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Biomedical subjects

J Kragstrup

Publications and source records attributed to J Kragstrup.

70 records · Page 4Linked to original sources

Pharmacokinetics of chronic fluoride ingestion in growing pigs.

The present study was undertaken to estimate bio-availability and biological half-life of fluoride and accumulation of fluoride in bone in the domestic pig. Eight animals receiving 2 mg F-/kg b.w. per day from age 8 to 14 months were compared with eight controls. Plasma fluoride concentrations just prior to the daily oral dose were measured at regular intervals. After 112 days post-dose, plasma fluoride levels were measured over a 48-hour period following the daily oral dose or a single intravenous dose. Mean bio-availability factor for the oral dose was 0.3 (range 0.2-0.4), and mean biological half-life was 59 days (range 49-72). Bone fluoride content calculated from the pharmacokinetic parameters derived from plasma data was similar to the content of fluoride measured in the bone at slaughter. The study showed that accumulation of fluoride in bone influences plasma fluoride levels during chronic administration of fluoride to growing pigs. The long biological half-life found showed that it was not possible to achieve steady-state plasma levels within the six-month experimental period used. This means that, for dose-response studies of dental fluorosis in this animal, it is not possible to achieve steady-state plasma concentrations as a basis for correlations to the degrees of pathological change observed in the teeth.

Administration, Oral↗

Radiologic assessment of bone maturity and cortical thickness in experimental osteo-fluorosis in the young pig.

Radiographs of the left forelimb were obtained after slaughter in 16 14-month-old pigs. From age 8-14 months, eight pigs in the experimental group received 2 mg F-/kg body weight per day. Bone maturity in F-animals was the same as in controls. Cortical thickness was increased by 10 per cent in the fluorotic animals (p less than 0.01) and their plasma-fluoride levels increased throughout the experimental period to approximate those reported for man in endemic fluorosis areas. Thus fluoride given in the dose used and over that period, did not affect maturation in the long bones but increased cortical bone mass in the diaphyses.

Animals↗

Experimental osteo-fluorosis in the domestic pig: a histomorphometric study of vertebral trabecular bone.

The experiment aimed at describing effects of fluoride on structure and remodeling of vertebral trabecular bone in pigs. Eight animals receiving a supplement of 2 mg F-/kg b.w. per day from age eight to 14 mo were compared with eight controls. Plasma fluoride increased from 0.7 +/- 0.1 microM/1 to 12.7 +/- 2.0 microM/1 in pigs receiving fluoride. At slaughter, the concentration of fluoride in dry fat-free bone was 149.3 +/- 10.5 mM/kg for fluorotic animals and 9.5 +/- 0.9 mM/kg for controls. Morphologic changes were assessed in un-decalcified specimens of the fourth lumbar vertebra by quantitative histology using fluorochromes as intra-vital tissue time markers. The volume of trabecular bone tissue (bone + marrow) was unchanged in fluorotic animals, but the volume density of bone was increased by 17%. Surface densities of cancellous bone were almost unchanged, whereas the thickness of trabeculae increased in fluorosis. Fluoride enhanced remodeling of trabecular surfaces: The fraction of surface occupied by resorption lacunae increased 40%, and the formative surface approximately 30%. No changes were demonstrated at surface points undergoing formation: Osteoid thickness, calcification rate, lamellar thickness, and completed wall thickness were normal. It is concluded that the observed findings cannot be explained by fluoride-induced changes in a single cell. Fluoride appears to affect all cells involved in remodeling by direct or indirect mechanisms.

Animals↗

Thickness of lamellae in normal human iliac trabecular bone.

The three-dimensional (3-D) thickness of lamellae in normal trabecular bone was estimated by means of a stereologic transformation of the apparent width measured on 7 mm stained sections of undecalcified iliac bone from 65 nondiseased individuals aged 16--90 years. The average 3-D thickness of double lamellae (one bright and one dark) was 6.4 mm with a coefficient of variation between individuals of approximately 5%. Among the 32 males, the thickness was unchanged with age, while double lamellar thickness increased with age in the females [thickness (mm) = 5.980 (mm) ;.008 (mm/year) x age (yr). Intra-individual distributions of the thickness of double lamellae resembled normal distributions and had a median coefficient of variation of 23%. Within the trabecular osteons, no correlation between lamellar number and thickness was demonstrated, and no difference in thickness was found between mineralized and nonmineralized lamellae. Redeterminations showed no intra-observer bias in the estimation of the mean double lamellar thickness. The low variance between individuals indicated that the lamellar thickness is important for some essential biologic function, most likely the mechanical strength of trabecular bone. It may, therefore, be a useful variable to study in metabolic bone diseases. Furthermore, counting lamellae may be a simple way of estimating the 3-D thickness of remodeling sites in trabecular bone.

Adolescent↗

Porosity of restorative resins.

Polyethylene tubes were filled with different types of composite resins using either the bulk-packing technique or the syringe injection technique. The porosity of the specimens was studied. Specimens made by light-activated systems were less porous compared to specimens made by two-paste systems. Use of the injection technique was followed by a reduction in porosity in both groups compared to use of the bulk-packing technique.

Chemical Phenomena↗

Reduced wall thickness of completed remodeling sites in iliac trabecular bone following anticonvulsant therapy.

The calcification rate and the completed wall thickness of remodeling sites in trabecular bone were estimated in undecalcified sections of tetracycline double-labeled iliac crest bone biopsies from 20 epileptic patients aged 19 to 50 years receiving long-term combined anticonvulsant therapy and 20 age- and sex-matched normal individuals. Surface distributions of thickness were obtained by a systematic equidistant sampling procedure and three-dimensional (3-D) values estimated from the two-dimensional (2-D) measurements by means of a stereologic transformation. The mean 3-D completed wall thickness was slightly reduced (P less than 0.01) in the epileptic patients (58.9 microns as compared to 62.8 microns), while no statistically significant change in the mean 3-D calcification rate (0.62 microns/day as compared to 0.64 microns/day) was found. Surface distributions of wall thickness and calcification rate were unimodal and resembled normal distributions in patients as well as in controls. The estimated duration of the formation period at remodeling sites was almost 4 months for the normal individuals and insignificantly shorter for the epileptic patients. Double determinations after 2 to 3 month intervals revealed no significant intraobserver bias in the estimates of the wall thickness or the calcification rate.

Adult↗

Estimation of the three-dimensional wall thickness of completed remodeling sites in iliac trabecular bone.

The wall thickness of completed remodeling sites in trabecular bone was estimated in 25 normal individuals and 5 patients with arthrosis of the knee, using 7 micron sections of undecalcified iliac crest bone. A systematic sampling procedure which gives a surface referent estimate of the thickness was applied. The efficiency of the sampling design was optimized by means of a cost-variance analysis. The proposed method of sampling which eliminates a common bias in bone histomorphometry is recommended for determinations of wall thickness, osteoid thickness, lamellar thickness, and distance between fluorochrome markers in trabecular bone. The intraindividual distributions of three-dimensional wall thickness were reconstructed from the measurements of apparent width by an unfolding procedure based on the geometric probability density function pertaining to randomly sectioned plates. Distributions of true wall thickness for the young normal individuals were unimodal and resembled normal distributions. The three-dimensional mean wall thickness was 61.4 +/- 4.4 micron (+/- SD). It was demonstrated that the conventionally applied stereological transformation, which calculates the three-dimensional mean wall thickness from the mean apparent width by multiplying the latter by pi/4, underestimates the three-dimensional mean wall thickness. An improved transformation is illustrated and is recommended for estimating three-dimensional mean thickness of plates from two-dimensional measurements in trabecular bone.

Adult↗

Osteon cross-sectional size in the iliac crest: variation in normals and patients with osteoporosis, hyperparathyroidism, acromegaly, hypothyroidism and treated epilepsia.

Cross-sectional osteon size was measured in undecalcified stained sections of iliac crest bone specimens from normal individuals (n = 68) and from patients with spinal osteoporosis (n = 27), primary hyperparathyroidism (n = 23), epilepsia (receiving chronic anti-convulsant therapy) (n = 11), acromegaly (n = 18), and hypothyroidism (n = 12). In each individual the shortest osteon diameter (D) and the corresponding Haversian canal diameter (d) were measured in a minimum of 20 completed secondary osteons by means of a micrometer eyepiece. Among normal males the areas of bone resorbed and formed increased with age (p less than 0.01), owing to an increase in the thickness of bone resorbed (p less than 0.01) and an unchanged thickness of bone formed. Among the females, both the areas of bone resorbed and formed decreased with age (p less than 0.05), owing to a reduction in the thickness of bone resorbed (p less than 0.05) as well as formed (p less than 0.001). Resorbed and formed areas were reduced in the epileptic (p less than 0.01) and acromegalic (p less than 0.01) groups but increased in the hypothyroid group (p less than 0.01) compared to sex- and age-matched controls. Neither the osteoporotic nor the hyperparathyroid group showed any alterations in osteon size. The Haversian canal diameter was slightly increased in the epileptic group but normal in the other patient groups. The observed changes reflect variations in the amount of work performed by osteoclasts and osteoblasts during bone remodelling and may be explained by variations in cellular activity and bone turn-over rates.

Acromegaly↗

Effects of thyroid hormone(s) on mean wall thickness of trabecular bone packets.

The mean wall thickness of iliac trabecular bone packets was determined in undecalcified iliac crest bone specimens from 14 hypothyroid patients, 14 hyperthyroid patients and 28 age- and sex-matched normal controls. Calcification rate and fractional resorption, formation and labeled surfaces in trabecular bone from the patients were measured by conventional histomorphometric methods after double-labeling with tetracycline. The mean wall thickness was increased in the hypothyroid patients (58,9 microns), while no change was demonstrated in the hyperthyroid group (52,5 microns) as compared to the controls (54,0 microns). Calculated estimates of trabecular bone remodeling at the "Basic Multicellular Unit" level showed longer periods of resorption, formation and total remodeling in the hypothyroid than in the hyperthyroid patients.

Adult↗

Three-dimensional morphology of trabecular bone osteons reconstructed from serial sections.

The anatomy of the remodeling sites in bone is only partly reflected by random histologic sections. This study is aimed at reconstructing the three-dimensional morphology of the osteons in human trabecular bone from serial sections of decalcified tissue. The osteons resembled broad bands, which were made up of parallel lamellae, bounded on one side by the marrow surface and on the other side by an irregular cement plane. The mean thickness was much less (less than 0.2) than the mean extent in the other dimensions. The plate may, therefore, be used as the morphologic model for stereologic studies. The plates were curved and irregular. One three-dimensional osteon can, therefore, give rise to a varying number of profiles in a single random section. The two-dimensional profiles, which are of unequal surface extent, are thus not appropriate sampling units for morphometric studies of, e.g., osteon thickness, osteoid thickness, or calcification rate in trabecular bone. When estimating thickness the number of measuring sites should be sampled proportional to the surface extent of the profiles.

Bone and Bones↗

Thickness of bone formed at remodeling sites in normal human iliac trabecular bone: variations with age and sex.

The thickness of the bone walls formed at completed remodeling sites was estimated by morphometry in iliac trabecular bone from 85 normal individuals (48 women and 37 men) aged 18-90 years. The mean three-dimensional (3-D) wall thickness was 59.4 +/- 5.9 micron. No sex difference was observed. The wall thickness decreased with age: Thickness (micron) = 65.56 micron - 0.14 micron/yr X age (yr). This reduction may lead to a loss of bone with increasing age. The coefficient of variation in completed wall thickness between individuals of the same age was 7%. The factors controlling the thickness are largely unknown, but it was noted that the intraindividual distributions of linear 3-D wall thickness (proportional to the mass of the wall) were symmetric, while distributions of reciprocal 3-D thickness (proportional to the conductivity for oxygen and waste products) were markedly rightskewed. A subgroup comprising 42 individuals aged 18-56 years had been double labeled with tetracycline. The average 3-D calcification rate was 0.63 +/- 0.11 micron/day. No relationship to age or sex was demonstrated. Based on the estimates of completed wall thickness and calcification rate, the mean duration of calcification at remodeling sites was calculated to be approximately 100 days.

Adolescent↗

Histomorphometric analysis of iliac trabecular bone in otosclerosis.

With the aim of investigating whether patients with otosclerosis suffer from a generalized bone disorder, a histomorphometric analysis of trabecular bone from the iliac crest was performed. Iliac crest biopsies from 10 patients with otosclerosis and 20 normal controls were obtained after tetracycline double labelling and examined by histomorphometry. No significant differences were found in the estimates of density and remodeling of bone between patients and sex and age-matched normal controls. Qualitatively the bone specimens showed no signs of any generalized bone disorder.

Adult↗