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Summary: 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. [ABSTRACT FROM AUTHOR]

: 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. [ABSTRACT FROM AUTHOR]

We previously showed that it is possible to cross-calibrate peripheral bone densitometers using the European Spine Phantom (ESP). We have now performed a multinational study of cross-calibrated radius bone density based on normal subjects of both sexes in eight European centers. Six centers were equipped with machines made by Scanco or Stratec for determining distal radial trabecular bone density by quantitative computed tomography (QCT) and two were equipped with Lunar SP2 single photon absorptiometry (SPA) equipment for measuring midshaft cortical bone density. Subjects recruited ranged from 20 to over 80 years of age. Over one hundred and fifteen men were studied by QCT and a different cohort of 104 men were studied with SPA; the equivalent figures for women were 235 and 123. Reference ranges were derived for bone density against age for each of the four groups, and their applicability is discussed in relation to between-center differences in the results obtained. There were insignificant differences (P > 0.05 with Bonferroni correction) between centers in the values obtained by QCT in the different populations. However, there were considerably larger and highly statistically significant differences between midshaft cortical bone density values of about 10% of overall means between subjects from eastern Finland and central Belgium (P < 0.001), with higher Finnish values. Women had considerably lower radial trabecular bone density values than men at all ages, a result that differentiates the radius from the spine. This sex difference widened after menopause. These results have important implications for understanding the contribution of bone density to the differential risk of Colles' fracture in the two sexes and suggest that further work is needed to establish young normal reference ranges for radial bone density in Europe. [ABSTRACT FROM AUTHOR]

Objective: Rheumatoid arthritis (RA) is an inflammatory joint disease with features of an autoimmune disease with female predominance. Candidate genes located on the X-chromosome were selected for a family trio-based association study., Methods: A total of 1452 individuals belonging to 3 different sample sets were genotyped for 16 single-nucleotide polymorphisms (SNP) in 7 genes. The first 2 sets consisted of 100 family trios, each of French Caucasian origin, and the third of 284 additional family trios of European Caucasian origin. Subgroups were analyzed according to sex of patient and presence of anti-cyclic citrullinated peptide (anti-CCP) autoantibodies., Results: Four SNP were associated with RA in the first sample set and were genotyped in the second set. In combined analysis of sets 1 and 2, evidence remained for association of 3 SNP in the genes UBA1, TIMP1, and IL9R. These were again genotyped in the third sample set. Two SNP were associated with RA in the joint analysis of all samples: rs6520278 (TIMP1) was associated with RA in general (p = 0.035) and rs3093457 (IL9R) with anti-CCP-positive RA patients (p = 0.037) and male RA patients (p = 0.010). A comparison of the results with data from whole-genome association studies further supports an association of RA with TIMPL The sex-specific association of rs3093457 (IL9R) was supported by the observation that men homozygous for rs3093457-CC are at a significantly higher risk to develop RA than women (risk ratio male/female = 2.98; p = 0.048)., Conclusion: We provide evidence for an association of at least 2 X-chromosomal genes with RA: TIMP1 (rs6520278) and IL9R (rs3093457).

The integrin alpha(v)beta3, whose alpha(v) subunit is encoded by the ITGAV gene, plays a key role in angiogenesis. Hyperangiogenesis is involved in rheumatoid arthritis (RA) and the ITGAV gene is located in 2q31, one of the suggested RA susceptibility loci. Our aim was to test the ITGAV gene for association and linkage to RA in a family-based study from the European Caucasian population. Two single nucleotide polymorphisms were genotyped by PCR-restriction fragment length polymorphism in 100 French Caucasian RA trio families (one RA patient and both parents), 100 other French families and 265 European families available for replication. The genetic analyses for association and linkage were performed using the comparison of allelic frequencies (affected family-based controls), the transmission disequilibrium test, and the genotype relative risk.We observed a significant RA association for the C allele of rs3738919 in the first sample (affected family-based controls, RA index cases 66.5% versus controls 56.7%; P = 0.04). The second sample showed the same trend, and the third sample again showed a significant RA association. When all sets were combined, the association was confirmed (affected family-based controls, RA index cases 64.6% versus controls 58.1%; P = 0.005). The rs3738919-C allele was also linked to RA (transmission disequilibrium test, 56.5% versus 50% of transmission; P = 0.009) and the C-allele-containing genotype was more frequent in RA index cases than in controls (RA index cases 372 versus controls 339; P = 0.002, odds ratio = 1.94, 95% confidence interval = 1.3-2.9). The rs3738919-C allele of the ITGAV gene is associated with RA in the European Caucasian population, suggesting ITGAV as a new minor RA susceptibility gene.

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.

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.

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., (Copyright 2002 by Elsevier Science Inc.)

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.

Hip geometry and bone mineral density (BMD) have been shown previously to relate, independently of each other, to risk of hip fracture. We used Lunar DPX "beta" versions of hip strength analysis (HSA) and hip axis length (HAL) software to analyze scans from ten representative age-stratified population samples in the European Prospective Osteoporosis Study (EPOS). All 1617 subjects were >50 years of age, and 1033 were women. The data were modeled with gender and center as categorical variables. The bone mineral density of the upper half of the femoral neck declined at a faster rate with age than that in the lower half. Femoral neck cross-sectional moment of inertia (CSMI), a measure of resistance to bending, showed no significant age reduction in either gender. However, height and weight effects on CSMI were significantly more beneficial in men than in women (0.002 < p < 0.012) and the weight effect appeared to be mediated by bone mineral content (BMC). Compressive stress (Cstress), defined as the stress in the femoral neck at its weakest cross section arising from a standardized fall, was higher in women. Although Cstress increased with body weight when BMC was held constant, in practice it fell through the association and statistical interaction of rising body weight with rising BMC. HAL, as expected, was strongly positively associated with male gender and also height (p < 0.0001). Hip strength-related indices were markedly center-dependent. Significant differences (p < 0.0001) were noted between the centers for all the variables investigated that related to hip geometry. Adjustment for femoral neck bone mineral content (totBMC) showed these center differences to account for >50% of center variation in hip strength, which remained highly significant (p < 0.0001). We conclude that there are substantial geographical differences in femoral neck geometry as well as in BMD. These geometric variations may contribute to the large variations in hip fracture risk across Europe. The effects of aging on hip strength need to be explored in longitudinal studies.

The aims of this study were to identify risk factors for hip fracture in men aged 50 years or more. We identified 730 men with hip fracture from 14 centers from Portugal, Spain, France, Italy, Greece and Turkey during the course of a prospective study of hip fracture incidence and 1132 age-stratified controls selected from the neighborhood or population registers. The questionnaire examined aspects of work, physical activity past and present, diseases and drugs, height, weight, indices of co-morbidity and consumption of tobacco, alcohol, calcium, coffee and tea. Significant risk factors identified by univariate analysis included low body mass index (BMI), low sunlight exposure, a low degree of recreational physical activity, low consumption of milk and cheese, and a poor mental score. Co-morbidity including sleep disturbances, loss of weight, impaired mental status and poor appetite were also significant risk factors. Previous stroke with hemiplegia, prior fragility fractures, senile dementia, alcoholism and gastrectomy were associated with significant risk, whereas osteoarthrosis, nephrolithiasis and myocardial infarction were associated with lower risks. Taking medications was not associated with a difference in risk apart from a protective effect with the use of analgesics independent of co-existing osteoarthrosis and an increased risk with the use of anti-epileptic agents. Of the potentially 'reversible' risk factors, BMI, leisure exercise, exposure to sunlight and consumption of tea and alcohol and tobacco remained independent risk factors after multivariate analysis, accounting for 54% of hip fractures. Excluding BMI, 46% of fractures could be explained on the basis of the risk factors sought. Of the remaining factors low exposure to sunlight and decreased physical activity accounted for the highest attributable risks (14% and 9% respectively). The use of risk factors to predict hip fractures had relatively low sensitivity and specificity (59.6% and 61.0% respectively). We conclude that lifestyle factors are associated with significant differences in the risk of hip fracture. Potentially remediable factors including a low degree of physical exercise and a low BMI account for a large component of the total risk.

We have previously shown considerable between-center variation in bone mineral density (BMD) in the 13 EVOS centers that performed bone densitometry on their sex- and age-stratified population samples, after adjusting for weight and age. We have now investigated whether part of the between-center variability may be attributed to between-center variations in the use of medications. Information was collected from 2088 women and 1908 men at baseline on whether the subjects had ever been prescribed calcium, calcitonin, anabolic steroids, fluoride, vitamin D, or glucocorticoids and, for the women, whether they had ever used the oral contraceptive pill (OCP) or hormone replacement therapy (HRT). Each of these variables was fitted into a regression model adjusted for age, height, weight, and center. Only OCP and HRT significantly affected BMD. Those who had ever used OCPs had spinal BMD 0.029 g/cm2 greater than those who had never used them. Users of HRT had higher BMD than nonusers: 0. 037 g/cm2 at the spine, 0.018 g/cm2 at the trochanter, and 0.018 g/cm2 at the femoral neck. As expected, there was a great variation between centers in the use of OCP and HRT, but there were no significant correlations between mean BMD at any site in a given center and the prevalence of OCP or HRT use in that center. The between-center variance in BMD at all three sites remained highly significant after adjusting for treatment (P < 0.001). We conclude that HRT and OCP use are associated with moderate increases in BMD. The geographical variability of BMD in Europe was not explained by treatment with pharmaceuticals.

The purpose of this study was to investigate variations in bone density between 16 European populations, 13 of which were participants in the European Vertebral Osteoporosis Study (EVOS). Men and women aged 50-80 years were recruited randomly from local population registers, stratified in 5-year age bands. The other three centres recruited similarly. Random samples of 20-100% of EVOS subjects were invited for dual-energy X-ray absorptiometry (DXA) densitometry of the lumbar spine and/or proximal femur using Hologic, Lunar or Norland pencil beam machines or, in one centre, a Sopha fan-beam machine. Cross-calibration of the different machines was undertaken using the European Spine Phantom prototype (ESPp). Highly significant differences in mean bone density were demonstrated between centres, giving rise to between centre SDs in bone density that were about a quarter of a population SD. These differences persisted when centres using Hologic machines and centres using Lunar machines were considered separately. The centres were ranked differently according to whether male or female subjects were being considered and according to site of measurement (L2-4, femoral neck or femoral trochanter). As expected, bone mineral density (BMD) had a curvilinear relationship with age, and apparent rates of decrease slowed as age advanced past 50 years in both sexes. In the spine, not only did male BMD usually appear to increase with age, but there was a highly significant difference between centres in the age effect in both sexes, suggesting a variability in the impact of osteoarthritis between centres. Weight was consistently positively associated with BMD, but the effects of height and armspan were less consistent. Logarithmic transformation was needed to normalize the regressions of BMD on the independent variates, and after transformation, all sites except the femoral neck in females showed significant increases in SD with age. Interestingly, the effect of increasing weight was to decrease dispersion in proximal femur measurements in both sexes, further accentuating the tendency in women for low body mass index to be associated with osteoporosis as defined by densitometry. It is concluded that there are major differences between BMD values in European population samples which, with variations in anthropometric variables, have the potential to contribute substantially to variations in rates of osteoporotic fracture risk in Europe.

The aims of this study were to determine common international risk factors for hip fracture in women aged 50 years or more. We studied women aged 50 years or more who sustained a hip fracture in 14 centers from Portugal, Spain, France, Italy, Greece, and Turkey over a 1-year period. Women aged 50 years or more selected from the neighborhood or population registers served as controls. Cases and controls were interviewed using a structured questionnaire on work, physical activity, exposure to sunlight, reproductive, history and gynecologic status, height, weight, mental score, and consumption of tobacco, alcohol, calcium, coffee, and tea. Significant risk factors identified by univariate analysis included low body mass index (BMI), short fertile period, low physical activity. lack of sunlight exposure, low milk consumption, no consumption of tea, and a poor mental score. No significant adverse effects of coffee or smoking were observed. Moderate intake of spirits was a protective factor in young adulthood, but otherwise no significant effect of alcohol intake was observed. For some risks, a threshold effect was observed. A low BMI and milk consumption were significant risks only in the lowest 50% and 10% of the population, respectively. A late menarche, poor mental score, low BMI and physical activity, low exposure to sunlight, and a low consumption of calcium and tea remained independent risk factors after multivariate analysis, accounting for 70% of hip fractures. Excluding mental score and age at menarche (not potentially reversible), the attributable risk was 56%. Thus, about half of the hip fractures could be explained on the basis of the potentially reversible risk factors sought. In contrast, the use of risk factors to "predict" hip fractures had moderate sensitivity and specificity. We conclude that variations in lifestyle factors are associated with significant differences in the risk of hip fracture, account for a large component of the total risk, and may be of some value in selecting individuals at high risk.

Measurements of the proximal femur by dual X-ray absorptiometry (DXA) are assuming increasing importance in clinical and epidemiological studies. However, different DXA manufacturers have adopted varying approaches to measuring the femoral neck and trochanter regions with the result that there is as yet no agreement on normal ranges and how to cross-calibrate between different machines. In this Concerted Action (of the EU's 2nd Framework Programme), 12 clinical centers in eight countries recruited a total of 855 female and 517 male Caucasian subjects who were judged to be free of conditions known to cause secondary osteoporosis and who had not been treated with drugs known to affect bone mass. The DXA machines used were made by Hologic, Lunar, and Norland. Each machine was cross-calibrated with the European Spine Phantom prototype designed by Kalender. All femoral neck and trochanter results were expressed as standardized values and were first examined for possible bias due to between-brand differences in choice of areas for measurement. On average, trochanter areas were similar between brands but Norland chose a narrower neck region for analysis. Bone mineral density (BMA or BMD g/cm2) was log-normally distributed for all groups at the femoral neck but normally distributed at the trochanter in men and postmenopausal women. There were substantial between-center differences after cross-calibration in age-adjusted mean values at both sites and also in the rates of apparent bone loss with age and the amounts of scatter within populations about mean age-adjusted values. With the proviso that locally derived normal ranges would allow more accurate comparisons for clinical purposes, European normal ranges were derived for both neck and trochanter. Data obtained with the three individual brands of machine fitted these overall ranges well. Bone loss was apparent in premenopausal women at the femoral neck but not the trochanter. Postmenopausal women's data was somewhat better fitted by reference to years since menopause than to chronological age. This work provides a basis for conducting future epidemiological and clinical studies with more than one brand of machine as long as each individual subject, if measured consecutively, is measured on the same machine throughout.

A semi-anthropomorphic 'distal radius like' phantom, developed by Kalender and Ruegsegger for use in peripheral bone densitometry using single photon (DPA) dual X-ray (DXA) and quantitative computed tomography (QCT) machines, has been studied with a view to cross-calibrating different types and brands of densitometers in current use. In the context of an EU 'Concerted Action' (second Framework Programme) the phantom was repeatedly measured on six SPA machines, three DXA machines and nine QCT machines (545 measurements). Linear regression equations were derived, individual to each machine, which allowed the derivation of 'standardized densities'. In this way we converted measurements made by machines of the same modality to a common scale of measurements. Two machines (one DXA, one SPA) showed statistically significant instability over time emphasising the need for rigorous quality control in the application of densitometry. In other respects these results provide an encouraging basis for the derivation of standardized normative ranges and the more effective use of peripheral densitometry in future clinical and epidemiological studies.

We assessed the incidence of hip fracture and ecological correlates in residents of 14 communities in six countries of Southern Europe. Hip fracture cases were recorded prospectively in defined catchment areas over a 1-year interval. A retrospective questionnaire was used to assess ecological differences between communities. During a 1-year period of observation a total of 3629 men and women over the age of 50 years were identified with hip fracture from a catchment of 3 million. In all communities the fracture rate increased exponentially with age. There were large and significant differences between centres in the doubling time for hip fracture risk with age and in crude and age-standardized rates. Greater than 4-fold and 13-fold differences in age-standardized risk were found amongst men and women respectively. The lowest rates were observed from Turkey and the highest from Seville, Crete and Porto. Fractures were significantly more frequent among women than men with the exception of three rural Turkish centres. Indeed, in rural Turkey the normal female/male ratio was reserved. Variations in incidence between regions were greater than the differences within centres between sexes, and there was a close and significant correlation between incidence rates for men and those for women in the regions studied. Excess female morbidity increased progressively from the age of 50 years but attained a plateau after the age of 80 years, suggesting a finite duration of the effect of the menopause. The retrospective questionnaire completed by 80% of cases suggested that differences in incidence between the communities studied could not be explained by differences in gonadal status in women. In both men and women cross-cultural associations were found with factors related to age or socioeconomic prosperity, the majority of which disappeared after adjustment for age. We conclude that there are marked and sizeable differences in the incidence rates of hip fracture throughout Southern Europe. The reasons for these differences are not known but affect both men and women, and are likely to be related to lifestyle or genetic factors rather than to differences in endocrine status.

The relationship between osteoarthritis and osteoporosis (hip fracture) was studied using the data from the MEDOS study, a large prospective epidemiological study of femoral neck fracture patients and age-matched controls in the Mediterranean area. Osteoarthritis was found to be protective against hip fracture in both men and women, with a significant reduction of the relative risk factor for osteoporosis (relative risk = 0.48 and 0.68, respectively, p < 0.001). The age-adjusted relative risk factor for osteoporosis remains even after adjustment for body mass index, indicating that body mass index and osteoarthritis are independent relative risk factors for hip fracture. The mean age of the group with co-existent osteoarthritis and hip fracture was significantly higher for both men and women, compared to the group with osteoporosis alone. This indicates that if osteoarthritic subjects develop osteoporotic fracture, they do so at a later age. The osteoarthritic cases compared to controls and hip fracture cases were significantly smaller in stature in both sexes, and women had a significantly higher body weight and body mass index. Extra-capsular hip fracture was significantly more frequent in cases with concomitant osteoarthritis. These findings confirm earlier observations that osteoarthritis and osteoporosis are two distinct diseases and not phenomena related solely to aging.