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Biomedical subjects

K Overgaard

Publications and source records attributed to K Overgaard.

At least 37 records · Page 2Linked to original sources
PubMed1996

The impact of degenerative conditions in the spine on bone mineral density and fracture risk prediction.

We examined the impact of degenerative conditions in the spine (osteophytosis and endplate sclerosis) and aortic calcification in the lumbar region on bone mineral content/density (BMC/BMD) measured in the spine and forearm by absorptiometry and on fracture risk prediction. The radiographs of 387 healthy postmenopausal women, aged 68-72 years, were assessed in masked fashion for the presence of osteophytosis, endplate sclerosis and aortic calcification in the region from L2 to L4. Vertebral deformities/fractures were assessed by different definitions. Osteophytes larger than 3 mm and in numbers of 3 or more resulted in a significantly (12%) higher spinal bone mass (p < 0.001). Endplate sclerosis had a similar effect (p < 0.001). In subjects with both degenerative conditions the BMC/BMD in the spine and forearm were significantly higher than in unaffected women (19% in the spine, 10% in the forearm; p < 0.001). The spinal BMD values were significantly lower in fractured women if both degenerative conditions were absent (p < 0.001), whereas fractured and unfractured women had similar values if degenerative conditions were present. Degenerative conditions did not alter the ability of forearm BMC to discriminate vertebral or peripheral fractures. Receiver operating characteristic (ROC) curves (true positive fraction versus false positive fraction) were generated for BMD of the lumbar spine and BMC of the forearm with regard to the discrimination between women with vertebral and peripheral fractures and healthy premenopausal women. The ROC curves for women without degenerative conditions were consistently above the curves for women affected by osteophytosis and endplate sclerosis in the lumbar spine (p < 0.001). In conclusion, osteophytes and endplate sclerosis have a considerable influence on spinal bone mass measurements in elderly postmenopausal women and affect the diagnostic ability of spinal scans to discriminate osteoporotic women. Our data suggest that in elderly women, unless the spine is radiologically clear of degenerative conditions, a peripheral measurement procedure should be considered an alternative for assessment of bone mineral content/density.

Aged↗
PubMed1996

A new biochemical marker of bone resorption for follow-up on treatment with nasal salmon calcitonin.

In a double-blind, placebo-controlled, randomized group comparison, new and specific biochemical markers for bone resorption as follow-up parameters on the therapeutic response to nasal salmon calcitonin (sCT) were evaluated. Evaluation took place at an outpatient clinic where osteoporosis was being researched. The subjects included 208 women aged 68-72 treated for 2 years with either 50 IU, 100 IU, or 200 IU of nasal sCT or placebo; all groups received a daily calcium supplementation of 500 mg. Only 164 women fulfilled the study as valid completers. Markers were applied to frozen urine samples of a previously published intervention study of a new fasting urinary (fU) biochemical marker for bone resorption (CrossLapstrade mark, ELISA) and the urinary excretion of cross-links (pyridinoline and deoxypyridinoline) was measured, all corrected for creatinine. Bone mineral density of the lumbar spine and rates of vertebral and peripheral fractures were measured after 2 years of treatment. The creatinine corrected urinary pyridinoline, deoxypyridinoline, and CrossLaps showed maximum decreases of 10-43% (95% confidence interval -29.5% to 9.6% and -75.1% to 9.3%; P < 0. 01-0.001) after 6-9 months, after which the response leveled off. A significant difference among the four treatment groups was seen in fU CrossLaps (P < 0.01). The changes in spinal bone mass were significantly related to the decreases in fU CrossLaps: women with the highest response in spinal bone mass had decreases in fU CrossLaps of 44% (-83.5% to 7.4%) and women without response of 5% (-57.6% to 99.9%) P < 0.001). In women who fractured during the 2-year period, fU CrossLaps remained unchanged, whereas decreases of 30% (-75.1% to 44.7%) were seen in women who did not fracture (P = 0. 002). The results suggest that biochemical markers can be used to determine the optimum treatment regimen of nasal sCT. The response of the new marker, fU CrossLaps, significantly reflects the responses in bone mass of the spine and fracture rates.

Administration, Intranasal↗
PubMed1996

Low bone mass and fast rate of bone loss at menopause: equal risk factors for future fracture: a 15-year follow-up study.

The aim of the study was to examine the role of peak bone mass and rate of postmenopausal bone loss for the subsequent risk of osteoporotic fracture. 182 women within 3 years of menopause were followed longitudinally for 15 years. Over the first 2 years, forearm bone mass (single photon absorptiometry) was measured nine times, the rate of bone loss was calculated, and the women were stratified into a group of "fast bone losers" (n = 49) and a group of "normal bone losers" (n = 133). Later, bone mass was also measured in the lumbar spine and hip with dual energy X-ray absorptiometry. At 15 years, the fast losers had significantly lower body weight (4.4 kG; p < 0.05) than the normal losers. Furthermore, the fast losers had significantly increased values of bone turnover (osteocalcin and C-terminal type I collagen breakdown products). In both the forearm, spine, and hip, the fast bone losers had at all sites significantly less bone mass than the normal bone losers (p < 0.001). 23 women had experienced a peripheral (Colles') fracture and 25 a spinal fracture. The fracture groups had generally significantly (p < 0.05) less bone mass than the group without fracture, both in the forearm, spine, and hip and they also had the highest rate of bone loss after menopause (p < 0.05). Baseline bone mass and rate of loss predisposed to the same extent to fractures with ODD's ratios of about 2. If both low bone mass and rate of loss were present, the ODD's ratio increased to about 3. We conclude that fast rate of bone loss and low bone mass are equally important for the risk of fracture. The identification of women at risk of osteoporosis should therefore consider both a measurement of bone mass status, and a determination of the postmenopausal rate of loss.

Bone Density↗
PubMed1996

High bone turnover is associated with low bone mass in both pre- and postmenopausal women.

In 979 healthy women, aged 30-75 years, bone mass was measured by DXA in the lumbar spine and proximal femur, and by SXA in the distal forearm. Bone turnover was assessed by urinary CrossLaps (CrossLaps ELISA), a new assay which measures type I collagen degradation products in urine and by osteocalcin (two-site N-Mid hOsteocalcin ELISA), a new assay which measures the N-terminal-mid fragment (1-43) as well as the intact (1-49) osteocalcin (OCN-Mid) in serum. For comparison data on urinary hydroxyproline (fU Hpr/Cr) and serum, total alkaline phosphatase were included (AP). In premenopausal women below 50 years of age, the concentrations of the biochemical markers were stable with age. At menopause CrossLaps and OCN-Mid increased abruptly to a level 60% and 35% above the premenopausal mean values (p < 0.001). Premenopausal women in the highest quartiles, stratified according to the concentration of CrossLaps and OCN-Mid corrected for height and weight, had 6%-11% lower bone mass in all regions (p < 0.01) as compared to women in the lowest quartiles. CrossLaps and OCN-Mid corrected for height and weight correlated with bone mass in the spine and proximal femur, r = -0.13 to r = -0.28, p < 0.05. In postmenopausal women, the difference in bone mass between the highest and lowest quartiles was 8%-14% (p < 0.001). CrossLaps and OCN-Mid correlated with bone mass measured in all regions, r = -0.14 to r = -0.32, p < 0.05. The correlation between bone mass and AP and Fu Hpr/Cr was lower; r = -0.06 to r = -0.20 for premenopausal women, NS to p < 0.01, and r = -0.01 to r = -0.23, NS to p < 0.001 for postmenopausal women. In conclusion, the present data indicate that high bone turnover is associated with a significantly lower bone mass in not only postmenopausal, but interestingly also in premenopausal women. In consistence with previous results, we found that bone turnover increased perimenopausally and in the early menopause.

Adult↗
PubMed1996

Ion gradients and contractility in skeletal muscle: the role of active Na+, K+ transport.

Intensive contractile activity is associated with a significant net loss of K+ and a comparable gain of Na+ in the working muscle fibres. This leads to an increase in the interstitial and T-tubular K+ concentration and to a decrease in the T-tubular Na+ concentration. It is well established that the exposure of muscles to high extracellular K+ or low extracellular Na+ inhibits contractile performance. More importantly, the combination of high extracellular K+ and low extracellular Na+ has a much more pronounced inhibitory effect on force than the sum of the individual effects of the two ions. The inhibitory effects of high extracellular K+ or low extracellular Na+ can be alleviated within 5-10 min by acute hormonal stimulation of the Na+, K+ pump. In contrast, reductions in the capacity for active Na+, K+ transport by pre-incubation of isolated muscles with ouabain or by prior K+ depletion of the animals significantly decreases contractile endurance during high-frequency electrical stimulation. Thus, muscles from K(+)-depleted rats exhibiting a 54% reduction in Na+, K+ pump concentration showed a 110% increase in force decline during 30 s of 60 Hz stimulation. Reducing the Na+, K+ pump capacity to a similar extent by pre-incubation with ouabain led to a comparable decrease in endurance. Moreover, reductions in the Na+, K+ pump capacity were associated with an increased intracellular accumulation of Na+ during electrical stimulation. These observations support the notion that excitation-induced decreases in Na+, K+ gradients contribute to fatigue during intensive exercise and suggest that the capacity for active Na+, K+ transport is a determining factor for contractile endurance.

Animals↗
PubMed1996

Bone mineral density in immigrants from southern China to Denmark. A cross-sectional study.

Immigration from Japan to USA has been shown to increase bone mineral density (BMD) and body fat in women. The effects of immigration between other geographical areas on bone mass and body composition are largely unknown, especially in men. In the present study, we measured bone mass and body composition by dual energy X-ray absorptiometry (Hologic QDR-2000) in 73 healthy premenopausal women (age 35 +/- 8 years) and 69 men (age 40 +/- 12 years) who had immigrated from southern China to Denmark 2 months to 36 years ago. The BMD measurements (Total BMD, trunk BMD and leg BMD) were related positively to years since immigration (YSI) (R2 = 0.10-0.16, p < 0.05) in premenopausal women, but not in men. Fat distribution was related mainly to age in both premenopausal women and men (R2 = 0.16-0.26, p < 0.05). For comparison, we included 51 white, Danish premenopausal women (age 36 +/- 6 years). Chinese premenopausal women with a YSI below or equal to 12 years (N = 38) had significantly lower total and regional BMD (trunk, legs, arms) (p < 0.05), while women with a YSI above 12 years (N = 35) had significantly lower BMD in the legs only (p < 0.05) when compared to the Danish premenopausal women. After correction for age weight and height, Chinese premenopausal women with a YSI below or equal to 12 years still had significantly lower BMD in all regions (4-7%, p < 0.05), whereas no differences in BMD were found between Chinese premenopausal women with a YSI above 12 years compared with Danish premenopausal women. In conclusion, Chinese premenopausal women who immigrated to Denmark more than 12 years ago have a similar BMD to that of Danish premenopausal women. In the group who immigrated less than 12 years ago, a significantly lower BMD was found.

Absorptiometry, Photon↗
PubMed1995

Spontaneous postmenopausal bone loss in different skeletal areas--followed up for 15 years.

We examined the spontaneous bone loss in two populations of healthy postmenopausal women, who were followed for 9.5 and 14.5 years without any treatment influencing the calcium metabolism. The bone mass was measured in different skeletal areas: the distal forearm, the lumbar spine, the proximal femur, and the total skeleton. The spontaneous bone loss in the distal forearm, the lumbar spine, and the total skeleton was fitted to an exponential model as a function of years since menopause. The overall bone loss averaged 20-25% of premenopausal bone mass 16 years after menopause. The patterns of bone loss were, however, different for the axial and the peripheral skeleton. Thus, the bone loss in the distal forearm approached a more linear model with a more consistent bone loss throughout the observation period. In contrast, the lumbar spine showed no significant loss 8 years after menopause. This arrest in bone loss could not be explained by the presence of degenerative changes in the lumbar spine and/or aortic calcifications, although these changes significantly contributed to 14% increased bone mineral density (p < 0.001). We conclude that bone loss averages 20-25% over the initial 16 years of menopause regardless of skeletal site and that patterns of bone loss are different in the axial and peripheral skeleton.

Absorptiometry, Photon↗
PubMed1995

Biochemical markers of bone turnover to monitor the bone response to postmenopausal hormone replacement therapy.

Hormone replacement therapy (HRT) prevents postmenopausal bone loss, and is therefore increasingly prescribed to prevent the development of postmenopausal osteoporosis. Because of individual differences in the response to HRT as well as problems with compliance, it has been debated how the skeletal response to HRT should be monitored. When estrogen production decreases at the menopause, a number of biochemical markers of bone turnover increase considerably in the order of 50%-100% from baseline. When HRT is instituted, the markers decrease again within the following 3-6 months. In the present prospective study we investigated whether the determination of biochemical markers of bone turnover may be useful for monitoring the skeletal effect of HRT. Seventy-six early postmenopausal women received HRT and 43 received placebo. The treatment period was 24 months and the women were followed with repeated bone mass measurements (every 3 months) which allowed calculation of the bone loss. Serum and urine samples were collected at 3, 6, 12 and 24 months. The placebo group lost a significant amount of bone mineral density in both the forearm and the spine (p < 0.001), whereas the HRT group did not. There was, however, a relatively large overlap of values between the HRT and placebo groups, especially in the spine. After 3 months' treatment the correlation between the changes in the markers and the bone loss was r = 0.59, and this value increased to r = 0.66 at 6 months and r = 0.76 and r = 0.77 at 12 and 24 months, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Biomarkers↗
PubMed1995

Thrombolysis in ischaemic stroke--how far from a clinical breakthrough?

Thromboembolic occlusions of the cerebral arteries often recanalize spontaneously, and patients with early recanalization have a better outcome than patients who do not recanalize. Clinical as well as experimental data support the concept of a time window within which brain tissue will profit from restoration of blood flow. In occlusion of middle cerebral artery, internal carotid artery, as well as vertebrobasilar arteries, open studies of intra-arterial administration of thrombolytic agents have demonstrated recanalization within hours in 40-100% of patients in small series. In intravenous drug administration, recanalization rate was obtained in 34-59% of patients. Favourable outcome was associated with recanalization. Intracerebral bleeding complications with clinical deterioration occurred in about 10% of patients. Three randomized controlled trials comprising 156 patients with acute ischaemic stroke have reported favourable outcome in treated patients, with no difference of intracerebral haemorrhagic complications between treated and controls. Results of ongoing randomized placebo controlled trials are expected in 1995 to disclose whether a clinical breakthrough is achieved or whether haemorrhagic complications will outweigh a beneficial effect of thrombolytic therapy in acute cerebral ischaemia.

Animals↗
PubMed1995

Insulin-like growth factors I and II in healthy women with and without established osteoporosis.

We measured serum concentrations of insulin-like growth factors I and II (IGF-I and IGF-II) by radioimmunoassay in 107 healthy women aged 28-78 years and in 116 women with established osteoporosis. The women with established osteoporosis were randomized to a 1-year double-blind, placebo-controlled treatment with continuous estrogen/progestogen, anabolic steroids, salmon calcitonin or placebo and the IGFs were measured every 6 months. Women less than 35 years of age had 29% higher levels of IGF-I (p < 0.001) as compared to women above that age. For women more than 35 years of age, we found no correlation between IGF-I and age (r = 0.02). Correspondingly, we found no significant changes in serum IGF-I in 10 women, who were followed with serial measurements of IGFs every 3 months from 2 years before to 1 year after menopause; IGF-II revealed no correlation with age (r = 0.04). In the group of 116 women with established osteoporosis, IGF-I was 30% lower (p < 0.01) as compared to a group of 19 height-, weight- and age-matched nonfractured women (mean age 64 years). The IGF-II levels were equal in the two groups. Over the 1-year therapeutic intervention period, an increase in IGF-I of 13-15% (p < 0.05) was seen in the nandrolone decanoate-treated group. The same tendency was seen for hormone replacement therapy, although it was not significant. In conclusion, the serum level of IGF-I is high in young women, when peak bone mass is attained, and low in postmenopausal women with established osteoporosis.

Adult↗
PubMed1995

The protein concentration of blood coagulation factor VII can be measured equally well in plasma and serum.

In the Northwick Park Heart Study, the coagulant activity of factor VII (FVII:C) has been identified as a risk marker of ischaemic heart disease. In the fasting state, the protein concentration of FVII (FVII:Ag) might be an even better risk marker, because of the low coefficient of variation of the antigen assay. Today, most analyses are performed in plasma samples, as it is unknown whether FVII, to some extent, is consumed during coagulation. In the present study, we have investigated, whether FVII:Ag can be measured equally well in plasma and serum. FVII:Ag was measured in 88 plasma and serum samples. Results were compared by means of linear regression, where y = 0.984 x +0.770, r = 0.96. No systematic variation existed between FVII:Ag in plasma and serum. The mean difference in FVII:Ag between plasma and serum was -1.17 (SD 11.92) arbitrary units, compared with a mean difference of 0.18 (SD 8.31) arbitrary units between duplicate measurements of the same plasma dilution. Our findings indicate that there is a good agreement between FVII:Ag in plasma and serum.

Adult↗
PubMed1994

The influence of body temperature on infarct volume and thrombolytic therapy in a rat embolic stroke model.

The effect of body temperature on cerebral infarcts and thrombolytic therapy was investigated in 91 rats embolized in the right carotid territory. Hypothermia of 32 degrees C for 2 h with preembolic onset (n = 15) or hyperthermia of 39 degrees C for 2 h with postembolic onset (n = 22) was compared to normothermic controls (n = 17). After 48 h of survival, neuropathological evaluation with measurement of infarct volume was performed. Median infarct volume in percent of affected hemisphere volume was 11% (9-21, quartiles) in rats treated with hypothermia alone, compared to 46% (14-59, quartiles) in normothermic controls (P = 0.04). Hyperthermia for 2 h increased median infarct volume to 65% (37-75, quartiles). There was a positive and significant correlation between infarct volume and body temperature (R = 0.53, P = 0.0002, n = 54). Mortality rate was significantly higher among rats treated with hyperthermia compared to normothermic controls (P = 0.005). A subset of 37 rats exposed to the same temperature regimen were treated with tissue plasminogen activator (20 mg/kg i.v. during 45 min) 2 h after embolization. Judged by posttreatment carotid angiography, hyperthermic rats (n = 11) had the best degree of recanalization (P = 0.03) compared to controls (n = 17), but median infarct volume in this group was (58% (27-67, quartiles)) significantly larger (P < 0.02) than normothermic (21% (15-39, quartiles), n = 14) and hypothermic (13% (7-31, quartiles), n = 12) rats treated with thrombolytic therapy. Thrombolytic therapy following 2 h of hypothermia, could not improve the effect of hypothermia alone.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1994

Premenopausal and postmenopausal changes in bone mineral density of the proximal femur measured by dual-energy X-ray absorptiometry.

Total and regional bone mineral density (BMD) of the proximal femur was measured by DXA in 1238 healthy white women. In the 389 premenopausal women, aged 21-54 years, no bone loss was observed before the menopause, except in the femoral neck and Ward's triangle, in which BMD decreased by 0.3%/year (SEE 0.2-0.9%/year, p < 0.001) and 0.6%/year (SEE 0.4-0.8%/year, p < 0.001), respectively. In the postmenopausal women aged 48-75 years, there was a highly significant exponential decay in BMD with age and years since menopause (YSM) in all regions (-0.58 < r < -0.48, p < 0.001). However, YSM was a better predictor of BMD than age. The decrease in BMD in the first 5 years postmenopause reached values of 9-13%. The estimated bone loss after 20 years was 17-30%, greatest in Ward's triangle and smallest in the intertrochanteric region. BMD correlated highly significantly with BMI (0.26 < r < 0.48, p < 0.001). In conclusion, the present study indicates a stable premenopausal bone mass of the proximal femur and a postmenopausal bone loss, which is influenced mainly by YSM within the first 10-15 years after menopause. BMD correlated with body mass index (BMI) in the postmenopausal years, confirming that low BMI constitutes a potential risk factor for osteoporosis.

Absorptiometry, Photon↗
PubMed1994

Effect of intranasal salmon calcitonin therapy on bone mass and bone turnover in early postmenopausal women: a dose-response study.

We examine the dose-related effect of intranasal salmon calcitonin (sCT) on the early postmenopausal bone loss and bone turnover; a 2-year, prospective, randomized, double-blind, placebo-controlled study was carried out with 134 healthy women who had passed a natural menopause within 6 months to 3 years. The women were allocated randomly to 2 years of treatment with either 100, 200, or 400 IU of sCT given intranasally or placebo. All groups received a calcium supplement of 500 mg. Twenty-one women left the study before its end and 91 complied with the study criteria throughout. Bone mineral content/density of the distal forearm and lumbar spine and biochemical parameters of bone turnover were measured. Although the measurements after 24 months revealed no significant difference between groups in bone mineral density of the lumbar spine, the average changes over time revealed prevention of bone loss in the groups treated with 200 and 400 IU of sCT (0.2 to -0.6%) and declines of 0.8-1.7% in the groups treated with 100 IU of sCT and placebo (P < 0.05-0.01; within-group testing). There was no dose-related response to sCT but there was a significant difference between the pooled groups treated with 200 plus 400 IU of sCT versus the 100 IU sCT and placebo-treated groups (P = 0.030-0.005). The same difference between groups was seen for biochemical parameters of bone turnover (P = 0.022-0.003). The biochemical parameters of bone turnover revealed decreases of 10-20% (P < 0.001; within group testing) in the groups treated with the two highest sCT doses.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Intranasal↗
PubMed1994

The diagnostic validity of urinary free pyridinolines to identify women at risk of osteoporosis.

The urinary excretion of pyridinolines either in the free form or linked to different peptide fragments of type I collagen are intensively studied as new biochemical markers of bone resorption. In the present study we compared the urinary excretion of free pyridinoline (F-Pyr) determined by enzyme-linked immunosorbent assay (ELISA) (Collagen Crosslinks Kit, Metra Biosystems) to pyridinoline (Pyr), and deoxypyridinoline (D-Pyr) determined by high performance liquid chromatography (HPLC) in early postmenopausal women treated with either hormone replacement therapy or placebo and in healthy age-matched premenopausal women. Other markers of bone metabolism were included for comparison. Compared with the premenopausal women, the postmenopausal women had significantly increased values of the biochemical parameters. F-Pyr, Pyr, D-Pyr, and T-Pyr (= Pyr + D-Pyr) decreased during hormone therapy. D-Pyr correlated with the rate of bone loss, whereas this was not the case for F-Pyr. The correlations between the markers yielded r values of 0.71 (F-Pyr vs Pyr), 0.67 (F-Pyr vs D-Pyr), and 0.71 (F-Pyr vs T-Pyr). In conclusion, the present study shows that the newly introduced ELISA for determination of the free pyridinolines is less sensitive than pyridinium crosslinks measured by high performance liquid chromatography (HPLC) in hydrolyzed urine for the changes in calcium metabolism that occur at menopause and during hormone replacement therapy. Whether this limitation will be balanced out by avoiding the inconvenience of the complicated, expensive, and time-consuming HPLC procedure is still being debated.

Adult↗
PubMed1994

Estimation of the effect of salmon calcitonin in established osteoporosis by biochemical bone markers.

We reviewed data on 42 postmenopausal women with established osteoporosis (forearm fracture or a low bone mass) who had been randomly treated for 1 year with either rectal salmon calcitonin (sCT), 100 IU daily (n = 25) or nasal sCT, 200 IU daily (n = 17) applying an estimation algorithm for bone loss rates. Both groups received a daily calcium supplement of 500 mg. A group of 18 age-matched women who received no treatment served as controls. The bone mineral content of the distal forearm (BMCarm) was measured every 3 months by single photon absorptiometry. The individual rates of change during the 1-year period were calculated by linear regression analysis (alpha BMCarm). Bone loss rates were estimated initially and after 1 year of therapy by measurements of serum alkaline phosphatase, plasma bone Gla protein, and fasting urinary hydroxyproline and calcium (both corrected for creatinine excretion) according to the estimation algorithm. Both administration forms revealed significant control group-corrected decreases in serum and urine markers of bone turnover of 15-40% (P < 0.05-0.01) and positive outcomes of 2% in alpha BMCarm (P < 0.01). The estimated effect on bone mass was expressed as the difference between the bone loss estimated after 1 year and initially (delta ESTBIO). A significant correlation was seen between alpha BMCarm and delta ESTBIO (r = 0.5, P < 0.0001). We conclude that the effect of sCT on bone can be followed up by biochemical markers for bone turnover, i.e., by an annual blood and fasting urine sample, applying an estimation algorithm for the rate of bone loss.

Absorptiometry, Photon↗