Biomedical subjects

L Mosekilde

Publications and source records attributed to L Mosekilde.

At least 307 records · Page 17Linked to original sources

PubMed1984

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↗

PubMed1984

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↗

PubMed1984

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↗

PubMed1984

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↗

PubMed1984

Calcium metabolism evaluated by 47Ca kinetics. Methodologic aspects with optimization of a whole-body counter.

Optimization of a four-crystal stretcher geometry whole-body (WB) counter was performed. The measured geometric characteristic did not differ significantly from the theoretically calculated characteristic (p greater than 0.05). The linearity of the WB counter was high in the range 3.7 kBq to 3.7 MBq. Longtime variability of local background was CV = 3.7 per cent. In vivo sensitivity was calculated to 18 cpm/kBq and the detection limit to about 5 kBq. The reproducibility was estimated to 0.7 per cent. The WB counter was used in 47Ca turnover and calcium balance studies of 15 normal individuals. The data were analysed according to a modification of the expanding calcium pool model using an improved Bauer-Carlsson-Lindquist formulation. Variability and method errors of main parameters for calcium metabolism were evaluated.

Adult↗

PubMed1984

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↗

PubMed1984

Treatment with high-dose oral vitamin D2 in patients with jejunoileal bypass for morbid obesity. Effects on calcium and magnesium metabolism, vitamin D metabolites, and faecal lag time.

Calcium and magnesium balance, 47Ca turnover studies, and measurements of vitamin D metabolites were performed before and after 7-10 months of vitamin D2 treatment (36,000 IU/day) in eight patients bypass-operated 3-6 years earlier for gross obesity. All patients had received a daily supplementation of calcium (27 mmol/day) since operation. Before treatment the net calcium absorption and calcium balance were normal compared with that of nine normal controls. Vitamin D metabolites were within normal limits. The endogenous faecal calcium level was increased and the faecal lag time shortened. Bone biopsies revealed osteomalacia in three of the patients. Vitamin D2 treatment induced an increase in calcium absorption and renal excretion of calcium, a reduced bone resorption rate, a more positive calcium balance, and healing of osteomalacia. Moreover, the vitamin D2 treatment induced a prolongation and normalization of faecal lag time, an increase in magnesium absorption, and a more positive magnesium balance. The effect might be mediated through 25-hydroxyvitamin D (25-OHD), which increased, whereas serum levels of 1,25-dihydroxyvitamin D (1,25-(OH)2D) and 24,25-dihydroxyvitamin D (24,25-(OH)2D) were unchanged. The results indicate that in some bypass-operated patients high-dose vitamin D2 has a beneficial effect on calcium and magnesium metabolism.

Adult↗

PubMed1983

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↗

PubMed1983

Calcium metabolism evaluated by 47Ca kinetics: estimation of dermal calcium loss.

Seventy-seven calcium balance and 47Ca turnover studies were performed in normal volunteers (n = 15) and in patients with osteoporosis (n = 12), primary hyperparathyroidism (n = 8), osteogenesis imperfecta (n = 5), medullary carcinoma of the thyroid (n = 4), thyrotoxicosis (n = 2) and intestinal bypass for obesity (n = 11). After intravenous injection of 20 microCi of 47Ca two retention curves of 47Ca were obtained: R1(t) directly measured on a whole-body counter and R2(t) calculated from the cumulated daily excretions of 47Ca in urine and faeces. The data were fitted to a modification of the continuously expanding exchangeable calcium pool model. Dermal calcium loss was estimated from the serum 47Ca specific radioactivity curve and the constantly increasing difference between the two retention curves. The median dermal calcium loss in 77 studies was 1.50 mmol 24 h-1 1.73 m-2 (range 0.13-4.60). The dermal calcium loss might be overestimated by redistribution of tracer or by eventual insufficient collection of urine and faeces. The possible influences of these errors have been evaluated. Patients with primary hyperparathyroidism had a greater (P less than 0.02) dermal calcium loss (2.64 mmol; range 0.80-4.50) than a control group (1.38 mmol; range 1.25-2.34).

Calcium↗

PubMed1983

Calcium metabolism evaluated by 47calcium-kinetics: a physiological model with correction for faecal lag time and estimation of dermal calcium loss.

Sixty-two calcium balance and 47Ca-turnover studies were performed in 51 individuals to evaluate the accuracy and the sensitivity of the methods. The data were analysed according to a modification of the expanding calcium pool model using an improved Bauer-Carlsson-Lindquist (BCL) formulation and an iterative computer procedure. A 7-day whole body retention curve (R1) combined with a retention curve constructed from excretion data alone (R2) was used to estimate dermal calcium loss (d) and to demonstrate the significance of individual corrections for delay in faecal excretion (faecal lag time = delta t). The mean d was 1.58 mmol Ca/day. The introduction of delta t improved the goodness of fit of the data to the model. delta t based on 47Ca-kinetics was superior to a fixed delta t of zero (P less than 0.01) or 2 days (P less than 0.05). The model derived renal calcium excretion rate was highly correlated (r = 0.98, P less than 0.001) to the chemical measured excretion rate. A similar highly significant correlation [RS = 0.78 (Spearman), P less than 0.001] was found between the model derived delta t and the carmine red delta t. These results indicate a high accuracy of the model. The directly measured parameters showed an excellent reproducibility with a coefficient of variation (CV) less than 4%. The reproducibility of the derived parameters was acceptable (CV = 10-20%) except for the balance (CV = 72%).

Adult↗

PubMed1982

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↗

PubMed1982

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↗

PubMed1982

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↗

PubMed1982

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↗

PubMed1982

Familial medullary thyroid carcinoma in multiple endocrine neoplasia (MEN) IIa: diagnosis and problems in treatment.

A family with MEN IIa (medullary thyroid carcinoma (MCT), pheochromocytoma and hyperparathyroidism) was identified. Three relatives had been treated for MCT earlier. Eleven asymptomatic family members had elevated pentagastrin (PG)-stimulated serum immunoreactive calcitonin (i-CT) concentrations, including one who earlier had a pheochromocytoma removed. Nine of these subjects underwent thyroidectomy, and histological examination revealed multifocal MCT in all. Although surgery was judged complete in all, elevated PG-stimulated serum i-CT levels postoperatively indicated residual disease in 5. The natural history of MCTs in the present family varied, with most cases behaving benignly. Occasionally, however, the disease pursued an aggressive course. As MCT often metastasizes before being clinically evident, high cure rates can only be obtained by early diagnosis and treatment, possibly in the pre-metastasizing phase of C-cell hyperplasia, detectable only by elevated PG-stimulated serum i-CT levels.

Adolescent↗

PubMed1982

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↗

PubMed1982

Vitamin D metabolism and osteomalacia in patients with fractures of the proximal femur.

A high frequency of histological osteomalacia (25 per cent) was seen in patients with fractures of the proximal femur. No correlation was found between the levels of circulating 25-hydroxyvitamin D (25-OHD) or 1,25-dihydroxyvitamin D (1,25-(OH)2D) and the bone histomorphometric changes. The serum 25-OHD levels were normal, which excludes a dietary vitamin D deficiency or a reduced hepatic hydroxylation of the vitamin. The mean serum 1,25-(OD)2D concentration was significantly reduced in the whole patient group, but surprisingly the levels were normal in those with histological osteomalacia, indicating that an impaired conversion of 25-OHD to 1,25-(OH)-2D was not the primary cause of the bone disease. A reduced sensitivity to 1,25-(OH)2D might be a possible explanation for the osteomalacia.

Anthropometry↗

PubMed1982

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↗