Merete Sanvig Christensen

Prevention of early postmenopausal bone loss: controlled 2-year study in 315 normal females.

Abstract. With the aim of preventing postmenopausal bone loss, a placebo‐controlled double‐blind trial of 2 years duration was performed. We randomized 315 healthy volunteers in their early natural menopause to seven treatment and three placebo groups: 17β‐oestra‐diol, oestriol and sequential norethisteron (hormones); bendroflumethiazide 5 mg/day (thiazide); hormones and thiazide; sodium fluoride 20 mg/day; vitamin D3 2000 IU/day (D3); fluoride and D3; and lα (OH) vitamin D3 0–25 μg/day (lαD3). All participants were given daily calcium supplement of 500 mg. Every 3 months we measured the bone mineral content (BMC) of both forearms by photon absorptiometry and chemical quantities in blood and 48 h urinary collections. The study was completed by 264 (84%).

Renal hypomagnesaemia in human diabetes mellitus: its relation to glucose homeostasis.

Abstract. Interrelations between magnesium and glucose metabolism were studied in 215 insulin‐treated diabetic out‐patients aged 7–70 years. All had normal serum creatinine concentrations (below 115 μmol/l) and none had other diseases or received drugs known to interfere with mineral metabolism. A definite hypomagnesaemia (< normal mean —2 SD) and hypermagnesiuria (> normal mean + 2 SD) occurred in 38.6% and 55% of the patients. In the presence of hypermagnesiuria the serum magnesium concentration was inversely correlated to the urinary magnesium excretion rate (R=–0.23, P<0.02). Serum magnesium correlated inversely with both fasting blood glucose (R=—0.32, P<0.001) and the urinary glucose excretion rate (R=–0.22, P<0.005). The urinary magnesium excretion rate correlated directly with the same variables (R= 0.27, P<0.001 and R= 0.58, P<0.001, respectively). These data indicate that the net tubular reabsorption of magnesium is decreased in diabetic patients in presence of hyperglycaemia, leading to hypermagnesiuria and hypomagnesaemia.

Effect of 1,25‐dihydroxy ‐ vitamin D3 in itself or combined with hormone treatment in preventing postmenopausal osteoporosis

Abstract. Eighty‐four normal women, 2.5‐5 years after their natural menopause, participated in a controlled double‐blind trial. The effect of various therapeutic regimens on postmenopausal bone mineral loss was measured by photonabsorptiometric determination of the bone mineral content of both forearms. The women were randomized into four treatment groups: 1,25‐dihydroxycholecalciferol (1,25(OH)2D3) alone in a daily dose of 0.25 μg, oestrogens/gestagen alone or combined with 1,25(OH)2D3, and placebo. The groups treated with oestrogens/gestagen (without and with 1,25(OH)2D3) showed a similar increase in bone mineral content of about 1% during one year of treatment. In contrast, both the placebo group and the 1,25(OH)2D3 group demonstrated a decrease of 1.9% and 2.1%, respectively, within the same period of time. While 1,25(OH)2D3 did not alter the rate of bone loss, it caused the characteristic and pronounced increase in urinary calcium excretion (15%).

Thiazide for the postponement of postmenopausal bone loss

The effect of thiazide on bone mineral loss in normal postmenopausal women was examined during a 3 yr placebo-controlled clinical trial. Sixty-three healthy women in their early menopause were randomized to treatment with bendroflumethiazide 5 mg/day or placebo for 2 yr, while both groups received placebo for the third year of the trial. Calcium supplement 0.5 g/day was given throughout the 36 mo to all participants. Bone mineral content (BMC) determined by 125I-photon absorptiometry of the forearms decreased 2% per year in the placebo group (p less than 0.001). In the thiazide group no fall in BMC was seen during the first 6 mo. whereafter BMC declined with the same rats as in the placebo group. At the end of the 3 yr trial BMC averaged 94.1% in the placebo group and 95.2% in the thiazide group (p greater than 0.05). Despite a daily supplement of 0.5 g calcium, thiazide induced a persistent fall in the urinary calcium excretion of 25% (p less than 0.001), whereas the calcium supplement in the placebo group caused a significant increase in mean urine calcium of 10%-20% (p less than .001). At stop of thiazide medication a rebound effect caused a marked rise in urine calcium. One month after withdrawal of the calcium supplement the urinary calcium excretion had returned to the initial level in both groups. It is concluded that despite a sustained urine calcium lowering action the effect of thiazide upon postmenopausal bone loss is shortlived.

Development of bone mineral loss in insulin‐treated diabetes: a 1 1/2 years follow‐up study in sixty patients

Abstract. The change in bone mass during 1 1/2 years was determined in a longitudinal study of sixty adult insulin‐treated diabetic out‐patients. During the study period the mean bone mass decreased by 1.30 ± 0.28 (SEM) % (P < 0.001), to a mean value of 91.0 ± 1.7% of normal (P < 0.001). The rate of bone loss was significantly higher in patients with 1–6 years of diabetes (n= 29, bone loss: 1.96 ± 0.32%/1 1/2 years) than in patients with longer duration of the disease (n= 31, bone loss: 0.61 ± 0.44%/l 1/2 years, P < 0.02). The endogenous insulin secretion estimated with the glucagonstimulated serum C‐peptide concentration decreased during the observation period in 58.6% of the patients with 1–6 years of diabetes compared to 16.1% among patients with 7–11 years of diabetes (P < 0.002). The rate of bone mineral loss was almost 3 times higher in the twenty‐two patients in whom endogenous insulin secretion had deteriorated (2.12 ± 0.30%/l 1/2 years) than in the thirty‐eight patients without as well as with unchanged or increased insulin secretion (0.78 ± 0.39%/l 1/2 years, P < 0.01). In twenty patients with an increased insulin dose during the study period the mean bone mineral loss was 2.05 ± 0.36%/l 1/2 years compared to a mean bone mineral loss of 0.91 ± 0.38%/l 1/2 years in the forty patients with unchanged or decreased insulin dosage (P < 0.05).

Optimal diagnosis in acute myocardial infarction. A cost-effectiveness study.

The predictive value of a diagnostic test estimates the likelihood for presence or absence of disease in a patient with a positive or negative test result (PV, O, or PVYR.,). We evaluated the predictive values of serum activities of the heart-specific creatine kinase isoenzyme MB (CK-MB), aspartate aminotransferase, lactate dehydrogenase, CK, and ECG in 401 consecutively admitted patients suspected of acute myocardial infarction (AMI). The study showed that CK-MB (PVPOI = 0.98, PV.g, = 1.00) was better than the other enzymes (single as well as serial) and ECG, evaluated both separately and in combinations. In all cases of AMI CK-MB was positive within 17 hours from admission. Replacement of the standard enzymes with CK-MB provides a faster and safer diagnosis of AMI and reduces hospitalization time considerably for patients without AMI.

Determination of zinc in serum and urine by atomic absorption spectrophotometry; relationship between serum levels of zinc and proteins in 104 normal subjects.

Serum and urine zinc were measured by atomic absorption spectrophotometry. The drift in base-line was continuously registered and corrections for the drift were made in the calculations of zinc measurements to avoid any adjustment in the instrument settings. Food intake was shown to lower the serum zinc concentration by 19% on average (p < 0.001). A diurnal variation of serum zinc was observed with a minimum at 7 p.m. Venous stasis elevated the mean serum zinc concentration by 13% (p < 0.001) and the mean serum protein level by 14% (p < 0.001). Weak correlations between serum zinc and both the serum concentration of proteins and of albumin were found in 104 normal subjects. There was no correlation between serum concentrations of zinc and α2-macroglobulin. The concentration of serum zinc was 9% higher in males than in females (p < 0.005) which was not explained by sex differences in serum protein concentrations. Furthermore, males had a higher excretion rate of zinc in urine than females, when expressed as μmol Zn/24 hour (p < 0.01). This difference disappeared when urine zinc was corrected to urinary excretion rate of creatinine. Our results show that blood samples for serum zinc measurement should be taken in the morning in fasting state. The urinary zinc excretion rate should be related to the creatinine excretion rate to avoid sex differences.

Hyperzincuria in insulin treated diabetes mellitus—its relation to glucose homeostasis and insulin administration

In order to elucidate some pathogenic factors of diabetic hyperzincuria we studied 60 adult insulin treated diabetic out-patients (40 males and 20 females), all with normal serum creatinine concentrations and absence of proteinuria during a 24-h period. Diabetic males and females both had significantly (p less than 0.01) increased zinc excretion rates (1.14 +/- 0.06 (S.E.M.) mumol/mmol creatinine and 1.37 +/- 0.10 mumol/mmol creatinine) compared with normal males and females (0.55 +/- 0.06 and 0.48 +/- 0.08, respectively). The urinary zinc excretion rate correlated positively with the degree of glycosuria (r = 0.36, p less than 0.01), but was not associated with the duration of the disease. However, serum zinc levels gave no evidence of a state of zinc depletion in these patients. It was calculated that zinc originating from a diabetic bone loss and the exogenous insulin administration accounted for only a small part of the hyperzincuria. Compensatory hyperabsorption and/or increased zinc content in the diabetic diet may therefore serve to explain the lack of zinc depletion in the presence of hyperzincuria.

Vitamin D metabolites in diabetic patients: Decreased serum concentration of 24,25-dihydroxyvitamin D

In order to elucidate if changes in vitamin D metabolism play a role for diabetic bone loss, the serum concentrations of the major vitamin D metabolites were studied in 26 adult male ambulatory insulin-treated diabetics, selected to have normal renal function and a duration of diabetes below 11 years. The patients were studied during usual metabolic control and exhibited wide ranges of hyperglycaemia and glycosuria. The serum concentrations of the major metabolites of vitamin D, 25-hydroxyvitamin D(2 + 3) (25OHD), 24,25-dihydroxyvitamin D(2 + 3) (24,25(OH)2D), and 1,25-dihydroxyvitamin D(2 + 3) (1,25(OH)2D), were measured in diabetics, and in age and sex matched controls. The diabetics had slightly decreased serum levels of 25OHD (42.0 nmol/l versus 55.5 nmol/l in normals, P less than 0.05), markedly decreased serum levels of 24,25(OH)2D (2.98 nmol/l versus 5.91 nmol/l, P less than 0.01), but serum levels of 1,25(OH)2D were virtually normal (64.2 pmol/l versus 68.3 pmol/l, ns). The close correlation between serum concentrations of 25OHD and 24,25(OH)2D observed in the normal subjects, was absent in the diabetics. There were no correlations between the serum levels of any of the vitamin D metabolites and the measured indices of glucose and calcium metabolism. It is concluded that insulin-dependent diabetic patients demonstrate definite alterations in serum levels of vitamin D metabolites, the significance of which remains unknown at present.

A Sensitive Radioimmunoassay of Parathyroid Hormone in Human Serum Using a Specific Extraction Procedure

A radioimmunoassay of human parathroid hormone (PTH) is described. PTH was extracted from serum by adsorption to and elution from microfine silica, causing a 3.2-fold greater hormone concentration in extract than in serum. The extraction procedure eliminated from the assay unspecific interference caused by serum factors. The detection limit was 10 pg bovine PTH. The concentration of PTH was measurable in serum from 95% of normal subjects (mean, 68 pg/ml; SD., 18), was undetectable in sera from hypoparathyroid patients, and elevated in 96% of sera from patients with primary hyperparathyroidism. The presented data suggest that the assay mainly measures PTH(1-84).