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Biomedical subjects

P Lips

Publications and source records attributed to P Lips.

At least 127 records · Page 7Linked to original sources

Loss of bone in the proximal part of the femur following unstable fractures of the leg.

We evaluated the subsequent loss of bone from the proximal part of the ipsilateral and contralateral femora and from the lumbar spine of seven men and nine women who had a fracture of the tibia. The average age was sixty years. All of the fractures were unstable, and the involved leg bore no weight for an average of eight weeks. The bone mineral density was measured with dual-energy x-ray absorptiometry of the lumbar spine and of the femoral neck and the trochanteric region of both hips immediately after the fracture, after the period of immobilization, and at approximately three, six, and twelve months after the fracture. During the period of immobilization, the bone mineral density of the trochanteric region decreased an average of 9 +/- 7 per cent on the side of the fracture, compared with the value immediately after the fracture, but there was no change on the contralateral side (p < 0.01). At twelve months, the average decrease in the trochanteric area was 15 +/- 10 per cent on the side of the fracture, compared with the value immediately after the fracture, but again there had been no change on the uninjured side (p < 0.01). The bone mineral density of the femoral neck on the side of the fracture had decreased 6 +/- 6 per cent at twelve months, compared with a decrease of 2 +/- 4 per cent on the uninjured side (p < 0.05). The bone mineral density of the lumbar spine decreased only during the period of unloading of the fractured leg (1 +/- 2 per cent, p = 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Absorptiometry, Photon↗

One-hour test for estimating intestinal absorption of calcium by using stable strontium as a marker.

Intestinal absorption of calcium is a relevant marker in a broad spectrum of diseases; however, its determination in clinical practice is difficult. Our aim was to design a simple test for this based on stable strontium (88Sr). The correlation between the intestinal absorption of simultaneously administered 45Ca and 88Sr was investigated in patients with various disorders of the bone and calcium metabolism. The area under the curve for the period 0-60 min after dosing (AUC0-60 in mmol.L-1.min), being a representative measure of intestinal absorption, showed a close correlation between both elements (r = 0.90, P < 0.001). Moreover, the measure of agreement in classifying the patients as low, intermediate, or high absorbers was high (kappa = 0.80). We conclude that a test based on measuring AUC0-60 of strontium is a fast and inexpensive way to obtain reliable information about the level of intestinal calcium absorption.

Adolescent↗

Determinants of bone mineral density and risk factors for osteoporosis in healthy elderly women.

Bone mineral density (BMD) and risk factors for osteoporosis were assessed in 348 apparently healthy women over 70 years of age (mean 82.3 years). BMD was measured at both hips and the dominant distal radius. With stepwise multiple regression the best determinants of BMD, selected from anthropometric measurements, age, and years since menopause, were body weight and years since menopause (R2 between 0.07 and 0.20, p < 0.001). Risk and protective factors for osteoporosis were analyzed as indicator variables by multiple regression and corrected for confounding by age, years since menopause, and body weight. Significantly lower BMD at the hip was found in participants with impaired mobility (-5%) and users of loop diuretics (-5%). Use of thiazide(like) diuretics did not influence BMD significantly at any site. Users of oral corticosteroids had a significantly lower BMD at the hip and the distal radius (range -9.1 to -24.3%). Participants with a history of Colles' fracture (n = 56) had a significantly lower BMD at the other radius (-12.9%). The mean calcium intake from dairy products was high (mean 921 mg/day), only 11% having an intake below 500 mg. A relation of calcium intake with BMD could not be detected at any measurement site. We conclude that BMD cannot be adequately predicted in elderly women. Risk factors for low BMD in the elderly are low body weight, high number of years since menopause, impaired mobility, and use of loop diuretics and oral corticosteroids. Calcium intake was not a risk factor in this study, but the number of individuals on a low calcium intake was small.

Aged↗

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↗

Non-invasive densitometry.

Several non-invasive methods are available to measure bone density in different regions of the skeleton. Bedrest and microgravity both lead to bone loss, which is more marked in the lower parts of the skeleton. The bone loss can be monitored by non-invasive techniques in longitudinal studies when precision (i.e. the ability to produce repeated measurements with the same value) is adequate. Bone mineral density (BMD) can be measured with single photon absorptiometry in the lower forearm and calcaneus and with dual energy X-ray absorptiometry (DXA) in almost any region of the skeleton. The latter technique pairs good precision with very low radiation exposure. With peripheral quantitative computed tomography very precise measurements of the lower forearm and tibia are feasible with low radiation dose. It has the additional option of separate measurement of cortical and trabecular bone. This could be of particular importance in microgravity studies, as trabecular bone loss is more severe in this condition. A new development is the measurement of ultrasound velocity or attenuation which depends on bone density and structure. Ultrasound data of the calcaneus correlate well with bone mineral density in spine and hip. The advantage of this technique is that it operates without radiation. However, the clinical value has to be established. The ultimate choice of technique and skeletal region for bone densitometry will depend on specific requirements.

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↗

The course of biochemical parameters of bone turnover during treatment with corticosteroids.

The mechanisms by which glucocorticoids cause osteopenia are incompletely understood. It is generally accepted that bone formation is depressed during corticosteroid treatment, but the cause of the ongoing bone resorption is less clear. Secondary hyperparathyroidism and changes in vitamin D metabolism are thought to play a role. This is based mostly on data from cross-sectional studies in heterogeneous patient groups. We, therefore, studied longitudinally the course of biochemical parameters and the hormones influencing bone turnover in a homogeneous group of 10 euthyroid patients with Graves' ophthalmopathy, all euthyroid for at least 1 yr before, during, and after a 12-week course of prednisone. Bone formation was depressed as reflected by a fall in serum osteocalcin (3.0 +/- 2.1, 1.7 +/- 1.1, and 2.4 +/- 1.9 micrograms/L at weeks 0, 4, and 12, respectively; P = 0.02) and in total alkaline phosphatase (1.15 +/- 0.33, 0.83 +/- 0.22, and 0.88 +/- 0.40 mukat/L; P = 0.001). Parameters of bone resorption (urinary hydroxyproline/creatinine ratio, serum acid phosphatase) and the levels of vitamin D metabolites remained unchanged. Serum intact PTH seemed to decrease slightly. Our findings suggest that glucocorticoid induced osteopenia is caused by a depressed bone formation in the presence of an unaltered but ongoing bone resorption. Secondary hyperparathyroidism and changes in vitamin D metabolism are apparently not involved.

Acid Phosphatase↗

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↗

High indices of remodelling in iliac trabecular bone predict reduced forearm cortical bone mass indices in patients with proximal femoral fractures.

To investigate whether high bone turnover could be a predictor of cortical bone loss and a candidate risk factor for fractures of the proximal femur, 33 7.5-mm transiliac biopsies taken at fracture fixation from 48 patients who participated in a study of potential risk factors have been quantitated. Twenty-four of the 33 patients made good recoveries and about 6 weeks postoperatively consented to bone densitometry of the forearm midshaft. Forearm bone density correlated negatively (r = 0.77, P = 0.001) with the surface of trabecular bone covered with osteoid, which in osteoporotic patients with crush fractures of the vertebrae was previously shown to relate both to rates of bone formation and resorption. An important minority of these femoral fracture patients appeared to be suffering from high rates of iliac trabecular bone resorption. Thus, high bone remodelling activity could lead to excessive cortical thinning. This has pathogenetic implications which may be clinically important.

Aged↗