Biomedical subjects

L Hyldstrup

Publications and source records attributed to L Hyldstrup.

At least 37 records · Page 2Linked to original sources

PubMed1994

Progressive escape from parathyroid suppression: a common phenomenon in primary hyperparathyroidism (a calcium clamp study).

OBJECTIVE: Induced aggravation of hypercalcaemia in vivo and in vitro causes partial suppression of parathyroid hormone (PTH) secretion in primary hyperparathyroidism (PHP). Furthermore, one in-vitro study also demonstrates progressive escape from such action. The aim of the present in-vivo study was to examine whether escape from suppression is a common feature of PHP. DESIGN: A rapid increment in blood ionized calcium (B-Ca2+) to 0.25-0.30 mmol/l above individual baselines was achieved by intravenous calcium infusions. This induced or aggravated hypercalcaemia was kept constant for 2 hours (controls) or 4 hours (patients). PATIENTS AND CONTROLS: The study of PHP comprised 19 patients (18 females and one male) aged 39-85 years (geometric mean 66). For comparison we included the results obtained in a control group of 24 healthy subjects (11 women and 13 men) aged 20-68 years (geometric mean 32). MEASUREMENTS: The individual levels of B-Ca2+ were controlled by frequent bedside measurements of B-Ca2+. The changes in serum intact parathyroid hormone (S-PTH(1-84)) were registered. RESULTS: After 30 minutes of calcium infusion average concentrations of S-PTH(1-84) had decreased from 7.9 (6.7-9.4) pmol/l in PHP and 2.5 (2.1-2.9) pmol/l in controls to their respective nadir values of 2.9 (2.1-4.1) pmol/l and 0.6 (0.5-0.8) pmol/l. While S-PTH(1-84) remained suppressed at a stable level for 120 minutes in controls, in PHP it started to escape progressively after 30 minutes to a level of 4.2 (3.0-5.8) pmol/l (P < 0.001). Linear regression analysis of the individual S-PTH(1-84) observations in PHP, from 30 to 240 minutes of study, revealed that five patients did not escape (group A) while the remainder 14 patients escaped progressively (group B). Within group B, seven patients escaped significantly after 120 minutes, 10 after 180 minutes and 14 after 240 minutes. Although comparable respecting B-Ca2+ before and during calcium infusion, group A and B presented different S-PTH(1-84) curves. Thus, at times zero, 30, 120 and 240 minutes their respective average concentrations of S-PTH(1-84) measured 9.9 (9.1-10.9) vs 7.3 (5.9-9.0) (P < 0.02), 4.6 (3.7-5.7) vs 2.5 (1.6-3.9) (P < 0.01), 5.0 (3.9-6.5) vs 3.0 (1.9-4.8) (P < 0.05) and 5.2 (3.6-7.4) vs 3.9 (2.6-6.0) (NS) pmol/l. CONCLUSIONS: We hypothesize that two different mechanisms are involved in the parathyroid response to the calcium clamp, an initial and fast inhibition of PTH release, while the subsequent course depends on the balance between the intra-glandular secretion rate of PTH and the intra-glandular capacity for PTH degradation. The escape from parathyroid suppression during a sustained stable increment in B-Ca2+ suggests that the basal secretion over-rides degradation in a majority of the patients with PHP.

Aged↗

PubMed1994

Effect of oral calcium on noninvasive indices of bone formation and bone mass in hemodialysis patients: a randomized double-blind placebo-controlled study.

The purpose of this study was to evaluate the effect of high-dose oral calcium on biochemical indices of bone formation, bone bisphosphonate clearance (BBC) and bone mineral content (BMC) of the distal forearm in patients undergoing hemodialysis. Eighteen patients agreed to participate and were randomized in a double-blind manner to receive either 2 g elemental calcium/day (n = 9) or placebo (n = 9) for 6 months. Previous treatment with aluminum-containing phosphate binders was continued unchanged throughout the study. In the placebo group, serum alkaline phosphatase and osteocalcin tended to increase by 8.0 and 10.2%, respectively, while BBC changed significantly by 49.5% (p < 0.05). In the calcium group the opposite was observed with small decreases in alakline phosphatase and osteocalcin by 8.2 and 11.0%, respectively, and no change in BBC. BMC decreased by 5.0% in the placebo group, but increased by 5.2% in the calcium group, resulting in a difference of 10.2% (p < 0.05). The present study demonstrates that high-dose oral calcium tends to reduce bone turnover and seems able to prevent bone loss in hemodialyzed patients.

Administration, Oral↗

PubMed1994

Cica clamp evaluation of parathyroid responsiveness in chronic hypoparathyroidism: a sequential citrate and calcium clamp study.

The objective of this study was to examine if the Cica clamp technique, sequential citrate and calcium administration sufficient to promote steady-state-blood-ionized calcium concentrations (B-Ca2+) of about 0.20 mmol/l below and above the individual baseline concentrations, was able to produce reciprocal changes in serum intact parathyroid hormone [S-PTH(1-84)] in chronic surgical hypoparathyroidism (HP; n = 10) and chronic idiopathic HP (n = 2). The calcium set point according to Brown [J Clin Endocrinol Metab 1993;56:572-581] was calculated when possible. Data from 22 controls were included for comparison. Within 5-10 min B-Ca2+ lowering in responding patients with surgical HP (n = 7) and controls demonstrated transient S-PTH(1-84) peaks from 1.3 +/- 0.7 to 3.5 +/- 3.2 pmol/l (p < 0.05) and from 3.4 +/- 1.2 to 19.1 +/- 6.7 pmol/l (p < 0.001), respectively. Subsequently S-PTH(1-84) declined to steady-state hypersecretion levels of about 1.9 +/- 1.2 and 8.6 +/- 2.6 pmol/l, respectively. An increase of B-Ca2+ made S-PTH(1-84) unmeasurable in all HP responders except one, while S-PTH(1-84) remained measurable, 0.9 +/- 0.4 pmol/l, in all controls. In responding patients with surgical HP and controls the respective calcium set points averaged 1.05 +/- 0.06 and 1.13 +/- 0.04 mmol/l, respectively (p < 0.001). The remaining nonresponders with surgical and idiopathic HP did not respond at all. To summarize, 7 out of 10 patients with surgical HP demonstrated a normal pattern of parathyroid response to sequential B-Ca2+ decreases and increases.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1993

Pharmacokinetic evaluation of pamidronate after oral administration: a study on dose proportionality, absolute bioavailability, and effect of repeated administration.

To evaluate dose proportionality and absolute bioavailability of a new enteric-coated pellet formulation of pamidronate disodium (AREDIA), nine females (aged 52-66 years) were given three different single peroral doses of pamidronate disodium (75, 150, and 300 mg) and an i.v. infusion of 15 mg over 30 minutes at constant infusion rate. Repeated peroral doses (75 and 150 mg) were administered to 12 females (aged 51-70 years) for 10 consecutive days. Urinary excretion of pamidronate after peroral and i.v. administration was used for estimation of pamidronate absorption. Renal excretion of pamidronate ranged from 0.01% to 0.35% of dose, with mean values of 0.11, 0.16, and 0.18% for 75, 150, and 300 mg, respectively. After i.v. infusion, the renal excretion of pamidronate was 26-53% of the dose, lower than for other bisphosphonates. The absolute bioavailability was 0.31% (range 0.08-0.7%) after 75 mg, 0.43% (0.01-1.20%) after the 150-mg dose, and 0.48% (0.07-1.06%) following 300 mg of pamidronate disodium. Urinary excretion after the 10th intake showed a significant increase (difference 0.07% (range -0.003-0.29%), P < 0.02) when compared with the first dose. In conclusion, intestinal uptake of pamidronate was low with high intraindividual variation, like other bisphosphonates.

Administration, Oral↗

PubMed1993

Oral calcium effectively reduces parathyroid hormone levels in hemodialysis patients: a randomized double-blind placebo-controlled study.

The objective of this study was to elucidate the effect of oral calcium supplement upon the severity of secondary hyperparathyroidism and hyperphosphatemia in patients undergoing hemodialysis. Twenty-three accepted to participate and were randomly allocated to receive in a double-blind manner either 2 g elemental calcium per day (n = 12) or placebo (n = 11) for 6 months. Three patients dropped out leaving 10 patients in each group. In the calcium group serum ionized calcium increased significantly during the 1st month from 1.15 +/- 0.02 to 1.29 +/- 0.04 mmol/l (mean +/- SE) and was then stabilized at an average of 1.26 +/- 0.02 mmol/l for the remaining 5 months. Serum intact parathyroid hormone (PTH) decreased in average by 54% within the 1st month and remained at that level for the following months. Hyperphosphatemia remained stable throughout. On the contrary, in the placebo group, serum concentrations of ionized calcium and intact PTH remained unchanged, while serum phosphate increased significantly. The present study demonstrates that oral calcium reduces secondary hyperparathyroidism and prevents the progression of hyperphosphatemia in patients undergoing hemodialysis.

Adult↗

PubMed1993

Bone metabolism in obesity: changes related to severe overweight and dietary weight reduction.

A non-invasive evaluation of bone metabolism was performed in 44 morbidly obese patients before and after a mean weight loss of 22.4 kg (range 7.9-43.4 kg) after 2 months and a further weight loss of 7.3 kg after 8 months (0.8-20.0 kg). This weight reduction was obtained by a nutritionally adequate very-low-calorie diet. Before treatment the bone mineral content of the distal forearm was increased compared to normals (51.9 U vs. 43.7 U, p < 0.001). Bone formation was evaluated by serum alkaline phosphatase and serum osteocalcin. Serum alkaline phosphatase was increased (187.8 U/l vs 147.4 U/l, p < 0.001) while serum osteocalcin was lower than in the controls (0.67 nmol/l vs 0.98 nmol/l, p < 0.01). Bone resorption, as measured by the urinary hydroxyproline/creatinine ratio, was not increased in the obese patients (19.2 molar ratio x 10(-3) vs 16.7 molar ratio x 10(-3), NS). After 2 months, the bone mineral content had declined by 3.3%. Serum alkaline phosphatase remained unchanged (187.8 U/l vs 186.9 U/l, NS) but serum osteocalcin demonstrated a significant rise (3.94 nmol/l vs 10.53 nmol/l, p < 0.001), parallel to changes in the hydroxyproline/creatinine ratio (19.2 molar ratio x 10(-3) vs 25.2 molar ratio x 10(-3), p < 0.001). At 8 months, no further change in the bone mineral content was seen. The hydroxyproline/creatinine ratio did still increase (from 25.8 molar ratio x 10(-3) to 30.1 molar ratio x 10(-3), p < 0.05), while serum alkaline phosphatase and serum osteocalcin remained unchanged.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1992

Bisphosphonate kinetics in patients undergoing continuous ambulatory peritoneal dialysis: relations to dynamic bone histomorphometry, osteocalcin and parathyroid hormone.

In the evaluation of renal osteodystrophy bone biopsy is often performed. However, a reliable noninvasive test could be very useful, and recently the estimation of osseous tracer uptake as an index of bone formation has been introduced-the bone bisphosphonate clearance (BBC). The aim of the present investigation therefore was to compare BBC with parameters of bone histology, serum levels of osteocalcin, alkaline phosphatase, and parathyroid hormone in patients (n = 8) undergoing continuous ambulatory peritoneal dialysis (CAPD). No significant correlations were found between BBC values and the bone histomorphometrical variables measured. A positive correlation was seen between serum osteocalcin and resorption and active resorption surface (p < 0.05), as well as tetracycline-labelled surface, bone formation rate, surfaces, volume and tissue referents, respectively (p < 0.01). Furthermore, levels of alkaline phosphatase showed significant correlations to mineral appositional rate, tetracycline-labelled surface and bone formation rate, volume referent (p < 0.05). Values of parathyroid hormone were significantly correlated to resorption surface (p < 0.02), active resorption surface, mineral appositional rate and mineralization lag time (p < 0.05). In conclusion, BBC was of no use in patients treated with CAPD as a noninvasive test for evaluation of bone histomorphometry. However, osteocalcin correlated best with resorption and bone dynamics indices. Levels of alkaline phosphatase and parathyroid hormone were of a more limited value.

Adult↗

PubMed1992

Late Calcium Metabolic Consequences of Jejuno-ileal Bypass.

Seventeen patients with previous jejuno-ileal bypass operation (JIB) for obesity were included in a follow-up study 11 to 19 years after JIB. Evaluation of calcium-parathyroid hormone axis was performed by a highly sensitive two-site IRMA assay for serum intact parathyroid hormone and serum ionized calcium. Evidence of a varying degree of secondary hyperparathyroidism was found. The observed hyperparathyroidism was of clinical significance in a subpopulation characterized by increased bone turnover and reduced bone mineral content. As a consequence, the calcium metabolism with special attention to the parathyroid function must be carefully monitored in JIB patients. Serum ionized calcium alone and vitamin D metabolites do not identify patients at risk of bone loss.

Journal Article↗

PubMed1992

Calcium clamp technique: suppression of serum intact PTH by induced hypercalcaemia in normal man and primary hyperparathyroidism.

The aim of the study was to investigate the interrelation between induced hypercalcaemia and serum intact parathyroid hormone (S-PTH(1-84)) in normal man and in patients with primary hyperparathyroidism (PHPT) by measuring blood ionized calcium (B-Ca++) and S-PTH(1-84) before and during a controlled calcium infusion. Guided by frequent measurements of B-Ca++, we adjusted the calcium infusion rate continuously, thereby keeping B-Ca++ in a steady state at a pre-determined level approximately 0.25 mmol l-1 above baseline values. This calcium clamp technique (CCT) applied to 14 normal volunteers for 120 min established a standardized reference for parathyroid suppression and the renal physiological PTH response. The reproducibility of the method and the results obtained by the CCT were satisfactorily assessed in six of the 14 normal subjects. In normal subjects B-Ca++ was raised from 1.25 +/- 0.3 mmol l-1 (mean +/- SD) to 1.49 +/- 0.02 mmol l-1 suppressing S-PTH(1-84) to 264 +/- 9.9% of pre-infusion levels. We applied the CCT to 10 patients with PHPT for 120 min raising B-Ca++ from 1.41 +/- 0.09 mmol l-1 to 1.69 +/- 0.08 mmol l-1, thereby suppressing S-PTH(1-84) to 47.9 +/- 16.3% of pre-infusion levels. The renal handling of calcium and phosphate during CCT demonstrates the biological effects of suppressed activity of PTH on the renal tubules showing increments in the maximal tubular phosphate reabsorption in relation to the glomerular filtration rate (TmP/GFR) and decreased tubular reabsorption fraction of calcium. The described CCT is a safe and reliable dynamic test.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1991

Changes in calcium homoeostasis and bone formation in patients recovering from acute myocardial infarction: effect of verapamil treatment. Danish Study Group on Verapamil in Myocardial Infarction.

The effect of the calcium antagonist verapamil on calcium homoeostasis and bone metabolism has been investigated in a double-blind randomized placebo-controlled study. Ten patients randomized to verapamil 120 mg t.i.d. and 9 patients randomized to placebo in The Danish Verapamil Infarction Trial II took part in the study. Bone formation, estimated by 24-h whole body retention of diphosphonate (WBR), osteocalcin, alkaline phosphatase and calcium metabolic indices, was recorded before the start of medication and after 1 and 6 months of treatment. Baseline calcium metabolic variables were not significantly different between the two study groups. There were no significant differences in WBR (0.38 vs 0.37), osteocalcin level (8.2 vs 8.0 micrograms/l) or alkaline phosphatase (218 vs 200 U/l) after treatment for 6 months with verapamil compared to placebo. Serum PTH, calcium and phosphate levels were also not affected by verapamil. The results suggest that prolonged treatment with clinical doses of verapamil does not affect indices of calcium and bone metabolism in humans.

Alkaline Phosphatase↗

PubMed1991

Bone disorder in men with chronic alcoholism: a reversible disease?

Disturbances in bone metabolism and histology have been recognized in chronic alcoholism. It has not been established whether they are reversible and the cause remains unclear. We studied various serum and urine variables (including serum PTH, calcium, D-vitamins, and osteocalcin concentrations), bone mineral content, and bone histomorphometrics in men who at present abused alcohol and compared the results to those from men who previously had abused alcohol but who had abstained from alcohol for at least 2 yr and from normal men. No significant differences were found in bone mineral content at the two measuring sites (distal forearm, lumbar spine) between drinkers, abstainers, and controls though a considerable proportion of both current drinkers and abstainers had subnormal values. Bone formation rate and turnover (expressed by the activation frequency) was significantly reduced in the current drinkers who also had lower serum PTH, 1,25-dihydroxycholecalciferol, and osteocalcin concentrations. Men who had abstained from alcohol consumption for at least 2 yr had results similar to those from normal men, suggesting that the disturbances in bone metabolism in men abusing alcohol are reversible. The decrease in bone turnover in the drinkers may be explained by the observed reduction in plasma PTH concentration or a direct toxic effect of ethanol on bone tissue leading to a deficient recruitment of osteogenic cells.

Alcoholism↗

PubMed1989

Arterio-venous concentration difference of [51Cr]EDTA after a single injection in man. Significance of renal function and local blood flow.

The present investigation was undertaken in order to study (1) the difference in arterial (Ca) and venous (Cv) concentration of [51Cr]EDTA (ethylenediaminetetraacetate) after a single intravenous injection, (2) the impact of different physiological variables on this difference, and (3) the error introduced in the measurement of renal plasma clearance and total plasma clearance by using venous blood samples instead of arterial. In 13 patients with GFR ranging from 29 to 150 ml min-1, Ca was higher than Cv immediately after the injection. After mean 38 min (range 12-82 min) the two curves crossed, and 180-300 min post-injection (p.i.) Cv was 5.9% higher than Ca (range 0.5-13.9%, P less than 0.001). The more reduced renal function, the smaller was the concentration difference. The areas under the arterial and the venous plasma concentration curves did not differ significantly at either 0-infinity or 0-300 min p.i. whereas the venous area 0-100 min p.i. underestimated the arterial area in the same period by 4.1% (P less than 0.05). In a computer simulation model, variation in the forearm capillary permeability-surface area product did not have any significant influence on the Cv-Ca difference, whereas the difference was very sensitive to even small changes in forearm blood flow within the physiological range. For measurement of renal plasma clearance it is recommended to use one long period: from the time of injection until 300 min p.i. or longer. If the clearance period is too short, the use of venous samples will overestimate the true renal clearance. Plasma clearance determined by venous and arterial blood samples does not differ significantly as long as the concentration is followed from the time of injection and a long period is applied. When simplified plasma clearance techniques are used, different results may be obtained from venous and arterial samples. The simplified techniques using venous blood samples--which usually include some empirical corrections--should be sufficiently reliable in daily clinical practice provided the forearm blood flow is reasonably high, e.g. exposure to cold should be avoided.

Adult↗

PubMed1989

24 hour whole body retention of 99mTc-methylene-diphosphonate in the assessment of bone formation. Methodological evaluation, clinical applications and comparison with serum alkaline phosphatase and serum osteocalcin.

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Alkaline Phosphatase↗

PubMed1988

Secondary hyperparathyroidism of morbid obesity regresses during weight reduction.

In order to test the relation between obesity and the secondary hyperparathyroidism found in markedly overweight subjects, 24 morbidly obese patients were studied before and after a weight loss of 35.9 kg obtained by a nutritionally adequate, intermittent very-low-calorie diet. Overweight was reduced from 98 +/- 34% to 44 +/- 19%. Serum total calcium did not change, but serum ionized calcium (Ca2+) increased from 1.22 +/- 0.04 mmol/L to 1.25 +/- 0.04 mmol/L (P less than .001). A corresponding fall was observed in serum parathyroid hormone (s-PTH), which decreased from 47.2 +/- 21.7 pmol/L to 35.2 +/- 19.4 pmol/L (P = .01). The change of s-PTH was positively associated with the reduction of body weight (r = .50, P less than .05) and with the reduction of overweight (r = .55, P less than .01). Regarding calcium binding substances, serum albumin remained low. The initially lowered serum phosphate and bicarbonate both rose (P less than .001). Plasma lactate and plasma free fatty acids (FFAs) decreased (P less than .001). The study supports our hypothesis that the change profile of calcium complexing anions in obesity interferes with the tubular reabsorption of calcium, which in turn lowers serum Ca2+, thus promoting hyperparathyroidism. Along with weight loss, concentrations of calcium complexing anions returns towards normal values and the secondary hyperparathyroidism regresses.

Adult↗

PubMed1988

GFR-corrected 24-hour whole body retention of diphosphonate: an improved index of bone metabolism.

The 24-hour whole body retention of diphosphonate (WBR) depends on bone uptake and renal clearance of diphosphonate. To evaluate the influence of glomerular filtration we measured WBR, creatinine clearance (CrCl) and s-alkaline phosphatase (s-AP) in 91 normals and 79 patients with different calcium metabolic disorders. As presumed, a negative correlation between CrCl and WBR exists (r = -0.67, p less than 0.001). By defining CrCl = 100 ml/min as standard, we have introduced a new mathematical model which allows recalculation of the measured WBR to WBR at CrCl = 100 ml/min (WBR100): WBR100 = [(1-WBR) x 100/WBR x CrCl +1]-1 Whole body retention at a clearance of 100 ml/min is demonstrated to be independent of CrCl (r = 0.14, NS). Using this approach we estimate that deviations of CrCl below 70 ml/min and above 150 ml/min lead to more than 25% increase/decrease in WBR. Using s-alkaline phosphatase as a standard, it is shown that WBR overestimates bone formation when CrCl is low. This new model permits the interpretation of WBR measurements in terms of bone turnover in patients with low glomerular filtration rates.

Adult↗

PubMed1988

Non-invasive evaluation of bone formation: measurements of serum alkaline phosphatase, whole body retention of diphosphonate and serum osteocalcin in metabolic bone disorders and thyroid disease.

Three noninvasive indices of bone formation, serum alkaline phosphatase (s-AP), 24-h whole body retention of diphosphonate (WBR), and serum osteocalcin (s-OC), the two lastnamed clearance-corrected, were compared in 121 patients with various bone disorders and in 50 patients with thyroid disease. In conditions with qualitatively normal matrix formation and mineralization, i.e. thyrotoxicosis, primary hyperparathyroidism, myxoedema and osteoporosis, the three indices deviated from average normal by about the same extent: 134%/128%/200%, 120%/113%/133%, 105%/100%/79% and 89%/86%/69%, respectively. A disproportionately marked deviation of s-AP was observed in states of abnormal matrix formation or mineralization, i.e. osteomalacia and Paget's disease: 430%/145%/282% and 348%/145%/202%, respectively. Furthermore, the formation indices correlate differently with s-calcium in hyper- and hypocalcaemic conditions. In primary hyperparathyroidism the respective r-values were 0.32/0.62/0.68, while an inverse pattern was observed in osteomalacia: -0.60/-0.51/-0.47. As very little is known about the secretion of AP and OC and their role in bone formation and mineralization, the cause(s) for the observed differences remain(s) uncertain.

Adult↗

PubMed1987

Studies on diphosphonate kinetics. Part I: Evaluation of plasma elimination curves during 24 h.

To improve the understanding of diphosphonate affinity to metabolically active bone, the underlying diphosphonate kinetics have been evaluated and compared to Cr-EDTA kinetics. MDP binds to plasma proteins, varying from 25% initially to approximately 70% after 24 h. The renal clearance of diphosphonate is found to be equal to Cr-EDTA clearance. Using simultaneous bolus injection of 99Tc-MDP and 51Cr-EDTA, it has been possible to obtain a coarse estimate of bone uptake of MDP. This uptake is found to correlate well with s-alkaline phosphatase, but since MDP binding to bone is reversible, the plasma elimination curve is not monoexponential. Therefore it has not been possible to describe the uptake of MDP in bone mathematically.

Bone and Bones↗

PubMed1987

Studies on diphosphonate kinetics. Part II: Whole body bone uptake rate during constant infusion--a refined index of bone metabolism.

To elaborate the understanding of diphosphonate kinetics, a non compartmental analysis is introduced. Using continuous infusion of 99mTc-methylene diphosphonate (Tc-MDP) and 51Cr-EDTA, as a cotracer, the diphosphonate clearance to bone (BDC) can be calculated. BDC is found to correlate well with the 24 h whole body retention of diphosphonate (WBR) (r = 0.89, P less than 0.01) when renal function is normal, but not in cases of reduced 51Cr-EDTA clearance. These findings indicate that BDC measurements are superior to the WBR technique in the estimation of bone turnover, especially when renal function is reduced. The BDC measurements may also constitute a useful tool for studies of diphosphonate uptake in bone, the foundation of bone scintigraphy.

Bone and Bones↗