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Biomedical subjects

B J Riis

Publications and source records attributed to B J Riis.

At least 19 recordsLinked to original sources

Discriminatory ability of bone mass measurements (SPA and DEXA) for fractures in elderly postmenopausal women.

We investigated the discriminatory ability of forearm bone mineral content (BMCarm) measured by single photon absorptiometry (SPA) and spinal bone mineral density (BMDspine) measured by dual-energy X-ray absorptiometry (DEXA) in 387 elderly postmenopausal women. Of these, 22 had never sustained a fracture (normal), 91 had had less than three vertebral wedge fractures (mild), 51 had experienced a peripheral fracture (moderate), and 24 had had more than three vertebral wedge or compression fractures (severe). BMCarm exceeded BMDspine slightly in the ability to discriminate the mild and moderate groups (P less than 0.01-0.001), whether calculations were performed on raw values or the Z-scores compared with premenopausal women. Receiver operating (ROC) analysis showed that at every cutoff level BMCarm had a similar ability as BMDspine to discriminate between the vertebral fracture (mild and severe) groups and healthy premenopausal and nonfractured postmenopausal women (normal), whereas BMCarm had a significantly higher discriminatory ability of peripheral fractures (P less than 0.05) (moderate) group compared with premenopausal women. We conclude that SPA and DEXA are equally capable as diagnostic procedures in women with established osteoporosis.

Absorptiometry, Photon

Secretory endometrial protein PP14 in serum from post-menopausal women receiving continuous combined oestradiol-cyproterone acetate: correlation with serum hormone concentrations and bleeding patterns.

The secretory endometrial protein PP14 was measured in serum from 49 healthy, early post-menopausal women receiving continuous combined oestradiol valerate/cyproterone acetate (2 mg E2V + 1 mg CPA daily) or placebo over a period of 2 years. In the hormone group, serum PP14 increased from 2.1 micrograms/l to a maximum of 8.1 micrograms/l after 1 month of treatment, then fell after 3 months to 3.8 micrograms/l and remained at that level for the rest of the 2-year period. After the first month, the occurrence of uterine bleeding was associated with significantly increased serum PP14 levels. Bleeding was not correlated with the serum concentration of 17 beta-oestradiol (E2) or CPA, or the CPA/E2 ratio. Serum PP14 was significantly dependent on the serum concentration of E2, but not on that of CPA. The present data confirm that serum PP14 levels reflect the secretory phase of the endometrium and that bleeding during continuous combined hormone replacement therapy is probably caused by a sub-optimal hormonal balance.

Androgen Antagonists

Serum placental protein 14 (PP14) reflects endometrial status during hormone replacement therapy.

Healthy post-menopausal women were randomly assigned to treatment groups receiving 28 day treatment cycles of oestradiol valerate (2 mg, days 1-28) sequentially combined with levonorgestrel (75 micrograms, days 17-28) (n = 19); oestradiol valerate (2 mg, days 1-28) continuously combined with cyproterone acetate (1 mg, days 1-28) (n = 18), or placebo (n = 22). Treatment continued for 2 years. After therapy, the women receiving the sequential combination had an early secretory phase (74%) or atrophic endometrium (26%). All women receiving the continuous combination or placebo had inactive or atrophic endometrium, or the tissue was inadequate for assessment. Biochemical parameters of endometrial secretion [oestradiol dehydrogenase (EDH), isocitrate dehydrogenase (ICDH)] measured in endometrial tissue and placental protein (PP14) measured in serum were all low in the groups receiving the continuous combination and placebo. During sequential treatment, all biochemical parameters showed significantly higher mean values. Serum PP14 accurately reflected this pattern. Furthermore, in the sequentially treated group, serum PP14 correlated highly significantly with EDH (r = 0.70; P less than 0.001) and ICDH (r = 0.57; P = 0.01). These correlations were of the same magnitude as the correlations between the endometrial markers, which indicates that serum PP14 reflects the endometrial status. Furthermore, serum PP14 measurements at 3 months and at 2 years of treatment were highly correlated, reflecting the long-term validity of the measurement. The present data suggest that PP14 measured in serum may be used to assess endometrial status. Further studies are required to determine whether serum PP14 will discriminate pathological endometrial conditions.

Cyproterone Acetate

Two new combinations of estrogen and progestogen for prevention of postmenopausal bone loss: long-term effects on bone, calcium and lipid metabolism, climacteric symptoms, and bleeding.

Bone mass, calcium and lipid metabolism, climacteric symptoms, bleeding, blood pressure, and weight changes were studied in 62 healthy postmenopausal women at 3-month intervals throughout 2 years of treatment with continuous estradiol valerate (2 mg) plus cyproterone acetate (1 mg), sequential estradiol valerate (2 mg) plus levonorgestrel (75 micrograms), or placebo. During the 2 years of the study, bone mineral content of the distal and ultradistal regions of the forearm (measured by single-photon absorptiometry) remained unchanged in the hormone groups, whereas bone mineral content at these sites decreased by 5 and 6%, respectively, in the placebo group. Bone mineral density in the spine (measured by dual-photon absorptiometry and dual-energy x-ray absorptiometry) increased by 3-4% in the hormone groups and decreased by 2% in the placebo group. Biochemical estimates of bone turnover (serum alkaline phosphatase and fasting urinary calcium/creatinine) decreased significantly to premenopausal levels in the hormone groups, but remained unchanged in the placebo group. Serum concentrations of total and low-density lipoprotein cholesterol were significantly reduced by 5-10% (P less than .05-.01) in the estradiol + cyproterone acetate group and by 10-15% (P less than .001) in the estradiol valerate + levonorgestrel group. There were no significant changes in high-density lipoprotein cholesterol in the hormone groups. Virtually no changes were observed in the placebo group. Climacteric symptoms and hot flushes were significantly reduced in both hormone groups compared with the placebo group.(ABSTRACT TRUNCATED AT 250 WORDS)

Bone Density

Sequential estrogen and progestogen therapy: assessment of progestational effects on the postmenopausal endometrium.

Healthy postmenopausal women were randomly assigned to groups receiving 28-day treatment cycles of estradiol (E2) valerate (2 mg, days 1-21) combined with medroxyprogesterone acetate (10 mg, days 12-21) (N = 18), 17 beta-estradiol (1.5 mg, days 1-24) combined with desogestrel (150 micrograms, days 13-24) (N = 20), or placebo (N = 18). The progestational effects on the endometrium were assessed by histology, uterine bleeding pattern, and biochemical markers of secretion measured in endometrial tissue (E2 and isocitrate dehydrogenase) and serum (placental protein 14). After 2 years of therapy, 24 women in the hormone groups had secretory endometrium and 13 had atrophic endometrium; in the placebo group, the results were one and 15, respectively. Withdrawal bleeding generally started between days 9-12 after the addition of progestogen in the E2-medroxyprogesterone acetate group, and between days 14-17 in the E2-desogestrel group. All three biochemical markers of secretion were increased in each of the hormone-treated groups compared with the placebo group (P less than .01-.001). Serum placental protein 14 was twice as high in the secretory as in the atrophic phase (P less than .01). Isocitrate dehydrogenase, but not E2 dehydrogenase, was also higher in the secretory phase (P less than .05). Only serum placental protein 14 was significantly related to the uterine bleeding pattern (P less than .01). We conclude that serum placental protein 14 reflects both endometrial histology and bleeding pattern and may be a useful marker of progestational effects on the endometrium. The markers of secretion measured in endometrial tissue are not as reliable for endometrial histology or bleeding pattern.

Desogestrel

Role of peak bone mass and bone loss in postmenopausal osteoporosis: 12 year study.

OBJECTIVE: To examine the role of peak bone mass and subsequent postmenopausal bone loss in the development of osteoporosis and the reliability of identifying women at risk from one bone mass measurement and one biochemical assessment of the future bone loss. DESIGN: Population based study. SETTING: Outpatient clinic for research into osteoporosis. SUBJECTS: 178 healthy early postmenopausal women who had participated in a two year study in 1977. 154 of the women underwent follow up examination in 1989, of whom 33 were excluded because of diseases or taking drugs known to affect calcium metabolism. MAIN OUTCOME MEASURES: Bone mineral content of the forearm and values of biochemical markers of bone turnover. RESULTS: The average reduction in bone mineral content during 1977-89 was 20%, but the fast losers had lost 10.0% more than had the slow loser group (mean loss 26.6% in fast losers and 16.6% in slow losers; p less than 0.001). Prediction of future bone mineral content using baseline bone mineral content and estimated rate of loss gave results almost identical with the actual bone mineral content measured in 1989. Seven women had had a Colles' fracture and 20 a spinal compression fracture. The group with Colles' fracture had low baseline bone mineral content (34.7 (95% confidence interval 31.3 to 38.1) units v 39.4 (38.1 to 40.8) units in women with no fracture) whereas the group with spinal fracture had a normal baseline bone mineral content (38.1 (35.0 to 41.1) units) but an increased rate of loss (-2.4 (-3.5 to -1.3)%/year v -1.8 (-2.1 to -1.5)%/year in women with no fracture). CONCLUSIONS: One baseline measurement of bone mass combined with a single estimation of the rate of bone loss can reliably identify the women at menopause who are at highest risk of developing osteoporosis later in life. The rate of loss may have an independent role in likelihood of vertebral fracture.

Age Factors

Potential risk factors for development of postmenopausal osteoporosis--examined over a 12-year period.

In a longitudinal study, we investigated the influence of risk factors on bone mass at menopause and postmenopausal bone loss in 121 healthy postmenopausal women. These women had completed a 2-year prospective study in 1979 and a follow-up examination in 1989. Measurements of the bone mineral content in the distal forearm (single photon absorptiometry) were performed 9 times during the initial study and once at the follow-up examination. Bone mass at menopause (initial measurement), rate of early postmenopausal bone loss, and the subsequent rate of bone loss over 10 years were thus determined. In addition, the bone mineral density of the lumbar spine and proximal femur was measured by dual-energy X-ray absorptiometry (DXA) in 1989. Information about risk factors was assessed by standardized questionnaires and included reproductive history and lifestyle factors (intake of calcium and vitamin D supplements, consumption of alcohol and caffeine, smoking habits, and physical activity). Lactation, oral contraceptive use, and dietary calcium intake above 1500 mg per day was associated with significantly increased bone mass at menopause. The number of pregnancies reduced the rate of early postmenopausal bone loss, whereas moderate alcohol consumption reduced the subsequent rate of bone loss. Smoking significantly reduced femoral bone mineral density. In conclusion, the present prospective study showed that some of the examined putative risk factors positively influenced bone mass at menopause, especially calcium intake, whereas the postmenopausal bone loss was virtually unaffected. Assessment of risk factors in postmenopausal women thus seems to have limited value for reducing future risk of osteoporosis.

Aged

Bleeding patterns during continuous combined estrogen-progestogen therapy.

Bleeding and climacteric symptoms were recorded in two groups of postmenopausal women receiving either continuous combined estradiol and norethisterone acetate or estradiol and cyproterone acetate. Out of a sample of 99 postmenopausal women aged 45 to 54 years, 86 completed a 2-year, double-blind, placebo-controlled study. Comparison of the bleeding patterns in the two groups revealed a statistically significant difference: More women in the estradiol-cyproterone acetate group experienced bleeding and for a longer duration. Thirteen women in the estradiol-norethisterone acetate group were amenorrheic, compared with two in the other group. The Kupperman index score in both groups declined to about 30% to 40% of initial values (p less than 0.001). The hot flushes in both treatment groups decreased to a highly significant degree (p less than 0.001), to a value below 20% of baseline values. We conclude that a continuous combination of estrogen and progestogen can produce amenorrhea and symptomatic relief. However, the progestogen components seem to differ in their ability to control bleeding.

Amenorrhea

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

Serum-free gamma carboxyglutamic acid (free Gla) is a poor biochemical marker of bone resorption in early postmenopausal women.

In this study, we assessed the potential value of serum-free Gla to reflect changes of bone turnover at menopause. Serum-free Gla was measured in 49 healthy postmenopausal women and 19 healthy age-matched premenopausal women. No difference in serum-free Gla concentrations was observed between the two groups. In a double-blind longitudinal study of 36 postmenopausal women (a subgroup of the above 49 women) treated with either oral oestradiol valerate in a cyclical combination with cyproterone acetate (n = 19) or placebo (n = 17) for nine months, the serum-free Gla concentration was unchanged with placebo and decreased by only 10% after hormonal replacement therapy. Initial serum-free Gla concentrations in postmenopausal women did not correlate with other biochemical markers of bone turnover. The predictive value of serum-free Gla concentration for the spontaneous rate of bone loss in early postmenopause was also assessed, and the marker showed no correlation to bone loss. These data indicate that the serum concentration of free Gla is not a useful marker of the bone turnover rate in the early postmenopause.

Biomarkers

Desogestrel in hormone replacement therapy: long-term effects on bone, calcium and lipid metabolism, climacteric symptoms, and bleeding.

Seventy-three healthy, postmenopausal women, aged 45-54 years, were randomly assigned to one of three groups for 2 years of treatment: 17 beta-oestradiol 1.5 mg on days 1-12 and 17 beta-oestradiol 1.5 mg + desogestrel 150 micrograms on days 13-24 (E2/DG) or oestradiol valerate 2 mg on days 1-11 and oestradiol valerate 2 mg + medroxyprogesterone acetate 10 mg on days 12-21 (E2V/MPA) or placebo. Fifty-seven women (78%) completed the study. Bone mineral content of the distal regions of the forearms (measured by single photon absorptiometry, SPA) and bone mineral density of the spine (measured by dual energy X-ray absorptiometry, DXA) showed increases of 0.5-1% and 4-5%, respectively, in the hormone groups over 2 years. The placebo group exhibited a decrease in spinal bone density of 2% per year, and in the forearm of 2.5-3.5% per year. Biochemical estimates of bone turnover (serum alkaline phosphatase and fasting urinary calcium) decreased significantly to premenopausal levels in the hormone groups but remained unchanged in the placebo group. In both hormone groups total cholesterol decreased by about 9% (P less than 0.001), whereas low density lipoprotein cholesterol decreased by 16% in the E2/DG group and 20% in the E2V/MPA group (P less than 0.001). High density lipoprotein cholesterol showed only minor, insignificant changes in the hormone groups. The placebo group had virtually unchanged values. Climacteric symptoms, including hot flushes, were significantly reduced in both hormone groups. Bleeding occurred regularly in about 80% of the women.(ABSTRACT TRUNCATED AT 250 WORDS)

Absorptiometry, Photon

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

[Evaluation of risk factors in development of osteoporosis].

Bone mass may be measured by several techniques. The most recently developed equipment has sufficient accuracy to diagnose the low peak bone mass or a low bone mass later in life and sufficient precision to be able to follow the effects of a given treatment. Future bone loss can be estimated around the menopause by a combination of biochemical estimates and bone turnover. Together with measurement of bone mass at the menopause this method is helpful in deciding who should receive preventive treatment.

Absorptiometry, Photon

Screening procedure for women at risk of developing postmenopausal osteoporosis.

The present study includes 70 healthy, immediately postmenopausal women stratified according to future rate of bone loss. The stratification was performed by means of four parameters of bone turnover: serum alkaline phosphatase, fasting urinary calcium and hydroxyproline, and body weight, used in an equation developed in a previous study. After the stratification the women were followed without intervention for the next 24 months, with bone mass measurements every 3 months. The bone loss estimated at baseline by means of the equation correlated with the bone loss measured in the forearm (y = 0.72x - 1.52; r = 0.61; P less than 0.001). Plasma bone gla protein (BGP, osteocalcin), which is a new specific marker of bone formation, was now added to the model (replacing body weight). This increased the diagnostic validity (y = x; r = 0.76; P less than 0.001). From the present study we conclude that the postmenopausal bone loss can be predicted by means of four biochemical parameters determined in plasma and urine in women just after the menopause.

Biomarkers

Does a single local absorptiometric bone measurement indicate the overall skeletal status? Implications for osteoporosis and osteoarthritis of the hip.

Regional bone mineral content (BMC) and density (BMD) (head, arms, chest, spine, pelvis, legs) of a total body dual photon 153Gd absorptiometry (DPA) scan were measured in 20 healthy postmenopausal women, 27 postmenopausal women with hip fracture, and 17 postmenopausal women with osteoarthritis of the hip. In addition, local BMC and BMD were measured in the proximal and distal regions of the distal forearm (BMCprox, BMDprox, BMCdist, BMDdist) by single photon absorptiometry (SPA); and in the lumbar spine (BMCL2-L4 and BMDL2-L4) by 153Gd DPA. The overall impression was a reduction of bone mass in hip fracture patients compared with healthy controls and an increase in the bone mass of osteoarthritic patients. These results were valid using both regional values of the total body scan, and local forearm and lumbar spine measurements, and statistically significant using one-way analysis of variance. There were, however, also significant within-group between-region differences (one-way analysis of variance), showing that the bone mass of the pelvis and legs in hip fracture patients was more reduced than in the remaining skeleton; in osteoarthritic patients it was not increased but rather unchanged or slightly reduced. The differences between the level of the three local measurements (BMDprox BMDdist BMDL2-L4), on the one hand, and the level of the six regional BMD values, on the other hand, were investigated by the two-way analysis of variance: local measurements = rows; regional values = columns. This analysis showed that none of the three local measurements was statistically better than the other two in predicting the overall level of skeletal bone mass as judged by the six regional values. We conclude that serious osteoporotic bone loss has a generalized nature, however, with a tendency towards lower values in the regions affected by fracture (viz: low bone mass in the legs of femoral neck fracture patients). Osteoarthritis may be associated with a high bone mass in most areas, but low values in the affected regions. Local lumbar spine measurement of bone mass by DPA is not superior to local forearm measurement of bone mass by SPA in predicting the nature of overall osteoporotic or osteoarthritic bone change.

Absorptiometry, Photon

Comparison of vitamin D metabolism in early healthy and late osteoporotic postmenopausal women.

We studied 20 healthy premenopausal women aged 36.5 +/- 4.0 years (mean +/- 1 SD), 123 healthy postmenopausal women aged 50.0 +/- 2.4 years, and 103 postmenopausal women aged 65.1 +/- 5.6 years with symptomatic osteoporosis (forearm and spinal fracture). Serum levels of vitamin D metabolites [25(OH)D, 24,25(OH)2D3, and 1,25-(OH)2D] were compared with (1) bone mass in the forearm (single photon absorptiometry) and in the spine (dual photon absorptiometry); (2) biochemical indices of bone formation (serum alkaline phosphatase, plasma bone Gla protein), and bone resorption (fasting urinary hydroxyproline); and (3) other biochemical estimates of calcium metabolism (serum calcium, serum phosphate, 24-hour urinary calcium, intestinal absorption of calcium). The present study revealed no difference in any of the vitamin D metabolites between the premenopausal women, the healthy postmenopausal women and the osteoporotic women as a group. The concentrations of 1,25(OH)2D and 25(OH)D were significantly lower in patients with spinal fracture than in those with forearm fracture. In the early postmenopausal women serum 1,25(OH)D was related to forearm bone mass (r = -0.20; P less than 0.05), intestinal calcium absorption (r = 0.18; P less than 0.05), and 24-hour urinary calcium (r = 0.21; P less than 0.05); serum 25(OH)D was related to spinal bone mass (r = 0.23; P less than 0.01). In the osteoporotic women, serum vitamin D metabolites were not related to bone mass, but 1,25(OH)2D was related to bone Gla protein (r = 0.33; P less than 0.001), serum phosphate (r = -0.27; P less than 0.01), and 24-hour urinary calcium (r = 0.43; P less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

24,25-Dihydroxyvitamin D 3