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Biomedical subjects

B Abrahamsen

Publications and source records attributed to B Abrahamsen.

34 records · Page 2Linked to original sources
PubMed2001

Discordance between changes in bone mineral density measured at different skeletal sites in perimenopausal women--implications for assessment of bone loss and response to therapy: The Danish Osteoporosis Prevention Study.

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; p < 0.01), 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; p < 0.01). 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.

Absorptiometry, Photon↗
PubMed2000

Hormonal replacement therapy reduces forearm fracture incidence in recent postmenopausal women - results of the Danish Osteoporosis Prevention Study.

OBJECTIVES: To study the fracture reducing potential of hormonal replacement therapy (HRT) in recent postmenopausal women in a primary preventive scenario. METHODS: Prospective controlled comprehensive cohort trial: 2016 healthy women aged 45-58 years, from three to 24 months past last menstrual bleeding were recruited from a random sample of the background population. Mean age was 50. 8+/-2.8 years, and the number of person years followed was 9335.3. There were two main study arms: a randomised arm (randomised to HRT; n=502, or not; n=504) and a non-randomised arm (on HRT; n=221, or not; n=789 by own choice). First line HRT was oral sequential oestradiol/norethisterone in women with intact uterus and oral continuous oestradiol in hysterectomised women. RESULTS: After five years, a total of 156 fractures were sustained by 140 women. There were 51 forearm fractures in 51 women. By intention-to-treat analysis (n=2016), overall fracture risk was borderline statistically significantly reduced (RR=0.73, 95% CI: 0.50-1.05), and forearm fracture risk was significantly reduced (RR=0.45, 95% CI: 0.22-0.90) with HRT. Restricting the analysis to women who had adhered to their initial allocation of either HRT (n=395) or no HRT (n=977) showed a significant reduction in both the overall fracture risk (RR=0.61, 95% CI: 0.39-0.97) and the risk of forearm fractures (RR=0.24, 95% CI: 0.09-0.69). Compliance with HRT was 65% after five years. CONCLUSIONS: It is possible to reduce the number of forearm fractures and possibly the total number of fractures in recent postmenopausal women by use of HRT as primary prevention.

Age Factors↗
PubMed2000

Cytokine RNA levels in transiliac bone biopsies from healthy early postmenopausal women.

The cytokines interleukin-1beta (IL-1beta), tumor necrosis factor-alpha (TNF-alpha), and IL-6 induce osteoclast formation and may contribute to the development of postmenopausal osteoporosis. Cross-sectional studies have suggested that both IL-1 and IL-1ra secretion increase on estrogen withdrawal, and that postmenopausal osteoporosis is associated with an inadequate increase in monocyte IL-1ra secretion with age. We measured cytokine mRNA (IL-1beta, IL-1ra, IL-6, and TNF-alpha) directly in bone biopsies from early postmenopausal women to determine if a lower compensatory increase in IL-1ra mRNA could be demonstrated in women with rapid bone loss after the menopause. Biopsies were obtained from 23 early postmenopausal women (mean age 53.9 years) who participated in a randomized study of hormone replacement therapy (HRT) and risk factors for osteoporosis. Bone mineral density was assessed by duel energy X-ray absorptiometry at 0, 1, 2, and 5 years. Women in the control group were recruited to the biopsy study based on their observed rate of bone loss (upper or lower tertile). Consent was also obtained from 11 participants receiving HRT. Biopsies were taken at 2 years, frozen in nitrogen, and homogenized. Cytokine mRNA was measured by competitive reverse transcriptase polymerase chain reaction. The IL-1ra/IL-1beta mRNA slope for the slow-loss group was steeper (deltaF = 23.3, p < 0.01) than that observed in the fast-loss group, indicating that slower bone loss was associated with higher IL-1ra mRNA levels relative to IL-1beta. During HRT, the IL-1beta mRNA level was inversely correlated with serum estradiol (log r2 = 0.77, p < 0.01), and women with a serum estradiol below 200 pmol/L during HRT had IL-1beta, mRNA levels identical to the control group. In contrast, IL-1ra mRNA was independent of serum estradiol. Histomorphometric analysis revealed weak correlations between IL-1beta mRNA and activation frequency (r2 = 0.26, p = 0.06) and between IL-1ra and volume referent bone resorption rate (r2 = 0.19, p = 0.11). TNF-alpha was not associated with the bone loss rates or with serum estradiol, and only three samples were positive for IL-6 mRNA. The findings support the hypothesis that IL-1beta production within bone increases with declining estrogen levels, and that an increase in II-1ra protects against accelerated bone loss.

Base Sequence↗
PubMed2000

Correlations between insulin sensitivity and bone mineral density in non-diabetic men.

AIMS: To investigate relationships between bone mineral density (BMD), insulin secretion and insulin sensitivity, controlling for body composition, in view of data suggesting that hyperglycaemia [corrected] leads to decreased osteoblast proliferation and a negative calcium balance and that insulin stimulates osteoblast differentiation and collagen synthesis, with no clear evidence if this response in impaired in insulin resistance. METHODS: Femur and whole body (WB) BMD was measured in 55 male patients with ischaemic heart disease and 40 healthy men, using a Hologic QDR-2000 densitometer. Insulin sensitivity (Si) was estimated as the rate of glucose disappearance divided by the area under the insulin curve during an intravenous glucose tolerance test. RESULTS: Insulin and C-peptide levels were not correlated with BMD, but Si was a significant predictor of femur (log, r = 0.35) and WB BMD (log r = 0.29, both P<0.01), even after controlling for weight and age. Fat mass (FM) was a predictor of BMD (femur: r = 0.33 P<0.01, WB: r = 0.43 P<0.001). In the femur the association with FM disappeared when log(Si) was entered in the regression. Lean body mass (LBM) contributed significantly to BMD (r = 0.50 and r = 0.66, both P<0.001). CONCLUSIONS: These results are compatible with a direct influence of lean body mass on bone, while the impact of fat mass may consist of insulin resistance with increased insulin exposure of bone. It is hypothesized that patients with insulin resistance in the metabolic pathway do not exhibit resistance to the skeletal actions of insulin.

Blood Glucose↗
PubMed2000

Cytokines and bone loss in a 5-year longitudinal study--hormone replacement therapy suppresses serum soluble interleukin-6 receptor and increases interleukin-1-receptor antagonist: the Danish Osteoporosis Prevention Study.

The proinflammatory cytokines interleukin-1 beta (IL-1 beta) and IL-6 may play a central role in the acceleration of postmenopausal bone loss, but observational studies have led to contradictory results. Estrogen-dependent changes in the production of IL-1 receptor antagonist (IL-1ra) and the soluble IL-6 receptor (sIL-6R) potentially modify cytokine bioactivity. We therefore assessed the impact of menopause and hormone replacement therapy (HRT) on cytokines and activity modifiers in serum within a 5-year longitudinal study. One hundred sixty perimenopausal women (age 50.1 +/- 2.8 years) were randomized to HRT or no treatment. Serum IL-6 increased with age (r = 0.16; p < 0.05), but cytokines did not correlate with baseline bone mineral density (BMD). HRT led to small increases in IL-1ra (p < 0.001) and IL-6 (p < 0.05), with a decrease in sIL-6R (p < 0.01) and no change in IL-1 beta. No changes were observed in the control group. IL-1ra was inversely correlated with bone loss at the ultradistal forearm (r = 0.29; p < 0.05) and to a lesser degree at the spine (r = 0.20; p = 0.09). In addition, there was a weak positive correlation between sIL-6R and bone loss at the ultradistal forearm (r = 0.26; p < 0.05). High IL-6 levels were associated with slower bone loss (spine r = 0.31, p < 0.01) and controlling for age did not diminish this association. The percent change in sIL-6R during HRT was correlated with the bone loss at the femoral neck (r = -0.29; p < 0.01) and weakly with bone loss in the spine (r = -0.16; p = 0.17). In conclusion, serum IL-1ra and sIL-6R are influenced by HRT and are associated with the rate of bone loss in perimenopausal women.

Adult↗
PubMed1998

Vitamin D receptor alleles do not predict bone mineral density or bone loss in Danish perimenopausal women.

A BsmI restriction enzyme polymorphism in the vitamin D receptor (VDR) gene has been reported to be associated with bone mineral density (BMD) and bone turnover. However, findings in other studies suggest the presence of considerable interaction by race, body size, and environmental factors. Therefore, we VDR BsmI genotyped 200 healthy perimenopausal Danish white women (mean age 50.8 years, mean calcium intake 900 mg/day) in a comprehensive, longitudinal, community-based population study. Bone loss was assessed by dual-energy X-ray absorptiometry (DXA) using cross-calibrated Hologic QDR-1000W and QDR-2000 densitometers, with a mean follow-up period of 4 years (range 1-5 years). Despite a distribution of genotypes similar to that of other white populations (28% bb, 49% Bb, 23% BB), VDR genotypes were not associated with lumbar or femoral baseline BMD, subsequent bone loss rates, or biochemical markers of bone metabolism (bone-specific alkaline phosphatase, urinary hydroxyproline, and serum osteocalcin). Controlling for body size, calcium intake, and serum levels of 25-hydroxyvitamin D3 [25(OH)D3] did not alter this finding. The possible existence of a threshold effect was subsequently investigated by restricting analysis to women with low serum 25(OH)D3 levels or low calcium intake. VDR BsmI genotypes showed no significant impact on bone density or bone loss in healthy Danish early postmenopausal women, even when allowance was made for calcium intake, serum 25(OH)D3, and body size.

Absorptiometry, Photon↗
PubMed1998

Diagnosis of osteoporosis by planar bone densitometry: can body size be disregarded?

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.

Absorptiometry, Photon↗
PubMed1997

Improving compliance with hormonal replacement therapy in primary osteoporosis prevention.

OBJECTIVES: 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. MATERIAL AND METHODS: 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. RESULTS: 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%, P < 0.001 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, P < 0.001) 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, P < 0.01). CONCLUSIONS: 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.

Cohort Studies↗
PubMed1997

Cytokines and T-lymphocyte subsets in healthy post-menopausal women: estrogen retards bone loss without affecting the release of IL-1 or IL-1ra.

Interleukin (IL)-1 is a potent inducer of bone resorption, and an increased secretion of the IL-1 agonists IL-1 alpha and IL-1 beta relative to the IL-1 receptor antagonist (IL-1ra) has been proposed as a mechanism leading to post-menopausal osteoporosis. T-lymphocytes are capable of secreting bone resorptive cytokines and have also been linked with bone metabolism and the development of osteoporosis. Cytokine secretion from whole blood cell cultures was compared between two randomized groups of healthy early post-menopausal women (mean age 52.5 yrs, N = 91) and lymphocyte subsets were quantitated by flow cytometry. One group received cyclic estrogen-gestagen replacement therapy (ERT) while the other group was untreated. In spite of a significant bone maintaining effect of ERT, the basal and LPS-stimulated secretion of IL-1 alpha, IL-1 beta, and IL-1ra was identical in the two groups. There was no association between cytokine release and bone mass or loss assessed over 2 yrs. The only exception was a weak estrogen-independent correlation between basal IL-1ra secretion and bone loss (r = -0.21, p < 0.05). Flow cytometry did not confirm a relationship between CD4/CD8 T-cell ratios and bone density or loss, and there was no effect of ERT on lymphocyte subsets. The number of CD3+ CD56+ T-cells showed a highly significant negative correlation with femoral and lumbar bone density in untreated women (r = -0.42, p < 0.01) similar to that found in patients with established osteoporosis, indicating that these adherent mononuclear cells may be important in the pathophysiology of post-menopausal bone loss. The possibility that IL-1ra acts as an independent bone-sparing factor unrelated to estrogen withdrawal warrants further investigation. In conclusion, ERT maintains bone without affecting the release of the IL-1 family of cytokines in whole blood cultures.

Bone Density↗
PubMed1997

Site of osteodensitometry in perimenopausal women: correlation and limits of agreement between anatomic regions.

Because the bone mineral density (BMD) in different anatomic regions is heterogenous the number of women who fulfill the World Health Organization definition of osteopenia or osteoporosis increases with the number of regions examined. The purpose of this study was to investigate the agreement between measurements of the spine, femur, forearm, and whole body following menopause. Two thousand and five healthy, perimenopausal women, mean age 50.6 years, were studied using Hologic QDR-1000/W and QDR-2000 densitometers. Though the BMD of different anatomic regions were correlated (r = 0.40-0.77, p < 0.01), the variability in each patient regarding T and Z scores between regions was considerable. For example, despite a high correlation (r = 0.67, p < 0.01) and no systematic difference between the T scores for total femoral and lumbar BMD, the limits of agreement (mean difference +/- 2 SD) for the comparison were -1.89 to 1.87. Femoral neck T scores were 0.5 SD lower than those of the other regions, confirming reports that the young adult reference for this measurement is disproportionally high. The prevalence of osteoporosis was 1.2% when femur total BMD was considered alone and 5.9% when lumbar and ultradistal forearm results were included. However, as many as 7.9% showed osteoporosis of the femoral neck when the Hologic T score was used, compared with 0.7% using National Health and Nutrition Examination Survey (NHANES) values. The choice of anatomic region and availability of appropriate young adult reference data has considerable impact on the apparent prevalence of osteoporosis. Given the heterogeneity between regions, a combination of spinal and femoral densitometry should be used in diagnosing osteoporosis, though this increases the prevalence of osteoporosis by 50% or more in perimenopausal women.

Absorptiometry, Photon↗
PubMed1996

Impact of hemodialysis on dual X-ray absorptiometry, bioelectrical impedance measurements, and anthropometry.

Dual X-ray absorptiometry (DXA) performs noninvasive assessment of bone and soft tissue with high precision. However, soft tissue algorithms assume that 73.2% of the lean body mass is water, a potential source of error in fluid retention. We evaluated DXA (model QDR-2000; Hologic Inc, Waltham, MA), bioelectrical impedance analysis (BIA), and simple anthropometry in 19 patients (9 women and 10 men, mean age 46 y) before and after hemodialysis, removing 0.9-4.3 L (x: 2.8L) of ultrafiltrate. The reduction in fat-free mass (FFM) measured by DXA was highly correlated with the ultrafiltrate, as determined by the reduction in gravimetric weight (r = 0.975, P < 0.0001; SEE: 233 g), whereas BIA was considerably less accurate in assessing FFM reductions (r = 0.66, P < 0.01; SEE: 757 g). Lumbar bone mineral density (BMD) was unaffected by dialysis, as were whole-body fat and BMD. Whole-body bone mineral content, however, was estimated to be 0.6% lower after dialysis. None of the simple anthropometric measurements correlated significantly with the reduction in FFM. In an unmodified clinical setting, DXA appears to be superior to other simple noninvasive methods for determining body composition, particularly when the emphasis is on repeated measurements.

Absorptiometry, Photon↗
PubMed1995

Cross calibration of QDR-2000 and QDR-1000 dual-energy X-ray densitometers for bone mineral and soft-tissue measurements.

Replacement of dual energy X-ray densitometry (DXA) equipment may be necessary in many labs with time, or new equipment may be added. In this context we compared patient scans between a Hologic QDR-1000W and a QDR-2000 (n = 29-43, depending on anatomic region) and between QDR-2000 single beam (SB) and fan beam (FB) modes (n = 40-62) as a quality control measure. A total of 83 subjects (79 females and four males) with a wide range of bone mineral densities (BMD) were studied. There was a linear relationship between results with the QDR-1000W and QDR-2000 in SB mode, and between SB and FB mode on the QDR-2000, but the magnitude of the coefficients and constants differed for the different anatomic regions. In SB mode the QDR-2000 underestimated whole body and forearm BMD by 3% relative to the QDR-1000W, even after cross calibration using a spine phantom. Femoral total BMD was slightly, but not significantly, underestimated. Thus, additional postanalysis correction had to be applied to forearm and whole-body scans. In FB with the QDR-2000, spine and whole-body BMD was underestimated by 3%, but femur total and neck BMD was overestimated by 2.2 and 2.8%, respectively, compared with SB scans on the same device. Soft-tissue composition with FB (enhanced analysis protocol) on the QDR-2000 differed greatly from that obtained using SB (standard protocol). Lean tissue mass was 4 kg lower and fat mass 4 kg higher in FB mode.(ABSTRACT TRUNCATED AT 250 WORDS)

Absorptiometry, Photon↗
PubMed1992

[Angina pectoris after sumatriptan (Imigran)].

Developed for the treatment of migraine, sumatriptan is an agonist of 5-hydroxytryptamine-1-receptors. Though a pressure sensation is a common complaint, significant ECG changes have not been reported after subcutaneous administration of sumatriptan. A case history is given where angina pectoris after sumatriptan self-administration was experienced on two occasions by a 61-year old man with a history of minor myocardial infarction--without post-infarction angina--two years previously. The angina after sumatriptan was accompanied on both occasions by significant ST-segment depression on ECG-monitoring. An extracranial vasoconstrictor action of sumatriptan in patients with ischaemic heart disease is suggested.

Angina Pectoris↗
PubMed1992

Relevance of Ki-67 expression in the classification of non-Hodgkin's lymphomas: a morphometric and double-immunostaining study.

The proliferation of reactive and neoplastic cells was retrospectively assessed in 92 cases of non-Hodgkin's lymphoma by morphometry using a double-immunoenzymatic technique including surface markers and the monoclonal antibody Ki-67. The findings were compared with the histological diagnosis. The overall Ki-67 positivity is not always a good measure of the corresponding corrected values and therefore we recommend that a correction should be made for the total number of complementary lymphocytes in the tumour. Taking the macrophages and the Ki-67 positivity of the reactive cells into account does not generally add any information. There was no difference in reactive cell content between follicular (counted within follicles) and diffuse lymphomas within the tumour areas. The value of the group mean for low-grade follicular (nodular) lymphomas was significantly higher than that of diffuse low-grade lymphomas, but not significantly different from that of intermediate-grade lymphomas. High-grade lymphomas exhibited significantly greater Ki-67 positivity than those of intermediate grade. In 76% of the cases there was significant agreement between malignancy grade (low/intermediate malignant versus high malignant) at 45% corrected Ki-67 counts.

Adolescent↗
PubMed1988

Periodontal health in a group of industrial employees.

The aim of this study was to evaluate the dental health conditions of male employees in a large aluminum factory. The present report deals only with the periodontal findings. Five percent of the 181 examined subjects between 25 and 60 yr were edentulous, and all dentate individuals had some degree of periodontal disease. Surfaces harboring stainable plaque were high in all age groups, varying between 65 and 85%. Surfaces without retention factors were 31% and decreased with increasing age. The percentage of sites with bleeding increased from about 40% in the lowest to about 60% in the highest age group. Teeth with probing depths greater than or equal to 4 mm increased from about 30% in the age group 25-29 yr to about 45% in the age group 30-34 yr, after which it increased gradually with increasing age. The difference in bone scores (marginal bone loss) was the most extensive between the ages of 25 and 34 yr, but with a significant increase throughout the age groups. The administrators had a somewhat better oral hygiene, fewer retention factors, less bleeding, fewer pockets and some more marginal bone support than the workers. Still, the administrators had more missing teeth than the workers.

Adult↗