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Purpose: To evaluate the influence of time of day on the circulating concentrations of 14 frequently used clinical biochemical parameters in the Bispebjerg study of diurnal variations., Materials and Methods: Venous blood samples were obtained under controlled environmental, activities and food conditions from 24 healthy young men every third hour through 24 hours, nine time points in total. At each time point, the parameters' concentrations were measured. The data were analyzed by rhythmometric statistical methods and in addition the biological variations were calculated., Results: Significant oscillation of melatonin with an amplitude (amp) of 19.84 pg/ml and a peak at 03:34 h confirmed the normal 24-hour rhythms of the participants. Potassium (p < 0.0001, amp = 0.18 mmol/L), sodium (p < 0.0001, amp = 1.10 mmol/L) creatine kinase (p = 0.01, amp = 17.18 U/L), bilirubin (p < 0.0001, amp = 2.36 μmol/L) and aspartate aminotransferase (p < 0.0001, amp = 1.66 U/L) oscillated with gradually falling mean concentrations through the day to nadir around midnight. Urea nitrogen (p = 0.01, amp = 0.22 mmol/L) oscillated with gradually increasing mean concentrations through the day peaking around midnight. Lactate dehydrogenase (p < 0.0001, amp = 9.76 U/L) oscillated with gradually increasing concentrations through the early day peaking in the afternoon. Uric acid (p = 0.03, amp = 0.013 mmol/L) oscillated with gradually increasing concentrations through the night peaking in the morning. Potassium and sodium had the highest 24-hour oscillations in proportion to the reference intervals of the parameters for healthy young men., Conclusions: In the clinical setting, diurnal variations of clinical biochemical parameters commonly used through the day and night must be considered when concentration changes in the parameters are evaluated especially potassium and sodium.

Objective: The aim of this study was to assess the evidence for the association between different biochemical markers at admission and mortality through a meta-analysis., Data Sources: PubMed-, Embase-, Cochran Library and the Web of Knowledge were searched for cohort studies., Study Selection: Eligible studies were observational studies with a study population larger than 150 subjects, a mean age above 60 years and a study duration below 730 days., Data Extraction: Characteristics of studies and outcomes of all-cause mortality were extracted from the retrieved articles. Data were pooled across studies for the individual biomarker using random- or fixed-effect analysis., Data Synthesis: 15 eligible studies of 5 different markers on mortality were studied. The following markers were found to be of prognostic value on mortality in hip fracture patients: low haemoglobin (odds ratio, 2.78; 95% confidence interval, 2.17-3.55; P<0.00001, 3148 subjects included), low total lymphocyte count, TLC (odds ratio, 2.60; 95% confidence interval, 1.61-4.20; P<0.00001, 1689 subjects included), low albumin (odds ratio, 1.83; 95% confidence interval, 1.31-2.56; P=0.0004, 1680 subjects included), low albumin/low TLC (odds ratio, 3.00; 95% confidence interval, 1.81-4.99; P<0.0001, 704 subjects included), low albumin/high TLC (odds ratio, 3.39; 95% confidence interval, 1.83-6.29; P=0.0001, 704 subjects included), high creatinine (odds ratio, 1.58; 95% confidence interval, 1.25-1.99; P=0.0001, 3761 subjects included), and high PTH (odds ratio, 15.43; 95% confidence interval, 3.60-66.14; P=0.0002, 525 subjects included)., Conclusion: Biochemical markers at admission are valid predictors of mortality in hip fracture patients., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

Introduction: Previously, little attention has been paid as to how disturbances in the parathyroid hormone (PTH)-calcium-vitamin D-axis, such as secondary hyperparathyroidism (SHPT), relate to mortality amongst hip fracture patients. This study aimed to (1) determine if SHPT is associated with mortality in this group of patients, (2) investigate the association between serum (s-) PTH, s-total calcium, s-25-hydroxyvitamin D (s-25(OH)D) and mortality and (3) determine the prevalence of SHPT amongst hip fracture patients and a control group., Method: The study included 562 hip fracture patients (HF) (age ≥ 70 years) admitted to a Danish university hospital. The hip fracture patients were prospectively enrolled in a dedicated hip fracture database. Each hip fracture patient was exactly matched according to age and sex with two controls randomly chosen from a control population of 21,778 subjects who had s-PTH, s-total calcium and s-25(OH)D measured at the Copenhagen General Practitioners Laboratory after referral from their general practitioner. The control group (Con) thus consisted of 1124 subjects., Results: General 1-year mortality: Con-female 8.4%, Con-male 15.3%, HF-female 24.6%, HF-male 33.3%, p<0.0001 (log rank). SHPT AND RELATED 1-YEAR MORTALITY: Con-no SHPT 8.9%, Con-SHPT 16.8%, HF-no SHPT 22.7%, HF-SHPT 34.9%, p<0.0001 (log rank). The mortality rates were higher for controls with SHPT (OR 2.06, 95% CI: 1.32-3.23), hip fracture patients without SHPT (OR 3.00, 95% CI: 2.14-4.20) and hip fracture patients with SHPT (OR 5.46, 95% CI: 3.32-8.97) compared to the controls without SHPT. PREVALENCE OF SHPT: Con 16%, HF 20%, p=0.09 (Chi-square)., Conclusions: Our study clearly shows that SHPT is significantly associated with mortality in both hip fracture patients and the control group. In the multivariate Cox regression analysis, s-PTH and s-total calcium were both significantly associated with mortality, whereas s-25(OH)D was not associated with mortality in this analysis. Our study furthermore indicates that SHPT is almost equally prevalent amongst the hip fracture patients and the control group., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

Background: There is a 5- to 8-fold increased risk of mortality during the first 3 months after a hip fracture. Several risk factors are known. We studied the predictive value (for mortality) of routine blood tests taken on admission., Methods: 792 hip fracture patients were included prospectively; blood tests were taken on admission. Follow-up data on mortality were obtained from the civil registration system. Patients were divided into 2 groups based on whether they had survived at least 90 days after the hip fracture. To estimate which laboratory tests could be used to predict outcome, we used receiver operation characteristic (ROC) curves., Results: 3-month mortality could be predicted with 69% accuracy from the level of plasma creatinine in standard admission blood tests. The mortality in patients with elevated levels of creatinine was almost 3-fold that of the patients with normal creatinine. Mortality was also associated with age, low blood hemoglobin, high plasma potassium, and low plasma albumin levels., Interpretation: Our findings could be of use in identifying patients who might benefit from increased attention perioperatively.

Background. The prone position is applied to facilitate surgery of the back and to improve oxygenation in the respirator-treated patient. In particular, with positive pressure ventilation the prone position reduces venous return to the heart and in turn cardiac output (CO) with consequences for cerebral blood flow. We tested in healthy subjects the hypothesis that rotating the head in the prone position reduces cerebral blood flow. Methods. Mean arterial blood pressure (MAP), stroke volume (SV), and CO were determined, together with the middle cerebral artery mean blood velocity (MCA V(mean)) and jugular vein diameters bilaterally in 22 healthy subjects in the prone position with the head centered, respectively, rotated sideways, with and without positive pressure breathing (10 cmH(2)O). Results. The prone position reduced SV (by 5.4 ± 1.5%; P < 0.05) and CO (by 2.3 ± 1.9 %), and slightly increased MAP (from 78 ± 3 to 80 ± 2 mmHg) as well as bilateral jugular vein diameters, leaving MCA V(mean) unchanged. Positive pressure breathing in the prone position increased MAP (by 3.6 ± 0.8 mmHg) but further reduced SV and CO (by 9.3 ± 1.3 % and 7.2 ± 2.4 % below baseline) while MCA V(mean) was maintained. The head-rotated prone position with positive pressure breathing augmented MAP further (87 ± 2 mmHg) but not CO, narrowed both jugular vein diameters, and reduced MCA V(mean) (by 8.6 ± 3.2 %). Conclusion. During positive pressure breathing the prone position with sideways rotated head reduces MCA V(mean) ~10% in spite of an elevated MAP. Prone positioning with rotated head affects both CBF and cerebrovenous drainage indicating that optimal brain perfusion requires head centering.

Background: Clinical differentiation between parkinsonian syndromes (PS) remains a challenge despite well-established clinical diagnostic criteria. Specific diagnostic biomarkers have yet to be identified, though in recent years, studies have been published on the aid of certain brain related proteins (BRP) in the diagnosing of PS. We investigated the levels of the light subunit of neurofilament triplet protein (NF-L), total tau and phosphorylated tau, amyloid-β(1-42), and the soluble α- and β-cleaved fragments of amyloid precursor proteins in a cohort of patients with various PS., Methods: Seventy-one patients with different PS and cerebellar disorders were included consecutively over 21 months. CSF was collected at inclusion. Clinical follow-up was performed after 16 months (median; range: 9-30). Statistical comparison was performed after follow-up on 53 patients in four subgroups of PS: multiple system atrophy (MSA)(n = 10), progressive supranuclear palsy (PSP)(n = 10), dementia with Lewy bodies (DLB)(n = 11), and Parkinson's disease (PD)(n = 22), using the non-parametric Kruskal-Wallis test., Results: A statistically significant difference was found for NF-L (p < 0.0001, lowest values for PD), Aβ(1-42,) (p = 0.002, lowest values for DLB), and sAPPα and sAPPβ (p = 0.03 and 0.02, lower values observed for DLB and MSA)., Conclusion: We demonstrate a potential role for sAPPα and sAPPβ in distinguishing between PS, a finding that needs to be confirmed in future studies of larger cohorts. There is a tendency towards low levels of Aβ(1-42) in DLB patients in our cohort. Further, our results support findings from previous studies, which indicate an ability to separate atypical PS from PD based on levels of NF-L., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

Purpose: To evaluate the influence of time of day on the circulating concentrations of 21 hematology parameters., Materials and Methods: Venous blood samples were obtained under standardized circumstances from 24 healthy young men every third hour through 24 hours, nine time points in total. At each time point, the level of melatonin, iron, transferrin, transferrin saturation, ferritin, cobalamin, folate, red blood cells and white blood cells was measured. The data were analysed by rhythmometric statistical methods. The biological variations were calculated., Results: Significant oscillation of melatonin (p < 0.0001) with an amplitude (amp) of 19.84 pg/ml and a peak level at 03:34 h confirmed the normal 24-hour rhythms of the participants. Erythrocytes (p < 0.0001, amp = 0.15 × 10(12)/L), hemoglobin (p < 0.0001, amp = 0.29 mmol/L), hematocrit (p < 0.0001, amp = 0.01), iron (p < 0.0001, amp = 4.00μmol/L), transferrin (p = 0.03, amp = 1.41μmol/L), transferrin saturation (p < 0.0001, amp = 6.37%) and folate (p < 0.0001, amp = 1.55nmol/L) oscillated significantly, with gradually falling mean levels through the day to nadir around midnight. Leukocyte count (p < 0.0001, amp = 0.78 × 10(9)/L), neutrophils (p = 0.001, 0.31 × 10(9)/L), eosinophils (p < 0.0001, amp = 0.04 × 10(9)/L), monocytes (p = 0.0009, amp = 0.06 × 10(9)/L), lymphocytes (p < 0.0001, amp = 0.49 × 10(9)/L) oscillated significantly with gradually increasing mean levels through the day peaking at midnight. Iron, leukocytes and hemoglobin had the highest 24 hour oscillations in proportion to the reference intervals of the parameters for healthy young men., Conclusions: Biochemical screenings are biased by diurnal variations, which must be considered when blood concentrations of these parameters are interpreted in the clinical setting.

A 26-year-old male bodybuilder was admitted to the surgical department of a Danish community hospital for hematemesis. During the clinical interview, he revealed that he had recently finished a course of anabolic steroids and erythropoietin. The patient also had a previous history of infections and chronic ulcers due to paraffin-oil injections in both upper arms one year before. Over the course of the next few hours, the patient developed signs of multi-organ dysfunction, including pancreatitis, hemorrhagic gastritis, nephropathy with temporary anuria, and respiratory insufficiency, and was transferred to the ICU. After manometric monitoring on the patient's upper arms proved difficult, invasive blood pressure monitoring was used and revealed that the patient was in a state of hypertensive crisis. This case of multi-organ dysfunction was possibly caused by multi-substance-induced hypercalcemia., (© Georg Thieme Verlag KG Stuttgart · New York.)

Introduction: The objective of the study was to identify possible prognostic factors in patients with salicylic poisoning., Material and Methods: A chart review on 53 patients with salicylic poisoning was performed. Clinical and biochemical data were registered for all patients with a serum level of salicylic acid higher than or equal to 2 mmol/l in the 2004-2008 period. The patients were divided into groups according to the outcome of the poisoning. A complicated outcome was defined as: hospital stay > 48 hours, dialysis, persisting complications at discharge or death., Results: In the group with complicated outcome, chronic poisoning (43% versus 13%, p = 0.02) and medical diseases (24% versus 9%, p = 0.07) were more prevalent and the proportion of elderly (55 years versus 38 years, p = 0.003) and alcoholics (48% vs. 25%, p = 0.09) were higher. The mortality was low, with only one fatality among the acutely poisoned and none among the chronically poisoned. Neurological symptoms (somnolence and confusion) were the only symptoms which differed significantly between the two groups (67% versus 28%, p = 0.006), as well as being the only variable independently emerging as a risk factor in the multivariate logistic regression analysis with an odds ratio of 6.6 (95% confidence interval: 1.5-28.9) for a complicated outcome. A significantly lower level of bicarbonate was seen in the group with complicated outcome. Among the other biochemical data, only haemoglobin and certain liver enzymes differed between the two groups, probably due to pre-existing differences., Conclusion: Mortality after salicylic poisoning is low. Chronic poisonings, old age or concurrent medical diseases are associated with a complicated outcome. If neurological symptoms or low standard-HCO3- are present, the prognosis is poor.

The assembly, structure, and stability of DNA nanocages with the shape of truncated octahedra have been studied. The cages are composed of 12 double-stranded B-DNA helices interrupted by single-stranded linkers of thymidines of varying length that constitute the truncated corners of the structure. The structures assemble with a high efficiency in a one-step procedure, compared to previously published structures of similar complexity. The structures of the cages were determined by small-angle X-ray scattering. With increasing linker length, there is a systematic increase of the cage size and decrease of the twist angle of the double helices with respect to the symmetry planes of the cage structure. In the present study, we demonstrate the length of the single-stranded linker regions, which impose a certain degree of flexibility to the structure, to be the important determinant for efficient assembly. The linker length can be decreased to three thymidines without affecting assembly yield or the overall structural characteristics of the DNA cages. A linker length of two thymidines represents a sharp cutoff abolishing cage assembly. This is supported by energy minimization calculations suggesting substantial hydrogen bond deformation in a cage with linkers of two thymidines.

Atrial natriuretic peptide (ANP) and B-type natriuretic peptide (BNP) have important local functions within the myocardium, where they protect against accelerated fibrosis. As circadian expression of cardiac natriuretic peptides could be of importance in local cardiac protection against disease, we examined the diurnal changes of the mRNAs encoding ANP, BNP, and their common receptor NPR-A in atrial and ventricular myocardium. Forty eight mice were killed at the following ZT times: 4, 8, 12, 16, 20, and 24, where ZT designates Zeitgeber; ZT 0 corresponds to lights ON and ZT 12 corresponds to lights OFF. Eight animals (4 males and 4 females) were included at each time point. Another 48 animals were killed during the second cycle of dark/dark (designated Circadian Time or CT: CT 4, CT 8, CT 12, CT 16, CT 20, and CT 24). The cellular contents of the clock genes Per1 and Bmal1 as well as ANP, BNP, and their common receptor (NPR-A) were determined using RT-PCR. Per1 and Bmal1 mRNA contents oscillated in antiphase in both atrial and ventricular regions, where Bmal1 mRNA peaked 12h out of phase relative to Per1 mRNA. ANP and NPR-A atrial mRNA contents revealed borderline significant diurnal changes, whereas ventricular BNP mRNA contents exhibited pronounced oscillation during constant darkness with nadir at CT 12 (P<0.0001). In conclusion, we report a chamber-dependent circadian profile of cardiac BNP mRNA contents, which is not paralleled by the related ANP gene. Our findings suggest that the BNP mRNA pattern could be associated with increased cardiac susceptibility and response to disease., (Copyright 2009 Elsevier B.V. All rights reserved.)

We previously demonstrated the conversion of a single human topoisomerase I mediated DNA cleavage-ligation event happening within nanometer dimensions to a micrometer-sized DNA molecule, readily detectable using standard fluorescence microscopy. This conversion was achieved by topoisomerase I mediated closure of a nicked DNA circle followed by rolling circle amplification leading to an anchored product that was visualized at the single molecule level by hybridization to fluorescently labeled probes (Stougaard et al. ACS Nano 2009, 3, 223-33). An important inherent property of the presented setup is, at least in theory, the easy adaptability to multiplexed enzyme detection simply by using differently labeled probes for the detection of rolling circle products of different circularized substrates. In the present study we demonstrate the specific detection of three different enzyme activities, human topoisomerase I, and Flp and Cre recombinase in nuclear extracts from human cells one at a time or multiplexed using the rolling circle amplification based single-molecule detection system. Besides serving as a proof-of-principle for the feasibility of the presented assay for multiplexed enzyme detection in crude human cell extracts, the simultaneous detection of Flp and Cre activities in a single sample may find immediate practical use since these enzymes are often used in combination to control mammalian gene expression.

Objective: To investigate the impact of HIV co-infection on mortality in patients infected with hepatitis C virus (HCV)., Methods: From a nationwide Danish database of HCV-infected patients, we identified individuals diagnosed with HCV subsequent to an HIV diagnosis. For each co-infected patient, four control HCV patients without HIV were matched on age, gender and year of HCV diagnosis. Data on comorbidity, drug abuse, alcoholism and date of death were extracted from two healthcare databases. We constructed Kaplan-Meier curves and used Cox regression analyses to estimate mortality rate ratios (MRRs), controlling for comorbidity., Results: We identified 483 HCV-HIV co-infected and 1932 HCV mono-infected patients, yielding 2192 and 9894 person-years of observation with 129 and 271 deaths, respectively. The 5-year probability of survival was 0.74 [95% confidence interval (CI) 0.69-0.80] for HCV-HIV co-infected patients and 0.87 (95% CI 0.85-0.89) for HCV mono-infected patients. Co-infection was associated with substantially increased mortality (MRR 2.1, 95% CI 1.7-2.6). However, prior to the first observed decrease in CD4 counts to below 300 cells/muL, HIV infection did not increase mortality in HCV-infected patients (MRR 0.9, 95% CI 0.5-1.50)., Conclusions: HIV infection has a substantial impact on mortality among HCV-infected individuals, mainly because of HIV-induced immunodeficiency.

Objective: To investigate the influence of smoking on bone during therapy with nasally administrated estradiol in sequential combination with oral progesterone in early postmenopausal women. In addition, to observe the consequences of smoking on bone in untreated women., Methods: Post-hoc exploratory analyses of data from 270 postmenopausal women randomized to 2 years' therapy with daily nasal administration of 17beta-estradiol or placebo sequentially combined with oral micronized progesterone in the active groups or placebo in the placebo group., Results: During treatment with nasal estradiol, the bone mineral density (BMD) of the lumbar spine had increased less at 2 years in smokers as compared to non-smokers (2.6% vs. 3.9%, p = 0.03). Parallel changes were seen in the placebo group (-3.6% vs. -2.4%, p = 0.08). In the total hip BMD, there was no difference in the response to estradiol in smokers vs. non-smokers (1.4% vs. 1.4%, p = 0.89), whereas the change in the hip on the placebo was similar to that seen in the spine (-3.7% vs. -2.6%, p = 0.08). Supportive changes were seen in urinary CTX and in serum osteocalcin., Conclusions: These results indicate that cigarette smoking may reduce the efficacy of nasal estradiol to increase bone mass in early postmenopausal women. In addition, smoking may increase spontaneous bone loss in untreated women.

We wanted to investigate whether the use of sunbeds with sunlamps emitting mainly UVA and only 0.5% or 1.4% UVB will increase the level of serum 25-hydroxyvitamin D (25(OH)D). In a randomized, controlled, open study on healthy, Caucasian females (> 50 years) sunbed radiation was given as follows: four 6-min sunbed sessions (days 0, 2, 4 and 7) and four 12-min sunbed sessions (days 9, 11, 14 and 16 ) with sunlamps emitting 0.5% UVB (n = 20) or with sunlamps emitting 1.4% UVB (n = 15). The controls (n = 21) had no intervention. Serum levels of 25(OH)D were measured on days 0, 9 and 18 in all three groups. The average increase in serum 25(OH)D from day 0 to day 9 was 12 nmol L(-1) (SD 11 nmol L(-1), P = 0.0002) in the 0.5% UVB group and 27 nmol L(-1) (SD 9 nmol L(-1), P < 0.0001) in the 1.4% UVB group. From day 9 to day 18 a further but not significant increase in serum 25(OH)D of 3 nmol L(-1) (SD 9 nmol L(-1), P = 0.2) in the 0.5% UVB group and 0.6 nmol L(-1) (SD 18 nmol L(-1), P = 0.9) in the 1.4% UVB group was seen. No significant changes were found in the control group. Increasing with UVB dose and exposure time, 37-64% of the sunbed sessions resulted in side effects such as erythema or polymorphic light eruption. The results showed that sunbeds emitting 0.5% and 1.4% UVB increased 25(OH)D serum levels. The increases were dose dependent but reached a plateau after few sessions. Sunbed use as vitamin D source is, however, not generally recommendable due to the well-known carcinogenicity and high frequency of acute side effects.

Objectives: To evaluate the rate of postoperative complications, length of stay, and 1-year mortality before and after introduction of a comprehensive multidisciplinary fast-track treatment and care program for hip fracture patients (the optimized program)., Design: Retrospective chart review with historical control., Setting: Orthopedic ward (110 beds) at a university hospital (700 beds)., Participants: Five hundred thirty-five consecutive patients aged 40 and older (94%>or=60) hospitalized for hip fracture between January 1, 2003, and March 31, 2004. Three hundred and thirty-six patients (70.3%) were community dwellers before the fracture and 159 (29.7%) were admitted from nursing homes., Intervention: The fast-track treatment and care program included a switch from systemic opiates to a local femoral nerve catheter block; an earlier assessment by the anesthesiologist; and a more-systematic approach to nutrition, fluid and oxygen therapy, and urinary retention., Results: In the intervention group, the rate of any in-hospital postoperative complication was reduced from 33% to 20% (odds ratio=0.61, 95% confidence interval=0.4-0.9; P=.002). Rates of confusion (P=.02), pneumonia (P=.03), and urinary tract infection (P<.001) were lower in the intervention group than in the control group, and length of stay was 15.8 days in the control group, versus 9.7 days in the intervention group (P<.001). For community dwellers, 12-month mortality was 23% in the control group versus 12% in the intervention group (P=.02). Overall 12-month mortality was 29% in the control group and 23% in the intervention group (P=.2)., Conclusion: The optimized hip fracture program reduced the rate of in-hospital postoperative complications and mortality. Randomized clinical trials are needed to confirm these results and elucidate the elements of the program that have the greatest effect on clinical outcomes and mortality.

Background: Quantitative bibliometric measurements of research activity are frequently used, e.g. for evaluating applicants for academic positions. The purpose of this investigation is to assess research activity within the medical speciality of Clinical Biochemistry by comparing it with a matched control group from other medical specialities in Denmark., Materials and Methods: A list of all physicians registered in Denmark (23,127 persons) was drawn from the database "Laeger.dk". Of these, 5,202 were generalists (not included) while 11,691 were from other specialities. Of the 126 specialists from Clinical Biochemistry, 57 fulfilled the inclusion criteria. Each of these 57 was matched according to medical title with two randomly chosen specialists from other specialities, totaling 114. Using Medline and the Web of Science, the number of publications and the number of citations were then ascertained., Results: 25% of the 11,691 specialists held a PhD degree or doctoral degree, DMSci, (Clinical Biochemistry: 61%). The 171 specialists included in the study had 9,823 papers in Medline and 10,140 papers in the Web of Science. The number of Medline papers per specialist was 71 for Clinical Biochemistry compared to 51 for the control group. The number of citations per specialist was 1,844 for Clinical Biochemistry compared to 816 for the control group. The top ten H-indices (of which 8 were in Clinical Biochemistry) ranged from 30 to 69., Conclusion: Both the number of papers and the number of citations were higher for Clinical Biochemistry than for the control group. The difference was most pronounced among professors.

Objective: To study the influence of smoking on uterine bleeding patterns during sequentially administered oral hormone therapy (HT)., Methods: Using a post-hoc strategy, we included four sequential oral HT groups from two studies. The therapies consisted of estradiol from days 1 to 28 (estradiol or estradiol valerate) and progestogen (levonorgestrel or gestodene) on days 17-28. A total of 111 healthy, early postmenopausal women (38 smokers and 73 non-smokers) followed for 2 years were included in the analyses. Uterine bleeding data were collected from bleeding calendars., Results: On the regimen containing levonorgestrel, smoking women had a cyclical bleeding significantly earlier than non-smoking women (about 2 days' difference). Moreover, smoking women had significantly longer bleeding than non-smoking women (about 1 day in difference). This was in contrast to the three regimens containing gestodene, where smoking seemed to have far less influence on uterine bleeding., Conclusions: On a regimen containing levonorgestrel, smokers exhibit an earlier and longer uterine bleeding than do non-smokers. This is in contrast to regimens containing gestodene, where smoking women are less likely to differ from non-smoking women with regard to bleeding. This indicates that smoking influences progestogen metabolism, and that this influence may vary with different progestogens. Further studies are needed.

Introduction: Postoperative urinary retention can cause serious complications. An ultrasound bladderscanner has been shown to be useful in distinguishing between patients who need catheterisation and patients who do not. We wished to investigate if clinical assessment including inspection, percussion and palpation of the bladder is of any use in this perspective. In this study we compare clinical findings with ultrasound examinations., Material and Methods: Two trained doctors each investigated 25 postoperative patients clinically immediately after ultrasound examination in the recovery room. Ultrasound examination was carried out by trained nurses using BladderScan BVI 3000. Assessed and measured volumes as well as patient height, weight, asa-class and sex were registered., Results: We found a high negative predictive value of 92% for a cut-off limit of 500 ml. The corresponding positive predictive value was a modest 38%. This tendency was seen for cut-off-limits exceeding 300 ml., Conclusion: Clinical assessment of bladder size might be useful in terms of ruling out a big volume postoperatively. Because of the low positive predictive value, we recommend verifying urinary retention judged by clinical assessment with ultrasound examination before catheterisation. Also, one has to remember that urinary retention occurs with different volumes in different patients.

Understanding bone remodeling is essential for understanding bone as a whole. Bone remodeling takes place through a stepwise cellular process, with osteoclasts carving small cavities, also known as resorption pits, into the surface of trabecular bone, followed by osteoblasts, which refill the pits with new soft bone collagen matrix tissue (osteoid). The detailed structure of the surface in the frontier of a resorption pit before, during, and after the osteoid is being laid down is not well known. We present detailed atomic force microscope (AFM) images from the edge, the front end, and the bottom of a resorption pit in a human trabecular bone sample that showed signs of incomplete remodeling. The images reveal a scalloped surface left behind by the osteoclasts and the surface morphology of preexisting bone tissue and new bone tissue. In addition, we display the bone formation front in the pit showing the anchor points between the new bone and the existing bone. We also found evidence of microcracking in the front end of the pit, suggesting that microcracking was the initiator of this particular resorption pit. We anticipate that AFM may initiate a more detailed understanding of the influence of the remodeling process on the structure of bone, as well as a better understanding of the surface on which new bone tissue can be anchored.

Displaced femoral neck fractures are known to be associated with high rates of mortality. The purpose of the present study is to investigate pre- and postoperative factors which influence this mortality in a series of 1186 consecutive Danish patients presenting to one hospital's orthopaedic department with Garden type 3-4 fractures. Subsequent mortality data was obtained from the state population register (224 were still alive). The stepwise Cox proportional hazards model was used for multivariate analysis in order to obtain the predictors of postoperative mortality. The median survival of male subjects fell from 5.2 years in an age-matched control population to 1.6 years in the patients. In women survival time fell from 6.6 to 2.8 years. Almost all excess mortality occurred during the first 3 months following hemiarthroplasty. In order of significance, key factors negatively influencing mortality at 3 months were: cardiac complications, dementia, male sex, age, waiting time before operation, stroke and dislocation of the prosthesis and perioperative fracture. Of these, waiting time for surgery and dislocation of the prosthesis could be modified. A number of other studies have confirmed the importance of optimising these factors.

The MTHFR c.677C>T polymorphism has been shown to have significant effects on skeletal health in middle-aged to elderly women and men. Despite an accumulating amount of data on MTHFR genetics and the association between homocysteine levels and fracture, it remains unknown if MTHFR c.677C>T genotype affects bone mineral accretion in youth or bone loss in adulthood. The purpose of this cross-sectional study was to examine the effects of this common allelic polymorphism on peak bone mass and bone turnover. We performed MTHFR genotyping in 780 healthy Danish men, aged 20 to 29 years, participating in the Odense Androgen Study. BMD at the spine, hip and whole-body was measured using a Hologic QDR-4500 densitometer. Genotype frequencies were compatible with Hardy-Weinberg equilibrium. Spine BMD was significantly associated with genotype, with a decrease in BMD of 0.20 SD for each copy of the T-allele. Effects were independent of age, BMI, smoking and serum levels of vitamin D and IGF-I. Associations with BMD of the hip and whole body were short of statistical significance. MTHFR genotype showed no association with the bone turnover markers 1-CTP, bone specific alkaline phosphatase or osteocalcin. In conclusion, significant skeletal effects of this common polymorphism were present at the lumbar spine in men at the age of 25 years.

AFM images were taken of the exterior surface of a single trabecula, extracted from a human femoral head removed during surgery for a hip fracture in an old women with former fractures. The images showed a dense structure of bundled collagen fibrils banded with 67 nm periodicity. Bundles were seen to run in parallel in layers confirming the collagen structure seen by other techniques. Single collagen fibrils were seen to cross the bundles, thus forming cross-links between neighboring bundles of collagen fibrils. Some of these crossing fibrils did not have the 67 nm band pattern and their dimensions were about half compared to the neighboring collagen fibrils. Very little mineral was found on the surface of the trabecula. An AFM image of a fracture plane was also displayed. The trabecula was extracted from a region close to the hip fracture. However, there were in this case no obvious features in the images that could be linked directly to osteoporosis, but altered collagen banding and collagen protrusions may alter mechanical competence. A path to extensive studies of the nanometer scale structure of bone was demonstrated.

The purpose of this study is to investigate the association of serum osteoprotegerin (OPG) and the A163G polymorphism in the OPG promoter with peripheral measures of bone mass and with odds ratios for wrist and hip fracture in a case-control study of postmenopausal Danish women. The study included 66 women with lower forearm fracture, 41 women with hip fracture, and 206 age-matched controls. All had broadband ultrasound attenuation (BUA) and speed of sound (SOS) measured at the heel as well as bone mineral density (BMD) measured by DXA at the distal forearm. S-OPG was measured by ELISA. The A163G genotypes were determined by PCR-RFLP analysis. S-OPG levels correlated positively with age ( r = 0.45; P << 0.0001) and negatively with distal forearm BMD ( r = -0.31; P << 0.0001), heel BUA ( r = -0.23; P << 0.0001), and heel SOS ( r = -0.22; P << 0.0001). Comparing the highest quartile of S-OPG to the lowest, the odds ratio for osteoporotic fracture was 2.5 (95% CI, 1.3-4.7; P = 0.006). The G allele of the A163G was associated with significantly lower t-scores of both lower forearm BMD, heel BUA, and heel SOS as well as being significantly more frequent in the fracture patients compared to the controls. Patients with a combination of the highest quartile of S-OPG and presence of the G allele ( n = 23) had a significantly elevated fracture odds ratio, 4.0 (95% CI, 1.7-9.9). A significant negative association between S-OPG with peripheral measures of bone mass and with increased fracture odds ratios was found. Furthermore, the A163G mutation in the OPG promoter had a significant influence on bone mass and fracture status independently of S-OPG level.

Elevation in plasma total homocysteine (tHcy) is believed to be causally related to cardiovascular disease. Like age and sex, the thermolabile variant of methylenetetrahydrofolate reductase (MTHFR(C677T)) is an important nonmodifiable determinant of tHcy, which may be considered when describing normal ranges of tHcy in the general population. We investigated the simultaneous effect of sex, age, and MTHFR(C677T) genotype on the distribution of tHcy in a cross-sectional study design. THcy concentrations and MTHFR(C677T) genotype were determined in a population-based sample of 2,788 Danish men and women aged 30-60 years participating in the Inter99 Study. The prevalences of MTHFR(C677T) genotypes were 48.8% (CC), 42.4% (CT), and 8.8% (TT). The overall median tHcy was 8.1 micromol/l, and the 2.5-97.5 percentiles were 4.8-17.8 micro mol/l. The estimated proportionally higher level of tHcy in men compared to women was 14.3% (P<0.001). A significant interaction term was found between age and MTHFR(C677T) genotype (P<0.001). The estimated changes in tHcy per 5 years of age were 1.5% in CC individuals (P<0.01), 2.1% in CT individuals (P<0.001), and -4.1% in TT individuals (P<0.01). The T allele was associated with elevated tHcy. However, the proportionally higher level of tHcy in TT individuals compared to CT and CC individuals decreased with increasing age. The MTHFR(C677T) polymorphism explained 6% of the phenotypic variation in tHcy. In conclusion, we found that tHcy is associated with sex, age, and MTHFR genotype. Our results indicate that the effect of age is modified by MTHFR genotype., (Copyright 2003 Wiley-Liss, Inc.)

A genetic contribution to the development of osteoporosis is well documented. Although the association between the common allelic variation of apolipoprotein E (APOE), fracture risk, bone loss and bone mineral density (BMD) has been examined in several studies, the results of these investigations are contradictory. The aim of this study was to examine the association between polymorphisms of APOE, BMD of the lower forearm, quantitative ultrasound of the calcaneus and osteoporotic fractures in a population of postmenopausal women with hip or lower forearm fractures admitted to a department of orthopaedic surgery and age-matched controls from the population register. The APOE genotypes of 327 women were studied: 73 with lower forearm fractures, 43 with hip fractures and 211 age-matched controls. The participants were not receiving antiosteoporotic treatment. Polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP) was used to detect the APOE genotypes. Quantitative ultrasound was measured at the calcaneus. Bone mineral density (BMD) of the lower forearm was measured with dual-energy X-ray absorptiometry. The distributions of genotype frequencies in this study were: E2/E2: 0.3%; E2/E3: 16.5%; E2/E4: 2.5%; E3/E3: 54.7%; E3/E4: 24.2%; E4/E4: 1.8%. All subpopulations were in Hardy-Weinburg equilibrium. There was no association between bone mass parameters and the APOE allele groups. Logistic regression analysis did not show any association between fractures and APOE allele groups. In conclusion, this study showed no association between bone mass parameters (BMD, speed of sound (SOS), broadband ultrasound attenuation (BUA)), hip or lower forearm fracture and APOE genotypes in a population of postmenopausal women and age-matched controls.

Twin studies indicate a substantial genetic component in the development of osteoporosis. One of the latest studied candidate genes is the one coding for methylene tetrahydrofolate reductase (MTHFR) (C677T) in which a point mutation gives rise to a thermolabile variant of MTHFR. The aim of this study was to investigate the influence of this mutation on peripheral measures of bone density and on the odds ratios (OR) for hip and lower forearm fracture in a case control study of Danish postmenopausal women. A total of 74 women with lower forearm fracture, 41 women with hip fracture, and 207 age-matched controls were included. All had broadband ultrasound attenuation (BUA) and speed of sound (SOS) measured at the heel as well as bone mineral density (BMD) measured by dual X-ray absorptiometry at the distal forearm. The MTHFR (C677T) genotypes were determined using polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP). Only 2 of 21 individuals with the TT genotype had sustained a fracture as opposed to 46 of 142 with the CT genotype and 67 of 159 with the CC genotype (P = 0.007). Using logistic regression, the following odds ratios were found when comparing the individuals homozygotic for the C-allele with those homozygotic for the T-allele: lower forearm fracture OR = 3.93 (1.25; 12.40, P = 0.02), hip fracture OR = 6.99 (l.35; 36.92, P = 0.02) and the fractures combined OR = 4.33 (1.73; 10.81, P = 0.002). In this study, the MTHFR (C677T) genotypes were not significantly associated with BMD at the lower forearm or with ultrasound parameters measured at the calcaneus. However, a significant increase in the odds ratio of fracture was found for the wild-type C-allele.

Background: Pancreaticoduodenectomy is the only potentially curative treatment for peripapillary pancreatic tumors. However, postoperative morbidity and mortality are high, and different approaches have been tried to improve results, such as preoperative biliary drainage in patients with jaundice. This meta-analysis investigated the effect on postoperative outcome of preoperative biliary drainage by endoscopic biliary stent placement in patients who are jaundiced and who have peripapillary pancreatic tumors., Methods: A Medline search for the period 1985 to 2001 was performed. Eight retrospective studies and 2 prospective randomized controlled trials were included. Selection criteria for the primary analysis were as follows: patients with peripapillary pancreatic cancer, endoscopic stent placement versus no stent, radical surgery, and assessment of postoperative morbidity and mortality. A secondary analysis included both radical and palliative surgery., Results: In the primary analysis, 337 patients underwent preoperative endoscopic biliary stent placement, and 412 patients had no endoscopic biliary stent placement (controls). The overall odds ratio for postoperative complications (stent vs. no stent) is estimated as 0.79: 95% CI [0.36, 1.73] and the estimated odds ratio for postoperative mortality is 0.81: 95% CI [0.33, 1.99]. In the secondary analysis, 1008 patients underwent preoperative EBS versus 720 control patients. The odds ratio for postoperative complications in this analysis was 0.93: 95% CI [0.65, 1.33] and for postoperative mortality is 1.12: 95% CI [0.62, 2.01]., Conclusion: No evidence was found of either a positive or adverse effect of preoperative endoscopic biliary stent placement on the outcome of surgery in patients with pancreatic cancer.

Reduced physical activity or immobilisation have several negative effects on the skeleton. Significant reductions in bone mass have been observed after prolonged bed rest, in patients with injury to the spinal cord and hemiplegia, and after transitory immobilisation of the extremities, for instance after fractures. The aim of this literature review was to evaluate the effect of exercise on bone mass in elderly people and to determine whether exercise programmes could be appropriate in the prevention of fractures in this segment of the population. We identified four randomised and two non-randomised, prospective studies for the analysis of the effect of exercise on bone mass. Four studies reported a statistically significant difference in the intervention group, as compared to the control group, whereas two studies failed to find any significant differences in bone mass. We conclude that exercise has a beneficial and measurable effect on bone mass in the elderly, which may lead to a decline in the rate of fractures.

Background: To evaluate the prognostic value of screening for irregular antibodies late in pregnancy (third trimester) in rhesus positive women. Only those cases where irregular antibodies have not previously been demonstrated during routine screening in the first trimester with regard to clinically relevant complications in the newborn, were studied., Materials and Methods: All women living in Frederiksborg county and giving birth in 1996 (n = 4216) were assessed for inclusion in the study. This was done by gathering the files at the Hillerød and Hørsholm Hospitals' blood banks for antibody test results. Six hundred women were excluded because of the lack of either the rhesus type or the late antibody test., Results: Of the 3616 women, 3046 were rhesus positive, and 3012 of these had a negative first trimester screen test. Fifteen of the 3012 women later developed irregular antibodies in the third trimester, and were included in the study. This corresponds to only 0.5%, and none of these cases entailed perinatal complications for the mother or the child., Conclusion: Routine screening of rhesus positive pregnant women in the third trimester is not rational from a cost-benefit perspective, if the only purpose is to prevent hemolytic disease of the newborn.

Background: Dual-energy X-ray absorptiometry (DXA) measured at the lumbar spine and particularly at the hip remain the gold-standard for diagnosing osteoporosis. However, devices for assessing the peripheral skeleton present several advantages in terms of lower price and portability. A major concern when using peripheral densitometry is the poor correlation with the central measurements. The main aim of this study is, therefore, to assess the possibility of expressing ultrasound measurements at the heel and bone mineral density (BMD) measured at the distal forearm as fracture odds ratios rather than an absolute measure of bone mass., Methods: A total of 76 women with lower forearm fracture, 47 women with hip fracture and 231 age-matched women (controls) were included. All had broadband ultrasound attenuation (BUA) and speed of sound (SOS) measured at the heel using the DTU-one ultrasound scanner as well as BMD measured by dual X-ray absorptiometry on the DTX-200 at the distal forearm., Results: BUA, SOS and BMD at the distal forearm were all significantly lower in fracture patients compared with their respective control groups. The odds ratio for lower forearm fracture was 3.1 (95% CI: 1.8; 5.2) for heel-BUA (T-score cutoff: -2.3), 4.1 (2.3; 7.4) for heel-SOS (-2.1) and 2.2 (1.3; 3.7) for lower forearm BMD (-2.7). The odds ratio for hip fracture was 3.4 (1.5-7.7) for heel-BUA (-2.7), 3.6 (1.6; 8.1) for heel-SOS (-2.6) and 3.2 (1.4; 7.4) for lower forearm BMD (-2.9)., Conclusion: Peripheral densitometry can discriminate between hip- and lower forearm fracture patients and age-matched controls. Significantly elevated odds ratios for incurring these fractures can be calculated using device- and site specific t-score cutoff values. The results from this case-control study need to be confirmed by prospective cohort studies.

The World Health Organisation (WHO) has proposed a set of guidelines for the diagnosis of osteoporosis in adult women based on a measurement of bone mineral density (BMD) expressed as the number of SD below young adult mean (t-score). In this study, we investigated the number of subjects classified as either osteopenic or osteoporotic according to these guidelines using dual X-ray absorptiometry (DXA), at the hip, at the spine and at the lower forearm and quantitative ultrasound (QUS), at the heel. A total of 247 men, 209 postmenopausal women and 195 premenopausal women were included in the study. Furthermore, the study provides the first normative data showing the influence of sex, age and menopause on broadband ultrasound attenuation (BUA) and speed of sound (SOS), as measured by the DTU-one imaging ultrasound scanner. The difference between the number of patients classified into either diagnosis group by the investigated parameters is large ranging from 25.9% of the women being diagnosed as osteopenic by BUA at the heel to 43.0% by BMD at the femoral neck. For men, the same range is from 20.5% by BUA to 44.1% by BMD at the femoral neck. For the classification into the osteoporotic group, the range is from 2.5% by intertrochanteric BMD to 24.4% by BMD at Ward's triangle for women and from 0% by SOS to 29.0% by BMD at Ward's triangle for men. Using total hip BMD as the reference parameter to categorize the subjects as normal, osteopenic or osteoporotic, the agreement of the other parameters with this classification is assessed in terms of sensitivity and specificity. We conclude that there are significant differences in the classification of osteoporosis/osteopenia depending on the site measured and the technique used for the bone mass assessment. Furthermore, we suggest that development of technique and site specific cut-off values may increase the accuracy of the classification of osteoporosis/osteopenia in both men and women.

Quantitative ultrasound (QUS) bone measurement is a relatively new technique for the diagnosis of osteoporosis which is cheaper and easier to use than the more established method of bone densitometry (measurement of bone mineral density, BMD) by x-ray absorptiometry. The two QUS parameters currently measured are BUA (broadband ultrasound attenuation) and SOS (speed of sound). The reported age related changes for healthy women range from -0.27% to -1.62% per year for BUA and from -0.06% to -0.19% per year for SOS. Precision ranges from 1.0-3.8% (CV) for BUA and 0.19-0.30% (CV) for SOS. QUS is believed to reflect mainly BMD. However, studies indicate that QUS also reflects trabecular orientation and other determinants of bone strength independently of BMD. In both cross sectional and prospective studies, QUS seems to be as good a predictor of osteoporotic fractures as BMD.

The polymorphisms of the estrogen receptor (ER) gene defined by the restriction enodonucleases PvuII and XbaI have recently been reported to be associated with bone mineral density (BMD) in postmenopausal women. To investigate the possible relation of the PvuII and XbaI restriction fragment-length polymorphisms of the ER gene with BMD in Danish postmenopausal women, two studies were undertaken: 1) a cross-sectional study of 499 postmenopausal women, where the ER genotypes and alleles were related to BMD of the hip, spine, and lower forearm; and 2) a longitudinal study of 101 postmenopausal women followed up for 18 years. In the latter study, late postmenopausal bone loss in the hip and spine was determined over a period of 6 years in women (mean age of 63 to 69 years), and long-term postmenopausal bone loss in the lower forearm was determined over a period of 18 years in women (mean age of 51 to 69 years). Genotyping was performed through the restriction cleavage of polymerase chain reaction-amplified genomic DNA with the two restriction enzymes, PvuII and XbaI. Restriction fragment-length polymorphisms were represented as P or p (PvuII) and X or x (XbaI), with the lower case letters signifying the presence of the restriction site. The frequencies of the ER genotypes were similar to previously published genotype frequencies in Caucasian and Asian populations. No significant effect of the ER genotypes or alleles on BMD was found at any site, nor was there a relation between ER genotypes and the rate of bone loss either in the hip and spine over 6 years, or in the lower forearm over 18 years. In conclusion, we could not demonstrate any major effect of the ER gene polymorphisms on BMD or rate of bone loss in healthy postmenopausal Danish women.

The paper analyses the development of the total number of journal articles indexed in the Medline database published by authors affiliated to Denmark 1989-1998 in medicine compared to the development in the European Union during the same period. The publication analysis is then compared to the citation impact of articles published in the central journals indexed in Science Citation Index (ISI) 1987-1996 through use of the National Science Indicators (NIS, ISI) database. The total number of Danish journal articles has remained relatively constant compared to a 50% increase in the EU as a whole. The number of Danish articles published in central journals, however, has increased by 20% (compared to 27% for the EU) and the number of citations obtained by these articles by 58% (compared to 66% for the EU) in the 1987-1996 period. By population, Denmark ranked third in total number of articles in 1998. In conclusion, Denmark is very active in medical research but neither the quantity nor the quality of Danish medical research has increased at the same rate as the EU average.

Quantitative ultrasound measurements of the os calcis have recently been upgraded with imaging facilities. This has made measurements of a specific region of interest possible and improved the reproducibility of the method, but the diagnostic ability of imaging ultrasound has not yet been investigated thoroughly. We measured broadband ultrasound attenuation (BUA) and speed of sound (SOS) using imaging ultrasound as well as forearm bone mineral density (BMDarm) using dual-energy X-ray absorptiometry in three age-matched groups of women: (1) 25 women who were admitted to hospital due to a hip fracture; (2) 23 women who were admitted to hospital due to a fall without any fracture; and (3) 26 normal women. Furthermore, BMD of the hip (BMDhip) was measured in a subgroup of the hip fracture patients and those who had fallen. All measurements were performed during the index hospitalization in order to avoid any influence from bone loss due to immobilization after the fracture. We found a -0.48 SD deviation from expected age-matched values in BUA among the hip fracture patients, whereas the patients who had fallen showed a +0.16 SD deviance. For SOS, the figures were -0.70 SD for the hip fracture group and -0.06 SD for the patients who had fallen. For BMD of the arm we found values of -0.65 SD and +0.08 SD, respectively, whereas the figures for BMD of the hip were -0.66 SD and +0.13 SD, respectively. All parameters were significantly lower in the hip fracture group compared with the patients who had fallen. None of the parameters in the patients who had fallen deviated significantly from expected normal age-matched values. Neither BMD of the arm or BMD of the hip separated hip fracture patients and patients who had fallen significantly better than ultrasound (BUA or SOS) did. We conclude that imaging ultrasound (BUA or SOS) separates age-matched groups of hip fracture and non-fracture patients as well as BMD measurements do.

Broadband ultrasound attenuation was measured in 28 premenopausal women, 30 postmenopausal women, and 25 men using a new imaging device, the DTU-one. Short term in vivo precision was 1.2 CV%. The r-values for the correlation of BUA vs BMD at the hip, spine and lower forearm were 0.66, 0.64 and 0.62, respectively.

The aim of this study was to determine whether common allelic variation at the vitamin D receptor locus is related to bone mineral density and postmenopausal bone loss. Five hundred and ninety-nine healthy women aged 27 to 72 and 125 women with low bone mass aged 55-77 were measured once in a cross-sectional design. Furthermore, 136 women aged 45-54 were followed longitudinally for 18 years. The vitamin D receptor genotypes were determined using Polymerase Chain Reaction-Restriction Fragment Length Polymorphism analysis for three different polymorphic restriction sites (BsmI, ApaI and TaqI). Bone mineral density was measured by photon and X-ray absorptiometry. The cross-sectional study showed no significant relationship between vitamin D receptor genotype and bone mineral density. The maximum difference between homozygotes was 1.3%, P = 0.33, N = 723. The low bone mineral density group had virtually the same genotype frequencies as the normal bone mineral density group. The results of the longitudinal study showed that vitamin D receptor genotype was neither related to early postmenopausal bone loss: age 51-53 (total bone loss at the lower forearm: -3.6% [3.6%], mean [standard deviation]), late postmenopausal bone loss: age 63-69 (total bone loss at the hip: -6.2% [8.7%]) nor to long term postmenopausal bone loss: age 51-69 (total bone loss at the lower forearm: -24.5% [11.4%]). Using analysis of variance to test for differences in the rates of bone loss between the vitamin D receptor genotypes, P values ranged from 0.07 to 0.79. We conclude that common allelic variation at the vitamin D receptor locus as defined by the endonucleases ApaI, BsmI and TaqI is neither related to bone mineral density nor to the rate of bone loss in healthy postmenopausal Danish women.

Quantitative ultrasound (QUS) bone measurement is a promising, relatively new technique for the diagnosis of osteoporosis. Unlike to the more established method of bone densitometry [measurement of bone mineral density (BMD) e.g. using dual X-ray absorptiometry (DEXA)], QUS does not use ionizing radiation. It is cheaper, takes up less space and is easier to use than densitometry techniques. The two QUS parameters currently measured are broadband ultrasound attenuation (BUA) and speed of sound (SOS). The reported age-related changes for healthy women range from -0.27% to -1.62% per year for BUA and from -0.06% to -0.19% per year for SOS. Precision ranges from 1.0 to 3.8% (CV) for BUA and from 0.19 to 0.30% (CV) for SOS. The new method of imaging ultrasound has improved the precision of QUS measurements. QUS is significantly correlated with BMD. Studies with the latest equipment have shown r-values between 0.6 and 0.9 in site-specific measurements, and QUS is thus believed to reflect mainly BMD. However, other studies indicate that QUS measures something other than the actual mineral content of bone, namely bone quality, e.g. in vitro studies have shown that QUS reflects trabecular orientation independently of BMD. In both cross-sectional and prospective studies, QUS seems to be as good a predictor of osteoporotic fractures as BMD. In two large prospective studies, QUS also predicted fracture risk independently of BMD. QUS has just begun to be used systematically for monitoring the response to anti-osteoporotic treatments in prospective trials. In the studies performed, QUS has been found to be useful in the follow-up of patients. QUS is thus a promising new technique for bone assessment.

Quantitative ultrasound (QUS) bone measurement is a promising, relatively new technique for the diagnosis of osteoporosis. Contrary to the more established method of bone densitometry (measurement of bone mineral density, BMD, e.g., using dual X-ray absorptiometry, DEXA), QUS does not employ ionizing radiation. It has, however, been a problem to achieve sufficient reproducibility of the QUS measurements. The aim of this study is to evaluate the possible advantages of measuring broadband ultrasound attenuation (BUA) at a region of interest (ROI) instead of at a fixed position, in terms of in vivo precision and correlation to hip bone mineral density. BUA was measured in 27 premenopausal women, 28 postmenopausal women, an 22 men on the DTU-one. Using high resolution images, a ROI is defined in the posterior part of the os calcis as an area with a local minimum of attenuation and a fixed position within the os calcis is defined relative to the water bath. All BUA measurements were performed twice. BMD at the hip was measured on the QDR-2000. The mean BUA values were significantly different between pre- and postmenopausal women, p = 0.0001 for both the ROI (BUAROI) and the fixed position (BUAFIX). The ROI was found in all subjects and was readily reproducible. The precision at the ROI: 1.20 CV% (95% CI: 1.01-1.29 CV%) was significantly better than at the fixed position: 3.87 CV% (95% CI: 3.23-4.48 CV%). BUAROI (r = 0.64) correlated significantly better than BUAFIX (r = 0.35) with HIP BMD. In conclusion, the use of an imaging technique enables BUA measurements to be performed at a ROI. The precision of BUA at the ROI is significantly better than at the fixed position. BUA measured at the ROI correlates better with HIP BMD than BUA measured at the fixed position.

Objective: To determine whether common allelic variation at the vitamin D receptor locus is related to bone mineral density and postmenopausal bone loss., Design: Cross sectional and longitudinal population study., Setting: Outpatient clinic in research centre., Subjects: 599 healthy women aged 27 to 72 and 125 women with low bone mass aged 55-77 had bone mineral density measured once in the cross sectional study. 136 women aged 45-54 were followed up for 18 years in the longitudinal study., Main Outcome Measures: Bone mineral density measured at the lumbar spine, hip, and forearm and rate of bone loss at different times over 18 years in relation to vitamin D receptor genotype as defined by the endonucleases ApaI, EsmI, and TaqI., Results: Vitamin D receptor genotype was not related to bone mineral density at any site. The maximum difference between homozygotes was 1.3% (P = 0.33, n = 723). Women with low bone mineral density had almost the same genotype frequencies as the women with normal bone mineral densities. Vitamin D receptor genotype was not related to early postmenopausal bone loss from age 51 to 53 (mean (SD) total loss at the lower forearm -3.6% (3.6%)), late postmenopausal bone loss from age 63 to 69 (at the hip-6.2% (8.7%)), or to long term postmenopausal loss from age 51 to 69 (at the lower forearm-24.5% (11.4%))., Conclusion: Common allelic variation at the vitamin D receptor locus as defined by the endonucleases ApaI, EsmI, and TaqI is related neither to bone mineral density nor to the rate of bone loss in healthy postmenopausal Danish women.