Prevention of postmenopausal osteoporosis by estrogen/gestagen substitution therapy.
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Aged↗
Biomedical subjects
C Christiansen
Publications and source records attributed to C Christiansen.
Nucleotide sequence of the 3' end of the Mycoplasma strain PG50 rrnA operon.
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Base Sequence↗
Does calcium supplementation prevent postmenopausal bone loss? A double-blind, controlled clinical study.
During a two-year study, we examined the effect of calcium supplementation on postmenopausal bone loss in 43 women in the early postmenopausal period who were assigned to one of three treatment groups: percutaneous 17 beta-estradiol (combined with progesterone during the second year), oral calcium (2000 mg daily), and placebo. All participants were examined every three months. Bone mineral content in the forearm (measured by single-photon absorptiometry) and in the entire body and spine (measured by dual-photon absorptiometry) remained constant in the estrogen-treated group but decreased significantly in the groups receiving calcium and placebo. In the calcium-treated group, we observed a tendency toward a slowed loss of compact bone (in the proximal forearm and total skeleton) as compared with the placebo group, while the rate of loss of trabecular bone (the distal forearm and spine) was the same as in the placebo group. Our preliminary data suggest that calcium supplementation in the dosage we used is not as effective as estrogen therapy for the prevention of early postmenopausal bone loss. Calcium supplementation may have had a minor effect on the loss of cortical bone, but it had no effect on the trabecular bone.
Bone and Bones↗
Bone turnover in spinal osteoporosis.
We have investigated biochemical indices of bone formation and bone resorption: serum alkaline phosphatase (sAP) plasma bone Gla protein (pBGP), fasting urinary hydroxyproline corrected for creatinine (FuHP/Cr), and fasting urinary calcium corrected for creatinine (FuCa/Cr) in 43 postmenopausal women with spinal fractures. Furthermore, histomorphometric indices of bone resorption and bone formation, as well as whole body retention (WBR) of 99m-technetium-diphosphonate (99mTc-DP), were determined. The results are compared to pre- and postmenopausal normal subjects. The results showed that indices of bone formation were mutually correlated except for sAP vs. WBR. sAP, WBR, and pBGP increased with age. sAP and WBR were not different between osteoporotics and age-matched controls, while pBGP and probably histological indices of bone formation were lower in osteoporotics than in age-matched controls. pBGP--and to a lesser extent sAP--were significantly correlated with all histological parameters reflecting bone formation. Finally, biochemical indices of bone resorption were high in osteoporotic patients and poorly correlated with histological bone resorption. The discrepancy between biochemical markers of bone formation may be related to the low sensitivity of sAP and WBR. Conversely, pBGP, sAP, and WBR may reflect different aspects of osteoblastic activity and bone mineralization. Finally, our data suggest that bone turnover increases with aging and that osteoporotic patients have higher bone resorption and probably lower bone formation than age-matched controls.
Adult↗
Whole body retention of 99mTc-diphosphonate. Relation to biochemical indices of bone turnover and to total body calcium.
Whole body retention (WBR) and urinary excretion (UE) of 99mTc-diphosphonate were determined in 161 healthy adults and the results were compared to accepted biochemical markers of bone turnover. WBR was corrected for total body bone mineral (TBBM) and UE for forearm bone mineral content (BMC). Both uncorrected and corrected retention measurements were highly significantly correlated to the biochemical markers (P less than 0.001), but the r values were low (0.22-0.64). All bone turnover variables demonstrated considerably higher levels of bone turnover in postmenopausal women than in premenopausal women (P less than 0.001), whereas the variables were unchanged with age in men. The correction of WBR for TBBM and UE for BMC increased the validity of the retention methods and the two calculations gave exactly the same results on a group basis, both demonstrating significantly higher bone turnover in women than in men in each age group (P less than 0.05-P less than 0.001). All the turnover variables were measured in a group of perimenopausal women (n = 33). The data clearly demonstrated that bone turnover is menopause dependent, whereas age in itself is of minor significance.
Adult↗
Serum concentration of vitamin D metabolites in rheumatoid arthritis.
One-hundred and two patients with rheumatoid arthritis (RA) were studied. They were divided into three groups according to treatment with gold salts, penicillamine or glucocorticoids. Blood samples were drawn between November and January and four different metabolites of vitamin D (25(OH)D3, 24,25 (OH)2D3, 25,26 (OH)2D and 1,25 (OH)2D) were measured and compared to values from normal subjects. The mean serum concentrations of 25(OH)D3 in all three patient groups were significantly lower than those of the controls (p less than 0.01-0.001). The mean serum concentrations of 24,25 (OH)2D3 and 25,26 (OH)2D were not significantly different from the control values, whereas 1,25 (OH)2D concentrations were significantly lower in the penicillamine and steroid groups (p less than 0.05-0.01). When patients were stratified according to functional classes, we found a significant inverse relation between serum concentrations of 25(OH) D3, 24,25(OH)2D3, 25,26(OH)2D and the functional class, but not between 1,25(OH)2D and the functional class. We conclude that the decreased serum 25(OH)D3 concentration found in patients with RA is likely to be caused by decreased exposure to sunlight due to decreased activity, and thus is a result of the disease rather than a pathogenetic factor. Whether the small decrease in serum 1,25(OH)2D is of clinical significance and related to the development of osteoporosis in patients with RA is probably doubtful.
Adult↗
The effect of percutaneous estradiol and natural progesterone on postmenopausal bone loss.
The effect of percutaneous estradiol alone and combined with natural progesterone on postmenopausal bone loss was studied. A total of 57 women who had experienced a natural menopause 6 months to 3 years previously entered the study. After an initial examination the women were allocated in a blinded pattern to treatment with 3 mg of percutaneous estradiol or placebo. The code was broken after 1 year of treatment, and the women receiving estradiol continued with a cyclic addition of progesterone, whereas those receiving placebo continued with placebo. The women were examined every 3 months during the 2 years of treatment. Measurement of the bone mineral content in the forearms (single photon absorptiometry) and the spine and total skeleton (dual photon absorptiometry) showed a significant decrease of 5% to 7% in the placebo group during the 2 years of treatment, whereas it remained constant in all bone compartments in the estradiol group. Addition of progesterone did not influence the results. Biochemical estimates of calcium metabolism changed toward a premenopausal level in the estradiol group but remained unchanged in the placebo group. We conclude that percutaneous estradiol is effective as preventive therapy of postmenopausal bone loss and that addition of progesterone does not influence bone or calcium metabolism.
Administration, Cutaneous↗
Long-term effects of percutaneous estrogens and oral progesterone on serum lipoproteins in postmenopausal women.
Serum lipids and lipoproteins were examined in a group of 45 healthy postmenopausal women who were treated for 2 years with either 3 mg of percutaneous estradiol (n = 20) or placebo (n = 25). Percutaneous estradiol was given alone during the first year of treatment and in combination with oral micronized progesterone (200 mg) for 12 days of each cycle during the second year. The women were examined every 3 months throughout the 2 years. Percutaneous estrogen therapy significantly reduced total serum cholesterol and low-density lipoprotein cholesterol, whereas no significant differences were observed in serum triglycerides and high-density lipoprotein cholesterol. Addition of oral progesterone during the second year of treatment did not produce any significant alterations in serum total cholesterol or low-density lipoprotein cholesterol, both of which remained significantly reduced. Serum triglycerides remained virtually unchanged, whereas a slight but significant increase (p less than 0.05) was observed in high-density lipoprotein cholesterol levels at the end of the study period. We conclude that percutaneous estrogen administration produces changes in total serum cholesterol and low-density lipoprotein cholesterol levels similar to those observed after oral estrogen administration. However, the magnitude and time course of the response seem to be modulated by the route of administration. Addition of oral micronized progesterone does not influence the beneficial estrogenic actions on serum lipids and lipoproteins and seems to be a proper "progestogen" in percutaneous estrogen therapy.
Administration, Cutaneous↗
Climacteric symptoms after oral and percutaneous hormone replacement therapy.
One hundred and ten (110) healthy early post-menopausal women with mild subjective vasomotor symptoms (mean Kupperman index score 11) participated in a long-term, double-blind, placebo-controlled therapeutic trial. The effects of 2 hormone regimens were evaluated. Group I received percutaneous oestrogen therapy for 2 yr, opposed by oral micronized progesterone (200 mg) during the second year, while Group II received oral 17 beta-oestradiol valerate together with cyproterone acetate (CPA). The serum oestrogen concentrations differed markedly in the 2 treatment groups. In Group I the serum/oestrone/oestradiol ratio was 1 (comparable to the pre-menopausal value), but in group II the ratio was greater than 5. Despite the difference in the serum oestradiol and oestrone concentrations, the mean symptom scores were rapidly and similarly reduced in both treatment groups (P less than 0.001). They remained low throughout the study and were not significantly different from pre-menopausal values.
Administration, Cutaneous↗
Dose-response effects on serum lipids and lipoproteins following combined oestrogen-progestogen therapy in post-menopausal women.
The dose-response effects on serum lipids and lipoproteins were studied in 87 healthy post-menopausal women treated for 1 yr with three different doses of sequential oestrogen/progestogen (4 mg, 2 mg and 1 mg 17 beta-oestradiol cyclically combined with 1 mg norethisterone acetate) or placebo. Total serum cholesterol levels were significantly reduced by 4-10% (P less than 0.05-P less than 0.001) in a dose-related way in the hormone groups. This was mainly caused by a similar reduction in low-density-lipoprotein (LDL) cholesterol, whereas the changes in high-density-lipoprotein (HDL) cholesterol were not significantly different from those observed in the placebo group. It is concluded that treatment with sequentially combined oestrogen and progestogen, using norethisterone acetate in combination with 17 beta-oestradiol in clinically relevant doses, does not produce any adverse effects on serum lipids or lipoproteins.
Cholesterol, HDL↗
Bone mass, bone structure and vertebral fractures in osteoporotic patients.
The clinical severity of bone disease was studied in 44 post-menopausal osteoporotic women. Spinal x-rays were assessed and compared to objective measurements of bone mass and bone structure; forearm bone mineral content (BMCarm) by single photon absorptiometry, total body bone mineral content (TBBM), and spinal bone mineral content (BMCspine) by dual photon absorptiometry, and corrected cortical width (C Cor W), trabecular bone volume (TBV), and indices of trabecular microstructure by iliac crest biopsy. For comparison data of BMCarm, TBBM and BMCspine in 25 post-menopausal normals are shown. The results showed a reduction in amount of both cortical and trabecular bone in the fracture patients compared to normals. A subdivision of the fracture patients into two groups constituting 26 patients with wedge fractures alone and 18 patients with compression (+wedge) fractures showed that the latter group had a further predominantly trabecular bone loss and a further deteriorated trabecular microstructure. On an individual basis no agreement between clinical severity of bone disease and amount and structure of bone could be demonstrated.
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Plasma bone Gla protein concentrations in healthy adults. Dependence on sex, age, and glomerular filtration.
Plasma bone Gla protein (BGP) was determined by radio-immunoassay in 266 healthy adults, men (n = 132) and women (n = 134), aged 20-79 years. In the women aged 30-69 years, plasma BGP increased significantly with age (r = 0.44, p less than 0.001), and a particularly steep increase was seen from 1.1 +/- 0.5 (mean +/- 1 SD) in the fifth decade to 2.0 +/- 1.4 nmol/l in the seventh decade. In men, aged 30-69 years, no correlation was found between plasma BGP and age (r = -0.07, NS). Plasma bone Gla protein is removed from the circulation mainly by the kidneys and the increased plasma BGP in the women could be caused by decreased renal clearance. The interrelationship was analysed by means of partial correlation. When creatinine clearance was held constant in women, BGP still correlated positively with age (r = 0.40, p less than 0.001), but not with creatinine clearance (r = 0.003, NS) when age was fixed. Plasma BGP was significantly increased above normal in 35 patients with chronic renal failure (10.2 +/- 14.6 nmol/l). Non-linear regression analysis showed that plasma BGP was within the normal range when 24-h creatinine clearance was greater than 30 ml/min, and large increases in plasma BGP did not occur until the 24-h creatinine clearance was below 20 ml/min. We conclude that, in normal subjects and patients with mild to moderate renal failure, plasma elevations of BGP reflect increased bone turnover rather than decreased renal clearance.
Adult↗
Vitamin D deficiency after highly selective vagotomy.
While bone disease is occasionally seen after gastrectomy, the influence of vagotomy on calcium and vitamin D metabolism is uncertain. We have, therefore, investigated 23 male patients who had undergone highly selective vagotomy for ulcer 4.3 +/- 1.2 years previously. The 25OHD concentrations were decreased (p less than 0.05), the 1,25(OH)2D concentrations elevated (p less than 0.05) and the immunoreactive parathyroid hormone concentrations normal. Local and total bone mass were normal compared to age-matched men, and there was no biochemical evidence of increased bone turnover. We suggest that the changes in calcium absorption, which are described in the literature after vagotomy, are mediated by 1,25(OH)2D. Although the changes in vitamin D metabolism do not lead to calcium-metabolic disturbances in selected patients, we believe that some will eventually develop vitamin D deficiency and that vitamin D supplementation should be considered.
Adult↗
Dietary calcium intake and blood pressure in normotensive subjects.
Epidemiological and prospective studies in man and animals have indicated an inverse relationship between calcium intake and cardiovascular mortality and blood pressure (BP). We have therefore studied the effect of dietary calcium on blood pressure in two groups of women. In a cross-sectional study 103 early postmenopausal women were stratified into three groups according to daily calcium intake calculated from a questionnaire. Both diastolic and systolic blood pressures were identical in the three groups. We thereafter conducted a prospective placebo-controlled trial on the effect of calcium supplementation. Twenty-eight healthy women were randomized to placebo treatment (n = 14) or calcium supplementation 2,000 mg daily (n = 14) for one year. In both groups BP remained at initial levels throughout the study and was identical in the two groups at measurements every three months. We thus conclude that calcium supplementation has no effect on BP in normotensive subjects on a high calcium diet.
Blood Pressure↗
Bone metabolism and bone status in osteoporotic patients.
We have studied bone turnover and bone status in 29 patients with hip fractures and compared them with normal subjects and patients with arthritis of the hip. Markers for bone formation, bone Gla protein, alkaline phosphatase and whole body retention of 99mTc-diphosphonate, and fasting urinary hydroxyproline, a marker for bone resorption, were all significantly higher in the hip fracture group than in the control group. The serum concentrations of 1,25-dihydroxyvitamin D were similar in the three groups, whereas the serum 25-hydroxyvitamin D concentration in the control group was higher than in the patient groups. The bone mineral content (BMC) measured in the distal forearm and the spine was lower than normal in the hip fracture group. We conclude that patients with hip fractures have an increased bone turnover with no signs of bimodality and low BMC values at all locations.
Aged↗
Cyproterone acetate, an alternative gestagen in postmenopausal oestrogen/gestagen therapy.
Seventy-six healthy, early postmenopausal women (aged 45-54 years) were allocated to 2 years of treatment with a cyclic combination of 2 mg oestradiol valerate (21 d) and 1 mg cyproterone acetate (11 d) or placebo. Sixty-five women (86%) completed the study. In the placebo group the bone mineral content in the forearms (measured by single photon absorptiometry) and the bone mineral content in the lumbar spine and total skeleton (measured by dual photon absorptiometry) decreased significantly and at the same magnitude (P less than 0.001), whereas all bone mass measurements remained unchanged in the hormone-treated group. In the hormone-treated group there was a significant decrease in biochemical estimates of bone turnover (serum alkaline phosphatase, serum phosphate, fasting urinary calcium and hydroxyproline), whereas these values were unchanged in the placebo treated group. We conclude that treatment with a cyclic combination of 2 mg oestradiol valerate and 1 mg cyproterone acetate is effective as prophylaxis of postmenopausal bone loss.
Calcium↗
Familial hypocalciuric hypercalcaemia. III: Bone mineral metabolism.
Bone mineral metabolism was studied in 10 subjects with familial hypocalciuric hypercalcaemia (FHH) and 10 age-, sex- and surface area matched healthy controls. Bone turnover was estimated by urinary calcium and hydroxyproline excretions relative to creatinine (Ca/Creat and OHPr/Creat, respectively), serum bone Gla-protein (S-BGP) and serum alkaline phosphatase (S-ALP). Bone status was evaluated by measurement of bone mineral content (BMC) on both forearms and X-ray examinations of the hands. Ca/Creat and OHPr/Creat (indices of bone resorption) were both significantly higher in the FHH group than in the controls. S-BGP and S-ALP (indices of bone formation) tended towards a higher level in the FHH subjects, but the differences were not significant. The BMC values were similar in the two study groups and did not change with time. We conclude that these patients with FHH might have a bone turnover higher than normal, and that the increased bone resorption must be paralleled by an increased bone formation.
Bone and Bones↗
Continuous oestrogen-progestogen treatment and serum lipoproteins in postmenopausal women.
Serum lipids and lipoproteins were examined in 44 healthy postmenopausal women every 3 months during 1 year of treatment with either continuous oestrogen-norethisterone acetate or placebo. Total serum cholesterol and LDL-cholesterol levels were reduced by approximately 15% and 20% (P less than 0.001), respectively in the hormone group but were unchanged in the placebo group. Serum triglycerides levels remained constant in both groups. HDL-cholesterol levels were significantly reduced by approximately 10% in the hormone group but significant reductions of 5-10% also occurred in the placebo group so that differences between the two groups were only significant after 3 months of treatment. Vaginal bleedings were experienced during the first 3 months by eight of the 21 women receiving hormones, but in only one woman after 9 months of therapy. The addition of norethisterone acetate to postmenopausal oestrogen therapy in clinically relevant doses had no adverse effects on lipoproteins as previously reported, even though administered continuously. Moreover, the low frequency of bleeding with continuous oestrogen-progestogen therapy would make this an appropriate alternative in postmenopausal replacement therapy.
Cholesterol, HDL↗