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Biomedical subjects

C Hassager

Publications and source records attributed to C Hassager.

At least 91 records · Page 5Linked to original sources

Changes in calcanean bone mineral occurring spontaneously and during hormone replacement therapy in early post-menopausal women.

The spontaneous calcanean bone loss occurring in healthy early post-menopausal women and the effect of two hormone replacement therapies (HRT's) were investigated in a longitudinal study. There was no difference between the right and left calcanean BMC or BMD (p > 0.15). The spontaneous bone loss was similar at all the skeletal sites measured, with a mean spontaneous loss in calcanean BMD of 1.6% over one year. Both HRT's significantly (p < 0.01) prevented the bone loss from all skeletal sites irrespective of the weight-bearing or content of trabecular bone, and (for the weight-bearing bones) there was even a gain in calcanean BMC and BMD and spinal BMD (p < 0.01). Bone mineral of the calcaneus and the spine correlated equally to body weight (r approximately 0.4, p < 0.001), whereas bone mineral in the forearm was not correlated to body weight. The correlations between the changes in bone mineral at the sites measured were all significant (r approximately 0.2-0.4).

Bone Density↗

Procalcitonin NH2-terminal cleavage peptide has no mitogenic effect on normal human osteoblast-like cells.

The NH2-terminal cleavage peptide of procalcitonin (N-proCT) recently was reported to be a bone cell mitogen (Burns DM et al., Proc Natl Acad Sci USA 86:9519-9523, 1989). We have investigated the effect of N-proCT on the proliferation of normal human cells that have the phenotype of mature osteoblasts (hOB cells). N-proCT treatment for 24, 48, or 96 h in concentrations from 1 nM to 1 microM did not significantly increase [3H]thymidine uptake (means ranged from -19% to 38% of control, no significant differences) in hOB cells (6-10 cell strains per experiment) plated at four different densities. However, the hOB cells responded significantly to treatment with transforming growth factor beta (3 ng/ml), bovine insulin (300 micrograms/ml), or 30% fetal calf serum, which were included in all experiments as positive controls. The [3H]thymidine uptake data were confirmed in a direct cell count experiment tested at 96 h. Thus our data do not support the hypothesis that N-proCT is a potent mitogen for normal human osteoblasts.

Calcitonin↗

The impact of measurement errors on the diagnostic value of bone mass measurements: theoretical considerations.

It has become clear over the last decade that correlations between measurements of forearm bone mineral content (BMCarm) by single-photon absorptiometry (SPA) and measurements of spinal bone mineral density (BMDspine) by dual-photon absorptiometry (DPA) in healthy subjects and patients with spinal fractures are invariably significant, but not very powerful (i.e. r = 0.5-0.7). Nonetheless, several recent studies have shown that appendicular bone mass measurements discriminate between spinal fracture and non-fracture at least as well as do spinal DPA measurements. Correlations of a given parameter with measured BMDspine are less important than those with true BMDspine. To establish the latter we made the following assumptions: (1) accuracy errors or SPA BMCarm and DPA BMDspine measurements of 2%-4% and 8%-10%, respectively; and (2) a measured biological variation of SD = 14% for both BMCarm and BMDspine, corresponding to that of healthy women at the menopause. On these assumptions, we found that a correlation between true BMCarm and true BMDspine at about r = 0.8-0.9 yields a correlation between measured BMCarm and measured BMDspine at about r = 0.6--corresponding to experimental data in healthy women at the menopause. Furthermore, we found that the correlation between DPA measured BMDspine and true BMDspine is about the same as that between the SPA measured BMCarm and the true BMDspine. Thus, with the assumptions given above, spinal (DPA) and fore-arm (SPA) measurements appears to predict equally the true BMDspine in healthy perimenopausal women.

Bone Density↗

The carboxy-terminal propeptide of type I procollagen in serum as a marker of bone formation: the effect of nandrolone decanoate and female sex hormones.

Seventy-nine osteoporotic (prior forearm or vertebral fracture), but otherwise healthy, postmenopausal women (aged 55 to 75 years) were allocated to two double-blind trials: (1) 39 women received either nandrolone decanoate (anabolic steroid) 50 mg as an intramuscular depot injection or a placebo injection every 3 weeks for 1 year; and (2) 40 women received either 2 mg 17 beta-estradiol plus 1 mg norethisterone acetate or placebo tablets daily for 1 year. Sixty-seven (85%) completed the 1 year of treatment. Serum concentration of type I procollagen carboxy-terminal propeptide (PICP) was measured before and at 3, 6, 9, and 12 months of therapy. In addition, 32 of the women had an iliac bone biopsy taken after double tetracycline labeling. Initial serum PICP correlated significantly with histomorphometrically measured rate of bone formation (r = .4; P less than .05) and plasma bone Gla protein (r = .6; P less than .001), but not with histomorphometrically measured bone resorption or biochemical estimates of bone resorption (fasting urinary hydroxyproline and calcium). Estrogen-progestogen therapy significantly decreased (P less than .001) serum PICP by about 30%, whereas anabolic steroid therapy hardly affected it. We conclude that serum PICP may be used as a noninvasive measurement of bone formation on a group basis. Whereas bone formation is clearly decreased during estrogen-progestogen therapy, it is not affected by long-term therapy with anabolic steroids.

Aged↗

The effect of growth hormone (GH) therapy on urinary pyridinoline cross-links in GH-deficient adults.

OBJECTIVE: The aim was to study the effect of growth hormone (GH) on new markers of bone resorption (fasting urinary excretion of pyridinium cross-links (pyridinoline and deoxypyridinoline)) in GH-deficient adults. DESIGN: Randomized, double-blind, placebo-controlled cross-over study. The treatment periods (GH 2 IU/m2 subcutaneously, or placebo daily for 4 months) were separated by a 4-month washout period. PATIENTS: Twenty GH-deficient adults (aged 18-39). MEASUREMENTS: Blood and fasting urine samples were collected at the end of each 4-month treatment period. Plasma bone Gla protein was measured by radioimmunoassay and urine pyridinoline and deoxypyridinoline were measured by spectrofluorometry after high performance liquid chromatography and corrected for urinary creatinine. RESULTS: GH increased fasting urinary excretion of pyridinoline (287 +/- 123%, P less than 0.001) and deoxypyridinoline (313 +/- 140%, P less than 0.001). The GH-induced increment in these parameters correlated with the increase seen in plasma bone Gla protein (r = 0.83-0.86, P less than 0.001). CONCLUSION: Four months of GH substitution in GH-deficient adults increases bone resorption as well as bone formation. The effect on bone mass has yet to be assessed.

Adolescent↗

Validation of body composition by dual energy X-ray absorptiometry (DEXA).

The present study validates the use of dual energy X-ray absorptiometry (DEXA) for measurement of body composition. The precision error was expressed as the SD (CV%) for fat mass, FAT%, lean tissue mass, and total body bone mineral: 1.1 kg (6.4%), 1.6% (5.7%), 1.4 kg (3.1%), and 0.03 kg (1.2%), respectively. The accuracy study in vitro used (1) mixtures of water and alcohol, (2) mixtures of ox muscle and lard, and (3) dried bones. In the clinically relevant range of values there were only small influences on DEXA measurements of variations in amount and composition of the soft tissue equivalents. The accuracy study in vivo compared the components of body composition measured recently by DEXA and earlier by dual photon absorptiometry, counting of naturally occurring total body 40K, and body density by underwater weighing in 25 healthy adult subjects. We found agreement between fat percentage (and lean body mass) by DEXA and the three established measurements modalities; mean differences were (-5.3 to -0.4%) and (-0.7 to 2.5 kg) for fat percentage and lean body mass, respectively. We conclude that DEXA provides a new method of measuring body composition with precision and accuracy errors, which are compatible with the application of DEXA in group research studies and probably also in clinical measurements of the single subject.

Absorptiometry, Photon↗

Body composition and calcium metabolism in adult treated coeliac disease.

Twenty two treated adult patients with coeliac disease (aged 20-70 years) were examined. Body composition was assessed from anthropometry and directly measured by dual photon absorptiometry. Bone mineral content was measured in the spine (dual photon absorptiometry) and at two forearm sites (single photon absorptiometry). Compared with age matched healthy subjects, treated coeliac patients had lower body mass index (-5%, p less than 0.05) and lower directly measured total body fat mass (-30%, p less than 0.001). They also had decreased bone mineral content (-9 to -13%, p less than 0.01) in the spine and in the forearms. The serum concentrations of albumin, D vitamin binding protein, and iron were reduced (-6 to -22%, p less than 0.01), but otherwise blood and urine analyses were normal. We conclude that this group of treated adult coeliac patients had a reduced fat mass and bone mineral content compared with the general population.

Adult↗

Serum lipids, lipoproteins, and apolipoproteins during postmenopausal estrogen replacement therapy combined with either 19-nortestosterone derivatives or 17-hydroxyprogesterone derivatives.

PURPOSE: To study the influence of combined hormone replacement therapy on levels of serum lipids, lipoproteins, and apolipoproteins. PATIENTS AND METHODS: One hundred thirty-nine healthy early postmenopausal women selected by means of a questionnaire, a medical examination, and a laboratory screening procedure to be a representative sample of postmenopausal Danish women aged 45 to 55 years old were randomized to four treatment and two placebo groups. The four groups receiving hormone replacement therapy were given 2 mg estradiol valerate equivalents (E), either sequentially combined with 75 micrograms levonorgestrel (E/LNG), 10 mg medroxyprogesterone acetate (E/MPA), or 150 micrograms desogestrel (E/DG), or continuously combined with 1 mg cyproterone acetate (E/CPA). Serum lipids, lipoproteins, and apolipoproteins were measured before institution of hormone replacement therapy and at nine well-defined times during the following 84 days. Total response and cyclical variations were calculated. RESULTS: All active treatment regimens reduced serum low-density lipoprotein cholesterol (LDL-C) significantly: E/CPA, 6% (95% confidence limits 0.3% to 11.3%); E/LNG, 10.9% (4.9% to 16.6%); E/MPA, 14.4% (7.4% to 20.9%); E/DG, 10.7% (3.3% to 17.6%). The changes in serum total cholesterol and apolipoprotein B were similar but smaller than those in LDL-C. None of these treatment regimens induced significant overall changes in serum high-density lipoprotein cholesterol (HDL-C) or apolipoprotein A1 (Apo A1). The sequentially combined hormone treatments induced significant cyclical variations in HDL-C, with an increase during estrogen therapy and a decrease during combined therapy: E/LNG, 13.3% (7.4% to 19.4%); E/MPA, 6.9% (1.6% to 12.6%); E/DG, 10.3% (5.8% to 14.9%). No cyclical changes in HDL-C were found in the group receiving continuously combined hormone replacement therapy (E/CPA). The changes in Apo A1 parallel those in HDL-C. CONCLUSION: All the treatment regimens produced changes in levels of serum lipids, lipoproteins, and apolipoproteins that may be considered favorable in terms of cardiovascular disease.

Androgen Antagonists↗

Influence of smoking, body fat distribution, and alcohol consumption on serum lipids, lipoproteins, and apolipoproteins in early postmenopausal women.

The impact of smoking, alcohol consumption, obesity, and body fat distribution (measured either directly by dual photon absorptiometry as abdominal fat% (AF%) or as the waist-to-hip ratio (WTH] on serum lipids, lipoproteins, and apolipoproteins was investigated in 148 early postmenopausal women. All the women were healthy and none were taking medication known to influence the parameters studied. Smokers had significantly higher levels of triglycerides, low density lipoprotein cholesterol (LDL-C), and apolipoprotein B (P less than 0.05), and higher ratios of LDL-C/HDL-C and apolipoprotein B/A-I (P less than 0.01), but lower levels of high density lipoprotein cholesterol (HDL-C) and apolipoprotein A-I (P less than 0.01). Moderate alcohol consumption was positively associated with HDL-C and apolipoprotein A-I (P less than 0.001). Body weight and body mass index (BMI) tended to be positively associated with an atherogenic lipoprotein and apolipoprotein profile. However, body fat distribution parameters (AF% and WTH) were stronger predictors of lipoproteins and apolipoproteins than were body weight and BMI, which did not seem to be independent predictors of lipoproteins and apolipoproteins. We conclude that cigarette smoking and a central fat distribution have a significant, independent, negative influence on lipids, lipoproteins, and apolipoproteins, whereas moderate alcohol consumption has a positive effect on these parameters in early postmenopausal women.

Adipose Tissue↗

Collagen synthesis in postmenopausal women during therapy with anabolic steroid or female sex hormones.

The effect of anabolic steroid therapy and estrogen-progestogen substitution therapy on serum concentration of procollagen type III aminoterminal peptide (PIIINP), a measure of collagen synthesis, in postmenopausal women was studied in two double-blind studies: (1) 39 women allocated to treatment with either 50 mg nandrolone decanoate as an intramuscular depot or placebo injections every third week for 1 year, and (2) 40 women allocated to receive either 2 mg 17 beta-estradiol plus 1 mg norethisterone acetate daily or placebo tablets for 1 year. Serum PIIINP was measured every 3 months during the study. Anabolic steroid therapy resulted in a more than 50% increase (P less than .001) in serum PIIINP at 3 months, which thereafter decayed but remained significantly increased throughout the study period. Serum PIIINP showed the same pattern during estrogen-progestogen therapy, but to a lesser degree. We conclude that anabolic steroids stimulate type III collagen synthesis in postmenopausal women, while estrogen-progestogen therapy may have such an effect, but only to a lesser degree.

Aged↗

Bone mass measured by photon absorptiometry: comparison of forearm, heel, and spine.

We assessed bone mass quantification at different skeletal sites by single and dual photon absorptiometric (SPA and DPA) methods. Improved DPA measurement of spinal bone mineral density in young healthy subjects showed a short- and long-term precision of 1.2% and 1.6%. Compared to the conventional DPA method the imprecision was reduced by more than 50%. The appendicular measurements were more precise (0.5-1.2%). We present the intercorrelations and predictive errors between peripheral measurements and improved spinal and total body bone measurements in early postmenopausal women (n = 144) recruited in 1988. To compare the improved system with the conventional methods, we retrieved data on age-matched early postmenopausal women (n = 151) recruited in 1983. In the 1988 population all peripheral methods had similar predictive errors in estimation of spinal bone mineral density (SEE = 11-13%) and total body bone mineral density (SEE = 4-5%). Measurement of trabecular bone in the heel and distal forearm did not improve the validity of predicting spinal bone mass. In a cadaver study (n = 11) the predictive error in estimation of the spinal ash weight from forearm measurements was of the same magnitude (15%) as that in estimation of the spinal BMC from the forearm (16%). We conclude that the predictive error in estimation of spinal bone mass from peripheral bone measurements is more likely to be caused by intra-skeletal variation in bone mass than by precision errors. However, this does not reflect the inability of peripheral bone mass measurements to predict fracture risk.

Absorptiometry, Photon↗

Comparison of two immunoinhibitory methods with agarose gel-electrophoresis for measuring the MB isoenzyme of creatine kinase in serum from cases of suspected myocardial infarction.

Two immunoinhibitory methods for measuring creatine kinase-MB (a dry chemical and a wet chemical method) were compared with the commonly used agarose gel electrophoretic method, using 563 serum samples from 235 patients with suspected acute myocardial infarction. Comparison of the electrophoretic and the dry chemistry methods showed the linear relationship: electrophoretic method = -6.5 U/l + 1.22 x dry chemistry method, r = 0.943. For the wet chemistry method the relationship was: electrophoretic method = -7.2 U/l + 1.19 x wet chemistry method, r = 0.854. Parallel determinations of total creatine kinase were also done and the methods were virtually identical in performance. Compared with the electrophoretic method (which showed a 15% prevalence of acute myocardial infarction), these classifications showed sensitivities of 0.92 and 0.67 and specificities of 0.94 and 0.99 (dry and wet chemistry, respectively; using methods recommended by the manufacturers). After optimization of discriminators the sensitivity was increased to 0.94/0.92 and the specificity to 0.99/0.99.

Adenylate Kinase↗

Vitamin D metabolism in osteoporotic women during treatment with estrogen, an anabolic steroid, or calcitonin.

We assessed the effects of a continuous oral combination of estradiol and norethisterone acetate, nandrolone decanoate, or salmon calcitonin on the vitamin D endocrine system. One hundred and nineteen postmenopausal women, aged 55-75 years, with at least one osteoporotic fracture, were randomly allocated to one year of treatment with estradiol and norethisterone acetate, nandrolone decanoate, or calcitonin, all drugs with a beneficial effect on bone. All three trials were double-blind and placebo-controlled; 104 women (87%) completed the study. We measured the total serum concentration of 1,25-dihydroxyvitamin D (1,25(OH)2D) and vitamin D-binding protein, and estimated the free 1,25(OH)2D index and the "24-hydroxylase activity" initially, and at 6 and 12 months. Furthermore, the 24-h urinary excretions of calcium, phosphate, and adenosine 3'-5'-cyclic monophosphate were assessed initially and at 12 months. The serum concentration of vitamin D-binding protein and 1,25(OH)2D increased transiently during estradiol and norethisterone acetate treatment and vitamin D-binding protein decreased transiently during nandrolone decanoate treatment. None of the other parameters were significantly affected by any of the three treatments. The risk of type II errors was below 10 per cent for all vitamin D measurements. We conclude that the vitamin D metabolites are unlikely to be of major importance for the mechanism by which these drugs exert their positive skeletal effects.

Aged↗

Direct measurement of abdominal fat by dual photon absorptiometry.

We have assessed photon absorptiometry as a new technique for direct measurement of the abdominal fat percentage (AF%). The accuracy of the method was assessed in vitro with phantoms consisting of ox muscle, lard, and a mixture of both. The results showed good linearity (r = 0.999). The in vitro reproducibility and the in vivo reproducibility were s.d. = 2.0 and s.d. = 2.8 (AF%), respectively. The AF% was measured in 148 healthy post-menopausal women and found to correlate with other measurements of fatness, such as total body fat per cent (r = 0.82, P less than 0.001), body mass index (r = 0.79, P less than 0.001) and the ratio of waist-to-hip circumference (r = 0.59, P less than 0.001). The waist-to-hip ratio, an important predictor of cardiovascular disease, was more tightly correlated with AF% than with body mass index. We conclude that this method may be a useful new research tool for direct measurements of abdominal fat, a possible cardiovascular risk factor.

Abdomen↗