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Biomedical subjects

L Mosekilde

Publications and source records attributed to L Mosekilde.

At least 289 records · Page 16Linked to original sources
PubMed1986

Trabecular bone remodeling and balance in primary hyperparathyroidism.

The total remodeling sequences in 19 primary hyperparathyroid patients and 16 approximately age-matched and sex-matched controls were reconstructed from histomorphometric analyses of bone specimens obtained after intravital tetracycline double labeling. In the primary hyperparathyroid group the total amount of work performed by resorptive cells was reduced, as indicated by the significantly lower three-dimensional mononuclear and preosteoblast-like cell resorption depths (35.8 microns vs 44.5 microns in normals, P less than 0.01 and 45.3 microns vs 56.6 microns in normals, P less than 0.01, respectively). The active resorption period (i.e., the function period for osteoclasts and mononuclear cells) was reduced to 19 days compared to 29 days in normals (P less than 0.05), but no difference with respect to bone resorption rates could be demonstrated between the two groups. The median bone formation period (Sigmaf) in primary hyperparathyroid patients was not different from the value obtained in normals (172 days vs 134 days, respectively), and the matrix appositional rate (Ama), as well as the mineralization lag time (tm), were also unchanged. The initial mineralization rate (Ami(i)) was not significantly different from the value obtained in normals, but averaged over the total bone formation period, a reduced mineralization rate could be demonstrated (0.32 micron3/micron2 per day vs 0.46 micron3/micron2 per day in normals, P less than 0.01). The measured final three-dimensional thickness of bone formed during Sigmaf (mcwTm) was reduced in the primary hyperparathyroid group (51.1 microns vs 55.9 microns in normals, P less than 0.02).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1986

A histomorphometric determination of iliac bone structure and remodeling in obese subjects.

Quantitative histomorphometric analyses of iliac crest biopsies were performed after tetracycline double labeling in 24 patients with morbid obesity and in 30 age- and sex-matched controls. The amount and structure of bone were determined from measurements of total biopsy length, fractional length of medullary space, fractional trabecular bone volume, trabecular thickness, and the intertrabecular distance. Static and dynamic variables of bone resorption and formation were determined, and the balance of the BMU level was estimated from final resorption depth and mean wall thickness of trabecular structural units. In the obese patients the total biopsy length was increased, with a normal proportion of medullary space to total biopsy length. The mean fractional trabecular bone volume was reduced due to an increased distance between trabeculae of normal mean thickness. The total biopsy length in the obese patients was found to be positively related to the intertrabecular distance and inversely related to the fractional trabecular bone volume. The remaining histomorphometric variables describing bone formation rate at tissue, BMU, and cellular levels, the amount of bone formed, the mineralization process, mineralization lag time, bone resorption, and the balance between resorption and formation were all normal in the obese group.

Adult↗
PubMed1986

Kinetics of trabecular bone resorption and formation in hypothyroidism: evidence for a positive balance per remodeling cycle.

Using a recently described model for reconstruction of the entire remodeling sequence in trabecular bone after tetracycline double labeling, bone remodeling was investigated in 18 hypothyroid female patients and 11 age- and sex-matched controls. In the hypothyroid group, the final resorption depth was reduced to 42 microns vs 53 microns in the control group (P less than 0.01). The total resorption period was increased to 76 days vs 32 days in the control group (P less than 0.001), and the resorption rate was lowered to 0.8 micron/day vs 2.1 microns/day in the control group (P less than 0.001). The function period for preosteoblast-like cells was 22 days compared to 14 days in normals (P less than 0.05). The total bone formation period was prolonged to 620 days in the hypothyroid group compared to 151 days in the control group (P less than 0.001), and the matrix and mineral appositional rates were lowered to 0.7 and 0.5 micron3/micron2 per day compared to 1.8 (P less than 0.001) and 1.4 (P less than 0.001) micron3/micron2 per day, respectively. The mineralization lag time in the hypothyroid group was 48 days vs 25 days in the control group (P less than 0.001), and at the start of bone formation this difference was even more pronounced (63 and 16 days, respectively, P less than 0.001). The mean completed wall thickness was increased in the hypothyroid group to 59.5 microns compared to 54 micron in the control group (P less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1986

Etidronate disodium for treating hypercalcaemia of malignancy: a double blind, placebo-controlled study.

The efficacy of intravenous etidronate disodium in controlling hypercalcaemia of malignancy was evaluated in a double blind, placebo-controlled study. Twenty patients with known malignant disease and hypercalcaemia were randomly assigned on a 2:1 basis to etidronate 7.5 mg kg-1 body weight or placebo for 3-5 days. All patients received 3000 ml saline and 40 mg furosemide per day. Eighteen patients completed the study. Eleven of twelve in the etidronate group reached normocalcaemia compared to two of six in the placebo group (P = 0.05). The etidronate group showed a greater decrease in serum calcium than the placebo group (P less than 0.02). The renal calcium excretion decreased significantly in the etidronate group, but not in the placebo group. A slight increase in serum creatinine was observed in the etidronate group compared to placebo on the first day of treatment. The difference however disappeared the following days. Intravenous etidronate treatment in combination with rehydration and furosemide constitutes a safe and efficient alternative in the treatment of hypercalcaemia of malignancy, although a first approach always should be rehydration.

Adult↗
PubMed1986

Primary hyperparathyroidism: evaluated by 47calcium kinetics, calcium balance and serum bone-Gla-protein.

Combined 47Calcium kinetic and calcium balance studies with correction for dermal calcium loss were performed in thirteen patients with primary hyperparathyroidism (PHP), in whom serum bone-Gla-protein (S-BGP) was measured, and in ten matched controls. Dietary calcium was normal in PHP but both net (7.9 +/- 1.4 mmol Ca day-1 in PHP v. 3.5 +/- 0.9 mmol Ca day-1 in normals (mean +/- SE] and true (11.1 +/- 1.6 v. 6.8 +/- 0.9 mmol Ca day-1) intestinal absorbed calcium were enhanced (P less than 0.05). The renal calcium excretion (10.9 +/- 0.8 v. 5.1 +/- 0.4 mmol Ca day-1, P less than 0.001) and the dermal calcium loss (2.5 +/- 0.3 v. 1.5 +/- 0.1 mmol Ca day-1, P less than 0.02) were increased in PHP. Both patients and controls were in a negative calcium balance (P less than 0.01 and P less than 0.001, respectively) without any difference between the groups (P greater than 0.10). Mineralization (12.0 +/- 1.7 v. 4.8 +/- 0.8 mmol Ca day-1, P less than 0.02) and resorption rates (17.6 +/- 2.5 v. 7.9 +/- 0.6 mmol Ca day-1, P less than 0.02) were increased in PHP and S-BGP correlated positively to both variables (r = 0.64, P less than 0.05 and r = 0.62, P less than 0.05, respectively). Serum immunoreactive parathyroid hormone correlated positively to serum calcium (r = 0.69, P less than 0.01) but not to the calcium kinetic data.

Adult↗
PubMed1986

Nuclear uptake of 1,25-dihydroxy[3H]-cholecalciferol in peripheral blood monocytes.

The active vitamin D metabolite, 1,25-dihydroxycholecalciferol induces differentiation of monocytes into macrophages. The pharmacological induction of differentiation of primitive, rapidly proliferating cell lines into more mature cells with lower proliferative potential is a new dimension in the treatment of myeloproliferative disorders, which may prove to be an important alternative to more traditional regimens. Furthermore, the cell primarily engaged in bone resorption--the osteoclast--represents another differentiated form of mononuclear phagocytes, and 1,25-dihydroxycholecalciferol increases the number of osteoclasts. Since the cellular action of 1,25-dihydroxycholecalciferol is exerted mainly through its binding to nuclear receptors, a detailed knowledge of ligand-receptor interactions is mandatory for future work in this area. In order to investigate the interaction between 1,25-dihydroxycholecalciferol and its receptor in mononuclear cells, the nuclear uptake of the hormone was studied using a whole cell assay. The nuclear uptake of 1,25-dihydroxy[3H]cholecalciferol in human monocytes at physiological temperature and pH was saturable, specific, and fully reversible. When eight normal individuals were investigated, the maximal binding capacity (Bmax) was 0.4-8.4 fmol/10(6) cells and the dissociation constants (Kd) were 0.12-0.45 nmol/l. The characterization of the nuclear uptake of 1,25-dihydroxy[3H]cholecalciferol in intact human monocytes shows that it is mediated by binding of the ligand to a specific nuclear receptor. The binding to the nuclear receptor is the result of the passage of ligand across the cytoplasmic membrane and of the cytoplasmic transport of ligand. In contrast to conventional receptor assays in hypertonic cellular extracts, this system provides information on the role of the cytoplasmic membrane in relation to the nuclear uptake of 1,25-dihydroxycholecalciferol, which may be closer to in vivo cellular conditions.

Binding, Competitive↗
PubMed1985

Bone mineral loss, bone histomorphometry and vitamin D metabolism in patients with rheumatoid arthritis on long-term glucocorticoid treatment.

Long-term glucocorticoid treatment might interfere with the vitamin D metabolism. The serum concentrations of 25-OHD were significantly reduced whereas the circulating levels of 1,25-(OH)2D were normal in 50 patients with rheumatoid arthritis on long-term treatment with small doses of prednisone. The bone mineral content of the forearm was significantly reduced, but the degree of bone loss did not correlate with duration of treatment or dose of prednisone given. Quantitative bone histomorphometry was performed in 18 patients. Apart from a significant correlation between serum 25-OHD and the fractional trabecular bone volume, no relationships were observed between bone histomorphometry and vitamin D metabolites or serum iPTH. The results indicate that the bone loss was due to a decreased osteoblastic activity rather than to an impaired vitamin D metabolism.

Adult↗
PubMed1985

Changes in vitamin D metabolites and bone histology in rats during recovery from rickets.

The relative roles of 25-hydroxyvitamin D (25-OHD), 1,25-dihydroxyvitamin D (1,25-(OH)2D) and 24,25-dihydroxyvitamin D (24,25-(OH)2D) in bone mineralization are largely unknown. Young vitamin D depleted rats were fed increasing amounts of vitamin D and grouped radiologically in accordance with the rat line test. They ranged from severely rachitic to normal. Radiology was correlated with serum levels of 25-OHD, 1,25-(OH)2D, 24,25-(OH)2D, ionized calcium, magnesium, and phosphate, with bone histology, and with the total mineral content of the animals. Serum 1,25-(OH)2D rose in a linear fashion to supranormal values during bone healing and correlated with the radiological degree of rickets. Serum 25-OHD was below detection limit in the most rachitic and low in the radiologically normal rats, whereas 24,25-(OH)2D was low in all groups. These two metabolites showed no correlation with the radiologic, histologic or biochemical parameters. In rachitic rats, 1,25-(OH)2D appears to play a major role in bone healing and possibly exerts a direct effect on bone cells. It cannot be ruled out, however, that the effect is mediated through a rise in serum levels of calcium and phosphorus, although signs of bone healing were seen in the presence of a subnormal calcium X phosphorus product. Initiation of mineralization can take place with unmeasurable 25-OHD, and 24,25-(OH)2D seems to be without importance.

Animals↗
PubMed1985

The effects of sodium fluoride, calcium phosphate, and vitamin D2 for one to two years on calcium and phosphorus metabolism in postmenopausal women with spinal crush fracture osteoporosis.

Calcium and phosphorus balances and 47Ca turnover studies were performed before and after 12-27 months of daily treatment with sodium fluoride (60 mg), calcium (30-45 mmol), phosphate (29-44 mmol), and vitamin D2 (18,000 IU) in 20 postmenopausal women with spinal crush fracture osteoporosis. Before treatment the mean calcium balance (-1.6 mmol Ca/day) was negative (P less than 0.05), whereas the mean phosphorus balance (-1.6 mmol P/day) did not differ from zero (P greater than 0.10). The treatment induced an increase in calcium absorption (P less than 0.01) with an unchanged renal excretion and dermal loss of calcium and an increase (P less than 0.02) in calcium balance, which became positive (P less than 0.01) (+3.3 mmol Ca/day). This enhancement in calcium balance was obtained by the combined effects of an increase (P less than 0.05) in bone mineralization rate and a decrease (P less than 0.05) in bone resorption rate. The observed increase in net phosphorus absorption (P less than 0.001) was more pronounced than the increase in renal excretion of phosphorus (P less than 0.001), and the phosphorus balance therefore increased (P less than 0.001) and became positive (P less than 0.001). A positive correlation was observed between net calcium and net phosphorus absorption (r = 0.065; (P less than 0.001) in the 32 studies where both calcium and phosphorus balance data were available. Furthermore, a positive correlation (r = 0.61; P less than 0.05) was found between the changes in net calcium and net phosphorus absorption during treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1985

Trabecular bone resorption depth decreases with age: differences between normal males and females.

The resorption depth below osteoclasts, mononuclear cells, and preosteoblast-like cells can be estimated by counting the number of lamellae of known thickness eroded below the three cell types. In a previous study on bone resorption in young normal individuals, we demonstrated that the mean depth below osteoclasts was smaller than the mean depth below mononuclear cells, which again was smaller than the mean depth below preosteoblast-like cells, the last taken as the final depth reached. In order to investigate the variation in resorption depth with age in both sexes, we examined bone biopsy specimens from 42 normal females and 34 normal males aged 17-90 years. For each patient the mean osteoclastic, mononuclear, and preosteoblast-like cell resorption depths were calculated, and the surface extensions of the three types of resorption lacunae were determined. The surface extent of preosteoblast-like cell lacunae increased with age in females (p less than 0.05). Osteoclastic resorption depth was constant throughout the ages in females as well as in males. Mononuclear and preosteoblast-like cell resorption depths decreased significantly with age in females (p less than 0.01 and p less than 0.05, respectively) as well as in males (p less than 0.05 and p less than 0.01, respectively). The mean depth of lacunae where resorption had terminated (i.e., preosteoblast-like cell resorption depth) was larger in females aged 30-60 years than in men of the same age (p less than 0.05). The reduction in final resorption depth with age is parallel to the decrease in mean thickness of completed walls previously described.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1985

Trabecular bone remodeling and bone balance in hyperthyroidism.

In vivo tetracycline double-labeled iliac crest bone biopsies from 15 hyperthyroid patients were used for the reconstruction of curves describing the variation of resorption depth and formation thickness with time. The curves emerging were compared to curves reconstructed from 13 age- and sex-matched normal individuals (mean age 44 years). The median function period for resorptive cells in hyperthyroid patients (16 days) was about one-third the resorptive period in normals (51 days). No significant difference between the osteoclast-, mononuclear-, or preosteoblast-like cell resorption depths could be demonstrated between the two groups. Consequently, the median resorption rate in hyperthyroid patients (3.8 microns/day) was more than 3 times higher than the value in the control group (1.1 micron/day). Median Sigma, was shorter in the hyperthyroid group (109 days) than in the control group (151 days, P less than 0.05), as was the median initial mineralization lag time (5 and 16 days, respectively, P less than 0.01). No significant difference between the measured mean completed wall thickness (mcwT) values in the hyperthyroid groups and the control group could be demonstrated (58.1 and 60.5 micron respectively). Median initial mineralization rate in the hyperthyroid group (1.2 micron3/micron2 per day) was not significantly higher than the value calculated in the control group (0.9 micron3/micron2 per day), but median initial matrix appositional rate in hyperthyroid (4.8 microns3/micron2 per day) was 3 times higher than the value calculated for normals (1.6 micron3/micron2 per day) (P less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1985

Correlation between the compressive strength of iliac and vertebral trabecular bone in normal individuals.

Intrabone and interbone variations and age-related changes in vertical and horizontal trabecular bone compressive strength (CS) were evaluated for loadbearing (vertebral) and nonloadbearing (iliac crest) trabecular bone from 30 normal individuals, 17 females and 13 males, aged 15-87 years. All had died suddenly. The vertebral bodies of Th6, L1, and L3 and the right and left iliac crests were frozen at -20 degrees C immediately after removal. Cylindrical bone samples in the vertical and horizontal direction were taken from the frozen bone, and load-deformation curves were recorded by a materials testing machine. For all vertebral bodies, the vertical CS was much larger than the horizontal CS (P less than 0.01), whereas no significant difference was found for the iliac crests. The anisotropy expressed as an index of vertical to horizontal CS, therefore, was higher in the vertebrae than in the iliac crest. The anisotropy index (Al) increased with age in the vertebrae but not in the iliac crest (r = 0.56, P less than 0.01). Age related, almost identical decreases in CS were observed in the vertebrae (vertical direction) (r = 0.81, P less than 0.01) and in the iliac crest (horizontal direction) (r = -0.69, P less than 0.01). In spite of the pronounced differences in the architecture between the vertebral body and iliac trabecular bone, the vertical vertebral CS could be predicted from the horizontal iliac crest CS (r = 0.88, P less than 0.01, SEE = 0.9 MPa). The vertical iliac crest CS showed a less significant correlation to the average vertical vertebral CS (r = 0.53, P less than 0.05, SEE = 1.25 MPa).

Adolescent↗
PubMed1985

Relationships between calcium and phosphorus homeostasis, parathyroid hormone levels, bone aluminum, and bone histomorphometry in patients on maintenance hemodialysis.

Serum biochemistry related to calcium and phosphorus homeostasis and parathyroid function was studied together with bone histomorphometry after double-labeling with tetracycline and staining for aluminum in 17 patients without symptoms of bone disease, treated with maintenance hemodialysis for at least 6 months. A close correlation was found between the serum level of parathyroid hormone (PTH) and bone resorption surfaces and bone formation rates, both at tissue and basic multicellular unit (BMU) levels. The patients could be divided into a high turnover group with a normal mineralization process and a low turnover group with markedly defective mineralization. The second group was further characterized by lower PTH and higher fractional aluminum-stained trabecular bone surfaces. For the whole patient material, the fractional aluminum-stained surfaces related inversely to tetracycline-labeled surfaces and to bone formation rates at both BMU and tissue levels, but not to the time on dialysis or to the cumulative ingested amount of aluminum hydroxide. The data provide evidence that PTH or PTH-related factors, besides activating bone remodeling, directly enhance bone formation in dialysis patients and that aluminum incorporation into bone is associated with a progressive disturbance of bone mineralization.

Adult↗
PubMed1985

Prostaglandin E2 receptors on human peripheral blood monocytes.

The prostaglandin E2 (PGE2) receptor on human peripheral blood monocytes is characterized. The receptor binding at physiological temperature and pH was saturable, specific, and reversible. Scatchard analysis of binding data revealed a linear plot giving a Kd = 1.1 X 10(-9) mol/l and Bmax = 4.1 fmol/10(7) cells, equal to 240 binding sites per cell. PGE2 increased intracellular cyclic adenosine 5'-monophosphate by a maximal factor of 3. PGF2 alpha and arachidonic acid had no stimulatory effects on adenyl cyclase, in accordance with their low binding to the cells. The characterization of the PGE2 receptor on human monocytes creates a basis for the study of the clinical significance of changes in PGE2-receptor binding in disease states involving PGE2-monocyte interactions such as various immunological disorders and bone resorption.

Arachidonic Acid↗
PubMed1985

Estimation of bone turnover evaluated by 47Ca-kinetics. Efficiency of serum bone gamma-carboxyglutamic acid-containing protein, serum alkaline phosphatase, and urinary hydroxyproline excretion.

Bone gamma-carboxyglutamic acid-containing (Gla) protein (BGP, osteocalcin) is a noncollagenous protein of bone present in plasma and removed by the kidney. Plasma BGP has been shown to be elevated in patients with certain bone diseases. The present study evaluates serum BGP (S-BGP), serum alkaline phosphatase (S-AP), and urinary hydroxyproline excretion (U-OHP) in diseases with differing bone turnover rates, and compares the accuracy of these measurements for estimating bone mineralization (m) and resorption (r) rates. S-BGP, S-AP, U-OHP, and creatinine clearance (Clcr) were measured in patients with primary hyperparathyroidism (n = 13), hyperthyroidism (n = 6), and hypothyroidism (n = 6). Bone mineralization and resorption rates were calculated from a 7-d combined calcium balance and 47Ca turnover study. A highly significant correlation (r = 0.69, P less than 0.001) was found between S-BGP and m. Multiple regression analysis disclosed a partial correlation between S-BGP and m when Clcr was taken into account (r = 0.82, P less than 0.001), and between S-BGP and Clcr when m was taken into account (r = -0.62, P less than 0.005). In accordance with this, a stronger correlation (r = 0.89, P less than 0.0001) was found between S-BGP X Clcr and m than between S-BGP and m. A less significant correlation was found between S-AP and m (r = 0.45, P less than 0.05). Furthermore, U-OHP showed a highly significant positive correlation to r (r = 0.78, P less than 0.001). Thus, in the studied disorders of calcium metabolism, individual serum levels of BGP depend on both mineralization rate and renal function. Serum levels of BGP corrected for alterations in renal function are superior to uncorrected S-BGP and to S-AP levels in the estimation of bone mineralization rates.

Adult↗