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Biomedical subjects

F Melsen

Publications and source records attributed to F Melsen.

At least 109 records · Page 6Linked to original sources

A histomorphometric analysis of subchondral bone in juvenile arthropathy of the dog knee.

Subchondral bone changes in arthropathy were investigated in an animal model using mongrel dog knees. Unilateral arthritis of the knee was induced by repeated intra-articular instillations of Carrageenin solution in 14 mongrel puppies. Histomorphometric analysis of cartilage and bone was performed blindly in both knees of each dog. Arthritis resulted in a significant increase in the joint cartilage thickness and a significant decrease in subchondral epiphyseal trabecular bone volume (VTB%) and trabecular thickness (TRTH), suggesting negative bone balance. No significant changes in osteoid surfaces (OS%) and resorptive surfaces (RS%) were found. The dynamic parameters suggest an increased bone turnover in the arthritic subchondral bone.

Animals↗

Reconstruction of the resorptive site in iliac trabecular bone: a kinetic model for bone resorption in 20 normal individuals.

The variations with time in function and morphology at the resorptive site in normal iliac crest trabecular bone were reconstructed from tetracycline double-labeled iliac crest bone biopsies from 20 normal individuals. Resorption depths below osteoclasts, mononuclear cells, and preosteoblast-like cells were measured by counting the number of lamellae of known thickness eroded. Mean resorption depth below osteoclasts was 19.0 (+/- 4.9) micron. Lacunae containing mononuclear cells were deeper (P less than less than 0.0001), with a mean resorption depth of 49.1 (+/- 10.2) micron. The deepest lacunae were lacunae containing preosteoblast-like cells, with a mean resorption depth of 62.6 (+/- 12.5) micron. This depth was significantly deeper (P less than 0.001) than the resorption depth found below mononuclear cells. Median total resorption period was 48 days (31-68; 95% confidence interval). Median osteoclastic function period was 8 days (6-12), median mononuclear cell function period was 34 days (24-48), and median period where preosteoblast-like cells were present in lacunae before matrix synthesis started was 9 days (6-13). Distribution curves describing the occurrence of the three cell types in relation to resorption depth showed that osteoclasts occupied the more superior parts of the resorption lacunae, with mononuclear cells and preosteoblast-like cells situated in the deeper parts. The distribution curves support the hypothesis that osteoclasts precede mononuclear cells, which again precede preosteoblast-like cells. Based on this hypothesis, curves showing the variation in resorption depth with time were constructed in duplicate. Resorption rates were calculated for three periods.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Reconstruction of the formative site in iliac trabecular bone in 20 normal individuals employing a kinetic model for matrix and mineral apposition.

A stereologic procedure for the reconstruction of matrix and mineralized bone growth curves at formative sites in trabecular bone is presented. Iliac crest bone biopsies obtained from twenty normal individuals after tetracycline double-labeling were investigated histomorphometrically. Corresponding values for osteoid width and apparent distance between bone markers and width of mineralized bone walls were classified using a sector plotting system. Observed structure widths were converted to three-dimensional structure thicknesses by a stereologic unfolding procedure. Osteoid thickness, calcification rate, and fractional labeling of osteoid varied characteristically with increasing wall thickness and permitted the construction of curves describing the time-dependent variations in matrix and wall thicknesses. The mean thickness of completed walls was 61.9 +/- 1.5 micron (SE), and the mean bone formation period (Sigma f) was 145 days (124-168; 95% confidence interval.). The initial appositional rates for bone matrix (2.1 microns3/microns2/day) (1.4-2.9) and bone mineral (1.1 micron3/micron2/day) (0.4-1.9) declined gradually toward zero at the end of Sigma f. The initial mineralization lag time was 15 days (12-24) and increased to a maximum of 27 days during the first 45% of Sigma f. Thereafter, it decreased gradually toward zero. The height of the osteoblast nuclei gradually declined from 6.7 +/- 0.5 micron at the start of bone formation to 1.2 +/- 0.1 micron at the end. The study demonstrates that it is possible to reconstruct growth curves for trabecular bone walls based on three-dimensional values for structure thicknesses using different sections for light and fluorescence microscopy and avoiding classification according to osteoblastic nuclear morphology.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Effect of propranolol treatment on bone mass, bone mineral content, bone remodelling, parathyroid function and vitamin D metabolism in hyperthyroidism.

The effect of propranolol 160-640 mg/day for 3 months on the accelerated loss of bone matrix and mineral in hyperthyroidism was studied in seventeen patients. A rise in serum thyroxine (P less than 0.01) during the first 3 weeks was followed by a fall (P less than 0.02). Serum triiodothyronine declined during the study (P less than 0.02). The enhanced bone mineral mobilization and collagen turnover continued during treatment and the bone mineral content decreased 3.2% (P less than 0.01). The secondary adaptive changes in serum parathyroid hormone and vitamin-D metabolites and in renal phosphate handling stayed unchanged. Iliac crest bone biopsies after tetracycline double-labelling showed initially a high bone turnover (P less than 0.01) with a reduced amount of cortical and trabecular bone (P less than 0.05). Following treatment bone formation rate decreased at both cellular and tissue level (P less than 0.01). No significant changes were observed in the amount of cortical and trabecular bone. The investigation shows that propranolol, in contrast to antithyroid medication, lacks any curative effect on the accelerated bone loss in hyperthyroidism.

Adult↗

Navicular bone disease: results of treatment using egg-bar shoeing technique.

Although the diagnostic criteria of navicular disease are generally accepted in practice, their limitations are recognised. However, the authors believe that navicular disease per se is reversible and that only secondary changes like adhesions to the deep flexor tendon or spur formations are irreversible. This hypothesis is supported by the results presented of the effect of the application of an egg-bar shoe, which caused permanent cessation of signs of navicular disease in more than 50 per cent of treated cases. The egg-bar shoeing technique can be usefully applied in practice.

Animals↗

Vitamin D levels and trabecular bone remodelling before and after surgery for medullary thyroid carcinoma.

We previously reported increased mean serum 1,25-dihydroxyvitamin D (1,25-(OH)2D) and increased trabecular bone remodelling in patients with medullary thyroid carcinoma (MCT) and hypercalcitoninaemia. In the present paper we report that serum 1,25-(OH)2D and trabecular bone remodelling decreased following surgical cure for MCT and hypercalcitoninaemia in 4 patients despite no detectable post-surgical hypoparathyroidism or hypothyroidism. The results obtained in the present small number of patients suggest that the altered vitamin D metabolism and trabecular bone remodelling in patients with MCT is caused by the hypercalcitoninaemia.

24,25-Dihydroxyvitamin D 3↗

Osteopenia with normal vitamin D metabolites after small-bowel resection for Crohn's disease.

Thirty-six unselected patients were investigated 3-24 years (mean, 7.8 years) after small-bowel resection for Crohn's disease (mean small intestinal resection, 105 cm). Iliac crest bone biopsies after in vivo tetracycline double-labelling showed a markedly reduced trabecular bone mass (controls, 0.25 +/- 0.06; patients, 0.15 +/- 0.05; p less than 0.01). The average bone remodeling and osteoid mineralization was normal, and only two patients demonstrated signs of frank but slight osteomalacia. The mean serum levels of the three vitamin D metabolites 25-hydroxyvitamin D, 24,25-dihydroxyvitamin D, and 1,25-dihydroxyvitamin D were normal. The observed reduction in trabecular bone mass may theoretically be followed by an increased risk of spontaneous fractures.

24,25-Dihydroxyvitamin D 3↗

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↗

Aspects of the pathology of stifle bone cysts in the horse.

The gross and histological appearance of subchondral bone cysts in six Thoroughbred or partbred horses is described. The lesions were all situated in the centre of the medial femoral condyle and were not associated with any other damage to the articular surface of the femorotibial or femoropatellar joints. In three cases the cysts were unilateral but had an early non-cystic lesion present in the opposite stifle. All the cysts had a narrow channel at their distal extremity which communicated with the femorotibial joint. The more recently developed ones were fluid filled and contained fibrous strands, while those in the older horses contained dense fibrotic detritus. No signs of significant ossification of the cysts were detected. The likely pathogenesis of these lesions is discussed in the light of the pathological findings.

Animals↗

The postnatal development of the palatomaxillary region studied on human autopsy material.

Greater understanding of the postnatal region of the maxilla is necessary if the normal growth of the maxillary complex, as well as its reaction to orthopedic forces, is to be comprehended. The area in question was studied at various stages of development, both on dry skulls and on autopsy material. The skull material demonstrated an increasing approximation between the palatal bone and the adjacent bones, the maxilla and pterygoid process. Disarticulation of the bones studied was possible only on skulls representing the infantile and earliest adolescent periods. Attempted disarticulation in the later juvenile and early adolescent periods was always accompanied by fracture of the heavily interdigitated osseous surfaces. The complexity of the articulating surfaces was studied further and, by means of quantitation of the bony surfaces, an "index of complexity" was calculated. The findings of the present study that the palatal bone acts as a "buffer" between two areas of differing intrinsic growth pattern and that the remodeling processes in the area seem to reflect different functional demands to the bony pharynx and the maxillary complex. The rigidity of the area as a result of the observed sutural complexity indicates that the center of rotation for the observed spatial changes in the maxillary complex as a result of orthopedic forces could be localized in the palatomaxillary region.

Adolescent↗

Serum levels of vitamin D metabolites and bone remodelling in hyperthyroidism.

Serum levels of 25-hydroxyvitamin DF, 24,25-dihydroxyvitamin D and 1,25-dihydroxyvitamin D were measured in 25 untreated hyperthyroid patients in whom histomorphometric evaluations of iliac crest bone biopsies were performed after in vivo tetracycline doublelabeling. The serum concentration of 25-hydroxyvitamin D was normal. The serum concentration of 1,25-dihydroxyvitamin D was reduced (p less than 0.02) compared to normal whereas the serum concentration of 24,25-dihydroxyvitamin D was increased (p less than 0.02). The bone changes were characterized by an enhanced turn-over in trabecular and cortical bone leading to an increased porosity of cortical bone and mobilisation of bone mineral. The observed changes in vitamin D metabolism could be explained by a reduced renal 1-alpha-hydroxylase activity secondary to hypercalcaemia with suppressed parathyroid secretion and hyperphosphataemia. The bone changes were unrelated to the serum levels of vitamin D metabolites. In trabecular bone the appositional rate and mineralization rates of osteoid were increased and the mineralization lag time was shortened showing that the mineralization and formation of osteoid in the hyperthyroid state can progress with an enhanced rate in spite of a reduced mean serum level of the active vitamin D metabolite, 1,25-dihydroxyvitamin D.

24,25-Dihydroxyvitamin D 3↗

Altered vitamin D metabolism and bone remodelling in patients with medullary thyroid carcinoma and hypercalcitoninemia.

Fourteen patients with medullary carcinoma of the thyroid (MCT) and hypercalcitoninemia were studied. Serum concentrations of calcium, phosphorus and iPTH (C-terminal) were normal. Serum 1,25-dihydroxyvitamin D (1,25-(OH)2D) levels were increased (p less than 0.001) in spite of reduced serum 25-hydroxyvitamin D (25-OHD) levels (p less than 0.02) indicating an enhanced activity of the renal 1 alpha-hydroxylase. Serum 24,25-dihydroxyvitamin D levels were normal and correlated positively with serum 25-OHD. Histomorphometric analyses of iliac crest bone biopsies after in vivo tetracycline double-labelling were performed in patients and controls. The patients showed a normal trabecular bone volume. The mean size of the cortical osteocytic lacunae was increased (p less than 0.001). Significant increases were found in fractional formation surfaces (p less than 0.05), fractional labelled surfaces (p less than 0.01) and fractional resorption surfaces (p less than 0.005) in trabecular bone. The appositional rate of newly mineralized bone was reduced (p less than 0.025). The mean osteoid seam width was normal due to an unchanged mineralization lag time and a normal osteoid appositional rate. The bone formation rate at tissue level was high normal. The altered vitamin D metabolism may be caused by a direct effect of hypercalcitoninemia on the renal l alpha-hydroxylase or may represent an adaptive change in calcium-phosphorus homeostasis. The dynamic bone changes are similar to those found in primary hyperparathyroidism and may be caused by an enhanced sensitivity to circulating PTH induced by the increased 1,25-(OH)2D.

Adolescent↗

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↗

Histological study of navicular bone disease.

A histological investigation of navicular bones from 8 horses with navicular disease was carried out to investigate the aetiology of the radiological findings. Two of the horses were double labelled with tetracycline before slaughter in order to assess the vitality of the diseased navicular bone. The examinations revealed no evidence of loss of vitality in the diseased bone areas or in surrounding tissues. A very high rate of remodelling indicated by resorption and formation of bone was present in all cases. This was shown microscopically by the high number of osteoclasts and osteoblasts present, osteoid formation and particularly by a high rate of intravital uptake of tetracycline by the bone. The findings are considered to indicate that navicular disease is not primarily caused by ischaemia and subsequent necrosis, but rather is a consequence of increased activation of bone remodelling caused by altered pressure from the deep flexor tendon on the bone and increased load on the caudal part of the foot. This is further supported by the clinical changes seen after alterations occur in the hoof conformation. The disease is, therefore, considered to be reversible and may be alleviated by altering the load on the navicular bone by special shoeing. Only secondary lesions such as adhesions and spur formation render the disease irreversible.

Animals↗

Acute effects of parathyroid hormone on vitamin D metabolism in patients with the bone loss of aging.

This study was carried out to evaluate the effects of an iv injection of parathyroid extract on serum levels of 1,25-dihydroxyvitamin D [1,25-(OH)2D3] in elderly osteopenic patients and age-matched nonosteopenic controls. Serum concentrations of 1,25-(OH)2D were reduced in elderly osteopenic subjects (mean +/- SEM, 20 +/- 3 pg/ml) compared with values in age-matched nonosteopenic controls (35 +/- 3 pg/ml), whereas no differences were found in serum 24,25-dihydroxyvitamin D levels (1.5 +/- 0.3 and 2.2 +/- 0.5 ng/ml, respectively). An iv injection of parathyroid extract was followed by a significant increase in serum 1,25-(OH)2D levels in both osteopenic patients (16 +/- 6 pg/ml) and controls (15 +/- 5 pg/ml). The mean 4-h increases in serum 1,25-(OH)2D of 11-18 pg/ml were not significantly different in the two groups. The results indicate that the reduced 1,25-(OH)2D concentrations in the osteopenic patients are secondary to changes in factors that normally stimulate this enzyme system.

24,25-Dihydroxyvitamin D 3↗