmenopausal women with vitamin D insufficiency, we compared levels of bone turnover markers, bone mineral density (BMD), body composition, and body weight between subjects with SHPT and FHPT. RESULTS: Plasma 25-hydroxyvitamin D (P-25OHD) levels were slightly higher (P < 0.05) in SHPT compared with FHPT. SHPT was associated with higher levels of osteocalcin and bone-specific alkaline phosphatase, whereas whole body BMD and hip- and lumbar spine-BMD were significantly reduced. Subjects with SHPT had a 7% (P < 0.01) higher body weight and a 23% higher fat mass (P < 0.01) than subjects with FHPT, whereas lean tissue mass did not differ between groups. In SHPT, fat mass was increased by 14% (P < 0.001) at the upper and lower extremities and by 33% (P < 0.001) at the trunk. In a regression model, significant predictors of fat mass was P-PTH (r(p) = 0.248, P < 0.01) and P-osteocalcin (r(p) = -0.115, P = 0.02), with no effects of P-25OHD or P-creatinine levels. CONCLUSIONS: Effects of vitamin D insufficiency on bone is associated with the PTH responses. The increased body weight and fat mass in SHPT compared with FHPT may imply that PTH excess contributes to fat accumulation.

To determine vitamin D and bone status in adolescent girls, pre-menopausal women and men of Pakistani origin, to single out determinants of vitamin D status and to determine the association between vitamin D status, bone metabolism and bone status.Cross-sectional study, Copenhagen (55 degrees N), January-November. Serum 25-hydroxyvitamin D (S-25OHD), serum intact parathyroid hormone (S-iPTH), bone turnover markers and whole body and lumbar spine bone mineral density were measured. Sun, smoking and clothing habits, age, body mass index (BMI), and vitamin D and calcium from food and from supplements were recorded. Thirty-seven girls (median age, range: 12.2 years, 10.1-14.7), 115 women (36.2 years, 18.1-52.7) and 95 men (38.3 years, 17.9-63.5) of Pakistani origin (immigrants or descendants with Pakistani parents) took part in the study.Median concentration of S-25OHD was 10.9, 12.0 and 20.7 nmol/l for girls, women and men, respectively. Forty-seven per cent of the girls, 37% of the women and 24% of the men had elevated S-iPTH, and there was a negative relationship between S-iPTH and S-25OHD. Use of vitamin D-containing supplements had a positive association with S-25OHD for men (P=0.04) and women (P=0.0008). Twenty-one per cent of the women and 34% of the men had osteopenia. Neither S-25OHD nor S-iPTH was associated with lumbar spine or whole body bone mineral content.Severely low vitamin D status and elevated S-iPTH is common among Pakistani immigrants in Denmark. The low vitamin D status is not associated with bone markers or bone mass among relatively young Pakistanis.

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).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.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 %.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.

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.

To determine the vitamin D status (serum 25-hydroxyvitamin D; S-25OHD) in adolescent girls and elderly community-dwelling women living in four countries of northern Europe and to explain differences in S-25OHD concentrations between and within the countries.A cross-sectional observational study conducted in a standardised way during February-March. S-25OHD was analysed by high-performance liquid chromatography. Vitamin D and calcium intake was calculated using a standardised food composition database.Denmark, Finland, Ireland, and Poland.A total of 199 girls (mean (s.d.) age 12.6 (0.5) y) and 221 women (mean (s.d.) age 71.8 (1.4) y).The median (inter quartiles) concentration of S-25OHD was 29.4 (20.3, 38.3) nmol/l for the girls and 40.7 (28.0, 54.2) nmol/l for the women. S-25OHD below 25 nmol/l was found in 37% of the girls and 17% of the women, and S-25OHD below 50 nmol/l was found in 92% of the girls and 37% of the women. Positive significant determinants for S-25OHD in girls were use of vitamin D supplements, and in women sun habits, dietary vitamin D intake, use of vitamin D and calcium supplements. Body mass index and smoking were negative determinants in women. For women predictors could explain the differences between countries (P(country) = 0.09, R(2) = 0.39), but for girls the difference remained significant even after including predictors (P(country) = 0.03, R(2) = 0.15).Vitamin D status is low in northern Europe during winter. More than one-third of the adolescent girls have vitamin D status below 25 nmol/l and almost all are below 50 nmol/l. Two-thirds of the elderly community-dwelling women have vitamin D status below 50 nmol/l. Use of vitamin D supplements is a significant positive determinant for S-25OHD for both girls and women (P = 0.001).The European Fifth Framework Programme (Contract No. QLK1-CT-2000-00623).

The objective of this study was to investigate the influence of a high-sodium, high-protein diet on bone metabolism in postmenopausal women (aged 49-60 y) stratified by hormone replacement therapy (HRT) use. In a crossover trial, 18 women (n = 8 HRT users (+HRT) and n = 10 nonusers (-HRT)) were randomly assigned to a diet high in protein (90 g/day) and sodium (180 mmol/day) (calciuric diet) or a diet moderate in protein (70 g/day) and low in sodium (65 mmol/day) for 4 weeks followed by crossover to alternative dietary regimen for a further 4 weeks. The calciuric diet significantly (P0.05) increased urinary sodium, calcium and nitrogen in both groups. While the calciuric diet increased urinary N-telopeptide crosslinks of collagen (by approximately 25%, P = 0.003) in the -HRT group, it had no effect in the +HRT group. It appears that postmenopausal HRT use attenuates the increase in a marker of bone resorption associated with a calciuric diet.

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.

The significance of an interrelation between nongenetic factors and genotype effects in the regulation of bone mass is not clear. In this prospective study of 429 healthy early postmenopausal Danish women, we investigated the association between bone mineral density (BMD) and the FokI and BsmI polymorphisms in the vitamin D receptor (VDR) gene. Participants were allocated to either hormone-replacement therapy (HRT) or no treatment by randomization or personal choice. After 5 years, 332 women with unchanged treatment status were available for analyses, 98 of these women were still on HRT. No association with initial BMD or 5-year change in BMD was found for either polymorphism. In women with body mass index (BMI) < 25 (n = 282), the f allele was associated with lower BMD of the hip (p < 0.001) and forearm (p = 0.001), and the b allele was associated with lower spine BMD (p = 0.02). Comparing thin/normal weight women with overweight/ obese women of the same genotype, FF women had similar BMD at all measured sites in contrast to Ff and ff women in whom BMD, as expected, was higher in the overweight/obese women. Similar results were found for the BsmI polymorphism with no difference in BMD between BMI groups in BB women. Segregation into groups according to dietary calcium intake did not reveal any genotype association with BMD. These results provide some evidence of a modifying effect of nongenetic factors, specifically BMI, on the association between VDR genotype and BMD. High BMI may protect against lower BMD seen in association with thef or b alleles. In some genotypes (FF and BB), BMI had relatively little effect on BMD.

Objectives: to predict spinal and femoral bone mineral density (BMD) in perimenopausal women from simple clinical and biochemical variables. Methods: 2016 women 3–24 months past last menstrual bleeding. Mean age 50.1±2.8 years. Age, height, weight, number of full term pregnancies, weekly hours of physical activity, sunbathing habits, use of sun bed, daily intake of calcium and vitamin D, smoking habits, consumption of alcohol, coffee, and tea, history of forearm or femoral neck fractures among the parents, serum osteocalcin (S-OC), serum bone specific isoenzyme of alkaline phosphatase (BSAP), and urine hydroxyproline/creatinine ratio (U-OHP) were used as predictors in three different mathematical models. Lumbar spine (L2–L4) and femoral neck BMD were measured by DEXA. Three mathematical models (multiple regression, logistic regression, and discriminant analysis) were applied. Results: the multiple regression explained 19–21% of the total variation, and the logistic regression and discriminant function had a sensitivity between 53 and 67% with specificity ranging from 67 to 80%. Age, S-OC, serum bone specific alkaline phosphatase, and a maternal history of forearm or femoral neck fractures seemed to be reproducible risk factors for low bone mineral density irrespective of the mathematical model applied. When applied to a separate population, the models performed poorly. Conclusions: Simple clinical and biochemical variables are not useful to predict spinal and femoral BMD in the individual perimenopausal woman.

Assessing bone loss and gain is important in clinical decision-making, both in evaluating treatment and in following untreated patients. The aim of this study was to correlate changes in bone mineral density (BMD) at different skeletal sites during the first 5 years after menopause and determine if forearm measurements can substitute for dual-energy X-ray absorptiometry (DXA) of the spine and hip. BMD was measured at 0, 1, 2, 3, and 5 years using Hologic 1000/W and 2000 densitometers in 2,016 perimenopausal women participating in a national cohort study. This analysis comprises 1,422 women remaining in the study after 5 years without changes to their initial treatment (hormone-replacement therapy [HRT], n = 497, or none, n = 925). Despite correlated rates of change between forearm and spine (r2 = 0.11; p0.01), one-half of those who experienced a significant decrease in spine BMD at 5 years showed no significant fall in forearm BMD (sensitivity, 50%; specificity, 85%; kappa = 0.25). The total hip had significant better agreement with spine (sensitivity, 63%; specificity, 85%; kappa = 0.37; p0.01). Analysis of quartiles of change also showed significant better agreement with spine and whole body for the total hip than for the femoral neck or ultradistal (UD) forearm. In a logistic regression analysis for identification of group (HRT or control), the prediction was best for whole body (82.6%) and spine (80.9%), followed by total hip (78.5%) and forearm (74.7%). In conclusion, changes at the commonly measured sites are discordant, and DXA of the forearm is less useful than DXA of the hip or spine in determining the overall skeletal response to therapy or assessing bone loss in untreated women.

Objective: To assess the influence of smoking on serum parathyroid hormone (PTH), serum vitamin D metabolites, serum ionized calcium, serum phosphate, and biochemical markers of bone turnover in a cohort of 510 healthy Danish perimenopausal women. Design: A cross-sectional study. Setting: Copenhagen, Denmark. Subjects: Five-hundred-and-ten healthy women aged 45–58 y, included 3–24 months after last menstrual bleeding. None were using hormone replacement therapy. Methods: The women were grouped according to their current smoking status. The two groups were compared with regard to serum levels of 25-hydroxyvitamin D (25OHD) and 1,25-dihydroxyvitamin D (1,25-(OH)2D), intact PTH, ionized calcium and phosphate, osteocalcin, as well as urine pyridinolines. Bone mineral density (BMD) was measured with DEXA-scans. Multiple regression analyses were performed to detect the effect of potentially confounding lifestyle factors, such as calcium and vitamin D intakes, alcohol and coffee consumption, sunbathing, and physical exercise. Results: Fifty percent were current smokers. Smokers had significantly reduced levels of serum 25OHD (P=0.02), 1,25(OH)2D (P=0.001), and PTH (P

Brot C, Jorgensen N, Madsen OR, Jensen LB, Sorensen OH (Copenhagen Municipal Hospital, Copenhagen, Denmark). Relationships between bone mineral density, serum vitamin D metabolites and calcium:phosphorus intake in healthy perimenopausal women. J Intern Med 1999; 245: 509–516. Objectives. To determine the relationships between serum vitamin D metabolites, bone mass, and dietary calcium and phosphorus in a cohort of 510 healthy Danish perimenopausal women. Design. A population-based cross-sectional study. Subjects. A total of 510 healthy women aged 45–58 years, with amenorrhoea for 3–24 months. None of the women was using hormone replacement therapy. Measurements. Measurements of total bone mineral content and regional bone mineral density were performed by dual-energy X-ray absorptiometry. Analyses of serum levels of 25-OHD and 1,25-(OH)2D, intact PTH, ionized calcium and phosphate, as well as biochemical markers of bone turnover in blood and urine. Assessment of calcium and phosphorus intake using dietary records. Results. A consistent inverse relationship between serum 1,25-(OH)2D and bone mineral content/density was found in whole-body mineral content (P = 0.001), spine (P = 0.005) and femoral neck (P

We studied 30 patients with arthrosis in one knee operated on with a cemented (n 26) or an uncemented total knee arthroplasty (TKA) (n 4). Full weight-bearing from the first postoperative day was allowed in all patients, and they received standard postoperative physiotherapy. 1 week prior to surgery, and after 3 and 6 months, isokinetic and isometric muscle strength in both legs were measured, using a Cybex 6000 dynamometer. Isokinetic tests showed a bilateral, significant, and progressive increase (30-53%) in flexor muscle strength most pronounced in the operated legs. Isokinetic extensor strength increased significantly (14-18%) in the operated legs, while in the contralateral legs, a limited increase was found. Isometric flexion strength significantly decreased in the operated knees (17%). Isometric extension strength showed a temporary decrease at 3 months, which returned to the preoperative level. No significant change in isometric strength was observed in the contralateral legs. The knee pain during the muscle strength measurements decreased significantly from the preoperative level, which may indicate that the substantial pain relief within 3 months after a TKA is an important factor for evaluation of muscle strength.

Several papers have reported on vitamin D, parathyroid hormone (PTH), and other regulators of calcium metabolism in patients with Crohn's disease, but results have been conflicting. Bone mineral density (BMD) has been found to be reduced in several papers. A recent study from our laboratory suggested that the expected reduction in BMD disappears when the patients are compared with sex-, age-, and weight-matched healthy controls. The relationship between BMD and regulators of calcium homeostasis is not well established in patients with Crohn's disease.BMD and biochemical regulators of calcium metabolism were measured in 115 unselected patients with Crohn's disease, most of whom were in remission.Vitamin D deficiency (25-OHDor = 10 pg/ml) was present in 44% of patients. Secondary hyperparathyroidism was present in 2% of unoperated patients and in 18% of patients subjected to bowel operations.1) Vitamin D deficiency is common in patients with Crohn's disease even when the disease is in remission and regardless of the location of the disease. 2) Secondary hyperparathyroidism is most frequently seen in patients who have undergone intestinal resection(s). 3) PTH correlates with BMD in a large group of unselected patients with Crohn's disease; 25-OHD only correlates with BMD of the forearm.

To evaluate whether introduction of treatment alternatives would improve compliance with hormonal replacement therapy (HRT) as primary osteoporosis prevention in women not tolerating the first line osteoporosis prevention schedule.Follow-up in four hospitals participating in the Danish Osteoporosis Prevention Study. A total of 706 peri- and postmenopausal women aged 45-57 years between 3 and 24 months from last menstrual bleeding took part, 489 women were randomised to HRT and 217 received HRT by personal choice. A total of 135 (19%) women were hysterectomised. HRT was given as oral or transdermal oestradiol supplemented with progestogen. If the initial treatment allocation was not acceptable several alternatives were available in a pragmatic approach.Compliance with first treatment schedule was lower in women with intact uterus (at 5 years: 48.3 +/- 2.4% compliance) than in hysterectomised (64.7 +/- 5.8%, P0.001 in a Cox analysis) but did not differ after the introduction of HRT alternatives (67.0 +/- 2.9 vs 77.8 +/- 5.9, P = 0.12). Compliance decreased with increasing age at treatment start (RR = 1.11, P0.001) in women with intact uterus but not in hysterectomised women (P = 0.96). Headache/migraine was more frequent among women with intact uterus on oral sequential oestrogen plus progestogen than among hysterectomised women receiving oral continuous oestrogen (RR = 11.3, P0.01).It seems possible to maintain a high HRT compliance by a pragmatic approach including offering alternative HRT formulations to women not tolerating the primary HRT. Further research into long-term compliance with HRT and cost-benefit is warranted.

To determine seasonal variation in vitamin D status in healthy Caucasian adolescent girls and elderly community-dwelling women living in Denmark, and to quantify the impact of sun exposure and intake on the seasonal changes in vitamin D status.A 1-year longitudinal observational study of 54 girls (11-13 years) and 52 women (70-75 years). The participants were examined three times (winter-summer-winter). Serum 25-hydroxyvitamin D (S-25OHD) concentration and vitamin D intake were measured at each visit. Sun exposure was measured during summer.S-25OHD concentrations (winter, summer, winter) were median (25, 75 percentiles) 23.4 (16.5, 36.4), 60.3 (42.7, 67.7), 29.5 (22.2, 40.4) and 47.2 (27.3, 61.1), 67.3 (35.1, 79.2), 50.5 (32.7, 65.5)nmol/l for girls and women, respectively. The usual sun habits were determinant (P=0.002) for change in vitamin D status from winter to summer. Vitamin D intake from supplements (P0.0001) and diet (P=0.002) were determinants for change in vitamin D status from summer to winter. Winter vitamin D status of 50 nmol/l is achievable when vitamin D status the previous summer was ≈ 100 nmol/l. If summer vitamin D status is only ≈ 60 nmol/l, vitamin D status the following winter would be ≈ 28 nmol/l.Low vitamin D status among adolescent girls and elderly women during two consecutive winter seasons, improved vitamin D status during the summer and better vitamin D status in women than in girls was found. The estimations show that a summer S-25OHD concentration ≈ 100 nmol/l is needed to achieve a concentration of ≈ 50 nmol/l the following winter.

High PTH levels increase bone turnover and decrease bone mineral density (BMD). Low plasma 25-hydroxyvitamin D (25OHD) levels cause secondary hyperparathyroidism, but the relative contribution of low 25OHD and high PTH levels on risk of fracture is largely unknown. Within the cohort of women (n = 2,016) included in the Danish Osteoporosis Prevention Study (DOPS), we studied risk of fracture according to parathyroid status. Analyses were performed on effects of high PTH levels (i.e., in the upper tertile, ≥4.5 pmol/L) on risk of incident fractures at different 25OHD levels during 16 years of follow-up. Incident fractures were assessed using a nationwide hospital discharge register. In addition, effects of high PTH levels on BMD and vertebral fractures were assessed by DXA scans and spinal X-ray examination after 10 years of follow-up. High PTH levels were associated with a decreased body mass index, adjusted BMD, and an increased risk of any fracture (HR = 1.41, 95% CI 1.11-1.79) as well as an increased risk of osteoporotic fractures (HR = 1.59, 95% CI 1.20-2.10). Plasma 25OHD levels per se did not affect fracture risk, but high PTH levels were associated with an increased fracture risk only at 25OHD levels50 nmol/L and 50-80 nmol/L. High PTH levels did not increase risk of fracture at 25OHD levels80 nmol/L. In conclusion, PTH levels in the upper part or above the upper level of the reference interval increase risk of fracture in the presence of low vitamin D levels.

AbstractRelationship between fasting glucose, vitamin D and PTH in early postmenopausal womenSúsanna við Streym Thomsen (1), Lars Rejnmark (1), Peter Vestergaard (1), Christine Brot (2), Pia Eiken (3), Pernille Hermann (4) Leif Mosekilde (1). (1) Department of Medicine and Endocrinology C, Aarhus University Hospital, Århus Sygehus, Tage Hansens Gade 2, 8000 Århus C. Susanna.Thomsen@ki.au.dk, (2) Osteoporosis and Metabolic Bone Unit, Hvidovre Hospital, Copenhagen, Denmark, (3) Department of Cardiology and Endocrinology, Hillerød Hospital, Hillerød, Denmark, (4) Department of Endocrinology, Odense University Hospital, Odense, Denmark. Background: Studies have shown an increased risk of type 2 diabetes with low 25-hydroxyvitamin D (25OHD) levels.Hypothesis: Low vitamin D is associated with a high level of blood glucose. Aim: To investigate any association between blood glucose and 25OHD adjusted for Body Mass Index (BMI), body composition, PTH and physical activity in postmenopausal women.Design: Cross-sectional study in postmenopausal women. Material and Methods: Data are based on analyses from the Danish Osteoporosis Prevention Study (DOPS), which is a cohort study in early postmenopausal Caucasian women (n=2016) aged 45 to 58 years old. Measurements: Fasting blood glucose was measured after an overnight fast by standard laboratory methods. Serum levels of 25OHD were measured by a competitive assay using rachitic rat binding protein. The fat and lean mass was measured by DXA-scan. Serum intact parathyroid hormone was measured by DPC Immulite (chemilucens) with an inter-assay CV of 11% and an intra-assay CV of 6%. Data on physical activity was collected through a questionnaire. Results: Results from bivariate analysis are shown in the table, indicating a significant relation between fasting blood glucose and 25OHD and all studied indices. In a multivariate linear regression analyzing fasting blood glucose was significantly associated with BMI (b=0.038 ±0.007 (SE), 2pThe mean and SEM for Glucose was 4.72 mmol/l (± 0.02) and 25OHD 25.1 ng/ml (± 0.3).Conclusion: The apparent relationship between fasting blood glucose and serum 25OHD seems to be mediated by serum PTH, BMI and physical activity. As 25OHD is known to lowering PHT levels interventional trials with vitamin D supplements are warranted in order to term whether improvement of vitamin D status may improve glucose tolerance. Table: Pearson correlation Blood Glucose25 OHDBMIFatLeanPhysical activityPTHBlood Glucose- 25 OHD-0.069xx- BMI0.238xx-0.134xx- Fat0.178xx-0.119xx0.920xx- Lean0.1752xx-0.059xx0.605xx0.536xx- Physical activity-0.653xx0.051x-0.020-0.065xx0.022- PTH 0.106xx-0.142xx 0.219xx 0.221xx0.097xx0.012- x = p xx = p

When plotted versus concentration in an inert solvent, the dielectric Kirkwood g factor of most normal alcohols exhibits a minimum lower than unity followed by a rise up to values larger than unity in the neat alcohol. This behaviour is interpreted by the fact that H-bond association favours cyclic multimers at low concentrations and open multimers at high concentrations. A quantitative model using chain statistics and predicting this behaviour is summarized. A comparison is made between the results of this model and literature data on n -hexan-1-ol diluted in cyclohexane at 25 and 55°C. From the fitted values of the dissociation constants at these two temperatures it is deduced that the enhalpy for the destruction-formation of a hydrogen bond in this alcohol is about 20 kJ moL −1 .

The aim of this study was to develop and validate a high-pressure liquid chromatography (HPLC) method for assessing vitamin D status as 25-hydroxyvitamin D(2) (S-25OHD(2)) and 25-hydroxyvitamin D(3) (S-25OHD(3)) in serum.We assessed the within- and between-subject variation of vitamin D status in serum samples from four different dietary intervention studies in which subjects (n = 92) were supplemented with different doses of vitamin D(3) (5-12 microg/day) and for different durations (4-20 months).The HPLC method was applicable for 4.0-200 nmol S-25OHD/L, while the within-day and between-days variations were 3.8 % and 5.7 %, respectively. There was a concentration-dependent difference between results obtained by a commercial radioimmunoassay and results from the HPLC method of -5 to 20 nmol 25OHD/L in the range 10-100 nmol 25OHD/L. The between-subject variation estimated in each of the four human intervention studies did not differ significantly (p = 0.55). Hence, the pooled standard deviation was 15.3 nmol 25OHD(3)/L. In the studies with 6-8 samplings during 7-20 months of supplementation, the within-subject variation was 3.9-7.2 nmol 25OHD(3)/L, while vitamin D status was in the range 47-120 nmol/L.The validated HPLC method was applied in samples from human intervention studies in which subjects were supplemented with vitamin D(3). The estimated standard deviation between and within subjects is useful in the forthcoming decision on setting limits for optimal vitamin D status.

Udgivelsesdato: 2008-Jan Folate, vitamin B(2) (riboflavin), and vitamin B(12 )may affect bone directly or through an effect on plasma homocysteine levels. Previously, a positive association has been found between plasma levels and bone mineral density (BMD) as well as risk of fracture. However, there are limited data on whether dietary intakes affect bone. Our aim was to investigate whether intake of folate, vitamin B(2,) and vitamin B(12), as assessed by food records affects BMD and fracture risk. In a population-based cohort including 1,869 perimenopausal women from the Danish Osteoporosis Prevention Study, associations between intakes and BMD were assessed at baseline and after 5 years of follow-up. Moreover, associations between intakes and 5- and 10-year changes in BMD as well as risk of fracture were studied. Intakes of folate, vitamin B(2), and vitamin B(12) were 417 (range 290-494) mug/day, 2.70 (range 1.70-3.16) mg/day, and 4.98 (range 3.83-6.62) mug/day, respectively, i.e., slightly above the intakes recommended by the United Nations Food and Agriculture Organization. At year 5, but not at baseline, cross-sectional analyses showed positive correlations between daily intake from diet and from diet plus supplements of folate and BMD at the femoral neck (P < 0.01). However, no associations were found between intakes and changes in BMD. During 10 years of follow-up, 360 subjects sustained a fracture. Compared with 1,440 controls, logistic regression analyses revealed no difference in intakes between cases and controls. A high dietary intake of folate, but not vitamin B(2) or B(12), exerts positive effects on BMD; but further studies are needed to confirm this association.

Rigid non-polar molecules whose shape is convex and can be approximated by an ellipsoid arc considered. Using the formalism of the "effective polarizability increments" previously developed, it is shown that, starting from combination of different experiments bearing on a solution of such molecules in an isotropic solvent, it is possible to determine the principal elements of the intrinsie (in vacuo) polarizability tensor of the molecule under study. These experiments are the dielectric increment of the solution, its Kerr constant, and the NMR splitting under an electric field of certain atoms of the solute.In the case of benzene the results so obtained arc in excellent agreement with vapor phase data from the literature. In the case of anthracene, the values which are obtained for the three principal components of the polarizability tensor seem reasonable.

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.

The influence of a high-Na, high-protein (calciuric) diet on Ca and bone metabolism was investigated in postmenopausal women (aged 50–67 years) who were stratified by vitamin D receptor (VDR) genotype. In a crossover trial, twenty-four women were randomly assigned to a diet high in protein (90 g/d) and Na (180 mmol/d) or a diet adequate in protein (70 g/d) and low in Na (65 mmol/d) for 4 weeks, followed by crossover to the alternative dietary regimen for a further 4 weeks. Dietary Ca intake was maintained at usual intakes (about 20 mmol (800 mg)/d). Urinary Na, K, Ca, N and type I collagen cross-linked N-telopeptide (NTx; a marker of bone resorption), plasma parathyroid hormone (PTH), serum 25-hydroxycholecalciferol (25(OH)D3), 1,25-dihydroxycholecalciferol (1,25(OH)2D3), osteocalcin and bone-specific alkaline phosphatase (B-Alkphase) were measured in 24 h urine samples and fasting blood samples collected at the end of each dietary period. The calciuric diet significantly (P3, 1,25(OH)2D3, PTH, osteocalcin or B-Alkphase in the total group (n24). There were no differences in serum markers or urinary minerals between the basal and calciuric diet in either VDR genotype groups. While the calciuric diet significantly increased urinary NTx (by 25·6 %,Pf+ VDR group (n10; carrying one or more (f)FokI alleles), it had no effect in thef− VDR group (n14; not carrying anyFokI alleles). It is concluded that the Na- and protein-induced urinary Ca loss is compensated for by increased bone resorption and that this response may be influenced by VDR genotype.

Only a limited number of foods naturally contain vitamin D such as fish, meat and offal, and eggs, and milk and dairy products. However, all these foods in addition contain the metabolite 25-hydroxyvitamin D (25OHD). From the few systematic studies which have been performed the food contents of 25OHD in animal foods are usually low but vary. Contents are typically very low in milk and fish (

The aim of this study was to study the influence of hormone replacement therapy (HRT) on weight changes, body composition, and bone mass in early postmenopausal women in a partly randomized comprehensive cohort study design. A total of 2016 women ages 45-58 years from 3 months to 2 years past last menstrual bleeding were included. One thousand were randomly assigned to HRT or no HRT in an open trial, whereas the others were allocated according to their preferences. All were followed for 5 years for body weight, bone mass, and body composition measurements. Body weight increased less over the 5 years in women randomized to HRT (1.94 +/- 4.86 kg) than in women randomized to no HRT (2.57 +/- 4.63, p = 0.046). A similar pattern was seen in the group receiving HRT or not by their own choice. The smaller weight gain in women on HRT was almost entirely caused by a lesser gain in fat. The main determinant of the weight gain was a decline in physical fitness. Women opting for HRT had a significantly lower body weight at inclusion than the other participants, but the results in the self-selected part of the study followed the pattern found in the randomized part. The change in fat mass was the strongest predictor of bone changes in untreated women, whereas the change in lean body mass was the strongest predictor when HRT was given. Body weight increases after the menopause. The gain in weight is related to a decrease in working capacity. HRT is associated with a smaller increase in fat mass after menopause. Fat gain protects against bone loss in untreated women but not in HRT-treated women. The data suggest that women's attitudes to HRT are more positive if they have low body weight, but there is no evidence that the conclusions in this study are skewed by selection bias.

We conducted this study to assess the prevalence of vitamin D insufficiency in a population of normal perimenopausal women, to examine the influence of sun exposure and vitamin D intake on the concentration of 25-hydroxyvitamin D (25OHD) and to examine the association between parathyroid hormone (PTH) and 25OHD. A total of 2016 healthy women aged 45‐58, who had recently undergone a natural menopause, were enrolled over a 2·5-year period in the Danish Osteoporosis Prevention Study. A marked seasonal fluctuation of 25OHD was seen, with an abrupt rise in June and high values until October. The fluctuation could be related to number of hours of sunshine per month with a two months time lag. Dietary vitamin D intake, vitamin supplementation, sunlight exposure, and use of sun-bed were all significantly related to 25OHD concentrations. Sun exposure seemed to contribute the most. The overall prevalence of vitamin D deficiency (defined as serum 25OHDa, 25 nmol=l) was 7 %. However, in the subgroup avoiding direct sunshine and abstaining from vitamin D supplementation 32·8 % were vitamin D deficient in the winter‐spring period. Although mean PTH was increased in the group with low serum 25OHD, PTH was not a sensitive marker of hypovitaminosis D in the individual, as only 16 % of those with vitamin D deficiency had PTH levels above normal range. Thus, we have shown, that healthy middle-aged Danish women are prone to vitamin D insufficiency in the winter‐spring period, if they avoid sun exposure in the summer period and abstain from vitamin D supplementation. 25-Hydroxyvitamin D: Parathyroid hormone: Vitamin D deficiency

Effective bone remodeling requires the coordination of bone matrix deposition by osteoblastic cells, which may occur via soluble mediators or via direct intercellular communication. We have previously identified two mechanisms by which rat osteoblastic cell lines coordinate calcium signaling among cells: autocrine activation of P2 (purinergic) receptors leading to release of intracellular calcium stores, and gap junction-mediated communication resulting in influx of extracellular calcium. In the current work we asked whether human osteoblastic cells (HOB) were capable of mechanically induced intercellular calcium signaling, and if so, by which mechanisms. Upon mechanical stimulation, human osteoblasts propagated fast intercellular calcium waves, which required activation of P2 receptors and release of intracellular calcium stores but did not require calcium influx or gap junctional communication. After the fast intercellular calcium waves were blocked, we observed slower calcium waves that were dependent on gap junctional communication and influx of extracellular calcium. These results show that human osteoblastic cells can propagate calcium signals from cell to cell by two markedly different mechanisms and suggest that these two pathways may serve different purposes in coordinating osteoblast functions.

Bone densitometry using dual energy X-ray absorptiometry (DXA) is frequently used to diagnose osteoporosis and to identify patients at risk of later fractures. The parameters of interest are bone mineral content (BMC) and bone mineral areal density (BMD). Bone densitometry results have a large overlap between normals and patient with fractures. This would suggest that other factors are important for the development of fractures or that bone densitometry is not used optimally. It is generally believed that the conversion of BMC to BMD by division of the former by the projected bone area is a good normalization procedure. Other normalization procedures have been attempted in the past with little success. We hypothesized that this might be due to a blurring effect of time since menopause, and that body size could be demonstrated to have an effect on measured BMC and BMD, if this time effect could be eliminated. The results of this study, comprising 1625 early post-menopausal women studied at virtually the same time since menopause, confirm that this is the case. Body surface area was the parameter among conventional body size variables showing the highest correlation with BMC and BMD. It was clearly shown that low values of BMD were seen more often in the lowest than in the highest body surface area quartile. The difference between quartiles was statistically significant. Simple division of BMC by actual body surface area or division of BMD by the square root of body surface removed the uneven distribution between the body surface area quartiles for lumbar spine and femoral neck measurements, and reduced it at peripheral measuring sites. It is suggested that BMC and BMD of the lumbar spine and the femoral neck should be normalized as described to avoid overdiagnosis of osteoporosis in persons of petite body stature and underdiagnosis in tall ones.

Brot C, Jensen LB, Smensen OH (Copenhagen Municipal Hospital, Copenhagen, Denmark). Bone mass and risk factors for bone loss in perimenopausal Danish women Objectives: To determine risk factors for low bone mass at menopause and risk factors for subsequent bone loss in the following period. Design: A cross-sectional study and a 2-year prospective follow-up. Setting: The catchment area of Sundby Hospital in Copenhagen. Subjects: Four hundred and thirty-three women aged 45–58 years, with amenorrhea for 3–24 months, of whom 87 were followed for a 2-year period. Measurements: Registration of life-style and anthropometric variables, reproductive history, and family history of fractures. Total body bone mineral content (BMC) was measured with dual energy X-ray absorptiometry. Results: By means of multiple regression analysis height, body weight, and length of reproductive period were found to be positively related to whole body BMC (P < 0.001), whilst a negative relationship was found to age (P < 0.001), smoking (P < 0.001), and family history of fractures (P < 0.005). In the longitudinal study, only body weight at the inclusion (P = 0.005) and subsequent changes in body weight and fat mass (P < 0.001) were related to the changes in bone mass. Conclusion: The most significant predictors for bone loss were changes in body weight and fat mass. Hence, weight loss is a risk factor for bone loss in the early postmenopausal period, whereas weight gain seems to preserve bone.

It is unclear whether patients with knee osteoarthritis (OA) and hip OA differ regarding soft tissue composition and bone mineral density (BMD). A total of 42 women waiting for a replacement of the hip (n = 20) or the knee (n = 22) due to OA were examined. Fat mass (FM), percent body fat (%fat), lean mass (LM) and BMD were measured by dual energy X-ray absorptiometry (DEXA). Knee extensor and flexor strength was measured by an isokinetic dynamometer. No significant differences in age, height, disease duration, Lequesne score or pain scores were found between the groups. Comparing the radiographic changes of the knees with those of the hips, changes were most severe in the joints which were to be replaced. Body weight, body mass index, total and regional FM, and %fat were more than 15% higher in patients waiting for a knee replacement (p0.001). Also lean mass tended to be higher in the knee patients. Differences in BMD did not remain statistically significant after correction for body weight. Muscle strength was similar in the two groups but was reduced by 20% in the legs in which the joint was to be replaced compared to the contralateral legs. However, the mean difference in lean mass between the two legs was only 3% (p0.05). The scores for pain felt during strength testing were significantly higher for the involved legs than for the contralateral legs. In conclusion, fat mass values were considerably higher in patients scheduled for a knee replacement. Impaired strength performance in OA may be more strongly associated with pain than with reduced muscle mass.

The intra-session and inter-session reproducibility of knee extensor and flexor strength measurements were examined in 21 gonarthrotic subjects (ten women and eleven men). Using the Cybex 6000 dynamometer, isokinetic peak torque and total work at 30 and 120 degrees/second and isometric peak torque were measured three times on separate days within two weeks by the same examiner. The reproducibility of walking and stair climbing time measurements was also assessed. The concept of critical difference (i.e. the difference between two measurements which would be statistically significant when applied to a reference group in steady state) for the interpretation of muscle strength data obtained by monitoring individual patients is presented. Individual coefficients of variation (CV) were calculated for each muscle strength variable. Depending on the velocity and on whether peak torque or total work were measured, the median CV of intra-session and inter-session extensor strength measurements ranged from 1.5-4.9% and 7.4-10.1%, respectively. CVs for flexor strength measurements were significantly higher. Substantial variability of within subject variances were found, e.g. the 80% central range of CVs for extensor torque at 30 degrees/second was 2.5-29.5% (inter-session). Calculated from CVs, critical differences for inter-session measurements exceeded 30% for all muscle strength variables. Median CVs for walking and stair-climbing time were 7.0% and 4.9%, respectively. In conclusion, the large CVs and corresponding critical differences may be a major limitation in the use of muscle strength measurements in the individual gonarthrotic patient.

Much work has been devoted to the Acousto-Optic Tunable Filters (AOTF) for wavelength multiplexed optical communications. Lithium niobate in X-cut Y-propagating is the best candidate to realize that function[1,2].

Molecular dynamics simulation of a sample of a two-dimensional fluid of Stockmayer molecules (i.e. particles interacting via a central Lennard-Jones interaction plus a point dipole interaction) are reported. The dipolar interaction adopted is that required by two-dimensional electrostatics, so that the convergence problem is conserved. The sample (≈13 molecular diameters in size) is kept in vacuo by a steep circular potential barrier. It is first shown that for distances greater than 3 to 5 molecular diameters the macroscopic laws of electrostatics apply, by checking that the mean squared moment of an inner disc, as a function of the diameter of the disc, can be fitted with a single dielectric constant, which is thus determined. The Kirkwood correlation factor for an infinite sample is then evaluated. For highly polar systems, it is greater than unity. Also the radial vector correlation function h Δ(r), which describes the weight of in an expansion of the angle-dependent pair distribution f...

In the previous papers of this series it was shown, by molecular dynamics simulations, that 2D fluid systems of pure Stockmayer molecules have a higher dielectric constant than predicted by the Onsager model or, equivalently, that their Kirkwood orientational correlation factor g k is greater than unity. In this paper this observation is further considered; it is shown that it is due to the fact that the longitudinal positive correlations are enhanced, while the negative correlations in the transverse direction are diminished, compared with those induced in a continuum by a polar molecule. Modified Stockmayer model molecules are then studied. The adopted modifications are of two kinds: (i) the molecular point dipole is excentred and (ii) a central quadrupole is added to the central dipole. In both cases g k is found to be closer to unity than for the pure Stockmayer systems. However, this is not due to a better local validity of the Onsager picture: rather, the map of the local polarization around a refer...

Relative measurements of the intensities of the light scattered by three anisotropic molecules diluted in weakly depolarizing solvents are reported. Our aim was to test the expression recently derived by Brot for the model of the molecule in an ellipsoidal cavity embedded in a continuum. Our results are in good agreement with this expression, the fit of the ellipticity of the cavity yielding reasonable values, contrary to the results of an earlier treatment.

On considere d'abord, dans le cadre d'un modele a cavite ellipsoidale, l'equation dielectrique de molecules anisometriques dans un solvant isotrope, en utilisant le champ interne de Onsager-Scholte...