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.

Multifunctional catheters combining intracardiac ultrasound imaging and electrophysiology sensing.

A family of 3 multifunctional intracardiac imaging and electrophysiology (EP) mapping catheters has been in development to help guide diagnostic and therapeutic intracardiac EP procedures. The catheter tip on the first device includes a 7.5 MHz, 64-element, side-looking phased array for high resolution sector scanning. The second device is a forward-looking catheter with a 24-element 14 MHz phased array. Both of these catheters operate on a commercial imaging system with standard software. Multiple EP mapping sensors were mounted as ring electrodes near the arrays for electrocardiographic synchronization of ultrasound images and used for unique integration with EP mapping technologies. To help establish the catheters' ability for integration with EP interventional procedures, tests were performed in vivo in a porcine animal model to demonstrate both useful intracardiac echocardiographic (ICE) visualization and simultaneous 3-D positional information using integrated electroanatomical mapping techniques. The catheters also performed well in high frame rate imaging, color flow imaging, and strain rate imaging of atrial and ventricular structures. The companion paper of this work discusses the catheter design of the side-looking catheter with special attention to acoustic lens design. The third device in development is a 10 MHz forward-looking ring array that is to be mounted at the distal tip of a 9F catheter to permit use of the available catheter lumen for adjunctive therapy tools.

Self-focused ZnO transducers for ultrasonic biomicroscopy.

A simple fabrication technique was developed to produce high frequency (100 MHz) self-focused single element transducers with sputtered zinc oxide (ZnO) crystal films. This technique requires the sputtering of a ZnO film directly onto a curved backing substrate. Transducers were fabricated by sputtering an 18 µm thick ZnO layer on 2 mm diameter aluminum rods with ends shaped and polished to produce a 2 mm focus or f-number equal to one. The aluminum rod served a dual purpose as the backing layer and positive electrode for the resultant transducers. A 4 µm Parylene matching layer was deposited on the transducers after housing and interconnect. This matching layer was used to protect the substrate and condition the transfer of acoustic energy between the ZnO film and the load medium. The pulse-echo response for a representative transducer was centered at 101 MHz with a -6 dB bandwidth of 49%. The measured two way insertion loss was 44 dB. A tungsten wire phantom and an adult zebrafish eye were imaged to show the capability of these transducers.

Self-focused ZnO transducers for ultrasonic biomicroscopy.

A simple fabrication technique was developed to produce high frequency (100 MHz) self-focused single element transducers with sputtered zinc oxide (ZnO) crystal films. This technique requires the sputtering of a ZnO film directly onto a curved backing substrate. Transducers were fabricated by sputtering an 18 mum thick ZnO layer on 2 mm diameter aluminum rods with ends shaped and polished to produce a 2 mm focus or f-number equal to one. The aluminum rod served a dual purpose as the backing layer and positive electrode for the resultant transducers. A 4 mum Parylene matching layer was deposited on the transducers after housing and interconnect. This matching layer was used to protect the substrate and condition the transfer of acoustic energy between the ZnO film and the load medium. The pulse-echo response for a representative transducer was centered at 101 MHz with a -6 dB bandwidth of 49%. The measured two way insertion loss was 44 dB. A tungsten wire phantom and an adult zebrafish eye were imaged to show the capability of these transducers.

Relationship between change in femoral neck bone mineral density and hip fracture incidence during treatment with strontium ranelate.

OBJECTIVE: Strontium ranelate (SR) increases bone mineral density (BMD) in postmenopausal osteoporotic women and reduces vertebral and non-vertebral fracture incidence. Hip fracture reduction has also been observed during 3-year treatment with SR in osteoporotic women at high risk of hip fracture. The objective of this study is to analyse the association between BMD changes and hip fracture incidence during treatment with SR. MATERIAL AND METHODS: In this post-hoc analysis, 465 women aged over 74 years with low BMD at the femoral neck (T-score < or = -2.4 according to NHANES normative values) were selected from the population of a recently published study (the Treatment of Peripheral Osteoporosis Study - TROPOS). BMD was assessed at the femoral neck at baseline and after a follow-up of 3 years. Hip fractures were reported by study investigators. RESULTS: After adjusting for age, body mass index, femoral neck BMD at baseline and number of prevalent vertebral fractures, we found that for each 1% increase in femoral neck BMD observed after 3 years, the risk to experience a hip fracture after 3 years decreased by 7% (95% CI: 1-14%) (p = 0.04). In patients experiencing a hip fracture over 3 years of treatment with SR, femoral neck BMD increased by (mean [SE]) 3.41 (1.02)% compared to 7.23 (0.81)% in patients without hip fracture (p = 0.02). CONCLUSION: In this post-hoc analysis of women undergoing 3 years of SR treatment, an increase in femoral neck BMD is associated with a decrease in hip fracture incidence.

Intracerebral Hodgkin's lymphoma in a patient with human immunodeficiency virus.

Central nervous system (CNS) involvement by Hodgkin Lymphoma (HL) is rarely reported. Retrospective and prospective cohort studies suggest an incidence of 0.2-0.5%, mostly in relapsed disease. In spite of a 3 to 18-fold increased risk of HL in patients with human immunodeficiency virus (HIV), only two cases have been reported so far. In this paper, we now report a third case of HIV patient with HL who progressed with isolated CNS infiltration after a standard chemotherapy induced clinical remission. In 1991, when the first case of intracerebral involvement in HIV+ HL was reported an increase of this type of cases would have been expected, but only one more case has been reported since then.

Geographic and other determinants of BMD change in European men and women at the hip and spine. a population-based study from the Network in Europe for Male Osteoporosis (NEMO).

INTRODUCTION: While the determinants of BMD change have been studied in women, there have been few longitudinal studies in men. As part of the Network in Europe for Male Osteoporosis (NEMO) study, data were analysed from 1337 men and 1722 women aged 50-86y (mean=67 years) from 13 centres across Europe to assess determinants of BMD change and between-gender contrasts. METHODS: BMD was measured at the femoral neck, trochanter and/or L2-L4 spine on 2 occasions 0.8-8 years apart (mean=3.5 years) using DXA densitometers manufactured by Hologic (n=6), Lunar (n=5) and Norland (n=2). Each was cross-calibrated using the European Spine Phantom and annual rates of BMD change (g/cm(2)/year) were calculated from the standardised paired BMD values. The EPOS risk factor questionnaire was administered at baseline. RESULTS: In multivariate linear regression models, there were large between centre differences in the mean rates of BMD change in all 3 sites for both genders (P<0.0001) with the standard deviation of the between centre heterogeneity in the adjusted means being 0.005 g/cm(2)/year at the femoral neck. The overall adjusted mean annual rates of BMD change in g/cm(2)/year (95% CI) pooled across centres by random effects meta-analysis in men were: femoral neck -0.005 (-0.009, -0.001); trochanter -0.003 (-0.006, -0.001); and spine 0.000 (-0.004, 0.004). In women the respective estimates were: -0.007 (-0.009, -0.005); -0.004 (-0.006, -0.003); and -0.005 (-0.008, -0.001). The I(2) statistic for heterogeneity was between 81% and 94%, indicating strong evidence of between centre heterogeneity. Higher baseline BMD value was associated with subsequent greater decline in BMD (P<0.001). Preserved BMD was associated with higher baseline body weight in all 3 sites in men (P<0.012) but not in women. Weight gain preserved BMD (P<0.039) in all 3 sites for both genders, except the male spine. Increasing age was associated with faster BMD decline at the trochanter in both genders (P<0.026) and with a slower rate of decline at the female spine (P=0.002). Effects of lifestyle, physical activity, medications, and reproductive factors were not consistent across sites or between genders. CONCLUSION: These results show major geographic variations in rates of BMD change in men and women over 50 years of age across diverse European populations and demonstrate that body weight and weight gain are key determinants of BMD change in men.

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.

Design and modeling of inversion layer ultrasonic transducers using LiNbO3 single crystal.

Using inversion domain engineering controlled by heating temperature, the LiNbO(3) (LNO) piezoelectric plate with both odd and even-order thickness-extensional modes can be excited simultaneously. Therefore, the inversion layer ultrasound transducer is expected to be capable of operating over a wider frequency range. In this paper, the electrical impedance and the acoustic characteristics of LiNbO(3) (LNO) inversion layer transducer have been studied by finite element modeling (FEM). The transducer designed for this study uses a 36 degrees rotated Y-cut LiNbO(3) thin plate with an active element thickness of approximately 100 microm. First the electrical and elastic properties of the 36 degrees rotated Y-cut LNO were obtained by transforming a basic piezoelectric matrix for Z-cut LNO. In order to validate the FEM using the transformed properties several pieces of pure and 50% inversion layer LNO were tested on the electrical impedance analyzer. The modeled impedance characteristics were consistent with the measured data. Next the model was used to design 50-60 MHz transducers using pure and 30% inversion LNO. Two lambda/4 matching layers and a Tungsten loaded epoxy backing were used in these designs. The modeled results show that an over 90% bandwidth transducer can be made with proper matching and 30% inversion layer.

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.

Back pain, disability, and radiographic vertebral fracture in European women: a prospective study.

Vertebral fractures are associated with back pain and disability. There are, however, few prospective data looking at back pain and disability following identification of radiographic vertebral fracture. The aim of this analysis was to determine the impact of radiographically identified vertebral fracture on the subsequent occurrence of back pain and disability. Women aged 50 years and over were recruited from population registers in 18 European centers for participation in the European Prospective Osteoporosis Study. Participants completed an interviewer-administered questionnaire which included questions about back pain in the past year and various activities of daily living, and they had lateral spine radiographs performed. Participants in these centers were followed prospectively and had repeat spine radiographs performed a mean of 3.7 years later. In addition they completed a questionnaire with the same baseline questions concerning back pain and activities of daily living. The presence of prevalent and incident vertebral fracture was defined using established morphometric criteria. The data were analyzed using logistic regression with back pain or disability (present or absent) at follow-up as the outcome variable with adjustment made for the baseline value of the variable. The study included 2,260 women, mean age 62.2 years. The mean time between baseline and follow-up survey was 5.0 years. Two hundred and forty participants had prevalent fractures at the baseline survey, and 85 developed incident fractures during follow-up. After adjustment for age, center, and the baseline level of disability, compared with those without baseline prevalent fracture, those with a prevalent fracture (odds ratio [OR] = 1.4; 95% confidence interval [CI] 1.0 to 2.0) or an incident fracture (OR = 1.7; 95% CI, 0.9 to 3.2) were more likely to report disability at follow-up, though the confidence intervals embraced unity. Those with both a prevalent and incident fracture, however, were significantly more likely to report disability at follow-up (OR = 3.1; 95% CI, 1.4 to 7.0). After adjustment for age, center, and frequency of back pain at baseline, compared with those without baseline vertebral fracture, those with a prevalent fracture were no more likely to report back pain at follow-up (OR = 1.2; 95% CI, 0.8 to 1.7). There was a small increased risk among those with a preexisting fracture who had sustained an incident fracture during follow-up (OR = 1.6; 95% CI, 0.6 to 4.1) though the confidence intervals embraced unity. In conclusion, although there was no significant increase in the level of back pain an average of 5 years following identification of radiographic vertebral fracture, women who suffered a further fracture during follow-up experienced substantial levels of disability with impairment in key physical functions of independent living.

Health-related quality of life and radiographic vertebral fracture.

BACKGROUND: Vertebral fractures are associated with back pain and disability; however, relatively little is known about the impact of radiographic vertebral fractures on quality of life in population samples. The aim of this study was to determine the impact of a recent radiographic vertebral fracture on health-related quality of life (HRQoL). METHODS: Men and women aged 50 years and over were recruited from population registers in 12 European centers. Subjects completed an interviewer-administered questionnaire and had lateral spine radiographs performed. Subjects in these centers were followed prospectively and had repeat spinal radiographs performed a mean of 3.8 years later. Prevalent deformities were defined using established morphometric criteria, and incident vertebral fractures by both morphometric criteria and qualitative assessment. For each incident fracture case, three controls matched for age, gender, and center were selected: one with a prevalent deformity (at baseline) and two without prevalent deformities. All subjects were interviewed or completed a postal questionnaire instrument which included Short Form 12 (SF-12), the EQ-5D (former EuroQol), and the quality of life questionnaire of the International Osteoporosis Foundation (QUALEFFO). The median time from the second spinal radiograph until the quality of life survey was 1.9 years. Comparison between cases and their matched controls was undertaken using the signed rank test. RESULTS: 73 subjects with incident vertebral fracture (cases), mean age 64.8 years (of whom 23 had a baseline deformity), and 196 controls, mean age 63.9 years (of whom 60 had a baseline deformity), were studied. There were strong correlations between the domain scores for each of the three instruments. There was no statistically significant difference in any of the domain scores between cases and those controls with a prevalent deformity. However, compared with the controls without a prevalent deformity the cases had significantly impaired quality of life as determined using the total QUALEFFO score (38.2 vs 33.7), the physical component score of the SF-12 (39.9 vs 43.7) and the health status score of the EQ-5D (62.3 vs 69.9). When the analysis was repeated after stratification of the cases by baseline deformity status (i.e., cases with and without a prevalent deformity at baseline), cases with a prevalent deformity had impaired quality of life compared with their matched controls, both with and without a prevalent deformity. In contrast there was no significant difference in quality of life among the cases without a prevalent deformity and either control group. CONCLUSIONS: In this population-based study a recent vertebral fracture was associated with impairment in quality of life, though this was mainly among those who had sustained a previous vertebral deformity.

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.

Cardiac troponin I in cats with hypertrophic cardiomyopathy.

The molecular structure of cardiac troponin I (cTnI) is highly conserved across mammalian species and assays developed for its measurement in human patients have been validated in a number of veterinary species. A raised concentration of circulating cTnI is a sensitive and specific marker of cardiac myocyte injury. Raised levels have been documented in a variety of cardiac diseases in both human and veterinary patients. This study compared serum cTnI concentrations between 16 cats diagnosed with hypertrophic cardiomyopathy (HCM) using echocardiography and 18 control cats. The results show that cats with HCM have significantly higher concentration of serum cTnI (median 0.95 ng/ml, range 0.2-4.1 ng/ml) than control cats (median <0.2 ng/ml, range <0.2-0.25 ng/ml) [P<0.0001]. Furthermore in cats with cardiomyopathy a weak correlation was found between the thickness of the left ventricular freewall in diastole measured by ultrasound and serum cTnI concentration (r(2)=0.28;P=0.036). These results suggest that measurement of serum cTnI concentration may enable cats with cardiomyopathy to be distinguished from normal cats using the assay described here.

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.