Hormone replacement therapy--with or without added progestin--and which progestin?
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Drug Therapy, Combination↗
Biomedical subjects
C Christiansen
Publications and source records attributed to C Christiansen.
Insulin resistance, exercise capacity and body composition in subjects with two hypertensive parents.
OBJECTIVE: To study insulin resistance in subjects with strong genetic predisposition to essential hypertension, compared with non-disposed subjects. SUBJECTS: Thirty normotensive subjects aged 18-35 years whose parents both had essential hypertension, and 30 age- and sex matched subjects whose parents were both normotensive, were studied. Subjects or parents with diabetes and morbid obesity were excluded. METHODS: The study comprised (1) a frequent sampling oral glucose tolerance test; (2) an isoglycemic hyperinsulinemic clamp study; (3) an analysis of body composition by dual-energy X-ray absorptiometry; (4) an exercise test with gas exchange analysis; and (5) investigation of composition of usual diet by diet registration for 5 days. RESULTS: The 24-h diastolic blood pressure was higher in subjects predisposed to hypertension compared with the controls: 78.1 versus 74.0 mmHg (confidence interval for the difference between the means; -0.5; -7.9), but the insulin sensitivity index was similar: 312 versus 362 I(2) min(-1) pmol(-1) kg(-1) (28; -129). The two groups were similar in terms of body composition, exercise capacity and composition of usual diet. Resting and 24-h diastolic blood pressures were correlated to abdominal fat mass but not to insulin sensitivity. CONCLUSION: Subjects with a strong genetic predisposition to essential hypertension had increased diastolic blood pressure compared with subjects with normotensive parents, but they were not insulin resistant. This may be due to the subjects being highly selected as to confounding factors. The increased blood pressure in the hypertension prone subjects could not be attributed to differences in body composition, exercise capacity or dietary habits.
Absorptiometry, Photon↗
Monitoring of alendronate treatment and prediction of effect on bone mass by biochemical markers in the early postmenopausal intervention cohort study.
To establish whether biochemical markers could be used to monitor alendronate (ALN) treatment and predict long-term response in bone mass, we used results from an ongoing, randomized trial of ALN treatment for prevention of postmenopausal osteoporosis (n = 1202). In women treated with ALN (5 mg), change from baseline at month 6 in urine N-telopeptide cross-links of type I collagen (NTX) and osteocalcin (OC) correlated with change from baseline at month 24 in spine, hip, and total body bone mineral density (BMD) [r = -0.28 to -0.31 (NTX) and r = -0.16 to -0.25 (OC), P<0.001]. This corresponded to a 4- to 5-fold greater increase at month 24 in BMD in the tertiles, with the greatest decrease at month 6 in NTX or OC. In women treated with ALN (5 mg) who had a change at month 24 in spine BMD of at least 0%, 86% (NTX) and 79% (OC) had a decrease at month 6 of at least 40% (NTX) or 20% (OC) (sensitivity). The corresponding specificities were 48% (NTX) and 53% (OC). In conclusion, change at month 6 in NTX and OC, in groups of women treated with ALN, indicated the numeric long-term response in BMD within these groups. In individual women, a decrease at month 6, in NTX or OC below the cut-point, validly identified women who responded, on ALN treatment, with a stabilization or an increase in bone mass. However, lack of decrease below the cut-point in NTX or OC could not be used to identify women with a bone loss during ALN treatment.
Alendronate↗
Monofluorophosphate combined with hormone replacement therapy induces a synergistic effect on bone mass by dissociating bone formation and resorption in postmenopausal women: a randomized study.
Sodium fluoride stimulates bone formation and has been used to treat osteoporosis for decades despite debate about the antifracture efficacy. Hormone replacement therapy (HRT) results in only modest increases in bone mineral density (BMD). However, for women with low bone mass, the ideal therapy should not only inhibit bone resorption but simultaneously stimulate bone formation to increase bone mass above the fracture threshold. We thus performed a randomized, double-blind, placebo-controlled intervention study to prospectively investigate the effect of a low dose of fluoride, in combination with HRT, on BMD and biochemical markers of bone turnover. One hundred healthy postmenopausal women (60-70 yr old) were thus randomly assigned to: 1) HRT [transdermal 17beta-estradiol, releasing 50 microg/day; plus oral norethisterone acetate (NETA), 1 mg/day]; or 2) oral monofluorophosphate (MFP; equivalent to fluoride, 20 mg/day); or 3) HRT+MFP; or 4) placebo, for 96 weeks. All participants received a calcium supplement of 1000 mg/day. Sixty-eight women completed the study. We found a pronounced, linear increase in spinal BMD during treatment with HRT+MFP [11.8% (1.7% SEM)], which was significantly greater than the increase in the HRT group [4.0% (0.5% per yr); P < 0.05]. MFP produced a smaller increase [2.4% (0.6% per yr)], whereas there was no change in the placebo group [0.0% (0.5% SEM)]. Similar changes were found at the other skeletal sites (distal forearm, hip, and total body). Markers of bone formation showed a fall in the HRT group, which was significantly more pronounced than in the combined HRT+MFP group. A nonsignificant increase was found in the MFP group, whereas the placebo group showed a decrease caused by calcium treatment. The marker of bone resorption decreased significantly more in the HRT and the HRT+MFP groups than in the placebo group but tended to increase in the MFP group. In conclusion, this study shows, by use of biochemical markers of bone turnover, that bone resorption and formation may be dissociated, as a result of actions of two compounds with diverging effects on bone turnover. Furthermore, the synergistic effects of relatively low doses of the compounds suggested statistically and clinically significant increases in trabecular and probably also cortical bone. Adverse effects were relatively rare and mild.
Aged↗
Low body mass index is an important risk factor for low bone mass and increased bone loss in early postmenopausal women. Early Postmenopausal Intervention Cohort (EPIC) study group.
Thinness (low percentage of body fat, low body mass index [BMI], or low body weight) was evaluated as a risk factor for low bone mineral density (BMD) or increased bone loss in a randomized trial of alendronate for prevention of osteoporosis in recently postmenopausal women with normal bone mass (n = 1609). The 2-year data from the placebo group were used (n = 417). Percentage of body fat, BMI, and body weight were correlated with baseline BMD (r = -0. 13 to -0.43, p < 0.01) and 2-year bone loss (r = -0.14 to -0.19, p < 0.01). Women in the lowest tertiles of percentage of body fat or BMI had up to 12% lower BMD at baseline and a more than 2-fold higher 2-year bone loss as compared with women in the highest tertiles (p </= 0.004). Women with a lower percentage of body fat or BMI had higher baseline levels of urine N-telopeptide cross-links (r = -0.24 to -0.31, p < 0.0001) and serum osteocalcin (r = -0.12 to -0.15, p < 0.01). To determine if the magnitude of treatment effect of alendronate was dependent on these risk factors, the group treated with 5 mg of alendronate was included (n = 403). There were no associations between fat mass parameters and response to alendronate treatment, which indicated that risk of low bone mass and increased bone loss caused by thinness could be compensated by alendronate treatment. In conclusion, thinness is an important risk factor for low bone mass and increased bone loss in postmenopausal women. Because the response to alendronate treatment is independent of fat mass parameters, prevention of postmenopausal osteoporosis can be equally achieved in thinner and heavier women.
Alendronate↗
Bactericidal effect of 0.95-mW helium-neon and 5-mW indium-gallium-aluminum-phosphate laser irradiation at exposure times of 30, 60, and 120 seconds on photosensitized Staphylococcus aureus and Pseudomonas aeruginosa in vitro.
BACKGROUND AND PURPOSE: Studies have demonstrated a bactericidal effect of laser irradiation when lasers with power outputs of (6 mW are directed toward pathogenic or opportunistic bacteria previously treated with a photosensitizing agent. The purpose of this study was to determine the bactericidal capabilities of irradiation from lasers with power outputs of less than 6 mW on photosensitized microorganisms. METHODS: Two bacteria that commonly infect skin lesions, Staphylococcus aureus and Pseudomonas aeruginosa, were used. The 2 lasers used, the 0.95-mW helium -neon laser and the 5-mW indium-gallium-aluminum-phosphate laser, emit light at a wavelength close to the absorption maxima of the sensitizing agent chosen, toluidine blue O. This agent was used because of its proven effectiveness in sensitizing bacteria. For each bacterial strain, toluidine blue O was added to a 108 cells/mL solution until a 0.01% weight/volume ratio was obtained. These mixtures were spread on agar-coated petri dishes, which were then exposed to 1 of the 2 lasers for 30, 60, and 120 seconds. The cultures were then grown overnight and examined for one or more visible zones of inhibition. The areas surrounding the irradiated zone provided a control for the effects of toluidine blue O alone. To determine the effects of laser irradiation without prior toluidine blue O sensitization, separate plates were established using unsensitized bacteria. RESULTS: Although inconsistencies between plates were noted, both lasers produced at least one zone of inhibition in both bacterial species at all 3 time periods. The 5-mW laser, however, produced a greater number of these zones. CONCLUSION AND DISCUSSION: Laser-induced microbial killing of photosensitized organisms could have clinical applications in the treatment of infected skin lesions, pending in vivo studies.
Colony Count, Microbial↗
Prevention of bone loss with alendronate in postmenopausal women under 60 years of age. Early Postmenopausal Intervention Cohort Study Group.
BACKGROUND: Estrogen-replacement therapy prevents osteoporosis in postmenopausal women by inhibiting bone resorption, but the balance between its long-term risks and benefits remains unclear. Whether other antiresorptive therapies can prevent osteoporosis in these women is also not clear. METHODS: We studied the effect of 2.5 mg or 5 mg of alendronate per day or placebo on bone mineral density in 1174 postmenopausal women under 60 years of age. An additional 435 women who were prepared to receive a combination of estrogen and progestin were randomly assigned to one of the above treatments or open-label estrogen-progestin. The main outcome measure was the change in bone mineral density of the lumbar spine, hip, distal forearm, and total body measured annually for two years by dual-energy x-ray absorptiometry. RESULTS: The women who received placebo lost bone mineral density at all measured sites, whereas the women treated with 5 mg of alendronate daily had a mean (+/-SE) increase in bone mineral density of 3.5+/-0.2 percent at the lumbar spine, 1.9+/-0.1 percent at the hip, and 0.7+/-0.1 percent for the total body (all P<0.001). Women treated with 2.5 mg of alendronate daily had smaller increases in bone mineral density. Alendronate did not increase bone mineral density of the forearm, but it slowed the loss. The responses to estrogen-progestin were 1 to 2 percentage points greater than those to the 5-mg dose of alendronate. Alendronate was well tolerated, with a safety profile similar to that of placebo or estrogen-progestin. CONCLUSIONS: Alendronate prevents bone loss in postmenopausal women under 60 years of age to nearly the same extent as estrogen-progestin.
Alendronate↗
[Relation between common allelic variation in a cross-sectional longitudinal population study. Vitamin D receptor locus, bone mineral density and postmenopausal bone loss].
The aim of this study was to determine whether common allelic variation at the vitamin D receptor locus is related to bone mineral density and postmenopausal bone loss. Five hundred and ninety-nine healthy women aged 27 to 72 and 125 women with low bone mass aged 55-77 were measured once in a cross-sectional design. Furthermore, 136 women aged 45-54 were followed longitudinally for 18 years. The vitamin D receptor genotypes were determined using Polymerase Chain Reaction-Restriction Fragment Length Polymorphism analysis for three different polymorphic restriction sites (BsmI, ApaI and TaqI). Bone mineral density was measured by photon and X-ray absorptiometry. The cross-sectional study showed no significant relationship between vitamin D receptor genotype and bone mineral density. The maximum difference between homozygotes was 1.3%, P = 0.33, N = 723. The low bone mineral density group had virtually the same genotype frequencies as the normal bone mineral density group. The results of the longitudinal study showed that vitamin D receptor genotype was neither related to early postmenopausal bone loss: age 51-53 (total bone loss at the lower forearm: -3.6% [3.6%], mean [standard deviation]), late postmenopausal bone loss: age 63-69 (total bone loss at the hip: -6.2% [8.7%]) nor to long term postmenopausal bone loss: age 51-69 (total bone loss at the lower forearm: -24.5% [11.4%]). Using analysis of variance to test for differences in the rates of bone loss between the vitamin D receptor genotypes, P values ranged from 0.07 to 0.79. We conclude that common allelic variation at the vitamin D receptor locus as defined by the endonucleases ApaI, BsmI and TaqI is neither related to bone mineral density nor to the rate of bone loss in healthy postmenopausal Danish women.
Adult↗
Recommendations for the health economics analysis to be performed with a drug to be registered in prevention or treatment of osteoporosis.
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Aged↗
Task performance in virtual environments used for cognitive rehabilitation after traumatic brain injury.
OBJECTIVE: This report describes a reliability study using a prototype computer-simulated virtual environment to assess basic daily living skills in a sample of persons with traumatic brain injury (TBI). The benefits of using virtual reality in training for situations where safety is a factor have been established in defense and industry, but have not been demonstrated in rehabilitation. SUBJECTS: Thirty subjects with TBI receiving comprehensive rehabilitation services at a residential facility. METHODS: An immersive virtual kitchen was developed in which a meal preparation task involving multiple steps could be performed. The prototype was tested using subjects who completed the task twice within 7 days. RESULTS: The stability of performance was estimated using intraclass correlation coefficients (ICCs). The ICC value for total performance based on all steps involved in the meal preparation task was .73. When three items with low variance were removed the ICC improved to .81. Little evidence of vestibular optical side-effects was noted in the subjects tested. CONCLUSION: Adequate initial reliability exists to continue development of the environment as an assessment and training prototype for persons with brain injury.
Activities of Daily Living↗
Leptin in overweight postmenopausal women: no relationship with metabolic syndrome X or effect of exercise in addition to diet.
OBJECTIVE: To examine the effect of diet with exercise on serum leptin and whether leptin is associated with the metabolic syndrome X in a high risk population such as overweight postmenopausal women. STUDY DESIGN AND SUBJECTS: 121 healthy overweight, postmenopausal women (aged 49-58y, body mass index (BMI) 25-42 kg/m2) were randomized to: A low-energy-diet, 4.2 MJ/d (n = 51), low-energy-diet + standardized physical exercise (n=49) or no intervention (control: n=21) for 12 weeks, followed by 6 months follow-up without intervention. MEASUREMENTS: S-leptin was measured by Radio Immuno Assay (RIA), body composition and fat distribution by dual energy X-ray absorptiometry (DEXA) and anthropometry. Factors associated with the metabolic syndrome X and sex hormones were measured. RESULTS: S-leptin was two-fold higher than in normal-weight postmenopausal women and S-leptin was normalized after weight loss induced by the 12-week low-energy-diet, without any additive effect of the exercise. Of the factors associated with the metabolic syndrome X, serum-leptin correlated significantly only with sex-hormone-binding-globulin and plasminogen-activator-inhibitor-1, whereas factors associated with obesity per se correlated significantly with leptin. Changes in S-leptin correlated with changes in fat tissue mass during the follow-up, but not during the intervention. S-leptin at baseline did not correlate with either short term or long term weight loss. CONCLUSION: There is no effect of exercise added to diet on S-leptin in overweight postmenopausal women. Leptin does not seem to be associated with the metabolic syndrome X, but rather with fatness. S-leptin is probably associated with both dynamic and static effects of adipose tissue. S-leptin did not predict weight loss.
Body Composition↗
Regional body composition determined by dual-energy X-ray absorptiometry. Relation to training, sex hormones, and serum lipids in male long-distance runners.
This study investigated the regional distribution of fatty and lean tissue in long-distance runners, and the relation to training, sex hormones, and serum lipids. One hundred and twenty lean men (22 elite, 86 recreational runners and 12 non-running controls) aged 32 +/- 8.1 years (mean +/- SD) participated. Body composition (adipose and lean tissue) was measured by dual-energy x-ray absorptiometry in the total body and in the abdomen, the arms and the legs. Regional and total body fat correlated inversely with the performance at an incremental treadmill exercise test (-0.61 < r < -0.52, P < 0.0001), and the fat percentage in the abdomen and in the legs was 42% and 36% lower in the elite runners in comparison with the non-running controls. Sex hormonal status and serum lipids were unrelated to training. After multiple regression analysis the most significant determinant of the fat percentage in the legs was the weekly distance run (partial r = -0.40, P < 0.0001), whereas in the abdominal region the free testosterone index also contributed strongly (partial r = 0.39, P < 0.0001). In conclusion, long-distance runners had very low amounts of fatty tissue in the abdomen and in the extremities, and the fat percentages in the abdomen and in the legs were associated with both the training intensity and androgenic activity. Since the abdominal fatty tissue is a significant risk factor for cardiovascular disease, running may have a positive impact on the long-term risk.
Abdomen↗
Norethindrone acetate enhances the antiatherogenic effect of 17beta-estradiol: a secondary prevention study of aortic atherosclerosis in ovariectomized cholesterol-fed rabbits.
The influence of progestogens in combination with 17beta-estradiol (E2) on cardiovascular disease remains controversial. This study investigated the effect of norethindrone acetate (NETA) combined with E2 on aortic atherosclerosis. Eighty mature female rabbits were ovariectomized, then fed a cholesterol-rich diet (240 mg/d) for 14 weeks to induce aortic atherosclerosis. They were randomized to four equally large groups for the following 38-week intervention period. One group received placebo, another group oral E2 4 mg daily (E2), and the last two groups oral E2 4 mg daily combined with either NETA 1 mg (E2NETA1) or NETA 3 mg (E2NETA3). The cholesterol intake was reduced to a "maintenance" level of 80 mg/d during the intervention period. Total serum cholesterol and ultracentrifuged lipoproteins were analyzed enzymatically throughout the study. The cholesterol content in the aortic wall was 2.76+/-0.44 micromol/cm2 (mean+/-SEM) in the E2NETA1 group, 1.77+/-0.37 micromol/cm2 in the E2NETA3 group, 5.46+/-0.77 micromol/cm2 in the E2 group, and 7.20+/-0.94 micromol/cm2 in the placebo group (ANOVA P<0.0001). The difference (in the aortic cholesterol accumulation) between the E2 and each of the combined E2/NETA groups was statistically significant (P<0.01) but could only partly be explained by the differences in serum lipids and lipoproteins. In conclusion, NETA enhances the antiatherogenic effect of E2 in cholesterol-fed rabbits. This effect is only partially mediated through changes in serum lipids and lipoproteins.
Animals↗
Postmenopausal bone remodelling and hormone replacement.
Osteoporosis is a serious, frequently occurring disease. Sensitive, specific and precise biochemical measures of bone remodelling, thus, are important tools in the evaluation of bone loss, fracture risk and treatment response. Bone turnover is predictive of the subsequent rate of loss. A high bone turnover documented by increased levels of biochemical markers predicts an increased rate of loss in bone mass. Additionally, as a high bone turnover leads to an increase in the extent of bone resorption as well as an increase of the erosion depth, this may also cause deterioration of the bone structure, thereby leading to an increased risk of fracture. That the predictive values of bone mass and markers of bone turnover are additive suggests that these measures describe different properties of bone. Hormone replacement induces a reduction in postmenopausal bone turnover, arrests loss of bone mass and decreases fracture risk. The skeletal response to therapy is reflected by bone markers and these may be used for monitoring purposes. Those who are in most need of treatment can be identified by a combination of bone mass and bone marker measurement. Furthermore, those who need the treatment most will demonstrate the best response in terms of bone mass. Concern has arisen because of a relatively large day-to-day variation, especially in urinary markers; however, this seems to be resolved through use of the new serum markers.
Bone Remodeling↗
Practical application of risk assessment.
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Age Factors↗
Serum CrossLaps One Step ELISA. First application of monoclonal antibodies for measurement in serum of bone-related degradation products from C-terminal telopeptides of type I collagen.
We have developed a two-site ELISA for measurement in serum of bone-related degradation products derived from C-terminal telopeptides of type I collagen. The assay is based on the application of two highly specific monoclonal antibodies against the amino acid sequence of AHD-beta-GGR, where the aspartic acid residue (D) is beta-isomerized. In a one-step incubation procedure, the degradation products containing cross-linked diisomerized EKAHD-beta-GGR peptides are captured by a biotinylated antibody and a peroxidase-conjugated antibody. The generated complex is then bound to the streptavidin surface via the biotin conjugate. Desalted urinary antigens are used for standardization, and parallelism is observed with serum samples. Results are obtained in <2.5 h, and both inter- and intraassay imprecision are <8%. The serum CrossLaps concentration was 1748+/-740 pmol/L (mean +/- SD) in premenopausal women (n = 65) and 2952+/-1325 pmol/L in a group of healthy postmenopausal women (n = 169). The Serum CrossLaps One Step ELISA was capable of detecting a highly significant (P <0.001) effect of hormone replacement therapy in a retrospective study involving 22 postmenopausal women.
Adult↗
Clinical evaluation of the Serum CrossLaps One Step ELISA, a new assay measuring the serum concentration of bone-derived degradation products of type I collagen C-telopeptides.
The Serum CrossLaps One Step ELISA is a sandwich assay using two monoclonal antibodies specific for a beta-aspartate form of the epitope EKAHDGGR derived from the carboxy-terminal telopeptide region of type I collagen alpha1-chain. Our objective was to assess the clinical value of the Serum CrossLaps assay for monitoring antiresorptive therapy in osteoporosis treatment. Samples obtained from postmenopausal women treated with different doses of cyclic or continuous hormone replacement therapy (HRT) with an estrogen analog (tibolone) or with a bisphosphonate (ibandronate) were measured in the Serum CrossLaps One Step ELISA at baseline and at various time points during therapy. The corresponding urine samples were measured in the urine CrossLaps ELISA and corrected for creatinine excretion. The serum CrossLaps measurements and corresponding urinary CrossLaps measurements were highly correlated (r >0.8 for all studies). The serum and urine CrossLaps measurements showed a significant decrease among the women treated with clinically relevant doses of either of the antiresorptive agents. Furthermore, the annual percentage change in bone mineral density (BMD) correlated with the measured changes in CrossLaps concentration. The serum CrossLaps assay showed a specificity of 83-100% and a sensitivity of 59-83% for assessing BMD changes. The corresponding values for the creatinine-corrected urinary measurements were 83-92% specificity and 68-79% sensitivity. We conclude that performance of the convenient Serum CrossLaps One Step ELISA is at least equivalent to that of the urine text for follow up of antiresorptive treatment in osteoporosis. Further studies are needed to optimize its use in this and other clinical applications.
Aged↗
Effects of raloxifene on bone mineral density, serum cholesterol concentrations, and uterine endometrium in postmenopausal women.
BACKGROUND: Long-term estrogen therapy can reduce the risk of osteoporotic fracture and cardiovascular disease in postmenopausal women. At present, however, these beneficial effects are not separable from undesirable stimulation of breast and endometrial tissues. METHODS: We studied the effect of raloxifene, a nonsteroidal benzothiophene, on bone mineral density, serum lipid concentrations, and endometrial thickness in 601 postmenopausal women. The women were randomly assigned to receive 30, 60, or 150 mg of raloxifene or placebo daily for 24 months. RESULTS: The women receiving each dose of raloxifene had significant increases from base-line values in bone mineral density of the lumbar spine, hip, and total body, whereas those receiving placebo had decreases in bone mineral density. For example, at 24 months, the mean (+/-SE) difference in the change in bone mineral density between the women receiving 60 mg of raloxifene per day and those receiving placebo was 2.4+/-0.4 percent for the lumbar spine, 2.4+/-0.4 percent for the total hip, and 2.0+/-0.4 percent for the total body (P<0.001 for all comparisons). Serum concentrations of total cholesterol and low-density lipoprotein cholesterol decreased in all the raloxifene groups, whereas serum concentrations of high-density lipoprotein cholesterol and triglycerides did not change. Endometrial thickness was similar in the raloxifene and placebo groups at all times during the study. The proportion of women receiving raloxifene who reported hot flashes or vaginal bleeding was not different from that of the women receiving placebo. CONCLUSIONS: Daily therapy with raloxifene increases bone mineral density, lowers serum concentrations of total and low-density lipoprotein cholesterol, and does not stimulate the endometrium.
Bone Density↗