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Biomedical subjects

L Nilas

Publications and source records attributed to L Nilas.

At least 37 records · Page 2Linked to original sources

Influence of menopause on serum lipids and lipoproteins.

The influence of the menopause on serum lipids and lipoproteins was examined longitudinally at 6-week intervals for 2-3 years in pre-menopausal women undergoing the menopause. Serum lipid and lipoprotein profiles were also examined cross-sectionally in 4 groups of pre-menopausal, peri-menopausal and post-menopausal women, who were followed up longitudinally at 3-monthly examinations for 1-2 years. The results covering 1360 examinations and 270 woman-years are reported here. Serum concentrations of total cholesterol (P = 0.001), low-density-lipoprotein (LDL) cholesterol (P = 0.001) and triglycerides (P less than 0.05) increased significantly as a consequence of the menopause and all increases occurred within 6 months of cessation of menstrual periods. High-density-lipoprotein (HDL) cholesterol decreased significantly (P less than 0.05) as a consequence of the menopause, but the decline occurred gradually over the 2 years preceding cessation of menses. In addition to the menopausal changes, serum concentrations of total cholesterol and LDL-cholesterol increased gradually in the pre-menopausal and post-menopausal years, but were significantly related to biological age only in the pre-menopausal groups (P less than 0.05). Serum triglycerides and HDL-cholesterol levels remained virtually unchanged in the pre-menopausal as well as the post-menopausal groups and were only influenced by the actual menopause. Serum lipids and lipoproteins are thus significantly altered as a consequence of the menopause. The result is a more atherogenic lipid profile which may partly explain the increased risk of cardiovascular disease observed in post-menopausal women.

Adult↗

The pathophysiology of peri- and postmenopausal bone loss.

Changes in sex hormones and bone turnover were studied longitudinally in 31 women aged 47-54 years who were approaching the menopause. Every 6 weeks for 2-3 years, hormones and biochemical estimates of the bone turnover were determined and the bone mass was measured at two forearm sites by single photon absorptiometry. Spinal bone mass was measured every 6 months. The bone turnover was normal in women aged 47-54 years with regular menstruation, whereas the estimates of bone resorption were high in the women with irregular menstruation. In nine women, who reached the menopause during the study, bone resorption increased significantly, whereas bone formation showed only a small increase. When the results of the nine women were combined with those of 50 women, who had passed a natural menopause within the preceding 3.5 years, the bone resorption indices reached their peak within the first postmenopausal year, whereas bone formation increased until 1.5-2 years after the last menstrual cycle. At the ultradistal forearm site the rate of bone loss was maximal (5% per year) immediately after the menopause and subsequently declined, which suggests that trabecular bone is more sensitive than cortical bone to changes in bone turnover. Spinal bone loss was identical in late peri- and early postmenopausal women. We conclude that bone resorption starts to increase during the last perimenopausal years, with a beginning acceleration in bone loss, which then becomes sharp after the menopause. The changes are related to the decline in oestrogens, but other mechanisms may also play a role.

Aged↗

Regional bone mineral in healthy and osteoporotic women: a cross-sectional study.

Regional bone mineral content and density (BMC and BMD) was measured in six regions (head, arms, chest, spine, pelvis, and legs) using dual photon 153Gd absorptiometry (DPA) in 128 healthy women aged 21-77 years, and in 45 women presenting with Colles' fracture (mean age 65 years), 46 women with vertebral crush or wedge fracture (mean age 68 years), and 27 women with femoral neck-fracture (mean age 74 years). The age-related normal bone loss was generalized, uniformly distributed, and best described by a combination of a premenopausal linear and a postmenopausal exponential regression in all six regions. Looking at BMD, the overall expected bone loss from age 20 to age 80 was approximately 20% in all the regions. When the fracture patients were examined, we found also generalized bone deficit as the prominent feature, amounting to about 20% of the premenopausal level for Colles' and spinal fractures, and about 25% for femoral neck-fracture. However, there was a regional bias in the fracture patients, as the Colles' and spinal fracture patients had a preferential reduction in spinal and pelvic BMD, whereas the patients with femoral neck-fracture had a preferential reduction in pelvic and leg BMD. We conclude that age-related and osteoporotic bone loss is generalized. Furthermore, we propose that regional differences in osteoporotic bone loss are brought about by a simple biological variability of the range of (i) relative amount of trabecular and cortical bone, (ii) rate of loss in the two types of bone tissue, and (iii) time of onset of trabecular relative to cortical bone loss.

Absorptiometry, Photon↗

Discriminative ability of total body bone-mineral measured by dual photon absorptiometry.

We investigated the discriminative ability of total body bone-mineral expressed as the total body bone-density (TBBD) measured by dual photon absorptiometry (DPA) in 79 healthy premenopausal women, 27 healthy postmenopausal women, and 120 female osteoporotic fracture patients presenting with either Colles' fracture, vertebral fracture or femoral neck-fracture. TBBD was compared to the bone-mineral density of the lumbar spine (BMDspine) also measured by DPA, and to the bone-mineral content of the forearms (BMCforearm) measured by single photon absorptiometry (SPA). TBBD, BMDspine and BMCforearm showed that all the fracture patient groups had significantly reduced bone-mass. Using receiver operating characteristic (ROC) analysis, we found that TBBD had a tendency towards better discriminative ability than BMDspine or BMCforearm with regard to the discrimination between healthy premenopausal women and the three types of osteoporotic fractures (not significant in spinal fracture patients). BMCforearm had an intermediate position, whereas BMDspine had the smallest discriminative ability. TBBD also discriminated better between healthy postmenopausal women and hip-fracture patients than BMDspine or BMCforearm, whereas there was no significant difference between the three methods regarding the discrimination between the healthy postmenopausal women and the Colles' and spinal fracture patients. We conclude that the TBBD measurement by DPA has a discriminative potential which is better than the local spine or forearm measurements.

Absorptiometry, Photon↗

Lack of seasonal variation in bone mass and biochemical estimates of bone turnover.

Three previous studies have indicated a seasonal variation in bone mineral content, with values during the summer being 1.7% to 7.5% higher than during the winter. We have examined the seasonal influence on both bone mass, biochemical estimates of bone turnover and vitamin D metabolites in 86 healthy women, aged 29-53 years. All participants were followed up for 2 years with examinations every 6 weeks or 3 months. Bone mineral content in the proximal and distal part of the forearm (single photon absorptiometry) did not reveal any significant seasonal variation, whereas bone mineral density of the lumbar spine (dual photon absorptiometry) indicated that the highest values occurred in winter. None of the biochemical parameters showed any statistically significant cyclical changes. Serum concentrations of 25-hydroxyvitamin D and 24,25-dihydroxyvitamin D3 showed a highly significant seasonal variation, whereas the serum 1,25-dihydroxyvitamin D concentration was virtually unchanged. We conclude that seasonal variation in bone mineral content and bone turnover should not be taken into account when interpreting data from longitudinal studies of healthy pre- and postmenopausal women on a sufficient vitamin D nutriture.

Adult↗

Rates of bone loss in normal women: evidence of accelerated trabecular bone loss after the menopause.

We have followed the changes in bone mass over 2 years in 42 premenopausal, seven perimenopausal and 76 postmenopausal women. The latter had passed a natural menopause between 6 months and 7 years previously. Bone mass was measured every 3 months at the proximal and distal forearm sites by single photon absorptiometry, and every 6 and 12 months in the lumbar spine and whole body by dual photon absorptiometry. The relative content of trabecular bone is approximately 15, 50, 60 and 20% at these four sites. Before the menopause there was a significantly low rate of bone loss from the two forearm sites and the whole body, whereas the spinal loss was insignificant. The rate of loss was five- to ten-fold higher at all sites after the menopause (P less than 0.001). With increasing menopausal duration the rate of loss declined at the two forearm sites and whole body (P less than 0.01). The distal forearm loss was larger than the proximal, both before and after the menopause (P less than 0.01). From the forearm results we thus conclude that a slightly larger loss of trabecular than cortical bone takes place both before and immediately after the menopause. The loss of both types of bone is, however, much larger after the menopause and this rapid bone loss seems to take place throughout the skeleton.

Adult↗

Age-related bone loss in women evaluated by the single and dual photon technique.

Bone mass and density were measured at two forearm sites (proximal and distal BMC/BMD) and in the spine (spinal BMC/BMD) by respectively single and dual photon absorptiometry in 141 healthy women aged 20-80 years. The proximal forearm site contains approximately 15% trabecular bone and the distal site equal amounts of trabecular and cortical bone. At all three sites linear regression analysis on pre- and postmenopausal women separately revealed accelerated decline in bone density after the menopause. Polynomial regressions in BMC and BMD versus menopause-adjusted age fitted the changes better than a linear regression in the peripheral skeleton, but not in the spine. In both the forearms and the spine the age-related reduction in bone could be described by a combined model, assuming a linear decrease before the menopause and an exponential one thereafter. According to this model, the premenopausal annual changes were 0.067% (proximal site), 0.187% (distal site) and 0.098% (spine). The annual changes during the first postmenopausal year were 3.7, 3.7 and 4.6%. No matter which model was applied to the data, the reduction in the oldest women was lowest in the spine. These data indicate that there are some small differences in the age-related changes in cortical and trabecular bone, but that the reduction of both types of bone accelerates after the menopause.

Adult↗

Long-term precision of dual photon absorptiometry in the lumbar spine in clinical settings.

We have investigated the long-term in vivo precision of a dual photon spine scanner using three different Gd sources and compared it with that of the single photon scanner. Standard values were significantly different with the three Gd sources. With the second there was also a systematic increase of 2% per 60,000 cps in the 44 KeV channel as the source decayed, whereas no such shift was found with the other two sources. This resulted in a significant in vivo intrasource (P less than 0.05) and intersource (P less than 0.01) variation and a six-month reproducibility ranging from 3.7 to 8.1%. After correction for these systematic errors the clinically important 2-year reproducibility in 26 premenopausal women was 3.4 +/- 1.3% for spinal BMC and 3.7 +/- 1.7% for spinal BMD. In comparison, the forearm single photon scanner had a long-term precision of 1.0 +/- 0.3%. With the presented techniques spinal measurements may therefore require 11.6 times (3.4(2):1.0(2] as many participants as the forearm measurements to detect the same changes in bone mass.

Adult↗

Accuracy of lumbar spine bone mineral content by dual photon absorptiometry.

The accuracy of measurement of the bone mineral content (BMC, g) and bone mineral density (BMD, g/cm2) of the lumbar spine by dual photon absorptiometry (DPA) was estimated by means of two different spine scanners (a Nuclear Data 2100 and a Lunar Radiation DP3). The lumbar spines of 13 cadavers were used. BMC and BMD were measured in situ and on the excised vertebrae in a solution of water/ethanol; and covered with ox muscle/porcine muscle/lard. The actual mineral weight and areal density were determined after chemical maceration, fat extraction, drying to a constant weight, ashing for 24 hr at 600 degrees C, and correction for the transverse processes. The true are was measured by parallax free X rays and planimetry. All measurements of BMC or BMD were highly interrelated (r = 0.94-0.99). The standard error of estimate (s.e.e.) of BMC in situ versus BMC in water/ethanol was 5.2%. The agreement between the BMD values of the two scanners was very good (s.e.e. = 2.9%). BMC in situ predicted the actual vertebral mineral mass with an s.e.e. of 8.1%. BMD in situ and BMD in water/ethanol predicted the actual area density with s.e.e.s of 10.3% and 5.0%, respectively. This study discloses the correlation and accuracy error of spinal DPA measurements in situ in whole cadavers versus the actual BMC and BMD. The error, which is underestimated in in vitro studies, amounts to 10%.

Adult↗

Whole body retention of 99mTc-diphosphonate. Relation to biochemical indices of bone turnover and to total body calcium.

Whole body retention (WBR) and urinary excretion (UE) of 99mTc-diphosphonate were determined in 161 healthy adults and the results were compared to accepted biochemical markers of bone turnover. WBR was corrected for total body bone mineral (TBBM) and UE for forearm bone mineral content (BMC). Both uncorrected and corrected retention measurements were highly significantly correlated to the biochemical markers (P less than 0.001), but the r values were low (0.22-0.64). All bone turnover variables demonstrated considerably higher levels of bone turnover in postmenopausal women than in premenopausal women (P less than 0.001), whereas the variables were unchanged with age in men. The correction of WBR for TBBM and UE for BMC increased the validity of the retention methods and the two calculations gave exactly the same results on a group basis, both demonstrating significantly higher bone turnover in women than in men in each age group (P less than 0.05-P less than 0.001). All the turnover variables were measured in a group of perimenopausal women (n = 33). The data clearly demonstrated that bone turnover is menopause dependent, whereas age in itself is of minor significance.

Adult↗

Long-term effects of percutaneous estrogens and oral progesterone on serum lipoproteins in postmenopausal women.

Serum lipids and lipoproteins were examined in a group of 45 healthy postmenopausal women who were treated for 2 years with either 3 mg of percutaneous estradiol (n = 20) or placebo (n = 25). Percutaneous estradiol was given alone during the first year of treatment and in combination with oral micronized progesterone (200 mg) for 12 days of each cycle during the second year. The women were examined every 3 months throughout the 2 years. Percutaneous estrogen therapy significantly reduced total serum cholesterol and low-density lipoprotein cholesterol, whereas no significant differences were observed in serum triglycerides and high-density lipoprotein cholesterol. Addition of oral progesterone during the second year of treatment did not produce any significant alterations in serum total cholesterol or low-density lipoprotein cholesterol, both of which remained significantly reduced. Serum triglycerides remained virtually unchanged, whereas a slight but significant increase (p less than 0.05) was observed in high-density lipoprotein cholesterol levels at the end of the study period. We conclude that percutaneous estrogen administration produces changes in total serum cholesterol and low-density lipoprotein cholesterol levels similar to those observed after oral estrogen administration. However, the magnitude and time course of the response seem to be modulated by the route of administration. Addition of oral micronized progesterone does not influence the beneficial estrogenic actions on serum lipids and lipoproteins and seems to be a proper "progestogen" in percutaneous estrogen therapy.

Administration, Cutaneous↗

Vitamin D deficiency after highly selective vagotomy.

While bone disease is occasionally seen after gastrectomy, the influence of vagotomy on calcium and vitamin D metabolism is uncertain. We have, therefore, investigated 23 male patients who had undergone highly selective vagotomy for ulcer 4.3 +/- 1.2 years previously. The 25OHD concentrations were decreased (p less than 0.05), the 1,25(OH)2D concentrations elevated (p less than 0.05) and the immunoreactive parathyroid hormone concentrations normal. Local and total bone mass were normal compared to age-matched men, and there was no biochemical evidence of increased bone turnover. We suggest that the changes in calcium absorption, which are described in the literature after vagotomy, are mediated by 1,25(OH)2D. Although the changes in vitamin D metabolism do not lead to calcium-metabolic disturbances in selected patients, we believe that some will eventually develop vitamin D deficiency and that vitamin D supplementation should be considered.

Adult↗

Dietary calcium intake and blood pressure in normotensive subjects.

Epidemiological and prospective studies in man and animals have indicated an inverse relationship between calcium intake and cardiovascular mortality and blood pressure (BP). We have therefore studied the effect of dietary calcium on blood pressure in two groups of women. In a cross-sectional study 103 early postmenopausal women were stratified into three groups according to daily calcium intake calculated from a questionnaire. Both diastolic and systolic blood pressures were identical in the three groups. We thereafter conducted a prospective placebo-controlled trial on the effect of calcium supplementation. Twenty-eight healthy women were randomized to placebo treatment (n = 14) or calcium supplementation 2,000 mg daily (n = 14) for one year. In both groups BP remained at initial levels throughout the study and was identical in the two groups at measurements every three months. We thus conclude that calcium supplementation has no effect on BP in normotensive subjects on a high calcium diet.

Blood Pressure↗

Bone mass and its relationship to age and the menopause.

To examine the influence of age and the menopause on bone loss we studied 178 healthy women, aged 29-78 yr. Bone mass was measured at 2 forearm sites, in the total spine, in the lumbar spine, and in the whole body by single and dual photon absorptiometry. Women of the same age but different menopausal status had significantly different bone masses, whereas a 5-yr difference in age had no effect on bone mass in women with the same menopausal status. At the menopause the hormone changes (low serum estrogen and high serum gonadotropin levels) occurred simultaneously with the appearance of biochemical indices of increased bone turnover. Neither biochemical values nor bone measurements indicated significant bone loss before the menopause. We conclude that the menopause has a greater effect on bone loss than does chronological age.

Adult↗

Does calcium potentiate the effect of estrogen therapy on postmenopausal bone loss?

Calcium metabolism were examined in 66 healthy postmenopausal women every 3 months during 2 years of treatment with oral or percutaneous 17 beta-estradiol combined with different doses of calcium supplementation. Bone mineral content measured in the forearm (single photon absorptiometry) in the spine and in the total skeleton (dual photon absorptiometry) was unchanged in all estrogen-treated groups during the two years of treatment, and the responses in the groups with and without calcium supplementation were not significantly different. Furthermore, the responses were independent of route of administration of the estrogen. Biochemical indices of bone turnover (serum alkaline phosphatase and fasting urinary hydroxyproline/creatinine) decreased highly significantly during estrogen treatment (P less than 0.001) independent of route of administration of the estrogen and of the calcium supplementation. We conclude that calcium supplementation has no additive effect to estrogen therapy in the prevention of the early postmenopausal bone loss.

Calcium↗

Bone composition in the distal forearm.

Recent data have indicated that measurements of bone mass in the very distal part of the forearm is superior to more proximal measurements in identifying osteoporosis. Bone slices from the distal part of the forearm were obtained from 16 necropsies and the trabecular fraction of the total dry bone weight was measured in adjacent bone slices, 8 mm thick. Prior to autopsy bone mass at the corresponding sites was measured using a multipath single photon absorptiometric method by which scans are obtained proximal (proximal BMC) and distal (distal BMC) to the site, where the ulna and radius are 8 mm apart. The accuracy of bone measurements at the two sites was virtually similar (r = 0.98 and r = 0.94, respectively). In both areas the amount of trabecular bone increased towards the metaphysis with a trabecular/cortical ratio ranging from 10 to 60% (wt/wt). If bone composition is known it is possible to estimate rates of bone loss from the two compartments.

Adult↗

Usefulness of regional bone measurements in patients with osteoporotic fractures of the spine and distal forearm.

Bone mineral mass was measured in normal subjects and osteoporotic patients at two forearm sites (proximal and distal of the 8 mm site between the two forearm bones) by single photon absorptiometry and in the spine and whole body by dual photon absorptiometry. There were no signs of preferential low spinal bone mass in 28 patients with vertebral fractures. Their bone mass was at all sites 26% to 37% lower than the premenopausal mean value and 7% to 13% lower than in age-matched normal women. In 45 patients with forearm fractures bone reduction was also universal but only 3% to 6% lower than in healthy women of comparable age. The spinal bone mass in all the patients was significantly related to both forearm measurements with coefficients of correlation of 0.58-0.61 and s.e.e. of 18%. Compared to the premenopausal normal range the distal forearm site had a greater sensitivity in identifying patients with vertebral fractures than had the spinal measurement (chi-square test, p less than 0.01). We thus conclude that patients with vertebral fractures have universal osteoporosis and that measurement of spinal BMC had no predictive advantages over that of the forearm bone mass for population studies.

Aged↗