Cardiometabolic health, visceral fat and circulating irisin levels: results from a real-world weight loss study.

BACKGROUND: The aim of this pragmatic intervention study was to investigate changes in cardiometabolic outcomes, irisin plasma concentration, and body composition during a 4-month intervention in unselected obese individuals. MATERIALS AND METHODS: In 111 obese women aged 36.73 ± 7.2 years, we measured changes in weight, lipid profiles, glucose, insulin, Homeostatic Model Assessment-Insulin Resistance Index (HOMA-IR), uric acid, aminotransferases, and irisin. Body composition including lean mass (LM) and total (TF), gynoid (GF), android (AF), and visceral fat (VF) was assessed using densitometry. Physical activity was assessed using the International Physical Activity Questionnaire (IPAQ). The participants received tailored written advice targeting lifestyle according to current guidelines. At follow-up, patients rated their adherence in the self-administered questionnaire. RESULTS: Mean weight loss in the whole group was 3.12 kg (- 3.3%); 26% of the women achieved the desired target of weight loss (> 5% of the initial weight), whereas weight decreased moderately in 50% and increased in 14%. In 86 women with weight loss, there were significant changes in HOMA-IR (- 13.8%), insulin (- 11.2%), alanine aminotransferase (- 8.0%), VF (- 7.0%), AF (- 5.4%), TF (- 4.7%), GF (- 2.8%) and LM (- 1.5%), whereas irisin and HDL-C levels and the mean IPAQ score did not change. CONCLUSIONS: In this real-world evidence study, a successful weight loss achieved only 26% of patients, with overall much better adherence to diet restriction than to exercise. However, even mild to moderate weight loss resulted in significant improvements in cardiometabolic health. Weight loss was associated with a modest LM decrease but did not influence plasma irisin.

Thyroid Peroxidase Antibodies in Non-Autoimmune Hyperthyroidism Treated with Radioactive Iodine.

Introduction: Earlier studies suggest increased serum levels of thyroid peroxidase antibodies (TPOAb) in some cases with non-autoimmune hyperthyroidism. The aim of the study was to assess the incidence of hypothyroidism in patients with nodular toxic goitre and toxic adenoma at 12 months after radioactive iodine therapy in the relation to TPOAb levels. Patients & Measurements: The study comprised 100 patients (83 females; 17 males) treated with radioactive iodine therapy. Serum concentrations of thyrotropin, free thyroxin, TPOAb, and anti-TSH receptor antibodies were assessed at baseline and 12 months after radioactive iodine therapy. Results: High TPOAb level (>60.0 IU/mL) was found in 27% of patients at baseline and 32% at the follow-up. Baseline TPOAb values were higher in subjects with coexisting non-thyroid autoimmune disease (p=0.041). After radioactive iodine therapy, the mean TPOAb level increased in patients with normal baseline TPOAb (p=0.03) and the rates of euthyroidism and hypothyroidism were 61 and 34%, respectively. The rate of hypothyroidism after radioactive iodine therapy was not significantly different in groups with normal and high baseline TPOAb. Conclusions: 27% of patients with non-autoimmune hyperthyroidism were positive for TPOAb. However, baseline TPOAb level did not influence the rate of hypothyroidism at 12 months after radioactive iodine therapy. Our results suggest a more close surveillance after radioactive iodine therapy of patients harboring these antibodies.

Intergenerational transmission of macrosomia in women with gestational diabetes and normal glucose tolerance.

OBJECTIVES: It has been suggested that neonatal macrosomia may contribute to increased risk of obesity and type 2 diabetes in later life. Much less is known about the association between maternal birth weight (MBW) and offspring birth weight (OBW). This retrospective study evaluated the prevalence of macrosomia in women with treated gestational diabetes mellitus (GDM) and normal glucose tolerance during pregnancy. The study also investigated associations between MBW and OBW. STUDY DESIGN: Medical records of 519 pregnant women with treated GDM and 766 women with normal glucose tolerance, referred to the Gestational Diabetes Outpatient Clinic in Szczecin, Poland, were analyzed. The following data were assessed: maternal age, pregravid body weight, height, gestational weight gain, prior GDM, prior macrosomia, MBW and OBW. Birth weight was classified as small for gestational age (SGA), appropriate for gestational age (AGA), large for gestational age (LGA) and macrosomia (≥4000g). OBW was obtained from birth certificates, and MBW was obtained from birth certificates or self-report. RESULTS: The overall prevalence of macrosomia was 8.1%, and was comparable in subgroups of women with and without GDM (7.7% and 8.4%, respectively; p=0.905). The frequencies of SGA, AGA and LGA did not differ between study groups. A positive correlation was found between MBW and OBW in women with treated GDM (r=0.211, p<0.001) and in women with normal glucose tolerance (r=0.220, p<0.001). Regardless of glucose tolerance status during pregnancy, the greatest proportion of macrosomic babies were born to mothers who were themselves born macrosomic (26.5% in mothers with GDM and 20.0% in mothers with normal glucose tolerance; p=0.631). On logistic regression, MBW was found to be a robust predictor of macrosomia in offspring [odds ratio (OR) 1.64, 95% confidence interval (CI) 1.15-2.36 in women with treated GDM; OR 1.35, 95% CI 1.07-1.76 in women with normal glucose tolerance). Other independent predictors of fetal macrosomia were gestational weight gain, prior macrosomia and pregravid body mass index (BMI). CONCLUSIONS: MBW, prior macrosomia, pregravid BMI and gestational weight gain were predictors of macrosomia in offspring, but GDM was not. High MBW seems to contribute to intergenerational transmission of macrosomia.

Vertebral Scheuermann's disease in Europe: prevalence, geographic variation and radiological correlates in men and women aged 50 and over.

UNLABELLED: In 27 centres across Europe, the prevalence of deforming spinal Scheuermann's disease in age-stratified population-based samples of over 10,000 men and women aged 50+ averaged 8% in each sex, but was highly variable between centres. Low DXA BMD was un-associated with Scheuermann's, helping the differential diagnosis from osteoporosis. INTRODUCTION: This study aims to assess the prevalence of Scheuermann's disease of the spine across Europe in men and women over 50 years of age, to quantitate its association with bone mineral density (BMD) and to assess its role as a confounder for the radiographic diagnosis of osteoporotic fracture. METHODS: In 27 centres participating in the population-based European Vertebral Osteoporosis Study (EVOS), standardised lateral radiographs of the lumbar and of the thoracic spine from T4 to L4 were assessed in all those of adequate quality. The presence of Scheuermann's disease, a confounder for prevalent fracture in later life, was defined by the presence of at least one Schmorl's node or irregular endplate together with kyphosis (sagittal Cobb angle >40° between T4 and T12) or a wedged-shaped vertebral body. Alternatively, the (rare) Edgren-Vaino sign was taken as diagnostic. The 6-point-per-vertebral-body (13 vertebrae) method was used to assess osteoporotic vertebral shape and fracture caseness. DXA BMD of the L2-L4 and femoral neck regions was measured in subsets. We also assessed the presence of Scheuermann's by alternative published algorithms when these used the radiographic signs we assessed. RESULTS: Vertebral radiographic images from 4486 men and 5655 women passed all quality checks. Prevalence of Scheuermann's varied considerably between centres, and based on random effect modelling, the overall European prevalence using our method was 8% with no significant difference between sexes. The highest prevalences were seen in Germany, Sweden, the UK and France and low prevalences were seen in Hungary, Poland and Slovakia. Centre-level prevalences in men and women were highly correlated. Scheuermann's was not associated with BMD of the spine or hip. CONCLUSIONS: Since most of the variation in population impact of Scheuermann's was unaccounted for by the radiological and anthropometric data, the search for new genetic and environmental determinants of this disease is encouraged.

Patient-reported outcomes in women with gestational diabetes: a longitudinal study.

BACKGROUND: Gestational Diabetes Mellitus (GDM) is a common health problem among pregnant women and may be associated with distress. PURPOSE: The purpose of the study was to describe changes in patient-reported outcomes in women with GDM and identify factors associated with increased distress in these patients. RESEARCH DESIGN: The study was conducted in 205 women diagnosed with GDM. Study participants underwent a physical examination and completed a questionnaire two times during pregnancy. On average, the questionnaire was completed at 27 weeks of gestation at baseline and 36 weeks at follow-up. The questionnaire included socio-demographic and clinical variables, standardized patient-reported outcome measures, and questions about the impact of GDM on daily life, satisfaction with care, knowledge about GDM, and social and professional support. Our main outcome of interest was diabetes-related distress, measured by the Problem Areas in Diabetes (PAID) questionnaire. Data were analyzed using descriptive statistics and multivariable regression models. RESULTS: At baseline, 80% of the women were satisfied with their diabetes care and 58% said they managed their diabetes well. The proportion reporting little or no knowledge of GDM dropped from almost 50% at baseline to 14% at follow-up. However, the proportion reporting that GDM affected their social life increased from 26 to 35%, and the proportion reporting interference with family life increased from 14 to 26%. Insulin treatment, frequency of blood glucose measurements, lack of knowledge about GDM, and lack of support from family and health care providers were strongly and significantly associated with distress. CONCLUSION: In women with GDM, intensified treatment and lack of informational and social support are associated with distress. These aspects of GDM care appear to be appropriate targets for future research and interventions aimed at reducing the level of distress in these patients.

Serum adiponectin, bone mineral density and bone turnover markers in post-menopausal women with newly diagnosed Type 2 diabetes: a 12-month follow-up.

OBJECTIVE: During a period of 12 months, we evaluated the longitudinal impact of metabolic control of diabetes on selected bone turnover markers, bone mineral density and serum adiponectin concentrations in post-menopausal women with newly diagnosed Type 2 diabetes. METHODS: Serum total adiponectin, bone alkaline phosphatase, HbA(1c), urinary deoxypyridinoline excretion, bone mineral density of the total body, lumbar spine and total hip were measured in 57 women aged 50-78 years with newly diagnosed Type 2 diabetes. RESULTS: At baseline, women had normal bone-specific alkaline phosphatase, deoxypyridinoline and bone mineral density, as evaluated by t- and z-scores. After 12 months of treatment, a significant decrease in body weight, waist circumference and HbA(1c) was observed. Bone mineral density of the total body, lumbar spine and total hip decreased by 0.4, 0.2 and 1.0% (P = 0.018) per year, respectively. Adiponectin was inversely correlated with bone mineral density at three sites (R = -0.28, -0.24 and -0.19, respectively). There was a transient increase (P < 0.05) in serum adiponectin within the first 6 months, followed by a slow decrease toward the baseline value during the next 6 months. An improvement in diabetes control had no impact on bone turnover marker levels, which did not change significantly during the entire study period. CONCLUSIONS: Bone turnover markers, bone mineral density and the rate of bone loss are within normal ranges in post-menopausal women with newly diagnosed Type 2 diabetes. Bone mineral density of the total body, lumbar spine and total hip is inversely correlated with total adiponectin.

Pregravid body mass index as a predictor of gestational diabetes mellitus.

AIMS: It has been well documented that overweight or obesity before pregnancy is a strong predictor of gestational diabetes mellitus (GDM). The aim of this study was to assess the risk of GDM in women who were classified on the basis of pregravid body mass index (BMI) as normal weight and underweight. SUBJECTS AND METHODS: We analysed medical records of 1121 women with GDM who were referred to the Outpatient Clinic for Diabetic Pregnant Women in Szczecin (north-west part of Poland) between January 2001 and December 2005. The control group consisted of 1011 healthy pregnant women. All the women were Caucasian, were aged > or = 18 years and had single pregnancies. RESULTS: The cut point for BMI as a risk indicator for GDM was 22.85 kg/m(2) (odds ratio = 1.91; 95% confidence interval 1.5-2.1; sensitivity 47.8%, specificity 65.9%). In all of the analysed BMI ranges, except for the underweight group, significant relationships between pregravid BMI and GDM were found and BMI was the strongest predictor for GDM treated with insulin. Of all women with GDM, 25.7% were treated with insulin. The percentage of women requiring insulin therapy significantly increased with an increase of BMI across all studied categories. CONCLUSIONS: Not only in overweight but also in normal-weight women, the risk for GDM increases with increases in pregravid BMI and adjustment for confounding variables (age, prior GDM and parity) did not influence this relationship. Pregravid BMI is a strong predictor for GDM requiring insulin treatment.

The association between past Chlamydia pneumoniae infection and markers of chronic inflammation in obese women.

It has been widely accepted that obesity is associated with chronic, low-grade inflammation that affects the adipose tissue as well as the entire system. The aim of this study was to assess whether past Chlamydia pneumoniae infection influences obesity phenotypes and serum levels of low-grade inflammation markers in obese, healthy premenopausal women. The study was performed on 48 obese and 42 normal-weight women, aged 31.2 +/- 7.2 years. Serum levels of C-reactive protein (CRP), tumor necrosis factor alpha (TNFalpha) and its soluble receptor R2 (sTNF-R2), and interleukin 6 (IL-6) were measured. Body composition was assessed by bioimpendance. Insulin sensitivity was assessed by quantitative insulin sensitivity check index (QUICKI). The seroprevalence of C. pneumoniae infection was 69.1% and was similar in obese and normal-weight women (75.2% and 61.9%, respectively; P = 0.18). Obese women had higher CRP than healthy controls (P < 0.05). IL-6, TNFalpha, and sTNF-R2 showed no significant differences when comparing obese and normal-weight or C. pneumoniae infected and uninfected women. In multivariate regression analysis, fat mass (P < 0.001) and QUICKI (P < 0.01), accounting for 35% of the variance of CRP and C. pneumoniae infection, did not significantly contribute to this model (P = 0.51). In conclusion, past C. pneumoniae infection was not associated with changes in chronic inflammation markers in premenopausal obese women.

Serum acylated ghrelin, adiponectin and leptin levels in normal-weight and obese premenopausal women.

Ghrelin, leptin, and adiponectin play an important role in the regulation of energetic homeostasis, but physiological relationships between these hormones have not been elucidated. This study was therefore designed to characterize the association between serum acylated ghrelin, leptin, and adiponectin levels, as well as insulin resistance evaluated by homeostasis model of assessment in 32 normal-weight and 60 age-matched metabolically healthy obese women. In normal-weight, but not in obese women, we found a positive linear correlation between leptin and ghrelin (r=0.375; p=0.034). In the multiply regression analysis we observed the change of direction of leptin influence on acylated ghrelin level from positive in normal-weight (p=0.001) to negative in obese women without insulin-resistance (p=0.033); in obese women with insulin resistance leptin was not significantly associated with ghrelin. In neither group was any linear correlation found between ghrelin and adiponectin. However, by multivariate analysis adiponectin was positively associated with ghrelin, but only in obese women without insulin resistance (p=0.01). In conclusion, in normal-weight women leptin is positively correlated with acylated ghrelin. In obese women without insulin resistance different interactions between both hormones might reflect a physiological mechanism of adaptation to a positive energy balance.

Not insulin but insulin sensitivity, leptin, and cortisol are major factors regulating serum acylated ghrelin level in healthy women.

It has been suggested that insulin and glucose are the most important factors for ghrelin secretion. Most of these studies were performed using total ghrelin assays, detecting two forms of ghrelin (acylated and desacyl), derived from the same peptide precursor but having different biological effects. This study was therefore designed to characterize associations between serum acylated ghrelin levels (Ghr), selected adipocytokines, hormones, and carbohydrate metabolism parameters in healthy women in stable energy metabolism. The study was performed on 32 healthy, normal-weight, non-pregnant women with normal [body mass index (BMI) 18.9-24.2 kg/m2] and stable (the difference between two measurements performed within 1 month being less than 0.5 kg) body weight, aged 22-47 yr. Leptin, Ghr, GH, IGF-I, cortisol, insulin, and glucose were measured in the early follicular phase of the menstruation cycle. Insulin sensitivity was measured using quantitative insulin sensitivity check index (QUICKI). Body composition was assessed by bioimpedance. We found a positive linear correlation between leptin and Ghr (r=0.375; p=0.034) and negative correlation between insulin and Ghr (r=-0.374; p=0.034). GH, IGF-I, adiponectin, and body composition parameters did not correlate with Ghr. In multiple regression analysis only QUICKI, leptin, glucose, and cortisol (positively) and age (negatively) accounted for 50% variation of Ghr. Insulin and BMI did not contribute significantly to the model. Our results suggest that in healthy women basal Ghr level is regulated by multiple factors, mainly by insulin sensitivity, leptin, and adrenal glands activity. However, further studies are needed to elucidate the physiological mechanisms involved in acylated Ghr secretion.

Whom to treat? The contribution of vertebral X-rays to risk-based algorithms for fracture prediction. Results from the European Prospective Osteoporosis Study.

INTRODUCTION: Vertebral fracture is a strong risk factor for future spine and hip fractures; yet recent data suggest that only 5-20% of subjects with a spine fracture are identified in primary care. We aimed to develop easily applicable algorithms predicting a high risk of future spine fracture in men and women over 50 years of age. METHODS: Data was analysed from 5,561 men and women aged 50+ years participating in the European Prospective Osteoporosis Study (EPOS). Lateral thoracic and lumbar spine radiographs were taken at baseline and at an average of 3.8 years later. These were evaluated by an experienced radiologist. The risk of a new (incident) vertebral fracture was modelled as a function of age, number of prevalent vertebral fractures, height loss, sex and other fracture history reported by the subject, including limb fractures occurring between X-rays. Receiver Operating Characteristic (ROC) curves were used to compare the predictive ability of models. RESULTS: In a negative binomial regression model without baseline X-ray data, the risk of incident vertebral fracture significantly increased with age [RR 1.74, 95% CI (1.44, 2.10) per decade], height loss [1.08 (1.04, 1.12) per cm decrease], female sex [1.48 (1.05, 2.09)], and recalled fracture history; [1.65 (1.15, 2.38) to 3.03 (1.66, 5.54)] according to fracture site. Baseline radiological assessment of prevalent vertebral fracture significantly improved the areas subtended by ROC curves from 0.71 (0.67, 0.74) to 0.74 (0.70, 0.77) P=0.013 for predicting 1+ incident fracture; and from 0.74 (0.67, 0.81) to 0.83 (0.76, 0.90) P=0.001 for 2+ incident fractures. Age, sex and height loss remained independently predictive. The relative risk of a new vertebral fracture increased with the number of prevalent vertebral fractures present from 3.08 (2.10, 4.52) for 1 fracture to 9.36 (5.72, 15.32) for 3+. At a specificity of 90%, the model including X-ray data improved the sensitivity for predicting 2+ and 1+ incident fractures by 6 and 4 fold respectively compared with random guessing. At 75% specificity the improvements were 3.2 and 2.4 fold respectively. With the modelling restricted to the subjects who had BMD measurements (n=2,409), the AUC for predicting 1+ vs. 0 incident vertebral fractures improved from 0.72 (0.66, 0.79) to 0.76 (0.71, 0.82) upon adding femoral neck BMD (P=0.010). CONCLUSION: We conclude that for those with existing vertebral fractures, an accurately read spine X-ray will form a central component in future algorithms for targeting treatment, especially to the most vulnerable. The sensitivity of this approach to identifying vertebral fracture cases requiring anti-osteoporosis treatment, even when X-rays are ordered highly selectively, exceeds by a large margin the current standard of practice as recorded anywhere in the world.

Low BMD is less predictive than reported falls for future limb fractures in women across Europe: results from the European Prospective Osteoporosis Study.

We have previously shown that center- and sex-specific fall rates explained one-third of between-center variation in upper limb fractures across Europe. In this current analysis, our aim was to determine how much of the between-center variation in fractures could be attributed to repeated falling, bone mineral density (BMD), and other risk factors in individuals, and to compare the relative contributions of center-specific BMD vs. center-specific fall rates. A clinical history of fracture was assessed prospectively in 2451 men and 2919 women aged 50-80 from 20 centers participating in the European Prospective Osteoporosis Study (EPOS) using standardized questionnaires (mean follow-up = 3 years). Bone mineral density (BMD, femoral neck, trochanter, and/or spine) was measured in 2103 men and 2565 women at these centers. Cox regression was used to model the risk of incident fracture as a function of the person-specific covariates: age, BMD, personal fracture history (PFH), family hip fracture history (FAMHIP), time spent walking/cycling, number of 'all falls' and falls not causing fracture ('fracture-free') during follow-up, alcohol consumption, and body mass index. Center effects were modeled by inclusion of multiplicative gamma-distributed random effects, termed center-shared frailty (CSF), with mean 1 and finite variance theta (theta) acting on the hazard rate. The relative contributions of center-specific fall risk and center-specific BMD on the incidence of limb fractures were evaluated as components of CSF. In women, the risk of any incident nonspine fracture (n = 190) increased with age, PFH, FAMHIP, > or =1 h/day walking/cycling, and number of 'all falls' during follow-up (all P < 0.074). 'Fracture-free' falls (P = 0.726) and femoral neck BMD did not have a significant effect at the individual level, but there was a significant center-shared frailty effect (theta = 0.271, P = 0.001) that was reduced by 4% after adjusting for mean center BMD and reduced by 19% when adjusted for mean center fall rate. Femoral trochanter BMD was a significant determinant of lower limb fractures (n = 53, P = 0.014) and the center-shared frailty effect was significant for upper limb fractures (theta = 0.271, P = 0.011). This upper limb fracture center effect was unchanged after adjusting for mean center BMD but was reduced by 36% after adjusting for center mean fall rates. In men, risk of any nonspine fracture (n = 75) increased with PFH, fall during follow-up (P < 0.026), and with a decrease in trochanteric BMD [RR 1.38 (1.08, 1.79) per 1 SD decrease]. There was no center effect evident (theta = 0.081, P = 0.096). We conclude that BMD alone cannot be validly used to discriminate between the risk of upper limb fractures across populations without taking account of population-specific variations in fall risk and other factors. These variations might reflect shared environmental or possibly genetic factors that contribute quite substantially to the risk of upper limb fractures in women.

Determinants of the size of incident vertebral deformities in European men and women in the sixth to ninth decades of age: the European Prospective Osteoporosis Study (EPOS).

UNLABELLED: More severe vertebral fractures have more personal impact. In the European Prospective Osteoporosis Study, more severe vertebral collapse was predictable from prior fracture characteristics. Subjects with bi-concave or crush fractures at baseline had a 2-fold increase in incident fracture size and thus increased risk of a disabling future fracture. INTRODUCTION: According to Euler's buckling theory, loss of horizontal trabeculae in vertebrae increases the risk of fracture and suggests that the extent of vertebral collapse will be increased in proportion. We tested the hypothesis that the characteristics of a baseline deformity would influence the size of a subsequent deformity. METHODS: In 207 subjects participating in the European Prospective Osteoporosis Study who suffered an incident spine fracture in a previously normal vertebra, we estimated loss of volume (fracture size) from plane film images of all vertebral bodies that were classified as having a new fracture. The sum of the three vertebral heights (anterior, mid-body, and posterior) obtained at follow-up was subtracted from the sum of the same measures at baseline. Each of the summed height loss for vertebrae with a McCloskey-Kanis deformity on the second film was expressed as a percentage. RESULTS AND CONCLUSIONS: In univariate models, the numbers of baseline deformities and the clinical category of the most severe baseline deformity were each significantly associated with the size of the most severe incident fracture and with the cumulated sum of all vertebral height losses. In multivariate modeling, age and the clinical category of the baseline deformity (crush > bi-concave > uni-concave > wedge) were the strongest determinants of both more severe and cumulative height loss. Baseline biconcave and crush fractures were associated at follow-up with new fractures that were approximately twice as large as those seen with other types of deformity or who previously had undeformed spines. In conclusion, the characteristics of a baseline vertebral deformity determines statistically the magnitude of vertebral body volume lost when a subsequent fracture occurs. Because severity of fracture and number of fractures are determinants of impact, the results should improve prediction of the future personal impact of osteoporosis once a baseline prevalent deformity has been identified.

Determinants of incident vertebral fracture in men and women: results from the European Prospective Osteoporosis Study (EPOS).

The aim of this analysis was to determine the influence of lifestyle, anthropometric and reproductive factors on the subsequent risk of incident vertebral fracture in men and women aged 50-79 years. Subjects were recruited from population registers from 28 centers across Europe. At baseline, they completed an interviewer-administered questionnaire and had lateral thoraco-lumbar spine radiographs performed. Repeat spinal radiographs were performed a mean of 3.8 years later. Incident vertebral fractures were defined morphometrically and also qualitatively by an experienced radiologist. Poisson regression was used to determine the influence of the baseline risk factor variables on the occurrence of incident vertebral fracture. A total of 3173 men (mean age 63.1 years) and 3402 women (mean age 62.2 years) contributed data to the analysis. In total there were 193 incident morphometric and 224 qualitative fractures. In women, an age at menarche 16 years or older was associated with an increased risk of vertebral fracture (RR = 1.80; 95%CI 1.24, 2.63), whilst use of hormonal replacement was protective (RR = 0.58; 95%CI 0.34, 0.99). None of the lifestyle factors studied including smoking, alcohol intake, physical activity or milk consumption showed any consistent associations with incident vertebral fracture. In men and women, increasing body weight and body mass index were associated with a reduced risk of vertebral fracture though, apart from body mass index in men, the confidence intervals embraced unity. For most variables the strengths of the associations observed were similar using the qualitative and morphometric approaches to fracture definition. In conclusion our data suggest that modification of other lifestyle risk factors is unlikely to have a major impact on the population occurrence of vertebral fractures. The important biological mechanisms underlying vertebral fracture risk need to be explored using new investigational strategies.

Incidence of limb fracture across Europe: results from the European Prospective Osteoporosis Study (EPOS).

The aim of this population-based prospective study was to determine the incidence of limb fracture by site and gender in different regions of Europe. Men and women aged 50-79 years were recruited from population registers in 31 European centers. Subjects were invited to attend for an interviewer-administered questionnaire and lateral spinal radiographs. Subjects were subsequently followed up using an annual postal questionnaire which included questions concerning the occurrence of new fractures. Self-reported fractures were confirmed where possible by radiograph, attending physician or subject interview. There were 6451 men and 6936 women followed for a median of 3.0 years. During this time there were 140 incident limb fractures in men and 391 in women. The age-adjusted incidence of any limb fracture was 7.3/1000 person-years [pyrs] in men and 19 per 1000 pyrs in women, equivalent to a 2.5 times excess in women. Among women, the incidence of hip, humerus and distal forearm fracture, though not 'other' limb fracture, increased with age, while in men only the incidence of hip and humerus fracture increased with age. Among women, there was evidence of significant variation in the occurrence of hip, distal forearm and humerus fractures across Europe, with incidence rates higher in Scandinavia than in other European regions, though for distal forearm fracture the incidence in east Europe was similar to that observed in Scandinavia. Among men, there was no evidence of significant geographic variation in the occurrence of these fractures. This is the first large population-based study to characterize the incidence of limb fracture in men and women over 50 years of age across Europe. There are substantial differences in the descriptive epidemiology of limb fracture by region and gender.

Is the predictive power of previous fractures for new spine and non-spine fractures associated with biochemical evidence of altered bone remodelling? The EPOS study. European Prospective Osteoporosis Study.

BACKGROUND: In the European Prospective Osteoporosis Study (EPOS), a past spine fracture increased risk of an incident fracture 3.6 - 12-fold even after adjusting for BMD. We examined the possibility that biochemical marker levels were associated with this unexplained BMD-independent element of fracture risk. METHODS: Each of 182 cases in EPOS of spine or non-spine fracture that occurred in 3.8 years of follow-up was matched by age, sex and study centre with two randomly assigned never-fractured controls and one case of past fracture. Analytes measured blind were: osteocalcin, bone-specific alkaline phosphatase, total alkaline phosphatase, serum creatinine, calcium, phosphate and albumin, together with the collagen cross-links degradation products serum CTS and urine CTX. Most subjects also had bone density measured by DXA. RESULTS: Cases who had recent fractures did not differ in marker levels from cases who had their last fracture more than 3 years previously. No statistically significant effect of recent fracture was found for any marker except osteocalcin, which was 17.6% lower in recent peripheral cases compared to unfractured controls (p<0.05) and this was independent of BMD. CONCLUSION: Past fracture as a risk indicator for future fracture is not strongly mediated through increased bone turnover.

Incidence of vertebral fracture in europe: results from the European Prospective Osteoporosis Study (EPOS).

Vertebral fracture is one of the major adverse clinical consequences of osteoporosis; however, there are few data concerning the incidence of vertebral fracture in population samples of men and women. The aim of this study was to determine the incidence of vertebral fracture in European men and women. A total of 14,011 men and women aged 50 years and over were recruited from population-based registers in 29 European centers and had an interviewer-administered questionnaire and lateral spinal radiographs performed. The response rate for participation in the study was approximately 50%. Repeat spinal radiographs were performed a mean of 3.8 years following the baseline film. All films were evaluated morphometrically. The definition of a morphometric fracture was a vertebra in which there was evidence of a 20% (+4 mm) or more reduction in anterior, middle, or posterior vertebral height between films--plus the additional requirement that a vertebra satisfy criteria for a prevalent deformity (using the McCloskey-Kanis method) in the follow-up film. There were 3174 men, mean age 63.1 years, and 3,614 women, mean age 62.2 years, with paired duplicate spinal radiographs (48% of those originally recruited to the baseline survey). The age standardized incidence of morphometric fracture was 10.7/1,000 person years (pyr) in women and 5.7/1,000 pyr in men. The age-standardized incidence of vertebral fracture as assessed qualitatively by the radiologist was broadly similar-12.1/1,000 pyr and 6.8/1,000 pyr, respectively. The incidence increased markedly with age in both men and women. There was some evidence of geographic variation in fracture occurrence; rates were higher in Sweden than elsewhere in Europe. This is the first large population-based study to ascertain the incidence of vertebral fracture in men and women over 50 years of age across Europe. The data confirm the frequent occurrence of the disorder in men as well as in women and the rise in incidence with age.

Improving risk assessment: hip geometry, bone mineral distribution and bone strength in hip fracture cases and controls. The EPOS study. European Prospective Osteoporosis Study.

Hip geometry and bone mineral density (BMD) have previously been shown to relate independently to hip fracture risk. Our objective was to determine by how much hip geometric data improved the identification of hip fracture. Lunar pencil beam scans of the proximal femur were obtained. Geometric and densitometric values from 800 female controls aged 60 years or more (from population samples which were participants in the European Prospective Osteoporosis Study, EPOS) were compared with data from 68 female hip fracture patients aged over 60 years who were scanned within 4 weeks of a contralateral hip fracture. We used Lunar DPX 'beta' versions of hip strength analysis (HSA) and hip axis length (HAL) applied to DPX(L) data. Compressive stress (Cstress), calculated by the HSA software to occur as a result of a typical fall on the greater trochanter, HAL, body mass index (BMI: weight/(height)2) and age were considered alongside femoral neck BMD (FN-BMD, g/cm2) as potential predictors of fracture. Logistic regression was used to generate predictors of fracture initially from FN-BMD. Next age, Cstress (as the most discriminating HSA-derived parameter), HAL and BMI were added to the model as potentially independent predictors. It was not necessary to include both HAL and Cstress in the logistic models, so the entire data set was examined without excluding the subjects missing HAL measurements. Cstress combined with age and BMI provided significantly better prediction of fracture than FN-BMD used alone as is current practice, judged by comparing areas under receiver operating characteristic (ROC) curves (p<0.001, deLong's test). At a specificity of 80%, sensitivity in identification was improved from 66% to 81%. Identifying women at high risk of hip fracture is thus likely to be substantially enhanced by combining bone density with age, simple anthropometry and data on the structural geometry of the hip. HSA might prove to be a valuable enhancement of DXA densitometry in clinical practice and its use could justify a more proactive approach to identifying women at high risk of hip fracture in the community.

Falls explain between-center differences in the incidence of limb fracture across Europe.

There is important geographic variation in the occurrence of the major osteoporotic fractures across Europe. The aim of this study was to determine whether between-center variation in limb fracture rates across Europe could be explained by variation in the incidence of falls. Men and women, aged 50-79 years, were recruited from population-based registers in 30 European centers. Subjects were followed by postal questionnaire to ascertain the occurrence of incident fractures, and were also asked about the occurrence and number of recent falls. Self-reported fractures were confirmed, where possible, by review of the radiographs, medical record, or subject interview. The age- and gender-adjusted incidence of falls was calculated by center using Poisson regression. Poisson regression was also used to assess the extent to which between-center differences in the incidence of limb fractures could be explained by differences in the age- and gender-adjusted incidence of falls at those centers. In all, 6302 men (mean age 63.9 years) and 6761 women (mean age 63.1 years) completed at least one questionnaire concerning fractures and falls. During a median follow-up time of 3 years, 3647 falls were reported by men and 4783 by women. After adjusting for age and gender, there was evidence of significant between-center differences in the occurrence of falls. There was also between-center variation in the occurrence of upper limb, lower limb, and distal forearm fractures. Variation in the age- and gender-adjusted center-specific fall rates explained 24%, 14%, and 6% of the between-center variation in incidence of distal forearm and upper and lower limb fractures, respectively. Given the constraints inherent in such an analysis, in men and women aged 50-79 years, variation in fall rates could explain a significant proportion of the between-center variation in the incidence of limb fracture across Europe.

Prevalent vertebral deformity predicts incident hip though not distal forearm fracture: results from the European Prospective Osteoporosis Study.

The presence of a vertebral deformity increases the risk of subsequent spinal deformities. The aim of this analysis was to determine whether the presence of vertebral deformity predicts incident hip and other limb fractures. Six thousand three hundred and forty-four men and 6788 women aged 50 years and over were recruited from population registers in 31 European centers and followed prospectively for a median of 3 years. All subjects had radiographs performed at baseline and the presence of vertebral deformity was assessed using established morphometric methods. Incident limb fractures which occurred during the follow- up period were ascertained by annual postal questionnaire and confirmed by radiographs, review of medical records and personal interview. During a total of 40348 person-years of follow-up, 138 men and 391 women sustained a limb fracture. Amongst the women, after adjustment for age, prevalent vertebral deformity was a strong predictor of incident hip fracture, (rate ratio (RR) = 4.5; 95% CI 2.1-9.4) and a weak predictor of 'other' limb fractures (RR = 1.6; 95% CI 1.1-2.4), though not distal forearm fracture (RR = 1.0; 95% CI 0.6-1.6). The predictive risk increased with increasing number of prevalent deformities, particularly for subsequent hip fracture: for two or more deformities, RR = 7.2 (95% CI 3.0-17.3). Amongst men, vertebral deformity was not associated with an increased risk of incident limb fracture though there was a nonsignificant trend toward an increased risk of hip fracture with increasing number of deformities. In summary, prevalent radiographic vertebral deformities in women are a strong predictor of hip fracture, and to a lesser extent humerus and 'other' limb fractures; however, they do not predict distal forearm fractures.