Biomedical subjects

B J Riis

Publications and source records attributed to B J Riis.

At least 73 records · Page 4Linked to original sources

PubMed1990

Changes in vitamin D metabolism during natural and medical menopause.

Thirty-nine women were studied longitudinally for 3 yr, during which period 10 women passed a natural menopause. Vitamin D metabolites were determined every 3 months in these 10 women. The same variables were studied in 42 premenopausal women with endometriosis treated for 6 months with nafarelin acetate (a LHRH agonist) given alone in a dose of 200 or 400 micrograms or in a dose of 400 micrograms combined with 1.2 mg norethisterone (NET)/day and followed-up for a further 6 months. No changes were seen in 1,25-dihydroxyvitamin D [1,25-(OH)2D], vitamin D-binding protein, or the free index of 1,25-(OH)2D during the natural menopause. A small increase was found in 25-hydroxyvitamin D [25OHD] and 24,25-(OH)2D3 after correction for seasonal variation. All three nafarelin groups had a significantly decreased free index of 1,25-(OH)2D, which returned to the baseline value on withdrawal of the treatment. Serum 25OHD and 24,25-(OH)2D3 were increased at 6 months and thereafter decreased to baseline values. These changes were still visible after correction for seasonal variation. Vitamin D-binding protein showed a small transient increase in the nafarelin plus NET group, but was unchanged in the other two groups. The 24-h urinary excretion of calcium increased significantly in the groups receiving nafarelin alone, whereas it remained unchanged in the nafarelin plus NET group. We conclude that detectable changes in 1,25-(OH)2D do not occur in natural menopause. Treatment with LHRH agonists produces a significant decrease in serum 1,25-(OH)2D, which does not seem to be dependent on increased bone resorption. This suggests that LHRH agonists may induce a change in other pituitary hormones involved in vitamin D regulation.

24,25-Dihydroxyvitamin D 3↗

PubMed1990

17 Beta-estradiol and continuous norethisterone: a unique treatment for established osteoporosis in elderly women.

Forty women aged 64.7 +/- 5.1 yr with established postmenopausal osteoporosis were blindly allocated to 1 yr's treatment with either continuous combined estrogen/progestogen therapy (2 mg estradiol + 1 mg norethisterone acetate + 500 mg calcium daily) or placebo + 500 mg calcium daily. In the group treated with hormones bone mineral density in the spine (dual photon absorptiometry) and bone mineral content in the ultradistal forearm (single photon absorptiometry) increased highly significantly by 8-10% during the 1 yr of treatment. Bone mineral content in the mid-shaft of the forearm (single photon absorptiometry) and the total body bone mineral (dual photon absorptiometry) increased by 3-5% when compared to that in the placebo group, which showed virtually unchanged values at all measurement sites. Seven of the women treated with hormones were examined after a further year of treatment. BMC increased by another 3-6%, reaching a 12% increase in bone mineral density in the spine after 2 yr of treatment. Biochemical estimates of bone resorption (fasting urinary calcium and hydroxyproline) and bone formation (serum alkaline phosphatase and plasma osteocalcin), decreased significantly (P less than 0.001) in the group treated with hormones, but remained unchanged in the placebo group. The reduction in indices of bone resorption was more pronounced than that in bone formation after one year, indicating a positive bone balance. No further changes were seen in these bone turnover parameters during the second year of treatment. In the group treated with hormones, serum levels of triglycerides, total cholesterol, and low density lipoprotein cholesterol decreased by about 12% (P less than 0.05-P less than 0.01), whereas high density lipoprotein cholesterol decreased by about 8% (P less than 0.001). The high density lipoprotein cholesterol/low density lipoprotein cholesterol ratio was unchanged. The hormone treatment did not produce any major side effects, and only minor bleedings were experienced by a few women. The present study demonstrates that treatment with female sex hormones in this particular combination is a realistic approach to the treatment of women with established postmenopausal osteoporosis.

Aged↗

PubMed1990

Vitamin D metabolism in osteoporotic women during treatment with estrogen, an anabolic steroid, or calcitonin.

We assessed the effects of a continuous oral combination of estradiol and norethisterone acetate, nandrolone decanoate, or salmon calcitonin on the vitamin D endocrine system. One hundred and nineteen postmenopausal women, aged 55-75 years, with at least one osteoporotic fracture, were randomly allocated to one year of treatment with estradiol and norethisterone acetate, nandrolone decanoate, or calcitonin, all drugs with a beneficial effect on bone. All three trials were double-blind and placebo-controlled; 104 women (87%) completed the study. We measured the total serum concentration of 1,25-dihydroxyvitamin D (1,25(OH)2D) and vitamin D-binding protein, and estimated the free 1,25(OH)2D index and the "24-hydroxylase activity" initially, and at 6 and 12 months. Furthermore, the 24-h urinary excretions of calcium, phosphate, and adenosine 3'-5'-cyclic monophosphate were assessed initially and at 12 months. The serum concentration of vitamin D-binding protein and 1,25(OH)2D increased transiently during estradiol and norethisterone acetate treatment and vitamin D-binding protein decreased transiently during nandrolone decanoate treatment. None of the other parameters were significantly affected by any of the three treatments. The risk of type II errors was below 10 per cent for all vitamin D measurements. We conclude that the vitamin D metabolites are unlikely to be of major importance for the mechanism by which these drugs exert their positive skeletal effects.

Aged↗

PubMed1990

Dual-energy x-ray absorptiometry: a precise method of measuring bone mineral density in the lumbar spine.

We compared two methods of measuring spinal bone mineral content and density (BMC/BMD): conventional dual-photon absorptiometry (DPA) and a more recent method, dual-energy x-ray absorptiometry (DEXA). The clinical usefulness of both methods was compared in the measurement of BMC in the forearm. DEXA had a long-term in vivo precision of 1% which was significantly better than that of DPA. Changes in the distribution of fatty tissue influenced the accuracy of the two spinal methods in different ways. Forearm BMC discriminated between the bone mass of early and late postmenopausal women to the same degree as DPA and DEXA. The variability in the response to estrogen treatment and placebo was much lower with DEXA and forearm BMC than with DPA. We conclude that DEXA provides a fast and precise measurement of spinal BMC/BMD. The accuracy remains to be evaluated for in vivo studies.

Absorptiometry, Photon↗

PubMed1989

Effect of salcatonin given intranasally on early postmenopausal bone loss.

OBJECTIVE: To study the effect of salmon calcitonin (salcatonin) given intranasally on calcium and bone metabolism in early postmenopausal women. DESIGN: Double blind, placebo controlled, randomised group comparison. SETTING: Outpatient clinic for research into osteoporosis. SUBJECTS: 52 Healthy women who had had a natural menopause two and a half to five years previously. INTERVENTIONS: The 52 women were allocated randomly to two years of treatment with either salcatonin 100IU given intranasally (n = 26) or placebo (n = 26). Both groups received a calcium supplement of 500 mg daily. Seven of the women receiving salcatonin and six of those receiving placebo left the study before its end. MAIN OUTCOME MEASURES: Bone mineral content in the spine, the total skeleton, and the forearms after two years of treatment. RESULTS: Bone mineral content in the spine was significantly higher in the women who had received salcatonin than in those who had received placebo both after one year and after two years of treatment. After one year the difference was 3.8% (95% confidence interval 0.0 to 7.6%) and after two years it was 8.2% (3.8 to 12.6%). In contrast, the bone mineral content in the distal and proximal forearms and in the total skeleton declined similarly in both groups by about 2% each year, and after two years of treatment the differences between the groups were not significant. Biochemical estimates of bone turnover were not affected by salcatonin. CONCLUSION: The results suggest that salcatonin given intranasally in the dose used prevents bone loss in the spine of early post menopausal women but does not affect the peripheral skeleton.

Administration, Intranasal↗

PubMed1989

New methods for identifying "at risk" patients for osteoporosis.

Bone loss was determined in 178 women in the early postmenopausal period by photon absorptiometry measurement of forearm bone mineral content (BMC) every three months for two years. With a sequential cut-off technique, the results of a single determination of body fat mass, urinary calcium and hydroxyproline, and serum alkaline phosphatase, carried out at the first examination, correctly identified 79% of "fast bone losers" (bone loss greater than 3% annually) and 78% of "slow bone losers". The simple biochemical screening procedure was hereafter tested in a new group of 70 early postmenopausal women, who were followed for two years with measurement of local and total BMC. With this simple approach the majority of women at highest risk of osteoporotic fractures in later life can be identified in the early postmenopausal period and can be started on prophylactic hormone replacement therapy.

Bone and Bones↗

PubMed1989

Relation of body fat distribution to serum lipids and lipoproteins in elderly women.

Fat distribution measured by dual photon absorptiometry, serum lipids and lipoproteins were determined in 95 elderly women with mild osteoporosis. Increasing obesity, determined anthropometrically as body mass index (BMI) = body weight/(height)2, was associated with a more central fat distribution (P less than 0.001) Central fat distribution correlated positively and independently of BMI and body weight to serum cholesterol, low density lipoprotein-cholesterol (LDL-C), triglycerides and the ratio LDL-C/HDL-C (P less than 0.05), whereas the correlation between central fat distribution and high density lipoprotein-cholesterol (HDL-C) was negative (P less than 0.05). We conclude that the increased risk of cardiovascular disease observed in subjects with central fat distribution might be partly mediated through changes in the lipoprotein profile.

Absorptiometry, Photon↗

PubMed1989

Changes in soft tissue body composition and plasma lipid metabolism during nandrolone decanoate therapy in postmenopausal osteoporotic women.

Thirty-nine osteoporotic (prior spine or Colles' fracture) but otherwise healthy postmenopausal women were allocated to receive blindly either 50 mg nandrolone decanoate (ND) intramuscularly or placebo injections every 3 weeks for 1 year. Thirty-six women (92%) completed the study. ND treatment resulted in an increase in non-osseous lean weight and a corresponding decrease in fat mass (measured by dual photon absorptiometry). A 20% increase in the 24-hour urinary creatinine excretion indicated that the increase in non-osseous lean weight was caused mainly by an increase in muscle mass. With regard to serum lipids and lipoproteins, ND treatment slightly decreased high density lipoprotein (HDL) cholesterol without significantly affecting total cholesterol, low density lipoprotein (LDL) cholesterol or triglycerides. In conclusion, treatment with ND changes the soft tissue composition in osteoporotic postmenopausal women towards a leaner and more muscular body.

Adipose Tissue↗

PubMed1989

Treatment of postmenopausal osteoporosis: is the anabolic steroid nandrolone decanoate a candidate?

Thirty-nine postmenopausal women (aged 55-75 years) with at least one osteoporotic fracture were allocated to one year of treatment with the anabolic steroid nandrolone decanoate (50 mg i.m. every 3 weeks) or placebo injection. Both groups also received a daily intake of 500 mg calcium. Thirty-six women (92%) completed the study. In the nandrolone decanoate-treated group the fat corrected bone mineral content in the proximal part of the distal forearm (measured by single photon absorptiometry) showed a significant increase of 3% compared with placebo (P less than 0.01), and the same tendency was seen in the bone mineral content of the distal part of the distal forearm and density of the lumbar spine (measured by dual photon absorptiometry). However, this did not reach significance. In the placebo group all bone mineral measurements remained unchanged. The biochemical estimates of bone formation (plasma bone Gla protein (BGP), serum alkaline phosphatase) and whole body retention (WBR) of 99mTc-diphosphonates were not statistically significantly changed by the nandrolone decanoate therapy. We conclude that treatment with nandrolone decanoate does increase the bone mineral content; however, this may not be due to a direct increase in bone formation. The mechanism may theoretically be a combination of decreased bone resorption and increased muscle mass, which both play a beneficial role in conserving bone.

Aged↗

PubMed1989

Long-term and withdrawal effects of two different oestrogen-progestogen combinations on lipid and lipoprotein profiles in post-menopausal women.

Serum lipids and lipoproteins were studied in 86 healthy post-menopausal women at 3-monthly intervals throughout 2 yr of treatment with cyclic oestradiol valerate plus cyproterone acetate (E2V + CPA), continuous 17 beta-oestradiol plus norethisterone acetate (E2 + NETA), or placebo. Withdrawal effects were also investigated. Serum oestrogen levels were similar following the 2 hormone regimens. Serum total and low-density-lipoprotein (LDL) cholesterol were significantly reduced by 5-8% during cyclic E2V + CPA therapy and by 15-20% during continuous E2 + NETA treatment. The concentrations remained significantly reduced throughout the 2 yr of treatment. Virtually no changes were observed in the placebo group. High-density-lipoprotein (HDL) cholesterol concentrations were significantly reduced in relation to pretreatment values during the first year of continuous E2 + NETA therapy, but were not significantly different from the levels in the cyclic E2V + CPA or the placebo groups. Serum triglyceride levels remained almost constant in all the groups. Withdrawal of hormone therapy resulted in steep increases in total and LDL-cholesterol, the levels returning to pretreatment values. A similar increase in HDL-cholesterol was observed in the E2 + NETA group, following withdrawal. Vaginal bleeding episodes were experienced by all the women receiving the E2V + CPA regimen and they occurred regularly in 63% of the women. Fifty-two (52) percent of the women receiving E2 + NETA did not bleed at all. The results of the present study suggest that the continuous addition of NETA may enhance the oestrogen-induced changes in total and LDL-cholesterol, whereas only minor changes in the oestrogen-induced effects on these variables are produced by the cyclic addition of CPA. However, in the case of HDL-cholesterol, the antagonistic effect of CPA seems to be moderate in comparison with that of NETA.

Cholesterol, HDL↗

PubMed1989

Nandrolone decanoate treatment of post-menopausal osteoporosis for 2 years and effects of withdrawal.

This study investigated the effects of nandrolone decanoate (ND) therapy (50 mg i.m. every 3 or 4 wk) on bone mass and soft tissue body composition in post-menopausal women. Twenty-two (22) women were followed up over a period of 30 mth, during which they received ND therapy for 12-24 mth and were treatment-free for the other 6-18 mth. While they were receiving treatment forearm bone mineral content (BMC) and lean body mass (LBM) increased, whereas fat mass (FM) decreased. After withdrawal of ND therapy the BMC, LBM and FM values all tended to return to pretreatment levels. Serum high-density-lipoprotein cholesterol showed a non-significant decrease, while serum low-density-lipoprotein cholesterol and serum total cholesterol remained unchanged during therapy. It was concluded that ND therapy can achieve an increase in BMC in post-menopausal women, but this is maintained only for as long as therapy is continued.

Aged↗

PubMed1989

Nasal calcitonin for treatment of established osteoporosis.

Thirty-seven women with established osteoporosis completed a one-year double-blind, placebo-controlled study with the primary aim of examining the effect of nasal salmon calcitonin (200 IU daily) on bone and calcium metabolism. All the women received a daily calcium supplement of 500 mg. For comparison we also report data from an age-matched group of healthy women who did not receive calcium supplementation. The bone mineral measured in the forearm (single photon absorptiometry) and spine (dual photon absorptiometry) showed a similar pattern during treatment. The calcitonin group (n = 17) did not lose bone mineral in comparison with the placebo (n = 20) and the control groups (n = 19) (P less than 0.01). The biochemical estimates of both bone resorption and bone formation decreased highly significantly in the calcitonin group (P less than 0.001) and were unchanged in the control group, whereas the placebo (calcium) group showed intermediate values. Neither subjective nor objective side-effects occurred in any of the groups. We conclude that nasal calcitonin is a realistic treatment of established osteoporosis.

Administration, Intranasal↗

PubMed1989

The measurement of secretory endometrial protein PP14 in serum from postmenopausal women receiving unopposed estrogen or continuously combined estrogen/progestogen.

A highly sensitive radioimmunoassay was developed to measure the low serum concentrations of the endometrial secretory placenta protein 14 (PP14) in postmenopausal women. The assay was established by selecting optimum reaction conditions for radioactive labelling of PP14, combined with simple procedures for the purification of the labelled PP14. The PP14 assay was used in 2 groups of healthy, early postmenopausal women blindly receiving either estrogen monotherapy (n = 20, placebo n = 25) or continuously combined estrogen/progestogen therapy (n = 20, placebo n = 23). Neither of these regimens is believed to produce secretory endometrium. During the 12 months of estrogen monotherapy, serum PP14 (S-PP14) remained unchanged at 4.9 micrograms/l, when compared with placebo. Treatment with continuously combined estrogen/progestogen showed a small but significant increase in S-PP14 from 5.3 micrograms/l to 7.2 micrograms/l at 3 months. S-PP14 remained at this slightly elevated level throughout the treatment period of 24 months. Three months after hormone withdrawal, S-PP14 had returned to the pretreatment level. We suggest that S-PP14 might be a useful marker of secretory endometrium.

Drug Combinations↗

PubMed1988

Measurement of spinal or peripheral bone mass to estimate early postmenopausal bone loss?

This report presents data from 153 healthy, early postmenopausal women who were randomly allocated to two years of treatment with estrogen or placebo. Bone mineral content in the forearms was measured by single-photon absorptiometry, and bone mineral density of the lumbar spine and total-body bone mineral by dual-photon absorptiometry, before and after one and two years of treatment. At the end of the two years, there were highly significant differences of 6 to 7 percent between the estrogen and the placebo groups at all sites measured. The range of the changes of the spine measurement was twice that of the forearm and total-body measurements. It is concluded that measurement of the forearm by single-photon absorptiometry is superior to measurement of the spine by dual-photon absorptiometry both in clinical studies and in the individual patient for detecting estrogen-dependent bone loss and its treatment by estrogen replacement.

Double-Blind Method↗

PubMed1988

Iliac crest biopsy in longitudinal therapeutic trials of osteoporosis.

Changes in tetracycline-labelled iliac crest biopsies taken before and after 1 year of treatment with nandrolone decanoate + calcium, 17 beta-estradiol + norethisterone acetate + calcium or placebo were compared with changes in plasma bone Gla protein (pBGP), serum alkaline phosphatase (sAP), whole body retention (WBR) of Technetium-99m-diphosphonate [( 99mTc]DP) and bone mineral content (BMC) of the forearm. Based on a comparison between biopsy and noninvasive results, as well as on evaluation of the variation in the groups, certain guidelines for the use of bone histomorphometry in longitudinal therapeutic trials are suggested. It is proposed that bone biopsy is not used to monitor changes in amount of bone and that evaluation of changes in biopsy evaluated bone turnover is only attempted when the groups are large.

Aged↗

PubMed1988

Continuous oestrogen-progestogen treatment and bone metabolism in post-menopausal women.

The suggestion that norethisterone acetate (NETA) stimulates bone formation prompted us to investigate calcium and bone metabolism in post-menopausal women treated with a continuous combination of oestrogen and NETA. The study included 49 healthy post-menopausal women. After an initial examination the women were randomly allocated to 2 yr of treatment with either hormones or placebo; 43 women completed the study. Within the first year of treatment the hormone group showed a slight, but significant, increase in bone mineral content in the forearms (single photon absorptiometry) and in the total skeleton (dual photon absorptiometry). After this initial increase the bone mass remained constant throughout the trial. Bone mineral density of the spine (dual photon absorptiometry) showed a significant increase of more than 5% in the hormone group. There were significant decreases of 4-7% in bone mass in the placebo group over 2 yr. Biochemical estimates of bone turnover (plasma bone Gla protein, serum alkaline phosphatase, fasting urinary calcium and fasting urinary hydroxyproline) fell significantly in the hormone group, but remained unchanged in the placebo group. We conclude that continuous administration of NETA in combination with oestrogen provides effective prophylaxis against post-menopausal bone loss, although it does not produce a persistent positive calcium balance in early post-menopausal women.

Alkaline Phosphatase↗

PubMed1988

Plasma BGP: an indicator of spontaneous bone loss and of the effect of oestrogen treatment in postmenopausal women.

One hundred and ninety-one healthy early postmenopausal women, aged 45-54 years, were randomized to 2 years of treatment with (a) percutaneous 17 beta-oestradiol combined with progesterone (n = 29) or placebo (n = 28); (b) oral oestradiol valerate combined with cyproterone acetate (n = 37) or placebo (n = 39); (c) 24R, 25 (OH)2D3 (n = 29) or placebo (n = 29). We measured the plasma bone Gla-protein (BGP), bone mineral content of the proximal forearms (BMC), bone mineral density in the spine (BMDspine) and total body bone mineral (TBBM) in all the women before, and during, the study. In the groups of women receiving the oestrogen preparations, the plasma BGP decreased highly significantly (P less than 0.001) to a premenopausal level. The initial plasma BGP concentration was significantly related to the loss of BMC (P less than 0.001) in the placebo groups. The changes in plasma BGP were an indicator of the oestrogen response on BMC. We conclude that serial determinations of plasma BGP are useful for determination of the effect of oestrogen therapy in groups of patients, and that plasma BGP measured at the time of the menopause indicates what the rate of bone loss will be.

Calcium-Binding Proteins↗

PubMed1988

The effect of a gonadotropin-releasing hormone agonist analog (nafarelin) on bone metabolism.

The effect on bone metabolism of an agonist analog of GnRH, nafarelin, was studied in 16 premenopausal women, who received 200 micrograms nafarelin/day for 6 months, and 9 premenopausal women, who received 400 micrograms nafarelin/day for 6 months, followed by a 6-month follow-up period. Bone mineral content in the forearm (measured by single photon absorptiometry) and in the spine (measured by dual photon absorptiometry) significantly decreased after 6 months of treatment with 400 micrograms nafarelin, but 6 months after termination of treatment all bone mineral measurements had returned to pretreatment levels. The bone mineral measurements in the 200 micrograms group did not change throughout the study. In both treatment groups the biochemical estimates of bone turnover increased significantly to postmenopausal levels. Withdrawal of treatment resulted in an abrupt decrease in the bone resorption parameters (fasting urinary hydroxyproline to creatinine and calcium to creatinine excretion ratios and serum phosphate), whereas there was a protracted fall in the bone formation parameters (plasma bone Gla protein and serum alkaline phosphatase) 6 months after termination of treatment. Our findings demonstrate that nafarelin in both doses increased biochemical indices of bone turnover, that 400 micrograms/day nafarelin resulted in a significant decrease in bone mineral content, and that these effects were reversible.

Adult↗