Clara Gram Gjesdal

The Hordaland Homocysteine Study: A Community-Based Study of Homocysteine, Its Determinants, and Associations with Disease

The Hordaland Homocysteine Study (HHS) is a population-based study of more than 18,000 men and women in the county of Hordaland in Western Norway. The first investigation (HHS-I) took place in 1992-93, when the subjects were aged 40-67 y. In 1997-99, a follow-up study (HHS-II) of 7,053 subjects was carried out. In this large population, plasma levels of total homocysteine (tHcy) are associated with several physiologic and lifestyle factors and common diseases. Increasing age, male sex, smoking, coffee consumption, high blood pressure, unfavorable lipid profile, high creatinine, and the MTHFR 677C > T polymorphism are among the factors associated with increased tHcy levels; physical activity, moderate alcohol consumption, and a good folate or vitamin B-12 status are associated with lower tHcy levels. Subjects with raised tHcy levels have increased risk of cardiovascular morbidity, cardiovascular and noncardiovascular mortality, and are more likely to suffer from depression and from cognitive deficit (elderly). Among women, raised tHcy levels are associated with decreased bone mineral density and increased risk of osteoporosis. Women with raised tHcy levels also have an increased risk of having suffered from pregnancy complications and an adverse pregnancy outcome. Significant associations between tHcy and clinical outcomes are usually observed for tHcy levels > 15 micromol/L, but for most conditions, there is a continuous concentration-response relation with no apparent threshold concentration. Overall, the findings from HHS indicate that a raised tHcy level is associated with multiple clinical conditions, whereas a low tHcy level is associated with better physical and mental health.

Plasma Homocysteine, Folate, and Vitamin B12 and the Risk of Hip Fracture: The Hordaland Homocysteine Study†‡

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.

Glucocorticoid replacement therapy and pharmacogenetics in Addison's disease: effects on bone.

UNLABELLED Context Patients with primary adrenal insufficiency (Addisons disease) receive more glucococorticoids than the normal endogenous production, raising concern about adverse effects on bone. OBJECTIVE To determine i) the effects of glucocorticoid replacement therapy on bone, and ii) the impact of glucocorticoid pharmacogenetics. DESIGN, SETTING AND PARTICIPANTS A cross-sectional study of two large Addisons cohorts from Norway (n=187) and from UK and New Zealand (n=105). MAIN OUTCOME MEASURES Bone mineral density (BMD) was measured; the Z-scores represent comparison with a reference population. Blood samples from 187 Norwegian patients were analysed for bone markers and common polymorphisms in genes that have been associated with glucocorticoid sensitivity. RESULTS Femoral neck BMD Z-scores were significantly reduced in the patients (Norway: mean -0.28 (95% confidence intervals (CI) -0.42, -0.16); UK and New Zealand: -0.21 (95% CI -0.36, -0.06)). Lumbar spine Z-scores were reduced (Norway: -0.17 (-0.36, +0.01); UK and New Zealand: -0.57 (-0.78, -0.37)), and significantly lower in males compared with females (P=0.02). The common P-glycoprotein (ABCB1) polymorphism C3435T was significantly associated with total BMD (CC and CT>TT P=0.015), with a similar trend at the hip and spine. CONCLUSIONS BMD at the femoral neck and lumbar spine is reduced in Addisons disease, indicating undesirable effects of the replacement therapy. The findings lend support to the recommendations that 15-25 mg hydrocortisone daily is more appropriate than the higher conventional doses. A common polymorphism in the efflux transporter P-glycoprotein is associated with reduced bone mass and might confer susceptibility to glucocorticoid induced osteoporosis.

Impact of lean mass and fat mass on bone mineral density: The Hordaland Health Study

OBJECTIVES To examine the relationship between soft tissue composition and bone mineral density (BMD) of the hip and whether these relationships differ by gender and age. METHODS Femoral neck BMD and total body soft tissue composition were measured by dual X-ray absorptiometry in a population-based sample of 5205 men and women 47-50 and 71-75 years old. Analysis of covariance was used to explore possible modifying effects of sex and gender on the impact of fat and lean mass on BMD. RESULTS The difference in BMD per kilo lean mass (LM) was larger than the difference per kilo fat mass (FM). The effect of FM on BMD was significantly greater among women than among men. In multivariate adjusted analyses, 10kg increase in LM was associated with a 0.083 (95% confidence interval [CI]: 0.075, 0.092)g/cm(2) increase in BMD. A 10kg increase in FM was associated with 0.013 (0.007, 0.019)g/cm(2) increase in BMD among men and 0.021 (0.017, 0.026)g/cm(2) among women. There was indication of a steeper dose-response relationship at lower levels of FM among women. CONCLUSIONS Compared to FM, LM was generally more strongly related to BMD of the femoral neck in middle-aged and elderly men and women. FM was a significantly stronger predictor of BMD among women than among men, particularly at lower levels of FM.

Osteoporosis as a Risk Factor for Distal Radial Fractures. A Case-Control Study

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.

Mortality following the first hip fracture in Norwegian women and men (1999-2008). A NOREPOS study

Hip fractures are associated with increased mortality and their incidence in Norway is one of the highest worldwide. The aim of this nationwide study was to examine short- and long-term mortality after hip fractures, burden of disease (attributable fraction and potential years of life lost), and time trends in mortality compared to the total Norwegian population. Information on incident hip fractures between 1999 and 2008 in all persons aged 50 years and older was collected from Norwegian hospitals. Death and emigration dates of the hip fracture patients were obtained through 31 December 2010. Standardized mortality ratios (SMRs) were calculated and Poisson regression analyses were used for the estimation of time trends in SMRs. Among the 81,867 patients with a first hip fracture, the 1-year excess mortality was 4.6-fold higher in men, and 2.8-fold higher in women compared to the general population. Although the highest excess mortality was observed during the first two weeks post fracture, the excess risk persisted for twelve years. Mortality rates post hip fracture were higher in men compared to women in all age groups studied. In both genders aged 50 years and older, approximately 5% of the total mortality in the population was related to hip fractures. The largest proportion of the potential life-years lost was in the relatively young-old, i.e. less than 80 years. In men, the 1-year absolute mortality rates post hip fracture declined significantly between 1999 and 2008, by contrast, the mortality in women increased significantly relatively to the population mortality.

Low Serum Levels of 25-Hydroxyvitamin D Predict Hip Fracture in the Elderly: A NOREPOS Study

BACKGROUND Despite considerable interest, the relationship between circulating 25-hydroxyvitamin D and the risk of hip fracture is not fully established. OBJECTIVE The objective of the study was to study the association between serum 25-hydroxyvitamin D concentrations [s-25(OH)D] and the risk of hip fracture in Norway, a high-latitude country that has some of the highest hip fracture rates worldwide. METHODS A total of 21 774 men and women aged 65-79 years attended 4 community-based health studies during 1994-2001. Information on subsequent hip fractures was retrieved from electronic hospital discharge registers, with a maximum follow-up of 10.7 years. Using a stratified case-cohort design, s-25(OH)D was determined by HPLC-atmospheric pressure chemical ionization-mass spectrometry in stored serum samples in hip fracture cases (n = 1175; 307 men, 868 women) and in gender-stratified random samples (n = 1438). Cox proportional hazards regression adapted for the case-cohort design was performed. RESULTS We observed an inverse association between s-25(OH)D and hip fracture; those with s-25(OH)D in the lowest quartile (<42.2 nmol/L) had a 38% [95% confidence interval (CI) 9-74%] increased risk of hip fracture compared with the highest quartile (≥67.9 nmol/L) in a model accounting for age, gender, study center, and body mass index. The association was stronger in men than in women: hazard ratio 1.65 (95% CI 1.04-2.61) vs hazard ratio 1.25 (95% CI 0.95-1.65). CONCLUSION In this prospective case-cohort study of hip fractures, the largest ever reported, we found an increased risk of hip fracture in subjects in the lowest compared with the highest quartile of serum 25-hydroxyvitamin D. In accordance with the findings of previous community-based studies, low vitamin D status was a modest risk factor for hip fracture.

Vitamin D inadequacy is associated with low-energy distal radius fractures: A case–control study

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.

Plasma stearoyl-CoA desaturase indices: association with lifestyle, diet, and body composition.

Stearoyl‐coenzyme A desaturase‐1 (SCD1) is a key enzyme in fatty acid and energy metabolism. Increased hepatic SCD1 activity is associated with obesity and obesity‐related diseases. We examined the relations of two plasma SCD activity indices (16:1n‐7/16:0, 18:1n‐9/18:0) with body composition, and the association of lifestyle and dietary variables with the plasma SCD indices.

Intake of vitamin K1 and K2 and risk of hip fractures: The Hordaland Health Study

BACKGROUND Evidence of the effect of vitamin K on bone health is conflicting. The aim was to investigate the association between intake of vitamins K1 and K2 and subsequent risk of hip fracture in a general population sample, as well as potential effect modification by apolipoprotein E gene (APOE) status by presence of the E4 allele. METHODS 1238 men and 1569 women 71-75 years of age were included in the community-based Hordaland Health Study 1997-1999 in Western Norway. Information on hip fracture was obtained from hospitalizations in the region from enrolment until 31 December 2009. Information on intake of vitamins K1 and K2 collected at baseline was used as potential predictors of hip fracture in Cox proportional hazards regression analyses. RESULTS Participants in the lowest compared to the highest quartile of vitamin K1 intake had increased risk of suffering a hip fracture (hazard ratio (HR)=1.57 [95% CI 1.09, 2.26]). Vitamin K2 intake was not associated with hip fracture. Presence of APOE4-allele did not increase the risk of hip fracture, nor was there any effect modification with vitamin K1 in relation to risk of hip fracture. CONCLUSIONS A low intake of vitamin K1, but not K2, was associated with an increased risk of hip fractures.