Clinical and subclinical cardiovascular disease in female SLE patients: Interplay between body mass index and bone mineral density.

BACKGROUND AND AIMS: Since accelerated atherosclerosis has been reported in systemic lupus erythematosus (SLE), predictive biomarkers of cardiovascular disease (CVD) are needed. Among non-traditional risk factors, bone mineral density (BMD) has been related to CVD. However, its role in SLE remains controversial. This study aims to analyze the associations of subclinical atherosclerosis with traditional and non-traditional CV risk factors. METHODS AND RESULTS: In a cross-sectional study, atherosclerosis burden was compared between 112 female SLE patients and 31 controls. Plaque number and carotid intima-media wall thickness (cIMT) were assessed by ultrasonography. In a retrospective study, BMD determinations obtained 5-years before the ultrasonography assessment were analyzed in a subgroup of 62 patients. Plaque frequency was increased in SLE, even in patients without CV events or carotid wall thickening. cIMT was increased in patients with CVD, positively correlated with body mass index (BMI). Interestingly, a paradoxical effect of BMI on carotid parameters was observed. Whereas underweight patients (BMI < 20) showed increased prevalence of carotid plaques with low cIMT, those with BMI > 30 showed higher cIMT and plaque burden. Overweight patients (25 < BMI<30) exhibited both elevated cIMT and plaque number. BMI was an independent predictor of BMD. In our retrospective study, patients with either clinical or subclinical CVD exhibited lower BMD levels than their CV-free counterparts. A low lumbar spine BMD independently predicted CVD development after adjusting for confounders. CONCLUSION: SLE was associated with a higher subclinical atherosclerosis burden, a bimodal effect being observed for BMI. Decreased BMD can be a CV risk biomarker in SLE.

Association of matrix Gla protein gene functional polymorphisms with loss of bone mineral density and progression of aortic calcification.

UNLABELLED: Two matrix Gla protein (MGP) polymorphisms were associated with progression of aortic calcification and femoral neck bone loss in men. All these findings were also functionally corroborated in two vascular and bone in vitro systems indicating that MGP genetic variations can be partly responsible of higher risk of bone loss and vascular calcification. INTRODUCTION: MGP plays an important role in bone and vascular mineralization as confirmed by MGP-deficient murine model. We therefore aimed to find a genetic association among -138T>C, -7G>A, and Thr83Ala MGP single-nucleotide polymorphisms (SNPs), bone loss, and progression of aortic calcification in a randomly selected general population of 296 individuals who participated in the European Vertebral Osteoporosis Study. METHODS: To evaluate the rate of change in bone mineral density (BMD) and the progression of aortic calcification, dual X-ray absorptiometry and lateral spine X-rays were performed at baseline and after 4 years of follow-up. Genotyping for the three polymorphisms was carried out using polymerase chain reaction and restriction fragment length analysis. In addition, functional studies of MGP-7G>A and Thr83Ala SNPs were performed on transiently transfected osteoblast-like UMR-106 and vascular smooth muscle A7r5 cells. RESULTS: The proportion of men who had lost BMD in the femoral neck was higher among homozygous -7AA and 83Ala-Ala (p = 0.039 and p = 0.009, respectively), and also featured a higher risk of progression of aortic calcifications (OR = 5.6, 95% CI = 1.2-27.8 and OR = 6.8, 95% CI = 1.4-32.3, respectively). No effect was observed in women. The MGP-7A allele produced a reduction in luciferase activity compared to MGP-7G: 47% less in vascular cells and 34% less in bone cells (p = 0.001 and 0.012, respectively). In vascular cells under calcifying conditions, the MGP 83Thr allele showed a slightly higher, although not significant, inhibition than the MGP 83 Ala allele in calcium content suggesting functional differences between both variants. CONCLUSION: These results suggest that MGP genetic variations could predict a higher risk of bone loss and progression of vascular calcification in men.

Low calcidiol levels and risk of progression of aortic calcification.

UNLABELLED: In this observational study, we found a positive relationship between low calcidiol levels and the risk of aortic calcification progression. A 10-ng/mL increase of calcidiol was associated with a decrease in the risk of progression by 44%. This figure was higher than that observed if we increased age by 10 years. INTRODUCTION: The aim of this study was to investigate the relationship between serum calcidiol levels and the onset and progression of aortic calcifications in a community-based sample of ambulatory subjects. METHODS: Three hundred two men and women aged 50 and over underwent two lateral X-rays and were followed up for 4 years. Abdominal aortic calcifications were classified as absent, mild-moderate, and severe. The biochemical measurements of serum calcium, phosphorus, parathyroid hormone, total alkaline phosphatase, tartrate-resistant acid phosphatase, creatinine, calcidiol, calcitriol, and osteocalcin were determined. Subjects who had received anti-osteoporotic treatments were excluded from the analysis. RESULTS: Subjects with progression of aortic calcifications had significantly lower serum calcidiol levels than those without progression. In the multivariate analysis, using the agreed upon serum levels for calcidiol (>30 ng/mL) as the reference, those subjects with calcidiol levels between 10 and 20 ng/mL showed a higher risk of progression of aortic calcification (odds ratio (OR) = 3.95; 95% confidence interval (CI) = 1.16 to 13.40). An even higher OR was observed in subjects with calcidiol values <10 ng/mL (OR = 4.10; 95% CI = 1.12 to 14.99). In addition, an increase by 1 ng/mL in osteocalcin levels was associated with a 17% reduction of the risk of aortic calcification progression. CONCLUSIONS: An increase by 10 ng/mL of calcidiol was associated with a decrease in the risk of aortic calcifications progression by 44%. This figure was even higher than that observed if we increased age by 10 years. Levels of calcidiol higher than 30 ng/mL seem to be desirable to reduce the progression of aortic calcification and to maintain bone turnover.

Effects of estradiol, calcitriol and both treatments combined on bone histomorphometry in rats with chronic kidney disease and ovariectomy.

BACKGROUND: The aim of this experimental study was to analyze the histomorphometric changes observed when using different doses of estradiol, calcitriol and both treatments combined, in rats with both chronic kidney disease (CKD) and ovariectomy (OVX). METHODS: Six groups of rats with CKD+OVX were treated for 8 weeks with placebo, with different doses of 17beta-estradiol (E2), with calcitriol or with both treatments combined (E2+calcitriol). Histomorphometric studies were carried out at the proximal tibia segment. RESULTS: All groups that received active treatments showed a trabecular bone volume similar to those of rats with normal ovarian function. Treatment with E2 was effective, E2-10 diminished osteoid and eroded surfaces, and E2-30 was able to achieve a bone remodeling similar to that of the normal group. Calcitriol proved to have a positive effect on bone microarchitecture, achieving normal trabecular connectivity. The combined treatment with E2-30+calcitriol was the most effective treatment as it was not only capable of achieving normal trabecular remodeling and connectivity, but also normal trabecular bone volume. CONCLUSIONS: E2 and calcitriol seem to have independent effects on cancellous bone turnover in rats with CKD+OVX. In rats with chronic kidney disease and ovariectomy, these two agents are able to produce additive effects on bone and offer additional advantages as opposed to the use of both drugs independently.

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.

Bone metabolism, vascular calcifications and mortality: associations beyond mere coincidence.

Bone and cardiovascular disorders are common age-related disorders in the general population and also in patients suffering from chronic kidney disease (CKD). Recent studies have shown an association between these two disorders and the rate of mortality. This article addresses some limitations of the concept of osteoporosis in CKD and compares bone and vascular disorders and mortality between non-selected general population and dialysis patients from the same geographic area. In the general population, all metabolic disorders increase with age, as well as vascular calcifications. The progression of vascular calcification was associated with a higher prevalence and incidence of bone fractures. In addition, both vascular calcifications and vertebral fractures were associated with higher mortality. A similar pattern was observed in dialysis patients with no increments in vertebral fractures, although with higher prevalence of vascular calcifications also both associated with higher mortality. Age was the strongest variable associated with all the analysed parameters, but some of the associations remained significant after age adjustment indicating the likely role of other common factors in the pathogenesis of bone and vascular disorders.

Falls explain between-center differences in the incidence of limb fracture across Europe.

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.

[Effect of desferrioxamine and deferiprone on osteocalcin secretion in osteoblast-type cells]. / Efecto de la desferrioxamina y de la deferiprona sobre la secreción de osteocalcina en células tipo osteoblasto.

Desferrioxamine and deferiprone are both metal-chelating drugs often used in aluminum-overloaded dialysis patients. In these patients, desferrioxamine produces an improvement on bone mineralisation without a relevant decrease in bone aluminum. Thus, desferrioxamine might have a direct effect on bone cells. The aim of this study was to assess the effect of desferrioxamine and deferiprone on 1,25(OH)2D3-stimulated osteocalcin secretion in osteoblast--like cells. The study was carried out in MG-63 cell cultures. Cells were seeded at a density of 15,000 cel/cm2 and grown to confluence for 72 hours in DMEM supplemented with 10% FCS. The medium was then replaced by another medium containing 1% BSA, 10(-9) M 1,25(OH)2D3 and desferrioxamine 5, 10, 20, 40, 60, 80 microM or deferiprone 15, 30, 60, 120, 180, 240 microM. Tris-HCl at pH 7.4 was used as control. After 48 hours, supernatants were collected for the measurement of secreted osteocalcin. Desferrioxamine and deferiprone, at high doses (desferrioxamine: 60 microM, 80 microM; deferiprone: 180 microM, 240 microM), inhibited the 1,25(OH)2D3-induced osteocalcin secretion. On the contrary, at lower doses (desferrioxamine 5 microM; deferiprone 15 microM) stimulated the secretion. In summary, these results suggest that desferrioxamine and deferiprone exert a direct effect on bone cell metabolism that might be independent from their metal-chelating properties.

[Review of the concept of vitamin D "sufficiency and insufficiency"]. / Revisión del concepto de "suficiencia e insuficiencia" de vitamina D.

There has been a poor consensus in defining normal levels of 25(OH) D. It has been traditionally recognized that 25(OH)D serum levels below 5-7 ng/ml induce osteomalacia, serum levels below 10-12 ng/ml induce secondary hyperparathyroidism and osteoporosis, and serum levels above 18-20 ng/ml are usually considered normal or adequate. Due to the results obtained in several studies, a more functional classification has recently been proposed defining serum 25(OH)D levels > 40 ng/ml or > 100 nmol/l as "desirable", serum levels between 20 and 40 ng/ml or 50 and 100 nmol/l as hypovitaminosis D, levels between 10 and 20 ng/ml or 25 and 50 mmol/l as vitamin D insufficiency and 25(OH)D levels below 10 ng/ml or 25 nmol/l as deficient. These new cut-off levels, suggest that, in the past, we had been using a wrong statistical approach for defining "normal serum 25(OH)D levels". In agreement with this new classification, in a recent study conducted in a random sample of our population, a high prevalence of low levels of 25(OH)D and secondary hyperparathyroidism was found. In our study, only in those people having "excellent" renal function, representing only 15% of the sample (serum creatinine < 1 mg/dl in men and < 0.8 in women, mean age of 68 years) hyperparathyroidism was not diagnosed despite observing 25(OH)D serum levels around 18-30 ng/ml or 45-75 nmol/l). In the remaining people (85% of the sample), who showed the expected serum creatinine increments according to their age, secondary hyperparathyroidism was avoided only if the serum 25(OH)D levels were higher than 30 ng/ml or 75 nmol/l. These remarkable findings demonstrate the importance of maintaining higher 25(OH)D levels--in addition to normal calcitriol levels--in order to avoid stimulation of the parathyroid gland. In 87 patients with a functioning renal transplantation only a 11.5% of they had levels of 25(OH)D higher than 30 ng/ml and it was correlated with PTH. These remarkable findings demonstrate the importance of maintaining higher 25(OH)D levels--in addition to normal calcitriol levels--in order to avoid stimulation of the parathyroid gland in aged people. Thus, the deficiency or even "subtle deficiency" of 25(OH)D, currently neglected in the daily management of patients with chronic renal failure, may play an important role in the maintenance of hormonal and mineral homeostasis.

[Importance of estrogen insufficiency time in the efficacy of the bone response to hormonal therapy in experimental chronic renal insufficiency]. / Importancia del tiempo de insuficiencia estrogénica en la eficacia de la respuesta ósea a la terapia hormonal en la insuficiencia renal crónica experimental.

Bone disease develops relatively early in the development of CRF. The aim of this study was to evaluate the repercussion of estrogen insufficiency and the effectiveness of hormonal replacement therapy, after different periods of estrogen deprivation, on bone metabolism in an animal model with chronic renal failure and ovariectomy. A secondary purpose was to evaluate the effectiveness of bone densitometry for predicting changes in bone mass for comparison with bone histomorphometry. We used Sprague-Dawley rats with chronic renal failure and ovariectomy performed at the same time. Animals were divided into two phases according to the period of estrogen insufficiency, 4 weeks in the long estrogen insufficiency period and 1 week in the short estrogen insufficiency period. In both phases, the animals were divided into four treatment groups receiving placebo (corn oil), 17 beta-estradiol (15 micrograms/kg body weight/day), calcitriol (10 ng/kg body weight/day) or the combined treatment with estradiol and calcitriol. In both phases, a group of animals with chronic renal failure (normal ovarian function) was used as a control group. The period of treatment was 8 weeks. After this period the animals were sacrificed. This model emphasizes the importance of the period of estrogen insufficiency in the efficiency of the treatment. Four weeks of estrogen insufficiency resulted in an significant loss of trabecular bone, and less possibility of recovery. After one week of estrogen deprivation a response to the treatment was observed. The utilization of bone densitometry allowed to reproduce changes in bone mass observed afterwards by histomorphometric analysis.

[Prevalence of vertebral fractures and aortic calcifications in hemodialysis patients: comparison with a population of the same age and sex]. / Prevalencia de fracturas vertebrales y calcificaciones aórticas en pacientes en hemodiálisis: comparación con una población de la misma edad y sexo.

Dialysis patients have bone metabolic disorders and a higher prevalence of fractures, principally peripheral fractures. However, there are few studies focusing on the prevalence of vertebral fractures. Moreover, aortic calcifications are very common and are an independent predictive factor of vascular morbidity and mortality. The objective of this study was to assess the prevalence of vertebral fractures and vascular calcifications in haemodialysis (HD) patients (n = 99), in comparison with a random sample of general population of similar age and from the same geographical area (n = 624) and study their relationship with clinical, biochemical and therapeutical data. The prevalence of vertebral fractures in HD patients and general population was 19.1% and 24.1% respectively (non-significant statistical differences). In both, sexes, the presence of vertebral fractures was positively associated with age, mean maximum Ca, mean maximum CaxP. In women, time in HD was positively associated as well. On the other hand, the prevalence of aortic calcifications was much higher in HD patients (77.9% vs 37.5%, p < 0.001). HD was a risk factor for aortic calcification in women [OR = 7.7 (IC 95% = 2.6-22.9)] as in men [OR = 5 (IC 95% = 1.9-12.9)]. Severe vascular calcifications were more frequent in HD patients, it reached 57.4% compared with 17% of general population (p < 0.001). Both, in women (64.5% vs 13.3% p < 0.001) and in men (51.4% vs 20.9%), respectively (p < 0.001). In conclusion, the prevalence of vertebral fractures was similar in HD patients and in general population. Nevertheless, frequency and severity of aortic calcifications was higher in HD patients.

[Study of incidence of osteoporotic fractures in a cohort of individuals older than 50 years from Asturias, Spain, after a 6 year follow-up period]. / Estudio de incidencia de fracturas osteoporóticas en una cohorte mayor de 50 años durante un período de 6 años de seguimiento.

BACKGROUND: The present work, performed as follow-up of the prevalence study of vertebral fractures (EVOS Study), evaluates in a 6 year period the incidence of vertebral fractures and other osteoporotic fractures in Oviedo (Asturias, Spain) in people older than 50 years. SUBJECTS AND METHODS: The study was performed in a cohort from the Oviedo's local registry in 1986. 624 men and women were followed by 3 postal questionnaires. The first questionnaire referred to the history of falls and fractures that happened during the follow-up period performed. Between the 2nd and 3rd follow-up subjects were invited to repeat the X-rays previously performed in the initial study. RESULTS: The incidence of osteoporotic fractures was higher in women than in men. In both sexes, vertebral fracture was the one which reached the highest incidence. Compared with men, Colles' fracture in women occurred earlier, with 5 times higher incidence. The incidence of hip fracture was twice higher in women than in men. A prevalent vertebral fractures increased until 5 times the incidence of vertebral and hip fracture. CONCLUSIONS: Among the osteoporotic fractures, vertebral fracture had a highest incidence values in both sexes. Although vertebral and hip fractures were twice incident in women compared with men, the incidence of Colles fracture was five times higher in women. A pre-existing vertebral fracture is an important risk factor to develop a new vertebral or hip fracture.

[Prevalence of vertebral fracture in population older than 50 years in Asturias (Spain) defined following different radiological criteria]. / Prevalencia de fractura vertebral en población asturiana mayor de 50 años de acuerdo con diferentes criterios radiológicos.

BACKGROUND: In spite of vertebral fracture is one of the most frequent osteoporotic fracture, the epidemiology of this entity remains unknown. The aim of this study was to know the prevalence of vertebral fracture in Oviedo (Spain), according to the most used radiologic criteria in research. SUBJECTS AND METHODS: A random sample of 624 men and women older than 50 years from the Oviedo's municipality took part in this analysis. All participants performed two thoracic and lumbar spinal lateral radiographs. In 615 subjects the presence of vertebral fracture was performed using a semicuantitative radiological criteria (Genant) and two morphometric criteria (Eastell and McCloskey). RESULTS: Prevalence of vertebral fracture varies between 17.4 and 24.6%, according to the radiological criteria used. The prevalence was higher in women than in men, but the differences were lower than expected, and there was a relative high frequency of vertebral fractures in men from 50 to 65 years old. In both sexes, prevalence of vertebral fracture increased with age, although in a steeper manner in women. The incidence of vertebral fracture in women was almost twice than in men. The incidence increased with age. Every ten years the prevalence of vertebral fracture increased two times. CONCLUSIONS: Prevalence of vertebral fracture was high in women and men older than 50 years, mainly in women older than 70 years, independently of the radiological criteria used. The average prevalence of vertebral fracture in Oviedo (Spain) has been similar to that observed in studies of American, European and Asian populations.

[Effect of vertebral fracture on health related quality of life in a Spanish population older than 54 years]. / Efecto de la fractura vertebral sobre la calidad de vida relacionada con la salud en población asturiana mayor de 54 años.

BACKGROUND: Effect of vertebral fracture on the perceived health using the SF-36 Health Questionnaire in a representative population older than 54 years. SUBJECTS AND METHOD: Randomly cohort from the register of the city Hall of Oviedo. All the 299 subjects (147 men and 152 women) completed the traduced and validated Spanish SF-36 questionnaire four years after radiologic studies were performed to evaluate prevalent vertebral fractures. RESULTS: Vertebral fracture decreased the health related quality of life, particularly in physical function dimension in males and in mental health dimension in women. This effect was increased when osteopenia was present. CONCLUSIONS: This first study performed in both sexes shows worse perceived health in people with fractures.

The influence of alcohol consumption on the risk of vertebral deformity. European Vertebral Osteoporosis Study Group.

The influence of alcohol consumption on the risk of osteoporosis is not well established. The aim of this study was to determine the relationship between frequency of alcohol consumption and the risk of vertebral deformity across different European populations. A population survey method was used. Men and women aged 50 years and over were recruited from population-based sampling frames in 36 centres from 19 European countries. Subjects were invited to attend by letter of invitation for an interviewer-administered questionnaire and lateral spinal radiographs. Vertebral deformity was defined morphometrically using the McCloskey-Kanis method. Data from 14237 individuals were available for this analysis. Alcohol consumption was compared between the 809 men and 884 women with vertebral deformity and the 5905 men and 6639 women without vertebral deformity. The frequency of alcohol intake was greater in men than women. Overall, there was no detectable association between frequency of alcohol intake and vertebral deformity in either men or women. Stratification by age showed that women 65 years and over who took alcohol on more than 5 days per week had a reduced risk of vertebral deformity compared with those taking alcohol less than once per week. This protection was most obvious after adjusting for age, centre, body mass index, smoking, current level of physical activity and previous fractures (odds ratio [OR] = 0.65; 95% confidence intervals [CI] = 0.43, 0.99). There was a smaller and non-significant protective effect amongst men aged 65 years and over and this was most apparent amongst moderately frequent drinkers (1-4 days per week) (OR = 0.81; 95% CI = 0.62, 1.08). There was no association between the occurrence of vertebral deformity and frequency of alcohol consumption in younger men and women. Overall, the effects of the frequency of alcohol consumption on vertebral deformity were modest. In older women, regular consumption on more than 5 days per week is associated with a reduced risk. Further, prospective data are required to confirm these findings. It is also necessary to investigate, in terms of amount of alcohol consumed, at what level the benefits of regular intake are obviated by the increased risks from alcohol excess.

Effect of desferrioxamine and deferiprone (L1) on the proliferation of MG-63 bone cells and on phosphatase alkaline activity.

In the present work, we studied: (i) the effect of different doses of desferrioxamine and deferiprone on the proliferation of osteoblasts and the possible role of iron in this; and (ii) the effect of both chelators on the metabolic activity of these cells, using the quantification of alkaline phosphatase as an enzymatic marker of cellular activity or differentiation. Cellular proliferation was investigated at different concentrations of deferiprone and desferrioxamine, and the effect of the addition of iron citrate on this proliferation was measured. The production of alkaline phosphatase after incubation with deferiprone (150 and 300 microM) and desferrioxamine (20 and 100 microM) was also studied. Cellular proliferation was completely inhibited with 100 microM of desferrioxamine and 300 microM of deferiprone. In both cases, this effect was corrected by means of co-incubation with iron citrate. In the second phase, using the same dose that inhibited the proliferation, it was observed that after 24 h, both chelators slightly decreased alkaline phosphatase activity, while at 48 and 96 h they increased alkaline phosphatase activity. These results demonstrate that both desferrioxamine and deferiprone inhibit the proliferation of the osteoblast-like cell line MG-63; the effect seems to be related to the chelation of some fraction of available iron. In spite of the effect on bone cell proliferation, the chelators do not impair cellular activity.

Influence of hormonal and reproductive factors on the risk of vertebral deformity in European women. European Vertebral Osteoporosis Study Group.

The aim of this study was to determine whether variation in the level of selected hormonal and reproductive variables might explain variation in the occurrence of vertebral deformity across Europe. A population-based cross-sectional survey method was used. A total of 7530 women aged 50-79 years and over were recruited from 30 European centres. Subjects were invited to attend for an interviewer-administered questionnaire and lateral spinal radiographs which were taken according to a standard protocol. After adjusting for age, centre, body mass index and smoking, those in the highest quintile of menarche (age > or = 16 years) had an increased risk of vertebral deformity (odds ratio [OR] = 1.48; 95% confidence interval [CI] 1.16, 1.88). Increased menopausal age (> 52.5 years) was associated with a reduced risk of deformity (OR = 0.78; 95% CI 0.60, 1.00), while use of the oral contraceptive pill was also protective (OR = 0.76; 95% CI 0.58, 0.99). There was a smaller protective effect associated with one or more years use of hormone replacement therapy, though the confidence limits clearly embraced unity. There was no apparent effect of parity or breast-feeding on the risk of deformity. We conclude that oestrogen status is an important determinant of vertebral deformity. Ever use of the oral contraceptive pill was associated with a 25% reduction in risk of deformity though the effect may be a result of the higher-dosage oestrogen pills used in the past. Parity and breast-feeding do not appear to be important and would appear to have little potential for identification of women at high risk of vertebral deformity.

Prevention, diagnosis and treatment of renal osteodystrophy in Spain. Preliminary results from a multicentre enquiry.

Prevention, diagnosis and treatment of renal osteodystrophy are continually evolving. We submitted a postal questionnaire to all Spanish dialysis centres, comprising 30 questions, with the aim of obtaining information about the current management of this entity in Spain. The answers from 171 centres, 63% of the total registered (10,724 patients), were analysed. The centres performed an annual average of nine calcium and phosphorus determinations, three for parathyroid hormone (PTH), 1.5 for aluminium and one for bone radiology. For these parameters, nephrologists consider ideal levels to be 10-10.5 mg/dl for calcium (53% of centres), 4.5-5.5 mg/dl for phosphorus (77%) and 120-150 pg/ml for iPTH (75%). The calcium concentration used in the dialysis fluids was found to be variable: 2% of the centres used 2 mEq/l, 44% used 2.5 mEq/l, 28% used 3 mEq/l and 26% used 3.5 mEq/l. When using oral calcitriol, 82% of the centres do not change the calcium concentration in the dialysis fluids; this percentage falls to 51% when calcitriol administration is parenteral. In 78% of centres, vitamin D treatment was started when PTH was high, without taking into consideration the plasma calcium level. The dose varies; in 28% of the centres calcitriol pulse therapy was started when iPTH was >250 pg/ml; 52% when >500 pg/ml and 16% when >750 pg/ml. Seventy one percent of the centres claim to use calcitriol in doses proportional to the severity of hyperparathyroidism. With regard to response to treatment, 78% of the centres wait for 6 months before considering a patient as a 'non-responder' and 80% of the centres would carry out parathyroidectomy only when iPTH is >750 pg/ml. The data collected from the enquiry show that there are important variations in some aspects related to current patient management in the different units in Spain. Diagnostic criteria are relatively homogeneous whereas the therapeutic guidelines are less uniform.

Incidence of limb fracture across Europe: results from the European Prospective Osteoporosis Study (EPOS).

The aim of this population-based prospective study was to determine the incidence of limb fracture by site and gender in different regions of Europe. Men and women aged 50-79 years were recruited from population registers in 31 European centers. Subjects were invited to attend for an interviewer-administered questionnaire and lateral spinal radiographs. Subjects were subsequently followed up using an annual postal questionnaire which included questions concerning the occurrence of new fractures. Self-reported fractures were confirmed where possible by radiograph, attending physician or subject interview. There were 6451 men and 6936 women followed for a median of 3.0 years. During this time there were 140 incident limb fractures in men and 391 in women. The age-adjusted incidence of any limb fracture was 7.3/1000 person-years [pyrs] in men and 19 per 1000 pyrs in women, equivalent to a 2.5 times excess in women. Among women, the incidence of hip, humerus and distal forearm fracture, though not 'other' limb fracture, increased with age, while in men only the incidence of hip and humerus fracture increased with age. Among women, there was evidence of significant variation in the occurrence of hip, distal forearm and humerus fractures across Europe, with incidence rates higher in Scandinavia than in other European regions, though for distal forearm fracture the incidence in east Europe was similar to that observed in Scandinavia. Among men, there was no evidence of significant geographic variation in the occurrence of these fractures. This is the first large population-based study to characterize the incidence of limb fracture in men and women over 50 years of age across Europe. There are substantial differences in the descriptive epidemiology of limb fracture by region and gender.