The different influence of high levels of physical activity on the incidence of knee OA in overweight and obese men and women-a gender specific analysis.

OBJECTIVE: To investigate the influence of physical activity on incidence of knee osteoarthritis (OA) in overweight and obese men and women. DESIGN: Data were extracted from the Osteoarthritis Initiative cohort on 1,667 participants without symptomatic knee OA at baseline. We used logistic regression and marginal effect models to estimate the effect of body mass index (BMI) and reported physical activity score, together with the interaction between them, on the development of radiographic knee OA, symptomatic knee OA and joint space narrowing (JSN) after 96-months. RESULTS: Men in the most active quartile had almost double the likelihood of knee OA, independent of OA definition [e.g., odds ratio (OR) 2.4 (95%CI: 1.2-4.5) for radiographic knee OA]. Interaction analyses showed statistically significant interactions between physical activity and BMI on developing knee OA (i) radiographic OA interaction(P = 0.039), (ii) symptomatic OA interaction(P = 0.022), (iii) JSN interactionP = 0.012). The margin plots in men also demonstrated that the effect of physical activity on different measures of knee OA were modified by high levels of BMI. These effects were not mirrored in women where at all BMI levels, the level of reported physical activity did not influence likelihood of knee OA independent of OA definition. CONCLUSIONS: In overweight and obese men, there appears to be a threshold above which increasing levels of physical activity are associated with higher risk of knee OA. This is absent in women.

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.

Influence of age and sex steroids on bone density and geometry in middle-aged and elderly European men.

SUMMARY: The influence of age and sex steroids on bone density and geometry of the radius was examined in two European Caucasian populations. Age-related change in bone density and geometry was observed. In older men, bioavailable oestradiol may play a role in the maintenance of cortical and trabecular bone mineral density (BMD). INTRODUCTION: To examine the effect of age and sex steroids on bone density and geometry of the radius in two European Caucasian populations. METHODS: European Caucasian men aged 40-79 years were recruited from population registers in two centres: Manchester (UK) and Leuven (Belgium), for participation in the European Male Ageing Study. Total testosterone (T) and oestradiol (E(2)) were measured by mass spectrometry and the free and bioavailable fractions calculated. Peripheral quantitative computed tomography was used to scan the radius at distal (4%) and midshaft (50%) sites. RESULTS: Three hundred thirty-nine men from Manchester and 389 from Leuven, mean ages 60.2 and 60.0 years, respectively, participated. At the 50% radius site, there was a significant decrease with age in cortical BMD, bone mineral content (BMC), cortical thickness, and muscle area, whilst medullary area increased. At the 4% radius site, trabecular and total volumetric BMD declined with age. Increasing bioavailable E(2) (bioE(2)) was associated with increased cortical BMD (50% radius site) and trabecular BMD (4% radius site) in Leuven, but not Manchester, men. This effect was predominantly in those aged 60 years and over. In older Leuven men, bioavailable testosterone (Bio T) was linked with increased cortical BMC, muscle area and SSI (50% radius site) and total area (4% radius site). CONCLUSIONS: There is age-related change in bone density and geometry at the midshaft radius in middle-aged and elderly European men. In older men bioE(2) may maintain cortical and trabecular BMD. BioT may influence bone health through associations with muscle mass and bone area.

Gonadal sex steroid status and bone health in middle-aged and elderly European men.

SUMMARY: The influence of sex steroids on calcaneal quantitative ultrasound (QUS) parameters was assessed in a population sample of middle-aged and elderly European men. Higher free and total E(2) though not testosterone, were independently associated with higher QUS parameters. INTRODUCTION: The aim of this study was to investigate the association between QUS parameters and sex steroids in middle-aged and elderly European men. METHODS: Three thousand one hundred forty-one men aged between 40 and 79 years were recruited from eight European centres for participation in a study of male ageing: the European Male Ageing Study. Subjects were invited by letter to attend for an interviewer-administered questionnaire, blood sample and QUS of the calcaneus (Hologic-SAHARA). Blood was assessed for sex steroids including oestradiol (E(2)), testosterone (T), free and bio-available E(2) and T and sex hormone binding globulin (SHBG). RESULTS: Serum total T was not associated with any of the QUS parameters. Free T and both free and total E(2) were positively related to all QUS readings, while SHBG concentrations were negatively associated. These relationships were observed in both older and younger (<60 years) men. In a multivariate model, after adjustment for age, centre, height, weight, physical activity levels and smoking, free E(2) and SHBG, though not free T, remained independently associated with the QUS parameters. After further adjustment for IGF-1, however, the association with SHBG became non-significant. CONCLUSION: Higher free and total E(2) are associated with bone health not only among the elderly but also middle-aged European men.

Non-steroidal anti-inflammatory drug use does not appear to be associated with increased cardiovascular mortality in patients with inflammatory polyarthritis: results from a primary care based inception cohort of patients.

OBJECTIVES: There is controversy about the effects of non-steroidal anti-inflammatory drugs (NSAIDs) on cardiovascular disease (CVD) mortality. The aim of this study was to explore associations between NSAID use and mortality in patients with inflammatory polyarthritis (IP). SUBJECTS AND METHODS: A total of 923 patients with new onset (IP), recruited to the UK Norfolk Arthritis Register (NOAR) between 1990-1994, were followed up to the end of 2004. Current medication was recorded annually for the first 6 years and then every 2-3 years. Rheumatoid factor (RF) and C-reactive protein (CRP) were measured. Logistic regression was used to calculate all cause and CVD mortality odds ratios (OR) for NSAID use at baseline and during follow-up, adjusting for gender and time-varying covariates: RF, CRP, joint counts, smoking, steroid use, DMARD use and other medication use. RESULTS: By 2004 there were 203 deaths, 85 due to CVD. At baseline, NSAIDs were used by 66% of patients. In final multivariate models, baseline NSAID use was inversely associated with all cause mortality (adjusted OR 0.62, 95% CI 0.45 to 0.84) and CVD mortality (adjusted OR 0.54, 95% CI 0.34 to 0.86). Interval NSAID use had weaker mortality associations: all cause mortality (adjusted OR 0.72, 95% CI 0.52 to 1.00), CVD mortality (adjusted hazard ratio (HR) 0.66, 95% CI 0.40 to 1.08). CONCLUSION: No excess CVD or all cause mortality was observed in NSAID users in this cohort of patients with IP. This is at variance with the literature relating to NSAID use in the general population. It is unclear whether this represents unmeasured confounders influencing a doctor's decision to avoid NSAIDs in the treatment of IP.

Can clinical factors at presentation be used to predict outcome of treatment with methotrexate in patients with early inflammatory polyarthritis?

PURPOSE: Methotrexate (MTX) is the first choice conventional disease-modifying antirheumatic drug (DMARD) for rheumatoid arthritis. It is not universally effective, however; although to date it is not possible to predict with any accuracy which patients will respond to treatment. The aim of this analysis was to examine whether clinical and genetic variables could be used to predict response to MTX. METHODS: Patients recruited to the Norfolk Arthritis Register (NOAR), a primary care based inception cohort of patients with inflammatory polyarthritis, were eligible for this analysis if they were commenced on MTX as their first DMARD within 3 months of their baseline visit and had at least 2 years of follow-up data. Outcome on MTX was defined as: (1) stopped for adverse events; (2) stopped for inefficacy or second DMARD added; (3) stopped for other reasons; or (4) remained on MTX monotherapy. Multiple logistic regression was used to establish which variables (including demographics, disease activity and Health Assessment Questionnaire score) predicted stopping monotherapy for inefficacy or adverse event (with those remaining on treatment taken as the referent category). The area under the Receiver Operating Characteristic curves (AUC ROC), were used to determine how accurate the model was at predicting outcome. RESULTS: 309 patients were included in this analysis. At 1 year (2 years), 34 (46) patients had stopped for adverse events and 25 (49) had either stopped monotherapy for inefficacy or had a second DMARD added. 231 (188) patients remained on MTX monotherapy. The strongest predictor of inefficacy at both time points was shared epitope positivity: odds ratios (OR) 5.8 (95% confidence intervals (CI) 1.3 to 25.6) at 1 year, OR 3.0 (95% CI 1.3 to 7.3) at 2 years. High Health Assessment Questionnaire score (OR 1.84 95% CI 1.12 to 3.01) and female gender (OR 2.2, 95% CI 0.92 to 5.28) were associated with adverse events on MTX at 1 year. However, even the most optimal combinations of the factors analysed were only weakly predictive of treatment outcome: AUC ROC for adverse events 0.68 (95% CI 0.58 to 0.78) and for inefficacy AUC ROC 0.71 (95% CI 0.6 to 0.81). CONCLUSIONS: Within this cohort, routine clinical and laboratory factors were poor at predicting outcome of treatment with MTX. Given the major therapeutic advantage to be derived from accurate prediction of treatment outcome, further studies will need to investigate novel biological and other markers.

European biologicals registers: methodology, selected results and perspectives.

With the licensing of the first tumour necrosis factor (TNF)alpha inhibitors, independent academia-initiated but industry-sponsored drug registers were set up by the national rheumatology societies in several European countries in order to monitor the long-term safety and effectiveness of this new generation of drugs. Even though different in some respects of study design and monitoring, the registers share a number of common features: they include all licensed biological agents, they observe the patients for a defined period of time or indefinitely irrespective of the drug given and they use comparator cohorts or national registers in order to put the results into perspective. The registers have been collaborating closely since inception. Three of them (the British, Swedish and German registers) have agreed on a standardised reporting system of adverse events which ensures a high and uniform quality of data submitted to the companies, who subsequently report to the drug regulatory authorities, enabling regulatory requirements on safety surveillance to be fulfilled. In the present work, major results on drug safety with regard to infections, malignancies, cardiovascular events, pregnancy outcomes and deaths are summarised. With an increasing number of new drugs and multiple exposures of individual patients the assignment of events to specific treatments will become exceedingly difficult. This and other methodological challenges and the approaches to cope with them are discussed. A growing dialogue between drug regulatory authorities, academic medicine and companies in order to make best use of the potentials of academia-driven drug registers as new tools for pharmacovigilance with currently described rheumatology registers as prototypes is anticipated.

Evaluation of work-related psychosocial factors and regional musculoskeletal pain: results from a EULAR Task Force.

OBJECTIVES: To establish whether review articles provide consistent conclusions on associations between workplace psychosocial factors and musculoskeletal pain and, if differences exist, to explore whether this is related to the methods used. METHODS: Reviews, reported up to February 2007, that included consideration of workplace psychosocial factors and upper limb, back or knee pain were identified through searches of multiple databases. The specific work-related psychosocial factors considered were job demands, support, job autonomy and job satisfaction. The conclusions of each review on one or more of the psychosocial/musculoskeletal pain associations were extracted. RESULTS: 15 review articles were identified that considered one or more of the regional pain syndromes included in the study. For back pain, the most consistent conclusions (four reviews positive out of six) were with high job demands and low job satisfaction. The studies of upper limb pain were exclusively related to shoulder and/or neck pain, and the most consistent positive conclusions were with high and low job demands (four reviews positive out of six and two reviews positive out of three, respectively). For knee pain, only a single review was identified. For individual reviews of back and upper limb pain, there were marked differences in the number of associations concluded to be positive between reviews. CONCLUSIONS: The reasons for reviews coming to different conclusions included that they were often evaluating different bodies of evidence (according to their search criteria, the year when the review was conducted, the role that quality assessment played in whether studies contributed to evidence, and the combination of risk factors addressed in individual studies), but more important was whether the review specified explicit criteria for making conclusions on strength of evidence. These conclusions emphasise the importance of developing standardised methods for conducting such evaluations of existing evidence and the importance of new longitudinal studies for clarifying the temporal relationship between psychosocial factors and musculoskeletal pain in the workplace.

Investigating the determinants of international differences in the prevalence of chronic widespread pain: evidence from the European Male Ageing Study.

OBJECTIVES: To determine whether among middle-aged and elderly men there is evidence of international differences in the prevalence of chronic widespread pain (CWP) and whether any such differences could be explained by psychological, psychosocial factors or differences in physical health status. METHODS: The European Male Ageing Study (EMAS) sampled from population registers in cities (centres) of eight European countries. Each centre recruited an age-stratified sample of men aged 40-79 years. Information on pain was collected by questionnaire and subjects were classified according to whether they satisfied the American College of Rheumatology definition of CWP. Information was collected on social status, mental health, recent life events and co-morbidities. RESULTS: Across all centres 3963 subjects completed a study questionnaire, with participation rates ranging from 24% in Hungary to 72% in Estonia. There were significant differences in prevalence: between 5% and 7% in centres in Italy, England, Belgium and Sweden, 9-15% in centres in Spain, Poland and Hungary and 15% in Estonia. There were strong relationships between poor mental health, adverse recent life events, co-morbidities and CWP. Adjustment for these factors explained between half and all of the excess risk in the eastern European centres: the excess risk in Poland was explained (odds ratio (OR) 1.1, 95% CI 0.9 to 1.2) but there remained excess risk in Hungary (OR 1.6, 95% CI 1.4 to 1.8) and Estonia (OR 2.6, 95% CI 2.2 to 2.9). CONCLUSIONS: This study is the first directly to compare the occurrence of CWP internationally. There is an excess prevalence in countries of eastern Europe and this excess is associated with adverse psychosocial factors as well as poorer psychological and physical health.

Musculoskeletal pain is associated with a long-term increased risk of cancer and cardiovascular-related mortality.

OBJECTIVES: To test the hypothesis that individuals with regional and widespread pain disorders have an increased risk of mortality. METHODS: We conducted a prospective cohort study of 4515 adults. Subjects were an age- and sex-stratified sample who had participated in a population study of pain occurrence during 1996. Based on those reports subjects were classified as having no pain, regional pain or widespread pain. All subjects were identified on the National Health Service Central Register and followed up until April 2005, a total of 8.2 yrs, at which time information was obtained on vital status, and if applicable, date and cause of death. The relationship between pain status and subsequent death is expressed as mortality rate ratios with 95% CIs, adjusted for age, gender, ethnicity and practice. RESULTS: A total of 35.2% reported regional pain and 16.9% satisfied criteria for widespread pain. In comparison with those without pain, there was a 20% and 30% increased risk of dying over the follow-up period among subjects with regional and widespread pain, respectively. The specific causes of death in excess were cancer and cardiovascular disease. In addition, the mortality risk from both cancer and cardiovascular deaths was found to increase as the number of pain sites that subjects reported increased. CONCLUSIONS: This study supports a previous observation that persons with regional and widespread pain are at an increased risk of cancer death. Possible mechanisms should be explored.

Ethical and legal constraints on data sharing between countries in multinational epidemiological studies in Europe report from a joint workshop of the European League Against Rheumatism standing committee on epidemiology with the "AutoCure" project.

BACKGROUND: We report on a workshop on ethical and legal constraints on data sharing between countries in multinational epidemiologic research in Europe that was held in January 2007 in Potsdam, Germany. The participants were experienced epidemiologic and clinical researchers from eight European countries. The aim of the workshop was to share current knowledge on the above-mentioned topics, to identify areas for joint action and to enhance the likelihood of success for the new funding programmes. METHODS: Workshop sessions and review of findings. RESULTS: Key elements and recommendations have been drawn up. CONCLUSIONS: Epidemiologic and clinical studies are increasingly planned and conducted on a European level, and funds are available for this kind of studies. However, data sharing in multi-centre clinical and epidemiological studies is hampered by the different legal and ethical constraints individual national researchers face.

Environmental risk factors for the development of psoriatic arthritis: results from a case-control study.

OBJECTIVE: To identify potential risk factors for the onset of inflammatory arthritis (IA) in a large cohort of patients with psoriatic arthritis (PsA) of recent onset. METHODS: We recruited cases with psoriasis and an onset of IA within the past 5 years. Controls were patients who had psoriasis but no arthritis. We assessed potential factors associated with the development of IA using a detailed postal questionnaire. An unmatched analysis adjusted for age and gender was performed. Exposure was censored in the controls at a "dummy-date" assigned randomly in proportion to the percentage of cases developing IA in any given year. RESULTS: We studied 98 cases and 163 controls. Exposures showing a positive association before the onset of IA in patients with psoriasis were: rubella vaccination (OR (95% CI) = 12.4 (1.2 to 122)), injury sufficient to require a medical consultation (2.53 (1.1 to 6.0)), recurrent oral ulcers (4.2 (2.0 to 9.0)) and moving house (2.3 (1.2 to 4.4)). Cases were also more likely to have experienced a fractured bone requiring hospital admission (50% vs 9%, p = 0.040). CONCLUSIONS: We found a number of environmental exposures associated with the onset of IA in subjects with psoriasis. The strongest associations were with trauma thereby adding to the hypothesis of a "deep Koebner phenomenon" in PsA. Our data also suggest that exposure of the immune system to certain infection-related triggers may also be of relevance. Further studies are needed to verify these observations and to examine potential immunological mechanisms that underlie them.

Investigating the role of the HLA-Cw*06 and HLA-DRB1 genes in susceptibility to psoriatic arthritis: comparison with psoriasis and undifferentiated inflammatory arthritis.

OBJECTIVE: Psoriasis of early onset (type I; age of onset 40 years). HLA-DRB1*07, in linkage disequilibrium with HLA-Cw*06, was also associated with patients with PsA having type I psoriasis (OR 2.7, 95% CI 2.1, 3.7, p<0.00001). HLA-DRB1*04 alleles and the SE were associated with undifferentiated inflammatory arthritis but not with PsA. CONCLUSIONS: The SE is not a PsA susceptibility locus. HLA-Cw*06 and HLA-DRB1*07 are associated with patients with PsA having type I psoriasis, suggesting that the primary association is with age of onset of psoriasis. Patients with PsA having type I psoriasis, therefore, have a genetic background different to those with type II psoriasis, and adjustment for this is necessary in future studies that investigate the genetic susceptibility of PsA.

Mapping existing hip and knee replacement registries in Europe.

The general shortage of evidence regarding benefits and harms of medical devices has been highlighted following the serious safety concerns with metal-on-metal hip replacements and silicone breast implants and was again pointed out in a recent survey of European Health Technology Assessment institutions. In this context the new European medical device regulation will enforce post-marketing surveillance of existing and new implants. The usefulness of registry data as a source of information for medical device real-world clinical performance and safety has been demonstrated. However, these data might be under-used by researchers and policy makers. One reason for this is the insufficient awareness of their existence. The aim of this review is to provide information to relevant stakeholders on the extent and breadth of the data currently collected in European joint replacement registries. We identified 24 registries, most of them of national coverage. Total numbers of primary total hip and knee replacements included were over 3.1 and 2.5 million records, respectively. The current focus of these registries is on whole-lifespan implant surveillance via revision rate monitoring, quality assessment of surgical and perioperative care, and hospital performance assessment. More recently, national and international comparison and benchmarking have increasingly become part of their endeavors.

Forearm bone geometry and mineral content in UK women of European and South-Asian origin.

Ethnic variation in areal bone mineral density (BMD) has been well documented. Such variation may, however, reflects differences in bone geometry rather than volumetric BMD (vBMD). The aim of the study was to compare bone geometry, mineral content (BMC) and vBMD in two ethnic groups, and study the influence of body size, physical activity, reproductive variables, 25 hydroxy-vitamin D (25(OH)D) and parathormone (PTH) status on any observed differences. The data were from a population-based, cross-sectional survey of peak bone mass in South Asian and European women, the population consisted 230 pre-menopausal South Asian (n=118, mean age 28.6+/-4.6 years) and European (n=112, mean age 30+/-4.3 years) women of UK origin. Women who participated completed an interviewer assisted questionnaire, had blood taken for assessment of 25(OH)D and PTH and had measurements of their distal (4%) and diaphyseal (50%) radius geometry, BMC and vBMD using peripheral quantitative computed tomography. At the 50% radius, South Asians had lower vBMD (p<0.001), BMC (p<0.001), cortical area (p<0.001), cortical thickness (p<0.001), cross-sectional area (p=0.04) and increased medullary area (p<0.04). Cross-sectional muscle area and stress strain index, however, were not different. Adjustment for age, height and weight attenuated, the difference in cross-section area but did not account for any of the other observed differences. Further adjustment for reproductive variables a physical activity index, 25(OH)D and PTH, attenuated ethnic differences in cortical BMC, area and thickness which became non-significant; however, ethnic differences in cortical vBMD and medullary area persisted. At the 4% site, after adjusting for age, height and weight, there was no difference in total area, total or trabecular vBMD between ethnic groups. After further adjustment for physical activity, reproductive variables, 25(OH)D and PTH, trabecular vBMD was higher in the South Asians. In conclusion, there are differences in bone geometry, BMC and vBMD at the radial diaphysis between UK South Asians and Europeans which are not explained by differences in body size. Polar stress-strain index was similar, however, suggesting no important differences in bone strength.

Predictors of persistent neck pain after whiplash injury.

OBJECTIVE: To establish the aetiological influences of persistent neck pain following a motor vehicle collision and to construct a model for use in the emergency department for identifying patients at high risk of persistent symptoms. DESIGN: Prospective cohort study. Patients recruited from hospital emergency departments were sent a questionnaire to gather information on various exposures. They were followed up at 1, 3, and 12 months to identify those with persistent symptoms. MAIN OUTCOME MEASURE: Persistent neck pain (pain at 1, 3, and 12 months after collision). RESULTS: The baseline survey included 765 patients. Subsequently, 480 completed a questionnaire at each follow up time point, of whom 128 (27%) reported neck pain on each occasion. Few collision specific factors predicted persistent neck pain. In contrast, a high level of general psychological distress, pre-collision history of widespread body pain, type of vehicle, whiplash associated symptoms, and initial neck disability best predicted the persistence of symptoms. Furthermore, these factors, in combination, accounted for more than a fivefold increase in the risk of persistent neck pain. CONCLUSION: The greatest predictors of persistent neck pain following a motor vehicle collision relate to psychological distress and aspects of pre-collision health rather than to various attributes of the collision itself. With these factors, and those relating to initial injury severity, it is possible to identify a subgroup of patients presenting with neck pain with the highest risk of persistent symptoms. Thus, it is possible to identify whiplash patients with a poor prognosis and to provide closer follow up and specific attention to management in these individuals.

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.

Poor sleep and depression are independently associated with a reduced pain threshold. Results of a population based study.

To determine the relative contributions of psychological factors and sleep disturbance to reduced pain threshold we conducted a cross-sectional two-phase population-based study. A total of 424 subjects were recruited, stratified by pain and distress status. Subjects completed a postal questionnaire that asked about current pain and covered aspects of psychological status and sleep disturbance. Samples of subjects stratified by the extent of bodily pain they reported and psychological status were invited to participate in an examination of pain threshold. The association between psychological status, sleep disturbance and a low pain threshold was examined using ordinal regression. High levels of psychological distress (OR=1.6, 95% CI (1.02, 2.5)), disturbed sleep (OR=2.2, 95% CI (1.4, 3.5)) and high scores on the HAD depression scale (OR=2.1, 95% CI (1.3, 3.2)) were all associated with having a low pain threshold. In multivariate analysis disturbed sleep and depression remained independently associated with a low pain threshold. These relationships persisted after adjustment for pain status. This study had demonstrated that depression and poor sleep are associated with a reduced pain threshold.

The prevalence of vertebral deformity in european men and women: the European Vertebral Osteoporosis Study.

Our aim was to determine the prevalence of radiographically defined vertebral deformity, as a marker of vertebral osteoporosis, in different regions and populations within Europe. We used a cross-sectional population-based survey. Population-based sampling frames were obtained from 36 centers in 19 European countries. Stratified random sampling was used to recruit 15,570 males and females aged 50-79 years. Lateral spinal radiographs were taken according to a standardized protocol, and all X-rays were evaluated centrally. Vertebral deformity was morphometrically defined according to the published methods of McCloskey and Eastell. Based on the McCloskey method, the mean center prevalence of all deformities was 12% in females (range 6-21%) and 12% in males (range 8-20%). The prevalence increased with age in both sexes though the gradient was steeper in females. There was substantial geographical variation, with the highest rates in Scandinavian countries. Radiographically defined vertebral deformity is a common disorder and equally frequent in males and females. Using standardized methodology, there is important variation in occurrence across Europe, which might suggest clues to pathogenesis.

Risk factors for vertebral deformities in men: relationship to number of vertebral deformities. European Vertebral Osteoporosis Study Group.

Recent epidemiological studies suggest a similar overall prevalence of vertebral deformity in men to that in women, though the influence of increasing age on the prevalence of vertebral deformity is less marked in men. However, most affected men have only a single or two vertebral deformities, which may be unrelated to osteoporosis. The aim of this study was to examine the role of risk factors, previously demonstrated to be associated with vertebral osteoporosis in females, in men with single/dual deformities compared to those with multiple deformities. Age stratified random samples of men aged 50 years and over were recruited from population registers in 30 European centers as part of the European Vertebral Osteoporosis Study (EVOS). Subjects had a lateral spinal radiograph and the presence of vertebral deformity was determined using the McCloskey algorithm. Lifestyle and other risk factor data were obtained from an interviewer-administered questionnaire. In all 6937 men with a mean age of 64.4 (SD = 8.5) years were studied of whom 738 (10.6%) subjects had one or two deformities, and 109 (1.6%) subjects had three or more deformities. There was a marked increase in the prevalence of multiple vertebral deformities with increasing age, but only a modest effect of age on the prevalence of single deformities. Associations between various risk factors for osteoporosis and vertebral deformity were analyzed separately in men with single/dual vertebral deformity from those with three or more deformities using logistic regression. After adjustment for age, there were statistically significant associations between the following risk factors and multiple deformities: previous hip fracture (odds ratio [OR] 10.5), lack of regular physical activity (OR 2.9), low body mass (OR 2.5), and previous steroid use (OR 2.3). By contrast, there were only weak associations with these same variables in males with single/dual deformities and, apart from poor self-reported general health, all of the 95% confidence intervals spanned unity. There was no difference in the reporting of very heavy levels of physical activity under the age of 50 years between men with single/dual deformities and those with multiple deformities. In conclusion, men with multiple deformities showed a similar pattern of risk factor association to those seen in women with vertebral deformity, in contrast to men with single/dual deformities.