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.

Metodología para mejorar la eficiencia en la migración y detección de células madre mesenquimales humanas en modelos murinos / No disponible

No disponible

Efecto de la fragilidad y la sarcopenia sobre el riesgo de caídas y de fracturas osteoporóticas en población no seleccionada / Effect of frailty and sarcopenia on the risk of falls and osteoporotic fractures in an unselected population

OBJETIVOS: Valorar si la fuerza de agarre y la dificultad para realizar actividades cotidianas podrían ser predictores de caídas y fracturas osteoporóticas. MATERIAL Y MÉTODOS: Se seleccionaron aleatoriamente 624 hombres y mujeres mayores de 50 años, que fueron seguidos durante 8 años para conocer la incidencia de caídas y fracturas osteoporóticas no vertebrales. Al inicio se midió la fuerza de agarre en manos y se cumplimentó un cuestionario con variables clínicas, factores de riesgo relacionados con la osteoporosis y cuestiones relativas a la dificultad o incapacidad para realizar actividades cotidianas. RESULTADOS: La fuerza de agarre en manos no se asoció con la incidencia de caídas y fracturas. Sin embargo, la imposibilidad o dificultad de "estar sentado más de 1 hora en silla dura", "quitarse los calcetines o las medias" e "inclinarse desde una silla para coger un objeto del suelo" se asoció con caídas: 1,83 (1,16-2,89); 1,85 (1,14-3,00) y 1,68 (1,04-2,70), respectivamente. Del mismo modo, la imposibilidad o dificultad de "llevar durante 10 metros un objeto de 10 kilos" y "levantar una caja con 6 botellas y ponerlas sobre una mesa" se asoció con fractura: 2,82 (1,21-6,59) y 2,54 (1,12-5,81) respectivamente. CONCLUSIONES: No se encontró asociación entre la fuerza de agarre e incidencia de caídas y fracturas osteporóticas, pero sí con dificultad o incapacidad para realizar actividades cotidianas. Las relacionadas con mayor fuerza se asociaron con fractura, mientras que las relacionadas con capacidad funcional se asociaron con caídas. Realizar cuestionarios sencillos podría ayudar a predecir eventos antes de que ocurran

OBJECTIVE: Assess whether grip strength and difficulty in carrying out daily activities could be predictors of falls and osteoporotic fractures. MATERIAL AND METHODS: 624 men and women over 50 years of age were randomly selected and followed for 8 years to determine the incidence of falls and non-vertebral osteoporotic fractures. At the beginning, the grip strength in the hands was measured and a questionnaire was filled out with clinical variables, risk factors related to osteoporosis, and questions related to difficulty or inability to perform daily activities. RESULTS: Grip strength in the hands was not associated with the incidence of falls and fractures. However, the impossibility or difficulty of "sitting for more than 1 hour in a hard chair", "taking off socks or stockings" and "leaning from a chair to pick up an object from the floor" were associated with falls: 1.83 (1.16-2.89); 1.85 (1.14-3.00) and 1.68 (1.04-2.70), respectively. Similarly, the impossibility or difficulty of "carrying a 10-kilogram object for 10 meters" and "lifting a box with 6 bottles and putting them on a table" was associated with fracture: 2.82 (1.21-6.59) and 2.54 (1.12-5.81) respectively. CONCLUSIONS: No association was found between grip strength and incidence of falls and osteoporotic fractures, but it was found with difficulty or inability to perform daily activities. Those related to greater strength were associated with fracture, while those related to functional capacity were associated with falls. Taking simple questionnaires could help predict events before they happen

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.

Niveles de calcidiol y mantenimiento de la función muscular, capacidad funcional y densidad mineral ósea en población española no seleccionada / Calcidiol levels and muscle function maintenance, functional capacityand bone mineral bone density in non-selected Spanish population

Introducción: La vitamina D posee efectos beneficiosos que supuestamente contribuirian a mantener la funcion musculo‐esqueletica. Objetivo: Analizar en una poblacion no seleccionada el efecto de los niveles de calcidiol sobre la funcion muscular en ambas manos, sobre actividades de la vida cotidiana y sobre los cambios en la densidad mineral osea (DMO). Material y métodos: Se utilizo la cohorte del estudio EVOS que realizo, entre otros, medidas de fuerza muscular de agarre en ambas manos, preguntas relativas a la dificultad para realizar actividades cotidianas, estudio densitometrico en columna lumbar y cadera, y bioquimica para determinar los niveles de calcidiol. Resultados: Valores de calcidiol ≥20 ng/mL se asociaron con mayor fuerza muscular de agarre en ambas manos. Tras ajuste por edad, sexo, IMC y estacionalidad, niveles de calcidiol <20 ng/mL se asociaron independientemente con menor fuerza muscular de agarre solo en la mano izquierda (OR=2,35; IC 95%: 1,03‐5,38). Del mismo modo, la incapacidad o tener dificultades para "coger un libro u objeto de una estanteria alta" e "incorporarse de la cama" se asociaron significativamente con niveles de calcidiol <20 ng/mL. Niveles de calcidiol <20 ng/mL se asociaron con mayores perdidas de DMO en cuello femoral y cadera total. Estas asociaciones se mantuvieron en el analisis multivariante. Conclusiones: Mantener niveles de calcidiol ≥20 ng/mL se asociaron con mayor fuerza muscular de agarre en las manos, mantenimiento de actividades cotidianas y menores perdidas de DMO en cadera. Este estudio corrobora la utilidad de mantener niveles adecuados de vitamina D para mantener la funcion musculo‐esqueletica

Introduction:Vitamin D offers beneficial effects that reportedly help maintain musculoskeletal function. Aim:To analyze the effect of calcidiol levels on muscle function in both hands, on activities of daily life and on changesin bone mineral density (BMD) in an unselected population.Material and methods:The EVOS study cohort was used, which carried out, among others, measures of muscularstrength of grip in both hands, questions related to difficulty in performing daily activities, densitometric study in thelumbar and hip spine, and biochemistry to determine the levels of calcidiol.Results: Calcidiol values ≥20 ng/mL were associated with greater grip strength in both hands. After adjusting for age,sex, BMI and seasonality, calcidiol levels <20 ng/mL were independently associated with lower grip strength only inthe left hand (OR=2.35; 95% CI: 1.03‐5.38). Likewise, the inability or difficulty to "pick up a book or object from a highshelf" and "get up from the bed" were significantly associated with calcidiol levels <20 ng/mL. Levels of calcidiol <20ng/mL were associated with greater BMD losses in the femoral neck and total hip. These associations were maintainedin the multivariate analysis.Conclusions:Maintaining levels of calcidiol ≥20 ng/mL was associated with greater muscular strength of grip in thehands, maintenance of daily activities and lower BMD losses in the hip. This study corroborates the utility of maintainingadequate levels of vitamin D to maintain musculoskeletal function

Hipometilación del gen de la PTH por elevado fósforo de la dieta: un posible agravante epigenético de la severidad del hiperparatiroidismo secundario en la enfermedad renal crónica / Hypomethylation of the PTH gene due to high dietary phosphorus: a possible aggravating of severe secondary hyperparathyroidism in chronic renal failure

Introducción: En pacientes con enfermedad renal crónica (ERC), la hiperfosfatemia agrava tanto la hiperplasia paratiroidea como la síntesis y secreción de PTH. La mayor hiperplasia se asocia a descensos en la expresión génica de los receptores de calcio (CaSR), vitamina D (VDR) y también de α-Klotho, induciendo resistencia de la glándula paratiroides para responder tanto al tratamiento como a los aumentos de FGF23. Este estudio examinó la posible contribución epigenética del fósforo elevado en agravar el hiperparatiroidismo secundario (HPTS). Material y métodos: Se comparó el grado de metilación mediante pirosecuenciación de bisulfito en secuencias ricas en CpG de los promotores en los genes del CaSR, VDR, PTH y α-Klotho en ADN de glándulas paratiroides de ratas urémicas alimentadas con dieta con contenido normal y elevado en fósforo. Resultados: La dieta rica en fósforo incrementó la expresión de PTH y causó una marcada reducción del grado de metilación en el promotor del gen de PTH. En cambio, las regiones promotoras de los genes de CaSR, VDR y α-Klotho no mostraron diferencias significativas en el porcentaje de metilación entre ambos grupos de ratas, no siendo, por tanto, éste el mecanismo determinante de la disminución de la expresión de estos genes observada en el HPTS. Conclusiones: Las alteraciones epigenéticas inducidas por la dieta rica en fósforo en el HPTS, en particular la hipometilación del gen de la PTH, podrían contribuir a los aumentos que se producen en la síntesis y secreción de esta hormona. La identificación de los mecanismos implicados permitiría diseñar mejores tratamientos para el HPTS en fases tempranas de la ERC (AU)

Introduction: Hyperphosphataemia aggravates both parathyroid hyperplasia and PTH secretion in patients with chronic kidney disease (CKD). Hyperplasia is associated with decreases in calcium receptor expression (CaSR), vitamin D (VDR) and α-Klotho, inducing resistance of the parathyroid gland to respond both to treatment and to increases in FGF23. This study examined the possible epigenetic contributions of raised phosphorus to aggravate secondary hyperparathyroidism (SHPT) in patients with (CRD). Material and methods: The degree of methylation was compared by pyrosequencing of bisulfite in CpGrich sequences of the promoters in the CaSR, VDR, PTH and α-Klotho genes in parathyroid gland DNA from uremic rats fed a normal and high phosphorus diet. Results: The diet rich in phosphorus increased PTH expression and caused a marked reduction in the degree of methylation in the promoter of the PTH gene. In contrast, the promoter regions of the CaSR, VDR and α-Klotho genes did not show significant differences in the percentage of methylation between the two groups of rats. Thus, it was not the determining mechanism for the decrease of the expression of these genes observed in the SHPT. Conclusions: The epigenetic alterations induced by the phosphorus rich diet in SHPT, particularly the PTH gene hypomethylation, could contribute to the increases that occur in the synthesis and secretion of this hormone. The identification of the mechanisms involved would allow better treatments for SHPT to be designed in the early stages of CKD (AU)

Efecto de dosis suprafisiológicas de calcitriol sobre la expresión proteica de células de músculo liso vascular / Effect of supra-physiological calcitriol doses on protein expression of vascular smooth muscle cells

Introducción: El calcitriol, fundamental para mantener la homeostasis del calcio y el fósforo en el organismo, puede perjudicar al sistema vascular a dosis elevadas, aumentando el riesgo de calcificación. Objetivo: Evaluar la expresión diferencial de proteínas en células de músculo liso vascular sometidas a una dosis suprafisiológica de calcitriol. Material y métodos: Se cultivaron células de músculo liso vascular de rata (SMAC-R) en presencia de 10-7 M de calcitriol durante 10 días. Se valoró el cambio de fenotipo muscular a óseo mediante actividad fosfatasa alcalina, inmunocitoquímica, reacción en cadena de la polimerasa cuantitativa a tiempo real (qPCR) y Western blot. Mediante electroforesis bidimensional y espectrometría de masas se evaluó el patrón diferencial de proteínas en presencia y ausencia de 10-7 M de calcitriol. Resultados: La exposición a una dosis alta de calcitriol disminuyó significativamente la expresión génica de elastina y la expresión génica y proteica de α-actina, aumentado la expresión génica de osteocalcina y Runx2 y la proteica de osteoprotegerina. A nivel proteómico se identificaron 10 proteínas diferencialmente expresadas, destacando el aumento en superóxido dismutasa mitocondrial, proteínas del citoesqueleto, de formación de vesículas y del inflamasoma. Por el contrario, hubo 4 proteínas que disminuyeron su expresión, destacando alguna de tipo muscular. Conclusiones: En un modelo de células de músculo liso vascular sometidas a una dosis suprafisiológica de calcitriol se observó un aumento de expresión de proteínas del citoesqueleto, que forman vesículas de matriz y que participan en depurar radicales libres y en la respuesta inflamatoria. La pérdida de fenotipo muscular se vio representada por descensos en la expresión de proteínas típicamente musculares (AU)

Introduction: Calcitriol, essential for maintaining calcium and phosphorus homeostasis in the body, may damage the vascular system in high doses, increasing the risk of calcification. Objective: To assess the differential expression of proteins in vascular smooth muscle cells subjected to a supra-physiological dose of calcitriol. Material and methods: Rat vascular smooth muscle cells (VSMC-R) were cultured in the presence of 10-7 M calcitriol for 10 days. The change of muscle to bone phenotype was assessed by alkaline phosphatase activity, immunocytochemistry, quantitative polymerase chain reaction in time (QPCR) and Western blot analysis. By means of two-dimensional electrophoresis and mass spectrometry was evaluated for the differential protein pattern in presence and absence of 10-7 M calcitriol. Results: Exposure to a high dose of calcitriol decreased elastin gene expression and the protein and gene expression of α-actin protein, increased gene expression of osteocalcin and Runx2 and expression of osteoprotegerin protein. At the proteomic level, 10 differentially expressed proteins were identified, highlighting the increase in mitochondrial superoxide dismutase, cytoskeleton proteins, vesicle formation and inflammasome. On the contrary, there were 4 proteins that diminished expression, highlighting some of muscular type. Conclusions: In a model of vascular smooth muscle cells submitted to a supra-physiological dose of calcitriol an increased expression of cytoskeleton proteins was observed. These proteins form matrix vesicles and participate in clearance of free radicals and in the inflammatory response. The loss of muscle phenotype was represented by decreased expression of typically muscle proteins (AU)

Efecto del estrés oxidativo sobre la calcificación vascular a través del microARN-377 / The effect of oxidative stress on vascular calcification through microRNA-377

Introducción: El estrés oxidativo ha sido implicado en el desarrollo y la progresión de la calcificación vascular (CV); sin embargo, aún existen interrogantes sobre esta asociación causal. Objetivo: Analizar en un modelo experimental de insuficiencia renal crónica (IRC) el efecto del estrés oxidativo sobre el desarrollo y la progresión de la CV, evaluando la implicación del microARN-377 (miR-377). Material y métodos: Se estudiaron 2 grupos de ratas Wistar con IRC. El grupo 1 recibió dieta normal en fósforo (IRC+PN). El grupo 2 recibió dieta con alto fósforo (IRC+PA). Se incluyó un grupo de ratas Sham. Trascurridas 20 semanas, las ratas fueron sacrificadas. Resultados: El fósforo y la parathormona séricos no aumentaron en el grupo IRC+PA respecto al IRC+PN, pero sí los niveles de factor de crecimiento fibrobástico 23 (FGF23). En el grupo IRC+PN aumentó tres veces el contenido aórtico de calcio respecto al grupo Sham, un aumento 17 veces superior en el grupo IRC+PA, donde la densidad mineral ósea en tibia proximal descendió significativamente. En el grupo IRC+PN la expresión del miR-377 disminuyó un 65%, sin efecto adicional de la dieta con alto contenido en fósforo. En el grupo IRC+PN aumentó 3 veces la expresión proteica de superóxido dismutasa 2 mitocondrial (SOD-2), y en el grupo IRC+PA lo hizo hasta 6 veces. Conclusiones: La IRC con o sin alto contenido en fósforo en la dieta desencadenó el descenso del miR-377. El exceso de fósforo incrementó la SOD-2 como mecanismo compensador para frenar el estrés oxidativo y el daño vascular. Controlar el contenido en fósforo en la dieta cuando la función renal se ve comprometida permitirá aminorar el daño vascular producido como consecuencia, entre otros factores, del estrés oxidativo (AU)

Introduction: Oxidative stress has been implicated in the development and progression of vascular calcification (VC). However, this causal association remains a matter of controversy. Objective: To analyze in an experimental model of chronic renal failure (CRF), the effect of oxidative stress on the development and progression of the VC, assessing the implication of microRNA-377 (miR-377). Material and methods: Two groups of Wistar rats with CRF were studied. Group 1 received normal diet in phosphorus (CRF+NP). Group 2 received a high phosphorus (CRF+HP) diet. A group of sham rats was included. After 20 weeks, the rats were sacrificed. Results: Serum phosphorus and parathormone did not increase in the CRF+HP group compared to CRF+NP, but fibroblast growth factor 23 (FGF23) levels significantly increased. In the CRF+NP group, aortic calcium content increased three-fold over the sham group, a 17-fold increase in the CRF+HP group, where the bone mineral density in the proximal tibia decreased significantly. In the IRC+NP group, the expression of miR-377 decreased by 65%, with no additional effect detected of the diet with high phosphorus content. In the IRC+NP group, the protein expression of mitochondrial superoxide dismutase 2 (SOD-2) increased 3-fold, and in the IRC+HP group it increased up to 6-fold. Conclusions: CRF, with or without high phosphorus dietary content, triggered the descent of miR-377. Excess phosphorus increased SOD-2 as a compensatory mechanism to curb oxidative stress and vascular damage. Controlling phosphorus content in the diet when the renal impairment function is compromised will reduce the vascular damage produced due oxidative stress, among other factors (AU)