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L Mosekilde

Publications and source records attributed to L Mosekilde.

At least 163 records · Page 9Linked to original sources
PubMed1995

Assessing bone quality--animal models in preclinical osteoporosis research.

As new agents are developed for osteoporosis prevention and intervention, the need for reliable animal models becomes more pressing. At the same time, the necessity of not focusing on bone mass as the sole efficacy parameter has become apparent. Before accepting any agent for clinical osteoporosis trials, FDA now requires that it has proven its efficacy in a small animal model and also in a larger animal model with known intracortical bone remodeling. This efficacy should be proven both concerning bone mass and bone biomechanical competence. In this paper, methods for testing bone quality in small and large animal models are presented, and the necessity of testing several skeletal sites: vertebrae, long bones, and femoral necks is discussed.

Animals↗
PubMed1995

Reconstruction of cortical bone remodeling in untreated primary hyperparathyroidism and following surgery.

Iliac crest bone biopsies from 39 patients (23 women, 16 men) with untreated primary hyperparathyroidism (PHP) were examined. Static histomorphometric parameters for cortical bone was compared with values obtained from 39 age- and sex-matched normal controls. Thirty-five of the patients were double-labeled with tetracycline before biopsy. The cortical remodeling cycle was reconstructed in these patients and compared with 24 sex-matched but younger normal controls. In 9 patients, a second intact bone biopsy was obtained 6-12 months after successful surgery for PHP. In these patients, pre- and post-treatment biopsies were compared. Cortical porosity was increased in PHP (p < 0.001) due to a high turnover state with expansion of the remodeling space (p < 0.001). The net balance of the remodeling cycle on the haversian surface was found unchanged in PHP, since the average haversian canal diameter remained unchanged. In the female PHP-patients, a significant increase in the final resorption depth (p < 0.01) was balanced by a proportional increase in the wall width (p < 0.001). Among all PHP patients, no significant decrease in cortical width was found. However, a significant reduction in absolute (p < 0.05) and fractional cortical width (p < 0.05) was seen in postmenopausal PHP women giving rise to a cortical bone loss. Reconstruction of the cortical remodeling cycle revealed a doubling in activation frequency from 0.6#/year in normals to 1.2#/year in PHP (p < 0.001), giving rise to a high turnover state. Surgical cure of PHP was accompanied by marked changes in cortical bone metabolism.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1995

Effects of fluoride on rat vertebral body biomechanical competence and bone mass.

For more than 30 years, sodium fluoride has been a commonly used therapeutic agent for established osteoporosis because of its repeatedly documented anabolic effect on trabecular bone mass. Recent clinical and experimental studies have, however, indicated a possible detrimental effect of fluoride on bone strength. Thus, the efficacy of fluoride therapy remains a controversial issue. The aim of this study was to investigate the effect of fluoride on both vertebral bone mass and quality in rats. Twenty-nine 3-month-old, female rats were randomized into three groups. One group served as a control group, and the other two groups received fluoridated water at different doses (100 ppm and 150 ppm). The rats were followed for 90 days. Three lumbar vertebrae were obtained from each rat, and changes in bone fluoride content, bone mass and biomechanical competence were assessed. The results revealed a significant increase in bone fluoride content, ash density and trabecular bone volume after fluoride treatment. Directly obtained load values and load corrected for cross-sectional area were constant. Load corrected for ash content, which is a measure of bone quality, decreased significantly after fluoride therapy. It is concluded that the increase in bone mass during fluoride treatment does not translate into an improved bone strength and that the bone quality declines. This investigation thereby supports the hypothesis of a possible negative effect of fluoride on bone quality.

Animals↗
PubMed1995

Epidemiology of osteoporosis. Implications for drug therapy.

Osteoporosis represents a major health problem. Fractures secondary to decreased bone mass and disrupted bone structure vastly increase morbidity in postmenopausal women, and morbidity as well as mortality in elderly people of either sex. Prophylaxis is possible, and indeed appears to be vital to ensure a high peak bone mass. Peak bone mass is reached during the second or third decade of life, i.e. 20 to 50 years before the appearance of osteoporotic fractures. Exercise and a sufficient calcium intake are possible measures in the early years. During menopause, estrogen replacement therapy will delay the accelerated bone loss and, most likely, also osteoporotic fractures. In established osteoporosis, a number of well documented therapies are now available. Depending on the age of the patient, bisphosphonates, calcitriol or other vitamin D preparations, calcium and calcitonin may be employed. This article reviews the epidemiology of osteoporotic fractures with special reference to the therapeutic implications.

Calcium, Dietary↗
PubMed1995

[Vitamin D and osteoporosis].

Vitamin D constitutes a complex endocrine-regulated system, and is both a prohormone for the endogenous synthesis of the active hormone, calcitriol, and a vitamin which may be administered to supply the organism's requirements. No single test or investigation is available for the demonstration of vitamin D deficiency. Both vitamin D intake and ability to synthesise vitamin D decrease with increasing age, and particularly the elderly in institutionalised care are at risk of developing vitamin D deficiency. Iceland excepted, mean daily vitamin D consumption in the Nordic countries is less then 5 micrograms; and in approximately 10-25 per cent of the population, daily intake is less than 2.5 micrograms which is insufficient to maintain an adequate serum calcidiol concentration in individuals unexposed to sunlight. The recommended daily intake of 5 micrograms, currently adopted in the Nordic countries, may be too low-an intake of 10 micrograms is probably necessary to satisfy requirements in the elderly.

Adrenal Cortex Hormones↗
PubMed1995

Additional weight-bearing during exercise is more important than duration of exercise for anabolic stimulus of bone: a study of running exercise in female rats.

Mechanical loading is necessary for maintenance of skeletal integrity, but the most effective type, intensity, and duration of exercise are not known. In vivo experiments have indicated that the strain generated by the stimulus is more important than the duration of the stimulus. To elucidate this question, we studied 5-month-old female Wistar rats exercised on a motor-driven exercise belt for 17 weeks, 5 days per week (average velocity 20 m/min). Group 1 served as controls, group 2 was trained for 30 min, group 3 was trained for 30 min with a 50-g backpack, and group 4 was trained for 15 min with a 50-g backpack. Total body bone mineral content (BMC), bone mass of the lower extremities (LEBMC), total body lean soft-tissue mass (LSTM), and total body fat-tissue mass (FTM) were measured by dual-energy absorptiometry (DXA) at 0, 6, and 17 weeks. The BMC increased more in group 4 than in controls (15% vs. 8%, p < 0.03). In the other two intervention groups, no significant increases of total body BMC occurred compared with controls, although a trend was observed (12%). The LEBMC increased significantly in all exercising groups after 17 weeks, being 16% in group 2, 15% in group 3, and 20% in group 4, compared with 6% in controls (p < 0.05). The increase in LSTM after 6 weeks was most pronounced in group 3, at 20%, compared with 10% in the control group (p < 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Absorptiometry, Photon↗
PubMed1994

[Glucocorticoid-induced osteopenia].

This article reviews the pathogenesis of glucocorticoid-induced osteopenia (GIO). GIO is a result of direct and indirect mechanisms leading to: 1) decreased intestinal calcium absorption, 2) decreased renal calcium reabsorption, 3) increased osteoclast activity with increased bone resorption, 4) decreased osteoclast activity with decreased bone formation. The mainly osteoclast activity is raised on the basis of secondary hyperparathyroidism. The different possible treatments in order to prevent GIO are reviewed on the basis of the results of the most important studies about the subject. We conclude that before a secure recommendation about prophylactic treatment can be made more prospective studies with fracture incidence as a measure should be made. However, on the basis of the studies that have already been made, it seems rational to give patients in longterm glucocorticoid treatment a calcium supplement of 0.5-1 g/day either in tablet form or by changing the diet, combined with a vitamin-D supply: either ergocalciferol 600-800 IU/day (e.g. in the form of 2 multivitamin tabs/day) or calcitriol 0.5 microgram/day.

Bone Diseases, Metabolic↗
PubMed1994

[The importance of nutrition for the prevention of osteoporosis].

The prevalence of osteoporosis is increasing, and is a significant burden on society. Dietary composition is an important determinant of the bone mineral density in the growth period, and of the magnitude of the age related bone mineral loss, in particular among postmenopausal women. Therefore, an improvement of the diet has an important role in the prevention of osteoporosis. A sufficient intake of calcium and vitamin D can reduce the risk of fractures in postmenopausal women, and it is likely that a low calcium intake may affect peak bone mass negatively. Calcium in the Danish diet comes mainly from dairy products. Half a litre of milk and 25 g of cheese will cover most people's calcium requirement. Part of the calcium requirement may also be covered by consuming other foods such as cabbage, broccoli and beans. Children, adolescents and elderly individuals who avoid dairy products are recommended to take a calcium supplement. The status of vitamin D among the elderly can be improved by a daily outdoor stay and by a frequent intake of fatty fish such as herrings. Elderly persons who stay indoors are recommended to take a vitamin D supplement.

Adolescent↗
PubMed1994

Long-term exercise of young and adult female rats: effect on femoral neck biomechanical competence and bone structure.

The present study was designed to examine the effect of exercise on femoral neck bone structure and strength in female rats after 4 and 10 months of exercise. Female Fischer rats aged 2 months were exercised for 4 h a day, 5 days a week on a motor-driven treadmill the speed of which was gradually increased until a daily distance of 2 km was reached. The training level was maintained for 4 months (n = 15) and 10 months (n = 15). Sedentary age-matched rats served as controls (n = 30). At death the proximal third of both femora was obtained from each rat. The left femoral neck was tested in a materials-testing machine, and the right was used for either trabecular bone mass measurement (BV/TV) or scanning electron microscopy (SEM). Biomechanical testing revealed a significant training-induced increase in femoral neck bone strength after 4 months of exercise, which although not accelerated was preserved after 10 months of exercise. Histologic investigation revealed a significant training-induced increase in BV/TV, accounted for by a significantly smaller proportion of marrow space. No difference in cortical area was found. Both histology and SEM revealed a tendency to an earlier closure of the growth line in the exercised animals. However, the exercised animals aged 6 months had a significantly increased total femoral length compared with the sedentary rats. No difference was found in total femoral length between sedentary and exercised rats aged 12 months. On the basis of this study, it is concluded that exercise has a positive effect on femoral neck bone strength.(ABSTRACT TRUNCATED AT 250 WORDS)

Aging↗
PubMed1994

Normal osteoclastic and osteoblastic responses to exogenous growth hormone in patients with postmenopausal spinal osteoporosis.

The cause of bone loss in patients with osteoporosis is not known, but both increased bone resorption and decreased bone formation have been reported. Theoretically, these effects may result from either increased activity of osteoclasts or decreased activity of osteoblasts, or both. In vivo, growth hormone (GH) administration leads to activation of osteoclasts and osteoblasts as evidenced by increased biochemical markers of bone resorption and bone formation. To test for disturbances in responsiveness of bone cells to exogenous hormonal stimuli in osteoporosis, we compared 15 patients with postmenopausal osteoporosis with 15 healthy age-matched postmenopausal women before and during a 3 day stimulation test with GH (0.2 IU/kg/day). Serum insulin-like growth factor I increased in both groups (p < 0.001). GH treatment increased biochemical markers of bone resorption (serum carboxyl-terminal telopeptide of type I collagen [ICTP] [p < 0.001] and, to a lesser extent, 24 h urinary hydroxyproline/creatinine) in the two groups. Similarly, biochemical markers for bone formation increased in both groups [osteocalcin (p < 0.01) and procollagen type I C-terminal propeptide, PICP (p < 0.001)]. GH treatment reduced alkaline phosphatase (ALP, p < 0.05) and its bone-specific isoenzyme (bone ALP, p < 0.01) in both groups. The maximal response, the area under the curve (AUC) of response curves for IGF-I, bone resorption markers, and bone formation markers were not different between groups. Our data do not support the hypothesis that osteoporotic patients display major disturbances in responsiveness to GH.

Aged↗
PubMed1994

Surgically induced uremia in rats. II: Osseous PTH-susceptible signaling systems as predictors of bone resorption.

Predicting the course of parathormone (PTH)-elicited bone turnover in both humans and experimental rat models with moderate chronic uremia, using only standard clinical chemistry analyses, is often difficult. Consequently, rat bone from 1 + 2/3 nephrectomized animals, after 230 days of progressive renal failure, was examined for PTH-stimulated adenylate cyclase (AC) and phospholipase C (PL-C) activities. Correlations to biological parameters related to the function of bone and kidney were made. Reduced renal function was demonstrated by increased serum creatinine; circulating 1,25 dihydroxyvitamin D3 below detection level; diminished renal PTH-elicited AC activity; and decreased urinary cAMP excretion. PTH-activated renal PL-C was also reduced. However, no significant differences were seen in urine creatinine, calcium, phosphate, and hydroxyproline, nor in serum PTH, alkaline phosphatase, calcium, and phosphate. Notwithstanding, renal osteodystrophy developed as estimated by increased plasticity of the long bones, as well as reduction of the diaphyseal (Dd) and inner femoral mid-shaft (Di) diameters. Femoral cancellous bone exhibited a substantial elevation of both eroded surface (ES) and osteoid surface (OS) as well as a marked reduction in trabecular bone volume (TBV). Calvarial PTH-activated AC was enhanced, whereas corresponding PL-C was markedly reduced. PTH-enhanced AC correlated positively with ES and negatively with Di, respectively. PTH-enhanced PL-C, however, correlated positively with bone calcium content and negatively with ES. Our results indicate that bone modeling and remodeling are to a large extent related to PTH-elicited signaling systems, and cannot easily be predicted by standard clinical chemistry analyses.

Adenylyl Cyclases↗
PubMed1994

Human marrow stromal osteoblast-like cells do not show reduced responsiveness to in vitro stimulation with growth hormone in patients with postmenopausal osteoporosis.

Decreased osteoblastic activity seems to play an important role in the pathogenesis of postmenopausal osteoporosis. The aim of the present study was to examine the direct effects of human growth hormone (GH) on proliferation and differentiation of osteoblastic cells obtained from patients with postmenopausal osteoporosis and age-matched normals and to compare the cellular responses induced by GH between the two groups. Osteoblast cultures (human marrow stromal osteoblast-like cells) were established from bone marrow aspirates obtained from 9 osteoporotic patients and 12 age-matched normals. Effects on cell proliferation and cell differentiation markers [alkaline phosphatase (AP)], procollagen type I propeptide (PICP), and osteocalcin] were assessed. GH stimulated 3H-thymidine incorporation into DNA in cell cultures of osteoporotic patients to a maximum of 158 +/- 14% of no-treatment controls (n = 9, P < 0.001) and to 203 +/- 52% (n = 9, P < 0.001) in normals. GH increased cell number as measured by methylene blue (MB) assay in cells of osteoporotic patients to 138 +/- 10% (P < 0.05, n = 7) and in normals to 138 +/- 12 (P < 0.05, n = 7). GH alone reduced cellular AP production: 61 +/- 3.8% (P < 0.05, n = 7) versus 65 +/- 16% (P < 0.05, n = 7) and cellular PICP production: 79 +/- 6% (P < 0.05, n = 7) versus 69 +/- 16% (n.s., n = 7), in cell cultures of osteoporotics and normals, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1994

Effects of salmon calcitonin suppositories on bone mass and turnover in established osteoporosis.

The objective of this study was to test the efficacy and safety of salmon calcitonin (sCT) suppository in post-menopausal women with previous hip fractures as an inhibitory agent of bone loss. The study was a single blind, randomized, and placebo-controlled trial comparing three parallel groups of patients. Fifty-four healthy women were randomly allocated to 1 year's treatment with either sCT 100 IU/6 times a week, 200 IU/3 times a week, or placebo/6 times a week. All groups received a calcium supplement of 500 mg daily. Fifteen patients left the study before its end, six of those due to adverse events, such as abdominal and rectal pain, nausea, headache, and diarrhea. Bone mineral density of the spine and the femoral neck was measured every 26 weeks, and biochemical markers of bone turnover were measured at baseline and week 12, 26, and 52. There were no significant changes in bone mineral density in the spine and in the hip in any of the treatment groups. No significant changes were observed in serum alkaline phosphatase, serum osteocalcin, urine hydroxyproline, and urine pyridinoline or deoxypyridinoline. Conclusively, we did not observe any significant effect on bone metabolism in women with postmenopausal osteoporosis after 1 year of treatment with sCT suppositories at the doses used.

Aged↗
PubMed1994

A comparison of the effects of oestrogen/progestogen, high-dose oral calcium, intermittent cyclic etidronate and an ADFR regime on calcium kinetics and bone mass in postmenopausal women with spinal osteoporosis.

The effects of four different treatments for osteoporosis were compared in a prospective, randomized, 3-year study in 74 postmenopausal women with spinal crush fracture osteoporosis. Patients were randomly assigned to cyclic oestrogen/progestogen therapy (group 1, n = 20), a daily oral calcium dose of 2 g (group 2, n = 17), intermittent cyclic etidronate therapy (group 3, n = 19), or an ADFR treatment with triiodothyronine as activator and etidronate as depressor (group 4, n = 18). Spine and forearm bone mineral content was measured before entry and every 30 weeks. Combined calcium balance and 47Ca kinetic studies were performed before and after 1 and 3 years of treatment. Bone turnover, estimated by serum alkaline phosphatase and renal hydroxyproline excretion, decreased in all four groups during the first half of the treatment period but remained reduced during the second half in groups 1 and 3 only. Group 1 had a significantly positive calcium balance after 60 weeks of treatment. After 150 weeks, the positive effect on calcium balance was significant and greater in groups 1 and 3 than in the other groups. This was achieved by a greater reduction in resorption rate in group 1 at week 60 and in groups 1 and 3 at week 150 as compared with the other groups. Only group 1 had a significant increase in spinal bone mass while a decrease in bone mass at the distal forearm was observed in the etidronate-treated group. We conclude that treatment of postmenopausal osteoporosis with oestrogen/progestogen for 3 years results in net spinal bone gain and a positive effect on calcium balance slightly better than that of intermittent etidronate. These effects were inferior in the groups receiving a large calcium supplementation or the ADFR group where no change in calcium balance or bone mass was found.

Administration, Oral↗
PubMed1994

Spine deformity index in osteoporotic women: relations to forearm and vertebral bone mineral measurements and to iliac crest ash density.

Bone densitometric measurements are widely used for monitoring therapeutic regimens for osteoporosis. However, it is a matter of debate which measurement site is most appropriate for prediction of individual fracture risk. The aim of this cross-sectional study was to investigate the relationship between bone mineral measurements at various sites and spine deformity index (SDI) in osteoporotic women. The SDI was determined in 37 osteoporotic women aged 56-87 years (mean 70.9 years). Peripheral (single-photon absorptiometry of the distal forearm, and iliac crest ash content) and axial (dual-photon absorptiometry of the lumbar spine) bone mass measurements were obtained. SDI increased with age (r = 0.34, p < 0.05), whereas forearm BMC (r = -0.52, p < 0.002) and forearm BMD (r = -0.62, p < 0.0001) decreased. No significant age-related changes were observed in lumbar BMC or iliac crest ash content in these osteoporotic women. A highly significant correlation was found between SDI and lumbar BMC (r = -0.60, p < 0.01). A significant, but less pronounced correlation was found between SDI and forearm BMC (r = -0.37, p < 0.05), whereas no relation was revealed between SDI and forearm BMD or iliac crest ash content. In a multiple regression model, the relationship between lumbar BMC and SDI remained significant after adjusting for the influence of age, whereas the relationship to forearm BMC disappeared. Furthermore, a multiple regression analysis was performed in order to evaluate the ability of all four bone mass measurements and age to predict variations in SDI.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1994

Assessment of bone remodeling using biochemical indicators of type I collagen synthesis and degradation: relation to calcium kinetics.

In this study, we investigated the relation between calcium kinetic indices of bone remodeling (resorption rate, r; and formation rate, m, respectively) and two serum markers of type I collagen turnover: the pyridinoline cross-linked carboxyterminal telopeptide domains of type I collagen (S-ICTP a marker of bone matrix degradation) and the carboxyterminal propeptide of human type I procollagen (S-PICP, a marker of bone matrix formation). We studied three groups: (i) healthy controls (n = 19), (ii) a mixed group of high and low-turnover bone diseases without mineralization defects (myxedema, thyrotoxicosis and primary hyperparathyroidism n = 38), and (iii) osteoporosis (n = 52). In healthy controls, a significant regression of S-PICP on m was obtained (R = 0.53, SEE/Y = 0.44, P < 0.02). Significant regressions were also demonstrable in high- and low-turnover bone disease (R = 0.50, P < 0.001), SEE/Y = 61%) and osteoporosis (R = 0.49, P < 0.001, SEE/Y = 50%). In controls the regression coefficient for the regression of S-ICTP on r was 0.19 (NS), in high and low turnover bone disease 0.66, (SEE/Y = 59%, P < 0.001) and in the osteoporotic group 0.40 (SEE/Y = 61%, P < 0.01). We conclude that S-PICP and S-ICTP reflect whole skeletal bone formation and resorption rates in a variety of metabolic bone diseases including osteoporosis.

Adolescent↗