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Biomedical subjects

L Mosekilde

Publications and source records attributed to L Mosekilde.

At least 19 recordsLinked to original sources
PubMed1992

[Research on aging: biological perspectives].

Aging is a part of the continuous process from conception to death and is strongly modulated by environmental factors throughout the lifespan. Variability in functional capacity between different organs and between individuals therefore increases with aging. This review will discuss two tissues of importance for the fitness of the aging human being: connective tissue and bone. Connective tissues become stiffer with age, which can be mitigated by physical exercise. The physical-chemical stability of collagen is a precise measure for the functional age of the organism. While in the aged, the healing (formation of connective tissue scar) of uncomplicated incisional wounds is slightly impaired, the healing of ischemic wounds is endangered. The clinical observation that "simple" wounds also heal less well in the aged might be due to the presence of diseases with ischemia and other pathologies. During normal aging bone loses mass, structural continuity, and strength. When pronounced, these changes cause osteopenia and osteoporotic fractures. The age-adjusted incidence of osteoporotic fractures is increasing on account of changes in our lifestyle. Preventive efforts, with increased physical activity as the main feature, must be implemented to alter this trend. Our knowledge of the mechanisms of aging is not yet sufficient to formulate a policy containing preventive measures enabling man to achieve his maximum biological lifespan with good physical health and a high quality of life. Multidisciplinary efforts by biologists, clinicians and epidemiologists are warranted to achieve this goal.

Aged↗
PubMed1992

Assessment of bone formation by biochemical markers in metabolic bone disease: separation between osteoblastic activity at the cell and tissue level.

In this study , serum levels of classical serum markers of bone formation [carboxyterminal propeptide of procollagen type I (S-PICP), bone Gla protein (S-BGP)], and total alkaline phosphatase (S-AP)) were related to the calcium kinetic index of whole skeletal mineralization rate (m) by regression analysis in a variety of metabolic bone diseases. For each disease, the regression coefficient (r) as well as the fraction: standard error of estimate/mean dependent variable (SEE/Y) were determined. In a group of 19 normals, only the regression of S-PICP on m reached significance (r = 0.53, P < 0.02, SEE/Y = 0.44), whereas regressions of S-AP and S-BGP on m were nonsignificant. In a pooled material of high- and low-turnover bone diseases without mineralization defects or spinal fracture [myxedema, thyrotoxicosis, and primary hyperparathyroidism (n = 48)], a highly significant positive regression of S-PICP on m was demonstrable (r = 0.50, SEE/Y = 0.63, P < 0.001). The regression coefficients obtained for S-BGP and S-AP were 0.74 (P < 0.001, SEE/Y = 0.41) and 0.42 (P < 0.01, SEE/Y = 0.55), respectively. When analyzing individual diseases in this group, significant differences among the three markers were detectable. In a group of 52 osteoporotics, S-PICP correlated significantly to m (r = 0.49, P < 0.001, SEE/Y = 0.50). Corresponding r-values for S-BGP and S-AP were 0.21 (NS) and 0.48 (P < 0.001, SEE/Y = 0.61), respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1992

Long-term effect of orchidectomy on cortical bone from rat femur: bone mass and mechanical properties.

The study comprised seven groups of intact rats killed at 9, 12, 15, and 24 months of age, and three groups of rats castrated at the age of 9 months and killed together with the intact rats 3, 6, and 15 months after castration. The composition, dimension, and mechanical properties of intact bone as well as the constituent bone collagen from femoral diaphyses were investigated in relation to both age (9-24 months) and castration. Castration had no effect on density and only minor effect on ash and collagen contents. An age-related increase in bone mass, cross-sectional area, and wall thickness of the diaphyses was arrested (bone mass, area) or even reversed (to a decrease in wall thickness) after castration. Therefore, a growing difference, pronounced from 6 months after castration, between intact and castrated rats was observed in bone mass, cross-sectional area, and wall thickness. The compressive mechanical strength of intact bone normalized with regard to cross-sectional area was unaffected by castration, whereas castration tended to increase the stiffness of the bone collagen. When observed in a polarization microscope, two different zones in cross sections of the diaphyses were apparent. The average diameter of the border line separating the two zones was independent of age and castration. By measuring the average thickness of each of the two zones, age-related periosteal bone formation and endosteal bone resorption were demonstrated. After castration, the rate of bone formation was reduced and the rate of bone resorption was accelerated. Castration was thus found to affect the composition and the quality of the cortical bone to a minor extent only.(ABSTRACT TRUNCATED AT 250 WORDS)

Aging↗
PubMed1992

Effects of a short course of oral phosphate treatment on serum parathyroid hormone(1-84) and biochemical markers of bone turnover: a dose-response study.

To investigate the possible use of oral phosphate as an activator of bone remodeling in coherence treatment of osteoporosis, 82 postmenopausal females, aged 50-75 years, were randomized to treatment with oral phosphate (750, 1500, or 2550 mg/day) or placebo for 7 days and followed for 4 months thereafter. All patients had sustained at least one previous fracture of the distal forearm and had a bone mineral content of the contralateral forearm or bone mineral density of the lumbar spine lower than normal mean for age. Urinary phosphate/creatinine ratio increased in a dose-dependent fashion during treatment (P less than 0.001), whereas no significant changes were seen in serum phosphate or serum calcium. Serum parathyroid hormone (PTH) rose significantly (P less than 0.05) during treatment to a maximum of 36 and 33% in the groups receiving 1500 and 2250 mg/day, respectively, whereas serum 1,25-dihydroxycholecalciferol remained unchanged. In the group receiving 1500 mg/day, mean serum osteocalcin was increased in the period from day 1 to day 28 (P less than 0.05), but no significant changes were observed in urinary hydroxyproline/creatinine ratio, or serum bone alkaline phosphatase. We conclude that a short course of oral phosphate treatment increases serum PTH considerably. Furthermore, 1500 mg/day but not 2250 mg/day increases serum osteocalcin. No clear biochemical evidence, however, of increased activation of bone remodeling could be demonstrated in either group.

Administration, Oral↗
PubMed1992

Reconstruction of the formative site in trabecular bone by a new, quick, and easy method.

Ordinary measurements of the wall thickness (the end result of the osteoblastic work) of trabecular bone packets (completed remodeling sites) describe the average thickness of walls formed during the previous two to three years. If the bone biopsy is obtained shortly after onset of disease or initiation of treatment, only a few of the measured sites will represent walls formed under the new conditions. With a reconstruction of the formative site true information of the performed osteoblastic work can be obtained, since it is based upon observations of the actual formative events and not the end result (completed walls). Previously published methods have the disadvantage of being time consuming and technically difficult. Furthermore, the method by Eriksen et al. includes rather complicated mathematical calculations. In the present study a new method for reconstruction of the formative phase is presented, which can be performed from measurements normally obtained in a routine histomorphometric analysis and from paired values of osteoid thicknesses and uncompleted wall thickness. The method does not introduce a new time consuming step in the histomorphometric analyses of the bone biopsy. Furthermore, calculations needed to reconstruct the events of the formative phase can easily be performed using a personal computer and a spread-sheet. The new method for reconstruction presented in this paper gives growth curves for matrix and bone mineral, which are virtually identical with the growth curves previously published by Eriksen et al. for the same 20 normal individuals.

Adult↗
PubMed1992

Primary hyperparathyroidism: iliac crest trabecular bone volume, structure, remodeling, and balance evaluated by histomorphometric methods.

Iliac bone biopsies from 69 patients (48 females, 21 males; median age 58 years; range 17-79 years) with primary hyperparathyroidism (PHP) were examined, and static histomorphometric parameters compared to 30 age- and sex-matched normal controls. The control group for the dynamic parameters constituted 20 sex-matched younger normal controls. Fractional volume of trabecular bone was normal, but the trabeculae were thinner (p less than 0.05) in PHP. The structural parameters marrow space star volume, intertrabecular distance, and mean trabecular plate density were not significantly different in PHP patients compared to normal controls, but the age-related increase, for females, in marrow space star volume and decrease, for both sexes, in mean plate density observed in the controls were not noticed in the PHP group. Trabecular bone remodeling was found significantly increased in the PHP patients reflected by increased extension of eroded (p less than 0.001), osteoid (p less than 0.001), and labeled surfaces (p less than 0.05). The activation frequency was increased by approximately 50% (p less than 0.001). Neither PHP patients nor controls showed age-related decrease in trabecular thickness, and accordingly in both groups the bone balance per remodeling cycle was very close to and not significantly different from zero. Normal postmenopausal women (age greater than or equal to 50 yr) had lower trabecular bone volume (p less than 0.001) and higher intertrabecular distance than normal pre-menopausal women (age less than 50 yr).(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1992

Calcium metabolism in postmenopausal osteoporotic women is determined by dietary calcium and coffee intake.

Eighty-five patients, age 48 to 77 y with postmenopausal crush fracture osteoporosis, were investigated using a 7-d combined calcium balance and 47Ca tracer-kinetic turnover method taking the dermal calcium loss into account. Individual dietary records were obtained based on a 4-d registration at home before hospital admission and on questioning by a dietitian. The following dietary constituents were estimated: energy content, protein, methionine, cysteine, calcium, phosphate, magnesium, coffee, fiber and vitamin C. All patients were served individual diets based on the dietary records during study. Dietary calcium was measured in duplicates of all the meals served. All urine and feces were collected and analyzed for calcium content. The 47Ca kinetic data were analyzed according to a modification of the expanding calcium pool model. The overall calcium balance correlated significantly to energy content (r = 0.31, P less than 0.005), protein (r = 0.22, P less than 0.05), calcium (r = 0.28, P less than 0.01), phosphate (r = 0.27, P less than 0.02) and coffee (r = -0.21, P less than 0.05). However, a multiple backward linear regression analysis disclosed that only calcium (rp = 0.38, P less than 0.0005) and coffee intake (rp = -0.25, P less than 0.05) significantly influenced calcium balance. The equation was: calcium balance (mmol/d) = 0.14 x (dietary calcium, mmol/d) - 0.0016 x (coffee intake, mL/d) - 3.62. A coffee intake in excess of 1000 mL could induce an extra calcium loss of 1.6 mmol calcium/d, whereas intakes of 1-2 cups of coffee per day would have little impact on calcium balance.

Aged↗
PubMed1992

Ultrastructure of human osteoblasts and associated matrix in culture.

The ultrastructure, as visualized by transmission electron microscopy, of cells obtained from human bone explants and subsequently cultured is described along with the electron microscopic appearance of the associated intercellular matrix. The cells were characterized as osteoblasts on the basis of immunohistochemical, enzymatic, and functional criteria. Although the osteoblasts could be cultured in standard culture media and always appeared singly, not forming syncytia, the cultures were eventually confluent and formed multilayers. The cells were fusiform or cuboidal with diameters ranging between 10-15 microns. The cytoplasm was characterized by numerous large mitochondria, and especially by a very prominent RER. The intercellular matrix was woven with collagen fibres surrounding large numbers of matrix vesicles. In areas with matrix vesicles, evidence for osteoblast activity, i.e. mineralization related to matrix vesicles, could be observed after incubation with beta-glycerophosphate. In conclusion, we provide evidence that human osteoblasts cultured in vitro synthesize collagen and produce a matrix with vesicles capable of initiating mineralization processes.

Calcification, Physiologic↗
PubMed1992

Inhibition of the morning cortisol peak abolishes the expected morning decrease in serum osteocalcin in normal males: evidence of a controlling effect of serum cortisol on the circadian rhythm in serum osteocalcin.

Osteocalcin (OC) in serum varies in a remarkably constant circadian rhythm with zenith at night and nadir in the morning. The factors controlling this rhythm are unknown, but several studies indicate that serum cortisol could be of major importance. We tested this hypothesis in a double-blind, placebo-controlled, cross-over study comprising 10 normal male volunteers (aged 23-31 yr) by measuring the response in serum OC and cortisol rhythms to a single dose of metyrapone (30 mg/kg body weight) administered at midnight. During placebo, serum cortisol consistently peaked early in the morning before 0730 h. Ingestion of metyrapone at 2400 h significantly postponed and flattened this peak (P less than 0.01). On both occasions, serum OC increased towards peak levels around 0300 h (P less than 0.01) with no overall differences in the OC profiles. However, when the serum OC time series were synchronized according to the individual cortisol nadirs, we found a significant (P less than 0.01) decrease in serum OC on the placebo day approximately 4 h after the cortisol nadir, whereas no significant changes (P greater than 0.50) were seen on the metyrapone day. Moreover, the mean serum OC level tended to be higher (P less than 0.10 in the interval 0-12 h, and P = 0.06 in the interval 4-8 h) on the metyrapone day compared with the placebo day. On the placebo day, the mean level of serum cortisol during the interval 0-4 h correlated inversely with the mean level of serum OC in the interval 4-8 h (r = 0.77, P less than 0.05). This relation was not found on the metyrapone day. In conclusion, administration of metyrapone, which reduced and postponed the early morning cortisol peak, abolished the normal morning decrease in serum OC. This strongly supports that changes in endogenous serum cortisol are of major importance for the circadian rhythm in serum OC.

Adult↗
PubMed1992

Effects of short-term growth hormone treatment on PTH, calcitriol, thyroid hormones, insulin and glucagon.

We measured changes in serum insulin-like growth factor-1 (IGF-1), calcitriol, parathyroid hormone (PTH), thyroid hormones, insulin, and plasma glucagon in response to seven days of treatment with a pharmacological dosage of recombinant human growth hormone (r-hGH) (0.1 IU/kg sc twice daily) or placebo in 20 normal male volunteers to evaluate whether the effect of r-hGH on biochemical bone markers could be attributed to changes in these hormones. Serum IGF-1 (p < 0.001) and vitamin D-binding protein (p < 0.001) increased steadily during treatment returning to baseline at day 14. Total calcitriol (p < 0.01) and free calcitriol index (p < 0.001) increased transiently at day 4. Furthermore, serum insulin (p < 0.001) and both total (p < 0.001) and free triiodothyronine (p < 0.02) increased during treatment, while serum PTH and plasma glucagon remained unchanged. In conclusion, pharmacological doses of r-hGH increased not only IGF-1 but also free-calcitriol index, insulin, and free T3. The increase in these hormones may be co-responsible for some of the observed effects of r-hGH on bone turnover and calcium homeostasis.

Adult↗
PubMed1991

Acute effect of 1,25-dihydroxyvitamin D3, prednisone, and 1,25-dihydroxyvitamin D3 plus prednisone on serum osteocalcin in normal individuals.

Suppression of osteoblastic function plays an important pathogenic role for the development of glucocorticosteroid-induced osteoporosis. Serum osteocalcin (OC) is a sensitive marker of bone formation. The diurnal rhythm in serum OC can be changed by administration of single doses of either 1,25-(OH)2D3 or prednisone. However, the two steroids have opposing effects: 1,25-(OH)2D3 increases and prednisone decreases serum OC. The aim of the present study was to examine whether 1,25-(OH)2D3 can oppose the acute suppressive effect of prednisone on serum OC in normal subjects. We compared the effect of a combined dose of 2 micrograms 1,25-(OH)2D3 and 10 mg prednisone on the diurnal rhythm of serum OC with the effect of 2 micrograms 1,25-(OH)2D3 + placebo in a crossover study. Seven normal subjects aged 23-36 years were investigated twice at an interval of 1 week. Blood samples were collected every 60 minutes from 1900 until 1100 h the following day. Study drugs were given at 2000 h. The data from the present investigation were compared with data obtained from a similar study with placebo and prednisone in the same subjects. After administration of 1,25-(OH)2D3 serum OC followed the placebo curve during the first 8 h, but in contrast to the placebo curve it then continued to increase and remained elevated throughout the observation period (p less than 0.05). Prednisone inhibited and reversed the nocturnal rise in serum OC levels (p less than 0.01). The course of serum OC after administration of 1,25-(OH)2D3 + prednisone almost paralleled the course after placebo. We conclude that 1,25-(OH)2D3 and prednisone have opposing effects on serum OC.

Adult↗
PubMed1991

Effects of a combined estrogen-gestagen regimen on serum levels of the carboxy-terminal propeptide of human type I procollagen in osteoporosis.

Estrogen stimulates osteoblastic collagen production in vitro, but whether the same stimulation takes place in vivo is still unknown. To test the stimulatory effects of a combined estrogen-gestagen regimen in vivo we monitored serum levels of the carboxy-terminal propeptide of human type I procollagen (S-PICP) in a group of 12 osteoporotic women over a 150 week treatment period. Spinal bone mineral content (BMC) increased to a maximum of 5% over pretreatment values around week 90. Serum alkaline phosphatase (S-AP) and serum bone gla protein (S-BGP) both fell from initial values of 220 U/liter and 39 ng/ml, respectively, to 146 U/liter (p less than 0.01) and 27.2 ng/ml (NS) around week 60 and remained reduced over the remaining treatment period. S-PICP also fell from 117 to 68 micrograms/liter at week 60 and 70 micrograms/ml at week 150 (P less than 0.01). This is equal to a reduction to 32 +/- 10% pretreatment levels. The reduction in S-PICP was not significantly different from that of the other two markers of bone formation (S-AP and S-BGP). Thus, provided the metabolic clearance of PICP remains unaltered after hormone replacement therapy, no major stimulation of osteoblastic collagen type I synthesis was demonstrable during estrogen-gestagen treatment in this population of osteoporotic women. The changes in bone markers seen in this study are therefore consistent with an estrogen-mediated reduction in the frequency of remodeling activation. Because of the reduction in bone turnover and methodologic limitations of bone marker assays, however, smaller increases in the amount of bone formed per activation could remain undetectable.

Aged↗
PubMed1991

Diurnal rhythm in serum osteocalcin: relation with sleep, growth hormone, and PTH(1-84).

We examined the role of sleep, growth hormone (GH), and parathyroid hormone [PTH(1-84)] as regulators of the diurnal rhythm of the osteoblastic bone marker, serum osteocalcin (OC). Nine normal subjects were followed with hourly blood sampling during one 24-hour period with normal sleep pattern, and one 24-hour period with absolute sleep deprivation. We found that the rhythm in serum OC did not exhibit significant changes (P greater than 0.50). Serum OC (mean +/- SE) was 30.9 +/- 2.5 micrograms/liter during sleep (2330-0730 hours) versus 29.9 +/- 4.9 micrograms/liter during sleep deprivation (not significantly different). The serum GH rhythm was significantly different on the two occasions (P less than 0.01). A maximum GH peak (mean +/- SE) of 10.3 +/- 2.4 micrograms/liter occurred at 0136 hours +/- 6 minutes during sleep compared with a maximal peak of 7.6 +/- 1.2 micrograms/liter (P less than 0.01) at 0245 hours +/- 20 minutes (P less than 0.01) during sleep deprivation. During sleep (2330-0730 hours), mean serum GH was 3.61 +/- 0.60 micrograms/liter compared with 2.39 +/- 0.40 micrograms/liter during sleep deprivation (P less than 0.005). Small insignificant changes occurred in serum PTH (1-84) and serum ionized calcium during the two occasions. We conclude that sleep and GH are not acute controlling factors of the diurnal rhythm in serum OC and the role of serum PTH(1-84) remains unsettled.

Adult↗
PubMed1991

Skeletal size and bone mineral content in Turner's syndrome: relation to karyotype, estrogen treatment, physical fitness, and bone turnover.

Bone mineral content (BMC), bone mineral density, and metacarpal dimensions were studied in 50 women with Turner's syndrome aged 21-45 years in relation to karyotype, estrogen treatment, physical fitness, and biochemical markers of bone turnover. No differences were found between the 25 women with karyotype 45.X and women with other karyotypes. Forty-six women had received estrogen. Significant partial correlations were found between bone mineral density of the forearm and duration of estrogen treatment and physical fitness. BMC of the lumbar spine corrected for vertebral height (BMC(C)spine) was directly correlated with duration of estrogen treatment and height, marginally correlated with physical fitness, and inversely correlated with age. Outer metacarpal width was positively correlated with duration of estrogen treatment, age at initiation of therapy, and body weight. The diameter of medullary space showed negative correlation with physical fitness and height, and positive correlation with age at initiation of estrogen treatment. Cortical thickness was positively correlated with duration of estrogen treatment, physical fitness, and height. No convincing effects of estrogen could be demonstrated in women below the age of 30. Above the age of 30, all bone mineral measurements were markedly elevated in women treated for longer than the average of this age group. BMC(C)spine was inversely correlated with biochemical markers of bone formation. Our results demonstrate that estrogen treatment and physical fitness are important determinants of bone mineral status in Turner's syndrome and add to the evidence that estrogen treatment increases BMC in Turner's syndrome.

Adult↗
PubMed1991

A reconstruction of the remodelling cycle in normal human cortical iliac bone.

This paper describes the reconstruction of the remodelling cycle in normal iliac crest cortical bone from static and dynamic variables after double labelling with tetracycline in 10 young normal individuals. The average duration of the resorptive period was 27 days during which the average rate of resorption was 4.7 microns/day. The final resorption depth was 76 microns. The diameter of osteoclast containing cutting cones was significantly smaller (P less than 0.05) than cutting cones containing mononuclear cells, indicating an initial osteoclastic resorption phase preceding a mononuclear resorption phase. The average mineralization lag-time was 8 days and the formative period 89 days. Osteoid thickness during this period averaged 5.8 microns. The seam thickness varied with the underlying uncompleted wall thickness, i.e., during the course of the formative period, with matrix deposition initially exceeding, later equalling and finally lower than the rate of mineralization. The mineral appositional rate (MAR) was 1.2 microns/day and the adjusted mineral appositional rate (Aj.AR) 0.9 micron/day. Both MAR and Aj.AR decreased during the formative period. A completed wall thickness of 62 microns left a Haversian canal with a diameter of 29 microns. After a quiescent period of 438 days the osteon (or parts of it) was reactivated. The average activation frequency was 0.93 per year.

Adult↗