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Biomedical subjects

L Mosekilde

Publications and source records attributed to L Mosekilde.

At least 235 records · Page 13Linked to original sources

Proportion of human vertebral body bone that is cancellous.

The concept that vertebral fractures are caused by excessive loss of cancellous bone has been challenged by a recent study (J Bone Min Res 2:221, 1987) suggesting that vertebral bodies are composed mainly of cortical bone rather than cancellous bone. To resolve disagreement we used two independent methods to quantify the proportions of cortical and cancellous bone in 400 microns thick sections of the bodies of the second lumbar vertebrae from six men (aged 21-58 years) and seven women (aged 25-58 years). Based on the ash weight of the manually dissected components, 80% of the total bone in men and 72% in women was cancellous bone. Based on computer-assisted scanning of sections with a microdensitometer, 81% of the total bone in men and 71% in women was cancellous bone. We conclude that the traditional concept is correct: the vertebral body is composed mainly of cancellous bone.

Absorptiometry, Photon↗

Diurnal rhythm and 24-hour integrated concentrations of serum osteocalcin in normals: influence of age, sex, season, and smoking habits.

In the present study we examined whether the diurnal pattern and the 24-hour integrated serum concentration of osteocalcin (S-OC(I] showed any variation due to age, sex, season, or smoking habits in 31 normal subjects, aged 23-47 years. Blood samples were drawn every 60 minutes from 4 p.m. until 6 p.m. the following day. Serum osteocalcin showed diurnal variation as described earlier but no influence of age or sex on the diurnal variation could be demonstrated. Ten subjects were smokers, all consuming more than 10 cigarettes daily, but the diurnal variation in OC with time was not different from an age-, sex-, and height-matched group of strictly nonsmokers. Sixteen of the subjects were initially examined in March and 15 in November. Eight subjects were examined during a period in both November and March, and 5 of these went through an additional study period in July. These seasonal studies showed that the diurnal time course pattern during different seasons of the year were statistically indistinguishable from each other. The S-OC(I) was significantly higher in subjects below 29 years of age compared with subjects aged 30-40 years (P less than 0.01). Men had higher values than women (P less than 0.05). Moreover, S-OC(I) was higher in November compared to March (P less than 0.05). There was no effect of smoking on S-OC(I). A significant correlation existed between S-OC(I) and age (r = 0.50, P less than 0.005). Multiple regression showed that among age, height, and weight, only age and height were significant determinants for S-OC(I) (r = 0.50, P = 0.02).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Consequences of the remodelling process for vertebral trabecular bone structure: a scanning electron microscopy study (uncoupling of unloaded structures).

Cylindrical trabecular bone specimens were obtained from the central part of the third lumbar vertebral body from 29 normal individuals aged 26-90 years (18 men, 11 women). The marrow was cleaned from the bone samples, but no removal of organic material was performed. The cylinders were freeze-dried and coated with gold. A Jeol JSM-840 scanning electron microscope was used for the investigation. The scanning electron microscopy (SEM) showed the loss of connectivity in the trabecular network with age--and the remodelling process causing this. Thin horizontal trabeculae with osteoclastic perforations could be demonstrated. These trabeculae, once disconnected and therefore no longer strained, seemed removed by an 'aggressive' osteoclastic resorption. On vertical trabeculae, microcallus formation was frequently seen in elderly individuals. Furthermore, the three-dimensional morphology of trabecular remodelling sites was also readily apparent. The remodelling sites covered areas of varying sizes (50 x 20-1000 x 1000 micron 2). SEM is an easy and refined tool for analysis of the mechanisms behind age-related changes in vertebral trabecular bone. It enables the whole remodelling process to be studied in the three-dimensional trabecular lattice and confirms and highlights the pathophysiological mechanisms suggested by normal histological studies.

Adult↗

Sex differences in age-related changes in vertebral body size, density and biomechanical competence in normal individuals.

Size, ash-density and biomechanical competence were investigated on whole vertebral bodies (L2) from 90 normal individuals (47 males and 43 females), aged 15-91 years. At all ages, cross-sectional area was significantly greater in males than in females. Furthermore, in males a significant increase of 25-30% in cross-sectional area was demonstrated with aging (r = 0.33, p less than 0.05). Conversely, no age-related change in cross-sectional area was detected in females (r = 0.03, n.s.). A significant and identical age-related decrease (p less than 0.001) in apparent ash-density was found for both males and females. Biomechanical compression tests revealed significant and identical decreases (p less than 0.001) in vertebral body load and stress with age in both males and females. However, because of their greater cross-sectional area and an increase in this with age, the level for the load-values was higher in men than in women up to the age of 75 years (p less than 0.05). The present study has demonstrated that in men there is a significantly greater cross-sectional area and a significant increase in vertebral body size, due to continuous periosteal growth. This could, to some extent, compensate for the unavoidable loss of vertebral bone density and stress with age. No age-related compensatory mechanism could be demonstrated in women.

Adolescent↗

Primary hyperparathyroidism: changes in trabecular bone remodeling following surgical treatment--evaluated by histomorphometric methods.

Iliac bone biopsies from 11 patients who underwent successful surgery for primary hyperparathyroidism were examined before and median 7 months after surgical treatment. Trabecular bone volume increased (p less than 0.05) and eroded (p less than 0.005) and osteoid covered surfaces decreased (p less than 0.005) in the postoperative period. Also, a decline in tetracycline labeled surfaces was noticed (p less than 0.02). Osteoid thickness, mineral appositional rate and mineralization lag time were unchanged. Bone formation rate at the level of the basic multicellular unit (BMU) was unaffected, but at the tissue level bone formation rate diminished (p less than 0.02). The surgical cure of primary hyperparathyroidism was found accompanied by a change in bone metabolism as the trabecular bone remodeling decreased from a high turnover to a low turnover state. The spongy bone mass increased after parathyroidectomy but the clinical significance of this finding was not clear.

Aged↗

A model of vertebral trabecular bone architecture and its mechanical properties.

An idealized, structural model of vertebral trabecular bone is presented. The architecture of the model (thick vertical columns and thinner horizontal struts) is based on studies of samples taken from the central part of vertebral bodies from normal individuals aged 30 to 90 years. With trabecular diameters and spacings typical for persons aged 40, 60, and 80 years respectively, the model accounts reasonably well for age-related changes in vertical and horizontal stiffness and trabecular bone volume, as seen in experimental data. By introducing a measure for the randomness of lattice joint positions in the modeled trabecular network, it is demonstrated that the apparent stiffness varies by a factor of between 5 and 10 from a perfect cubic lattice to a network of maximal irregularity, even though trabecular bone volume remains almost constant. A considerable change in mechanical behaviour is also seen, without changing the overall trabecular bone volume, when the bone material is slightly redistributed among vertical and horizontal trabeculae. It is concluded that measured bone mass should not be the sole indicator of trabecular bone biomechanical competence (stiffness and stress). It is crucial that measurements of bone density are considered in combination with a detailed description of the architecture.

Adult↗

The effect of carbonic anhydrase inhibition on calcium and bone homeostasis in healthy postmenopausal women.

Carbonic anhydrase localized in bone resorptive cells generates the protons necessary for bone resorption. Inhibition of the enzyme is a potential mechanism for decreasing bone resorption. Eight healthy post-menopausal women received oral acetazolamide 250 mg twice daily for 28 d. Bone resorption, evaluated by serum acid phosphatase activity and the renal excretion of hydroxyproline, was unaltered, as was bone formation estimated by serum levels of alkaline phosphatase and osteocalcin. The fasting renal excretion of calcium was increased, whereas serum ionized calcium was unchanged. The maximal renal reabsorption of phosphate decreased, but it was not an effect of PTH as it decreased significantly during the treatment period. In conclusion, no significant effect on biochemical markers of bone remodelling could be detected during the study period. The observed changes in calcium and phosphate metabolism may be secondary to the renal effect of acetazolamide.

Acetazolamide↗

Changes in biochemical markers of osteoblastic activity during the menstrual cycle.

Serum levels of osteocalcin [OC; bone Gla protein (BGP)] and bone alkaline phosphatase (B-AP) are both correlated to osteoblastic activity, which may be regulated by several hormones, including estrogen, 1,25-dihydroxyvitamin D3 [1,25-(OH)2D3], and PTH. Estrogen shows reproducible variations during the menstrual cycle, while available data on variations in serum 1,25-(OH)2D3 and serum immunoreactive PTH show midcyclic increases or no changes. In the present study we evaluated osteoblastic activity by measuring serum OC and B-AP during the menstrual cycle in eight healthy women, aged 20-47 yr. The cycles were synchronized by LH peaks, and follicular and luteal periods were normalized by lengths. Repeated measures analysis of variance showed that serum OC varied significantly (P less than 0.05), with highest levels during the luteal period. Although the same pattern was seen for serum B-AP, the variation just failed to reach significance (P less than 0.10), but the mean level was significantly higher during the luteal than during the follicular period (P less than 0.05). Gonadotropins and ovarian sex hormones showed significant variations. There were no significant changes in serum vitamin D-binding protein, serum total and free 1,25-(OH)2D3 index, or serum immunoreactive PTH-(1-84), but serum levels of somatomedin-C showed a significant variation, with the highest level during the luteal period (P less than 0.05). Blood levels and urinary excretion of minerals exhibited no significant variations. Cross-correlation studies between OC and estradiol showed the highest correlation coefficient, when OC was lagged about 7 days after estradiol (r = 0.69; P less than 0.05). Moreover, a high correlation was found between OC and somatomedin-C when matched at concurrent time points (r = 0.76; P less than 0.01). No significant correlations were found between the other calcium-regulating hormones and OC when matched at concurrent time points. In conclusion, we found a significant effect of the menstrual cycle on the serum levels of two osteoblastic bone markers, OC and B-AP. The changes indicated that osteoblastic activity is higher during the luteal period. However, whether the changes are caused by direct or indirect effects of the fluctuations in calciotropic hormones is still unresolved.

Adult↗

Diurnal rhythm in serum activity of wheat-germ lectin-precipitable alkaline phosphatase: temporal relationships with the diurnal rhythm of serum osteocalcin.

Serum levels of osteocalcin (S-OC) and lectin-precipitable alkaline phosphatase activity (S-LAP) are sensitive markers of osteoblastic activity. Diurnal variation has been found for S-OC but has not been reported for S-LAP. We measured S-LAP and serum total alkaline phosphatase (S-TAP) in samples drawn every 60 min during a 24-h study period in nine normal subjects and correlated the findings with the diurnal variation in S-OC. A significant (p less than 0.05) diurnal variation in S-LAP characterized by peaks at 1430 hours and 2330 hours and nadir at 0630 hours was found. Peak levels were 30% higher than nadir level (p less than 0.05). S-TAP also varied significantly (p less than 0.05) with nadir at 0630 hours, showing a difference of 23% between peak and nadir levels (p less than 0.05). Significant cross-correlation was found between S-OC and S-LAP and S-TAP when these lagged 4 h after S-OC: r = 0.51 (p less than 0.02) and r = 0.65 (p less than 0.003), respectively. In other words, changes in S-LAP and S-TAP preceded changes in S-OC by 4 h. There were no significant cross-correlations between the non-lectin-precipitable fraction of AP and S-OC. In conclusion, S-LAP varies in a diurnal rhythm closely related with the diurnal rhythm of S-OC. The almost similar patterns in the diurnal serum levels of these two osteoblastic products strongly suggest that osteoblastic activity fluctuates rhythmically during the day in humans.

Adult↗

Effects of thyroid hormones on bone and mineral metabolism.

Because of pronounced symptoms and early detection, severe hyperthyroidism is usually treated before skeletal symptoms are evident. However, previous hyperthyroidism may involve a risk of later postmenopausal or senile osteoporosis, since some of the bone loss apparently is irreversible. Borderline hyperthyroidism in clinically euthyroid patients may induce accelerated bone loss and thereby increase the risk of low-energy fractures. Moreover, it is unknown whether interindividual differences exist in skeletal sensitivity to circulating thyroid hormones and thereby in the rate of bone loss. From these considerations it appears that disturbed thyroid function may be involved in the pathogenesis of osteoporosis, one of the major health problems in the western hemisphere.

Bone and Bones↗

Spect bone scintigraphy in assessment of cranial Paget's disease.

Single photon emission computed tomography (SPECT) bone scintigraphy was used in the assessment of Paget's disease in 3 patients with skull involvement. In comparison with conventional scintigraphy, SPECT improved the three-dimensional perception and made precise outlining of involved bones possible. The radionuclide uptake in lesions expressed as counts per pixel was 1.5 to 10 times that of normal bones. Routine use of SPECT in cranial Paget's disease for staging and monitoring the effect of treatment is proposed.

Aged↗

[Treatment of Paget's osteitis deformans].

Specific treatment of osteitis deformans (OD, Paget's disease of bone) is indicated when symptoms are associated with signs (biochemical or by bone scintigraphy) of active disease. OD in the base of the skull and osteolytic lesions in weight-bearing bones should be treated irrespective of symptoms. The effect of calcitonin (CT) on symptoms and skeletal blood-flow is achieved rapidly and healing of osteolytic lesions may occur. However, CT is only effective in approximately 60%, is discontinued due to side effect in 20% of patients, and must be administered parenterally. EHDP (Etidronate) is administered orally but the use of even small doses carries a risk of mineralisation defect and possibly fracture. EHDP should, therefore, be given intermittently and should not be used in osteolytic lesions of weight-bearing bones. Second-generation bisfofonates are devoid of this side effect and are very effective in OD. The effect of mithramycin is only transient and because of the risk of serious side effects the use should be restricted to severe cases of OD resistant to the other lines of treatment.

Adenosine Diphosphate↗

[Paget's osteitis deformans. Epidemiology and clinical picture].

Osteitis deformans is a focal disease of the osteoclasts characterised by increased bone resorption subsequently followed by increased bone formation leading to abnormal bone. A viral etiology seems increasingly probable, but remains unproven. 5-30% of the patients present with symptoms such as pain, deformity and fracture. Hearing loss, nerve- or root-compression, arthrosis and hyperuricaemia may complicate the disease while malignant degeneration, hypercalcemia and high output cardiac failure are rare. The diagnosis is based on X-ray findings but biopsy may be necessary in selected cases. The extent of the disease is revealed by bone scintigraphy and the activity of the disease reflected by urine hydroxyproline excretion and serum alkaline phosphatase.

Adult↗

Effects of sodium fluoride, vitamin D, and calcium on cortical bone remodeling in osteoporotic patients.

The purpose of this histomorphometric study of iliac bone biopsies from 10 postmenopausal osteoporotic patients was to describe the effects of sodium fluoride (combined with calcium and vitamin D) on remodeling in cortical bone after 6 months and after 5 years of treatment. Biopsies had been fixed in absolute methanol, embedded undecalcified in methylmetacrylate, and cut on a heavyduty microtome. The therapy had no effect on the thickness of cortical bone in the iliac crest but increased the porosity slightly. It had no statistically significant effect on depth of resorption or thickness of new walls formed at remodeling sites but treatment increased the fraction of osteons undergoing remodeling in cortical bone. After 6 months of treatment, the increase was due to an enhanced activation of new remodeling sites, but in biopsies taken after 5 years of treatment, some degree of mineralization defect was observed and the duration of the remodeling cycle appeared to be prolonged. The mechanism underlying this qualitative change in the response to treatment is unknown, and it is unclear whether the mineralization defect may be prevented by, e.g., an altered supplementation of vitamin D or calcium.

Aged↗

Efficacy of wheat germ lectin-precipitated alkaline phosphatase in serum as an estimator of bone mineralization rate: comparison to serum total alkaline phosphatase and serum bone Gla-protein.

Serum levels of total alkaline phosphatase activity (S-T-AP), wheat germ lectin-precipitated alkaline phosphatase activity (S-L-AP), and bone Gla-protein immunoreactivity (S-BGP) were measured in 26 patients (23 females and 3 males) aged 35-73 years (mean 59 years) with primary hyperparathyroidism (n = 7), hyperthyroidism (n = 9), and hypothyroidism (n = 10) in whom the bone mineralization rate (m) was determined by 47Ca-kinetics (continuously expanding calcium pool model). A weak positive correlation (r = 0.42, P less than 0.05) was found between S-T-AP and m, which in the range from 0-18 mmol Ca/day could be estimated with a standard error of 4.6 mmol/day. A closer correlation (r = 0.65, P less than 0.001) was found between S-L-AP and m which was estimated with an error of 3.9 mmol Ca/day. The AP activity in the supernatant showed no significant correlation to m (r = 0.11, P greater than 0.50). The highest correlation coefficient (r = 0.81, P less than 0.001) was found between S-BGP and m which could be predicted with an error of 3.4 mmol Ca/day. S-BGP showed a closer correlation to S-L-AP (r = 0.71, P less than 0.001) than to S-T-AP (r = 0.58, P less than 0.01). We concluded that S-L-AP predicts bone mineralization at organ level better than S-T-AP in selected metabolic bone disorders and that the supernatant activity shows no relation to bone turnover.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

X-ray quantitative computed tomography: the relations to physical properties of proximal tibial trabecular bone specimens.

Cylindrical bone specimens from the proximal epiphysis of ten normal human proximal tibiae were randomly assigned to a destructive axial compression test-series (N = 94) or to a protocol of standardized mechanical conditioning followed by non-destructive repeated testing to 0.6% strain and a final destructive test (N = 121). Specimen X-ray quantitative computed tomography (QCT) obtained at different scanning energies (100, 120 and 140 kVp) yielded closely related results (r = 1.00). Accordingly, predictions of physically measured densities or mechanical properties were not improved by using more than one scanning energy. QCT and physically measured densities were intimately related (QCT at 140 kVp to apparent density using linear regression: r = 0.94, and to apparent ash density: r = 0.95) and did not differ significantly in their ability to predict the mechanical properties, thus favouring the more easily implemented QCT for routine work. Evaluation of the relation of apparent density to Young's modulus and ultimate strength suggested that a power law regression model is preferable to a linear model, although linear model prediction of mechanical properties does not have significantly worse accuracy within the narrow density range investigated. The effect of conditioning on the behaviour of bone specimens subjected to destructive compression tests was to increase the stiffness and strength by approximately 50 and 20% respectively.

Absorptiometry, Photon↗

Determinants for serum 1,25-dihydroxycholecalciferol in primary hyperparathyroidism.

Serum levels of 1,25-dihydroxyvitamin D3 (1,25(OH)2D3), 25-hydroxyvitamin D3 (25(OH)D3), C-terminal immunoreactive PTH (iPTH), calcium and phosphate, and endogenous creatinine clearance (Clcr) were measured in 34 patients with primary hyperparathyroidism. Clcr ranged from 13 to 161 ml/min (mean 72). S-iPTH was elevated in 82% of the patients and correlated positively to serum calcium (r = 0.74, P less than 0.001) and inversely to Clcr (r = -0.50, P less than 0.02). S-25(OH)D3 was reduced in 28% of the patients and depended on regular multivitamin supplementation (P less than 0.005). S-1,25(OH)2D3 was increased in 26% of the patients and decreased in 9%. It was positively correlated to S-25(OH)D3 (r = 0.39, P less than 0.05) and Clcr (r = 0.42, P less than 0.02) and inversely to serum levels of calcium (r = -0.39, P less than 0.05), phosphate (r = -0.42, P less than 0.02) and iPTH (r = -0.40, P less than 0.05). Multiple regression analysis revealed a positive correlation to 25(OH)D3 when Clcr was taken into account and to Clcr when S-25(OH)D3 was taken into account. When both variables were considered no significant partial correlations were found between S-1,25(OH)2D3 and serum calcium, phosphate and PTH, respectively. It is concluded that serum levels of 25(OH)D3 and renal function are the main determinants for S-1,25(OH)2D3 in primary hyperparathyroidism.

Adult↗