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S Ljunghall

Publications and source records attributed to S Ljunghall.

At least 73 records · Page 4Linked to original sources
PubMed1997

Population-based screening for primary hyperparathyroidism with serum calcium and parathyroid hormone values in menopausal women.

BACKGROUND: Population-based screenings for primary hyperparathyroidism have failed to systematically use intact parathyroid hormone (PTH) values for diagnosis, to explore prevalence and diagnostic criteria of normocalcemic hyperparathyroidism, and to attempt surgical verification of the disorder. METHODS: A total of 5202 women (ages, 55 to 75 years) attending a population-based mammography screening were investigated for primary hyperparathyroidism. In women lacking a family history of hypercalcemia, significant renal impairment, or low urinary calcium excretion hyperparathyroidism was diagnosed on the basis of predetermined criteria encompassing lower intact serum PTH levels in hypercalcemia (serum PTH 25 ng/L or greater; reference range, 12 to 55 ng/L) than in two intervals of normocalcemia (serum PTH 35 or greater, greater than 55 ng/L). RESULTS: Prevalence of hyperparathyroidism was 2.1% (n = 109). At diagnosis total serum calcium and serum PTH levels were 2.32 to 3.19 mmol/L and 34 to 300 ng/L, respectively, and 66% of the women exhibited normocalcemia. Repeated examination showed persistent normocalcemia in 30 patients, and all but two of them had normal ionized plasma calcium levels. Significantly higher serum calcium, serum PTH, and urine calcium--but not serum creatinine--levels were found in patients with hyperparathyroidism compared with matched control subjects from the screened population. Within an ongoing stratified treatment program, 59 of 60 patients who underwent operation exhibited pathologic parathyroid tissue (mean weight, 591 mg). CONCLUSIONS: Substantial prevalence of sporadic primary hyperparathyroidism is demonstrated in a risk group. Although criteria for hyperparathyroidism recognition included patients with truly mild biochemical derangement, operative findings suggested underdiagnosis of the disorder.

Aged↗
PubMed1997

Serum calcium: a new, independent, prospective risk factor for myocardial infarction in middle-aged men followed for 18 years.

BACKGROUND: Primary hyperparathyroidism (HPT) is a disease characterized by hypercalcemia, and associated with an increased mortality in cardiovascular diseases. However, serum calcium levels within the normal range have not been evaluated as a prospective cardiovascular risk factor. METHODS: A cohort of males aged 50 (n = 2183) were investigated in 1970-1973 for serum calcium and known cardiovascular risk factors. They were then followed up over the next 18 years. RESULTS: During the follow-up period, 180 subjects experienced a myocardial infarction (MI). The serum calcium levels were significantly elevated at the baseline (2.37 +/- 0.09 SD versus 2.35 +/- 0.09 mmol/l, p < 0.03) in the subjects who developed a MI when compared with the rest of the cohort. Also blood pressure, body mass index (BMI), fasting insulin, serum cholesterol, serum triglycerides, and the atherogenic index were significantly elevated in the MI group (p < 0.01), while HDL-cholesterol was lower at the baseline investigation (p < 0.01). Cox's proportional hazard analysis showed that only serum calcium (p < 0.01), BMI (p < 0.0003), diastolic blood pressure (p < 0.0009), and the atherogenic index (p < 0.002) were significantly independent risk factors for MI. The range of serum calcium levels from the mean value, -2 SDs to the mean value +2 SDs corresponds to a variation in estimated risk for MI ranging from 0.06 to 0.15. CONCLUSIONS: Serum calcium was found to be an independent, prospective risk factor for MI in middle-aged males suggesting a role for extracellular calcium levels in the atherosclerotic process.

Calcium↗
PubMed1997

Serum levels of parathyroid hormone are related to the mortality and severity of illness in patients in the emergency department.

Hypocalcaemia is a common finding in intensive care patients. In addition, raised levels of parathyroid hormone (PTH) have been described. The explanation and clinical importance of these findings are yet to be revealed. To investigate the occurrence of hypocalcaemia and elevated PTH levels and their relationship to morality and the severity of disease, serum levels of PTH, ionized calcium (Ca2+) and the cytokines interleukin 6 (IL-6) and tumour necrosis factor alpha (TNF-alpha) were measured on arrival in the emergency department in a broad spectrum of 140 acutely ill patients patients suffering from common diseases such as stroke, acute abdominal disorders, obstructive lung diseases, heart failure, acute myocardial infarction, angina pectoris, trauma and infectious diseases. A score (APACHE II) was calculated to assess the severity of disease. Elevated PTH levels (> 55 pg ml-1) were seen in 16% of the patients, being most frequent in patients with myocardial infarction (28%) and congestive heart failure (42%). The levels were significantly correlated with the APACHE II score (r = 0.48, P < 0.0001) and with the length of stay in hospital (r = 0.26, P < 0.002). PTH was also significantly (P < 0.03) elevated in non-survivors compared with survivors and was found to be a stronger predictor of mortality (P < 0.01) than the APACHE II score (P < 0.02) in Cox's proportional hazard analysis. No close relationships were found between the cytokine levels and the indices of calcium metabolism. In conclusion, a rise in serum levels of PTH was common and related to the severity of disease and mortality in a mixed emergency department population.

APACHE↗
PubMed1997

Cloning of a novel retinoic acid-inducible mRNA from human osteoblast-like cells.

Retinoids have long been known to influence skeletal development and bone remodeling. Cells of the osteoblastic lineage play a key role in these processes. In this study we have used the differential display PCR technique to identify retinoic acid (RA)-induced mRNAs in human osteoblast-like cells. We report the cloning and sequencing of one such mRNA, AT-RA 6, which was specifically induced by all-trans RA both in normal human osteoblast-like cells and in MG-63 osteosarcoma cells. Maximal expression was found after 60 min, suggesting that this may be an early response gene. Expression was found in all tissues examined. No homology to known mRNA sequences was detected.

Cell Line↗
PubMed1997

Reduced serum levels of the growth hormone-dependent insulin-like growth factor binding protein and a negative bone balance at the level of individual remodeling units in idiopathic osteoporosis in men.

Idiopathic osteoporosis in younger individuals could be related to reduced bone formation rather than increased bone resorption, and disturbances in GH or insulin-like growth factor (IGF)-I production could be involved in its pathogenesis. In the present study, men with idiopathic osteoporosis were compared with healthy men, with respect to bone histomorphometry and to serum levels of IGF-I, IGF-II, IGF binding protein (IGFBP)-2 and IGFBP-3, and 24-h urinary excretion of GH. Mean wall thickness was reduced in the patients (48.3 +/- 7.2 vs. 61.7 +/- 5.4 microns, P < 0.001). Also, resorption depth was decreased, albeit to a lesser degree (54.4 +/- 3.8 vs. 60.7 +/- 5.3 microns, P < 0.01), thus creating a pronounced negative balance (-6.04 +/- 9.8 vs. 0.96 +/- 3.2 microns, P < 0.05). In the patients, serum concentrations of IGFBP-3 were reduced, compared with controls, with a 46% lower mean value; whereas levels of IGF-I, IGF-II, IGFBP-2, and GH were similar in the two groups. Thus, there was a significant negative balance caused by a pronounced decrease in wall thickness in men with idiopathic osteoporosis. The finding of low IGFBP-3 levels in these patients is interesting, in view of previous clinical and experimental findings, but its pathophysiological significance remains to be determined.

Adult↗
PubMed1997

Regulation of interleukin-6 secretion from mononuclear blood cells by extracellular calcium.

Interleukin-6 (IL-6) is known to enhance osteoclast recruitment, and thereby bone resorption. Thus, IL-6 has been proposed to mediate hypercalcemia in multiple myeloma and the enhanced osteoclastic activity seen in postmenopausal osteoporosis. We recently reported that the calcium concentration in plasma affects IL-6 secretion from mononuclear blood cells. To investigate the underlying mechanism, we have studied the effect of calcium on IL-6 formation in mononuclear blood cells ex vivo and in vitro. Thirteen healthy volunteers were given 1 g of calcium orally after overnight fasting. Plasma levels of ionized calcium (pCa2+) and serum levels of parathyroid hormone (sPTH) were measured after 2 and 4 h, with all subjects still fasting. After 2 h, pCa2+ was increased and sPTH decreased in all 13 persons. IL-6 secretion ex vivo from mononuclear blood cells drawn 4 h after calcium intake was increased 185% as compared with IL-6 secretion from cells drawn just before calcium intake. In control experiments without calcium intake, there was no alteration in pCa2+ and no effect on IL-6 secretion from mononuclear blood cells. In vitro studies revealed that stimulation of isolated mononuclear blood cells with physiological concentrations of calcium dose-dependently increased IL-6 secretion with an estimated EC50 at 1.2 mM Ca2+. No effect on the IL-6 secretion was seen following treatment of the isolated mononuclear blood cells with PTH or calcitonin. These observations demonstrate that the plasma calcium concentration affects IL-6 secretion from mononuclear blood cells. The in vitro data indicate the involvement of a direct calcium sensing mechanism. These findings might have implications in hypercalcemia and should also be borne in mind when considering the role of cytokines in osteoporosis.

Administration, Oral↗
PubMed1996

Screening for osteopenia and osteoporosis: selection by body composition.

There is a great need for simple means of identifying persons at low risk of developing osteoporosis, in order to exclude them from screening with bone mineral measurements, since this procedure is too expensive and time-consuming for general use in the unselected population. We have determined the relationships between body measure (weight, height, body mass index, lean tissue mass, fat mass, waist-to-hip ratio) and bone mineral density (BMD) in 175 women of ages 28-74 years in a cross-sectional study in a county in central Sweden. Dual-energy X-ray absorptiometry was performed at three sites: total body, L2-4 region of lumbar spine, and neck region of the proximal femur. Using multiple linear regression models, the relationship between the dependent variable, BMD, and each of the body measures was determined, with adjustment for confounding factors. Weight alone, in a multivariate model, explained 28%, 21% and 15% of the variance in BMD of total body, at the lumbar spine and at the femoral neck according to these models. The WHO definition of osteopenia was used to dichotomize BMD, which made it possible, in multivariate logistic regression models, to estimate the risk of osteopenia with different body measures categorized into tertiles. Weight of over 71 kg was associated with a very low risk of being osteopenic compared with women weighing less than 64 kg, with odds ratios (OR) of 0.01 (95% confidence interval (CI) 0.00-0.09), 0.06 (CI 0.02-0.22) and 0.13 (CI 0.04-0.42) for osteopenia of total body, lumbar spine and femoral neck, respectively. Furthermore a sensitivity/specificity analysis revealed that, in this population, a woman weighing over 70 kg is not likely to have osteoporosis. Test specifics of a weight under 70 kg for osteoporosis (BMD less than 2.5 SD compared with normal young women) of femoral neck among the postmenopausal women showed a sensitivity of 0.94, a specificity of 0.36, positive predictive value (PPV) of 0.21, and negative predictive value (NPV) of 0.97. Thus, exclusion of the 33% of women with the highest weight meant only that 3% of osteoporotic cases were missed. The corresponding figures for lumbar spine were sensitivity 0.89, specificity 0.38, PPV 0.33, and NPV 0.91. All women who were defined as being osteoporotic of total body weighed under 62 kg. When the intention was to identify those with osteopenia of total body among the postmenopausal women we attained a sensitivity of 0.92 and a NPV of 0.91 for a weight under 70 kg, whereas we found that weight could not be used as an exclusion criterion for osteopenia of femoral neck and lumbar spine. Our data thus indicate that weight could be used to exclude women from a screening program for postmenopausal osteoporosis.

Absorptiometry, Photon↗
PubMed1996

Insulin-like growth factor I does not stimulate bone resorption in cultured neonatal mouse calvarial bones.

Insulin-like growth factor I (IGF-I) has documented anabolic effects on osteoblasts, whereas its influence on osteoclasts and on bone resorption is unclear. We have investigated the effects of IGF-I on osteoclast recruitment and bone resorption in vitro. IGF-I (at and above 1 nM) stimulated the formation of multinucleated tartrate-resistant acid phosphatase positive cells in murine bone marrow cultures, incubated for 9 days. The number of multinucleated cells increased to 540 +/- 160% of control (mean +/- SEM) in cultures treated with 10 nM IGF-I. IGF-I (0.1-100 nM) had no effect by itself on 45Ca-release from prelabelled neonatal mouse calvarial bones. However, IGF-I (100 nM) had an inhibitory effect on bone resorption induced by prostaglandin E2 and 1,25(OH)2D3. These findings indicate that IGF-I enhances the formation of osteoclasts-like cells in long-term bone marrow cultures. In bone organ cultures, however, IGF-I has an inhibitory effect on stimulated bone resorption, suggesting that IGF-I inhibits existing osteoclasts and, alternatively, that IGF-I interferes with the osteoblast-derived factor(s) that stimulate existing osteoclasts.

Animals↗
PubMed1996

Parathyroid tissue in normocalcemic and hypercalcemic primary hyperparathyroidism recruited by health screening.

Parathyroid tissue from 57 women (mean age 65.5 years) with sporadic primary hyperparathyroidism (HPT) was analyzed mainly to clarify its characteristics versus tissue from those with normocalcemia. Patients were recruited by population-based health screening of menopausal women. Analysis of three or four total serum calcium values showed normocalcemia in 16 patients (mean 2.53 mmol/L); 20 and 21 of the women were consistently (mean 2.82 mmol/L) or intermittently (mean 2.59 mmol/L) hypercalcemic, respectively. Parathyroid operation demonstrated a single adenoma in 81% of the individuals, and these lesions were most prevalent and commonly dominated by oxyphil parathyroid cells in the persistently hypercalcemic patients. Chief cell hyperplasia (two or three abnormal glands) of the nodular type was found more often in the normocalcemic patients. Total glandular weight was the smallest (mean 270 mg) among the normocalcemic women and contributed to delicate decisions with regard to the extent of resection. Immunostaining of cryosections with a monoclonal antibody recognizing a putative Ca2+ sensor demonstrated variably heterogeneous down-regulation of the recognized glycoprotein in the pathologic parathyroid glands from all the individuals. Dose-response relations for PTH release and the cytoplasmic Ca2+ concentration ([Ca2+]i) were determined in Ca2+ 0.5-3.0 mmol/L by examining dispersed cells with radioimmunoassay and microfluorometry after fura-2 loading, respectively. ED50 for PTH release and [Ca2+]i and the [Ca2+]i concentrations at Ca2+ 3.0 mmol/L were the least deranged in cells from pathologic glands of the normocalcemic patients. The findings substantiate that the abnormal parathyroid tissue of normocalcemic HPT principally is characterized by the same, albeit less extensive, morphologic and functional derangements, which consistently have been demonstrated in patients with HPT accompanied by hypercalcemia and detected clinically.

Adenoma↗
PubMed1996

Biochemical markers of bone metabolism after short and long time ethanol withdrawal in alcoholics.

The etiology of ethanol-associated osteopenia is not fully understood. A direct inhibitory effect of ethanol on osteoblast function has been suggested by in vitro and in vivo studies. In this study, we measured biochemical markers for bone formation (osteocalcin, bone specific alkaline phosphatase, procollagen-1-c-terminal peptide) and resorption (c-terminal telopeptide and urine deoxypyridinoline) in 18 otherwise healthy, but severely alcoholic men during a 10-day period of alcohol withdrawal. The same tests were performed in a group of 18 male abstainers, with more than 5 years of proven alcohol withdrawal. The results were compared with 29 male controls, randomly selected. In the group of alcoholics, osteocalcin (Oc) was significantly decreased at day 1 (p > 0.001; compared with controls). The low serum Oc levels normalized during the observation period and no significant difference was seen after 10 days. After a 5-year withdrawal, the bone-specific alkaline phosphatase was increased (p = 0.040) and there was a tendency, but not significant, of a persistent high level of Oc when compared with controls. A significant increase in fasting urinary secretion of deoxypyrodinoline was seen among the alcoholics (p = 0.001 compared with controls). The increase did not normalize during the 10-day observation period. Also, the abstainers had a significantly higher fasting urinary secretion of deoxypyridinoline after a 5-year alcohol withdrawal (p = 0.022 compared with controls). The present study suggests that there is an imbalance between bone formation and bone resorption among alcoholics that could result in rapid bone loss. Although most directions tended to normalize shortly after alcohol withdrawal, biochemical data suggest that there may still be a persistent high bone turnover after more than 5 years.

Adult↗
PubMed1996

Evaluation of modified multicompartment models to calculate body composition in healthy males.

The purpose of this study was to develop flexible and accurate multicompartment equations to calculate body composition and compare the results with methods using common two-compartment equations. Twenty-two healthy male volunteers 22-59 y of age were studied. Body volume was measured by underwater weighing (UWW) or with a skinfold caliper, bone mineral by dual-energy X-ray absorptiometry (DXA), and body water by bioelectrical impedance analysis (BIA). The percentage of water and bone mineral in fat-free mass (FFM) had a significant effect on the difference in percentage fat obtained by the two-compartment model compared with a four-compartment model. FFM density was negatively (r = -0.76, P < 0.001) and percentage water in FFM was positively correlated with age (r = 0.75, P < 0.001). The three-compartment model based on field-adapted methods (skinfold thickness + BIA) to calculate percentage body fat correlated significantly with the more complex four-compartment model (UWW + BIA + DXA; r = 0.95, P < 0.001). The advantages of three- and four-compartment equations are that they compensate for differences in body content of bone mineral and water.

Absorptiometry, Photon↗
PubMed1996

Effect of prefracture versus postfracture dietary assessment on hip fracture risk estimates.

BACKGROUND: Dietary factors are presumed to have influence on bone mass and hence fracture susceptibility. Most information in this respect is based on retrospective assessment of previous dietary habits. In a population-based case-control study nested within a cohort, we collected dietary information both before and after a first hip fracture. Thus it was possible to study reported changes in dietary habits, intentional as well as unintentional, among hip fracture patients after a first hip fracture and to compare postfracture with prefracture dietary information. METHODS: More than 65 000 women born 1914-1948 in two counties in central Sweden completed a food frequency questionnaire regarding their usual current dietary habits, before attending a mammographic screening between the years 1987 and 1990. Subsequently 123 of them sustained a first hip fracture and were defined as cases in the present study. For every case, one control, individually matched by age and county of residence, was selected from the cohort. A second identical food frequency questionnaire was mailed to both cases and controls on average 2 years after the hip fracture event. In total 98 case/control pairs could be included in the analysis. The association between diet and hip fracture was evaluated and the results from the two dietary assessments were contrasted. Women who themselves claimed that they had not changed their diet in recent years were analysed separately. RESULTS: The hip fracture cases, compared with the controls, had reduced their reported dietary intake of dairy products after the fracture. Apparently this was not intentional since this effect was more pronounced among those cases who claimed that their diet was unchanged. The changes were most apparent among the younger cases with a more recent hip fracture and with a body mass index above the median. Half of the cases, more than twice the frequency in controls, who were initially classified as having high intake of dairy products were classified as having low intake (<800 mg calcium/day) after the hip fracture. This also lowered, in fact reversed, the relative risk estimates of hip fracture both for intake of dairy products and calcium. Crude odds ratios of highest quartile of intake versus lowest, changed from 3.0 to 0.6 for dairy products and from 2.6 to 0.9 for calcium. No other foods or nutrients displayed such notable differences between the two surveys. CONCLUSION: We conclude that the use of current and retrospective dietary information after a hip fracture can lead to a differential misclassification in dietary studies and to biased estimates of hip fracture risk as compared with prospectively collected dietary information.

Age Distribution↗
PubMed1996

Biochemical markers of bone metabolism during distance running in healthy, regularly exercising men and women.

The purpose of the present study was to evaluate the effects of long distance running on bone metabolism, using the biochemical markers ICTP (the carboxyterminal cross-linked telopeptide of type I collagen), PICP (the carboxyterminal propeptide of type I procollagen), osteocalcin and bALP (bone specific alkaline phosphatase) as well as parathyroid hormone (PTH) and serum calcium. Twenty healthy, regularly exercising individuals, 10 women and 10 men, participated in a running competition. The mean age was 38 (range 22-55) and 39 (range 22-53) years respectively, the performed distance 15 (range 5-30) and 28 (range 15-30) km respectively, with a speed of 5:30, 5:02 per kilometer respectively. Fasting blood samples were drawn in the morning the day before the race, and also the day after and two days after. A decrease of PICP concentrations among women was evident the day after the competition (from 170 +/- 17 micrograms/l to 158 +/- 17 micrograms/l) which returned to pre-exercise levels two days after the race (167 +/- 19 micrograms/l). Furthermore, a decrease of osteocalcin could be seen in the men one day after the exercise (from 12.1 +/- 1.1 micrograms/l to 10.3 +/- 1.1 micrograms/l). In the men, there was also an increase of ICTP concentrations two days after (3.98 +/- 0.35 micrograms/l) this long-term and demanding exercise, when compared with pre-exercise levels (3.67 +/- 0.28). One single bout of long-term, exhaustive running exercise in well-trained men and women seems to induce a temporary inhibition of bone formation as well as a stimulation of bone resorption.

Adult↗
PubMed1996

Effects of growth hormone and insulin-like growth factor I in men with idiopathic osteoporosis.

Injections with growth hormone (GH) or insulin-like growth factor I (IGF-I) have been proposed for anabolic therapy in osteoporosis. In a cross-over study, 12 men with idiopathic osteoporosis received daily subcutaneous injections of GH (2 IU/m2) or IGF-I (80 micrograms/kg) for 7 days with 12 weeks of wash-out. Serum levels of procollagen type I increased by 29% following treatment with GH (P < 0.001) and by 43% with IGF-I (P < 0.001 compared with pretreatment levels; P < 0.05 compared with GH injections), whereas both treatments rendered a 20% increase in osteocalcin concentrations (P < 0.001), indicating enhanced bone formation. There was also evidence of stimulated bone resorption, as the urinary levels of deoxypyridinoline increased by 44% following GH injections (P < 0.001) and by 29% following IGF-I (P < 0.001), and there were 28% higher serum concentrations of IGF-I after GH than after IGF-I injections. Although markers of bone metabolism increased under both treatments, comparison of the treatments suggests that IGF-I enhanced formation of collagen type I more than did GH. Furthermore, the stimulation of bone resorption was detected as soon as 4 days after the initiation of GH injections. Some of the differences might be dose-dependent, but could also indicate separate mechanisms at the cellular level.

Adult↗
PubMed1996

Growth hormone and insulin-like growth factor-I do not activate identical genes in normal human osteoblasts.

In this study, we have examined the expression of mRNAs induced by growth hormone (GH) and insulin-like growth factor-I (IGF-I) in normal human osteoblasts using the differential display PCR method. Cells were incubated in the presence of 10(-7)M GH or IGF-I, RNA isolated and reverse-transcribed using an oligonucleotide primer, T11AC, anchored to the polyadenylate tail of a subset of mRNAs. The cDNA was then amplified using T11AC and an arbitrary 10-mer in the presence of [alpha-35S] dCTP. The PCR products were subsequently separated on a 6% DNA sequencing gel. The obtained patterns demonstrate that most, but not all, mRNAs induced by GH or IGF-I are identical. We conclude that GH and IGF-I do not induce expression of identical mRNAs in human osteoblasts. Our results support the dual effector theory of growth hormone action.

Cells, Cultured↗
PubMed1996

[Osteoporosis--what can and should be done in Sweden 1996? Swedish Osteoporosis Society].

Very recently we have seen the advent of new approaches to the investigation, treatment and prevention of osteoporosis. Pending the results of large prospective studies, a Swedish panel of experts has attempted to appraise currently available scientific knowledge of osteoporosis and make recommendations. A summary of this appraisal includes advice on bone densitometry, and on the treatment and management of patients with suspected or verified osteoporosis. It is suggested that individually tailored physical activity should be a fundamental feature of prevention and treatment, and that women in the 50-70-year-old age group, and perhaps older women as well, should have a daily calcium intake of 1200 mg. Vitamin D supplementation is recommended for the elderly under institutional care who spend no time outdoors. Oestrogen replacement therapy should be considered as prophylaxis in women at greater risk-e.g., due to manifest heredity, early menopause, low body weight, heavy smoking, or low bone mass, and in patients at risk of secondary osteoporosis.

Absorptiometry, Photon↗