[Alveolitis fibrosa: an exogenically determined syndrome?].
Explore the source record for details and available documents.
Biomedical subjects
Publications and source records attributed to L Mosekilde.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Increased bone, resorption previously found in hyperthyroidism might be caused by a direct stimulating effect of thyroid hormone(s) on bone cells or by an increased sensitivity to circulating parathyroid hormone. In order to disclose qualitative differences in the response of bone resorbing cells to excess parathyroid hormone and excess thyroid hormone(s), histomorphometric analysis of iliac crest biopsies was performed in 25 hyperparathyroid and 40 hyperthyroid patients after tetracycline double-labelling. The main target cells for parathyroid and thyroid hormones were different. Parathyroid hormone stimulated osteocytic osteolysis and increased osteoclastic resorption surfaces equally in trabecular and cortical bone. The osteoclastic resorption was inactive. Thyroid hormone(s) had no effect on osteocytes but increased the osteoclastic resorption surfaces in trabecular and cortical bone, with a pronounced preponderance in cortical bone. The osteoclastic resorption was active and followed by a significant loss of both cortical and trabecular bone. The findings support the assumption that increased bone resorption in hyperthyroidism is caused by a direct stimulating effect of thyroid hormone(s).
Bone biopsies were performed after tetracycline double-labelling by transfixing the right iliac crest in fourteen hypothyroid patients. The bone changes in cortical and trabecular bone were determined by simple measurement and point counting on decalcified and undecalcified stained sections and compared to normal controls and to sex and age matched hyperthyroid patients. The amount of trabecular bone and the cortical porosity were unchanged in the hypothyroid patients compared to normal controls, whereas the mean cortical thickness was increased. The amount of osteoid and the length of the osteoid seams were normal, whereas the mean width of the osteoid seams was decreased. The linear calcification rate in cancellous bone was decreased, as were the active calcification surfaces (tetracycline-labelled) and the percentage of osteoid covered surfaces active in mineralization. The osteoclastic resorption surfaces were unchanged in trabecular bone, whereas the osteoclastic activity in cortical bone was decreased. The osteocytic osteolysis was normal. The bone changes in hypothyroidism were opposite to the changes in hyperthyroidism characterized by a very low bone turn-over with a reduced osteoid apposition and bone mineralization rate, an inactive osteoclastic resorption in trabecular bone and a decreased osteoclastic resorption in cortical bone.
An evaluation of the following histomorphometric parameters: absolute trabecular bone volume (ATBV), osteoid surfaces (OS), osteoid volume (OV), resorption surfaces (RS), and mean size of periosteocytic lacunae (POL) was carried out. Double determination on sections, obtained from an area 2 cm below the summit and 2 cm behind the anterior, superior, spine of the iliac crest from 20 normal individuals aged 20-40 years, showed that the precision of method by far outweighed the inter-individual variation. Parameters obtained from 9 different localizations within the iliac bone revealed that the volume of bone was the only parameter which was influenced if the bone specimen was removed more than 2 cm below or behind the standard localization. Randomly selected sections alternately stained with Masson trichrome and toluidin blue were used for the study of the influence of the staining method on the osteoid parameters. It was shown that Masson trichrome staining would generally result in a slightly higher value of osteoid surfaces. There was, however, a high correlation between the parameters obtained with the two methods. (OS: r = 0.96; OV: r = 0.87).
Bone specimens from a standardized area of the iliac crest were obtained at autopsy in 105 individuals after sudden unexpected death and at biopsy in 30 living volunteers. Seven micron thick sections of the plastic embedded undecalcified material were produced and stained. The amount of cancellous and cortical bone and the parameters attached to description of bone remodelling were determined by point counting and simple measurements, in order to establish normal mean values and range in a Danish population. A decrease in the amount of bone, trabecular as well as cortical, was found with increasing age in both males and females. The extent, volume and width of osteoid seams and the osteoclastic resorption were found to be age-independent. The osteoclastic resorption in cortical bone in males decreased, however, with increasing age. The reported values are of the greatest importance for the use of histomorphometric analysis of bone biopsies as a diagnostic tool in metabolic bone diseases. It is stressed, however, that supplementary information of the dynamic aspects of the bone remodelling would be necessary for the understanding of the pathogenesis of bone changes. Such information might be obtained by using tetracyline double labelling.
The effect of antithyroid treatment on the disturbed calcium-phosphorus metabolism in hyperthyroidism was studied in 16 patients. Elevated serum concentrations and urinary excretions of calcium and phosphorus were almost normalized 4 weeks after the start of medical treatment. Serum immunoreactive parathyroid hormone was decreased in the hyperthyroid state and became normal after medical treatment. Serum alkaline phosphatase levels were elevated throughout the study with an increase to a maximum peak after 8 weeks of antithyroid treatment. Urinary hydroxyproline excretion was initially markedly increased and fell rapidly during therapy. The observed changes suggest decreased bone resorption and increased bone formation with deposition of bone mineral after antithyroid treatment. Alterations in the serum albumin concentration during the investigation period influenced the total serum calcium concentration. Using albumin adjusted serum calcium values no hypocalcaemia was found during medical treatment or after a subsequent subtotal thyroidectomy.
Histomorphometric analysis of iliac crest biopsies was performed after tetracycline double-labelling in 22 hyperthyroid patients before and after medical antithyroid treatment for an average period of 4 months. The initially increased cortical porosity was normalized during treatment whereas the amount of trabecular bone was unchanged. The osteoclastic resorption in cortical bone decreased but was still elevated. The osteocytic osteolysis remained slightly increased. In trabecular bone, however, the bone turn-over decreased to a subnormal level following treatment and the surfaces were inactive in bone resorption and bone formation. An increase was observed in the amount, extent and width of osteoid seams due to an increase in the lifespan of bone forming sites and a prolongation of the maturity period of osteoid. The observed increased deposition of cortical bone after antithyroid treatment may explain the positive calcium balance in this period.
Bone phosphorus/hydroxyproline ratio (P/Hypro) was compared to bone histomorphometry in thirty-four normal individuals. Bone P/Hypro ratio correlated significantly to both the relative mineralized bone volume (r = 0.38, P less than 0.05), the relative osteoid volume (r = -0.38, P less than 0.05) and the percentage of osteoid covered surfaces in trabecular bone (r = -0.38, P less than 0.05).
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Bone biopsies were performed after tetracycline double-labelling by transfixing the right iliac crest in forty hyperthyroid patients. The bone changes in cortical and trabecular bone were determined by simple measurement and point counting on decalcified and undecalcified stained sections. A slight decrease in the amount of cancellous bone was found. The mean cortical width was normal. The amount of osteoid and the length of the osteoid seams were increased, whereas the mean width of osteoid seams was decreased. The cortical osteoclastic activity and porosity were markedly increased. The trabecular osteoclasic activity was moderately increased and the mean size of periosteocytic lacunae was slightly increased. The calcification rate in cancellous bone was increased as were the active calcification surfaces (tetracycline-labelled). The osteoclastic activity in cortical bone was positively correlated to the free thyroxine index and to the urinary calcium and phosphorus excretion. The findings indicate that the bone changes in hyperthyroidism are specific and that thyroid hormone(s) stimulates both bone formation and resorption followed by increased porosity in cortical bone and by mobilization of bone mineral.
Quantitative morphometric analyses of iliac crest biopsies from 20 epileptic patients receiving chronic anticonvulsant therapy have been performed before and after 4-8 months of vitamin D2 treatment with 9 000 U per day. Biochemical quantities, including serum 25-hydroxycholecalciferol (25-HCC) and serum parathyroid hormone (iPTH), were measured. The anticonvulsant osteomalacia found in the initial bone biopsies was characterized by an increased amount of ummineralized bone, an increased bone resorption and, contrary to vitamin D deficiency, an increased bone mineralization and bone formation. Bone resorption and bone formation were probably equally increased since the amount of cancellous bone was normal. Except for a slight increase in osteoidcovered surfaces and osteoclastic resorption surfaces, the bone changes were normalized after vitamin D2 treatment, leading to a mean serum level of 25-HCC 2.4 times above normal. Serum iPTH was normal before and unchanged during D2 therapy. The urinary calcium excretion remained decreased. The investigation characterizes anticonvulsant osteomalacia as a specific bone disease different from that of vitamin D deects of vitamin D metabolites on receptor cells.
About 30% of patients with clinical osteoporosis had histological signs of osteomalacia, in spite of normal serum 25-hydroxyvitamin D3 (25-OHD3). The excess osteoid disappeared during treatment with 1alpha-hydroxyvitamin D3 (1alpha-OHD3). These patients might have reduced ability to convert 25-OHD3 to 1,25-dihydroxyvitamin D3 (1,25-(OH)2D3). The intestinal calcium absorption increased during treatment with 1alpha-OHD3, but this was accompanied by a rise in urinary calcium excretion. Photon absorptiometry of the forearm indicated increased bone mineral content during treatment with a daily dose of 2 microgram 1alpha-OHD3 and a supplement of 1 g of calcium. This therapeutic combination, however, caused frequent episodes of hypercalcaemia, so further studies are necessary to evaluate an appropriate dose of 1alpha-OHD3 with or without a calcium supplement.
Serum 25-hydroxycholecalciferol (25-HCC) and serum parathyroid hormone (iPTH) were measured in 59 randomly selected adult epileptic outpatients receiving chronic anticonvulsant therapy. Quantitative morphometric analysis of iliac crest biopsies was performed. A mild degree of osteomalacia was found which was inversely correlated to dietary vitamin D intake. Serum 25-HCC was reduced in the epileptic patients compared to a control group, although dietary intake of vitamin D was higher than the mean daily intake in the Danish population. Serum 25-HCC was positively correlated to dietary vitamin D intake, but not correlated to the severity of bone changes, indicating that other factors than circulating 25-HCC are responsible for the development of anticonvulsant osteomalacia. Serum 25-HCG was inversely correlated to serum iPTH in patients with a low dietary calcium intake. The mean value of serum iPTH was not increased, and there was no correlation between serum iPTH and bone morphometry.
Serum immunoreactive parathyroid hormone (S-iPTH) was measured together with serum and urinary calcium and phosphorus in 45 hyperthyroid patients in order to assess parathyroid fe of hyperthyroidism. The prevalence of hypercalcaemia was 51.1% using serum calcium values corrected for individual variations in serum albumin concentration compared to 15.6% using the uncorrected calcium values. S-iPTH was decreased and inversely correlated to serum calcium values. S-iPTH was decreased and inversely correlated to serum calcium (corrected). Subnormal levels of S-iPTH were found in 28.9% of the patients. The urinary excretion of calcium and phosphorus was increased and positively correlated to the degree of hyperthyroidism. The tubular reabsorption of calcium (TRCa%) was decreased, positively correlated to S-iPTH and inversely correlated to serum calcium. Increased mobilisation of bone mineral in hyperthyroidism is suggested mainly to be responsible for the elevated serarathyroid function.
Iliac-crest biopsies were obtained from 40 untreated hyperthyroid patients after double-labelling with tetracycline. Histomorphometric analyses were performed on undecalcified and decalcified bone sections. The morphometric and chemical data were compared with those in normal control groups and the results of the morphometric analyses were related to thyroid function and to chemical quantities of calcium-phosphorus metabolism. The bone turn-over was increased in the hyperthyroid patients with an increase both in bone resorption and bone formation. Serum alkaline phosphphatase was increased and positively correlated to the amount of osteoid and to the extent of tetracycline-labelled surfaces. The osteoclastic resorption was positively and the bone formation inversely correlated to thyroid activity. This might explain the reduced amount of trabecular bone found in hyperthyroidism. The most striking feature was, however, a pronounced increase in osteoclastic activity in cortical bone followed by increased porosity. The osteoclastic resorption in cortical bone was positively correlated to serum concentrations and urinary excretions of calcium and phosphorus. This indicates that increased cortical osteoclastic resorption is mainly responsible for bone mineral mobilisation in hyperthyroidism.