Accuracy of measurements of total-body soft-tissue composition by dual energy X-ray absorptiometry in vivo.
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Absorptiometry, Photon↗
Biomedical subjects
C Hassager
Publications and source records attributed to C Hassager.
The effect of the menopause and hormone replacement therapy on serum carboxyterminal propeptide of type I collagen.
We investigated the effect of the menopause and postmenopausal hormone replacement therapy on the serum concentration of carboxyterminal propeptide of type I procollagen (PICP), which is a biochemical marker of type I collagen synthesis. A group of 124 healthy postmenopausal women, aged 45-53 years, had about 20% higher serum PICP than did a group of 40 healthy premenopausal women aged 35-52 years (114 +/- 35 micrograms/l vs. 95 +/- 26 micrograms/l (mean +/- SD); p = 0.002). The 124 postmenopausal women were also participating in a double-masked longitudinal study with two placebo groups and four different hormone replacement therapy groups. The four hormone regimens resulted in similar responses in serum PICP. Compared with placebo, 1 year of treatment with any of the four hormone replacement therapies significantly decreased serum PICP to premenopausal levels. We conclude that the formation of type I collagen is increased shortly after the menopause and that hormone replacement therapy reverses this increase.
Adult↗
Effect of an energy-restrictive diet, with or without exercise, on lean tissue mass, resting metabolic rate, cardiovascular risk factors, and bone in overweight postmenopausal women.
PURPOSE: To study the effect of exercise added to an energy-restrictive diet in overweight postmenopausal women. SUBJECTS AND METHODS: In a longitudinal clinical study, 121 healthy, overweight postmenopausal women (age 53.8 +/- 2.5 years, body mass index: 29.7 +/- 3.1 kg/m2) were randomly assigned to 3 groups: controls, a 4,200 kJ/d diet, or a 4,200 kJ/d diet with combined aerobic and anaerobic exercise. Body composition (measured by dual-energy x-ray absorptiometry), fat distribution, resting metabolic rate, blood pressure, serum lipids and lipoproteins, bone mineral densities, and markers of collagen and bone turnover were measured before and after 12 weeks of intervention. RESULTS: One hundred eighteen women completed the study. The mean loss of body weight (9.5 kg versus 10.3 kg, NS) was similar in the intervention groups, but compared with the diet-only group, the diet-plus-exercise group lost more fat (7.8 kg versus 9.6 kg, p < 0.001) and no lean tissue mass (1.2 kg versus -0.0 kg, p < 0.001). The resting metabolic rate (per kg wt) was increased in the diet-plus-exercise group compared with the control group (11% versus 4%, p < 0.009). The levels of serum triglycerides, total cholesterol, low-density lipoprotein, and very-low-density lipoprotein decreased, and the ratio of high-density lipoprotein to low-density lipoprotein increased by 20% to 30% in both intervention groups compared with the control group (p < 0.001). The systolic blood pressure dropped, and the waist-to-hip circumference ratio and abdominal-to-total body fat decreased in both intervention groups compared with the control group (10%, p < 0.003, and 3.5%, p < 0.0001). There were no consistent, major differences between the groups in terms of changes in total body, spinal, or forearm bone mineral densities, or in markers of collagen and bone turnover. CONCLUSION: Overweight postmenopausal women benefit from addition of combined aerobic and anaerobic exercise to an energy-restrictive diet. The diet itself has a positive effect on cardiovascular risk factors.
Blood Pressure↗
Impact of regional and total body composition and hormones on resting energy expenditure in overweight postmenopausal women.
The independent impact of regional and total body composition and sex and thyroid hormone levels on resting energy expenditure (REE) was assessed in 121 healthy, overweight (body mass index [BMI], 25 to 42 kg/m2), postmenopausal women (aged 49 to 58 years). REE was measured by indirect calorimetry with a ventilated hood, and the total, trunk, and peripheral body composition by dual-energy x-ray absorptiometry (DXA). Sex and thyroid hormone levels were also measured. REE correlated significantly (P < .05) better with trunk lean tissue mass ([LTM] r = .61) than with total-body (r = .53) or peripheral LTM (r = .30). Trunk LTM (R2 = .37), total-body fat tissue mass ([FTM] R2 = .04), androstenedione (R2 = .03), and total triiodothyronine ([T3] R2 = .02) were all significantly independently associated with REE. Together they explained 46% (model R2) of the interindividual variation in REE, with a standard error of estimate (SEE) of 549 kJ/d. We conclude that the interindividual variation in REE is explained mainly by differences in the visceral component of LTM, with additional minor information from the total-body FTM, androstenedione, and T3.
Absorptiometry, Photon↗
Accuracy of measurements of body composition by dual-energy x-ray absorptiometry in vivo.
The accuracy of body-composition measurements in vivo by dual-energy x-ray absorptiometry (DEXA) was assessed in seven pigs (weight: 35-95 kg) by measurement by DEXA in vivo and chemical analysis after postmortem homogenization. The regression lines between these measurements were not significantly different from the line of identity (P > 0.05), the r values were > 0.97, and the corresponding SEEs were 2.9%, 1.9 kg, and 2.7 kg for percent fat, fat tissue mass, and lean body mass, respectively. Changes in fat and lean tissue mass (simulated by placing 8.8 kg porcine lard on the trunk of six women) were accurately measured by DEXA. The measured total-body bone mineral (TBBM) was significantly affected by the lard (P < 0.05). In conclusion, DEXA is an accurate method for measurement of soft-tissue body composition. TBBM measurements in longitudinal studies may, however, be difficult to interpret if considerable change in soft-tissue composition has occurred.
Absorptiometry, Photon↗
Heterogeneous response to calcium by individual parathyroid cells.
Classical stimulus-secretion theory suggests that each individual cell responds to a given stimulus. We tested this theory by determining the response of single bovine parathyroid cells to calcium with the reverse hemolytic plaque assay (RHPA), an assay that measures hormone release from individual cells. As calcium concentrations decreased, the amount of parathyroid hormone (PTH) released per cell increased, and cells were recruited to release PTH. To confirm that adequate stores of PTH were present, immunocytochemistry and in situ hybridization were performed. To test if cells that did not release PTH were capable of secretion, we performed a sequential RHPA; 47.8% of cells did not release PTH after the first stimulus. After the second exposure to low concentrations of calcium, 26.5% of these "nonsecretory" cells were able to release PTH. We conclude that parathyroid cells are homogeneous for PTH content and synthetic capability. Parathyroid cells respond to changes in extracellular calcium heterogeneously in that more PTH per cell is released, and individual parathyroid cells are "recruited" to release PTH at low calcium concentrations. In addition, parathyroid cells can be induced to secrete suggesting that cells are viable but in a depressed secretory state. Parathyroid cells may exist in an "on" or "off" secretory state.
Adrenocorticotropic Hormone↗
Regulation of parathyroid hormone release by protein kinase-C is dependent on extracellular calcium in bovine parathyroid cells.
The purpose of this study was to evaluate regulation of PTH secretion by protein kinase-C (PKC) in adult bovine parathyroid cells. Extracellular calcium (Ca2+e) is the main physiological regulator of PTH secretion. Putative second messengers include intracellular calcium (Ca2+i), cAMP, inositol trisphosphate, and diacylglycerol (DAG). Both DAG and Ca2+i activate PKC. Certain phorbol esters mimic the effect of DAG and cause prolonged stimulation of PKC. The stimulatory phorbol esters 12-O-tetradecanoylphorbol acetate (1 microM) and phorbol-12,13-dibutyrate (1 microM) did not affect PTH secretion at low Ca2+e, but increased both individual cell secretion and recruitment of cells to secrete at high Ca2+e. The PKC inhibitors H7 (1 microM), tamoxifen (10 microM), and sphinganine (5 microM) inhibited PTH release at low Ca2+e (0.1 and 0.2 mM) and decreased cell recruitment over the physiological range of Ca2+e. The nonstimulatory phorbol esters 4 alpha-phorbol-12,13-didecanoate (1 microM) and phorbol-13-monoacetate (1 microM) had no effect on PTH secretion. To assess the mechanism by which certain phorbol esters stimulated PTH secretion, in situ hybridization for PTH mRNA was performed. Phorbol-12,13-dibutyrate (1 microM) qualitatively increased steady state PTH mRNA levels compared to control values. We conclude that 1) PKC stimulation increased PTH secretion at high Ca2+e, but not at low Ca2+e; 2) PKC inhibition decreased PTH secretion at low Ca2+e; and 3) PKC stimulation increased steady state PTH mRNA levels. These data suggest that PKC plays an important regulatory role in the synthesis and secretion of PTH.
Animals↗
Possible variation in bone resorption during the normal menstrual cycle.
In order to determine whether bone turnover varies during the normal menstrual cycle, we measured biochemical markers of bone resorption (serum pyridinoline cross-linked carboxy-terminal telopeptide of type I collagen (sICTP), fasting urinary hydroxyproline/creatinine, fasting urinary pyridinoline/creatinine and fasting urinary deoxypyridinoline/creatinine) and bone formation (plasma osteocalcin, serum carboxy-terminal propeptide of type I procollagen and serum alkaline phosphatase) in ten healthy premenopausal women every two or three days for a complete menstrual cycle. A cyclic pattern was detected in sICTP, with its nadir during the follicular phase and its peak during the luteal phase, and an overall variation of 17% during the menstrual cycle (p = 0.004). No cyclic changes were observed in the urinary parameters of bone resorption or in the biochemical markers of bone formation. We conclude that sICTP, a new biochemical marker of bone resorption, undergoes small variations during a normal menstrual cycle in premenopausal women, whereas the biochemical markers of bone formation remain constant.
Adult↗
Epidemiology, biochemistry and some results with treatment of postmenopausal osteoporosis.
The present chapter deals with postmenopausal osteoporosis. This is an important disease because it affects millions of people throughout the world. The most serious of the osteoporotic fractures, the hip fractures, needs hospitalization, causes a high degree of mortality, and results often in dependent people. Osteoporosis is thus a significant socioeconomic burden. At the menopause bone turnover increases and bone loss accelerates. Postmenopausal bone loss and osteoporosis may be prevented by oestrogen replacement therapy, but convincing therapy for established osteoporosis does not yet exist. Anabolic steroid therapy can, however, increase the bone mineral content a few percentages a year in postmenopausal osteoporotic women.
Aged↗
Measurement of abdominal and intra-abdominal fat in postmenopausal women by dual energy X-ray absorptiometry and anthropometry: comparison with computerized tomography.
The aim was to develop a model for prediction of intraabdominal adipose tissue (AT) with combined dual energy X-ray absorptiometry (DXA) and anthropometry in postmenopausal women. Intra-abdominal and subcutaneous AT from the 1st to the 4th lumbar intervertebral disk was measured by computerized tomography (CT) (as a reference method) in 25 postmenopausal women (BMI 19.9-35.1 kg/m2). Fat was measured in the corresponding region by DXA. Abdominal sagittal diameters, skinfold thicknesses, and circumferences were also measured. Measurements of abdominal fat by CT and DXA were valid (r = 0.9, s.e.e.%: 7%). Measurement of abdominal fat by DXA explained about 80% of the variation in the intra-abdominal AT (by CT), whereas the waist to hip ratio was the only variable that correlated significantly with the intra-abdominal to subcutaneous AT ratio. Abdominal fat measured by DXA, the waist to hip ratio, and the sum of trunk skinfold thicknesses could in combination accurately predict the intra-abdominal AT measured by CT (r2 = 0.91, s.e.e.% = 15%). The sagittal diameter, measured either anthropometrically or by CT, was not a superior predictor of the intra-abdominal AT. We conclude that the intra-abdominal AT can be predicted in postmenopausal women by DXA combined with anthropometry.
Abdomen↗
Relationships and independence of body composition, sex hormones, fat distribution and other cardiovascular risk factors in overweight postmenopausal women.
The relationships and independence of body composition, sex hormones, fat distribution and other cardiovascular risk factors were studied in 121 overweight postmenopausal women. Body composition and fat distribution were directly measured by dual energy X-ray absorptiometry (DXA); other parameters were waist-to-hip ratio (WTH), sex hormone binding globulin (SHBG), testosterone, androstenedione (A), oestradiol (E2), and lipids and lipoproteins; cigarette and alcohol consumption were recorded. SHBG was correlated with the fat distribution by DXA and WTH (r = -0.35, P < 0.01) and A with the fat mass (r = -0.3, P < 0.01). SHBG had a negative and alcohol and cigarette consumption a positive, independent relationship to a central fat distribution (by DXA and WTH, respectively) (P < 0.01). SHBG (r = 0.23, P < 0.05), fat distribution (WTH) and A (r = -0.2 to -0.3, P < 0.01) were correlated with high density lipoprotein cholesterol (HDL-C). However, only fat distribution (WTH) and A were independently related to HDL-C (P < 0.05). Fat distribution (WTH) and SHBG were independently related to triglycerides (P < 0.05), whereas fat distribution (by DXA) and E2 were independently associated with total cholesterol and low density lipoprotein cholesterol (LDL-C) (P < 0.05). Thus, in overweight postmenopausal women, androgenicity and cigarette and alcohol consumption were independently positively related to a central fat distribution. Furthermore, atherogenic levels of lipids and lipoproteins were independently related to a central fat distribution, androgenicity and low levels of oestrogens.
Absorptiometry, Photon↗
Is heritability a risk factor for postmenopausal osteoporosis?
We investigated heritability as a risk factor for the development of osteoporosis in two randomly selected populations of postmenopausal women and their premenopausal daughters. We determined the familial resemblance in bone mass at three sites; the distal forearm, lumbar spine, and proximal femur, premenopausally and with increasing maternal postmenopausal age. We also examined the bone mass of daughters in relation to mothers with and without osteoporotic fractures. Peak bone mass among premenopausal siblings was significantly correlated at all sites (r = 0.30-0.42, p less than 0.001). The same levels of resemblance were found between early postmenopausal mothers and premenopausal daughters. There was no significant difference in bone mass at any skeletal site between daughters of women with either peripheral or spinal fractures and daughters of women without fractures. We also examined familial resemblance with four biochemical markers of bone turnover (fasting urinary calcium and hydroxyproline, both corrected for creatinine, serum alkaline phosphatase, and plasma bone Gla protein). A generally significant resemblance were seen in premenopausal siblings (r = 0.25-0.39, hydroxyproline NS), but not between premenopausal daughters and postmenopausal mothers. We conclude that peak bone mass is hereditary in the distal forearm, lumbar spine, and proximal femur, but the mother-daughter resemblance explains only about 16% of the variability in daughters' bone mass. Furthermore, daughters of women with a moderate state of osteoporotic fractures are not substantially at an increased risk of having a low peak bone mass compared to the daughters of women without fractures.
Absorptiometry, Photon↗
Diurnal variation in serum markers of type I collagen synthesis and degradation in healthy premenopausal women.
There are several indications that the functions of human osteoblasts and osteoclasts have circadian rhythms with peak activities occurring at night. It is not known, however, whether the principal function of these cells, namely synthesis and degradation of the organic matrix of bone, of which about 90% is type I collagen, also has a circadian rhythm. This was therefore investigated for both the formation of type I collagen and the degradation of type I collagen in bone using two newly developed serum markers: the serum concentration of the carboxy-terminal propeptide of type I procollagen (PICP) as a marker of formation and the serum concentration of the carboxy-terminal pyridinoline cross-linked telopeptide of type I collagen (ICTP) as a marker of degradation. PICP and ICTP were measured by RIA in samples taken every 3 h over a 24 h period in 12 healthy premenopausal women (age 32 +/- 5 years, mean +/- SD). Both PICP (p = 0.003) and ICTP (p = 0.00003) showed a significant circadian rhythm, with about 20% higher values at night than in the afternoon. We conclude that serum markers of both the formation of new type I collagen and the degradation of old type I collagen in bone exhibit a clear circadian rhythm, with increased activity of both osteoblasts and osteoclasts at night. The etiology of this circadian rhythm is still unknown.
Adult↗
Measurements of bone mineral density of the proximal femur by two commercially available dual energy X-ray absorptiometric systems.
Two dual energy X-ray absorptiometric (DXA) instruments have recently become commercially available for local bone densitometry: the QDR-1000 (Hologic Inc.) and the DPX (Lunar Radiation Corp.). We report the precision, influence of femoral rotation, correlation and agreement of bone mineral measurements of the proximal femur by these two instruments. In vitro (femur phantom) short-term precision was 1.1%-3.5%, and the long-term precision was 1.2%-3.8%. In vivo (groups of 10 premenopausal and 10 post-menopausal women) short-term precision of duplicate measurements was 1.6%-4.7%, and long-term precision was 1.9%-5.5%. Overall, the precision for Ward's triangle was over 3% and that for the femoral neck and trochanter, 2%-3%. Rotation of a femur phantom produced a statistically significant change in the bone mineral density (BMD) of the femoral neck. Within a clinically relevant range of femoral rotation (20 degrees inward rotation +/- 5 degrees) the coefficient of variation (CV%) increased by a mean factor of 1.1-1.4. Although the correlation (r less than 0.9) between BMD measurements of the proximal femur by the DPX and QDR-1000 in 30 postmenopausal women was high, there was lack of agreement between the two instruments. We found no statistically significant differences between the right and left femur in 30 postmenopausal women. A bilateral femur scan took a mean total time of about 22 min. We conclude that with the introduction of DXA instruments, the precision of bone mineral measurements of the proximal femur has improved. However, for comparability between commercially available DXA instruments, it might be advantageous if units were standardized.
Absorptiometry, Photon↗
Effect of menopause and hormone replacement therapy on urinary excretion of pyridinium cross-links: a longitudinal and cross-sectional study.
OBJECTIVE: To study longitudinally the effect of the menopause and hormone replacement therapy on the new markers of bone resorption: urinary excretion of pyridinoline and deoxypyridinoline. DESIGN AND PATIENTS: Urinary pyridinoline and deoxypyridinoline were measured every 3 months for 2-3 years in 15 healthy women aged 45-54 years. Nine remained premenopausal and six became post-menopausal during the study. Urinary pyridinoline and deoxypyridinoline were also measured before and after 3 months of either placebo or hormone replacement therapy in 65 post-menopausal women, aged 45-54 years, who were participating in a double-blind study. MEASUREMENTS: Urinary pyridinoline and deoxypyridinoline were measured in fasting urine samples by spectrofluorometry after high performance liquid chromatography and corrected for creatinine excretion. RESULTS: Urinary pyridinoline and deoxypyridinoline remained almost constant during the premenopausal period. Both started to increase 6 months after the last menstrual bleeding and the mean post-menopausal values were 30-50% higher than the premenopausal values in the same subjects (values in nmol/mmol creatinine given as mean +/- SEM: urinary pyridinoline (premenopausal) = 29 +/- 2 vs urinary pyridinoline (post-menopausal) = 38 +/- 6, P < 0.05; urinary deoxypyridinoline (premenopausal) = 8 +/- 1 vs urinary deoxypyridinoline (post-menopausal) = 12 +/- 1, P < 0.05). Three months of post-menopausal hormone replacement therapy decreased (P < 0.001) both to premenopausal levels. CONCLUSION: Urinary pyridinoline and deoxypyridinoline, new markers of bone resorption, remain fairly constant in the years before the menopause and start to increase about 6 months after the last menstrual bleeding. This increase is reversed by hormone replacement therapy.
Amino Acids↗
Marked diurnal variation in urinary excretion of pyridinium cross-links in premenopausal women.
To investigate whether bone resorption exhibits a diurnal variation in healthy premenopausal women, we measured urinary excretion of pyridinoline and deoxypyridinoline cross-links (U-Pyr/Cr and U-D-Pyr/Cr) every 3 h over a 24-h period in 12 healthy premenopausal women (mean +/- 1 SD age, 32 +/- 5 yr). To study diurnal variation, U-Pyr/Cr and U-D-Pyr/Cr are the best available markers of bone resorption for a diurnal variation study, as they are not influenced by diet. Plasma osteocalcin and serum alkaline phosphatase (markers of bone formation) were also measured. A marked diurnal rhythm was observed in U-Pyr/Cr and U-D-Pyr/Cr, with the peak between 0500-0800 h and the nadir between 1400-2300 h. The fluctuation was 2-fold over the 24-h period, with a mean fall of 25-35% between 0800-1100 h. This study demonstrates a marked diurnal variation in the new biochemical markers of bone resorption, U-Pyr/Cr and U-D-Pyr/Cr, in premenopausal women. Furthermore, this study emphasizes the importance of regulating the time of the urine sample taken for measuring urinary pyridinium cross-links for clinical investigations as well as in clinical practice.
Adult↗
Basal and regulated secretion of insulin-like growth factor binding proteins in osteoblast-like cells is cell line specific.
Local secretion of insulin-like growth factor binding proteins (IGFBPs) may modulate the effects of IGF-I and IGF-II on bone cell metabolism and proliferation. Several osteoblast-derived cell lines are currently used as interchangeable models to study IGFBP production, although it is unknown whether findings in one cell line can be extrapolated to another cell line or to normal human osteoblasts. In this study, we examined by Western ligand blotting both basal and regulated secretion of IGFBPs in vitro in 1) normal human osteoblast-like (hOB) cells cultured from explants of human trabecular bone; 2) an SV40-transformed hOB (HOBIT) cell line; and 3) several human (U-2, MG-63, TE-85) and rat (ROS 17/2.8 and UMR-106-01) osteosarcoma cell lines. Constitutively, hOB and HOBIT cells produced a similar pattern of IGFBPs, while all other cell lines produced their own unique pattern of IGFBPs. The two rat cell lines differed from the human cell lines as well as from each other. The response to hormonal stimulation also varied among the cell lines. Treatment of hOB and HOBIT cells with IGF-I resulted in a 2-fold increase in medium levels of IGFBP-3; IGF-I decreased levels of 24-kilodalton (kDa) IGFBP in hOB cell-conditioned medium. In addition, IGF-I markedly increased levels of the 29/32/34 kDa IGFBP triplet in U-2 cells, but had little or no effect in the other human and rat osteosarcoma cell lines. PTH increased a 29-kDa IGFBP apparent only in UMR 106-01 cell-conditioned medium, whereas GH had no direct effect on IGFBP secretion in any of the osteoblast-like cells tested. We conclude that basal and regulated secretion of IGFBPs from osteoblast-like cells is cell-line specific. Spontaneously transformed human or rat osteoblast-like cells provide unique model systems to study features of distinct IGFBPs and their regulation; however, hOB cells and their derivatives may be more appropriate models for understanding the regulation of IGFs in human bone.
Animals↗
Skeletal responsiveness to endogenous parathyroid hormone in postmenopausal osteoporosis.
To test the hypothesis that increased sensitivity of bone to PTH may be a major cause of bone loss in postmenopausal osteoporosis, we induced acute calcium deprivation and measured bone responsiveness to endogenous PTH under physiological conditions. Eighteen osteoporotic and 17 normal postmenopausal women with similar dietary calcium intakes were studied before and after 4 days of calcium deprivation (dietary calcium 230 mg/day and treatment with a calcium-binding agent). Despite decreased serum PTH values, the baseline indices of bone turnover (serum osteocalcin level and 24-h urinary excretions of total deoxypyridinoline/creatinine and pyridinoline/creatinine corrected for total body bone mineral content), were higher in the osteoporotic women. During calcium deprivation, the changes in bone markers from baseline were similar in both groups, except for serum osteocalcin and serum type I procollagen carboxy-terminal propeptide. Changes in the normal and the osteoporotic women were, respectively: serum ionized calcium concentration decreased 3.3% and 2.1%; serum intact PTH increased 65% and 56%; plasma 1,25-dihydroxyvitamin D3 increased 29% and 39%; pyridinoline/creatinine increased 12% and 11%; and deoxypyridinoline/creatinine increased 27% and 12%. Serum osteocalcin increased 2.3% and serum procollagen carboxy-terminal propeptide decreased 9.4% in the normal women but did not change in the osteoporotic women. We conclude that women with postmenopausal osteoporosis do not have increased skeletal responsiveness to PTH compared with age-comparable normal postmenopausal women. Therefore, the higher bone turnover in postmenopausal osteoporosis, despite lower serum intact PTH concentration, must be due to other factors. Assessment of acute changes in bone turnover during physiological alterations in endogenous PTH secretion is a useful test in metabolic bone diseases.
Bone Density↗