R. Perez Cano

Risk Factors for Hip Fracture in Men from Southern Europe: The MEDOS Study

Abstract: 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.

The variable incidence of hip fracture in southern Europe: the MEDOS Study.

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.

Femoral Bone Mineral Density, Neck-Shaft Angle and Mean Femoral Neck Width as Predictors of Hip Fracture in Men and Women

The effect of femoral bone mineral density (BMD) and several parameters of femoral neck geometry (hip axis length, neck–shaft angle and mean femoral neck width) on hip fracture risk in a Spanish population was assessed in a cross-sectional study. All parameters were determined by dual-energy X-ray absorptiometry. There were 411 patients (116 men, 295 women; aged 60–90 years) with hip fractures in whom measurements were taken in the contralateral hip. Controls were 545 persons (235 men, 310 women; aged 60–90 years) who participated in a previous study on BMD in a healthy Spanish population. Femoral neck BMD was significantly lower, and neck–shaft angle and mean femoral neck width significantly higher, in fracture cases than in controls. The logistic regression analysis adjusted by age, height and weight showed that a decrease of 1 standard deviation (SD) in femoral neck BMD was associated with an odds ratio of hip fracture of 4.52 [95% confidence interval (CI) 2.93 to 6.96] in men and 4.45 (95% CI 3.11 to 6.36) in women; an increase of 1 SD in neck–shaft angle of 2.45 (95% CI 1.73 to 3.45) in men and 3.48 (95% CI 2.61 to 4.65) in women; and an increase of 1 SD in mean femoral neck width of 2.15 (95% CI 1.55 to 2.98) in men and 2.40 (95% CI 1.79 to 3.22) in women. The use of a combination of femoral BMD and geometric parameters of the femoral neck except for hip axis length may improve hip fracture risk prediction allowing a better therapeutic strategy for hip fracture prevention.Abstract: The effect of femoral bone mineral density (BMD) and several parameters of femoral neck geometry (hip axis length, neck–shaft angle and mean femoral neck width) on hip fracture risk in a Spanish population was assessed in a cross-sectional study. All parameters were determined by dual-energy X-ray absorptiometry. There were 411 patients (116 men, 295 women; aged 60–90 years) with hip fractures in whom measurements were taken in the contralateral hip. Controls were 545 persons (235 men, 310 women; aged 60–90 years) who participated in a previous study on BMD in a healthy Spanish population. Femoral neck BMD was significantly lower, and neck–shaft angle and mean femoral neck width significantly higher, in fracture cases than in controls. The logistic regression analysis adjusted by age, height and weight showed that a decrease of 1 standard deviation (SD) in femoral neck BMD was associated with an odds ratio of hip fracture of 4.52 [95% confidence interval (CI) 2.93 to 6.96] in men and 4.45 (95% CI 3.11 to 6.36) in women; an increase of 1 SD in neck–shaft angle of 2.45 (95% CI 1.73 to 3.45) in men and 3.48 (95% CI 2.61 to 4.65) in women; and an increase of 1 SD in mean femoral neck width of 2.15 (95% CI 1.55 to 2.98) in men and 2.40 (95% CI 1.79 to 3.22) in women. The use of a combination of femoral BMD and geometric parameters of the femoral neck except for hip axis length may improve hip fracture risk prediction allowing a better therapeutic strategy for hip fracture prevention.

Study of bone mineral density in lumbar spine and femoral neck in a Spanish population

The aim of this study was to generate standard curves for bone mineral density (BMD) in a Spanish population using dual-energy X-ray absorptiometry (DXA), at both lumbar spine and femoral neck sites. The total sample size was 2442 subjects of both sexes aged 20–80 years, stratified according to survival rates, demographic distribution by local regions and sex ratio in the Spanish population. Subjects with suspected conditions affecting bone metabolism or receiving any treatment affecting bone mineralization were excluded. The study was carried out in 14 hospitals and bone density measurements were performed, using a QDR/1000 Hologic device. In the female population, the highest value for lumbar spine BMD was found within the 30–39 years age group, being significantly lower after the age of 49 years. In the male population, the highest values for lumbar spine BMD are found one decade earlier than in the female population and become significantly lower after the age of 69 years. The highest values for femoral neck BMD in men and women was found in the 20–29 year age group. Values for femoral neck BMD in the female population become statistically lower after the age of 49 years, while in the male population this effect was seen after the age of 69 years. Values for femoral neck BMD were higher in men than women at all ages.

European semi-anthropomorphic spine phantom for the calibration of bone densitometers: Assessment of precision, stability and accuracy the European quantitation of osteoporosis study group

Up to now it has not been possible to reliably cross-calibrate dual-energy X-ray absorptiometry (DXA) densitometry equipment made by different manufacturers so that a measurement made on an individual subject can be expressed in the units used with a different type of machine. Manufacturers have adopted various procedures for edge detection and calibration, producing various normal ranges which are specific to each individual manufacturers brand of machine. In this study we have used the recently described European Spine Phantom (ESP, prototype version), which contains three semi-anthropomorphic “vertebrae” of different densities made of simulated cortical and trabecular bone, to calibrate a range of DXA densitometers and quantitative computed tomography (QCT) equipment used in the measurement of trabecular bone density of the lumbar vertebrae. Three brands of QCT equipment and three brands of DXA equipment were assessed. Repeat measurements were made to assess machine stability. With the large majority of machines which proved stable, mean values were obtained for the measured low, medium and high density vertebrae respectively. In the case of the QCT equipment these means were for the trabecular bone density, and in the case of the DXA equipment for vertebral body bone density in the posteroanterior projection. All DXA machines overestimated the projected area of the vertebral bodies by incorporating variable amounts of transverse process. In general, the QCT equipment gave measured values which were close to the specified values for trabecular density, but there were substantial differences from the specified values in the results provided by the three DXA brands. For the QCT and Norland DXA machines (posteroanterior view), the relationships between specified densities and observed densities were found to be linear, whereas for the other DXA equipment (posteroanterior view), slightly curvilinear, exponential fits were found to be necessary to fit the plots of observed versus specified densities. From these plots, individual calibration equations were derived for each machine studied. For optimal cross-calibration, it was found to be necessary to use an individual calibration equation for each machine. This study has shown that it is possible to cross-calibrate DXA as well as QCT equipment for the measurement of axial bone density. This will be of considerable benefit for large-scale epidemiological studies as well as for multi-site clinical studies depending on bone densitometry.

Bone density reduction in various measurement sites in men and women with osteoporotic fractures of spine and hip: the European quantitation of osteoporosis study.

Abstract. We have measured bone mineral density (BMD) using dual X-ray absorptiometry (DXA) of the spine and hip, spinal quantitative computed tomography (QCTspi), and peripheral radial quantitative computed tomography (pQCTrad) in 334 spine and 51 hip fracture patients. The standardized hip and spine BMD for each patient was calculated and compared with the combined reference ranges published previously, each densitometer having been cross-calibrated with the prototype European Spine Phantom (ESPp) or the European Forearm Phantom (EFP).Male and female fracture cases had similar BMD values after adjusting for body size, where appropriate. This suggests that the relationship between bone density (mass per unit volume) and fracture risk is similar between men and women. However, compared with age-matched controls, mean decreases in BMD ranged from 0.78 SD units (women with hip fracture, DXAspi) to 2.57 SD units (men with spine fractures, QCTspi).The proportion of spine and hip fracture patients falling below the cutoff for osteoporosis (T-score <−2.5 SD) proposed by the World Health Organization (WHO) study group varied according to different BMD measurement procedures (range 18–94%). This finding suggests that the WHO definition requires different thresholds when used with non-DXA BMD measurement techniques.Receiver operator characteristic (ROC) analysis was used to compare measurement techniques for their ability to discriminate between cases and controls. Among DXA sites, the proximal femur was preferred when evaluating generalized bone loss, particularly in elderly people. An additional spinal BMD measurement may add clinical value if spine fracture risk assessment has a high priority. Both axial and peripheral QCT techniques performed comparably to DXA in spinal osteoporosis, so investigators and clinicians may use any of the three technologies with similar degrees of confidence for the diagnosis of generalized or site-specific bone loss providing straightforward clinical guidelines are followed.

Dual X-ray absorptiometry—cross-calibration and normative reference ranges for the spine: Results of a European Community Concerted Action

Bone density measurements by dual X-ray absorptiometry (DXA) of the spine can now be made precisely, but there is no uniformity in reporting results and in presenting reference data. A European Union Concerted Action therefore devised a uniform procedure for cross-calibrating and standardizing instruments, using the European spine phantom (ESP) prototype. This phantom differs in a number of respects from the final version of the ESP. Eighteen centers in nine countries obtained 1619 records (1035 women) from Caucasian subjects, aged 20-80 years, drawn from normal populations. The DXA machines used were made by the Hologic, Lunar, and Norland companies. Highly statistically significant differences were evident between populations, both in apparent rates of bone loss with age and in the spread of values about the age-adjusted means. There were small residual differences in the results obtained with the three machine brands which could have been due to the relatively large between-center population differences we observed. The alternative or additional explanation that they were attributable, in part, to the design differences between the ESP prototype and the definitive ESP, which became available after this study was completed, was shown to be a valid possibility. Results from postmenopausal women reported in relation to the years that have elapsed since menopause showed reduced population variance when compared with conventional reporting in relation to age. After cross-calibration, the center with the highest age-adjusted normal density value averaged 23% more than the center with the lowest. It is therefore crucially important to select appropriate reference data in clinical and epidemiological studies.(ABSTRACT TRUNCATED AT 250 WORDS)

Risk factors for hip fracture in Spanish and Turkish women

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.

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

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

ADFR therapy in the prevention of bone loss after menopause

SummaryEstrogens retard bone loss after menopause and constitute the most logical therapy for the prevention of postmenopausal osteoporosis. Estrogens are contraindicated in some circumstances and some postmenopausal women are unwilling to accept them. We have used ADFR therapy as an alternative in the prevention of postmenopausal bone loss. One hundred women in the early postmenopausal period (6–24 months since the last menses) were introduced into the study. 50 were treated with placebo and 50 were treated with ADFR therapy (phosphorus 1.5 gr/day during 3 days, followed by SCT 100 UI/day during 10 days and calcium 1 gr/day). After 77 days without any therapy we repeated the cycles every 3 months. Bone mass was evaluated at the beginning and at 3, 6, 12 and 18 months by dual-photon absorptionmetry lumbar spine. In the control group, the mean spinal BMD decreased 7.31% after 12 months and 6.16% after 18 months (p>0.05). The ADFR group only had a mean spinal BMD decrease of 3.79% and 1.1% after 12 and 18 months respectively (NS). Bone loss was greater in control than in ADFR group after 12 and 18 months (p<0.05 at both times). We conclude that phosphorus and calcitonin like ADFR therapy may be a useful alternative to estrogen for the prevention of accelerated bone loss after menopause.