Unni Syversen - Academia.edu (original) (raw)

Papers by Unni Syversen

Bone, 2020

Estrogen deficiency causes bone loss and skeletal muscle dysfunction, and attenuates the musculos... more Estrogen deficiency causes bone loss and skeletal muscle dysfunction, and attenuates the musculoskeletal effects of exercise. The anti-diabetic drug metformin has been suggested to promote beneficial skeletal effects. To explore whether metformin can improve musculoskeletal training response during estrogen deficiency, we investigated the skeletal effects of plyometric exercise and metformin, in an ovarectomized (OVX) rat model of osteoporosis. Female Sprague Dawley rats, 12 weeks of age, rats were allocated to a sham-operated group (Sham), and four OVX groups; metformin (OVX-Met), exercise (OVX-Ex), combined metformin and exercise (OVX-MetEx) and a control group (OVX-Ctr), n = 12/group. Dual X-ray absorptiometry, micro computed tomography, fracture toughness testing, histomorphometry and plasma analyses were performed to explore skeletal effects. All intervention groups exhibited a higher gain in femoral bone mineral density (BMD) than OVX-Ctr (p < .01). The combined intervention also resulted in a higher gain in femoral and spine BMD compared to OVX-Met (p < .01). Both exercise groups displayed improved microarchitecture, including both cortical and trabecular parameters (p < .05). This was most evident in the OVX-MetEx group where several indices were at sham level or superior to OVX-Ctr (p < .05). The OVX-MetEx group also exhibited an enhanced toughening effect compared to the other OVX groups (p < .05). The beneficial skeletal effects seemed to be mediated by inhibition of bone resorption and stimulation of bone formation. The training response (i.e. jumping height) was also greater in the metformin treated rats compared to OVX-Ex (p < .01), indicating a performance-enhancing effect of metformin. Both exercise groups displayed higher lean mass than OVX-Ctr (p < .05). In conclusion, the combination of plyometric exercise and metformin improved trabecular microarchitecture and bone material properties relative to OVX controls. However, no additive effect of the combined intervention was observed compared to exercise alone.

Tidsskrift for Den norske lægeforening, 2011

Inntil nylig har antiresorptive medikamenter vaert det eneste alternativet i behandling av osteop... more Inntil nylig har antiresorptive medikamenter vaert det eneste alternativet i behandling av osteoporose. Parathyreoideahormon (PTH) representerer et ny prinsipp i behandlingen. Gi intermi erende stimulerer det osteoblastene og beinformasjonen. I denne artikkelen presenteres resultatene av parathyreoideahormonets effekt på beinmetabolisme, beinte het og frakturreduksjon, og vi diskuterer rollen det har i dagens behandling av osteoporose.

Tidsskrift for Den Norske Laegeforening, 2003

Frontiers in Endocrinology

ContextExercise is recognized as an important strategy to prevent bone loss, but its acute effect... more ContextExercise is recognized as an important strategy to prevent bone loss, but its acute effects on bone turnover markers (BTMs) and related markers remain uncertain.ObjectiveTo assess the acute effects of two different exercise modes on BTMs and related markers in young adults of both sexes and elderly men.Design, Setting, ParticipantsThis was a three-group crossover within-subjects design study with a total of 53 participants—19 young women (aged 22–30), 20 young men (aged 21–30 years), and 14 elderly men (aged 63–74 years)—performing two different exercise sessions [strength training (ST) and high-intensity interval training (HIIT)] separated by 2 weeks, in a supervised laboratory setting.Main Outcome MeasuresPlasma volume-corrected serum measurements of the BTMs C-terminal telopeptide of type 1 collagen (CTX-I) and procollagen of type 1 N-terminal propeptide (P1NP), total osteocalcin (OC), sclerostin, and lipocalin-2 (LCN2) at baseline, immediately after, and 3 and 24 h after ...

Research article Different skeletal effects of the peroxisome proliferator activated receptor (PP... more Research article Different skeletal effects of the peroxisome proliferator activated receptor (PPAR)α agonist fenofibrate and the PPARγ agonist pioglitazone

PLOS ONE, 2019

Background Vitamin A and D deficiency is prevalent in pregnant women worldwide. Both vitamins are... more Background Vitamin A and D deficiency is prevalent in pregnant women worldwide. Both vitamins are involved in fetal skeletal development. A positive association between maternal vitamin D levels and offspring bone mineral density (BMD) at adulthood has been observed. The impact of maternal vitamin A status in pregnancy on offspring peak bone mass remains unclear. Method and findings Forty-one mother-child pairs were recruited from a population-based prospective cohort study in Trondheim, Norway, where pregnant women were followed from gestational week 17. Their term-born infants were followed from birth (1986-88). Regression analyses were performed for vitamin A (retinol), 25-hydroxyvitamin D [25(OH)D] and 1,25-dihydroxyvitamin D [1,25(OH) 2 D] in maternal serum (gestational weeks 17, 33, 37) and cord blood. Offspring BMD and spine trabecular bone score (TBS), a measure of bone quality, were analyzed by dual x-ray absorptiometry at 26 years. Average levels during pregnancy of retinol, 25(OH)D and 1,25(OH) 2 D were 1.66 (0.32) μmol/L, 59.0 (20.6) nmol/L, and 251.3 (62.4) pmol/L, respectively. 1,25(OH) 2 D levels were similar in those with 25(OH)D levels <30 and >75 nmol/L. After adjustment for maternal age, BMI, smoking, and education, and offspring birth weight, maternal serum retinol was positively associated with offspring spine BMD [mean

PLOS ONE, 2018

To ensure optimal calcium accrual in the fetal skeleton, a substantial rise occurs in 1,25dihydro... more To ensure optimal calcium accrual in the fetal skeleton, a substantial rise occurs in 1,25dihydroxyvitamin D (1,25(OH) 2 D), but is dependent on sufficient 25-hydroxyvitamin (25(OH) D). Large longitudinal studies addressing free 25(OH)D and 1,25(OH) 2 D during pregnancy are scarce. We aimed to assess levels of and relationship between 25(OH)D, 1,25(OH) 2 D, vitamin D-binding protein (DBP), parathyroid hormone (PTH), and free 25(OH)D during pregnancy; determinants of vitamin D status; and association between vitamin D indices or PTH and pregnancy outcomes (gestational diabetes mellitus and birthweight). Altogether 855 pregnant Norwegian Caucasian women from Trondheim and Stavanger (latitude 63˚N and 58˚N) were recruited; 94 were lost to follow-up. The study was originally a randomized controlled trial (2007-2009) with gestational diabetes as primary outcome. Data were collected in second and third trimester. In third trimester, 246 (34%) had vitamin D insufficiency and 52 (7%) deficiency (25(OH)D <50 and <30nmol/L, respectively). During wintertime in third trimester, 61 (47%) from Trondheim and 23 (51%) from Stavanger exhibited vitamin D insufficiency. PTH was elevated in 27 (3.7%). Estimate of change between trimesters was (95% CI): 25(OH)D-1.8 (-2.8 to-0.7) nmol/L, DBP 0.62 (0.57 to 0.66) μmol/L, calculated free 25(OH)D-1.7 (-2.0 to-1.4) pmol/L, PTH 0.81 (0.72 to 0.90) pmol/L, 1,25(OH) 2 D (subanalysis) 31.4 (CI 24.7 to 38.2) pmol/L. A decrease in 1,25(OH) 2 D occurred in 45% of those with vitamin D deficiency, and they also exhibited lower levels than women with adequate vitamin D status. No association of vitamin D indices and PTH with pregnancy outcomes was observed. Women in Trondheim displayed lower 25(OH)D levels, despite minor latitudinal differences. Less than one-fifth adhered to the authorities' vitamin D recommendations. These findings demonstrate that hypovitaminosis D is prevalent among pregnant women

Bone Abstracts, 2016

The objective was to examine the effects of repetitive local administration of adiponectin on exp... more The objective was to examine the effects of repetitive local administration of adiponectin on experimental tooth movement in rats. Materials and methods: The maxillary right first molar of male Wistar rats (n = 24) was moved mesially for 14 days, with local adiponectin injections (0.2 or 2 μg) every third day. Micro-computed tomography was performed at days 0, 6 and 14 and molar movement, bone density and bone volume fraction were calculated from the scans. Changes in extracellular matrix collagen and cell numbers in the periodontal ligament were analyzed histologically, and levels of circulating cytokines were measured by Luminex and ELISA. Results: Adiponectin injections induced a reduction in tooth movement after 12 and 14 days compared to controls. No tooth movement was observed between days 3 and 14 in the group receiving the highest dosage (2 μg) of adiponectin. Differences in bone density and bone volume fractions between treatment and control groups were not identified. Relative size and morphology of collagen fibrils, and cell number in the periodontal region after adiponectin injections were unchanged compared to controls. Levels of circulating adiponectin or other selected factors in plasma were not influenced by the adiponectin injections. Conclusions: Submucosal injections of adiponectin prevented experimental tooth movement in rats. The effect was dosage-dependent and local. Adiponectin injections caused no detectable changes in bone density, periodontal cell number or collagen content.

$Research paper thumbnail of OP0039 Increased porosity in hand bones is strongly associated with distal radius fracture in elderly women$

Annals of the Rheumatic Diseases, 2013

Background Distal radius fracture (fx) is one of the most common osteoporotic fx. Osteoporosis de... more Background Distal radius fracture (fx) is one of the most common osteoporotic fx. Osteoporosis defined as T-score ≤-2.5 SD at spine and/or hip assessed by Dual Energy X-ray (DXA) has been identified as an independent risk factor for distal radius fx [1]. However, a large proportion of fragility distal radius fx occur in patients (∼68%) with T-score > -2.5 [2]. Assessment of bone structure e.g. cortical porosity may improve identification of individuals at high risk of fx [3]. Digital X-ray Radiogrammetry (DXR) used for quantitative measurement of metacarpal cortical hand bone mineral density (BMD) has been shown to predict distal radius fx [4]. This method also provides a quantitative measure of porosity. Objectives To explore the association between increased cortical hand porosity assessed by DXR and risk of distal radius fx in elderly women. Methods In this prospective case control study, women with distal radius fx (>50 years) were consecutively recruited from a community hospital. Age-matched controls were randomly identified in the national registry for the same catchment area and invited by mail. A hand radiograph from the non-dominant arm was used for DXR assessment and measurements included: BMD, porosity, cortical thickness and bone width. BMD at lumbar spine (L2-4) and femoral neck was measured by DXA. Statistical tests were applied using SPSS. Results No significant difference was observed between the 114 distal radius fx patients and the 156 controls for age (67.7 vs 67.2 years, p=0.7), height (164.9 vs 163.8cm, p=0.1) or weight (68.9 vs 71.5 kg, p=0.1) nor for smoking, exercise, use of vitamin-D, bisphosphonates, estrogen or glucocorticoids. BMD was significantly reduced in fx patients compared with controls both in femoral neck (0.793 vs 0.838 g/cm2, p=0.005) and spine (1.031 vs 1.099 g/cm2, p=0.003) and for DXR hand (0.495 vs 0.522, p=0.003). For the individual components from which DXR BMD is calculated, a significant difference was seen for porosity (0.0124 vs 0.0109, p<0.001) and cortical thickness (0.149 vs 0.160, p=0.002), but not for bone width (0.822 vs 0.811, p=0.055). In univariate regression analysis, expressed as odds ratio (OR), a reduction in the following variables were found to be significantly associated with a distal radius fx: DXR BMD (OR 1.005 per mg, p=0.004), DXA BMD (femoral neck OR 1.003 per mg, p=0.006, spine OR 1.002 per mg, p=0.004) and cortical thickness (OR 1.013 per mm, p=0.002), whereas an increase in porosity was found to be associated with an increased risk of distal radius fx (OR 7.3 per % point increase, p<0.000). In a multivariate regression model including variables with p<0.2 in the univariate analysis, (DXR BMD and cortical thickness exluded due to linearity) porosity remained significantly associated with distal radius fx (OR 10.08 per % point increase, p=0.001). Conclusions Our results suggest cortical bone porosity, a measure of bone structure, to play a major role in increasing distal fracture risk in elderly women. References Oyen et al. Osteoporosis Int 2010 Oyen et al. Osteoporosis Int 2009 Zebaze et al. Lancet 2010 Bouxein et al. Osteoporosis Int 2002 Disclosure of Interest None Declared

International Journal of Chronic Obstructive Pulmonary Disease, 2009

Patients with COPD have high risk for osteoporosis and fractures. Hip and vertebral fractures mig... more Patients with COPD have high risk for osteoporosis and fractures. Hip and vertebral fractures might impair mobility, and vertebral fractures further reduce lung function. This review discusses the evidence of bone loss due to medical treatment opposed to disease severity and risk factors for COPD, and therapeutic options for the prevention and treatment of osteoporosis in these patients. A review of the English-language literature was conducted using the MEDLINE database until June 2009. Currently used bronchodilators probably lack adverse effect on bone. Oral corticosteroids (OCS) increase bone resorption and decrease bone formation in a dose response relationship, but the fracture risk is increased more than reflected by bone densitometry. Inhaled corticosteroids (ICS) have been associated with both increased bone loss and fracture risk. This might be a result of confounding by disease severity, but high doses of ICS have similar effects as equipotent doses of OCS. The lifestyle factors should be modified, use of regular OCS avoided and use of ICS restricted to those with evidenced effect and probably kept at moderate doses. The health care should actively reveal risk factors, include bone densitometry in fracture risk evaluation, and give adequate prevention and treatment for osteoporosis.

Molecular and Cellular Endocrinology, 2002

The exocrine pancreatic cell line AR42J is also known to display some neuroendocrine (NE) feature... more The exocrine pancreatic cell line AR42J is also known to display some neuroendocrine (NE) features. We have extended this fact by showing that AR42J cells express mRNA of chromogranin A (CgA), display immunoreactivity (IR) to CgA, and secrete its cleavage product pancreastatin. A sparse occurrence of typical NE secretion granules, together with only a faint IR to conventional NE markers, indicates that the NE cells are of a poorly differentiated type. CgA promoter reporter plasmid experiments showed that gastrin, epidermal growth factor, and phorbol 12-myristate 13-acetate, induce upregulation of CgA after 24 h. By RT-PCR, it was found that AR42J expresses all of the five subtypes of the somatostatin (SST) receptor (SSTR) family, except SSTR4. The existence of functional SSTRs was confirmed by showing that the SST analog octreotide could inhibit gastrin-induced proliferation. Thus, the AR42J cell line may function as a valuable experimental model to study the regulation of CgA and SSTRs in poorly differentiated NE tumor cells.

The American Journal of Cardiology, 2007

Peroxisome proliferator-activated receptors (PPARs) are central regulators of lipoprotein metabol... more Peroxisome proliferator-activated receptors (PPARs) are central regulators of lipoprotein metabolism and glucose homeostasis that are considered particularly useful for improving glycemic control and comorbidities in patients with type 2 diabetes mellitus. Clinical trials of PPAR-␣ agonists have demonstrated efficacy in reducing cardiovascular events; however, these benefits have been confined to subgroups of patients with low levels of high-density lipoprotein cholesterol or high levels of triglycerides. While activators of PPAR-␥ reduce early atherosclerotic lesions and reduce cardiovascular events, these agents have the effect of increasing fluid retention in patients, which results in more hospitalizations for congestive heart failure. Future studies of PPAR-␥ agonists or dual PPAR-␣/␥ agonists will require further delineation of the risk profile to avoid adverse outcomes in susceptible patients.

International Journal of Environmental Research and Public Health

Given the scarcity of data on diabetes prevalence and associated risk factors among women in rura... more Given the scarcity of data on diabetes prevalence and associated risk factors among women in rural Nepal, we aimed to examine this, using glycated hemoglobin (HbA1c) as a diagnostic tool. A cross-sectional survey addressing reproductive health and non-communicable diseases was conducted in 2012–2013 among non-pregnant, married women in Bolde, a rural district of Nepal. HbA1c ≥ 6.5% (48 mmol/mol) was used as diagnostic criterion for diabetes, a cut-off of 7.0% (53 mmol/mol) was used to increase the specificity. HbA1c was measured in 757 women (17–86 years). The prevalence of diabetes and prediabetes was 13.5% and 38.5%, respectively. When using 7.0% as a cut-off, the prevalence of diabetes was 5.8%. Aging, intake of instant noodles and milk and vegetarian food (ns) were associated with increased risk for diabetes. Waist circumference was higher among women with diabetes, although not significant. The women were uneducated (87.6%), and only 12% had heard about diabetes. In conclusion,...

Nutrients

Hypovitaminosis D is prevalent worldwide, and especially in South-Asia. According to the Institut... more Hypovitaminosis D is prevalent worldwide, and especially in South-Asia. According to the Institute of Medicine (IOM), 25(OH)D levels below 30 nmol/L are defined as vitamin D deficiency (VDD) and levels between 30–50 nmol/L as insufficiency (VDI). Besides its role in calcium homeostasis, it has been postulated that vitamin D is involved in metabolic syndrome. Given the scarcity of data on vitamin D status in Nepal, we aimed to examine the prevalence of VDD and VDI, as well as the determinants and association with metabolic parameters (lipids, HbA1c), in a cohort of women in rural Nepal. Altogether, 733 women 48.5 ± 11.7 years of age were included. VDD and VDI were observed in 6.3 and 42.4% of the participants, respectively, and the prevalence increased by age. Women reporting intake of milk and eggs > 2 times weekly had higher 25(OH)D levels than those reporting intake < 2 times weekly. Women with vitamin D levels < 50 nmol/L displayed higher levels of cholesterol, LDL-chole...

Bone Reports, 2021

Due to gastrointestinal side effects of oral bisphosphonates (BPs), proton pump inhibitors (PPIs)... more Due to gastrointestinal side effects of oral bisphosphonates (BPs), proton pump inhibitors (PPIs) are often prescribed. PPIs may enhance the risk of osteonecrosis of the jaw, a rare side effect of BPs. Therefore, the objective of this study was to evaluate the effects of the oral BP alendronate (ALN) and the PPI omeprazole (OME) alone and in combination on primary human osteoblasts and gingival fibroblasts in vitro. Methods: Human gingival fibroblasts and normal human osteoblasts were incubated with either 5 μM of ALN or 1 μM of OME, or ALN + OME for 1, 3, 7 or 14 days. Effect on viability was evaluated by the lactate dehydrogenase activity in the medium and on proliferation by quantifying 3H-thymidin incorporation. Multianalyte profiling of proteins in cell culture media was performed using the Luminex 200TM system to assess the effect on selected bone markers and cytokines. Results: The proliferation of osteoblasts and fibroblasts was reduced upon exposure to ALN + OME. ALN induced an early, temporary rise in markers of inflammation, and OME and ALN + OME promoted a transient decline. An initial increase in IL-13 occurred after exposure to all three options, whereas ALN + OME promoted IL-8 release after 7 days. OME and ALN + OME promoted a transient reduction in vascular endothelial growth factor (VEGF) from osteoblasts, whereas ALN and ALN + OME induced a late rise in VEGF from fibroblasts. Osteoprotegerin release was enhanced by ALN and suppressed by OME and ALN + OME. Conclusions: ALN + OME seemed to exaggerate the negative effects of each drug alone on human osteoblasts and gingival fibroblasts. The anti-proliferative effects, modulation of inflammation and impairment of angiogenesis, may induce unfavorable conditions in periodontal tissue facilitating development of osteonecrosis.

BMC Pregnancy and Childbirth

Background: Vitamin D insufficiency is common in pregnant women worldwide. Regular prenatal exerc... more Background: Vitamin D insufficiency is common in pregnant women worldwide. Regular prenatal exercise is considered beneficial for maternal and fetal health. There is a knowledge gap regarding the impact of prenatal exercise on maternal vitamin D levels. The objective of this study was to investigate whether a prenatal exercise program influenced serum levels of total, free and bioavailable 25-hydroxyvitamin D (25(OH)D) and related parameters. This is a post hoc analysis of a randomized controlled trial with gestational diabetes as the primary outcome.