Biomedical subjects

L Mosekilde

Publications and source records attributed to L Mosekilde.

At least 217 records · Page 12Linked to original sources

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↗

PubMed1991

Hypercalcemia of malignancy: pathophysiology, diagnosis and treatment.

Malignancy is the most frequent cause of hypercalcemia in hospitalized patients. The pathophysiology of hypercalcemia of malignancy (HM) is complex. Increased bone resorption is involved in most cases caused either by extensive local bone destruction or by humoral factors. Tumor extracts from patients with humoral hypercalcemia of malignancy (HHM) often contain PTH-like bioactivity. Recently, cDNAs coding for a PTH-related protein (PTH-rP) has been cloned. The N-terminal amino acid sequence of this protein shows a considerable homology with human PTH. However, other bone resorbing factors including prostaglandins, transforming growth factors, colony stimulating factors, leucocyte cytokines and 1,25-dihydroxyvitamin D may be involved in different types of malignancy. HM is usually progressive with troublesome symptoms and a high mortality. Several treatment alternatives are available including rehydration, bisphosphonates, calcitonin, plicamycin, phosphate, and glucocorticoids. Others are under investigation. Treatment should be individualized taking into account the pathophysiological mechanisms involved, the extent of hypercalcemia and renal failure, and the prognosis related to the malignant disease.

Amino Acid Sequence↗

PubMed1991

Effect of a short course of 1,25-dihydroxyvitamin D3 on biochemical markers of bone remodeling in adult male volunteers.

To investigate the stimulatory effect of vitamin D on biochemical markers of bone remodeling, 15 normal men (aged 26-45 years, mean 33.2) were treated orally with 1,25-dihydroxyvitamin D3, 2 micrograms daily for 7 days, and followed for a total of 16 weeks. Serum concentrations of 1,25-dihydroxyvitamin D3 rose 43% during the first week (p less than 0.01), with no significant alteration in the level of 25-hydroxyvitamin D3. Serum level of immunoreactive parathyroid hormone (1-84) (iPTH) decreased markedly (p less than 0.02), and the maximal renal reabsorption capacity of phosphate (TmP/GFR) increased (p less than 0.05), both indicating the impact of the raised vitamin D level on target tissues. Serum phosphate and serum calcium increased during the treatment week (p less than 0.05), as did the fasting renal excretion of phosphate and calcium (p less than 0.01). However, a gradual fall in the excretion of hydroxyproline was seen in the observation period. The serum activity of acid phosphatase increased in the first weeks after vitamin D treatment, reaching significance at the end of week 2 (p less than 0.05). Acid phosphatase activity was still increased at the end of the observation period (p less than 0.02). These observations suggest a synchronization and recruitment of new bone resorptive cells. The immediate response to 1,25-dihydroxyvitamin D administration on the biochemical markers of formative bone cells was a marked increase in the serum level of osteocalcin (BGP), (p less than 0.002) with a gradually fall during the next weeks. A secondary increase, however, was observed in the last two months of the follow-up period.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1991

The effects of etidronate on trabecular bone remodeling in postmenopausal spinal osteoporosis: a randomized study comparing intermittent treatment and an ADFR regime.

Thirty-seven patients were randomized to receive intermittent cyclic etidronate (400 mg/day oral for 2 weeks, followed by 13 weeks off treatment) or an ADFR treatment (100 micrograms/day oral triiodothyronine for 7 days, followed by 400 mg/day etidronate for 2 weeks and 12 weeks off treatment). Supplemental calcium (120 mg/day) and vitamin D3 (400 IU/day) were given throughout the study period to all patients. Biochemical analyses, iliac-crest bone biopsies, and lumbar bone mineral content (BMC) measurements were performed before and during 60 weeks of treatment. Sixteen patients in the intermittent cyclic etidronate group and 15 in the ADFR group completed 60 weeks of treatment. Serum alkaline phosphatase decreased from 185 (43) (mean, (SD] to 144 (35) (p less than 0.001) and from 221 (69) to 156 (43) (p less than 0.002) during intermittent cyclic etidronate treatment and ADFR treatment, respectively, without any significant changes in renal hydroxyproline excretion. Final resorption depth, trabecular bone activation frequency, and bone formation rate decreased significantly from 51.5 (48.4/60.0) microns (median (25%/75% quartiles] to 44.0 (39.6/46.2) microns (p less than 0.04), from 0.30 (0.17/0.62) year-1 to 0.10 (0.02/0.19) year-1 (p less than 0.03) and from 0.035 (0.020/0.081) microns3/microns2/day to 0.015 (0.002/0.025) microns3/microns2/day, p less than 0.03 respectively, during intermittent cyclic etidronate treatment, but were unchanged during ADFR treatment. No significant changes in trabecular bone volume, bone balance per remodeling cycle, or BMC were noted in either treatment group; no evidence of osteomalacia was found. Intermittent cyclic etidronate treatment may be effective in preventing bone loss and in decreasing the risk of trabecular plate perforation, and thereby maintaining the integrity of bone architecture, in postmenopausal osteoporosis.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

PubMed1991

Biologically meaningful determinants of the in vitro strength of lumbar vertebrae.

Applying unbiased stereological methods and a new stereological parameter, star volume of cancellous bone, the bone structure of the first vertebral body was examined and compared with the compressive strength of the second lumbar vertebra. The material came from eight males, aged 33-69 years (mean 49 years) and seven women, aged 22-87 years (mean 52 years) without malignant or metabolic bone disease. From these individuals, first and second lumbar vertebral body were obtained at autopsy. The heights and weights of the individuals were recorded. The following structural parameters were estimated on undecalcified, seven-microns, Goldner-Trichrome stained vertical sections: fractional volume of trabecular bone (BV/TV%), mean trabecular thickness (Tb.Th.l1 microns), trabecular star volume (V*tr mm3), marrow space star volume (V* m.space mm3), and mean thickness of the lateral cortical ring (microns). The compressive strength of whole vertebral body, mean cross sectional area (cm2), and ash density (g/cm3) were estimated and the data were compared to bone histomorphometric estimates. A significant decrease with age for all parameters was found except for marrow space star volume, which increased. With compressive strength as the dependent variable and all other parameters as independent variables, it was shown by standard multiple regression analysis that the in vitro tested compressive strength could be predicted from mean cortical thickness, mean cross sectional area, and marrow space star volume or ash density with a multiple, squared coefficient of regression (r2) of 0.95 when the height and sex of the individual were known.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1991

Marrow space star volume in the iliac crest decreases in osteoporotic patients after continuous treatment with fluoride, calcium, and vitamin D2 for five years.

Iliac crest biopsies in osteoporotic patients were obtained before and after five years of continuous treatment with sodium fluoride (40-60 mg/d), vitamin D2 (18,000 IE/d), and calcium phosphate (45 mmol/d). Star volume of marrow space and trabeculae, mean trabecular thickness, and fractional amount of trabecular bone were estimated on so-called vertical sections before and after treatment. Results showed a significant decrease in marrow space star volume after five years of treatment (35 mm3 versus 19 mm3) (2p less than 0.02). No significant changes were observed in trabecular star volume (0.149 mm3 versus 0.104 mm3) (2p greater than 0.50) or mean trabecular thickness (85 microns versus 79 microns, 2p greater than 0.30). A slight but insignificant increase in the fractional amount of trabecular bone was found (9.7% versus 10.4%, 2p greater than 0.50). A rather close inverse correlation was obtained, however, between individual changes in trabecular bone volume fraction and marrow space star volume (r = -0.72, 2p = 0.011). The findings suggest that the large marrow "cavities" had been split into two or more "cavities" by some newly generated trabecular structures leading to increased trabecular connectivity. The strength of trabecular bone may be increased due to this beneficial effect of fluoride on trabecular bone structure.

Aged↗

PubMed1991

Dermal, intestinal, and renal obligatory losses of calcium: relation to skeletal calcium loss.

Calcium balance is the difference between dietary calcium intake on the one hand and dermal, fecal, and urinary losses on the other. Bone is lost throughout adult life by at least three different mechanisms. Whether all these processes are affected by dietary calcium is at present unknown. In case they are not, dietary calcium intake should balance an adjusted value estimated as obligatory skeletal calcium loss minus obligatory external (dermal + intestinal + urinary) calcium loss. Such a correction would reduce estimated calcium allowances. To solve this question it is important, however, to ascertain whether obligatory bone loss is affected by dietary intake of calcium, ie, Can a high dietary calcium or calcium supplementation influence bone metabolism and reduce bone loss at all ages?

Bone Development↗

PubMed1991

Antacid-induced osteomalacia: a case report with a histomorphometric analysis.

The case of a 75-year-old woman with severe osteomalacia secondary to ingestion of large amounts of an aluminum-containing antacid is reported. Biochemical analysis revealed signs of phosphate malabsorption and increased levels of bone markers (S-alkaline phosphatase and U-hydroxyproline). A 99mTc-bone scan revealed multiple areas of increased uptake. The patient was normocalcaemic, with normal serum levels of intact parathyroid hormone and 25-hydroxyvitamin D. Serum 1,25-dihydroxyvitamin D was high normal. A transiliac bone biopsy from the patient showed severe osteomalacia. Symptoms, biochemical parameters, bone scan and bone morphology were all normalized 1 year after stoppage of antacid ingestion and treatment with vitamin D2. calcium phosphate and sodium fluoride because of severe osteopeni. The characteristics of this condition and the role of phosphate depletion and aluminum in the pathogenesis of bone lesions are discussed.

Aged↗

PubMed1991

Formation of osteoclasts and osteoblast-like cells in long-term human bone marrow cultures.

A culture system for human osteoclasts is described. It is based on incubation of mononuclear marrow cells for three weeks in the presence of 1,25 dihydroxyvitamin D3. The resulting cells exhibited all the classic characteristics of osteoclasts. They formed a true syncytium with up to 25 nuclei per cell. The cells revealed a strong positive reaction for tartrate-resistant acid phosphatase and a ruffled border. When these cells were cultured on 100 microns thick human dentine slices for three weeks, typical resorption pits were formed. In the culture, alkaline phosphatase-positive osteoblast-like cells were formed in the vicinity of osteoclasts. This culture system permits studies of human osteoclasts and their interaction with osteoblast cell precursors in the human bone marrow.

Acid Phosphatase↗

PubMed1991

Formation of osteoblast-like cells from human mononuclear bone marrow cultures.

Osteoblast-like cells are commonly found in the vicinity of osteoclasts formed in long-term human bone marrow cultures, and they are believed to be derived from osteogenic cell precursors belonging to the stromal cell system. This paper describes a new culture method for human osteoblasts from the adherent cell population of long-term human mononuclear bone marrow cultures. The cells obtained exhibited all the classic characteristics of osteoblasts. They contained high intracellular concentrations of alkaline phosphatase and they secreted the osteoblast-specific marker bone Gla protein. Collagen production was mainly (95-98%) procollagen type I propeptide and only minute quantities of procollagen type III propeptide were detectable by radioimmunoassay in the conditioned medium. After eight weeks the cells formed a mineralized matrix on exposure to beta-glycerophosphate and ascorbic acid. This system provides a model for the study of osteoblast differentiation in vitro and may form the basis for the use of defined media in bone cell cultures due to the presence of high concentrations of osteoblast precursors.

Adult↗

PubMed1991

Osteopenia and osteomalacia after gastrectomy: interrelations between biochemical markers of bone remodelling, vitamin D metabolites, and bone histomorphometry.

The prevalence of metabolic disease in a population of 68 postgastrectomy patients was assessed using histomorphometric evaluation of transiliac bone biopsy specimens after tetracycline double labelling. Trabecular bone volume was significantly lower in the postgastrectomy group (p less than 0.01): 62% of the patients had increased osteoid surface, 56% increased osteoid thickness, and 24% increased mineralisation lag time. Only 18%, however, fulfilled the diagnostic criteria for osteomalacia--increased osteoid thickness and increased mineralisation lag time. Postgastrectomy patients had reduced serum concentrations of calcium (p less than 0.01), phosphate (p less than 0.01), and 25-hydroxyvitamin D, while levels of alkaline phosphatase and 1,25 dihydroxyvitamin D were high (p less than 0.01). The severity of the mineralisation defect as reflected by mineralisation lag time was positively correlated to serum 25-hydroxyvitamin D, but unrelated to serum 1,25-dihydroxyvitamin D. Multiple linear regression analysis showed that serum 25-hydroxyvitamin D, age, and the duration of postoperative follow up were significant determinants of the mineralisation defect in a given patient. The limited value of serum markers in the diagnosis of osteomalacia was emphasised by the fact that six of the eight patients with osteomalacia had normal serum levels of calcium and alkaline phosphatase, and five of the eight had values for 25-hydroxyvitamin D in the normal range for healthy control subjects. The results clearly show the need for vitamin D supplementation and regular control after gastric resection.

Adult↗

PubMed1991

The anabolic effects of human parathyroid hormone (hPTH) on rat vertebral body mass are also reflected in the quality of bone, assessed by biomechanical testing: a comparison study between hPTH-(1-34) and hPTH-(1-84).

PTH has a proven anabolic effect on bone mass, as has been shown in several animal models and treatment regimens. The aim of this study was to ascertain whether the positive effect on bone mass is also reflected in the quality of bone formed. The study was performed in a rat model using human PTH (hPTH). One hundred and twenty male Wistar rats, divided into 10 groups, were given either hPTH-(1-34) or hPTH-(1-84) in daily sc doses. Dose levels ranged from 0.11-3.00 nmol/100 g BW.day for a period of 30 days. At death all six lumbar vertebrae were obtained from each rat. A combination of methods was applied to these vertebral bodies in order to ascertain the effect of hPTH on vertebral bone volume, density, trabecular structure, and biomechanical competence. The results revealed a dose-dependent increase in total volume, dry weight, ash weight, and trabecular bone volume. Also, a dose-dependent increase in load values could be demonstrated. The increase in bone strength remained significant after normalization for both cross-sectional area and bone mass. This indicates that the increase in bone size and bone mass was not achieved at the expense of the quality of the bone present. When the two treatments were administered at the same molar dose level, no difference between hPTH-(1-34) and hPTH-(1-84) was revealed. On the basis of this study, it is concluded that PTH could prove to be a promising treatment in the management of osteopenic states.

Animals↗

PubMed1991

Relations between diurnal variations in serum osteocalcin, cortisol, parathyroid hormone, and ionized calcium in normal individuals.

Serum osteocalcin varies in a diurnal rhythm, with peak values during the night and minimum levels before noon, but the factors controlling this rhythm are unknown. In this study, we evaluated the temporal relations between the osteocalcin rhythm and variations in serum concentrations of cortisol, intact parathyroid hormone (PTH(1-84)), and ionized calcium (Ca2+) in 15 normal volunteers, aged 22-46 years. Serum cortisol varied in a typical way preceding inverse changes in serum osteocalcin by about 4 h (r = 0.78, p less than 0.0001). Changes in serum osteocalcin following the early morning increase in serum cortisol were statistically indistinguishable from the changes seen after oral administration of 2.5 or 10 mg of prednisone. Serum PTH (1-84) showed a diurnal rhythm (p less than 0.01) with peak values (4.06 +/- 0.42 pmol/l) at 20.30 h and nadir (2.81 +/- 0.10 pmol/l) around 10.30 h, preceding changes in serum osteocalcin in the same direction by 5 h (r = 0.55, p less than 0.02). Prednisone at a dose of 10 mg did not change the time course significantly. Serum Ca2+ varied in an almost bi-phasic pattern (p less than 0.01) with maximal mean levels around 16.30 and 09.30 h and minimal levels around 05.30 and 14.30 h. Serum Ca2+ correlated inversely with PTH (1-84) (r = 0.53, p less than 0.01), and serum osteocalcin was inversely related to Ca2+ at concurrent time points (r = 0.59, p less than 0.005). Prednisone caused a 2-3 h lasting increase in serum Ca2+ 3-5 h after ingestion (p less than 0.001). In conclusion, our results suggest that cortisol is strongly associated to the diurnal rhythm in serum osteocalcin. The biological relevance of the reported relation between serum osteocalcin and PTH (1-84) and serum Ca2+ is uncertain.

Administration, Oral↗

PubMed1991

[Familial hypercalciuric hypercalcemia].

Familial hypocalciuric hypercalcemia (FHH) or familial benign hypercalcemia is an autosomal dominant inherited disorder of calcium metabolism. It is characterized by lifelong asymptomatic hypercalcemia associated with a relative hypocalciuria and a tendency to hypermagnesemia. The biochemical features of this disorder are difficult to distinguish from mild primary hyperparathyroidism. Several patients have therefore been operated upon for hyperparathyroidism with no effect on calcium levels. The most important diagnostic criterion of FHH in a single individual is the demonstration of asymptomatic hypercalcemia in other family members including children. The pathophysiology of the disorder is unknown. A genetic defect of cellular calcium transport leading to a disturbed regulation of extracellular calcium by parathyroid glands and kidneys has been suggested. The hypercalcemia in this disorder is asymptomatic, usually without complications and does not require treatment. Partial parathyroidectomy has no effect on the hypercalcemia. However, it is important to diagnose this condition in order to avoid unnecessary neck explorations. Two complications have been described in some families: pancreatitis and neonatal primary hyperparathyroidism. The recommended management of these complications is total parathyroidectomy.

Adult↗

PubMed1990

A short course of recombinant human growth hormone treatment stimulates osteoblasts and activates bone remodeling in normal human volunteers.

The effects of recombinant human growth hormone (rhGH) on biochemical markers of bone turnover and bone mineral content (BMC) were investigated in 20 normal male volunteers (aged 22-31 years) randomized to treatment for 7 days with either rhGH (0.1 IU/kg subcutaneously twice a day) or placebo. Serum somatomedin C rose during treatment (p less than 0.001) but was not significantly different from baseline at day 14. The fasting urinary hydroxyproline/creatinine (p less than 0.001) and calcium/creatinine ratios (p less than 0.01) increased during treatment and remained elevated for 4 and 2 weeks, respectively. Serum bone gamma-carboxyglutamic acid-containing protein (BGP) increased during treatment (p less than 0.001) and remained elevated for 6 months (p less than 0.02). Serum bone alkaline phosphatase (B-AP), after an initial fall in the treatment period (p less than 0.001), increased slightly in the following months (p less than 0.01). In the rhGH group BMC was significantly higher than the prestudy value at day 14 (p less than 0.05) but was unaltered at the end of study. The simultaneous increase in markers of bone resorption and formation during rhGH treatment followed by a decline in resorption parameters within a few weeks and the prolonged effect on BGP and B-AP demonstrate that rhGH treatment stimulates osteoblasts and activates bone remodeling.

Absorptiometry, Photon↗

PubMed1990

Calcium metabolism in postmenopausal osteoporosis: the influence of dietary calcium and net absorbed calcium.

A group of 85 females aged 48-77 years with postmenopausal crush fracture osteoporosis were investigated using a 7 day combined calcium balance and calcium tracer kinetic turnover study to assess the influence of dietary calcium and net absorbed calcium on bone metabolism. During the study, patients were on their habitual diet, as determined by a prestudy registration. Dietary calcium was measured after double serving of all the meals. All urine and feces were collected and analyzed for calcium content. Bone mineralization rate and bone resorption rate were determined by applying the continuously expanding calcium pool model to the tracer kinetic data. Urine calcium excretion and net absorbed calcium were correlated (r = 0.64, p less than 0.0001) with the following equation: urinary excreted calcium (mmol/day) = 2.4 + 0.4 X net absorbed calcium (mmol/day). Dermal calcium loss was not correlated with net absorbed calcium or urinary calcium. The net amount of absorbed calcium necessary to balance urinary and dermal losses was calculated to be 4.2 mmol calcium per day. The daily calcium intake necessary for obtaining a net absorbed calcium in excess of the urinary and dermal calcium losses and thereby ensure skeletal integrity was estimated to be 34.2 mmol calcium per day compared to an average intake of 27.9 +/- 7.6 (mean +/- SD) mmol/day. Net absorbed calcium correlated negatively to bone resorption rate (r = -0.31, p less than 0.005) and positively to bone mineralization rate (r = 0.29, p less than 0.01) and to calcium balance (r = 0.66, p less than 0.0001). Dietary calcium intake and calcium balance correlated positively (r = 0.38, p less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗