Biomedical subjects

L Mosekilde

Publications and source records attributed to L Mosekilde.

369 records · Page 21Linked to original sources

PubMedDate not supplied

Stochastic simulation of vertebral trabecular bone remodeling.

Bone remodeling changes bone mass, architecture, and thereby bone strength, during normal aging. These changes seem to be accelerated during the menopause. Several therapeutic agents have been used in order to delay the onset of the menopause-related changes. The effects of these agents on the remodeling process have been determined histomorphometrically in several short-term clinical studies, but data from long-term clinical studies are difficult to achieve, as are data on the influence on bone strength. The aim of this study was to develop a computer stimulation model that could assist in predicting the long-term effects of changes in the remodeling process on bone mass, trabecular thickness, and perforations. The paper presents such a stochastic model of the remodeling process in human vertebral trabecular bone. The computer model is based on histomorphometric and structural data from human studies. It is presented in terms of flow charts, and simulations performed with the model are discussed in relation to measurements on human vertebral bone samples. The results show that a menopause-related doubling of the activation frequency causes a transient, mainly reversible bone loss. If the menopause is accompanied by an increase in both activation frequency and resorption depth, then the resulting bone loss will be more pronounced and with a larger part being irreversible bone loss (perforations). The two antiresorptive agents. Etidronate and estrogen both cause a slight increase in bone mass (reducing remodeling space), and Etidronate also seems capable of preventing perforations. During fluoride therapy, an initial increase in remodeling space followed by a reduction is seen. Very few perforations are found to take place during fluoride therapy. The present model has been validated by assessing the effects of the menopause and treatment with antiresorptive or anabolic agents. It was found that the results mirrored or anabolic agents. It was found that the results mirrored very closely the results (bone mass measurements) from short-term clinical studies. It is therefore concluded that the model provides a tool for evaluating existing and new therapeutic regimens.

Aged↗

PubMedDate not supplied

Marked decrease in trabecular bone quality after five years of sodium fluoride therapy--assessed by biomechanical testing of iliac crest bone biopsies in osteoporotic patients.

Sodium fluoride has for more than 2 decades been a commonly used therapeutic agent for established osteoporosis because of a repeatedly documented anabolic effect on trabecular bone mass. Recently, however, three controlled trials have failed to demonstrate any therapeutic advantage of NaF over placebo with respect to vertebral fracture rate. Also, there have been several reports of an increased incidence of nonvertebral fractures during fluoride administration. Thus, the efficacy of fluoride therapy remains a controversial issue. The aim of this longitudinal study was to investigate the effect of sodium fluoride (40-60 mg per day), calcium (45 mmol), and vitamin D2 (18,000 IU) on trabecular bone strength, assessed before and after 1 or 5 years of treatment for osteoporosis. Iliac crest biopsies were taken before and after 1 year of treatment in 12 patients, and before and after 5 years of treatment in 14 patients. Measurements were made of biomechanical competence, ash content, and bone fluoride content, and bone strength parameters were normalized for ash content, thereby obtaining a measure of trabecular bone quality. Bone fluoride content was significantly increased after both 1 and 5 years of treatment, indicating that the administered fluoride had been ingested. After 1 year of treatment, no difference was observed in iliac crest trabecular bone ash content. A general trend for decreased bone strength and bone quality was observed, but this was insignificant. After 5 years of fluoride treatment, an insignificant decrease in iliac crest trabecular bone ash content was observed.(ABSTRACT TRUNCATED AT 250 WORDS)

Absorptiometry, Photon↗

PubMedDate not supplied

PTH has a more pronounced effect on vertebral bone mass and biomechanical competence than antiresorptive agents (estrogen and bisphosphonate)--assessed in sexually mature, ovariectomized rats.

The aim of the study was to determine the effect of PTH, the antiresorptive agents estrogen and bisphosphonate (Risedronate), and also the combination of PTH with the antiresorptive drugs on vertebral bone mass and biomechanical competence in a sexually mature, ovariectomized rat model. A total of 138 3-month-old Sprague-Dawley rats were randomized into seven groups: (1) sham operated (control); (2) ovariectomized (OVX); (3) OVX plus estrogen; (4) OVX plus bisphosphonate [Risedronate (NE)]; (5) OVX plus hPTH (1-34); (6) OVX plus hPTH (1-34) and estrogen; and, finally, (7) OVX plus hPTH (1-34) and Risedronate. Treatment regimens were initiated 4 weeks after OVX and were continued for 5 and 15 weeks for each treatment group. Changes in bone mass (ash content) and biomechanical competence were assessed on lumbar vertebral body L4. The results revealed that the Risedronate-treated OVX animals had a higher vertebral bone mass than the OVX group. hPTH (1-34) on its own had a pronounced anabolic effect and increased bone mass 20-25% and bone strength 70-80% over control levels. Neither combination therapy with estrogen nor with Risedronate provided any further advantage. The combination of PTH with Risedronate, though, seemed to allow a continued increase in both bone mass and strength during the whole treatment period.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMedDate not supplied

Normal age-related changes in fluoride content of vertebral trabecular bone--relation to bone quality.

In several clinical osteoporosis studies, fluoride treatment has been shown to have a positive effect on bone mass but without a concomitant decrease in vertebral fracture rate. In contrast, some studies have shown that increases in spinal BMD are also paralleled by decreased vertebral fracture incidence. We have previously demonstrated, in a pig model, that 6-month treatment with fluoride increased bone mass but decreased bone quality. The aim of the present study was to elucidate whether normal age-related fluoride accumulation in human bone per se influences bone quality. From 73 normal individuals, aged 20-91 years (36 females, 37 males) two trabecular bone cylinders were obtained from the central part of L3. Biomechanical competence, ash density, and fluoride content were assessed in one cylinder, and trabecular bone volume was determined in the other. The results showed an age-related decrease in bone mass for both men and women. Bone strength normalized for bone mass (bone quality also identical with bone material strength) also showed an age-related decrease in men and women. Bone fluoride concentration increased significantly in both sexes (range 463-4000 ppm). Multiple regression analyses disclosed that fluoride by itself had no influence on bone quality, in this study with a limited number of cases, when the influence of sex and age were taken into account. It is concluded that normal age-related accumulation of fluoride in vertebral trabecular bone does not seem to affect the quality of bone. Whether this is also the case during fluoride therapy has to be assessed.

Adult↗

PubMedDate not supplied

Marked changes in iliac crest bone structure in postmenopausal osteoporotic patients without any signs of disturbed bone remodeling or balance.

Successful iliac crest bone biopsies were obtained from 63 women with postmenopausal vertebral crush fracture osteoporosis. Structural and static histomorphometric parameters were compared with 25 age-matched normal females, who had suffered an unexpected and sudden death. The control group for dynamic parameters comprised 13 younger normal females. Marked structural changes were observed in the osteoporotic patients in cortical as well as cancellous bone. Cortical width, trabecular volume, trabecular bone surface density and trabecular number were all reduced, whereas trabecular separation and star volume were increased. On the other hand trabecular thickness was normal in the patients. These structural changes in cancellous bone indicate that extensive perforations of trabecular plates have occurred or that whole trabecular elements have been removed. The remodeling cycles of cancellous bone surface and the frequency by which they were repeated (activation frequency) did not differ significantly between osteoporotic patients and normal younger women. The bone balance per remodeling cycle in osteoporotic patients and controls was not significantly different. No subset of individuals in the group of osteoporotic patients could be identified regarding extent of resorptive and formative surfaces, bone formation rate or activation frequency. In the present osteoporotic patients nothing in the ongoing remodeling process could explain the marked changes in bone structure. The pathophysiological changes leading to osteoporosis may therefore occur earlier in life, maybe long before the manifestation of the disease.

Aged↗

PubMedDate not supplied

Thermal stability of cortical bone collagen in relation to age in normal individuals and in individuals with osteopetrosis.

The thermal stability of cortical bone collagen was determined in iliac crest biopsies obtained from 41 normal individuals (21 women aged 20-96 years and 20 men aged 21-84 years) and 8 individuals with autosomal dominant osteopetrosis type I (4 women and 4 men aged 17-63 years). The cortical bone was decalcified and the bone matrix was cut into 80-microns-thick freeze sections parallel to the bone surface. Circular specimens punched out from the sections were used for determination of area shrinkage during gradual heating and shrinkage temperature, Ts (representing the temperature for 50% of the area shrinkage). In normal men, Ts was not found to decrease until the age of 60-65 years, but was markedly decreased in the elderly individuals. In normal women, Ts varied considerably throughout the age range tested, without relationship to age. In contrast to age-matched controls, Ts decreased with age in men with osteopetrosis, whereas Ts in affected women was neither related to age nor different from the highly variable values found in age-matched normal women. Previous findings in rats indicate that Ts decreases with the chronological age of the bone collagen. The present results agree with these findings, which imply that a reduction in turnover rate of bone results in an increasing age and a reduced Ts of the constituent collagen. Following this assumption, the turnover rate of bone seems to be more variable in women than in men and reduced in osteopetrotic men.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMedDate not supplied

Growth hormone (GH) and adult bone remodeling: the potential use of GH in treatment of osteoporosis.

Decreased osteoblastic activity seems to be of major importance in the pathogenesis of postmenopausal and senile osteoporosis and several lines of evidence suggest that GH may become useful in treatment of osteoporosis. GH stimulates osteoblastic proliferation and differentiation in vitro and increases production of Insulin-like Growth Factor-I and II (IGF-I and IGF-II) which both have profound stimulatory effects on osteoblasts and are important local regulators of bone remodeling. GH affects several other osteotropic hormones in vivo and increases bone turnover while the effect on bone mass is less pronounced and depends on the skeletal compartment. The few published clinical studies on the use of GH in treatment of osteoporosis have been inconclusive and well controlled studies of adequate size are greatly needed. Future research should focus on intermittent use of GH in combination with other hormones stimulating IGF production or antiresorptive agents.

Bone Remodeling↗

PubMedDate not supplied

Local differences in mineral content in vertebral trabecular bone measured by dual-energy computed tomography.

Twelve lumbar vertebral bodies from cadavers were examined with dual-energy CT, to measure the calcium content in a big central region of interest (ROI). In each of five vertebrae the calcium content was also measured in six small ROI. After completed scanning, six small cylinders were drilled out from each vertebra, and the ash-density of each cylinder was measured. The dual-energy CT measurements correlated well with the ash-density. Both ash-density and dual-energy CT showed a significantly higher mineral content in the posterior part of the vertebrae than in the anterior part, and this difference might be responsible for problems encountered with the reproducibility of dual-energy CT.

Absorptiometry, Photon↗

PubMedDate not supplied

Relations of bone mineral content, ash weight and bone mass: implication for correction of bone mineral content for bone size.

Bone mineral content (BMC) was measured by photon absorptiometry in fresh bone specimens: 35 iliac crest and 39 forearms were used. BMC was related to ash weight, fat-free weight and the amount of bone determined by quantitative histologic methods. Ninety-five per cent of the variation in bone mineral concentration (BMC') in the iliac crest could be explained by variation in ash weight, and 88% of the variation in BMC in the forearm could be explained by variation in the amount of bone determined histologically. The total cross-sectional bone area of radius and ulna could be calculated from the width of the structures measured on the photon absorption curves. Using this parameter and the relation between BMC and ash weight, the actual in-vivo bone mineral content in the forearm could be expressed in terms of ash-weight in grams per cm3 of total bone.

Anthropometry↗