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1.
Osteoporos Int ; 26(10): 2509-19, 2015 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-26021761

RESUMO

UNLABELLED: In 27 centres across Europe, the prevalence of deforming spinal Scheuermann's disease in age-stratified population-based samples of over 10,000 men and women aged 50+ averaged 8% in each sex, but was highly variable between centres. Low DXA BMD was un-associated with Scheuermann's, helping the differential diagnosis from osteoporosis. INTRODUCTION: This study aims to assess the prevalence of Scheuermann's disease of the spine across Europe in men and women over 50 years of age, to quantitate its association with bone mineral density (BMD) and to assess its role as a confounder for the radiographic diagnosis of osteoporotic fracture. METHODS: In 27 centres participating in the population-based European Vertebral Osteoporosis Study (EVOS), standardised lateral radiographs of the lumbar and of the thoracic spine from T4 to L4 were assessed in all those of adequate quality. The presence of Scheuermann's disease, a confounder for prevalent fracture in later life, was defined by the presence of at least one Schmorl's node or irregular endplate together with kyphosis (sagittal Cobb angle >40° between T4 and T12) or a wedged-shaped vertebral body. Alternatively, the (rare) Edgren-Vaino sign was taken as diagnostic. The 6-point-per-vertebral-body (13 vertebrae) method was used to assess osteoporotic vertebral shape and fracture caseness. DXA BMD of the L2-L4 and femoral neck regions was measured in subsets. We also assessed the presence of Scheuermann's by alternative published algorithms when these used the radiographic signs we assessed. RESULTS: Vertebral radiographic images from 4486 men and 5655 women passed all quality checks. Prevalence of Scheuermann's varied considerably between centres, and based on random effect modelling, the overall European prevalence using our method was 8% with no significant difference between sexes. The highest prevalences were seen in Germany, Sweden, the UK and France and low prevalences were seen in Hungary, Poland and Slovakia. Centre-level prevalences in men and women were highly correlated. Scheuermann's was not associated with BMD of the spine or hip. CONCLUSIONS: Since most of the variation in population impact of Scheuermann's was unaccounted for by the radiological and anthropometric data, the search for new genetic and environmental determinants of this disease is encouraged.


Assuntos
Doença de Scheuermann/epidemiologia , Idoso , Estatura/fisiologia , Densidade Óssea/fisiologia , Europa (Continente)/epidemiologia , Feminino , Colo do Fêmur/diagnóstico por imagem , Colo do Fêmur/fisiopatologia , Humanos , Vértebras Lombares/diagnóstico por imagem , Vértebras Lombares/fisiopatologia , Masculino , Pessoa de Meia-Idade , Prevalência , Radiografia , Reprodutibilidade dos Testes , Doença de Scheuermann/diagnóstico por imagem , Doença de Scheuermann/fisiopatologia
2.
Osteoporos Int ; 24(1): 311-20, 2013 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-22402673

RESUMO

UNLABELLED: We have examined the effect of oral monthly ibandronate on distal radius and tibia microarchitecture with high-resolution peripheral quantitative tomography compared with placebo, in women with osteopenia, and found that ibandronate did not significantly affect trabecular bone but improved cortical density and thickness at the tibia. METHODS: We have examined the effect of ibandronate on bone microarchitecture with peripheral high-resolution quantitative computed tomography (HR-pQCT) in a randomized placebo-controlled trial among 148 women with osteopenia. Patients received either oral 150 mg monthly ibandronate or placebo over 24 months. Bone microarchitecture was assessed at baseline, 6, 12, and 24 months, using HR-pQCT at the distal radius and tibia; areal bone mineral density (aBMD) was measured with DXA at the spine, hip, and radius. RESULTS: At 12 months, there was no significant difference in trabecular bone volume at the radius (the primary end point) between women on ibandronate (10.8 ± 2.5%) and placebo (10.5 ± 2.9%), p = 0.25. There was no significant difference in other radius trabecular and cortical microarchitecture parameters at 12 and 24 months. In contrast, at the tibia, cortical vBMD in the ibandronate group was significantly greater than in the placebo group at 6, 12, and 24 months, with better cortical thickness at 6, 12, and 24 months. With ibandronate, aBMD was significantly increased at the hip and spine at 12 and 24 months but at the radius was significantly superior to placebo only at 24 months. Most of the adverse events related to ibandronate were expected with bisphosphonate use, and none of them were serious. CONCLUSION: We conclude that 12 months of treatment with ibandronate in women with osteopenia did not affect trabecular bone microarchitecture, but improved cortical vBMD at the tibia at 12 and 24 months, and preserved cortical thickness at the tibia.


Assuntos
Conservadores da Densidade Óssea/administração & dosagem , Doenças Ósseas Metabólicas/tratamento farmacológico , Difosfonatos/administração & dosagem , Administração Oral , Idoso , Densidade Óssea/efeitos dos fármacos , Conservadores da Densidade Óssea/efeitos adversos , Conservadores da Densidade Óssea/uso terapêutico , Doenças Ósseas Metabólicas/patologia , Doenças Ósseas Metabólicas/fisiopatologia , Difosfonatos/efeitos adversos , Difosfonatos/uso terapêutico , Método Duplo-Cego , Esquema de Medicação , Feminino , Humanos , Ácido Ibandrônico , Pessoa de Meia-Idade , Rádio (Anatomia)/patologia , Rádio (Anatomia)/fisiopatologia , Tíbia/patologia , Tíbia/fisiopatologia , Tomografia Computadorizada por Raios X
3.
Osteoporos Int ; 24(8): 2345-52, 2013 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-23612793

RESUMO

UNLABELLED: This observational study showed that after 2 years, both risedronate and alendronate lowered the risk of hip and nonvertebral fractures compared with patients filling in a single bisphosphonate prescription. INTRODUCTION: Post hoc analyses of the placebo-controlled trials suggested earlier effects for risedronate (6-12 months) than for alendronate (18-24 months). The present study extends our 1-year observational data that confirmed an earlier fracture reduction with risedronate and evaluated the absolute and relative effectiveness of alendronate and risedronate in clinical practice over 2 years. METHODS: We observed three cohorts of women aged 65 years and older who initiated once-a-week dosing of bisphosphonate therapy; (1) patients adherent to alendronate (n = 21,615), (2) patients adherent to risedronate (n = 12,215), or (3) patients filling only a single bisphosphonate prescription (n = 5,390) as a referent population. Proportional hazard modeling compared the incidence of hip and nonvertebral fractures among the cohorts over 2 years after the initial prescription. RESULTS: In this cohort, we previously showed at 12 months a significant reduction of hip and nonvertebral fractures with risedronate but not with alendronate. At the end of 2 years, the cumulative incidence of hip fractures in the referent cohort was 1.9 %, and incidence of nonvertebral fractures was 6.3 %. Relative to the referent, 6 months after initiating therapy and continuing through 2 years, both risedronate and alendronate cohorts had approximately a 45 % lower incidence of hip fractures and a 30 % lower incidence of nonvertebral fractures. CONCLUSION: These observations suggest that both risedronate and alendronate are effective at reducing the risk of hip and nonvertebral fracture after 2 years of treatment and support the post hoc analyses of placebo-controlled trials indicating an earlier effect of risedronate.


Assuntos
Alendronato/uso terapêutico , Conservadores da Densidade Óssea/uso terapêutico , Ácido Etidrônico/análogos & derivados , Fraturas por Osteoporose/prevenção & controle , Idoso , Alendronato/administração & dosagem , Conservadores da Densidade Óssea/administração & dosagem , Difosfonatos/administração & dosagem , Difosfonatos/uso terapêutico , Esquema de Medicação , Ácido Etidrônico/administração & dosagem , Ácido Etidrônico/uso terapêutico , Feminino , Fraturas do Quadril/epidemiologia , Fraturas do Quadril/etiologia , Fraturas do Quadril/prevenção & controle , Humanos , Incidência , Adesão à Medicação/estatística & dados numéricos , Osteoporose Pós-Menopausa/complicações , Osteoporose Pós-Menopausa/tratamento farmacológico , Osteoporose Pós-Menopausa/epidemiologia , Fraturas por Osteoporose/epidemiologia , Fraturas por Osteoporose/etiologia , Ácido Risedrônico , Resultado do Tratamento , Estados Unidos/epidemiologia
4.
Osteoporos Int ; 23(9): 2321-7, 2012 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-22179418

RESUMO

UNLABELLED: The incidence of hip fracture, death and the estimated incidence of major osteoporotic fracture in France were used to determine the lifetime and 10-year probability of fracture and incorporated into a probability model (FRAX®) calibrated to the French population. INTRODUCTION: Fracture probabilities in the French population have not been determined. Our aim was to determine the incidence of hip fracture in France and the estimated 10-year probabilities of hip and major osteoporotic fractures. METHODS: The study population included adults over 50 years living in France in 2004. Incident hip fracture cases were identified from the French PMSI database. Incidence of the other major osteoporotic fractures was imputed from the relationship between hip fracture incidence and other major fracture in Sweden. These data were used to calculate population-based fracture probabilities according to age and BMD using cutoff values for femoral neck T-scores from the NHANES III data in Caucasian women. The probability model (FRAX®) calibrated to the French population was used to compute individual fracture probabilities according to specific clinical risk factors. RESULTS: We identified 15,434 men and 51,469 women with an incident hip fracture. The remaining lifetime probability of hip fracture at 50 years was approximately 10 and 30% respectively. With a femoral neck T-score of -2 SD, one in two women and one in five men would sustain a major osteoporotic fracture in their lifetime. The 10-year probability of other major osteoporotic fractures increased with declining T-score and increasing age. Low body mass index and other clinical risk factors had an independent effect on fracture probability whether or not BMD was included in the FRAX® model. CONCLUSION: This analysis provides detailed estimation on the risk of fracture in the French population and may help to define therapeutic guidelines.


Assuntos
Fraturas do Quadril/epidemiologia , Fraturas por Osteoporose/epidemiologia , Idoso , Feminino , França/epidemiologia , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Medição de Risco/métodos , Fatores de Risco , Fatores de Tempo
5.
Endocr Rev ; 28(2): 151-64, 2007 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-17200084

RESUMO

Minimal trauma fractures in bone diseases are the result of bone fragility. Rather than considering bone fragility as being the result of a reduced amount of bone, we recognize that bone fragility is the result of changes in the material and structural properties of bone. A better understanding of the contribution of each component of the material composition and structure and how these interact to maintain whole bone strength is obtained by the study of metabolic bone diseases. Disorders of collagen (osteogenesis imperfecta and Paget's disease of bone), mineral content, composition and distribution (fluorosis and osteomalacia); diseases of high remodeling (postmenopausal osteoporosis, hyperparathyroidism, and hyperthyroidism) and low remodeling (osteopetrosis, pycnodysostosis); and other diseases (idiopathic male osteoporosis, corticosteroid-induced osteoporosis) produce abnormalities in the material composition and structure that lead to bone fragility. Observations in patients and in animal models provide insights on the biomechanical consequences of these illnesses and the nature of the qualities of bone that determine its strength.


Assuntos
Doenças Ósseas/complicações , Osso e Ossos/química , Osso e Ossos/fisiologia , Fraturas Ósseas/etiologia , Animais , Fenômenos Biomecânicos , Densidade Óssea , Doenças Ósseas/patologia , Remodelação Óssea , Reabsorção Óssea/complicações , Osso e Ossos/patologia , Colágeno/análise , Colágeno/fisiologia , Fraturas Ósseas/patologia , Humanos , Minerais/análise , Modelos Biológicos
6.
Osteoporos Int ; 22(6): 1755-64, 2011 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-20838767

RESUMO

UNLABELLED: Identification of older men at high risk of peripheral fracture can be improved by assessing prevalent fractures (men aged ≤ 65), history of falls (men aged >65), bone width, and aortic calcifications. INTRODUCTION: Low bone mineral density (BMD) identifies 20% of men who sustain osteoporotic fracture. We studied (1) if the assessment of bone width, aortic calcifications, prevalent falls and fractures improves identification of men at high risk of fracture and (2) if the predictive value of these parameters varies with age. METHODS: Among 781 men aged 50 and over, 61 men sustained 66 low-trauma peripheral fractures during 10 years. History of falls and prevalent fractures was assessed by questionnaire. BMD and bone with were measured by dual X-ray absorptiometry. Abdominal aortic calcifications were assessed on the lateral radiographs of the lumbar spine. RESULTS: Low BMD, low bone width, extended aortic calcifications, prevalent fractures (mainly multiple fractures) and frequent falls were all associated independently with higher risk of fracture. In men aged ≤ 65, prevalent fractures are associated with a significant increase in the risk of fracture (two- to threefold for one and four- to fivefold for multiple prevalent fractures). In men aged >65, history of falls is associated with a higher risk of fracture, e.g. frequent falls are associated with a sixfold increase in the risk of fracture. CONCLUSIONS: Men aged ≤ 65 with multiple prevalent fractures and frequent fallers aged >65 are at particularly high risk of peripheral fracture regardless of BMD.


Assuntos
Fraturas por Osteoporose/etiologia , Acidentes por Quedas/estatística & dados numéricos , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Doenças da Aorta/epidemiologia , Índice de Massa Corporal , Densidade Óssea/fisiologia , Métodos Epidemiológicos , França/epidemiologia , Humanos , Masculino , Pessoa de Meia-Idade , Fraturas por Osteoporose/epidemiologia , Fraturas por Osteoporose/fisiopatologia , Recidiva , Calcificação Vascular/epidemiologia
7.
Osteoporos Int ; 21(4): 667-77, 2010 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-19597910

RESUMO

UNLABELLED: In postmenopausal osteoporotic women and up to 3 years of treatment with strontium ranelate, strontium was present only in recently deposited bone tissue resulting from formation activity during the period of treatment. Strontium was shown to be dose-dependently deposited into this newly formed bone with preservation of the mineralization. INTRODUCTION: Interactions between strontium (Sr) and bone mineral and its effects on mineralization were investigated in women treated with strontium ranelate. METHODS: Bone biopsies from osteoporotic women were obtained over 5-year strontium ranelate treatment from phases II and III studies. Bone samples obtained over 3-year treatment were investigated by X-ray microanalysis for bone Sr uptake and focal distribution, and by quantitative microradiography for degree of mineralization. On some samples, Sr distribution (X-ray cartography) was analyzed on whole sample surfaces and the percentage of bone surface containing Sr was calculated. Bone Sr content was chemically measured on whole samples. RESULTS: In treated women, Sr was exclusively present in bone formed during treatment; Sr deposition depended on the dose with higher focal content in new bone structural units than in old ones constantly devoid of Sr, even after 3-year treatment. A plateau in global bone Sr content was reached after 3 years of treatment. Cartography illustrated the extent of surfaces containing Sr, and formation activity during strontium ranelate treatment was higher in cancellous than in cortical bone. Mineralization was maintained during treatment. CONCLUSION: The quality of bone mineral was preserved after treatment with strontium ranelate, supporting the safety of this agent at the bone tissue level.


Assuntos
Conservadores da Densidade Óssea/farmacocinética , Compostos Organometálicos/farmacocinética , Osteoporose Pós-Menopausa/metabolismo , Tiofenos/farmacocinética , Idoso , Biópsia , Densidade Óssea/efeitos dos fármacos , Conservadores da Densidade Óssea/uso terapêutico , Osso e Ossos/metabolismo , Calcificação Fisiológica/efeitos dos fármacos , Relação Dose-Resposta a Droga , Método Duplo-Cego , Microanálise por Sonda Eletrônica/métodos , Feminino , Humanos , Ílio/metabolismo , Ílio/patologia , Microrradiografia/métodos , Pessoa de Meia-Idade , Compostos Organometálicos/uso terapêutico , Osteoporose Pós-Menopausa/tratamento farmacológico , Osteoporose Pós-Menopausa/patologia , Osteoporose Pós-Menopausa/fisiopatologia , Tiofenos/uso terapêutico
8.
Osteoporos Int ; 21(7): 1277-85, 2010 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-19802508

RESUMO

UNLABELLED: Changes in bone mineral density and bone strength following treatment with zoledronic acid (ZOL) were measured by quantitative computed analysis (QCT) or dual-energy X-ray absorptiometry (DXA). ZOL treatment increased spine and hip BMD vs placebo, assessed by QCT and DXA. Changes in trabecular bone resulted in increased bone strength. INTRODUCTION: To investigate bone mineral density (BMD) changes in trabecular and cortical bone, estimated by quantitative computed analysis (QCT) or dual-energy X-ray absorptiometry (DXA), and whether zoledronic acid 5 mg (ZOL) affects bone strength. METHODS: In 233 women from a randomized, controlled trial of once-yearly ZOL, lumbar spine, total hip, femoral neck, and trochanter were assessed by DXA and QCT (baseline, Month 36). Mean percentage changes from baseline and between-treatment differences (ZOL vs placebo, t-test) were evaluated. RESULTS: Mean between-treatment differences for lumbar spine BMD were significant by DXA (7.0%, p < 0.01) and QCT (5.7%, p < 0.0001). Between-treatment differences were significant for trabecular spine (p = 0.0017) [non-parametric test], trabecular trochanter (10.7%, p < 0.0001), total hip (10.8%, p < 0.0001), and compressive strength indices at femoral neck (8.6%, p = 0.0001), and trochanter (14.1%, p < 0.0001). CONCLUSIONS: Once-yearly ZOL increased hip and spine BMD vs placebo, assessed by QCT vs DXA. Changes in trabecular bone resulted in increased indices of compressive strength.


Assuntos
Conservadores da Densidade Óssea/administração & dosagem , Difosfonatos/administração & dosagem , Imidazóis/administração & dosagem , Osteoporose Pós-Menopausa/tratamento farmacológico , Absorciometria de Fóton/métodos , Idoso , Idoso de 80 Anos ou mais , Densidade Óssea/efeitos dos fármacos , Conservadores da Densidade Óssea/uso terapêutico , Força Compressiva/efeitos dos fármacos , Difosfonatos/uso terapêutico , Esquema de Medicação , Feminino , Colo do Fêmur/efeitos dos fármacos , Colo do Fêmur/fisiopatologia , Seguimentos , Articulação do Quadril/efeitos dos fármacos , Articulação do Quadril/fisiopatologia , Humanos , Imidazóis/uso terapêutico , Vértebras Lombares/efeitos dos fármacos , Vértebras Lombares/fisiopatologia , Osteoporose Pós-Menopausa/fisiopatologia , Tomografia Computadorizada por Raios X/métodos , Ácido Zoledrônico
9.
Calcif Tissue Int ; 87(1): 52-9, 2010 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-20383765

RESUMO

Low-intensity electrical stimulation (LIES) may counteract the effects of ovariectomy (OVX) on nitric oxide synthase (NOS) expression, osteocyte viability, bone structure, and microarchitecture in rats (Lirani-Galvão et al., Calcif Tissue Int 84:502-509, 2009). The aim of the present study was to investigate if these effects of LIES could be mediated by NO. We analyzed the effects of NO blockage (by L-NAME) in the response to LIES on osteocyte viability, bone structure, and microarchitecture in OVX rats. Sixty rats (200-220 g) were divided into six groups: sham, sham-L-NAME (6 mg/kg/day), OVX, OVX-L-NAME, OVX-LIES, and OVX-LIES-L-NAME. After 12 weeks, rats were killed and tibiae collected for histomorphometric analysis and immunohistochemical detection of endothelial NOS (eNOS), inducible NOS (iNOS), and osteocyte apoptosis (caspase-3 and TUNEL). In the presence of L-NAME, LIES did not counteract the OVX-induced effects on bone volume and trabecular number (as on OVX-LIES). L-NAME blocked the stimulatory effects of LIES on iNOS and eNOS expression of OVX rats. Both L-NAME and LIES decreased osteocyte apoptosis. Our results showed that in OVX rats L-NAME partially blocks the effects of LIES on bone structure, turnover, and expression of iNOS and eNOS, suggesting that NO may be a mediator of some positive effects of LIES on bone.


Assuntos
Óxido Nítrico/metabolismo , Animais , Apoptose/efeitos dos fármacos , Apoptose/fisiologia , Osso e Ossos/metabolismo , Caspase 3 , Feminino , Marcação In Situ das Extremidades Cortadas , NG-Nitroarginina Metil Éster/farmacologia , Óxido Nítrico Sintase/metabolismo , Óxido Nítrico Sintase Tipo II , Óxido Nítrico Sintase Tipo III/metabolismo , Osteócitos/metabolismo , Osteócitos/fisiologia , Ovariectomia , Ratos , Ratos Wistar
10.
Ann Rheum Dis ; 68(7): 1197-200, 2009 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-18713784

RESUMO

BACKGROUND: Defining the remission criteria of rheumatoid arthritis (RA) remains a critical issue. Markers of synovium activity, urinary glucosyl-galactosyl-pyridinoline (Glc-Gal-PYD) and of cartilage destruction, urinary C-terminal crosslinking telopeptide of type II collagen (CTX-II) have been shown to reflect disease activity and joint damage progression in RA. METHODS: The prospective study cohort comprised 66 RA patients treated with infliximab and methotrexate and 76 healthy controls. Measurements of urinary Glc-Gal-PYD and CTX-II were performed at baseline and at 1 year of infliximab therapy. RESULTS: At baseline, urinary Glc-Gal-PYD and CTX-II levels were increased in patients with RA and correlated with modified Sharp scores and progression of joint damage. Patients with more progressive joint destruction had higher Glc-Gly-PYD and CTX-II baseline levels. CONCLUSION: These markers reflected bone erosion evolution and might be useful for treatment monitoring and evaluation of RA. Markers remained high even in clinical responders after infliximab, suggesting persistence of synovitis.


Assuntos
Anticorpos Monoclonais/uso terapêutico , Antirreumáticos/uso terapêutico , Artrite Reumatoide/tratamento farmacológico , Metotrexato/uso terapêutico , Membrana Sinovial/metabolismo , Artrite Reumatoide/urina , Biomarcadores/metabolismo , Colágeno Tipo II/metabolismo , Reagentes de Ligações Cruzadas , Dissacarídeos/metabolismo , Feminino , Humanos , Infliximab , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Piridinas/metabolismo , Resultado do Tratamento
11.
Osteoporos Int ; 20(8): 1299-308, 2009 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-19291343

RESUMO

INTRODUCTION: Microdamage accumulation due to fatigue loading may lead to fracture. In addition, several studies using animal models have suggested in recent years that bisphosphonates might increase microdamage accumulation. METHODS: We have reviewed the literature after a PubMed search, to examine the techniques to look for microcracks, the relationship between microdamage and bone strength, and the influence of anti-osteoporosis agents. RESULTS: Currently, the search for microcracks relies on bulk staining of bone samples, which are then examined on optic microscopy and fluorescence or confocal microscopy. The accumulation of microdamage is associated with fatigue loading and is likely to trigger targeted bone remodeling, especially in cortical bone. Several studies examining beagle dogs receiving bisphosphonates have shown a dose-dependent accumulation of microdamage in bone, with conflicting results regarding the consequences on bone mechanical properties. In living humans, obtaining data is limited to the iliac crest bone. The potential association between long-term bisphosphonate use and microcrack accumulation at the iliac crest bone has not been established unequivocally. CONCLUSIONS: Bone microdamage is critical in the understanding of bone quality. Assessment of microdamage is technically difficult, especially in humans. The clinical impact of microdamage potentially induced by bone drugs has not been established in humans.


Assuntos
Fraturas Ósseas/diagnóstico , Fraturas de Estresse/diagnóstico , Animais , Conservadores da Densidade Óssea/efeitos adversos , Remodelação Óssea/fisiologia , Modelos Animais de Doenças , Cães , Feminino , Fraturas Ósseas/induzido quimicamente , Fraturas Ósseas/fisiopatologia , Fraturas de Estresse/induzido quimicamente , Fraturas de Estresse/fisiopatologia , Humanos , Osteócitos/fisiologia , Osteoporose Pós-Menopausa/tratamento farmacológico
12.
Osteoporos Int ; 20(3): 371-7, 2009 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-18636217

RESUMO

UNLABELLED: There was 75% variation in the trend in hip fracture incidence with age in women aged 50 to 85 in France. In southwest France, the women are at higher risk of hip fracture at younger ages. This finding should be taken into account when examining risk factors. INTRODUCTION: Few studies have analysed the geographical variations in the relationship between age and hip fracture incidence. Our goal was to assess these variations among women under 85 within the same country. METHODS: The study population included women aged 50 to 85 who were living in France in 2004. Hip fracture cases were identified in the French Diagnosis Related Groups (DRG)-like database using the diagnosis code for closed hip fractures and procedural codes for treatment. The Moran index and a spatial model using latitude and longitude were used to assess the geographical heterogeneities of cumulative incidence risk (CIR) and age effect. RESULTS: A total of 29,218 hip fracture cases were identified. A south-to-north CIR gradient ranging from 7 to 16% was observed. The variation in the number of years until double hip fracture incidence was 75% (i.e. 1.49 to 2.57 years). In the south, and more markedly in southwest France, the women are at higher risk of hip fracture at a younger age. CONCLUSION: The risk of fracture may be different between women of the same age. This may be hidden in a comparison of standardised ratios. This finding should be considered when examining risk factors and implementing public health interventions.


Assuntos
Fraturas do Quadril/epidemiologia , Idoso , Idoso de 80 Anos ou mais , Feminino , França/epidemiologia , Humanos , Incidência , Pessoa de Meia-Idade , Vigilância da População/métodos , Valores de Referência , Fatores de Risco
13.
Osteoporos Int ; 20(11): 1895-902, 2009 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-19296144

RESUMO

UNLABELLED: Two studies in postmenopausal women with osteoporosis provide information about the efficacy and safety of dosing oral risedronate 5 mg daily at a time other than before breakfast (i.e., 2 h before and 2 h after any food and drink other than plain water). A significant increase in lumbar spine BMD was observed for both treatment regimens in the two studies. However, smaller increases in lumbar spine BMD were observed with flexible dosing versus before-breakfast dosing. Geographic region, compliance, and consistency of dosing time appear to affect the amount of increase in BMD observed with flexible dosing. INTRODUCTION: Two studies in postmenopausal women with osteoporosis provide additional information about the efficacy and safety of dosing oral risedronate 5 mg daily at a time other than before breakfast (i.e., 2 h before and 2 h after any food and drink other than plain water). METHODS: One study, flexible dosing, was a 6-month North American study in 730 patients randomized to before-breakfast dosing or flexible dosing later in the day. A second study, IMPACT, was a large (N = 2382), 1-year multinational study in patients that chose their dosing regimen (before breakfast or later in the day). These studies were used to examine the bone mineral density (BMD) response with different dosing regimens. RESULTS: A significant increase in lumbar spine BMD was observed for both treatment regimens in the two studies. However, in both studies, the flexible dosing group had a smaller increase from baseline compared to the before-breakfast regimen (ratio of flexible dosing to before breakfast: flexible dosing study, 0.52; IMPACT study, 0.75). In addition, a relationship between geographic region and BMD response was observed with flexible dosing in both studies. Patients in the flexible dosing group who had greater dosing compliance (based on the number of times the bottle was opened) and consistency of dosing time (bottle opened within a 1.5-h window) had a greater increase in lumbar spine BMD. CONCLUSION: Results of these two studies demonstrate that overall flexible dosing of risedronate leads to smaller BMD gains compared to before-breakfast dosing. This result may be due to poorer adherence to the flexible dosing instructions that may be more pronounced in patients in certain geographic regions. If patients cannot abide by before-breakfast dosing and flexible dosing is an approved option, one can expect suboptimal BMD results with flexible dosing.


Assuntos
Conservadores da Densidade Óssea/administração & dosagem , Ácido Etidrônico/análogos & derivados , Osteoporose Pós-Menopausa/tratamento farmacológico , Idoso , Densidade Óssea/efeitos dos fármacos , Conservadores da Densidade Óssea/efeitos adversos , Conservadores da Densidade Óssea/uso terapêutico , Esquema de Medicação , Ácido Etidrônico/administração & dosagem , Ácido Etidrônico/efeitos adversos , Ácido Etidrônico/uso terapêutico , Feminino , Humanos , Vértebras Lombares/fisiopatologia , Pessoa de Meia-Idade , Osteoporose Pós-Menopausa/fisiopatologia , Cooperação do Paciente , Ácido Risedrônico , Método Simples-Cego
14.
Osteoporos Int ; 20(2): 291-7, 2009 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-18663402

RESUMO

UNLABELLED: This analysis was conducted to assess the effect of high versus lower doses of ibandronate on nonvertebral fractures. The results were adjusted for clinical fracture, age, and bone density. The treatment effect was dose-dependent. Higher doses of ibandronate significantly reduced the risk of nonvertebral fractures more effectively compared with lower doses. INTRODUCTION: The objective of this study was to assess the efficacy of different doses of ibandronate on nonvertebral fractures in a pooled analysis. METHODS: Eight randomized trials of ibandronate were reviewed for inclusion. Alternative definitions of high versus low doses based on annual cumulative exposure (ACE) were explored. A time-to-event analysis was conducted using Kaplan-Meier methodology. Hazard ratios (HR) were derived using Cox regression and adjusted for covariates. RESULTS: Combining higher ACE doses of > or = 10.8 mg (150 mg once monthly, 3 mg i.v. quarterly, and 2 mg i.v. every 2 months) versus ACE doses of 5.5 mg, from two trials, resulted in an HR 0.62 (95% CI 0.396-0.974, p = 0.038). There was a dose-response trend with increasing ACE doses (7.2-12 mg) versus ACE of 5.5 mg. CONCLUSIONS: A dose-response effect on nonvertebral fractures was observed when comparing high with low ACE doses. A significant reduction in nonvertebral fractures was noted when pooling data from trials using ACE doses of > or = 10.8 mg versus ACE < or = 7.2 mg; and with ACE > or = 10.8 mg versus ACE of 5.5 mg (38% reduction). Higher ibandronate dose levels (150 mg monthly or 3 mg i.v. quarterly) significantly reduced nonvertebral fracture risk in postmenopausal women.


Assuntos
Conservadores da Densidade Óssea/administração & dosagem , Difosfonatos/administração & dosagem , Fraturas Ósseas/prevenção & controle , Osteoporose Pós-Menopausa/tratamento farmacológico , Idoso , Densidade Óssea/efeitos dos fármacos , Conservadores da Densidade Óssea/uso terapêutico , Difosfonatos/uso terapêutico , Esquema de Medicação , Feminino , Fraturas Ósseas/complicações , Humanos , Ácido Ibandrônico , Pessoa de Meia-Idade , Osteoporose Pós-Menopausa/complicações , Modelos de Riscos Proporcionais , Ensaios Clínicos Controlados Aleatórios como Assunto , Resultado do Tratamento
15.
Calcif Tissue Int ; 84(6): 502-9, 2009 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-19458889

RESUMO

Low Intensity Electrical Stimulation (LIES) has been used for bone repair, but little is known about its effects on bone after menopause. Osteocytes probably play a role in mediating this physical stimulus and they could act as transducers through the release of biochemical signals, such as nitric oxide (NO). The aim of the present study was to investigate the effects of LIES on bone structure and remodeling, NOS expression and osteocyte viability in ovariectomized (OVX) rats. Thirty rats (200-220 g) were divided into 3 groups: SHAM, OVX, and OVX subjected to LIES (OVX + LIES) for 12 weeks. Following the protocol, rats were sacrificed and tibias were collected for histomorphometric analysis and immunohistochemical detection of endothelial NO synthase (eNOS), inducible NOS (iNOS), and osteocyte apoptosis (caspase-3 and TUNEL). OVX rats showed significant (p < 0.05 vs. SHAM) decreased bone volume (10% vs. 25%) and trabecular number (1.7 vs. 3.9), and increased eroded surfaces (4.7% vs. 3.2%) and mineralization surfaces (15.9% vs. 7.7%). In contrast, after LIES, all these parameters were significantly different from OVX but not different from SHAM. eNOS and iNOS were similarly expressed in subperiosteal regions of tibiae cortices of SHAM, not expressed in OVX, and similarly expressed in OVX + LIES when compared to SHAM. In OVX, the percentage of apoptotic osteocytes (24%) was significantly increased when compared to SHAM (11%) and OVX + LIES (8%). Our results suggest that LIES counteracts some effects of OVX on bone tissue preserving bone structure and microarchitecture, iNOS and eNOS expression, and osteocyte viability.


Assuntos
Osso e Ossos/fisiologia , Terapia por Estimulação Elétrica , Menopausa , Óxido Nítrico/metabolismo , Osteócitos/fisiologia , Animais , Apoptose/fisiologia , Osso e Ossos/metabolismo , Osso e Ossos/ultraestrutura , Caspase 3/metabolismo , Sobrevivência Celular/fisiologia , Feminino , Óxido Nítrico Sintase Tipo II/metabolismo , Óxido Nítrico Sintase Tipo III/metabolismo , Osteócitos/metabolismo , Osteócitos/ultraestrutura , Ovariectomia , Ratos , Ratos Wistar , Tíbia/citologia , Tíbia/fisiologia
16.
J Cell Biol ; 127(4): 1149-58, 1994 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-7962073

RESUMO

Osteocalcin, also called Bone Gla Protein (BGP), is the most abundant of the non-collagenous proteins of bone produced by osteoblasts. It consists of a single chain of 46-50 amino acids, according to the species, and contains three vitamin K-dependent gamma-carboxyglutamic acid residues (GLA), involved in its binding to calcium and hydroxylapatite. Accumulating evidences suggest its involvement in bone remodeling, its physiological role, however, is still unclear. In this study the adhesion properties and the biological effects of osteocalcin on osteoclasts have been analyzed using as an experimental model, human osteoclast-like cells derived from giant cell tumors of bone (GCT). Osteocalcin promoted adhesion and spreading of these cells, triggering the release of bone sialoprotein (BSP), osteopontin (OPN) and fibronectin (FN), that in turn induced the clustering in focal adhesions of beta 1 and beta 3 integrin chains. Spreading was dependent upon the synthesis of these proteins. In fact, when the cells were incubated in the presence of monensin during the adhesion assay, they still adhered but spreading did not occur, focal adhesions disappeared and BSP, OPN, and FN were accumulated in intracellular granules. Furthermore osteocalcin induced chemotaxis in a dose-dependent manner. The action of BGP on osteoclasts was mediated by an intracellular calcium increase due to release from thapsigargin-sensitive stores. These results provide evidences that BGP exerts a role in the resorption process, inducing intracellular signaling, migration and adhesion, followed by synthesis and secretion of endogenous proteins.


Assuntos
Cálcio/metabolismo , Quimiotaxia/efeitos dos fármacos , Proteínas da Matriz Extracelular/biossíntese , Osteocalcina/farmacologia , Osteoclastos/fisiologia , Transdução de Sinais/fisiologia , Neoplasias Ósseas , Adesão Celular/efeitos dos fármacos , Citosol/metabolismo , Fibronectinas/biossíntese , Tumores de Células Gigantes , Humanos , Sialoproteína de Ligação à Integrina , Integrinas/fisiologia , Cinética , Osteoclastos/efeitos dos fármacos , Osteopontina , Sialoglicoproteínas/biossíntese , Transdução de Sinais/efeitos dos fármacos , Fatores de Tempo , Células Tumorais Cultivadas
17.
Artigo em Inglês | MEDLINE | ID: mdl-19027371

RESUMO

A rapid high performance liquid chromatographic method was developed including an internal standard for the measurement of mature and senescent crosslinks concentration in non-demineralized bone hydrolysates. To avoid the demineralization which is a tedious step, we developed a method based on the use of a solid-phase extraction procedure to clean-up the samples. It resulted in sensitive and accurate measurements: the detection limits as low as 0.2 pmol for the pyridimium crosslinks and 0.02 pmol for the pentosidine. The inter- and intra-assay coefficients of variation were as low as 5% and 2%, respectively, for all crosslinks.


Assuntos
Osso e Ossos/química , Cromatografia Líquida de Alta Pressão/métodos , Colágeno/química , Animais , Bovinos , Fluorescência , Hidrólise , Padrões de Referência , Reprodutibilidade dos Testes , Sensibilidade e Especificidade
18.
Bone ; 43(5): 862-8, 2008 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-18708176

RESUMO

The increased hip fragility in osteoporosis has been attributed mainly to a thinning of the cortex. In contrast, hip arthritis (OA) is not associated with increased risk of hip fracture. The purpose of this study was to assess cortical and trabecular bone structures and their possible regional variability in the femoral neck taken from patients who sustained an osteoporotic hip fracture (OP) compared with patients with OA. We compared the distribution of bone in the ultradistal femoral neck in 21 postmenopausal women with OA (mean age: 66+/-7.8 years) and 20 postmenopausal women with an osteoporotic hip fracture (OP) (mean age: 79.5+/-1.9 years). Controlateral hip osteoporosis or osteopenia was confirmed in OP by DEXA (T-score: -2.5+/-0.8 in OP; -0.9+/-1.3 in OA). Histomorphometric parameters of bone structure, architecture and connectivity were measured on sections from the ultradistal part of the femoral neck, divided in 4 quadrants. When compared to OA, cortical thickness was significantly decreased in OP (p<0.0005) but was the highest in the inferior part in both groups. Cortical porosity was higher in OA (13.48+/-1.02 and 8.4+/-1.07% in OA and OP respectively). Compared to OA, the trabecular bone volume was decreased by 50% in OP (p<0.0001) with a diminution of the trabecular number (p<0.01) and thickness (p<0.0001). In parallel, OP group was characterized by a poor connectivity evaluated by the decreased number of nodes (p<0.0001), higher trabecular bone pattern factor (p<0.0001) and greater marrow star volume (p<0.0001). The connectivity was the lowest in the inferior quadrant in OP but not in OA. Our data suggest that in addition to the cortical thinning, the loss of the trabecular bone mass and connectivity plays a role in the skeletal fragility associated with hip fracture. Furthermore, the spatial distribution of the trabeculae differs between OP and OA whereas cortical thinning is homogenous.


Assuntos
Colo do Fêmur , Osteoartrite/patologia , Osteoporose/patologia , Idoso , Idoso de 80 Anos ou mais , Peso Corporal , Densidade Óssea , Feminino , Colo do Fêmur/anatomia & histologia , Colo do Fêmur/patologia , Fraturas do Quadril , Humanos , Pessoa de Meia-Idade , Osteoporose/complicações , Porosidade , Fatores de Risco
19.
Bone ; 43(3): 532-8, 2008 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-18599391

RESUMO

Degree of mineralization of bone (DMB) is a major intrinsic determinant of bone strength at the tissue level but its contribution to the microhardness (Vickers indentation) at the intermediary level of organization of bone tissue, i.e., Bone Structural Units (BSUs), has never been assessed. The purpose of this study was to analyze the relationship between the microhardness, the DMB and the organic matrix, measured in BSUs from human iliac bone biopsies. Iliac bone samples from controls and osteoporotic patients (men and women), embedded in methyl methacrylate, were used. Using a Vickers indenter, microhardness (kg/mm2) was measured, either globally on surfaced blocks or focally on 100 microm-thick sections from bone samples (load of 25 g applied during 10 sec; CV=5%). The Vickers indenter was more suited than the Knoop indenter for a tissue like bone in which components are diversely oriented. Quantitative microradiography performed on 100 microm-thick sections, allowed measurement of parameters reflecting the DMB (g/cm3). Assessed on the whole bone sample, both microhardness and DMB were significantly lower (-10% and -7%, respectively) in osteoporotic patients versus controls (p<0.001). When measured separately at the BSU level, there were significant positive correlations between microhardness and DMB in controls (r2=0.36, p<0.0001) and osteoporotic patients (r2=0.43, p<0.0001). Mineralization is an important determinant of the microhardness, but did not explain all of its variance. To highlight the role of the organic matrix in bone quality, microhardness of both osteoid and adjacent calcified matrix were measured in iliac samples from subjects with osteomalacia. Microhardness of organic matrix is 3-fold lower than the microhardness of calcified tissue. In human calcanei, microhardness was significantly correlated with DMB (r2=0.33, p=0.02) and apparent Young's modulus (r2=0.26, p=0.03). In conclusion, bone microhardness measured by Vickers indentation is an interesting methodology for the evaluation of bone strength and its determinants at the BSU level. Bone microhardness is linked to Young's modulus of bone and is strongly correlated to mineralization, but the organic matrix accounts for about one third of its variance.


Assuntos
Osso e Ossos/patologia , Osteoporose/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Biópsia , Densidade Óssea , Osso e Ossos/metabolismo , Calcificação Fisiológica , Estudos de Casos e Controles , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fatores Sexuais
20.
Bone ; 42(1): 139-49, 2008 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-17974517

RESUMO

We developed an in vitro model which provides the ability to test the effects of advanced glycation end products (AGEs), specifically pentosidine (PEN) and one of its inhibitors, the aminoguanidine (AMG), on cortical bone. This model allows modification of the extent of collagen cross-linking, while controlling other factors known to influence bone strength. In this in vitro model, young bovine cortical bone specimens were incubated in phosphate-buffered saline (PBS)+/-ribose (RIB, an inducer of AGEs formation)+/-AMG for 15 days at 37 degrees C. The mineral and organic matrix as well as biomechanical properties were examined. We found that (i) incubation+/-treatments did not induce collagen denaturation compared to specimens that were not incubated; (ii) neither treatment or incubation time effected the concentration of trivalent enzymatic cross-links pyridinoline and deoxypyridinoline. The non-enzymatic cross-link PEN was undetectable in specimens that were not incubated or that were incubated in PBS or AMG alone. However, PEN concentration increased significantly in specimens incubated with RIB, whereas ribose-induced PEN formation was markedly inhibited by AMG. (iii) Incubation+/-treatments did not change the mineral maturity, crystallinity or microhardness assessed by X-ray diffraction, X-ray microscopy analyses, FTIRM and micro-indentation tests. (iv) PEN concentration was not associated with biomechanical properties assessed by 3-point bending. In conclusion, this in vitro incubation model of young bovine cortical bone induced physiologic concentrations of PEN in the RIB+AMG group and is the first to show that AMG inhibits ribose-induced formation of PEN cross-links in bone while not affecting the organic and mineral phases. AGE concentration did not influence bending mechanical properties; however, the simple 3-point bending test we used was likely inadequate to demonstrate effects of AGEs on mechanical properties.


Assuntos
Fêmur/metabolismo , Glucose/biossíntese , Animais , Densidade Óssea , Bovinos , Colágeno/metabolismo , Fêmur/química , Modelos Animais , Porosidade , Espectroscopia de Infravermelho com Transformada de Fourier , Estresse Mecânico , Tomografia Computadorizada por Raios X , Difração de Raios X
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