Measurement of bone mineral density.
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Absorptiometry, Photon↗
Biomedical subjects
C Hassager
Publications and source records attributed to C Hassager.
Early postmenopausal diminution of forearm and spinal bone mineral density: a cross-sectional study.
Diminution of bone mineral density (BMD) in the spine and forearm was studied cross-sectionally in 363 women who were 6 months to 10 years postmenopausal. BMD was determined by dual-energy X-ray absorptiometry (DXA) (Hologic QDR-2000) in the lumbar spine, in both the supine lateral (LAT) and anteroposterior (AP) projections, and in the distal third of the forearm. The postmenopausal diminution of BMD was best described by an exponential fit. The initial rate of postmenopausal diminution of BMD was highest in the most trabecular sites (LAT > AP > forearm), but 10-year diminution was similar at all sites (12%-13%, corresponding to about 1.0-1.5 SD), and extrapolation suggested reverse order of the rates of diminution thereafter (forearm > AP > LAT). When bone mineral content of the entire L3 vertebra (tBMC) was measured in vivo, AP tBMC could account for only 67% of the variation in LAT tBMC, compared with r2 = 0.997 in vitro. This observation suggests an accuracy problem in vivo in one of the spine measurement methods. We conclude that the initial rate of BMD diminution after the menopause seems to be highest in the spine, especially when measured laterally, but that this rate levels off within the first decade. The lower precision error of a forearm measurement (0.8% v 1.6 for AP and 3.1 for LAT) therefore implies that this method may require a shorter observation period than spine measurements for the detection of bone loss 5-10 years after menopause. Long-term longitudinal spine and forearm measurements are, however, needed to confirm these conclusions.
Absorptiometry, Photon↗
Circadian rhythm in type I collagen formation in postmenopausal women with and without osteopenia.
A circadian rhythm in the serum concentration of the procollagen type I carboxyl-terminal propeptide (sPICP) has previously been demonstrated in premenopausal women. This study was performed to investigate the circadian rhythm in sPICP in healthy and osteopenic postmenopausal women. Blood samples were taken every third hour for 27 h from three groups of women: 12 early postmenopausal women (aged 55 +/- 2 years; mean +/- SD); 12 late postmenopausal women (aged 73 +/- 1 years); and 12 osteopenic but otherwise healthy late postmenopausal women (aged 73 +/- 1 years). A circadian rhythm in sPICP was found in all three groups, as shown by cosinor analysis (p = 0.000003-0.03). The circadian rhythm in sPICP was significantly different between the osteopenic group and the age-matched healthy group (p < 0.008). The amplitude of the circadian rhythm in sPICP was about twice as high in the osteopenic group, and the time of the maximum tended to be about 3 h later, as compared with the age-matched healthy group. The plasma concentration of osteocalcin, as measured by a recently developed two-site enzyme-linked immunosorbent assay, also showed a circadian rhythm in all three groups (p = 0.0001-0.05), with no significant differences between groups. In conclusion, we have found a significant circadian rhythm in sPICP in both early and late postmenopausal women. In osteopenic women the nightly peak in sPICP is larger and persists later into the night as compared with non-osteopenic women.
Aged↗
Age- and menopause-associated variations in body composition and fat distribution in healthy women as measured by dual-energy X-ray absorptiometry.
To assess the variation with age and menopause, 407 healthy normal women aged 18 to 75 years had body composition and fat distribution measured by dual-energy x-ray absorptiometry (DEXA). The mean +/- SD are given for different age decades. Postmenopausal women had significantly more fat, a more central fat distribution, and less lean tissue mass (LTM) than premenopausal women. In premenopausal and postmenopausal women, age only correlated with the abdominal to total-body fat tissue ratio (r approximately .24, P < .05), whereas the years since onset of menopause correlated with fat tissue mass (FTM), fat%, abdominal fat%, and the abdominal to total-body fat tissue ratio (r approximately .2, P < .05). To assess the independent impact of age, menopausal status, and years since menopause, multiple linear regressions were performed. FTM, fat%, and abdominal fat% were significantly related to menopausal status and years since menopause independently of age. The abdominal to total-body fat tissue ratio was statistically significantly related to age, but tended also to be independently related to years since menopause. LTM was statistically significantly related to menopausal status independently of age and years since menopause. In summary, we suggest that in healthy women total-body and abdominal fat may increase and LTM may decrease in the years after menopause, primarily in the perimenopausal years, without significant changes before menopause.
Absorptiometry, Photon↗
Creatinine clearance at menopause is not related to bone mass in later life.
OBJECTIVE: To investigate whether creatinine clearance (Ccr) at menopause is related to bone mass later in life. METHODS: Ccr was measured within 5 years after natural menopause in two groups of normal women. Bone mineral content (BMC) of the distal forearm, lumbar spine, and proximal femur were measured by photon absorptiometry and dual energy X-ray absorptiometry in these women 6 years (n = 47) and 14 years later (n = 98). RESULTS: Ccr corrected for body surface area just after the menopause did not correlate with BMC, 6.5 years and 14.5 years later. CONCLUSION: Low Ccr within the normal range at menopause is not an independent risk factor for osteopenia in later life.
Absorptiometry, Photon↗
Dual energy X-ray absorptiometry of the spine--decubitus lateral versus anteroposterior projection in osteoporotic women: comparison to single energy X-ray absorptiometry of the forearm.
We investigated the discriminatory ability of dual energy X-ray absorptiometry (DXA) of the lumbar spine in the anteroposterior vs. decubitus lateral projection in 53 elderly women with at least one vertebral fracture and 63 age-matched women without fracture. Twenty-three premenopausal healthy women served as a reference group. Spine measurements were compared to forearm measurements by single energy X-ray absorptiometry (SXA). Bone mineral density (BMD) of the women with fractures was 16% lower in the AP projection and 17% lower in the decubitus lateral projection compared to age-matched women without fractures. t-Scores (deviation from normal premenopausal values in SDs) were -2.1 to -2.3 in the women without fractures, and -3.9 (AP projection), -3.1 (lateral projection) and -3.8 (forearm) in the women with vertebral fractures. t-Scores as well as z-scores for bone mineral content of the vertebral body and the vertebral posterior elements (both measured with the lateral projection) were similar. ROC analysis showed no significant difference between the AP and the lateral projection of the spine. When subjects with vertebral endplate sclerosis (about 25% in each group, with considerably elevated spinal BMD) were excluded, it did not significantly change the diagnostic abilities for fractures. We found no diagnostic advantage of the lateral projection as compared to the AP projection or forearm measurement. Future studies will reveal whether absorptiometry in the lateral projection can be improved by supine lateral scanning.
Absorptiometry, Photon↗
Changes in the carboxyl-terminal propeptide of type I procollagen and other markers of bone formation upon five days of bed rest.
This study was performed in order to investigate the influence of skeletal unloading on the serum concentration of the carboxyl-terminal propeptide of type I procollagen (sPICP) and other markers of bone formation. Blood samples were taken every third hour from nine healthy premenopausal women (22-29 years) in two 24 h studies, before and at the end of five days of bed rest. Furthermore, a set of samples were taken 12 h apart after three days of bed rest. We measured sPICP, the serum concentration of intact and N-terminal-Mid fragment osteocalcin (sOC), and the serum concentration of alkaline phosphatase (sAP). During the five days of bed rest a gradual increase in sOC was observed, while sPICP gradually decreased. sAP was unchanged. Five days of best rest resulted in the following overall changes in the 24 h mean values: sPICP: -14% (p = 0.002); sOC: +9% (p = 0.009); sAP: -1% (not significant). The circadian patterns did not change significantly after bed rest. It is puzzling that the changes in the bone formation markers are of different magnitude, and for sPICP and sOC even in opposite directions. The increase in sOC may be caused by an increase in OC secretion by the osteoblasts or a release of bone-incorporated OC from resorbing sites; the accompanying decrease in sPICP may indicate that bone formation is actually transiently decreased after short term bed rest.
Adult↗
Bone and collagen turnover during treatment with inhaled dry powder budesonide and beclomethasone dipropionate.
OBJECTIVES: To assess bone and collagen turnover in asthmatic children treated with dry powder budesonide from the Turbuhaler and dry powder beclomethasone dipropionate from the Diskhaler in a dose of 800 micrograms/day. SUBJECTS: Thirteen prepubertal children with asthma. DESIGN: Open crossover study with two treatment periods and treatment free run-in and wash-out periods. All periods were of two weeks' duration. At day 14 in each period blood samples were taken for assessment of serum osteocalcin, the carboxyterminal propeptide of type I collagen (PICP), and the aminoterminal propeptide of type III collagen (PIIINP). At the same time urine was collected for assessment of creatinine corrected pyridinoline (uPYR/cr) and deoxypyridinoline (udPYR/cr) crosslinks. RESULTS: Osteocalcin concentrations were not influenced by any of the treatments. During budesonide treatment mean (SEM) PICP was reduced by 18% (8%) (p = 0.03), PIIINP by 24% (3%) (p = 0.0002), uPYR/cr by 16% (6%) (p = 0.03), and udPYR/cr by 21% (13%) (p = 0.12). During treatment with beclomethasone dipropionate mean (SEM) PICP was reduced by 20% (6%) (p = 0.01), PIIINP by 36% (3%) (p = 0.0002), uPYR/cr by 18% (4%) (p = 0.004), and udPYR by 13% (5%) (p = 0.02). The suppressive effect of beclomethasone dipropionate on PIIINP was more marked than that of budesonide (p = 0.001). CONCLUSION: Treatment with dry powder budesonide and beclomethasone dipropionate 800 micrograms/day is associated with suppression of bone and collagen turnover. The suppression seems to be more marked during treatment with beclomethasone dipropionate. Long term effects and effects of lower doses of budesonide and beclomethasone dipropionate on bone and collagen markers needs further study.
Administration, Inhalation↗
The effect of menopause and hormone replacement therapy on bone alkaline phosphatase.
We evaluated two different assays for the determination of bone-specific alkaline phosphatase (B-AP). One assay was a direct method using a two-site IRMA (AP(Hyb)). The other assay determined B-AP indirectly after precipitation with lectin (AP(BM)). The assays were compared to serum osteocalcin (levels) and total AP in 20 premenopausal women and in 40 early postmenopausal women before and after 9 months of treatment with hormone replacement therapy (HRT) (n = 20) or placebo (n = 20). Serum osteocalcin correlated with serum AP(Hyb) (r = 0.45), and with serum AP(BM) (r = 0.33) (both p < 0.001). The correlation between AP(Hyb) and AP(BM) was moderate, r = 0.71 (p < 0.001). When comparing postmenopausal to premenopausal women, serum osteocalcin had a t score (mean +/- SEM) of 2.30 +/- 0.29 followed by total AP(T-AP) (1.20 +/- 0.28), AP(Hyb) (1.05 +/- 0.33) and AP(BM) (0.64 +/- 0.21) (paired t-test: p < 0.01 for osteocalcin vs. other markers). After 9 months of HRT all markers had declined significantly to premenopausal levels (mean +/- SEM): osteocalcin with 44.5% +/- 6.1%; AP(BM) with 32.1% +/- 5.6%; AP(Hyb) with 36.4% +/- 4.4% and T-AP with 24.4% +/- 2.9%; p < 0.001. Of the markers, only serum osteocalcin correlated significantly with the rate of bone loss in the placebo group (r = 0.52, p < 0.02). We conclude that both assays for B-AP reflect bone turnover in postmenopausal women with and without HRT. Under controlled conditions they did not show any advantage of osteocalcin in diagnosing increased bone turnover or monitoring the effect of an anti-resorptive therapy in postmenopausal women.
Adult↗
The response to treatment of overweight in postmenopausal women is not related to fat distribution.
OBJECTIVE: To investigate whether fat distribution or sex hormone status in overweight postmenopausal women do influence the response to treatment of overweight. DESIGN: Longitudinal, clinical intervention study of a 4.2 MJ diet daily with or without exercise. SUBJECTS: 98 healthy, overweight, postmenopausal women (age: 49-58 y, BMI: 25-42 kg/m2). MEASUREMENTS: Various fatness and fat distribution parameters (by dual-energy x-ray absorptiometry and anthropometry), sex hormone-binding globulin (SHBG), sex hormones, and the resting energy expenditure (REE) at baseline and after 3 months. RESULTS: Reductions in weight and fat were independent of the initial fat distribution and the REE, but were significantly associated with high initial SHBG levels. Furthermore, loss of fat was significantly and independently associated with increases in SHBG and reductions in central fat distribution. CONCLUSION: Postmenopausal women with an android and gynoid fat distribution respond with similar weight loss to treatment of overweight. Furthermore, a more healthy, less android, fat distribution and sex hormone status may be achieved with increasing weight loss.
Absorptiometry, Photon↗
[Physical exercise as a supplement to diet. Effect on body composition, resting metabolic rate and cardiovascular risk factors in postmenopausal overweight women].
One hundred and twenty-one healthy, overweight, postmenopausal women were randomly assigned to three groups: controls (no intervention), a 4200 kJ/day diet, or 4200 kJ/day diet with combined aerobic and anaerobic exercise, for 12 weeks. One hundred and eighteen women completed the study. The loss of weight was similar in the two intervention groups, but compared with the diet-only group, the diet-plus-exercise group lost significantly more fat (7.8 vs 9.6 kg) and no lean tissue mass (1.2 vs 0.0 kg). The resting metabolic rate was increased in the diet-plus-exercise group as compared to the controls (11% vs 4%, p < 0.009). The cardiovascular risk factors (serum lipids and lipoproteins (except high density lipoprotein), systolic blood pressure, and the waist-to-hip ratio) decreased significantly in both intervention groups, as compared to the controls. There were no consistent, major differences between groups in changes in total body, spinal, or forearm bone mineral density. In conclusion, overweight postmenopausal women benefit from addition of combined aerobic and anaerobic exercise to an energy-restrictive diet.
Aged↗
Posture, age, menopause, and osteopenia do not influence the circadian variation in the urinary excretion of pyridinium crosslinks.
This study was performed to investigate whether the circadian variation in urinary pyridinium crosslinks is related to physical activity, age, the menopause, and asymptomatic osteopenia. We measured urinary pyridinoline/creatinine (Pyr/Cr) and deoxypyridinoline/creatinine (D-Pyr/Cr) in 9 healthy premenopausal women in two 27 h studies, before and at the end of 5 days of total bed rest. Both Pyr/Cr and D-Pyr/Cr showed highly significant circadian variations, with the peak at night and the nadir during the day (p < 0.001). The 5 days of complete bed rest produced no changes in the circadian pattern, but a general increase of 28% was observed in pyridinium crosslinks. A group of 12 healthy, early postmenopausal women (aged 55 +/- 2 years), 12 healthy, elderly postmenopausal women (aged 73 +/- 1 years), and 12 elderly osteopenic but otherwise healthy women (aged 73 +/- 1 years) were also studied for 27 h. All three groups showed highly significant (p < or = 0.001) circadian variations in the urinary excretion of pyridinium crosslinks. As expected, both Pyr/Cr (p < 0.05) and D-Pyr/Cr (p < 0.001) increased at the time of menopause, but the circadian variations in Pyr/Cr and D-Pyr/Cr were similar in all groups studied. We conclude that the circadian variation in the urinary excretion of pyridinium crosslinks is independent of physical factors. Furthermore, the circadian variation in pyridinium crosslinks was not related to age, menopausal status, or asymptomatic osteopenia.
Adult↗
The carboxy-terminal pyridinoline cross-linked telopeptide of type I collagen in serum as a marker of bone resorption: the effect of nandrolone decanoate and hormone replacement therapy.
Carboxy-terminal pyridinoline cross-linked telopeptide of type I collagen (ICTP) in serum has recently been proposed as a new biochemical marker of bone resorption. In the present study we compared serum ICTP with radiopharmaceutical and histomorphometric measurements of bone turnover in postmenopausal women with mild osteoporosis, and assessed the effect of hormone replacement therapy (HRT) (2 mg 17 beta-estradiol plus 1 mg norethisterone daily) and anabolic steroid therapy (50 mg nandrolone decanoate (ND) i.m. every 3 weeks) on serum ICTP in two double-blind placebo-controlled studies with 55 to 75-year-old women. Serum ICTP measured by radioimmunoassay (RIA) correlated significantly with the 24-hour whole body retention of 99m-technetium diphosphonate (Rho = 0.47, P < 0.001, n = 66), but not with histomorphometric measurements of bone turnover in iliac crest biopsies. One year of HRT (n = 16) versus placebo (n = 15) did not produce significant changes in serum ICTP. Compared with placebo (n = 17), 1 year of ND (n = 19) produced an increase in serum ICTP of 90 +/- 16% (P < 0.0001); 6 months after discontinuation of the treatment, serum ICTP had returned to pretreatment values. We conclude that serum ICTP does reflect bone metabolism in postmenopausal osteoporosis, but it is not a sensitive marker of the changes in bone resorption induced by hormone replacement therapy, and it does not correspond with other measures of bone resorption during anabolic steroid therapy.
Aged↗
Effect of the menopause and hormone replacement therapy on the carboxy-terminal pyridinoline cross-linked telopeptide of type I collagen.
We investigated the effect of the menopause and postmenopausal hormone replacement therapy (HRT) on the serum concentration of carboxy-terminal pyridinoline cross-linked telopeptide of type I collagen (ICTP), a potential new biochemical marker of bone resorption. A group of 44 healthy postmenopausal women, aged 45-54 years, had about 19% higher serum ICTP than did a group of 42 healthy premenopausal women aged 35-50 years (3.6 +/- 0.8 micrograms/l v 3.0 +/- 0.7 micrograms/l (mean +/- SD); p < 0.01), although there was a large overlap in the values. The 44 postmenopausal women also participated in a longitudinal clinical study, in which 20 received HRT and 24 received a placebo. Compared with the placebo group, those who received HRT had a significant (p < 0.05) decrease in ICTP of about 12% at the end of 1 year of treatment, but again there was considerable overlap in the values. The menopause- and HRT-induced changes in ICTP were less than those seen in serum osteocalcin, serum total alkaline phosphatase, and fasting urinary excretion of hydroxyproline, calcium, pyridinoline and deoxypyridinoline. We conclude that the menopause increases and HRT decreases ICTP, although these changes are less pronounced than those seen in other biochemical markers of bone turnover.
Animals↗
Non-responders to hormone replacement therapy for the prevention of postmenopausal bone loss: do they exist?
Hormone replacement therapy (HRT) prevents postmenopausal bone loss, but the prevalence of non-responders in healthy early postmenopausal women is not known. In order to study this, we reviewed data from three published studies, each carried out in a randomized, placebo-controlled, longitudinal design over 2 year, that used seven hormone replacement therapies. Bone mineral content (BMC) was measured in the distal forearm by single photon absorptiometry. A mathematical model for elimination of measurement errors was applied to published BMC data. After this correction, we found that only 1.2% of early healthy postmenopausal women who are receiving HRT in conventional doses will lose more than 1% of forearm BMC per year. In conclusion, most, if not all, healthy early postmenopausal women who might need HRT against loss of bone will respond positively in forearm BMC to such therapy.
Bone Density↗
Total and regional body-composition changes in early postmenopausal women: age-related or menopause-related?
Total and regional body composition were measured in 373 early postmenopausal women aged 49-60 y by dual-energy x-ray absorptiometry to evaluate whether the changes in body composition in the early postmenopausal years are related to menopause itself or merely to age. Both fat mass and fat distribution correlated with age (r = 0.12-0.21, P < 0.05-P < 0.001), but not with years since menopause (YSM). Lean tissue mass, on the other hand, decreased with YSM (r = -0.17, P < 0.001) but was not related significantly to age. Total body bone mineral density decreased with both YSM (r = -0.30, P < 0.001) and age (r = -0.21, P < 0.001). Our study suggests that postmenopausal changes in body fat and fat distribution are more dependent on age than on menopause, but we cannot exclude a separate effect of the menopause. Changes in fat-free mass, including a postmenopausal decline in both soft lean tissue mass and bone mass, are, however, mainly menopause-related
Adipose Tissue↗
Urinary excretion of pyridinium cross-links in healthy women; the long-term effects of menopause and oestrogen/progesterone therapy.
OBJECTIVES: We investigated the effect of the menopause when followed longitudinally for a decade to evaluate whether women with an increased bone loss continue to have elevated urinary excretion of pyridinium cross-links later in menopause. Furthermore, we investigated the effect of oestrogen/progesterone therapy on the urinary excretion of pyridinium cross-links. PARTICIPANTS: In the cross-sectional study: 18 healthy premenopausal, 142 healthy post-menopausal women and 41 osteopenic post-menopausal women. In the longitudinal study: 45 healthy post-menopausal women followed up for 7-10 years after the menopause; these women were further divided into two equal groups, according to their loss of forearm bone mineral content over 2 years. In the oestradiol/progesterone double-blind, placebo-controlled 2-year trial: early post-menopausal women were given either hormone replacement therapy (n = 38) or placebo (n = 16). MEASUREMENTS: The urinary excretion of pyridinoline/creatinine (Pyr/Cr) and urinary deoxypyridinoline/creatinine (D-Pyr/Cr), two new markers of bone resorption. RESULTS: Pyr/Cr and D-Pyr/Cr increased significantly after the menopause (Pyr/Cr, 77%; D-Pyr/Cr, 98%, P < 0.001). Hormone replacement therapy reversed this increase towards premenopausal levels. Both pyridinium cross-links remained fairly constant during the first decade of the menopause, when measured in the longitudinal study. When the women were divided according to loss in forearm BMC, those with a loss greater than 3.5%/2 years had significantly higher levels of pyridinium cross-links (P < 0.05-0.01). Furthermore, both Pyr/Cr and D-Pyr/Cr were significantly higher in elderly osteopenic women (aged 68-72 years) than in age-matched non-osteopenic women (P < 0.01-0.001). CONCLUSIONS: Both Pyr/Cr and D-Pyr/Cr, two new markers of bone resorption, increased significantly at the time of the menopause, thereafter remaining fairly constant during the first post-menopausal decade. Women with increased bone loss continue to have elevated urinary excretion of pyridinium cross-links during the first decade of the menopause. This post-menopausal change is reversed by hormone replacement therapy to the premenopausal level.
Adult↗
Six months' follow-up on exercise added to a short-term diet in overweight postmenopausal women--effects on body composition, resting metabolic rate, cardiovascular risk factors and bone.
The aim of this work was to study the long-term effects of the addition of exercise to a short-term diet in overweight postmenopausal women. A follow up study was made of 118 overweight, postmenopausal women, who 6 months earlier had completed 12 weeks of randomized intervention (three groups: 4.2 MJ/d diet, 4.2 MJ/d diet with exercise, and controls). The following were measured: body composition and fat distribution (measured by dual-energy X-ray absorptiometry), resting metabolic rate, serum lipids and lipoproteins, blood pressure, and bone mineral densities. It was found that weight was still significantly reduced (by about 8 kg). HDL-C was significantly increased (10%), and triglycerides decreased (20%), whereas the initial reductions in total cholesterol and LDL-C had disappeared at the follow-up. The women from the former diet-plus-exercise group, who were current exercisers at the follow-up, had a significantly greater reduction in weight (10.9 vs 6.6 kg), fat tissue mass (10.0 vs 5.4 kg) and abdominal-to-total-body fat tissue mass (9.6 vs 4.7), and a significantly greater increase in the resting metabolic rate (11.1 vs 1.1 kJ/kg/d), as compared with the non-exercisers from this group. There were no major detrimental changes in total body, spinal, or forearm bone mineral density or in markers of bone turnover. The short-term dietary treatment in this study may have beneficial long-term effects on weight, fat tissue mass and cardiovascular risk factors with no additional benefits from added exercise, unless the exercise is continued.
Body Composition↗