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Biomedical subjects

J C Netelenbos

Publications and source records attributed to J C Netelenbos.

At least 73 records · Page 4Linked to original sources

Intranasal calcitonin suppresses increased bone resorption during short-term immobilization: a double-blind study of the effects of intranasal calcitonin on biochemical parameters of bone turnover.

Immobilization is associated with increased bone resorption and decreased bone formation. We evaluated in a double-blind trial the effect of intranasal administration of salmon calcitonin on biochemical parameters of bone turnover in 32 patients immobilized for a prolapsed intervertebral disk. Calcitonin in a dose of two times 200 IU/day partially inhibited the increase in the fasting 2 h urinary hydroxyproline/creatinine ratio (OHPr/Cr) and calcium/creatinine ratio (Ca/Cr). The increase in OHPr/Cr was 40% less in the calcitonin group compared to the placebo group (P = 0.01), and the increase in Ca/Cr was 80% less in the calcitonin group (P = 0.04). Calcitonin also partially inhibited the increase in serum cross-linked carboxyl-terminal telopeptide of collagen type I (P < 0.05). The decrease in serum 1,25-dihydroxyvitamin D after 10 days of immobilization was significantly less in the calcitonin-treated group than in the placebo group (14 versus 29%, respectively; P < 0.05). Intranasal calcitonin did not influence the pain scores as measured with a visual analog scale (VAS). The tolerability of the nasal calcitonin preparation was excellent. We conclude that nasal salmon calcitonin counteracts the early increase in bone resorption induced by immobilization.

Administration, Intranasal↗

Effects of short-term low-dose heparin administration on biochemical parameters of bone turnover.

Heparin therapy may cause osteoporosis. The effects of short-term low-dose heparin are not known. We have studied the effects of short-term heparin administration, twice daily 5000 IU s.c., for 10 days on the biochemical parameters of bone turnover in six healthy male volunteers. No effects were observed on the urinary excretion of hydroxyproline and calcium. Serum levels of cross-linked carboxy-terminal telopeptide of type I collagen (ICTP), a new marker of bone resorption, did not change significantly. A slight but significant decrease in serum alkaline phosphatase was observed. TmP/GFR increased significantly during heparin administration. In all volunteers a uniform increase in serum transaminases appeared which completely reversed after discontinuation of heparin administration. We conclude that short-term low-dose heparin administration does not change biochemical parameters of bone resorption, but has a small significant suppressing effect on serum alkaline phosphatase levels. Heparin administration resulted in a significant but transient increase of serum transaminase levels.

Adult↗

Bone histomorphometry and serum concentrations of intact parathyroid hormone (PTH(1-84)) in patients with primary hyperparathyroidism.

The consequences of bone disease in primary hyperparathyroidism (PHPT) are still a matter of discussion. We studied transiliac bone biopsies of 24 patients (9 men and 15 women) with mild to moderate PHPT, proven by surgery. Histomorphometric data were compared with control values obtained from autopsy bone samples. The biopsies of the PHPT patients were characterized by increased trabecular bone volume (P < 0.01) and surface (P < 0.02), increased osteoid volume and increased osteoid and resorption surfaces (P < 0.001). Cortical porosity showed a non-significant increase in the PHPT patients. In the patients the fasting serum concentrations of parathyroid hormone (PTH(1-84)) correlated positively with cortical porosity (r = 0.50, P = 0.02), osteoid volume (r = 0.40, P = 0.05), osteoid surface (r = 0.50, P = 0.01), and eroded surface (r = 0.59, P < 0.01). It is concluded that moderate PHPT is associated with preservation of trabecular bone, whereas cortical bone may be lost in these patients. Cortical porosity and the parameters of bone turnover correlate well with the fasting serum PTH(1-84) concentration.

Adolescent↗

Human pharmacokinetics of orally administered (24 R)-hydroxycalcidiol.

To gain an insight in the regulation of (24R)-hydroxycalcidiol, we studied the pharmacokinetics of orally administered (24R)-hydroxycalcidiol in 6 healthy subjects without calcium supplementation, in 4 healthy subjects with calcium supplementation and in 6 patients with primary hyperparathyroidism. Various quantities related to calcium and vitamin D metabolism were also monitored. In the healthy subjects without calcium supplementation, the basal (24R)-hydroxycalcidiol concentration (Cb) in serum was 2.4 +/- 0.8 nmol/l (mean +/- SD, n = 5), the terminal serum half-time (t 1/2) 7.2 +/- 1.4 days, the production rate 0.05 +/- 0.01 nmol/kg.day, and the production rate/[calcidiol] ratio (1.5 +/- 0.4 x 10(-3) l/kg.day). In the healthy subjects studied, the serum concentration vs time curves exhibited a second maximum after administration, possibly due to binding by intestinal cells or (partial) uptake by the lymph system. In the calcium-supplemented healthy subjects, the pharmacokinetic quantities were not significantly different while the area under the serum concentration-time curve and the estimated bioavailability were significantly decreased. Basal concentration (Cb), production rate and the production rate/[calcidiol] ratio were significantly lower in patients with primary hyperparathyroidism but t 1/2 was unchanged. Exogenous (24R)-hydroxycalcidiol had no clear effect on calcium and vitamin D metabolism. In conclusion, a) exogenous (24R)-hydroxycalcidiol has no clear effect on calcium and vitamin D metabolism, b) clearance and production rate of (24R)-hydroxycalcidiol are not affected by calcium supplementation, c) bioavailability is lower in the calcium-supplemented state, d) basal concentration (Cb) and production rate are significantly decreased in patients with hyperparathyroidism.

24,25-Dihydroxyvitamin D 3↗

The relation between periodontitis and systemic bone mass in women between 46 and 55 years of age.

It has been suggested that periodontitis and systemic bone mass might be related. In order to evaluate this possible relationship, we performed an intra-oral examination and measured lumbar bone mineral density (lumbar BMD) and metacarpal cortical thickness (MCT) in 286 female volunteers between 46 and 55 years of age. In addition, the alveolar bone height was measured on bite wing radiographs of the dentate subjects. Of the subject, n = 60 (21%) were edentulous. Compared to the dentate subjects, the lumbar BMD and MCT of the edentulous women were not significantly different. In the dentate subjects, no significant correlation was observed between the clinical parameters of periodontitis (mean probing depth, occurrence of bleeding after probing and number of missing teeth) and the bone mass parameters (lumbar BMD and MCT); nor was a significant relation observed between the bone mass measurements and alveolar bone height. We therefore suggest that systemic bone mass is not an important factor in the pathogenesis of periodontitis.

Absorptiometry, Photon↗

Biochemical parameters of bone turnover during ten days of bed rest and subsequent mobilization.

Immobilization is associated with increased bone resorption. To investigate the early onset of increased bone resorption, we evaluated 14 patients who were immobilized for 10 days because of lumbar disc protrusion. The fasting urinary hydroxyproline/creatinine ratio increased significantly after four days (P less than 0.01), reached a peak after 10 days (16.4 +/- 3.3 mumol/mmol, 27.6 +/- 8.8 mumol mmol, P less than 0.01) and returned slowly to baseline values after mobilization. The fasting urinary calcium creatinine ratio followed a similar pattern. Serum calcium and phosphate increased during immobilization (P less than 0.01). Serum 1,25-dihydroxyvitamin D decreased significantly during immobilization (98 +/- 33 pmol/l vs. 79 +/- 36 pmol/l, P less than 0.05), and reached a nadir one week after mobilization (P less than 0.01). We conclude that there is an early significant increment in resorption parameters, with a slow return during the mobilization period. Serum 1,25-dihydroxyvitamin D is suppressed as a result of the increased serum calcium and serum phosphate levels.

Adult↗

Short-term effects of Org OD 14 and 17 beta-oestradiol on bone and lipid metabolism in early post-menopausal women.

The effects of 8 weeks of daily oral treatment with 1 mg 17 beta-oestradiol (E2), 2.5 mg Org OD 14 [7 alpha, 17 alpha)-17-hydroxy-7-methyl-19-norpregn-5(10)-en-20-yn-3-one) , a steroid with weak androgenic, weak oestrogenic and weak progestational activity, or placebo on calcium and lipid metabolism were compared in 21 healthy, early post-menopausal women in a randomised double-blind study. The treatment period was followed by a treatment-free period of 8 weeks to study the reversibility of drug-induced effects. The results show that both E2 and Org OD 14 reduce bone resorption, as indicated by the decreases in the urinary hydroxyproline/creatinine and calcium/creatinine ratios in 2-h fasting urine. In contrast to E2, Org OD 14 did not reduce serum calcium levels. As regards lipid parameters, E2 reduced the concentration of serum cholesterol and Org OD 14 decreased serum levels of high-density-lipoprotein cholesterol and triglycerides. All these effects appeared to be reversible after cessation of treatment. It is concluded that both of these steroids reduce bone resorption in early post-menopausal women, but that their mechanisms of action are most likely different.

Anabolic Agents↗

Stimulation and suppression of intact parathyroid hormone (PTH1-84) in normal subjects and hyperparathyroid patients.

OBJECTIVE: Because of an overlap between serum PTH values in healthy controls and hyperparathyroid patients we sought to evaluate a short stimulation and suppression test for differentiating the two groups. SUBJECTS: Subjects were 34 patients with primary hyperparathyroidism (PHPT) and 25 healthy controls. DESIGN: After stimulation with intravenous EDTA (10 mg/kg body weight in 5 minutes) blood samples were obtained for up to 15 minutes. After an oral calcium dose of 1 g, blood samples were obtained at 1 and 2 hours. After an intravenous calcium dose (2.5 mg/kg body weight in 30 seconds), blood samples were obtained serially for 20 minutes. MEASUREMENT: Serum PTH(1-84) was measured by a double antibody technique. RESULTS: The intravenous EDTA test resulted in an average 2.6-fold increase of serum PTH(1-84) in hyperparathyroid patients, whereas it increased 10.5-fold in controls. A response was absent in three of 23 patients. There was an overlap in results between patients with mild hyperparathyroidism and controls. The oral calcium dose decreased serum PTH(1-84) in patients to 0.73 and in controls to 0.55 of the basal value, but six of 15 patients and two of 12 controls did not respond. The intravenous calcium test resulted in a drop of serum PTH(1-84) in hyperparathyroid patients to 0.51 and in control subjects to 0.40 of the basal value, and non-responders were not observed. There was a strong correlation between the responses to the EDTA and the calcium infusion tests in the patients (r = 0.97, P less than 0.01). Fasting serum calcium and serum PTH(1-84) showed a positive correlation in PHPT patients (r = 0.75, P less than 0.001) and a negative correlation in control subjects (r = -0.41, P less than 0.05). Based on these relationships, hyperparathyroid patients and controls could be completely separated. CONCLUSION: The wide range of responses to stimulation and suppression tests and the correlation between these responses in hyperparathyroid patients indicate various degrees of autonomy. As the response to these tests is less marked in patients than in controls and both groups still overlap, these tests are not useful for the diagnosis of primary hyperparathyroidism.

Adolescent↗

Effect of a single infusion of aminohydroxypropylidene on calcium and bone metabolism in healthy volunteers monitored during 2 months.

Recently, bisphosphonates have been used to prevent postmenopausal bone loss. As the effects of bisphosphonates on normal bone metabolism are unknown, 3-amino-1-hydroxypropylidene-1,1-diphosphonate (APD) was studied in healthy subjects. The effects of a single 20-mg APD infusion on biochemical parameters of calcium and bone metabolism were investigated during 2 months in 10 healthy male volunteers. This single moderate dose of APD reduced biochemical parameters of bone resorption during the time of follow-up. After 2 months, urinary hydroxyproline excretion was still below the basal level. The decreased serum calcium levels did not return to basal values. Biochemical parameters of bone formation, serum alkaline phosphatase and osteocalcin, showed a slight increase during the first month after stimulation of the parathyroids and a corresponding increase in serum 1,25-dihydroxyvitamin D. These formation parameters decreased thereafter, probably representing coupling between bone resorption and bone formation.

24,25-Dihydroxyvitamin D 3↗

Calcium supplementation reduces vertebral bone loss in perimenopausal women: a controlled trial in 248 women between 46 and 55 years of age.

To study the effect of calcium supplementation on perimenopausal bone loss, 295 women were randomized into a control group and 2 supplementation groups receiving, respectively, 1000 and 2000 mg elemental calcium/day for a period of 2 yr. We observed a significant decrease in lumbar bone loss in relation to the calcium supplementation (mean loss after 2 yr of 3.5% in the control group vs. 1.3% and 0.7% in the 1000 and 2000 mg groups, respectively), a significant increase in urinary calcium excretion, and a significant decrease in the urinary hydroxyproline/creatine ratio, serum alkaline phosphatase, osteocalcin, and 1,25-dihydroxyvitamin D. The effect of calcium supplementation on lumbar bone loss was significant in the first year of supplementation, but not in the second. However, the urinary hydroxyproline/creatinine ratio and the serum alkaline phosphatase level remained significantly decreased in the treatment groups at the end of the study; this was not the case for serum osteocalcin. Calcium supplementation did not have a significant effect on metacarpal cortical bone loss. The difference in biochemical parameters between the 2 supplementation groups was small. No significant interaction was observed between the menopausal status of the subjects and the effect of calcium supplementation. We conclude that calcium supplementation retards lumbar bone loss in the first year of calcium supplementation by reducing bone turnover. However, the effect on lumbar bone loss over a longer time span is still uncertain.

Alkaline Phosphatase↗

Human pharmacokinetics of orally administered strontium.

Pharmacokinetics of orally administered SrCl2 (2.5 mmol) were studied in six healthy male volunteers. In the overall plasma concentration time (C-t) curves, two absorption phases were observed due to two dominant intestinal absorption loci. A method was devised to obtain separately the plasma C-t curves associated with each of the two absorption loci (curve 1 and curve 2). These curves and the overall plasma C-t curve were analyzed with a nonlinear estimation program (PCNONLIN). Pharmacokinetic parameters (mean +/- SD, n = 6) calculated from the overall curve were as follows: peak plasma concentration (Cmax) 3.55 +/- 1.22 micrograms/ml and area under the plasma C-t curve (AUC affinity) 9138 +/- 1930 micrograms.min/ml. The pharmacokinetic parameters calculated from curve 1 were as follows: terminal plasma elimination half-life time 47.3 +/- 7.9 hour, the plasma elimination half-life time of the preceding phase 5.2 +/- 3.3 hour, Cmax 1 3.09 +/- 0.95 micrograms/ml, the first-order absorption rate constant for absorption locus 1 (Ka,1) 5.7 +/- 1.2 * 10(-2) minute-1 and the time lag (tlag,1) 11.7 +/- 7.9 minute. In three of the subjects the pharmacokinetic parameters of absorption locus 2 could be evaluated: Ka,2 = 4.6 +/- 0.4 * 10(-2) minute-1, tlag,2 = 77.3 +/- 4.0 minute, tmax,2 = 153 +/- 16 minute, Cmax,2 = 0.9 +/- 0.4 micrograms/ml and AUC 2 affinity = 1204 +/- 565 micrograms. minute/ml. and AUC2 affinity = 0.14, indicating that 14% of the absorbed dose was absorbed via the second locus.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗

Lower mobility and markers of bone resorption in the elderly.

Immobilization may lead to severe bone loss. Physical activity decreases with age and lower mobility might influence bone loss. We have evaluated the degree of mobility and parameters of bone turnover in 70 residents of a nursing home (mean age +/- SD 81 +/- 9 years) and 68 residents of an old people's home (mean age +/- SD 84 +/- 6 years). The mobility was assessed with a standing and walking score from 1 (severely disabled) to 5 (standing/walking without help). When the subjects were arranged according to increasing walking score from 1 to 5, fasting urinary hydroxyproline/creatinine ratio gradually decreased from 31 +/- 19 to 14 +/- 5 mumol/mmol (P less than 0.001). There was also a significant linear decrease of fasting urinary calcium/creatinine ratio, and serum calcium concentration and a significant increase of serum albumin and 1,25-dihydroxyvitamin D concentrations with increasing walking score. These data indicate that lower mobility in the elderly leads to higher bone resorption, which may suppress the formation of 1,25-dihydroxyvitamin D.

Aged↗

Growth hormone (replacement) therapy in adults: bone and calcium metabolism.

Calcium uptake from the gut is increased by GH effects on vitamin D metabolism or action. Bone metabolism is stimulated by many factors, of which GH and insulin-like growth factor I (IGF-I) are only two examples. From various animal and human data, it can be shown that GH and IGF-I seem to influence bone formation more than bone resorption. However, GH excess, as seen in acromegaly, does not result in increased bone mass. GH was used to treat osteoporosis in a few clinical trials. In only one, in combination with calcitonin, an increase in bone mass was observed. In GH-deficient adult patients, substitution therapy resulted in a temporary increase in serum calcium levels. Effects on bone mineral mass were only found in a pilot study performed by us in a group of 8 GH-deficient adult patients. The mean increase of bone mineral mass was 0.04 g hydroxyapatite/cm2, p less than 0.05. These data indicate that GH substitution can result in increased bone mass.

Bone and Bones↗

Selective determination of hydroxyproline in urine by high-performance liquid chromatography using precolumn derivatization.

A method to measure total hydroxyproline in human urine was developed. Primary amino acids were derivatized with ortho-phthaldialdehyde, followed by derivatization of imino acids with 9-fluorenylmethyl chloroformate. The fluorescent 9-fluorenylmethyl chloroformate derivatives were separated by reversed phase high-performance liquid chromatography. 3,4-Dehydroproline was used as internal standard. Calibration curves for hydroxyproline and internal standard were linear from 1 to 200 pmol injected. Both within- and between-run precision were below 3.2%. Analytical recovery of hydroxyproline added to urine samples was 99.2 +/- 2.6%. Values for excreted hydroxyproline were determined by analysis of urine samples from adult volunteers. The hydroxyproline/creatinine ratio was found to be 15.8 +/- 4.6 mmol/mol (range 7.0-27.3) with no significant sex-related difference.

Chromatography, High Pressure Liquid↗