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Biomedical subjects

E F Eriksen

Publications and source records attributed to E F Eriksen.

At least 19 recordsLinked to original sources
PubMed1999

[Vitamin D deficiency. Easy to diagnose, often overlooked].

On the basis of five cases the typical clinical picture of patients with severe vitamin D deficiency is presented. The diagnosis can easily be mistaken and it is not uncommon that rheumatic or malignant diseases are suspected instead. By using a simple screening blood test consisting of 25-OH-vitamin D, PTH and alkaline phosphatase most cases will be diagnosed correctly. Important risk factors are reviewed, the most important being: elderly > 70 years, persons with low exposure to direct sunlight, gastrointestinal diseases and persons in anti-convulsive treatment. A treatment regimen consisting of oral supplementation of 1000-1500 mg calcium + 1000 IU vitamin D to patients with an isolated low 25-OH-vitamin D (< 20 nmol/l) is recommended. If the patient also has raised values of PTH or alkaline phosphatase an intramuscular dose of 100,000 IU ergocalciferol pr week for one month is given.

Aged↗
PubMed1999

[Polyneuropathies].

Explore the source record for details and available documents.

Deficiency Diseases↗
PubMed1999

Effects of the antiestrogenic environmental pollutant 3,3',4,4', 5-pentachlorobiphenyl (PCB #126) in rat bone and uterus: diverging effects in ovariectomized and intact animals.

The purpose of this study was to compare effects on rat bone and uterus of estrogen depletion and exposure to the coplanar PCB-congener 3,3',4,4',5-pentachlorobiphenyl (PCB #126) which exhibits anti-estrogenic properties. Half of the rats were ovariectomized (n = 20) and the other half were sham-operated. Ten of the ovariectomized rats and ten of the sham operated were exposed to PCB #126 (ip injections) for 3 months (total dose: 384 microgram/kg body wt). The remaining control rats were injected with corn oil (vehicle). The rats were killed and the tibiae and uteri were dissected. The left tibia was used for measurements of weight, length, and bone mineral density and the right for histomorphometrical analysis. The uteri were analyzed with respect to estrogen receptor content. PCB #126 exposure did not affect bone mineral density or trabecular bone volume of tibia in sham-operated rats. In ovariectomized rats PCB #126 exposure resulted in a decreased length and an increased bone mineral density of tibia. An obvious PCB #126 induced increase in osteoid surface was observed in sham-operated rats. The cortical thickness and the organic content of the tibia were also increased in these rats. In estrogen deprived tissue like the uteri of ovariectomized rats, PCB #126 showed weak estrogen agonistic activity. The observed effects of PCB #126 on bone and uterine tissues differed between ovariectomized and sham-operated rats.

Animals↗
PubMed1999

Telomere shortening during aging of human osteoblasts in vitro and leukocytes in vivo: lack of excessive telomere loss in osteoporotic patients.

We have compared the telomere length, as assessed by Southern analysis, of telomere restriction fragments (TRFs) generated by RsaI/HinfI digestion of genomic DNA in: (i) in vitro cultured human trabecular osteoblasts undergoing cellular aging; and (ii) peripheral blood leukocytes (PBL) obtained from three groups of women: young (aged 20-26 years, n = 15), elderly (aged 48-85 years, n = 15) and osteoporotic (aged 52-81 years, n = 14). The mean TRF length in human osteoblasts undergoing aging in vitro decreased from an average of 9.32 kilobasepairs (kb) in middle-aged cells to an average of 7.80 kb in old cells. The rate of TRF shortening was about 100 bp per population doubling, which is similar to what has been reported for other cell types, such as human fibroblasts. Furthermore, there was a 30% decline in the total amount of telomeric DNA in senescent osteoblasts as compared with young cells. In the case of PBL, TRF length in the DNA extracted from young women was slightly longer (6.76 +/- 0.64 kb) than that from a group of elderly women (6.42 +/- 0.71 kb). A comparison of TRFs in the DNA extracted from the PBL from osteoporotic patients and from age-matched controls did not show any significant differences (6.47 +/- 0.94 versus 6.42 +/- 0.71 kb, respectively). Therefore, using TRF length as a marker for cellular aging in vitro and in vivo, our data comparing TRFs from osteoporotic patients and age-matched controls do not support the notion of the occurrence of a generalized premature cellular aging in osteoporotic patients.

Adult↗
PubMed1999

[Attitude of general practitioners to the importance of gender and diet in disease prevention].

Three hundred and seventy-four general practitioners (GPs) in Denmark filled in a questionnaire on attitudes to include information on gender and diet in the strategy for prevention of coronary heart disease, cancer, osteoporosis, and overweight/underweight. Risk factors for disease in general were ranked as follows: smoking, alcohol, stress, diet, physical exercise, heredity and hygiene. The patients' lack of motivation, insufficient time for each patient, and inadequate knowledge about nutrition were stated as barriers to dietary counselling. The GPs stated that the gender of the patient was important only to the counselling on osteoporosis. Lack of time and insufficient knowledge were perceived as barriers for including gender specific issues in prevention. It is concluded that GPs consider dietary counselling important but lack time and knowledge. The results point at a need for better pre- and postgraduate training in nutrition, and for a better reimbursement system for time spent on prevention.

Attitude of Health Personnel↗
PubMed1999

[Prevention in general practice. Are female and male patients treated the same way? A questionnaire study].

Three hundred and seventy-four general practitioners (GPs) in Denmark filled in a questionnaire on practices regarding prevention of coronary heart disease (CHD), cancer, osteoporosis, and overweight/underweight. Half of the GPs were questioned about the issue of prevention based upon female case stories and the other half on male case stories with identical wording. The GPs more often in relation to: Prevention of CHD gave dietary counselling and recommended weight loss to slightly overweight male than female patients. Prevention of cancers gave dietary counselling and recommended weight loss and increase of exercise to female than to male patients. Prevention of osteoporosis recommended a supplement of calcium and vitamin D to female than to male patients. Treatment of underweight recommended weight gain and discussion of psycho-social issues to underweight female than male patients. In conclusion, GPs distinguish between men and women in relation to prevention strategies in general practice. There is a need for well-described prevention and action strategies with relevant gender differentiation for use in general practice.

Adult↗
PubMed1999

Hormone replacement therapy prevents osteoclastic hyperactivity: A histomorphometric study in early postmenopausal women.

In a randomized, double blind, clinical prospective trial comprising 35 women treated with either hormone replacement therapy (HRT) (cyclic estradiol/norethisterone acetate) or placebo we performed histomorphometric studies on paired bone biopsies obtained before and after 2 years of treatment. Untreated women developed a progressively more negative balance at individual bone multicellular units (BMUs) (i.e., wall thickness-erosion depth) (2.2 +/- 1.7 microm vs. -5.7 +/- 1.4 microm; p < 0.01), while women on HRT displayed preservation of bone balance (2.4 +/- 2.4 microm vs. 2.5 +/- 2.5 microm; NS). No significant differences in wall thickness between the two groups were demonstrable, but the untreated women developed a pronounced increase in erosion depth over 2 years (46.9 +/- 1.8 microm vs. 52.0 +/- 1.9 microm; p < 0.05), while the HRT group revealed no change (47.8 +/- 2.7 microm vs. 44.6 +/- 1.7 microm; NS). Furthermore, the placebo group displayed an increased osteoclastic erosion depth (17.8 +/- 1.6 microm vs. 25.0 +/- 1.7 microm; p < 0.001), compared with unchanged values in the HRT group (20.0 +/- 1.6 microm vs. 16.9 +/- 1.4 microm/day; NS). While the placebo group revealed a slight increase in volume referent resorption rate (35 +/- 8% vs. 38 +/- 8%; NS) the HRT group revealed a pronounced decrease (46 +/- 8% vs. 28 +/- 5%; p < 0.05). No significant changes in marrow star volume (an index of trabecular perforations) were demonstrable in either group. Our results demonstrate that bone remodeling in early postmenopausal women is characterized by progressive osteoclastic hyperactivity, which is reduced by cyclic HRT. This reduction of resorptive activity at the BMU level after HRT seems to precede the reduction in activation frequency demonstrated in previous studies on older postmenopausal women.

Bone Remodeling↗
PubMed1998

Withdrawal of parathyroid hormone treatment causes rapid resorption of newly formed vertebral cancellous and endocortical bone in old rats.

When administered intermittently, parathyroid hormone (PTH) is a strong anabolic agent, increasing both bone mass and bone mechanical strength and competence. This study evaluates the fate of PTH-induced bone in vertebral bodies after withdrawal of PTH treatment in normal old rats. Sixty-seven 21-month-old male rats were treated with 62 microg/kg/day PTH(1-34) for 8 weeks, followed by saline or bisphosphonate (risedronate, 5 microg/kg twice a week) for another 8 weeks. The rats were scanned by dual-energy X-ray absorptiometry at intervals. The bone mineral content (BMC) of L2-5 increased by 33% during the PTH treatment. The BMC started decreasing shortly after withdrawal of PTH and continued to decline during the 8 weeks after withdrawal of PTH. Risedronate, however, prevented this decrease in BMC. All rats were labeled with tetracycline and calcein 3 weeks and 1 week before the cessation of PTH therapy. In the cancellous bone, PTH increased the mineralized surface: 32.9% +/- 2.8% (mean +/- standard error of the mean) vs. controls 12.0% +/- 1.5%, the mineral appositional rate (0.65 +/- 0.02 to 0.88 +/- 0.06 microm/day), and the cancellous bone volume (BV/TV: 14.5% +/- 0.7% to 27.5% +/- 1.7%). Withdrawal of PTH induced a fast and pronounced bone resorption, decreasing both the extent of the fluorochrome labels and the cancellous bone volume to control values. Risedronate prevented this resorption. In the cortical bone of the vertebral shell, PTH induced large increases in the endocortical mineralized surface, mineral appositional rate, and cortical area. The endocortical fluorochrome labels were, however, resorbed after withdrawal of PTH. Risedronate maintained both the fluorochrome labels and the cortical area. At the periosteum, the response to PTH was less evident, however, and hardly any labeling was seen at the periosteum facing the vertebral canal either in the controls or in the PTH-treated rats. The compressive strength of the vertebral body specimens increased with PTH treatment whether measured in newtons (317 +/- 23 to 623 +/- 54 N), normalized to cross-sectional area (23.0 +/- 1.4 to 44.7 +/- 2.5 N/mm2), or to ash content per millimeter height (58 +/- 2 to 76 +/- 2 N x mm/mg). Withdrawal of PTH decreased the compressive strength and competence to control values. Risedronate, however, maintained the PTH-induced mechanical strength and competence. The study discloses that even in very old rats withdrawal of PTH treatment causes a rapid and pronounced decline in the bone mass deposited during PTH treatment; treatment with risedronate can, however, maintain the PTH-induced bone properties in the axial skeleton of old rats.

Absorptiometry, Photon↗
PubMed1998

The effects of IGF-I and IGF-II on proliferation and differentiation of human osteoblasts and interactions with growth hormone.

BACKGROUND: We have previously shown that growth hormone (GH) consistently stimulates proliferation of human osteoblasts in vitro. In rat osteoblasts, GH augments the effects of insulin-like growth factor (IGF) I on cell proliferation and differentiation. We therefore investigated the effects of IGF-I and -II alone and in combination with GH on human osteoblasts in vitro. METHODS: Human osteoblast-like cells (HOB) were established from trabecular explants (n = 18) and human marrow stromal cells (HMS) from marrow aspiration (n = 21). The cell cultures were stimulated with IGF-I or IGF-II (1, 10 or 100 ng mL-1) alone, in combination with hGH (100 ng mL-1) or after prestimulation with hGH. RESULTS: IGF-I alone, in combination with hGH and after pretreatment with hGH, increased proliferation of HOB and HMS by 49-190% (P < 0.05-0.01). IGF-II alone, in combination with hGH and after pretreatment with hGH increased proliferation of HOB by 57-158% (P < 0.01). In HMS only IGF-II in combination with hGH and after prestimulation with hGH increased proliferation. IGF-I alone and in combination with hGH decreased alkaline phosphatase (AP) in both cell types. IGF-II did not affect AP in HOB, but increased AP in HMS, this effect was abolished by hGH. In HOB, collagen production (PICP) was increased by IGF-II but unaffected by IGF-I. In HMS, PICP was decreased by IGF-I and -II but increased by hGH. Co-stimulation further increased PICP. CONCLUSION: IGF-I and -II exerted proliferative effects on both HOB and HMS. Co-stimulation with GH exhibited synergism in enhancing the proliferative response. In HMS prestimulation improved the proliferative response significantly. The effects of the IGFs on differentiation are more complex and dependent on cell maturation and of the IGF used.

Alkaline Phosphatase↗
PubMed1998

Long-term oral pamidronate treatment inhibits osteoclastic bone resorption and bone turnover without affecting osteoblastic function in multiple myeloma.

This study was performed as a cross-sectional substudy to the Danish-Swedish Pamidronate Study, a randomized placebo-controlled multicentre trial in multiple myeloma. The purpose was to evaluate the biological effects of long-term treatment with oral pamidronate 300 mg daily on bone metabolism by using histomorphometry and analysis of cytokines and biochemical markers of bone turnover. Sixteen patients were included after median 27.5 months of protocolized treatment; 10 patients received active treatment and 6 patients placebo. When compared with placebo, pamidronate treatment was associated with: (a) marked decreased osteoclastic resorption rate (0.86+/-0.59 microm/d vs. 5.7+/-5.0 microm/d, p=0.002), and diminished activation frequency (0.20+/-0.18 yr(-1) vs. 0.72+/-0.55 yr(-1), p=0.014); (b) compensatory reduced volume referent bone formation rate (0.17+/-0.21 yr(-1) vs. 0.71+/-0.54 yr(-1), p=0.007), but unaltered mineral appositional rate; (c) neutral (-0.66+/-5.6 mm) vs. negative (-2.15+/-2.2 microm, p=0.013) bone balance per remodelling cycle; (d) higher trabecular bone volume (21.0+/-6.2% vs. 13.0+/-3.7%, p=0.01); (e) suppressed urinary excretion and serum levels of some of the biochemical markers of bone metabolism; and (f) significant reduction of circulating soluble interleukin-6 receptor (IL-6sR) (25.9+/-4.1 ng/ml vs. 32.1+/-6.6 ng/ml, p=0.04), and (g) a uniform tendency of lower serum and marrow plasma levels of IL-6, IL-1beta, and TNFalpha. Thus oral pamidronate was absorbed in biologically active amounts, and reduced overall bone resorption and bone turnover without impairing osteoblastic bone formation. The observation that cytokine and cytokine receptor levels were reduced extends the possible and potential beneficial actions of bisphosphonates in multiple myeloma.

Administration, Oral↗
PubMed1998

An Sp1 binding site polymorphism in the COLIA1 gene predicts osteoporotic fractures in both men and women.

Genetic factors play an important role in the pathogenesis of osteoporosis, and recent studies have shown that a polymorphic Sp1 binding site in collagen type I alpha1 (COLIA1) gene is associated with bone mass and vertebral fractures in women from the U.K. Information on the predictive value of the COLIA1 Sp1 polymorphism in other populations is limited, however, and no studies have yet been performed in osteoporotic males. In view of this, we analyzed COLIA1 genotypes in relation to bone density and biochemical markers of bone turnover and the presence of osteoporotic fractures in a case-control study of Danish men and women. COLIA1 genotype was determined by polymerase chain reaction analysis of genomic DNA extracted from peripheral blood samples and related to bone mass, biochemical markers of bone turnover, and the presence of fracture in a study of 375 osteoporotic vertebral fracture patients and normal controls. There was no significant effect of COLIA1 genotype on bone mass or biochemical markers when data from the control group (n = 195) and fracture group (n = 180) were analyzed separately. However, the genotype distribution was significantly different in the fracture cases compared with age-matched controls (chi2 = 16.48, n = 249,p = 0.0003) due mainly to over-representation of the ss genotype in the fracture patients (14.3% vs. 1.4%), equivalent to an odds ratio for vertebral fracture of 11.83 (95% confidence interval 2.64-52.97) in those with the ss genotype. Similar differences in genotype distribution between osteoporotic patients and controls were observed in both men (chi2 = 11.52, n = 95, p = 0.0032, OR = 2.04) and women (chi2 = 6.90, n = 154, p = 0.032, OR = 1.37). In keeping with the above, logistic regression analysis showed that the ss genotype was an independent predictor of osteoporotic fracture (p = 0.028). This study confirms that the COLIA1 Sp1 polymorphism is significantly associated with osteoporotic vertebral fractures. The association is seen in both men and women, and the effect on fracture risk appears to be partly independent of bone mineral density. Our results raise the possibility that genotyping at the Sp1 site could be of clinical value in identifying individuals at risk of osteoporotic fractures in both genders.

Adult↗
PubMed1997

Demonstration of cellular aging and senescence in serially passaged long-term cultures of human trabecular osteoblasts.

The proliferative capacity and cellular and biochemical characteristics of human trabecular bone osteoblasts were analysed throughout their replicative lifespan in vitro. Like several other cell types, human osteoblasts demonstrated a typical Hayflick phenomenon of cellular aging comprising a period of rapid proliferation until cumulative population doubling level (CPDL) 22 to 24, followed by a phase of slow growth and the final cessation of cell division at CPDL 32 to 34. Comparing young cells (less than 20% lifespan completed) and old cells (more than 90% lifespan completed) revealed a progressive increase in population doubling (PD) time, a decrease in attachment frequency, a decrease in the number of S-phase positive cells, a decrease in the rates of DNA, RNA and protein synthesis, an increase in the protein content per cell and an increased proportion of senescence-specific beta-galactosidase positive cells. While osteoblastic production of collagen type I decreased progressively during aging, alkaline phosphatase activity dropped rapidly after the first few passages and then remained constant during the rest of the proliferative lifespan, Significant morphological changes from thin and spindle-shaped early passage young cells to large, flattened and irregularly shaped late passage old cells full of intracellular debris were observed. In comparison, osteoblasts established from an osteoporotic bone sample showed a maximum CPDL of less than 5, had a longer PD time and exhibited abnormal senescent morphology. Thus, we have demonstrated for the first time that human osteoblasts, like several other diploid cell types, have a limited proliferative capacity in vitro and undergo aging and senescence as measured by various cellular and biochemical markers. In addition, preliminary studies show that cells from osteoporotic bone have a severely reduced proliferative capacity. This model of bone cell aging facilitates study of the molecular mechanisms of osteoblast senescence as well as factors related to osteoblast dysfunction in patients with osteoporosis.

Adolescent↗
PubMed1997

A sequence variation: 713-8delC in the transforming growth factor-beta 1 gene has higher prevalence in osteoporotic women than in normal women and is associated with very low bone mass in osteoporotic women and increased bone turnover in both osteoporotic and normal women.

Bone mass is partly genetically determined. The genes involved are, however, still largely unknown. Transforming growth factor-beta 1 (TGF-beta 1) is considered a putative regulator of osteoclastic-osteoblastic interaction (coupling). The aim of the present study was therefore to examine whether possible variants of the TGF-beta 1 gene are related to bone mass and osteoporosis. We examined 161 osteoporotic women (at least one low energy spinal fracture) and 131 normal women. We investigated sequence variations in the TGF-beta 1 gene using the single-stranded conformation polymorphism (SSCP) technique combined with DNA sequencing. Seven patients were heterozygous for a cytosine to thymidine base substitution at position 76 in exon 5 (C788-T) (corresponding to position 788 in the TGF-beta 1 cDNA), resulting in a threonine to isoleucine amino acid shift at position 263 in the TGF-beta 1 propeptide (Thr263-Ile). Ten other patients had a one base deletion in the intron sequence 8 bases prior to exon 5 (713-8delC), which could influence splicing. Five normal women exhibited the C788-T sequence variant, and two the 713-8delC. The prevalence of 713-8delC was significantly higher in the osteoporotic group (chi 2 = 4.02, p < 0.05). Osteoporotic patients with the 713-8delC variant had increased levels of bone alkaline phosphatase (p < 0.05). If the osteoporotic patients with a z score of the lumbar spine below -1 were examined separately, we found increased serum levels of bone alkaline phosphatase (p < 0.05), increased urinary excretion of hydroxyproline (p < 0.05), and reduced bone mass of the lumbar spine (p < 0.05) in patients with 713-8delC. No correlation to bone mass was demonstrated in the normal women, but 713-8delC was associated with increased serum levels of bone alkaline phosphatase (p < 0.05). The sequence variation, 713-8delC, in the TGF-beta 1 gene is more frequent in patients with osteoporosis compared to normal controls. The 713-8delC variant seems to be associated with very low bone mass in osteoporotic women with low bone mass and increased bone turnover in both osteoporotic and normal women.

Adult↗