Nasal salmon calcitonin in osteoporosis.
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Administration, Intranasal↗
Biomedical subjects
B J Riis
Publications and source records attributed to B J Riis.
The diagnostic validity of urinary free pyridinolines to identify women at risk of osteoporosis.
The urinary excretion of pyridinolines either in the free form or linked to different peptide fragments of type I collagen are intensively studied as new biochemical markers of bone resorption. In the present study we compared the urinary excretion of free pyridinoline (F-Pyr) determined by enzyme-linked immunosorbent assay (ELISA) (Collagen Crosslinks Kit, Metra Biosystems) to pyridinoline (Pyr), and deoxypyridinoline (D-Pyr) determined by high performance liquid chromatography (HPLC) in early postmenopausal women treated with either hormone replacement therapy or placebo and in healthy age-matched premenopausal women. Other markers of bone metabolism were included for comparison. Compared with the premenopausal women, the postmenopausal women had significantly increased values of the biochemical parameters. F-Pyr, Pyr, D-Pyr, and T-Pyr (= Pyr + D-Pyr) decreased during hormone therapy. D-Pyr correlated with the rate of bone loss, whereas this was not the case for F-Pyr. The correlations between the markers yielded r values of 0.71 (F-Pyr vs Pyr), 0.67 (F-Pyr vs D-Pyr), and 0.71 (F-Pyr vs T-Pyr). In conclusion, the present study shows that the newly introduced ELISA for determination of the free pyridinolines is less sensitive than pyridinium crosslinks measured by high performance liquid chromatography (HPLC) in hydrolyzed urine for the changes in calcium metabolism that occur at menopause and during hormone replacement therapy. Whether this limitation will be balanced out by avoiding the inconvenience of the complicated, expensive, and time-consuming HPLC procedure is still being debated.
Adult↗
Premenopausal bone loss: fact or artifact?
Bone strength is closely related to bone mass, and sex differences in bone mass are the main reason for the greater frequency of osteoporotic fractures in elderly women than in men of the same age. Peak bone mass is lower and the subsequent rate of loss is greater in women. It has been debated whether there is a significant bone loss in women before menopause. This has been studied in cross-sectional studies with and without information on menopausal status, and in longitudinal studies following women through the menopause. The present review addresses this issue and discusses important cross-sectional and longitudinal studies on this question. The overall conclusion is that there probably is a minor premenopausal trabecular bone loss which can be found to be of statistical significance where many individuals are included in the study and very precise methods are used, but it is of a magnitude which probably is of no clinical significance.
Adult↗
Bleeding pattern and climacteric symptoms during different sequential combined HRT regimens in current use.
Four sequential combined oestrogen and progestogen regimens were compared in terms of bleeding pattern and relief of climacteric symptoms. Treatment was with either 2 mg 17 beta-oestradiol with 1 mg norethisterone acetate [E2 + NETA]; 2 mg oestradiol valerate with 75 micrograms levonorgestrel [E2V + LNG]; 2 mg oestradiol valerate with 10 mg medroxyprogesterone acetate [E2V + MPA]; or 1.5 mg 17 beta-oestradiol with 150 micrograms desogestrel [E2 + DG]. A placebo-controlled study lasting 12-24 months was completed by 143 healthy early postmenopausal women. Bleeding lengths were not substantially different; in all regimens the majority of women were bleeding for 3-6 days. Bleeding onset showed differences when related to the 11th day of progestogen addition; in the regimen with E2V + LNG, 21% of the women women were bleeding before the 11th day of progestogen addition 26% on, and 53% after that day. In the regimen with E2V + MPA, 56% of the women were bleeding before the 11th day, 28% on, and 17% after that day, whereas in the regimen with E2 + DG, 15% of the women were bleeding before the 11th day, 5% on, and 80% after that day. All regimens reduced climacteric symptoms to the same extent. Breast tenderness occurred in all the regimens, except in the E2 + DG. Conclusively, the differences between the responses to treatment were not conspicuous. However, our data indicate that one regimen (E2 + DG) resulted in optimal bleeding control, optimal effect on climacteric symptoms, and no production of breast tenderness.
Breast↗
Immunoassay for quantifying type I collagen degradation products in urine evaluated.
An enzyme-linked immunosorbent assay (ELISA) for measuring type I collagen degradation products in urine < 3 h was evaluated. The measuring range was 0.5-10.5 mg/L with a detection limit of 0.2 mg/L. Within-run and total CVs were 5.3% and 6.6%, respectively. Analytical recovery averaged 100%. The mean (+/- SD) concentrations in urine samples from a healthy premenopausal population (n = 102) were 250 +/- 110 mg/mol creatinine (Cr). A group of healthy postmenopausal women (n = 410) gave a mean value of 416 +/- 189 mg/mol Cr. Values obtained in the ELISA correlated well (r = 0.83) to HPLC values for the established bone resorption marker deoxypyridinoline (n = 214), slightly better than the correlation to hydroxyproline measurements (r = 0.78, n = 421). We conclude that the assay described here presents a useful tool for further elucidating the importance of type I collagen degradation products in urine.
Amino Acid Sequence↗
Biochemical markers of bone turnover. II: Diagnosis, prophylaxis, and treatment of osteoporosis.
Osteoporosis is a major health problem and is becoming increasingly important in our aging society. In many of the Western countries, patients with hip fracture occupy more hospital beds than patients with any other disease. Measures to combat osteoporosis are urgently needed, but the best way of doing so is uncertain. Osteoporosis prevention can be targeted at a subgroup of the population at high risk of disease. Alternatively, the intervention can be aimed at the entire population. Both preventive strategies have been proposed for osteoporotic fractures. Some researchers advocate population programs to increase weight-bearing exercise and calcium intake or to reduce smoking, but there is little direct evidence of their effectiveness. The most widespread opinion is that bone mass measurement is the most accurate predictor of fracture risk. Prediction of fracture risk may mean treatment for several years with drugs with not only effects, but also adverse effects. This encourages attempts to optimize the diagnostic procedures.
Biomarkers↗
Bone turnover in asthmatic children treated with oral prednisolone or inhaled budesonide.
Biochemical markers of bone turnover were studied in prepubertal school children with asthma in two randomized double-blind crossover trials with run-in, treatment, and wash-out periods of 2 weeks. One group (n = 11) was treated with 2.5 and 5.0 mg prednisolone, the other (n = 14) with 200 and 800 micrograms inhaled budesonide per day. Serum osteocalcin, serum total alkaline phosphatase, fasting urinary excretion of hydroxyproline and calcium, serum 25-hydroxyvitamin D, and 1,25 dihydroxyvitamin D were assessed. A dose-related reduction of serum osteocalcin (Page's test for trend: P = 0.04; z = -2.3) and of the fasting urinary hydroxyproline:creatinine ratio (Page's test for trend: P = 0.05; z = -2.0) was found in the children who were treated with prednisolone. Inhaled budesonide was not associated with statistically significant effects on any of the biochemical markers. Short-term treatment with low daily doses of prednisolone may cause a suppression of bone turnover in children with asthma. To reduce the risk of adverse effects on bone turnover, doses of inhaled budesonide up to 800 micrograms daily may be preferable to low doses of prednisolone. Bone turnover remains to be evaluated during long-term treatment.
25-Hydroxyvitamin D 2↗
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↗
Biochemical markers of bone turnover in diagnosis and assessment of therapy.
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Alkaline Phosphatase↗
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↗