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L Mosekilde

Publications and source records attributed to L Mosekilde.

At least 271 records · Page 15Linked to original sources
PubMed1988

Age-related changes in vertebral trabecular bone architecture--assessed by a new method.

Cylindrical trabecular bone specimens (d = 7 mm) were drilled in a vertical direction from the central part of the third vertebral body (L3) from 23 normal individuals aged 15-87 years (10 males and 13 females). The bone samples were embedded in methylmetacrylate and sawn in 400 microns thick sections with an arbitrary rotation but a fixed vertical axis. The sections were investigated in polarized light at a magnification of x 8. By using this technique, vertical and horizontal trabeculae were clearly separated due to different colors. Photographs were taken. These were magnified, and trabecular thickness and intertrabecular distance were measured, using a Zeiss-integration plate II. A significant age-related decrease was found in the mean horizontal trabecular thickness (r = -0.71, p less than 0.001), while the mean thickness of the vertical trabeculae was unchanged with age (r = 0.06, n.s.). Furthermore, a significant increase was found both for the mean distance between the horizontal trabeculae (r = 0.79, p less than 0.001) and between the vertical trabeculae (r = 0.75, p less than 0.001). The present study gave a clear and striking visual presentation of both the thinning and disappearance of the horizontal supporting struts in the vertebral trabecular lattice and the total removal of some of the vertical trabeculae--leading to the dramatic loss of bone strength previously demonstrated.

Adolescent↗
PubMed1988

Serum vitamin D metabolites and nuclear uptake of (3H)-1,25-dihydroxyvitamin D3 in monocytes from patients with autosomal dominant osteopetrosis: a study of two radiological types.

The nuclear uptake of (3H)-1,25 dihydroxyvitamin D3 in freshly isolated human monocytes and the serum levels of 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D were investigated in 13 patients with autosomal dominant osteopetrosis and in sex- and age-matched controls. Seven patients had type I osteopetrosis characterized by diffuse, symmetrical osteosclerosis with pronounced sclerosis of the skull and increased thickness of the cranial vault. The other six patients had type II with "Rugger Jersey Spine" and "endobones" as characteristic findings. In type I osteopetrosis the serum 1,25-dihydroxyvitamin D was significantly reduced (p less than 0.05), whereas serum 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D receptor binding were normal. In type II osteopetrosis the serum vitamin D metabolites were normal, as was the maximal binding capacity (Bmax) of 1,25-dihydroxyvitamin D to the nuclear receptor. The dissociation constant (Kd), however, was significantly increased (p less than 0.01) indicating a modest resistance to 1,25-dihydroxyvitamin D. It is concluded that a general end-organ resistance to 1,25-dihydroxyvitamin D at the receptor level does not exist in type I osteopetrosis, but may contribute to some of the radiological and biochemical findings in type II.

Adult↗
PubMed1988

The effects of short-term, high-dose treatment with prednisone on the nuclear uptake of 1,25-dihydroxyvitamin D3 in monocytes from normal human subjects.

Animal and cell culture studies indicate glucocorticoid regulation of 1,25-dihydroxyvitamin D3 receptors and interference with cellular effects of vitamin D. These investigations prompted us to examine the effects of prednisone on the nuclear uptake of 1,25-dihydroxyvitamin D3 in freshly isolated human monocytes. Eighteen normal subjects were studied in a randomized, double-blind, placebo-controlled study. Analysis of receptor kinetics revealed that the maximal nuclear uptake (Bmax) of (3H)-1,25-dihydroxyvitamin D3 in monocytes decreased 40% (P less than .001) after prednisone treatment. In the group treated with prednisone (40 mg/d for 5 days) s-1,25-dihydroxyvitamin D increased 46% (P less than .01). S-25-Hydroxyvitamin D, S-phosphat, S-calcium, and S-iPTH remained unchanged. Osteoblastic production of the matrix protein, bone gla protein (BGP) is stimulated by 1,25-dihydroxyvitamin D3. However, despite increased serum levels of 1,25-dihydroxyvitamin D3, the prednisone-treated group revealed a 75% reduction in s-BGP. The present data indicate that corticosteroids decrease the nuclear uptake of 1,25-dihydroxyvitamin D3 in human monocytes. Further investigations are necessary, however, to elucidate the biologic mechanism for this observation and whether the mechanism is operative in other human tissues including bone.

Adult↗
PubMed1988

Biochemical evidence of disturbed bone metabolism and calcium homeostasis in two types of autosomal dominant osteopetrosis.

Biochemical markers of bone resorption and bone formation were measured in 14 patients with autosomal dominant osteopetrosis, and compared with age- and sex-matched controls. There were eight patients with the radiological type I characterized by diffuse, symmetrical osteosclerosis with pronounced sclerosis of the skull and enlarged thickness of the cranial vault, and six patients with type II characterized by diffuse, symmetrical osteosclerosis, "Rugger-Jersey spine" and "endobones" (bone within a bone) in the pelvis. Serum levels of alkaline phosphatase and osteocalcin in types I and II did not differ from controls indicating normal bone formation. However, a significantly decreased fasting renal excretion of phosphate and hydroxyproline in both types compared with normal controls, suggests a reduced bone resorption. Serum levels of parathyroid hormone (PTH), albumin-corrected calcium, phosphate, and acid phosphatase were normal in type I. In type II serum levels of albumin-corrected calcium and PTH were significantly increased (p less than 0.05 and p less than 0.01). The level of acid phosphatase was markedly increased in this type (p less than 0.01). These findings suggest differences between the two types in calcium homeostasis and bone metabolism, and thus corroborate the evidence that the two radiological types reflect two different disorders of bone resorption.

Adult↗
PubMed1988

The effect of single oral doses of prednisone on the circadian rhythm of serum osteocalcin in normal subjects.

Serum osteocalcin (OC), which is a sensitive marker of bone formation, is reduced during chronic glucocorticoid treatment in accordance with the finding of reduced bone formation, and even short term glucocorticoid treatment reduces serum OC. In a double blind placebo-controlled study, we measured the effects of 2.5 and 10 mg prednisone, orally, on the circadian variation of serum OC in 15 normal subjects (8 women and 7 men), aged 22-46 yr. All subjects were studied twice at an interval of 1 week. Blood samples were collected every 60 min from 1630 until 1700 h the following day. Prednisone or placebo was given at 2000 h. Serum OC was measured by an in-house RIA. After placebo administration serum OC increased from 2230 h to a peak value around 0230 h, followed by a gradual decline to a nadir around 1500 h. Both doses of prednisone inhibited and even reversed the nocturnal rise in serum OC levels; the inhibition occurred within 3-4 h. There was no significant difference in the time from prednisone ingestion to maximal decrease (7.2 h vs. 9.8 h) or in the maximal decrease (52% vs. 54%). However, the duration of the inhibition was significantly shorter after 2.5 mg than after 10 mg prednisone (approximately 6 h vs. 12 h; (p less than 0.01). We conclude that serum OC is sensitive to small doses of prednisone, and that serial serum OC measurements may be a sensitive marker of the effect of exogenous glucocorticoids on osteoblastic activity in vivo.

Administration, Oral↗
PubMed1988

The effects of high-dose glucocorticoid administration on serum bone gamma carboxyglutamic acid-containing protein, serum alkaline phosphatase and vitamin D metabolites in normal subjects.

The effects of 40 mg of prednisone given daily for 5 days to normal individuals on serum levels of bone Gla-protein (BGP), alkaline phosphatase, calcium phosphate, 25-hydroxyvitamin D, 1,25-dihydroxyvitamin D and immunoreactive parathyroid hormone (S-iPTH) and on renal excretions of calcium, phosphate and hydroxyproline were evaluated in a double-blind, placebo controlled study. In the prednisone group a 75% decrease (P less than 0.001) was found in serum BGP compared to a 6% decrease (P less than 0.05) in serum alkaline phosphatase. The renal hydroxyproline excretion remained unchanged. Serum calcium was unchanged while the fasting urinary calcium excretion showed a 2-fold increase (P less than 0.001). Serum 1,25-dihydroxyvitamin D increased (P less than 0.01) in spite of unchanged serum 25-hydroxyvitamin D, serum phosphate and parathyroid function (as judged by S-iPTH and the maximal tubular reabsorption capacity for phosphate (TmP/GFR]. The data suggest a direct inhibition of osteoblast number and/or function by short-term glucocorticoid administration with unchanged bone resorption leading to a negative bone mineral balance. The increase in serum 1,25-dihydroxyvitamin D is probably due to a direct stimulation by glucocorticoids of the renal 1 alpha-hydroxylase. The effects of the vitamin D metabolite, however seem to be blunted.

Adult↗
PubMed1988

[Osteomalacia].

Explore the source record for details and available documents.

Humans↗
PubMed1987

Etidronate disodium in the management of malignancy-related hypercalcemia.

To evaluate the efficacy of intravenous etidronate disodium (etidronate) in controlling hypercalcemia of malignancy, 20 patients with known malignant disease and hypercalcemia were randomly assigned on a two-to-one basis to receive etidronate, 7.5 mg/kg of body weight, or placebo for three to five days. All patients received 3,000 ml of saline and 40 mg of furosemide per day. Eighteen patients completed the study. Eleven of 12 patients (92 percent) in the etidronate group attained normocalcemia, compared with two of six (33 percent) in the placebo group (p = 0.05). The etidronate group showed a greater decrease in the serum calcium level than did the placebo group (p less than 0.02). Renal calcium excretion decreased significantly in the etidronate group but not in the placebo group. Intravenous etidronate in combination with rehydration and furosemide constitutes a safe and effective alternative in the treatment of hypercalcemia of malignancy.

Adult↗
PubMed1987

Compressive strength, ash weight, and volume of vertebral trabecular bone in experimental fluorosis in pigs.

The aim of the investigation was to measure the effect of fluoride on vertebral trabecular bone compressive strength and to correlate this with fluoride-induced changes in bone density. This correlation would express changes in the quality of bone during fluoride treatment. Pigs were used in the experiment because their trabecular bone structure and remodeling sequences are very similar to the human. Eight animals receiving a supplement of 2 mg F-/kg b.w. per day from age 8-14 months were compared with 8 control animals. Morphologic measurements in the animals receiving fluoride supplement showed a significant increase of 17% in bone density and a smaller, insignificant increase of 3% in ash weight analyses. Meanwhile, the mechanical parameters for the fluorotic animals were unchanged (maximum compressive strength, maximum stiffness, and energy-absorption capacity) or decreased (normalized compressive strength = maximum compressive load corrected for ash density). It is concluded that the increased bone mass during the initial stages of fluoride treatment does not necessarily indicate an improved bone quality. The discrepancy between bone mass and strength could be either a permanent or a temporary phenomenon and requires further investigation.

Animals↗
PubMed1987

Bone turnover and balance evaluated by a combined calcium balance and 47calcium kinetic study and dynamic histomorphometry.

Bone resorption and formation rates were evaluated at the organ level using calcium kinetic methods and at the trabecular bone tissue level using dynamic histomorphometry in 20 patients with various metabolic bone diseases (primary hyperparathyroidism (N = 9), hyperthyroidism (N = 6), and hypothyroidism (N = 5). Highly significant correlations were demonstrated between resorption and formation rates at organ level (r = .90, P less than .001) and at tissue level (volume referent) (r = .93, P less than .001), indicating a high degree of coupling between resorption and formation within the three disease states. Tissue level resorption rates (surface referent, as well as volume referent) both correlated significantly (P less than .01) to organ level resorption rate (r = .60 and r = .63, respectively). Fractional active resorption surface and cellular level resorption rate did not reveal significant correlations to calcium kinetic estimates. No correlation could be demonstrated between organ level mineralization rate and formative or labeled trabecular surfaces. However, all tetracycline based tissue level formation rates revealed highly significant correlations (P less than .01) to organ level mineralization rate (calcification rate, r = .71; surface referent bone formation rate, r = .59; volume referent bone formation rate, r = .68). Based on histomorphometric parameters for resorption and formation, actual and predicted tissue level trabecular bone balances were calculated. Both the actual and predicted bone balance correlated significantly to the organ level calcium balance (P less than .05). Correction for skeletal size based on BMC measurements did not improve any of the correlations significantly.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1987

Exogenous triiodothyronine activates bone remodeling.

The effect of exogenous triiodothyronine (T3) as an activator of bone remodeling was investigated by measuring biochemical marker levels. Fourteen people received 100-160 micrograms of T3 for 1 week and were followed for a total of 10 weeks. Serum T3 increased markedly during the first week, whereas serum TSH and serum thyroxine (T4) decreased. Bone resorption was stimulated during the first week as evaluated from serum calcium and renal excretion of calcium, phosphate, and hydroxyproline. Serum osteocalcin showed an increase in the first week, probably caused by stimulation of existing osteoblasts. Serum alkaline phosphatase increased from week 6 to week 8, and serum osteocalcin increased at week 8 to a level higher than the initial level. The results indicate that T3 acts as an activator of bone remodeling and initiates bone resorption followed by bone formation. The observed timetable for the remodeling sequence is in accordance with that obtained by bone histomorphometry. Osteopenic states may be treated by synchronizing the skeletal remodeling processes and then selectively depressing bone resorption with calcitonin or diphosphonates (ADFR treatment). Synchronization may be achieved by short-term treatment with a drug that stimulates the formation rate of new remodeling cycles (an activator). The results from this study indicate that exogenous T3 may be used as an activator.

Adult↗
PubMed1987

Biomechanical competence of vertebral trabecular bone in relation to ash density and age in normal individuals.

Cylindrical trabecular bone samples from the central part of the first lumbar vertebral body were obtained from 42 normal people (27 females and 15 males) aged 15-87 years and analyzed by a compression test in either vertical or horizontal direction. Maximum stress, maximum stiffness, energy absorption capacity, and strain at maximum stress (compressibility) were calculated from the load-deformation curves. The ash density of the samples was measured after incineration. From age 20 to 80 years, the decline (P less than 0.01) in ash density was 48-50% compared to a 75-80% decrease (P less than 0.001) in vertical stress, stiffness, and energy absorption capacity. Qualitatively similar age-related changes (P less than 0.01) were observed by horizontal compression, but the absolute values were smaller. In both directions, highly significant positive correlations (P less than 0.01) were observed between the biomechanical properties and ash density stress, stiffness and energy absorption capacity still showed significant decreases with age (P less than 0.01). The vertical maximum strain values, which increased (P less than 0.05) with age, were inversely related to the other biomechanical variables (P less than 0.05) and to the ash density (P less than 0.05). It is concluded from the study that the biomechanical competence of vertebral trabecular bone depends not only on bone mass (ash density) but also on the continuity of the trabecular lattice, which changes with increasing age.

Adolescent↗
PubMed1987

Bisphosphonate whole body retention test: relations to bone mineralization rate, renal function and bone mineral content in osteoporosis and metabolic bone disorders.

The bisphosphonate whole body retention test (WBR) has been used to estimate bone mineralization rate (bone turnover). Bisphosphonates given i.v. are taken up by bone or excreted in urine. The aim of the present investigation was to test the efficacy of WBR in estimating bone mineralization rate (m) and to evaluate the influence of renal function (Clcr) and bone mass (forearm bone mineral content; BMC) on WBR. The 24-h retention of 3.7 MBq 99mTc-HMBP (1-hydroxymethylene-1,1-bisphosphonate) (Osteoscan) given i.v. was measured by a medium sensitive whole body counter in thirty-one patients with hyperparathyroidism (n = 14), hyperthyroidism (n = 8) or hypothyroidism (n = 9) (group 1) and in seventy-six females with postmenopausal spinal crush fracture osteoporosis (group 2). In the same individuals m was calculated from a 7-day 47Ca-kinetic study using the expanding calcium pool model. Multiple regression analysis of WBR vs. m and Clcr in group 1 disclosed that WBR correlated positively to m [rp = 0.49, P less than 0.01 (rp = partial correlation coefficient)] and inversely to Clcr (rp = -0.44, P less than 0.02). Inclusion of BMC in the analysis did not reveal any significant partial correlation between WBR and BMC (rp = -0.33, 0.05 less than P less than 0.10). In group 2 WBR correlated inversely to Clcr (rp = -0.48, P less than 0.001) but showed no significant relation to m (rp = 0.10, NS).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1987

Safety of osteoporosis treatment with sodium fluoride, calcium phosphate and vitamin D.

During an 8-year period, 163 consecutive patients with spinal crush fracture osteoporosis started a 5-year treatment with a combination of sodium fluoride (60 mg/day), calcium phosphate (45 mmol/day) and vitamin D2 (18,000 IU/day), and were followed in the outpatient clinic every 3 months. Fourty-three patients completed the 5-year treatment. Mean observation time was 2.8 years, totalling 460 patient-years. Fifty-one percent of the patients experienced joint-related (37%) or gastrointestinal (25%) side effects at one time or another. All side effects subsided after a median 6-week withdrawal of fluoride. Six percent of the patients withdrew from treatment due to side effects. Mean serum calcium values slightly decreased during treatment and no hypercalcemic episodes were seen. Urinary excretion of calcium did not change during treatment. No changes in renal, bone marrow or thyroid functions could be detected. The liver function might be slightly affected as indicated by minute increases in serum bilirubin and decreases in serum coagulation factors and albumin, but no other changes in liver function were observed.

Adolescent↗
PubMed1986

Mechanical properties of collagen from decalcified rat femur in relation to age and in vitro maturation.

Cortical bone collagen was obtained by decalcifying femoral bones from 2-, 5-, 15-, and 25-month-old male rats. Collagen specimens were cut longitudinal to the long axis of the femur and tested mechanically. The maximum load (ultimate strength) and maximum slope of the load-strain curve (maximum stiffness) were found to decrease with age. The age-related reduction in the mechanical parameters resulted from a change in the mechanical strength of the constituent collagen and a change in the morphology of the bone tissue. In vitro aging, produced by incubating for 0-5 months, did not change the mechanical strength of bone collagen specimens obtained from 2-month-old rats. The changes in the mechanical characteristics of bone collagen, accompanying in vivo and in vitro aging are the opposite of those observed in soft tissue collagen. In the latter there is an increase in the mechanical strength during in vivo and in vitro aging.

Animals↗
PubMed1986

Normal vertebral body size and compressive strength: relations to age and to vertebral and iliac trabecular bone compressive strength.

Three thoracic (T5-T7) and three lumbar (L1-L3) vertebral bodies and the anterior parts of both iliac crests were removed from 44 normal individuals aged 15-87 years who had died suddenly. Small, cylindrical samples of trabecular bone (length 5 mm, diameter 7 mm) from T6, L1, and L3 and from the standard site for iliac crest biopsies were compressed in an Alwetron-250 materials testing machine. Whole vertebral bodies from T5, T7, and L2 with cut planoparallel end-plates were compressed in an Instron materials testing machine. The maximum compressive stress value sigma max of the whole vertebral bodies and of the vertical vertebral trabecular bone decreased with age with almost parallel linear regression lines. At any age the sigma max for whole vertebral bodies was about 1.6 MPa (1 MPa = 100 N/cm2) higher than for the trabecular bone. The average cross-sectional area of the vertebral bodies increased by 25-30% from the age of 20 to 80 years. The anisotropic properties of the vertebral trabecular bone (expressed as the ratio between the vertical and horizontal sigma max) increased markedly with age. A highly significant positive correlation was observed between the vertical vertebral trabecular bone sigma max (X) and the total vertebral body sigma max (y = 0.90x + 1.75, r = 0.88, P less than 0.01). The slope was not significantly different from 1, whereas the intercept was positive (P less than 0.01). The average total vertebral body sigma max (range 1.5-7.8 MPa) could be predicted from mechanical tests on horizontal iliac crest bone biopsies with standard error of estimate (SEE) of 0.92 MPa.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗