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O Ljunggren

Publications and source records attributed to O Ljunggren.

At least 19 recordsLinked to original sources
PubMed2004

Muscle strength correlates with total body bone mineral density in young women but not in men.

BACKGROUND: Osteoporosis is a growing health problem. One of the proposed reasons for this is a more sedentary lifestyle. The aim of this study was to investigate the associations between muscle strength and total body bone mineral density (TBMD) in young adults at expected peak bone mass. METHODS: Sixty-four women and 61 men (total 125) 21 years of age were included. Handgrip strength, isokinetic knee-flexion and -extension muscle strength, TBMD, and body composition were measured. RESULTS: Univariate regression analyses showed that knee flexion and extension explained almost 30% of the variation in TBMD in women, whereas handgrip strength was not associated with TBMD. In men, no correlation between any measures of muscle strength and TBMD was evident. Stepwise regression analysis showed that knee-flexion and -extension muscle strength in women were associated with TBMD, R2=0.27. In men, lean body mass, fat mass, weight, and height were predictors for TBMD, R2=0.43, whereas muscle strength did not affect the prediction of TBMD. CONCLUSIONS: Muscle strength at weight-bearing sites is related to TBMD in women, whereas body composition is related to TBMD in men. The association of lower limb strength on TBMD only in young women indicates a gender difference.

Adolescent↗
PubMed2004

A deletion polymorphism in the RIZ gene, a female sex steroid hormone receptor coactivator, exhibits decreased response to estrogen in vitro and associates with low bone mineral density in young Swedish women.

Low bone mineral density (BMD) is a major risk factor for osteoporotic fracture, and the trait is under genetic control by a large number of genes. It is recognized that estrogen plays an important role in the maintenance of bone mass by binding to estrogen receptor alpha (ERalpha). RIZ1 has previously been shown to be a specific ERalpha coactivator and strongly enhances its function both in vivo and in vitro. We performed in vitro studies comparing the abilities of RIZ1 P704 polymorphic variants (homozygous presence, P704+; absence, P704-; heterozygosity P704(+/-) of a proline at position 704) to coactivate the ERalpha and also examined the polymorphism associated to BMD of 343 Swedish women, aged 20-39 yr. The expression vector containing P704- RIZ1 showed an impaired response in coactivating ERalpha in a ligand- and dose-dependent manner compared with P704+ RIZ (P < 0.0001). The genotype frequencies were 19% (P704+), 32% (P704-), and 49% (P704(+/-)) and were in Hardy-Weinberg equilibrium. BMD at the heel was higher in the P704+ genotype group than in the P704(+/-) group (P = 0.02), which was evident also after corrections for fat and lean mass (P = 0.03). We conclude that RIZ1 may be a new candidate gene for involvement in the variation seen in BMD.

Adult↗
PubMed2003

Association of the collagen type 1 (COL1A 1) Sp1 binding site polymorphism to femoral neck bone mineral density and wrist fracture in 1044 elderly Swedish women.

Identification of risk factors for osteoporosis has been essential for understanding the development of osteoporosis and related fragility fractures. A polymorphism of the binding site for the transcription factor Sp1 of the collagen I alpha 1 gene (COLIA1) has shown an association to bone mass and fracture, but the findings have not been consistent, which may be related to population differences. The Sp1 polymorphism was determined in 1044 women, all 75 years old, participating in the population-based Osteoporosis Prospective Risk Assessment study in Malmö (OPRA). Bone mineral density, heel ultrasound and all previous fractures were registered. BMD was 2.7% lower in the femoral neck in women carrying at least one copy of the "s" allele ( P = 0.027). There was no difference in bone mass at any other site, weight, BMI or age at menopause. Women with a prevalent wrist fracture (n = 181) had an increased presence of the "s" allele. The odds ratio for prevalent wrist fracture was 2.73 (95% CI 1.1-6.8) for the ss homozygotes and 1.4 (95% CI 1.0-2.0) for the Ss heterozygotes when compared with the SS homozygotes. In conclusion, in this large and homogeneous cohort of 75-year-old Swedish women, there was an association among the Sp1 COLIA1 polymorphism, bone mass, and fracture. The presence of at least one copy of the "s" allele was associated with lower femoral neck BMD and previous wrist fracture and in addition, it was related to an increased risk for wrist fracture.

Aged↗
PubMed2003

Single nucleotide polymorphisms in the human gene for osteoprotegerin are not related to bone mineral density or fracture in elderly women.

Osteoprotegerin (OPG), a secreted member of the tumor necrosis factor receptor family, is a potent inhibitor of osteoclast activation and differentiation. In animal models OPG prevents bone loss, and in humans bone resorption can be reduced by injections of OPG. OPG may also play a role in cardiovascular disease since mice lacking the OPG gene display arterial calcification. In a screening effort of the OPG gene, we recently discovered a single nucleotide polymorphism in the promoter region of OPG (T950C), and reported an association with vascular morphology and function in 59 healthy individuals. Due to the pronounced effect of OPG on bone turnover, the present study was conducted to investigate whether OPG polymorphisms are also associated with bone mineral density or with fracture. The relationship between single nucleotide polymorphisms in the promoter region of OPG (T950C) and the first intron (C1217T), and bone mineral density, measured by DXA in the hip or spine or ultrasound of the heel, was investigated in the Malmö OPRA-study of 1044 women, all 75 years old. The possible relation to fracture incidence was also analyzed. Among the 858 and 864 individuals respectively, genotyped, no significant associations between the investigated single nucleotide polymorphisms and bone mineral density measurements (T950C P = 0.50-0.64, C1217T P = 0.51-1.00), quantitative ultrasound measurements of the calcaneus, or fractures (T950C P = 0.61-0.66, C1217T P = 0.14-0.33) were found. Thus, our results show that polymorphisms in the OPG gene, one of which has previously been found to be associated with cardiovascular morphology and function, are not associated with bone mineral density in elderly Swedish women.

Aged↗
PubMed2003

A poly adenosine repeat in the human vitamin D receptor gene is associated with bone mineral density in young Swedish women.

Peak bone mass (PBM) and subsequent bone loss are important risk factors for development of osteoporosis later in life, and twin studies have reported strong genetic influence on PBM. The genetic factor influencing PBM is polygenetic, and many genes most likely exert relatively small effects on bone mass. The poly adenosine (A) microsatellite in the 3' untranslated region (UTR) of the VDR gene has been associated with both prostate and breast cancer risk but little is known about the effect of bone mineral density (BMD). In this report the poly A microsatellite and the linked BsmI SNP have been investigated in a population-based cohort of 343 Swedish women, aged 20-39. BMD was measured by dual x-ray absorptiometry at the spine, proximal femur, total body and heel and by quantitative ultrasound at the heel. Correlations were found between VDR genotypes and BMD at lumbar spine L2-L4, (ss versus LL, P = 0.03 and BB versus bb, P = 0.02, respectively), with a similar pattern concerning total hip (ss versus LL, P = 0.12 and BB versus bb, P = 0.16 respectively). After corrections for age, height, fat and lean mass, the VDR BsmI genotype was still associated to BMD at the lumbar spine (BB versus bb, P = 0.03). The polymorphisms were in linkage disequilibrium (Chi-square = 566, P < 0.0001). In conclusion, genetic variation in the VDR is associated with BMD in premenopausal women, and further studies are needed to evaluate a possible functional role of the VDR 3'UTR poly A repeat, a region that has shown to be of important for mRNA stability.

Absorptiometry, Photon↗
PubMed2002

Longitudinal bone loss in postmenopausal women with primary biliary cirrhosis and well-preserved liver function.

OBJECTIVES/DESIGN: Increased rate of bone loss has been reported in women with primary biliary cirrhosis (PBC) and varying degree of liver dysfunction. Whether bone loss is increased in patients without liver dysfunction is unclear. The aim of this study was to estimate retrospectively the rate of bone loss in postmenopausal women with PBC and well-preserved liver function. SUBJECTS/INTERVENTIONS: Forty-three women with PBC, and classified as Child-Pugh class A, were included. Bone mineral density (BMD) was measured by dual energy X-ray absorptiometry at the lumbar spine and the femoral neck. RESULTS: Median time between measurements of BMD was 26 months (range, 12-48 months). Twenty women were not receiving any bone protective treatment, i.e. hormone replacement therapy (HRT), bisphosphonates or vitamin D/calcium supplementation, whilst 23 women received such treatment. Mean annual bone loss in the former group was 0.38 +/- 2.56% and 0.42 +/- 2.29% at the lumbar spine and the femoral neck, respectively. Women receiving treatment, however, increased their BMD by 1.92 +/- 3.76% and 0.15 +/- 2.75% at the lumbar spine and the femoral neck, respectively. At the lumbar spine the difference with regard to changes in BMD between untreated and treated women was statistically significant (P = 0.02). Women who received HRT (n = 11) increased their BMD at the lumbar spine by 2.95 +/- 3.91%, P = 0.03 when compared with untreated women. CONCLUSION: Bone loss in postmenopausal women with PBC and well-preserved liver function is not increased above normal. Treatment with bone protective treatment, mainly HRT, improves BMD at the lumbar spine.

Adult↗
PubMed2001

Regulation of osteoprotegerin secretion from primary cultures of human bone marrow stromal cells.

Osteoprotegerin (OPG) is a soluble receptor for receptor activator of NF kappa B-ligand, a factor required for osteoclastogenesis. OPG secreted from bone marrow stromal cells is believed to inhibit osteoclast differentiation and several agents known to influence bone resorption have been demonstrated to regulate mRNA levels of OPG. In this report we have investigated the secretion of OPG protein from primary cultures of human bone marrow stromal cells. An ELISA was developed for measuring the concentration of OPG in culture medium. OPG secretion was decreased by 50% when the human bone marrow stromal cells were treated with 1 microM of prostaglandin E(2), possibly through activation of the protein kinase A-pathway since stimulation of protein kinase A by forskolin also inhibited OPG secretion. Treatment with phorbol 12,13 di butyrate, an activator of the protein kinase C-pathway, potently stimulated the secretion of OPG from human bone marrow stromal cells. The cells were also stimulated with inflammatory mediators and glucocorticoids. Treatment with interleukin-1 alpha (IL-1 alpha) and tumor necrosis factor-alpha (TNF-alpha) stimulated OPG secretion to 500% and 400% of control whereas dexamethasone decreased OPG production by 40%. In conclusion, an ELISA measuring OPG in cell culture media was developed. Using this ELISA, the amount of OPG secreted from human bone marrow stromal cells was clearly detectable, and the secretion of OPG-protein was potently regulated by prostaglandin E(2), forskolin, phorbol 12,13 di butyrate, IL-1 alpha, TNF-alpha, and dexamethasone.

Bone Marrow Cells↗
PubMed2001

Interleukin (IL)-13 and IL-4 inhibit proliferation and stimulate IL-6 formation in human osteoblasts: evidence for involvement of receptor subunits IL-13R, IL-13Ralpha, and IL-4Ralpha.

Interleukin-13 (IL-13) inhibits cell proliferation and stimulates interleukin-6 (IL-6) formation in isolated human osteoblasts (hOBs). Because the related cytokine, interleukin-4 (IL-4), is known to exert effects similar to IL-13 in other tissues, and because IL-4 has been implicated as a regulator of bone metabolism, we compared the effects of IL-13 and IL-4 on cell proliferation, IL-6 synthesis, the expression of osteoblastic phenotypic markers in hOB cultures. Also, the receptor proteins mediating these effects in hOBs have been partly characterized. IL-4 and IL-13 dose-dependently inhibited [(3)H]-thymidine incorporation into the DNA of human osteoblasts and stimulated secretion of IL-6 into culture supernatants. IL-13 and IL-4 also increased the mRNA levels of IL-6, as measured by RNAse protection assay. Furthermore, IL-13 and IL-4 dose-dependently enhanced alkaline phosphatase (ALP) activity, but did not affect osteocalcin or collagen type I synthesis. IL-4 was tenfold more potent than IL-13 in inducing both ALP activity and IL-6 secretion, whereas the cytokines were equipotent as inhibitors of cell proliferation. The expression of mRNA for receptor subunits previously implicated in IL-4 and IL-13 signaling was investigated by reverse transcriptase-polymerase chain reaction. IL-13R, IL-13Ralpha, and IL-4Ralpha mRNA were repeatedly detected in hOBs, whereas mRNA for IL-2Rgamma(C) was not detected. Receptor-blocking antibodies to IL-4Ralpha inhibited the induction of IL-6 formation by both IL-4 and IL-13, indicating that both cytokines utilize this receptor subunit in signaling. However, the antibodies did not affect the IL-4/-13-induced inhibition of [(3)H]-thymidine incorporation or the stimulation of alkaline phosphatase (ALP), suggesting that IL-4Ralpha does not mediate these effects of IL-4/-13 in hOBs. We conclude that the cytokines IL-13 and IL-4, through sharing of receptor components, induce similar effects on hOBs, causing inhibition of cell proliferation, stimulation of IL-6, and enhanced ALP activity.

Antibodies, Monoclonal↗
PubMed2001

Inverse relationship between circulating levels of leptin and bone mineral density in chronic liver disease.

BACKGROUND AND AIM: The pathophysiology of osteoporosis complicating chronic liver disease is unknown. Recent animal studies have found leptin to be a potent inhibitor of bone formation. The aim of this study was to investigate the relationship between serum leptin levels and bone mineral density in patients with chronic liver disease. METHODS: Fifty-eight patients, 39 females and 19 males, and age- and gender-matched controls were included. Bone mineral density was measured by using dual energy X-ray absorptiometry. Serum leptin was measured by using a radioimmunoassay. RESULTS: The mean serum leptin concentration was 10.4 +/- 11.3 and 15.2 +/- 17.9 ng/mL; P=0.11, in the patients and controls, respectively. Leptin correlated positively with body mass index in patients (r=0.40; P=0.003) and in controls (r=0.55; P < 0.0001). In patients classified as Child-Pugh grade B and C, serum leptin correlated negatively with bone mineral density in females at both the lumbar spine and the femoral neck (r=-0.78; P=0.04 and r=-0.86; P=0.03, respectively). In male patients, the correlation was only significant at the lumbar spine (r=-0.99; P=0.002 and r=-0.86; P=0.06, at the lumbar spine and femoral neck, respectively). No correlation was found between serum leptin and bone mineral density in the controls. CONCLUSION: An inverse relationship between serum leptin and bone mineral density was found in patients with advanced chronic liver disease. The reasons for these findings are uncertain, but a pathophysiological role of circulating leptin in osteoporosis in chronic liver disease is possible.

Absorptiometry, Photon↗
PubMed2001

The autosomal dominant hypophosphatemic rickets (ADHR) gene is a secreted polypeptide overexpressed by tumors that cause phosphate wasting.

The gene mutated in autosomal dominant hypophosphatemic rickets (ADHR), a phosphate wasting disorder, has been identified as FGF-23, a protein that shares sequence homology with fibroblast growth factors (FGFs). Patients with ADHR display many of the clinical and laboratory characteristics that are observed in patients with oncogenic hypophosphatemic osteomalacia (OHO), a disorder thought to arise by the secretion of a phosphate wasting factor from different mesenchymal tumors. In the present studies, we therefore investigated whether FGF-23 is a secreted factor and whether it is abundantly expressed in OHO tumors. After transient transfection of OK-E, COS-7, and HEK293 cells with the plasmid encoding full-length FGF-23, all three cell lines efficiently secreted two protein species into the medium that were approximately 32 and 12 kDa upon SDS-PAGE and subsequent Western blot analysis using an affinity-purified polyclonal antibody to FGF-23. Furthermore, Northern blot analysis using total RNA from five different OHO tumors revealed extremely high levels of FGF-23 mRNA, and Western blot analysis of extracts from a sixth tumor detected the 32 kDa FGF-23 protein species. In summary, FGF-23, the gene mutated in ADHR, is a secreted protein and its mRNA is abundantly expressed by several different OHO tumors. Our findings indicate that FGF-23 may be a candidate phosphate wasting factor, previously designated "phosphatonin".

Animals↗
PubMed2001

Diagnosis of a patient with oncogenic osteomalacia using a phosphate uptake bioassay of serum and magnetic resonance imaging.

A previously healthy man with no family history of fractures presented with muscle pain, back pain and height loss. Investigations revealed hypophosphataemia, phosphaturia, undetectable serum 1,25-dihydroxyvitamin D and severe osteomalacia on bone biopsy, suggestive of a diagnosis of oncogenic osteomalacia. Thorough physical examination did not locate a tumour. Support for the diagnosis was obtained by detection of phosphate uptake inhibitory activity in a blinded sample of the patient's serum using a renal cell bioassay. On the basis of detection of this bioactivity, a total body magnetic resonance (MR) examination was performed. A small tumour was located in the right leg. Removal of the tumour resulted in the rapid reversal of symptoms and the abnormal biochemistry typical of oncogenic osteomalacia. Inhibitory activity was also demonstrated using the bioassay in serum from two other patients with confirmed or presumptive oncogenic osteomalacia, but not in serum from two patients with hypophosphataemia of other origin. This is the first case to be reported in which the diagnosis of oncogenic osteomalacia was assisted by demonstration of inhibitory activity of the patient's serum in a renal cell phosphate bioassay that provided an impetus for total body MR imaging.

Adult↗
PubMed2000

Hypocalcemia and parathyroid hormone secretion in critically ill patients.

OBJECTIVE: To investigate possible causes of hypocalcemia and to assess parathyroid hormone (PTH) secretion in intensive care unit (ICU) patients. DESIGN: Combined cross-sectional and prospective study. SETTING: ICU in a university hospital. PATIENTS: Thirteen patients with sepsis and 13 patients who underwent major surgery. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Calcium metabolic indices were investigated during the first 24 hrs in the ICU and after 2 days. Eight of the surgical patients and five of the septic patients were subjected to a citrate/calcium infusion on day 1 in the ICU, to study the dynamics of PTH secretion. The blood ionized calcium (Ca2+) concentration was generally low in the septic patients (mean +/- SD, 1.03+/-0.08 mmol/L; reference value, 1.10-1.30) and increased, but not normalized, after 2 days. Hypocalcemia was only occasionally seen in the surgical patients. In the septic patients, urinary excretion of calcium was low; and, in both patient groups, elevated concentrations of two markers of bone resorption, deoxypyridinoline and ICTP (serum carboxy-terminal cross-linked telopeptide of type I collagen), were found. In cases of sepsis, the concentrations of proinflammatory cytokines were high (394+/-536 pg/mL for tumor necrosis factor-alpha and 5676+/-5190 pg/mL for interleukin-6, both normally <10-20). The Ca2+ concentration was inversely related to tumor necrosis factor-alpha and interleukin-6 (r2 = .35-.42; p<.01), as well as to procalcitonin (r2 = .71; p<.01). Despite normocalcemia in the surgical patients, serum PTH concentrations were elevated in both patient groups (97 and 109 ng/L) (reference value, <55 ng/L), both on day 1 and day 3 in the ICU. The citrate/calcium infusion revealed an increased secretory response of PTH to lowered Ca2+ concentrations in both groups of patients (p<.05), when compared with matched healthy controls. CONCLUSION: Hypocalcemia was common in septic ICU patients and was not the result of an increased urinary excretion of calcium or of an attenuated bone resorption, but seemed related to the inflammatory response. An increased PTH secretion was found in both patient groups.

APACHE↗
PubMed1999

Low body mass index and use of corticosteroids, but not cholestasis, are risk factors for osteoporosis in patients with chronic liver disease.

BACKGROUND/AIMS: Metabolic bone disease is known to complicate chronic liver disease. In a cross-sectional, controlled study we have studied the prevalence of osteoporosis in patients with various types of chronic liver disease. We also identified risk factors predisposing to osteoporosis in this patient group. METHODS: Seventy-two hospitalised patients, 46 females and 26 males, were included. Age- and sex-matched individuals from the background population served as controls. Bone mineral density was measured by dual energy X-ray absorptiometry at the lumbar spine and femoral neck. RESULTS: Bone mineral density was significantly lower in patients with chronic liver disease than in controls at the lumbar spine (Z-score: -0.35 SD+/-1.36 vs. 0.26 SD+/-1.19, p<0.01) but not at the femoral neck (Z-score: -0.18 SD+/-1.48 vs. 0.17 SD+/-1.08, NS). Patients with cholestatic chronic liver disease did not have lower bone mineral density compared with patients with non-cholestatic chronic liver disease (Z-score: -0.35 SD+/-1.30 vs. -0.34 SD+/-1.45). Osteoporosis was found in 30% of the patients and 15% of the controls, respectively. In a multivariate regression analysis on risk factors in the patient group, the following factors were associated with osteoporosis: use of corticosteroids (odds ratio=18.9; p<0.01), low body mass index (odds ratio=14.1; p=0.001), high age and female sex. CONCLUSION: Patients with chronic liver disease are at risk of developing osteoporosis. Risk factors for osteoporosis in chronic liver disease are low body mass index and corticosteroid therapy, in addition to high age and female sex. Cholestatic liver disease per se is not associated with an increased risk for osteoporosis.

Absorptiometry, Photon↗
PubMed1999

Three isolation techniques for primary culture of human osteoblast-like cells: a comparison.

The culture of osteoblast-like cells of human origin has become an important experimental model in bone biology. We report here a comparison and evaluation of three of the most widely used systems available today: bone marrow stroma cell cultures (BMSC), human osteoblast explant cultures (hOB) and osteoblast explant cultures from collagenase-treated bone (hOBcol). Cultures from 16 bone specimens obtained from various donors were established and their expression of the osteoblast phenotype were then compared in secondary cultures by use of biochemical markers. BMSC had the highest basal and 1,25-dihydroxyvitaminD3 (1,25(OH)2D3)-induced alkaline phosphatase activities in all cell isolations, with levels approximately twice those in explant cultures. Basal osteocalcin secretion was low-to-undetectable in all cell cultures but was detected in 1,25(OH)2D3-stimulated cultures. BMSC produced half of the amount of osteocalcin synthesized in explant cultures. The BMSC cultures also synthesized the lowest amounts of type I collagen, whereas collagen type III synthesis did not differ significantly among the various cultures. When secondary cultures were treated with 100 nM dexamethasone in the presence of ascorbic acid (50 microg/mL) and beta-glycerophosphate (10 mM), cultures deposited calcium mineral into the cell layer within 2-4 weeks. PTH-induced cAMP formation was detected in only 5 of 15 isolations and no consistent isolation-dependent response pattern was seen. We conclude that BMSC cultures differ significantly from explant cultures obtained from the same bone specimen. However, all cultures represent cells which can differentiate further and induce mineralization of the extracellular matrix in response to osteoinductive drugs.

Adolescent↗
PubMed1999

Thrombin, but not bradykinin, stimulates proliferation in isolated human osteoblasts, via a mechanism not dependent on endogenous prostaglandin formation.

Osteolysis or osteosclerosis often occurs in bone tissue adjacent to chronic inflammatory processes. Numerous cytokines and inflammatory mediators have been implicated as osteoclast-activating agents, explaining inflammation-induced bone resorption. In many cases, the cause of the sclerosis seen in these lesions is less thoroughly investigated. We have studied the effects of thrombin and bradykinin, 2 inflammatory mediators, on the rate of proliferation in isolated human osteoblasts (hOBs). Thrombin, at and above 1 U/mL, stimulated the rate of thymidine incorporation into hOBs. The absolute cell number also increased, as measured by an assay based on the detection of cell metabolism. A synthetic peptide ligand for the thrombin receptor enhanced the rate of [3H]thymidine incorporation in hOBs, indicating that thrombin-induced proliferation is mediated via the tetheric thrombin receptor. The thrombin-induced proliferation was not affected by indomethacin, excluding prostanoids as mediators of this effect. Bradykinin did not affect either the rate of thymidine incorporation, or number of cells in long-term cultures of hOBs. In conclusion, the inflammatory mediator, thrombin, stimulates proliferation in isolated human osteoblasts probably via the recently described G-protein-coupled tetheric thrombin receptor. Thrombin may therefore be involved as a mediator of inflammation-induced sclerosis and bone formation.

Anti-Inflammatory Agents, Non-Steroidal↗