Polymorphisms and haplotypes across the osteoprotegerin gene associated with bone mineral density and osteoporotic fractures.

UNLABELLED: Osteoprotegerin plays a key role in bone remodelling. We studied the association between 24 polymorphisms and haplotypes on the OPG gene and bone mineral density and fractures. After multiple-testing correction, one SNP and two block-haplotypes were significantly associated with FN BMD. Two other block-haplotypes were associated with fracture. INTRODUCTION AND HYPOTHESIS: Osteoprotegerin (OPG) plays a key role in bone remodelling. Here we studied the association between polymorphisms and haplotypes on the OPG gene and bone mineral density (BMD) and fractures. METHODS: Twenty-four single nucleotide polymorphisms (SNPs) were selected to cover six haplotypic blocks and were genotyped in 964 postmenopausal Spanish women. Haplotypes were established with HaploStats. Association was analysed by GLM (for BMD) and logistic regression (for fractures) both at single SNP and haplotype levels. RESULTS: Upon adjustment for multiple testing (p < 0.0073), one of the SNPs (SNP #17, rs1032129) remained significantly associated with FN BMD (p = 0.001). Four block-haplotypes stood multiple-testing correction. Two remained associated with FN BMD and two with fracture. The association of block-4 haplotype "AC" (of SNPs #18 and #17) with FN BMD (p = 0.0002) was stronger than that of SNP#17 alone and was the best result overall. A global assessment of the results indicated that all the alleles and haplotypes with a protective effect, at p < 0.05, belonged to a frequent long-range haplotype. CONCLUSIONS: In conclusion, these results provide a detailed picture of the involvement of common variants and haplotypes of the OPG gene in bone phenotypes.

COL1A1, ESR1, VDR and TGFB1 polymorphisms and haplotypes in relation to BMD in Spanish postmenopausal women.

INTRODUCTION AND HYPOTHESIS: Genetic studies of osteoporosis have focused on analysing single polymorphisms in individual genes - with inconclusive results. An alternative approach may involve haplotypes and gene-gene interactions. The aim of the study was to test the association between the COL1A1, ESR1, VDR and TGFB1 polymorphisms or haplotypes and bone mineral density (BMD) in Spanish postmenopausal women. METHODS: Sixteen polymorphisms were analysed in 719 postmenopausal women. ANOVA, ANCOVA and Xi2 tests were used to perform the statistical analysis. RESULTS: COL1A1 -1997G > T (p=0.04) and TGFB1 Leu10Pro (p=0.02) were found to be associated with adjusted lumbar spine (LS) BMD. Interactions were observed between: the COL1A1 -1997 G/T and Sp1 polymorphisms (p < 0.01 for LS BMD) and the COL1A1 -1663 indelT and VDR ApaI polymorphisms (p < 0.01 for femoral neck (FN) BMD). The COL1A1 GDs and ESR1 LPX haplotypes were associated with FN BMD (p=0.03 and p=0.03). CONCLUSIONS: Polymorphisms at COL1A1 and TGFB1 and haplotypes at COL1A1 and ESR1 were found to be associated with BMD in a cohort of postmenopausal Spanish women. Moreover, COL1A1 polymorphisms showed significant interactions among them and with the VDR 3' polymorphisms.

Metaanálisis de fracturas de cadera, vertebrales y de muñeca en mujeres posmenopáusicas con indicaciones preventivas o de tratamiento para osteoporosis con risedronato o raloxifeno / Meta-analysis of hip, vertebral and wrist fractures in postmenopausal women undergoing preventive therapy or treatment for osteoporosis with risedronate and raloxifene

Fundamento: Se presenta una revisión sistemática con metaanálisis de los efectos del uso de risedronato y raloxifeno en las fracturas y en la densidad mineral ósea (DMO), de cadera, vértebra y muñeca en las mujeres con osteoporosis posmenopáusica. Material y método: Se revisaron los ensayos clínicos publicados desde 1966 hasta septiembre de 2002 en MEDLINE, Cochrane Library, EMBASE, Pascal Biomed y publicaciones de la Sociedad Española de Reumatología, Sociedad Española de la Investigación Ósea y del Metabolismo Mineral y Fundación Hispana de Osteoporosis y Enfermedades Metabólicas Óseas. Resultados y discusión: Se incluyeron 8 ensayos clínicos con risedronato y 6 con raloxifeno. A las dosis recomendadas (5 mg de risedronato y 60 mg de raloxifeno) con seguimiento de 2 o más años, el riesgo relativo (RR) de fracturas de cadera fue de 0,74 (intervalo de confianza [IC] del 95 por ciento, 0,59-0,94) y 1,13 (IC del 95 por ciento, 0,66-1,96) con risedronato y raloxifeno, respectivamente; en fracturas vertebrales fue de 0,61 (IC del 95, por ciento 0,50-0,75) y 0,65 (IC del 95 por ciento, 0,53-0,79), respectivamente, y en fracturas de muñeca de 0,67 (IC del 95 por ciento, 0,42-1,07) y 0,88 (IC del 95 por ciento, 0,67-1,14), respectivamente. El incremento de la DMO para risedronato y raloxifeno vertebral fue del 4,32 por ciento (IC del 95 por ciento, 3,78-4,88) y del 2,62 por ciento (IC del 95 por ciento, 2,40-2,82); femoral del 2,77 por ciento (IC del 95 por ciento, 2,37-3,17) y 1,39 por ciento (IC del 95 por ciento, 1,03-1,75), y en el trocánter del 3,94 por ciento (IC del 95 por ciento, 3,29-4,58) y 1,72 por ciento (IC del 95 por ciento, 0,602,85), respectivamente. Risedronato disminuyó el riesgo de fractura en cadera, no así en muñeca, mientras raloxifeno no mostró un efecto reductor de fracturas ni en cadera ni en muñeca. La reducción del riesgo de fractura vertebral se produjo en ambos fármacos. En trocánter, fémur y vértebra, ambos fármacos produjeron aumentos en la DMO (AU)

Management of osteoporosis in general practice: a cross-sectional survey of primary care practitioners in Spain.

A cross-sectional survey was conducted to determine the current situation in Spain regarding diagnosis and care of patients with osteoporosis in the primary care setting. A total of 2,500 primary care physicians who were homogeneously grouped in autonomous communities throughout the country received a postal 30-item anonymous self-administered questionnaire. The questionnaire covered demographics and personal characteristics of the physicians, conditions in everyday consultation, and degree of knowledge with regard to risk factors, diagnosis, treatment, and follow-up of the disease. The overall response was 850 (34%). The mean age of physicians surveyed was 43 years (range 23-66 years). The percentage of physicians specialized in community and family medicine was 46.7%. In 55.2% of cases, years of practice ranged between 11 and 20, and 55.7% of physicians visited between 31 and 50 patients per day. Age and years of practice were not associated with daily number of visits. Only 4% of physicians stated that there were specific programs for osteoporosis implemented in their primary care center. Diagnostic complementary investigations that could be ordered included plain radiographs in 96.2% of cases and bone densitometry in 27.8%. Laboratory tests included serum hormones in 61.6% of cases, PTH in 50.2%, and bone alkaline phosphatase in 33.4%. The diagnosis of osteoporosis was made always personally in 25.2% of cases. Personal diagnosis and follow-up, as well as actions directed to detection of osteoporosis were significantly higher among physicians working in centers with specific programs for osteoporosis. With regard to knowledge about osteoporosis, the mean percentage of correct responses was 63%. The percentage of correct responses was inversely associated with age and years of practice, and positively associated with speciality of community and family medicine. Primary care providers are in a good position to assess risk factors and recommend prevention strategies, as well as to play an active role in the diagnosis, care, and follow-up of patients with osteoporosis. Practitioners of younger age and relatively few years of practice were those with more up-to-date information regarding the disease, and the existence of a specific program for osteoporosis seems to improve the management of this condition.

Moduladores selectivos de los receptores estrogénicos (SERM) / Selective estrogen receptor modulators (SERM)

No disponible

Estudio de la apoptosis en la coxartrosis: influencia de lascargas biomecánicas locales / Study of apoptosis in hip-osteoarthritis: influence of local biomechanical loading

Objetivo: Cuantificar el número de condrocitos apoptóticos en el cartílago articular de la cabeza femoral artrósica en las zonas de carga y no carga. Material y métodos: Se obtuvieron muestras de cartílago a partir de cabezas femorales de pacientes sometidos a artroplastia de cadera por coxartrosis primaria (n = 10). Se estudió la apoptosis en los polos superior e inferior de dicha cabeza femoral mediante la técnica de TUNEL y microscopia electrónica (ME). Los resultados se expresaron como media aritmética de los porcentajes ñ desviación estándar. Resultados: El estudio histológico utilizando la técnica de TUNEL demostró que el 11,9 ñ 17,6 por ciento de las células fueron positivas en los cartílagos procedentes del polo superior y el 10,6 ñ 9,1 por ciento en el polo inferior. El estudio ultraestructural de estos cartílagos reflejó que el 13,6 ñ 7,7 por ciento de las células presentaban cambios apoptóticos en el polo superior, mientras que el 16,7 ñ 12,0 por ciento presentaban apoptosis en el polo inferior. Conclusión: Los resultados de nuestro estudio no apoyan la existencia de una relación directa entre el porcentaje de condrocitos apoptóticos y las zonas de máxima y mínima carga de la articulación coxofemoral de pacientes artrósicos (AU)

Adaptación del ensayo de reabsorción osteoclástica utilizando el microscopio electrónico de barrido ambiental / Adaptation of osteoclasic resorption assay using the enviromental scanning electronic microscope

Los ensayos de actividad osteoclástica son muy útiles para poder desarrollar trabajos sobre la fisiología de estas células y su comportamiento in vitro frente a fármacos, cambios fisiológicos, comunicación celular, etc. Un inconveniente para este tipo de ensayos es la duración del procedimiento, que requiere una gran inversión de tiempo que a veces no se ve recompensada por los resultados obtenidos. Con el objetivo de mejorar el procedimiento mediante la reducción del tiempo empleado y la obtención de unos mejores resultados se propone la utilización del microscopio electrónico de barrido (ESEM). Mediante la utilización del ESEM se han obtenido imágenes de mayor nitidez de las células y de su actividad. Como conclusión, podemos decir que la aplicación de este procedimiento simplifica la metodología de trabajo y se obtienen mejores resultados en los ensayos de actividad osteoclástica (AU)

Cyclical etidronate versus sodium fluoride in established postmenopausal osteoporosis: a randomized 3 year trial.

To compare the effects of sodium fluoride and etidronate in severe postmenopausal osteoporosis, we conducted a 3 year, prospective, trial in 118 postmenopausal osteoporotic women with at least one vertebral fracture, who were randomly assigned to receive sodium fluoride (25 mg twice daily, as enteric-coated tablets) plus calcium (1000 mg/day) or intermittent etidronate (400 mg/day for 14 days) followed by calcium (1000 mg/day for 76 days). Lateral spine X-ray films and dual-energy X-ray absorptiometry (DXA) measurements of the lumbar spine and proximal femur were performed at enrollment and yearly. Nonvertebral fractures were recorded every 6 months. Thirty-one women in the fluoride group and 47 in the etidronate group completed the trial. At 36 months, the mean change from baseline of the lumbar bone density in the fluoride group was 8.5 +/- 2.04% (p = 0.001) and in the etidronate group was of 3.6 +/- 0. 84% (p < 0.001). The changes in the fluoride group were significantly higher than in the etidronate group (p = 0.01). Both groups showed nonsignificant changes in femoral neck bone density. There was no significant difference between groups in the cumulative proportion of women with new vertebral fractures, with an incidence in the fluoride group of 16% vs. 17% in the etidronate group. However, the number of new vertebral fractures was significantly lower in the fluoride group (6 fractures) than in the etidronate group (19 fractures) (p = 0.05). The number of patients with nonvertebral fractures was similar in both groups. A high incidence of side effects, mainly gastrointestinal symptoms and lower extremity pain syndrome, was observed in the fluoride group. Etidronate was well tolerated. We conclude that, in women with severe osteoporosis, although sodium fluoride is more favorable than cyclical etidronate for increasing lumbar bone mass, no differences were observed in the incidence of fractures.