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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.

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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.

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This study investigated the incidence and severity of hepatic osteodystrophy in patients with posthepatitic liver cirrhosis, and the role of hepatocellular injury in bone loss. Twenty-four patients (15 females and 9 males, mean age 49 +/- 13 years) with posthepatitic cirrhosis were enrolled in this study. The control group consisted of 22 healthy age and sex matched adults. The bone mineral density (BMD) was evaluated by dual energy x-ray absorptiometry of the L1-L4 vertebral bodies. A detailed questionnaire was used to assess the epidemiological findings. A statistically significant decrease in BMD of the patients was observed. There were no significant differences in the alkaline phosphatase, parathyroid hormone, calcitonin, 25-hydroxyvitamin D, osteocalcin, free testosterone, luteinizing hormone, follicle stimulating hormone, and estradiol levels, oral calcium intake, urinary calcium, phosphorus and hydroxypyroline excretion between patients and controls. The control group smoked more cigarettes, consumed more coffee and meat, and were exposed the sun light for a longer period than the study group. Multiple regression analysis showed that osteopenia depends significantly on the extent of liver disease. The data shows that the patients with posthepatitic cirrhosis had osteopenia, and that cirrhosis was a direct and independent risk factor.

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

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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.

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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.

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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.

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The aims of this study were to compare the incidence of hip fracture in different regions of Turkey and to investigate causes for potential differences. Hip fracture cases from two cities (Istanbul and Ankara) and three rural regions (Samsun, Erzurum and Diyarbakir) were compared with non-fractured controls from the same area with similar age and of the same sex. The risk of hip fracture was higher among persons living in rural areas than among persons living in urban areas, RR = 3.2 (p < 0.001) and 2.3 (p = 0.009) in men and women, respectively. Adjustment for differences in age and BMI between cases and controls did not substantially change these findings, RRadj = 2.7 (p < 0.001) and 2.1 (p = 0.036), neither did adjustment for exercise or differences in gonadal status in women. Education was the only adjustment factor that seemed to reduce differences between urban and rural areas, RRadj = 2.0 (p = 0.109) and 1.2 (p = 0.816). No difference in the risk of hip fracture could be detected between persons who migrated from rural to urban areas and persons born in urban areas. When restricting the analyses of differences between rural and urban areas to low-energy fractures, no difference in risk could be detected. When adjusting for differences in age and body mass index (BMI) the relative risks were RRadj = 0.8 (p = 0.873) and 1.2 (p = 0.852). The conclusion of these results is that the observed higher total risk of hip fracture in the rural areas of Turkey primarily can be explained by a larger proportion of high-energy fractures in the rural areas, whereas the risk of low-energy fractures seems to be similar.

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Hip fractures in elderly people are an important public health problem. The incidence varies with ethnic group and shows wide geographical variation. To examine the effect of body mass index, dietary calcium intake, fertile period, physical activity, and years of education on the risk of hip fracture, a case-control study was undertaken, as part of the MEDOS study, involving 519 women with hip fracture and 808 controls aged 50 or more years from Spain and Turkey. The results of this study suggest that low body mass index, low dietary calcium intake, low physical activity, a short fertile period, and a short period of education are associated with increased risk of hip fracture. The findings confirm previous reports of the influence of several potential risk factors for hip fracture and demonstrate for the first time a protective effect of education.

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OBJECTIVE: To examine the effects of taking drugs affecting bone metabolism on the risk of hip fracture in women aged over 50 years. DESIGN: Retrospective, population based, case-control study by questionnaire. SETTING: 14 centres in six countries in southern Europe. SUBJECTS: 2086 women with hip fracture and 3532 control women matched for age. MAIN OUTCOME MEASURES: Number of drugs affecting bone metabolism taken and length taken for. RESULTS: Women taking drugs affecting bone metabolism had a significantly decreased risk of hip fracture. After adjustment for differences in other risk factors, the relative risk of hip fractures was 0.55 (95% confidence interval 0.31 to 0.85) in women taking oestrogens, 0.75 (0.60 to 0.94) in those taking calcium, and 0.69 (0.51 to 0.92) in those taking calcitonin. The fall in risk was not significant for anabolic steroids (0.6 (0.29 to 1.22)). Neither vitamin D nor fluorides were associated with a significant decrease in the risk of hip fracture. The effect on hip fracture risk increased significantly with increasing duration of exposure (risk ratio 0.8 (0.61 to 1.05) for less than median exposure v 0.66 (0.5 to 0.88) for greater than median exposure). Drugs were equally effective in older and younger women, with the exception of oestrogen. CONCLUSIONS: Oestrogen, calcium, and calcitonins significantly decrease the risk of hip fracture. Short term intervention late in the natural course of osteoporosis may have significant effects on the incidence of hip fracture.

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The effect of exercises on vertebral trabecular bone mineral content (BMC) was investigated in 24 women with osteoporosis (OP) diagnosed by Quantitative Computed Tomography (QCT). Two groups were formed: an exercise and a control group with no exercise. Subjects in the exercise group exercised for one hour, twice weekly for a period of 6 months under the supervision of a physical therapist. A home exercise program which included the same exercises used in the hospital plus walking for half an hour every day was also assigned. Initial lumbar X-ray films, values obtained from laboratory investigations, physical activity scores and spinal BMC measurements were compared with those obtained after 6 months. The increase in the level of physical activity in the exercise group after exercise therapy was found statistically significant (p less than 0.001). After the exercise period, BMC values showed a 4.76% increase whereas in the control group, a decrease of 2.7% was found. The results demonstrated the beneficial effect of exercise in the prevention and management of OP.

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A series of 14 patients with Wilson's disease were evaluated in order to determine the characteristic bone changes found in this metabolic disorder. The following radiologic and clinical findings deserve to be summarized: (1) Osteoarticular pains as first manifestations of Wilson's disease were found in six patients. (2) In all but 2 of our patients, minor or moderate or even severe bone abnormalities characteristic for Wilson's disease were observed. (3) There were three groups of sibs. Among these sibs, the lesions were not only similar in type but were also acquired approximately at the same time, showing the influence of the different genes responsible for this metabolic disorder.

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