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Biomedical subjects

L Mosekilde

Publications and source records attributed to L Mosekilde.

At least 361 records · Page 20Linked to original sources

Liver biopsies in epileptics during anticonvulsant therapy.

Liver function tests, performed in 11 epileptics under antiepileptic treatment for 10-35 years, showed a slight increase in serum alanine amino-transferase in six patients and a marked increased level of serum alkaline phosphatases in four. Liver biopsies revealed few uni- or paucicellular necroses in five patients. Granulomatous hepatitis was found in one patient in whom sarcoidosis was later diagnosed. None of the biopsies showed signs of permanent liver damage.

Adolescent↗

Anticonvulsant osteomalacia determined by quantitative analysis of bone changes. Population study and possible risk factors.

Material has been obtained by biopsy from the right iliac crest of 60 adult epileptic out-patients receiving chronic anticonvulsant therapy with diphenylhydantoin (DPH), either in single-drug or combined-drug regime, and of 16 controls with the same distribution by sex and age. Four (7%) of the epileptics were hypocalcemic and 25 (42%) had elevated serum alkaline phosphatase values. A quantitative analysis of the morphological bone changes was performed on decalcified and undecalcified bone, using integrating filters and the point count principle. An increased amount of unmineralized bone was found in 32 (53%) of the epileptics. The trabecular osteoclastic resorption surfaces and the mean volume of periosteocytic lacunae were increased in 36 (69%) and 45 (75%) patients, respectively. The calcification rate was decreased in relation to what is referred to elsewhere as normal. The bone changes suggest a mineralization defect analogous to osetomalacia with secondary hyperparathyroidism. An increased osteoid volume or thickness and decreased calcification rate were correlated to low dietary vitamin D intake, low exposure to sunlight, high hepatic clearance rate of DPH, combined-drug treatment and the male sex. These parameters should be considered risk factors of anticonvulsant osteomalacia.

Adolescent↗

Thickness of bone formed at remodeling sites in normal human iliac trabecular bone: variations with age and sex.

The thickness of the bone walls formed at completed remodeling sites was estimated by morphometry in iliac trabecular bone from 85 normal individuals (48 women and 37 men) aged 18-90 years. The mean three-dimensional (3-D) wall thickness was 59.4 +/- 5.9 micron. No sex difference was observed. The wall thickness decreased with age: Thickness (micron) = 65.56 micron - 0.14 micron/yr X age (yr). This reduction may lead to a loss of bone with increasing age. The coefficient of variation in completed wall thickness between individuals of the same age was 7%. The factors controlling the thickness are largely unknown, but it was noted that the intraindividual distributions of linear 3-D wall thickness (proportional to the mass of the wall) were symmetric, while distributions of reciprocal 3-D thickness (proportional to the conductivity for oxygen and waste products) were markedly rightskewed. A subgroup comprising 42 individuals aged 18-56 years had been double labeled with tetracycline. The average 3-D calcification rate was 0.63 +/- 0.11 micron/day. No relationship to age or sex was demonstrated. Based on the estimates of completed wall thickness and calcification rate, the mean duration of calcification at remodeling sites was calculated to be approximately 100 days.

Adolescent↗

Estimation of vertebral body strength by dual photon absorptiometry in elderly individuals: comparison between measurements of total vertebral and vertebral body bone mineral.

The aim of the present study was to investigate the predictive value of bone mineral measurements by dual photon absorptiometry (DPA) in vitro for strength and ash weight of lumbar vertebral bodies in elderly, otherwise nonselected individuals. The material comprised 46 individuals: 26 males (43-95 years) and 20 females (63-95 years) without malignant diseases. Spinal segments, including L2, L3, and L4, were removed en bloc at autopsy. Bone mineral content (BMC) measurements imitating the normal DPA procedure were performed on the segments suspended in a water bath. The segments were measured in toto (BMCT) and remeasured after removal of the posterior elements (BMCB). The second lumbar vertebral body (L2) was then dissected and sawed below the endplates to obtain samples with planoparallel ends before compression in a materials testing machine. Finally, the bone specimens were incinerated for ash weight estimations. BMCT showed significant correlations to vertebral body ash weight (r = 0.79), compressive strength (load, r = 0.69), and stress (load per unit area, r = 0.47). The correlations were improved by removing the posterior elements (BMCB-ash weight, r = 0.86, BMCB-load, r = 0.74, BMCB-stress, r = 0.49). Correction of BMC for differences in vertebral body height (BMC/cm) further increased the correlation coefficients (BMCB/cm-ash weight, r = 0.92, BMCB/cm-load, r = 0.78, BMCB/cm-stress, r = 0.55). We conclude that lumbar BMC is predictive for lumbar vertebral body compressive strength in vitro and ash weight. The correlation coefficient is improved by removing the posterior non-weight-bearing element.(ABSTRACT TRUNCATED AT 250 WORDS)

Absorptiometry, Photon↗

Age- and sex-related changes in iliac cortical bone mass and remodeling.

Iliac crest bone biopsies were obtained from 64 normal individuals (41 women and 23 men) aged 19-90 (mean 48.2) years. Thirty-four were double-labeled with tetracycline before biopsy. The following variables were measured in all biopsies: biopsy core width (C.Wi), absolute (A.Ct.Wi) and fractional (F.Ct.Wi) cortical width, absolute (A.Cn.Wi) and fractional (F.Cn.Wi) cancellous width, cortical porosity (Ct.Po), osteon diameter (On.Dm), Haversian canal diameter (Ha.Ca.Dm), and wall thickness (W.Th). In the tetracycline-labeled biopsies the typical cortical remodeling cycle was reconstructed and the activation frequency was estimated. A negative cortical bone balance with aging was found in both sexes. In females F.Ct.Wi decreased (p < 0.02) with aging because of marrow expansion (p < 0.05). Furthermore, Ct.Po increased (p < 0.001) because of a decrease in W.Th (p < 0.01) and an increase in H.Ca.Dm (p < 0.001). In males the negative cortical bone balance with aging was exclusively caused by an increase in Ct.Po (p < 0.001) partially explained by an expanding H.Ca.Dm (p < 0.01). The On.Dm increased with aging (p < 0.01), but surprisingly, no fall in W.Th was observed. Reconstruction of the remodeling cycle did not reveal any significant difference between younger women and men. However, the activation frequency rose from 0.5 per year in premenopausal to 1.0 per year in postmenopausal women (p < 0.001), giving rise to a high turnover state, an increase in the remodeling space, and thereby the porosity in the cortical bone immediately after menopause. The present study has shown a reduction in cortical bone mass in elderly people, compared with younger, which may be explained by an age-related remodeling imbalance. This reduction is further increased in women in the postmenopausal state because of a postmenopausal accelerated bone turnover.

Adult↗

Calcium-restricted ovariectomized Sinclair S-1 minipigs: an animal model of osteopenia and trabecular plate perforation.

The ovariectomized rat model has now been generally accepted as a useful model for screening different therapeutic agents, but there is a major requirement to identify reliable large animal models for osteoporosis research. In this study, the calcium restricted, ovariectomized minipig has been thoroughly investigated in order to define a large animal model with trabecular and cortical bone remodeling which would be reliable for further testing of agents that had shown promise of efficacy during the screening procedure. Twenty six female, 4-month old minipigs were randomized into four groups and fed either normal diet (0.90% calcium (Ca.)) or diet with restricted calcium content (0.75%, 0.50%). At the age of ten months, 3 groups were ovariectomized (OVX) while one group on normal diet was shamoperated. The groups were followed for six months after the operation. At death, bone mass was determined by densitometry and by ashing. Additionally, biomechanical competence was assessed in trabecular bone cores from the vertebral bodies. Finally, histomorphometry (static and dynamic parameters) and structural analyses (star volume) were performed on the vertebral bodies. The study revealed an OVX-related decline of 6% in vertebral bone mineral density (BMD) and a decline of 15% in trabecular bone volume (BV/TV). In contrast, a 15% increase in mean trabecular plate separation (Tb.Sp.) and a small increase in marrow space star volume (Ma. Star V.) were detected. The structural changes became more pronounced when OVX was combined with mild Ca. restriction (0.75% Ca.) with an increase in Ma. Star V. to 164%.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Primary hyperparathyroidism: iliac crest cortical thickness, structure, and remodeling evaluated by histomorphometric methods.

Iliac crest bone biopsies from 62 patients (42 women, 20 men; median age 59 years; range 17-79 years) with primary hyperparathyroidism (PHP) were examined. Static and structural parameters were compared with 30 age- and sex-matched normal controls. Eighteen sex-matched younger controls were used for evaluation of the dynamic controls. On the endocortical surface increase in extension of eroded (p < 0.01) and formative (p < 0.01) surfaces was found in PHPs compared with normals. Endocortical bone formation rate was increased in PHPs (p < 0.05), but mineral appositional rate and adjusted appositional rate were normal. On the periosteal surface very little remodeling activity was found. Although bone formation rate was found increased in PHPs (p < 0.05), more than half of the labeled biopsies were without periosteal tetracycline in patients, and only 2 of 18 biopsies from normals contained periosteal tetracycline labels. No significant decreases in cortical width or relative cortical width were found in PHPs. In both patients and controls an age-related decrease in relative cortical width cortical width were found in PHPs. In both patients and controls an age-related decrease in relative cortical width was noted for women (PHPs: r = -0.52, p < 0.01; controls: r = -0.59, p < 0.001), but not for men. Cortical porosity was about 30% increased in PHPs (p < 0.02). Only normal women showed a positive age-related increase in porosity (r = 0.61, p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Ultrastructural investigations of bone resorptive cells in two types of autosomal dominant osteopetrosis.

In order to investigate the ultrastructure of bone resorptive cells in the two types of adult benign human osteopetrosis, iliac crest biopsies were obtained from 11 patients and 10 normal males, who served as a control group. Six patients had the radiological type I (4 women, 2 men, aged 23-58 years, mean = 36.5 years), and 5 type II disease (5 men, aged 20-48 years, mean = 29.8 years). The normal controls (aged 23-48 years, mean 34.1 years) were recruited from the medical staff. The biopsies were immediately divided. From each patients, half was embedded in paraffin for histochemistry and light microscopy, and half in epon for transmission electron microscopy. The osteoclasts were markedly reduced in number and size in Type I disease (0.2 +/- .7 cells vs. 2.9 +/- 1.0 cells per 2.7 mm2 of bone area, p < 0.01) compared to controls, and stained only weakly for tartrate-resistant acid phosphatase (TRAP). At the ultrastructural level, no signs of active bone resorption were identified, whereas numerous mononuclear cells were observed at the bone surfaces. In type II disease, the osteoclasts were large and highly multi-nucleated, with an increased number (8.3 +/- 2.3 cells vs. 2.9 +/- 1.0. cells per 2.7 mm2 of bone area, p < 0.01) compared to controls. In all patients with this type, but never in type I or in the controls, a smooth, TRAP-positive substance was seen between the osteoclasts and the bone surface. Ultrastructurally, this substance was amorphous, with a condensation along the cell membrane.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

The effect of long-term exercise on vertebral and femoral bone mass, dimensions, and strength--assessed in a rat model.

The rat model has previously been used to test the effect of ovariectomy and of PTH administration on vertebral bone mass, size, and biomechanical competence. In this study, we used the same "biomechanical rat model" to assess the effect of long-term exercise on vertebral bone mass and quality and also on femoral bone mass, dimensions, and strength. Sixty female Fischer rats were randomized into four groups. Two groups were exercised for 5 days a week on a treadmill with a running distance of 2 km per day. The exercise program was initiated at the age of 2 months. The two exercise groups were investigated after 4 and 10 months. Two sedentary groups (observed for 4 and 10 months) served as controls. At death, three lumbar vertebral bodies (L4-L6) and the left femur were obtained from each rat, and changes in bone mass (ash density, trabecular bone volume [BV/TV]), bone size, and biomechanical competence were assessed. The results revealed an age-related (4-10 months) increase in vertebral bone mass and strength. The additional effect of exercise on the vertebral bodies was an increase in cross-sectional area and bone biomechanical competence. In the femoral bone specimens, an age-related increase in bone mass, size, and strength was also disclosed, and while exercise by itself had no significant influence on biomechanical parameters it did reduce cortical-endosteal bone resorption. The study has demonstrated an anabolic effect of a light exercise regimen on both femoral cortical bone and vertebral bodies (mainly trabecular bone).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗