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1.
J Rheumatol ; 47(5): 722-729, 2020 05 01.
Article in English | MEDLINE | ID: mdl-31308209

ABSTRACT

OBJECTIVE: To determine the risk of cancer in a large Norwegian cohort of patients with giant cell arteritis (GCA). METHODS: This is a hospital-based, retrospective, observational cohort study including patients diagnosed with GCA in the Bergen Health Area during 1972-2012. Patients were identified through computerized hospital records using the International Classification of Diseases coding system. Medical records were reviewed. Each patient was randomly assigned population controls matched on age, sex, and geography from the Central Population Registry of Norway. Data on the occurrence of cancer were obtained from the Cancer Registry of Norway. The cumulative risk of malignancy was estimated using Kaplan-Meier methods and potential differences were analyzed using the Gehan-Breslow and log-rank tests. RESULTS: We identified 881 cases with a clinical diagnosis of GCA, of which 792 fulfilled the American College of Rheumatology (ACR) 1990 classification criteria and 528 were biopsy-verified. Cases with no registered cancer prior to GCA diagnosis were included in a time-to-event analysis, with first cancer as the event (n = 767 with clinical GCA diagnosis, 686 fulfilling ACR criteria for GCA, 463 biopsy-verified). These cases were matched with previously cancer-free population controls (n = 1437, 1284, 895, respectively). We found no significant difference in the risk of malignancy after time of diagnosis/matching for GCA patients compared to population controls (p > 0.05). CONCLUSION: In this study of a large and well-characterized cohort of patients with GCA, there was no difference in the risk of malignancy in patients with GCA compared to matched population controls.


Subject(s)
Giant Cell Arteritis , Neoplasms , Cohort Studies , Giant Cell Arteritis/complications , Giant Cell Arteritis/epidemiology , Humans , Neoplasms/complications , Neoplasms/epidemiology , Norway/epidemiology , Retrospective Studies
2.
Front Immunol ; 10: 1488, 2019.
Article in English | MEDLINE | ID: mdl-31338093

ABSTRACT

Rheumatoid arthritis (RA) is a chronic autoimmune, inflammatory disease, characterized by synovitis in small- and medium-sized joints and, if not treated early and efficiently, joint damage, and destruction. RA is a heterogeneous disease with a plethora of treatment options. The pro-inflammatory cytokine tumor necrosis factor (TNF) plays a central role in the pathogenesis of RA, and TNF inhibitors effectively repress inflammatory activity in RA. Currently, treatment decisions are primarily based on empirics and economic considerations. However, the considerable interpatient variability in response to treatment is a challenge. Markers for a more exact patient classification and stratification are lacking. The objective of this study was to identify markers in immune cell populations that distinguish RA patients from healthy donors with an emphasis on TNF signaling. We employed mass cytometry (CyTOF) with a panel of 13 phenotyping and 10 functional markers to explore signaling in unstimulated and TNF-stimulated peripheral blood mononuclear cells from 20 newly diagnosed, untreated RA patients and 20 healthy donors. The resulting high-dimensional data were analyzed in three independent analysis pipelines, characterized by differences in both data clean-up, identification of cell subsets/clustering and statistical approaches. All three analysis pipelines identified p-p38, IkBa, p-cJun, p-NFkB, and CD86 in cells of both the innate arm (myeloid dendritic cells and classical monocytes) and the adaptive arm (memory CD4+ T cells) of the immune system as markers for differentiation between RA patients and healthy donors. Inclusion of the markers p-Akt and CD120b resulted in the correct classification of 18 of 20 RA patients and 17 of 20 healthy donors in regression modeling based on a combined model of basal and TNF-induced signal. Expression patterns in a set of functional markers and specific immune cell subsets were distinct in RA patients compared to healthy individuals. These signatures may support studies of disease pathogenesis, provide candidate markers for response, and non-response to TNF inhibitor treatment, and aid the identification of future therapeutic targets.


Subject(s)
Arthritis, Rheumatoid/classification , Arthritis, Rheumatoid/diagnosis , CD4-Positive T-Lymphocytes/immunology , Monocytes/immunology , Tumor Necrosis Factor-alpha/metabolism , Adult , Aged , Arthritis, Rheumatoid/pathology , Biomarkers/metabolism , Female , Humans , Male , Middle Aged , Neutrophils/immunology , Proto-Oncogene Proteins c-akt/metabolism , Receptors, Tumor Necrosis Factor, Type II/metabolism
3.
BMC Geriatr ; 18(1): 65, 2018 03 05.
Article in English | MEDLINE | ID: mdl-29506481

ABSTRACT

BACKGROUND: Patients with hip fracture frequently have sarcopenia and are at great risk of loss of mobility. We have investigated if sarcopenia predicts change in mobility after hip fracture. METHODS: This is a prospective, multicenter observational study with one-year follow-up. Patients with hip fracture who were community-living and capable of walking before the fracture were included at three hospitals in Norway (2011-2013). The primary outcome of the study was change in mobility, measured by the New Mobility Score (NMS). Sarcopenia was determined postoperatively by anthropometry, grip strength, and NMS. RESULTS: We included 282 participants and sarcopenia status was determined in 201, of whom 38% (77/201) had sarcopenia, 66% (128/194) had low muscle mass, 52% (116/222) had low grip strength and 8% (20/244) had low pre-fracture mobility (NMS < 5). Sarcopenia did not predict change in mobility (effect 0.2 points; 95% CI -0.5 to 0.9, P = 0.6), but it was associated with having lower mobility at one-year (NMS 5.8 (SD 2.3) vs. 6.8 (SD 2.2), P = 0.003), becoming a resident of a nursing home (odds ratio 3.2, 95% CI 0.9 to 12.4, P = 0.048), and the combined endpoint of becoming a resident of a skilled nursing home or death (odds ratio 3.6, 95% CI 1.2 to 12.2, P = 0.02). CONCLUSIONS: Sarcopenia did not predict change in mobility in the year after hip fracture.


Subject(s)
Hip Fractures/diagnosis , Hip Fractures/epidemiology , Mobility Limitation , Sarcopenia/diagnosis , Sarcopenia/epidemiology , Aged , Aged, 80 and over , Female , Follow-Up Studies , Hip Fractures/surgery , Humans , Male , Norway/epidemiology , Predictive Value of Tests , Prospective Studies , Sarcopenia/surgery , Time Factors , Walking/physiology
4.
PLoS One ; 12(9): e0184780, 2017.
Article in English | MEDLINE | ID: mdl-28902873

ABSTRACT

BACKGROUND: Sarcopenia is prevalent in older persons and is a risk factor for falls, fractures, and mortality. The aim of this study was to determine a) the feasibility of determining sarcopenia in patients with acute hip fracture, b) the prevalence of sarcopenia and c) associations of sarcopenia with nutritional status and comorbidities. METHODS: A multicenter cross-sectional study on sarcopenia in male and female patients with acute hip fracture. Participants were previously ambulatory and living in the community. Sarcopenia was assessed postoperatively with muscle mass estimated by anthropometry using triceps skinfold, arm circumference, height, weight and sex. Grip strength was measured by Jamar dynamometer and pre-fracture mobility was by self-report using the New Mobility Score. RESULTS: Out of 282 patients, 202 were assessed for sarcopenia of whom 74 (37%) were diagnosed as sarcopenic. Sarcopenia was associated with age, odds ratio (OR) 1.4 per 5 years, 95% confidence interval (CI) [1.1, 1.8], ASA Physical Status Classification System score, OR 2.3 per point, 95% CI [1.3, 4.3] and number of medications at discharge, OR 1.2 per medication, 95% CI [1.0, 1.3] and inversely associated with BMI, OR 0.8, 95% CI [0.7, 0.9] and serum albumin, OR 0.9, 95% CI [0.8,1.0]. CONCLUSIONS: Thirty-seven percent of assessed subjects were diagnosed with sarcopenia. Our data demonstrates that the prevalence of sarcopenia is associated with older age, malnutrition and comorbidities. Determining sarcopenia at the bedside was feasible in postoperative hip fracture patients by using grip strength, estimation of muscle mass by anthropometry and self-reported mobility.


Subject(s)
Hip Fractures/complications , Sarcopenia/epidemiology , Aged , Aged, 80 and over , Body Composition , Body Weight , Comorbidity , Cross-Sectional Studies , Female , Humans , Male , Nutritional Status , Odds Ratio , Prevalence , Regression Analysis , Risk Factors , Sarcopenia/complications , Sarcopenia/diagnosis
5.
J Nutr ; 147(4): 572-578, 2017 04.
Article in English | MEDLINE | ID: mdl-28275104

ABSTRACT

Background: Choline is an important nutrient either obtained from a variety of foods or synthesized endogenously, and it is the precursor of betaine. We previously reported positive associations between plasma free choline and bone mineral density (BMD). Animal studies suggest an impact of dietary choline on bone metabolism, but the role of dietary intake of choline and betaine for human bone health is unknown.Objectives: The main aims were to examine the associations of dietary choline, choline species, and betaine with BMD and to study the relations between dietary and plasma free choline and betaine.Methods: Study subjects were participants in the Hordaland Health Study, including 2649 women and 1983 men (aged 46-49 or 71-74 y). BMD was measured by dual-energy X-ray absorptiometry, and dietary intake was obtained by using a validated 169-item food-frequency questionnaire. Risk associations were assessed by logistic regression and correlations by ρ (Spearman's bivariate rank order correlation).Results: Subjects in the lowest compared with the highest tertile of dietary total choline, free choline, glycerophosphocholine, phosphocholine, phosphatidylcholine, and sphingomyelin had a higher risk of low-femoral neck BMD, defined as the lowest BMD quintile. Particularly strong associations were found among middle-aged men for intake of free choline (OR: 1.83; 95% CI: 1.24, 2.69; P = 0.002) and glycerophosphocholine (OR: 2.13; 95% CI: 1.43, 3.16; P < 0.001) and among elderly women for total choline (OR: 1.96; 95% CI: 1.33, 2.88; P = 0.001) and phosphatidylcholine (OR: 1.94; 95% CI: 1.33, 2.84: P = 0.001) intake. No significant associations were observed between dietary betaine and BMD. Dietary total choline, free choline, glycerophosphocholine, phosphatidylcholine, and sphingomyelin correlated weakly with plasma free choline (ρ: 0.07, 0.05, 0.07, 0.07, and 0.05, respectively; P < 0.01). Dietary betaine correlated with plasma betaine (ρ: 0.23; P < 0.001).Conclusion: Dietary choline was positively associated with BMD in middle-aged and elderly participants.


Subject(s)
Aging , Bone Density/physiology , Choline/administration & dosage , Diet , Aged , Female , Humans , Male , Middle Aged , Odds Ratio
6.
Oncotarget ; 7(43): 69200-69215, 2016 Oct 25.
Article in English | MEDLINE | ID: mdl-27542236

ABSTRACT

Suboptimal vitamin D status is common among humans, and might increase bone resorption with subsequent negative effects on bone health. Fatty fish, including Atlantic salmon, is an important dietary vitamin D source. However, due to a considerable change in fish feed composition, the contribution of vitamin D from salmon fillet has been reduced. The main objective was to investigate if intake of vitamin D3 enriched salmon or vitamin D3 tablets decreased bone biomarkers (urinary N-telopeptides, deoxypyridinoline, serum bone-specific alkaline phosphatase, and osteocalcin) compared to a low vitamin D3 intake. The 122 healthy postmenopausal women included in this 12 weeks intervention trial were randomized into four groups: three salmon groups (150 grams/two times/week) and one tablet group (800 IU vitamin D and 1000 mg calcium/day). The salmon groups also received calcium supplements. The salmon had three different vitamin D3/vitamin K1 combinations: high D3+high K1, low D3+high K1, or high D3+low K1. Increased intake of salmon containing high levels of vitamin D3 (0.35-0.38 mg/kg/fillet) and supplements with the same weekly contribution had a positive influence on bone health as measured by bone biomarkers in postmenopausal women. Consequently, an increased level of vitamin D3 at least to original level in feed for salmonids will contribute to an improved vitamin D3 status and may improve human bone health.


Subject(s)
Bone Resorption/prevention & control , Cholecalciferol/administration & dosage , Diet , Dietary Supplements , Seafood , Vitamin K 1/administration & dosage , Animals , Biomarkers/blood , Biomarkers/urine , Body Composition/drug effects , Bone Resorption/blood , Bone Resorption/urine , Calcium/administration & dosage , Female , Humans , Middle Aged , Nutritional Status , Salmo salar , Vitamins/administration & dosage
7.
Rheumatol Int ; 36(5): 703-11, 2016 May.
Article in English | MEDLINE | ID: mdl-26803313

ABSTRACT

Fatigue occurs in all chronic inflammatory diseases, in cancer, and in some neurological conditions. Patients often regard fatigue as one of their most debilitating problems, but currently there is no established treatment and the mechanisms that lead to and regulate fatigue are incompletely understood. Our objective was to more completely understand the physiology of this phenomenon. Twenty-four patients with rheumatoid arthritis (RA) naïve to treatment with biological drugs were enrolled for the study. Fatigue was measured with a fatigue visual analogue scale (fVAS). Ethylenediaminetetraacetic acid (EDTA) plasma samples were subjected to gas chromatography-time-of-flight mass spectrometry (GC/MS-TOF)-based metabolite profiling. Obtained metabolite data were evaluated by multivariate data analysis with orthogonal projections to latent structures (OPLS) method to pinpoint metabolic changes related to fatigue severity. A significant multivariate OPLS model was obtained between the fVAS scores and the measured metabolic levels. Increasing fatigue scores were associated with a metabolic pattern characterized by down-regulation of metabolites from the urea cycle, fatty acids, tocopherols, aromatic amino acids, and hypoxanthine. Uric acid levels were increased. Apart from fatigue, we found no other disease-related variables that might be responsible for these changes. Our MS-based metabolomic approach demonstrated strong associations between fatigue and several biochemical patterns related to oxidative stress.


Subject(s)
Arthritis, Rheumatoid/metabolism , Fatigue/metabolism , Adult , Aged , Arthritis, Rheumatoid/complications , Fatigue/complications , Female , Gas Chromatography-Mass Spectrometry , Humans , Male , Metabolomics , Middle Aged
8.
Scand J Public Health ; 42(8): 804-13, 2014 Dec.
Article in English | MEDLINE | ID: mdl-25278275

ABSTRACT

AIMS: This paper describes the history, purpose, data collection and contributions in the research collaboration Norwegian Osteoporosis Epidemiologic Studies (NOREPOS). METHODS: NOREPOS encompasses almost 85,000 bone mineral density measurements within Cohort of Norway and data on almost 140,000 hip fractures in Norway 1994-2008. Included are anthropometric measurements, blood pressure, lipids and glucose, and 50 standard questions on sociodemographic factors, diseases and risk factors. Blood samples/DNA are stored. The main research question posed in NOREPOS is why hip fracture rates in Norway are the highest in the world. Data on hip fractures 2009-2013 will be added in 2014. RESULTS: Main findings include: Every hour a Norwegian suffers a hip fracture; hip fracture incidence rates declined after 1999; only 16% of patients used anti-osteoporosis drugs 1 year after hip fracture; 25% of patients died within 1 year after the fracture; 12% suffered a new hip fracture within 10 years; rural dwellers had lower hip and forearm fracture incidence than city dwellers; magnesium in tap water may be protective whereas bacterial contamination, cadmium and lead may be harmful to bone health; low serum vitamin D and E levels were associated with higher hip fracture risk; vitamin A was not associated with fracture risk; and abdominal obesity increased the risk of hip fracture when BMI was accounted for. CONCLUSIONS: NOREPOS encompasses a unique source of information for aetiological research, genetic studies as well as for biomarkers of osteoporosis and fractures. Because of the increasing number of elderly people in Europe, hip fractures will continue to pose an international public health and health care challenge.


Subject(s)
Cohort Studies , Osteoporosis/epidemiology , Humans , Norway/epidemiology
9.
Arch Osteoporos ; 9: 185, 2014.
Article in English | MEDLINE | ID: mdl-24893722

ABSTRACT

UNLABELLED: Bone mass achievement predicts later fracture risk. This population-based study describes bone mineral density (BMD) levels and associated factors in Norwegian adolescents. Compared with international reference ranges, BMD levels appear higher and physical activity levels are positively associated with BMD. PURPOSE: Norway has one of the highest reported incidences of osteoporotic fractures. Maximisation of peak bone mass may prevent later fractures. This population-based study compared BMD levels of Norwegian adolescents with international reference ranges and explored associated factors. METHODS: All first-year upper-secondary school students, aged 15-19 years in the Tromsø region were invited to the Fit Futures study in 2010-2011. Over 90 % of the invited participants attended, 508 girls and 530 boys. BMD was measured at total hip, femoral neck and total body by dual X-ray absorptiometry. Lifestyle variables were collected by self-administered questionnaires and interviews. All analyses were performed sex stratified, using linear regression models. RESULTS: In girls, mean BMD (SD) was 1.060 g/cm(2) (0.124), 1.066 g/cm(2) (0.123) and 1.142 g/cm(2) (0.077) at the total hip, femoral neck and total body, respectively. In boys, corresponding values were 1.116 (0.147), 1.103 (0.150) and 1.182 (0.097), with significant higher values than the Lunar pediatric reference at 16 years of age. In girls, height and self-reported intensive physical activity of more than 4 h a week and early sexual maturation were positively associated with BMD at both femoral sites (p < 0.047). Among boys age, height, body mass index, physical activity and alcohol intake were positively (p < 0.038), whereas early stages of sexual maturation and smoking was negatively (p < 0.047) related to BMD. CONCLUSIONS: Despite the heavy fracture burden, Norwegian adolescents' BMD levels are higher than age-matched Caucasians. Physical activity is associated with 1 SD increased BMD levels in those involved in competition or hard training.


Subject(s)
Bone Density/physiology , Osteoporotic Fractures/epidemiology , Absorptiometry, Photon , Adolescent , Age Distribution , Analysis of Variance , Cross-Sectional Studies , Exercise/physiology , Female , Femur Neck , Hip , Humans , Life Style , Male , Norway/epidemiology , Osteoporotic Fractures/physiopathology , Sex Distribution
10.
J Bone Miner Res ; 29(1): 242-50, 2014 Jan.
Article in English | MEDLINE | ID: mdl-23794246

ABSTRACT

Choline, obtained from diet and formed by biosynthesis, is the immediate precursor of betaine. Animal studies suggest an impact of choline on bone metabolism. We examined the associations of plasma choline and betaine with bone mineral density (BMD), the risk of hip fractures, and possible effect-modification by nicotine exposure. The Hordaland Health Study (1998 to 2000) included 7074 women and men (ages 46 to 49 or 71 to 74 years). In 5315, BMD was measured. The oldest (n = 3311) were followed for hip fractures through 2009. Risk associations were studied by logistic and Cox regression by comparing the lowest and middle tertiles with the highest, as well as trends across tertiles of plasma choline and betaine. In analyses adjusted for sex and age, participants in the lowest (odds ratio [OR] = 2.00, 95% confidence interval [CI] 1.69-2.37) and middle (OR = 1.39, CI 1.17-1.66) tertiles of plasma choline had an increased risk of low BMD (lowest quintile) (p trend < 0.001). Separate analyses for sex and age groups revealed the strongest relations in elderly women (lowest tertile: OR = 2.84, CI 1.95-4.14; middle tertile: OR = 1.80, CI 1.22-2.67, p trend < 0.001), and highest OR among those in the lowest tertile who were exposed to nicotine (OR = 4.56, CI 1.87-11.11). Low plasma choline was also associated with an increased risk of hip fracture in elderly women and men (lowest tertile: hazard ratio [HR] = 1.45, CI 1.08-1.94; middle tertile: HR = 1.13, CI 0.83-1.54, p trend = 0.012). In elderly women, the HR for hip fracture was 1.90 (CI 1.32-2.73) and 1.36 (CI 0.92-1.99) (p trend < 0.001) for lowest and middle tertiles of choline, and the highest HR was found among women in the lowest tertile exposed to nicotine (HR = 2.68, CI 1.16-6.19). Plasma betaine was not related to BMD or hip fracture. Low plasma choline was associated with low BMD in both sexes and increased the risk of hip fracture in elderly women. These results should motivate further studies on choline, nicotine exposure, and bone metabolism.


Subject(s)
Bone Density , Choline/blood , Hip Fractures/etiology , Nicotine/adverse effects , Absorptiometry, Photon , Aged , Betaine/blood , Female , Hip Fractures/epidemiology , Humans , Male , Middle Aged , Nicotine/pharmacology , Norway/epidemiology , Odds Ratio , Risk Factors
11.
Bone ; 48(5): 1140-5, 2011 May 01.
Article in English | MEDLINE | ID: mdl-21295169

ABSTRACT

INTRODUCTION: Vitamin D inadequacy is associated with hip fractures, but the relationship has not been explored for distal radius fractures. AIMS: To compare serum 25-hydroxyvitamin D (s-25(OH)D) status in low-energy distal radius fracture patients and a group of matched controls, and examine whether observed differences in s-25(OH)D between patients and controls would remain after adjusting for bone mineral density (BMD), body mass index (BMI), and smoking history. METHODS: A total of 575 female and 72 male low-energy distal radius fracture patients (50-90 years) and 534 female and 52 male matched controls were included. The primary measure was levels of vitamin D. Secondary measures were BMD assessed by dual energy X-ray absorptiometry, BMI and smoking history. RESULTS: Mean s-25(OH)D was 66.5nmol/L in female patients and 78.7nmol/L in controls (p<0.001). The corresponding figures in men were 64.5 and 77.0nmol/L (p=0.017). In adjusted conditional logistic regression analyzes, s-25(OH)D <50nmol/L (OR=2.32, 95% CI: 1.47-3.64, p<0.001), and 50-75 (OR=1.70, 95% CI: 1.17-2.47, p=0.005) were associated with distal radius fractures in women. s-25(OH)D <50nmol/L (OR=6.27, 95% CI: 1.17-33.66, p=0.032) was associated with distal radius fractures in men. CONCLUSIONS: Vitamin D inadequacy is associated with low-energy distal radius fractures in both women and men. Differences in vitamin D levels are independent of BMD, BMI or smoking history.


Subject(s)
Radius Fractures/complications , Vitamin D Deficiency/complications , Aged , Bone Density/physiology , Case-Control Studies , Demography , Female , Humans , Male , Middle Aged , Odds Ratio , Radius Fractures/blood , Radius Fractures/physiopathology , Risk Factors , Vitamin D/analogs & derivatives , Vitamin D/blood , Vitamin D Deficiency/blood , Vitamin D Deficiency/physiopathology
12.
J Bone Joint Surg Am ; 93(4): 348-56, 2011 Feb 16.
Article in English | MEDLINE | ID: mdl-21325586

ABSTRACT

BACKGROUND: Distal radial fractures occur earlier in life than hip and spinal fractures and may be the first sign of osteoporosis. The aims of this case-control study were to compare the prevalence of osteopenia and osteoporosis between female and male patients with low-energy distal radial fractures and matched controls and to investigate whether observed differences in bone mineral density between patients and controls could be explained by potential confounders. METHODS: Six hundred and sixty-four female and eighty-five male patients who sustained a distal radial fracture, and 554 female and fifty-four male controls, were included in the study. All distal radial fractures were radiographically confirmed. Bone mineral density was assessed with use of dual x-ray absorptiometry at the femoral neck, total hip (femoral neck, trochanter, and intertrochanteric area), and lumbar spine (L2-L4). A self-administered questionnaire provided information on health and lifestyle factors. RESULTS: The prevalence of osteoporosis was 34% in female patients and 10% in female controls. The corresponding values were 17% in male patients and 13% in male controls. In the age group of fifty to fifty-nine years, 18% of female patients and 5% of female controls had osteoporosis. In the age group of sixty to sixty-nine years, the corresponding values were 25% and 7%, respectively. In adjusted conditional logistic regression analyses, osteopenia and osteoporosis were significantly associated with distal radial fractures in women. Osteoporosis was significantly associated with distal radial fractures in men. CONCLUSIONS: The prevalence of osteoporosis in patients with distal radial fractures is high compared with that in control subjects, and osteoporosis is a risk factor for distal radial fractures in both women and men. Thus, patients of both sexes with an age of fifty years or older who have a distal radial fracture should be evaluated with bone densitometry for the possible treatment of osteoporosis.


Subject(s)
Osteoporosis/complications , Osteoporosis/diagnosis , Radius Fractures/diagnosis , Radius Fractures/etiology , Wrist Injuries/diagnosis , Wrist Injuries/etiology , Absorptiometry, Photon , Aged , Aged, 80 and over , Bone Diseases, Metabolic/complications , Bone Diseases, Metabolic/diagnosis , Bone Diseases, Metabolic/epidemiology , Case-Control Studies , Cross-Sectional Studies , Female , Humans , Male , Middle Aged , Norway , Osteoporosis/epidemiology , Radius Fractures/epidemiology , Reference Values , Risk Factors , Wrist Injuries/epidemiology
13.
Bone ; 44(5): 954-8, 2009 May.
Article in English | MEDLINE | ID: mdl-19168166

ABSTRACT

BACKGROUND: Plasma total cysteine (tCys) and homocysteine (tHcy) are associated with body composition, which in turn affects bone mineral density (BMD). OBJECTIVES: To investigate whether associations of tCys and tHcy with BMD are mediated through body composition (fat mass and/or lean mass). DESIGN: Using data from 5238 Hordaland Homocysteine Study participants, we fit multiple linear regression models and concentration-response curves to explore the relationships between tCys, tHcy, and BMD, with and without adjustment for body mass index (BMI), lean mass and/or fat mass. RESULTS: All associations were stronger in women. tCys was positively associated with BMD (women, partial r=0.11; men, partial r=0.07, p

Subject(s)
Body Composition/physiology , Bone Density , Cysteine/blood , Homocysteine/blood , Adult , Aged , Body Mass Index , Female , Humans , Linear Models , Male
14.
Am J Clin Nutr ; 88(3): 738-46, 2008 Sep.
Article in English | MEDLINE | ID: mdl-18779291

ABSTRACT

BACKGROUND: The lean phenotype of cystathionine beta-synthase-deficient homocystinuria and the positive association of plasma total cysteine (tCys) with body mass index (BMI) suggest that total homocysteine (tHcy) and tCys are associated with body composition. OBJECTIVES: We aimed to study associations of tCys and tHcy with body composition in the general population. DESIGN: Using data from 7038 Hordaland Homocysteine Study participants, we fitted regression models and dose-response curves of tCys and tHcy with BMI. In 5179 participants, we investigated associations of tCys and tHcy with fat mass and lean mass and examined whether changes in these aminothiols predicted body composition 6 y later. RESULTS: tCys showed positive associations with BMI (partial r = 0.28, P < 0.001), and fat mass (partial r = 0.25, P < 0.001), independent of diet, exercise, and plasma lipids. Women in the highest tCys quintile had fat mass 9 kg (95% CI: 8, 10 kg; P < 0.001) greater than that of women in the lowest quintile. The corresponding values for men were 6 kg (95% CI: 5, 7 kg; P < 0.001; P < 0.001 in both sexes, ANOVA across quintiles). The rise in tCys over 6 y was associated with greater fat mass at follow-up (P < 0.001), but there was no effect on lean mass. tHcy was not associated with lean mass, and it became significantly inversely associated with BMI and fat mass only after adjustment for tCys. The association between tHcy and lean mass was not significant. CONCLUSIONS: tCys concentrations show a strong positive association with BMI, mediated through fat mass. The link between cysteine and lipid metabolism deserves further investigation.


Subject(s)
Amino Acids/metabolism , Body Composition , Body Mass Index , Cysteine/blood , Homocysteine/blood , Lipids/physiology , Aged , Female , Humans , Male , Middle Aged , Norway , Obesity/epidemiology , Regression Analysis , Software , Thinness/epidemiology
15.
J Bone Miner Res ; 22(5): 747-56, 2007 May.
Article in English | MEDLINE | ID: mdl-17295607

ABSTRACT

UNLABELLED: Homocysteine and related factors were evaluated as risk factors for subsequent hip fractures among 4766 elderly men and women. High levels of homocysteine and low levels of folate predicted fracture, whereas vitamin B12 and genotypes were not related to fracture risk. High homocysteine may be a modifiable risk factor for hip fracture. INTRODUCTION: Elevated plasma total homocysteine (tHcy) and deficiencies of folate and vitamin B12 are associated with risk of osteoporosis and fracture. We examined whether plasma levels of tHcy, folate, and vitamin B12 and the methylenetetrahydrofolate reductase (MTHFR) 677C-->T and 1298C-->T polymorphisms predicted hip fracture. MATERIALS AND METHODS: This was a population-based prospective study of 2639 women and 2127 men who were 65-67 yr at enrollment in 1992-1993. Information on hip fracture was obtained from computerized records of discharge diagnoses from all hospitalizations in the region in the period between enrollment and November 30, 2005. Cox proportional hazard regression was used to estimate fracture risk according to levels of plasma tHcy, folate, and vitamin B12 and for different genotypes. RESULTS: Over a median follow-up period of 12.6 yr, hip fracture was recorded in 184 (7.0%) women and 90 (4.2%) men. The adjusted hazard ratio (95% CI) for fracture in subjects with high (>or=15 microM) compared with low levels (<9.0 microM) of tHcy was 2.42 (1.43-4.09) among women and 1.37 (0.63-2.98) among men. Dose-response analyses indicated a positive association between plasma tHcy and risk of fracture in both sexes and a negative association between plasma folate and risk of fracture among women only. Plasma vitamin B12 level or MTHFR genotype was not significantly related to risk of fracture after adjustments for confounding factors. The association between tHcy and risk of hip fracture was only slightly weakened by adjustments for plasma levels of vitamin B12 and folate. CONCLUSIONS: tHcy seems to be a predictor for hip fracture among elderly men and women. Folate was a predictor among women only, whereas vitamin B12 and MTHFR genotype did not predict hip fracture. Our data corroborate the hypothesis that homocysteine may play a role in the pathogenesis of osteoporotic fractures.


Subject(s)
Folic Acid/blood , Hip Fractures/blood , Homocysteine/blood , Vitamin B 12/blood , Adult , Aged , Biomarkers/blood , Female , Follow-Up Studies , Hip Fractures/enzymology , Hip Fractures/genetics , Hip Fractures/physiopathology , Humans , Male , Middle Aged , Osteoporosis/blood , Osteoporosis/enzymology , Osteoporosis/genetics , Osteoporosis/physiopathology , Oxidoreductases Acting on CH-NH Group Donors/blood , Oxidoreductases Acting on CH-NH Group Donors/genetics , Polymorphism, Single Nucleotide , Predictive Value of Tests , Prospective Studies , Risk Factors
16.
Arch Intern Med ; 166(1): 88-94, 2006 Jan 09.
Article in English | MEDLINE | ID: mdl-16401815

ABSTRACT

BACKGROUND: Plasma total homocysteine (tHcy) has been associated with hip fracture but not directly with bone mineral density (BMD). We examined the association of hip BMD with levels of plasma tHcy, folate, and vitamin B12 and the methylenetetrahydrofolate reductase (MTHFR) 677C-->T and 1298A-->C polymorphisms. METHODS: Bone mineral density was measured between 1997 and 2000 in 2268 men and 3070 women, aged 47 to 50 and 71 to 75 years, from the Hordaland Homocysteine Study cohort. Low BMD was defined as BMD in the lowest quintile for each sex and age group. Linear, logistic, and generalized additive regression models were used. RESULTS: Plasma levels of tHcy were inversely related to BMD among middle-aged and elderly women (P<.001) but not among men. The multiple adjusted odds ratio for low BMD among subjects with high (>or=15 micromol/L [>or=2.02 mg/L]) compared with low (<9 micromol/L [<1.22 mg/L]) tHcy level was 1.96 (95% confidence interval, 1.40-2.75) for women and was not significant for men. Additional adjustments for plasma folate level or intake of calcium and vitamin D did not substantially alter the results. Plasma folate level was associated with BMD in women only. We observed no association between BMD and vitamin B12 level or the MTHFR polymorphisms. CONCLUSIONS: Elevated tHcy and low folate levels were associated with reduced BMD in women but not in men. These findings suggest that tHcy may be a potential modifiable risk factor for osteoporosis in women.


Subject(s)
Bone Density , Homocysteine/blood , Age Distribution , Aged , Cohort Studies , Confidence Intervals , Female , Folic Acid/blood , Hematologic Tests , Homocysteine/genetics , Humans , Male , Methylenetetrahydrofolate Reductase (NADPH2)/blood , Methylenetetrahydrofolate Reductase (NADPH2)/genetics , Middle Aged , Multivariate Analysis , Odds Ratio , Polymorphism, Genetic , Regression Analysis , Sex Distribution , Vitamin B 12/blood
17.
J Rheumatol ; 32(9): 1734-6, 2005 Sep.
Article in English | MEDLINE | ID: mdl-16142869

ABSTRACT

OBJECTIVE: To study the outcome of pregnancy in patients with primary Sjögren's syndrome (pSS). METHODS: A questionnaire covering demographic data and the outcome of pregnancies was answered by 58 patients with pSS and 157 controls. For 36 patients and 93 controls, we analyzed detailed data about pregnancy, birth, and status of the newborn from the Medical Birth Registry of Norway (MFR) for birth order one, 2, and 3. Thirty-two of 36 patients registered in MFR were diagnosed with pSS after the last birth. RESULTS: Pregnancy outcomes were not different in patients compared to controls. Two patients (3.4%) reported giving birth to a child with congenital heart block. CONCLUSION: PSS had no impact on pregnancy outcome before disease onset. The most important condition associated with pSS in anti-SSA positive mothers was congenital heart block in the offspring.


Subject(s)
Pregnancy Complications/epidemiology , Pregnancy Outcome , Pregnancy, High-Risk , Sjogren's Syndrome/diagnosis , Adult , Aged , Case-Control Studies , Cohort Studies , Female , Gestational Age , Humans , Incidence , Infant, Newborn , Maternal Age , Middle Aged , Norway/epidemiology , Pregnancy , Pregnancy Complications/diagnosis , Probability , Reference Values , Risk Assessment , Sjogren's Syndrome/complications , Surveys and Questionnaires
18.
Obes Surg ; 14(3): 305-12, 2004 Mar.
Article in English | MEDLINE | ID: mdl-15072648

ABSTRACT

BACKGROUND: Jejunoileal (JI) bypass was a widely performed operation for morbid obesity in the 1970s. The aim of this study was to investigate the long-term status of bone mineral density (BMD) after weight loss induced by this technique. SUBJECTS AND METHODS: 18 female patients (age 48-79 y, BMI 23-43 kg/m2) had BMD measurements performed 25 years after JI bypass. Dual energy x-ray absorptiometry was used, and measured sites were the lumbar spine L2-L4, left femoral neck and total hip. Vitamin and mineral supplementation had not routinely been prescribed. An assessment was made on age-adjusted BMD values, and as to whether present BMD was related to present demographic and biochemical variables. RESULTS: No significant reduction of BMD was found beyond that which was expected for age. BMD was inversely and separately related to age and body weight. The serum level of vitamin D was low in 45% of the patients, and inversely correlated to body weight and BMI. Alk phosphatase and parathyroid hormone were the best markers for low BMD. CONCLUSION: These results suggest that JI bypass has not been detrimental to bone density in females. We recommend, however, vitamin D and calcium supplements after malabsorptive procedures for morbid obesity.


Subject(s)
Bone Density/physiology , Jejunoileal Bypass/adverse effects , Absorptiometry, Photon , Aged , Calcium, Dietary , Female , Follow-Up Studies , Humans , Middle Aged , Time Factors , Vitamin D Deficiency/etiology , Weight Loss/physiology
19.
Osteoporos Int ; 15(7): 525-34, 2004 Jul.
Article in English | MEDLINE | ID: mdl-14966666

ABSTRACT

The aim of this study was to compare bone mineral density (BMD) in a population-based sample of middle-aged and older Norwegians, with reference values provided by the manufacturer of the densitometer (Lunar) in order to evaluate whether these reference values are suitable for Norwegians. Additional aims were to estimate the prevalence of osteoporosis. Bone mineral density of the hip and total body was measured by dual-energy X-ray absorptiometry in 2303 men and 3105 women 47-50 and 71-75 years old, respectively, in western Norway, as part of the Hordaland Health Study (HUSK). Of these, 3403 white individuals were free of medications or diseases known to influence bone metabolism (reference group). Compared with the Lunar reference population, men and older women had a slightly but significantly lower BMD of trochanter and total femur and middle aged women had significantly higher total body BMD. Except for the higher mean BMD of total body among middle-aged women and the uniformly lower BMD values of Ward's triangle, the deviations from the reference values of the manufacturer were less than 4%. Approximately 2.6% of middle-aged men vs 0.9% of middle-aged women were classified as osteoporotic on the basis of BMD of femoral neck. While the BMD values for femoral neck in this healthy Norwegian population are similar to the reference population of Lunar, the values of trochanter and total femur are lower in all groups except middle-aged women; however, the discrepancies are not of sufficient magnitude to warrant rejection of this commonly used database among Norwegians. Use of the young adult means from the Lunar reference database classified a higher proportion of middle-aged men than women as osteoporotic and osteopenic.


Subject(s)
Bone Density/physiology , Femur/physiology , Age Distribution , Aged , Cross-Sectional Studies , Female , Humans , Male , Middle Aged , Norway/epidemiology , Osteoporosis/epidemiology , Population Surveillance/methods , Prevalence , Reference Values , Sex Distribution
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