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1.
J Bone Miner Metab ; 29(6): 756-64, 2011 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-21748462

RESUMO

The purpose of this study was to adapt various staining methods for the detection of microdamage in human bone, while preserving tetracycline labels. We describe two staining methods using calcein green and xylenol orange, first developed in ewe bone samples and validated in human trabecular bone samples. In ewe bones, we found that calcein green at 0.5 mM concentration diluted in 100% ethanol as well as xylenol orange at 5 mM were the most adequate fluorochromes both to detect microdamage and preserve the double tetracycline labeling. These results were verified in human trabecular bone (iliac crest for the tetracycline label, and vertebral bone for the double labeling). Results obtained in human bone samples were identical to those in ewes, so this combination of fluorochromes is now used in our laboratory.


Assuntos
Osso e Ossos/química , Corantes Fluorescentes/química , Coloração e Rotulagem/métodos , Animais , Humanos , Ovinos
2.
J Bone Miner Res ; 22(10): 1502-9, 2007 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-17824840

RESUMO

UNLABELLED: We sought whether microdamage could rise in postmenopausal osteoporotic women on long-term bisphosphonates, as suggested by recent animal studies. We found few microcracks in iliac bone biopsies, despite a marked reduction in bone turnover. INTRODUCTION: Animal studies suggest that bisphosphonates (BPs) could increase microdamage frequency in a dose-dependent manner, caused by excessively suppressed bone turnover. However, there is limited data in humans receiving BP therapeutic doses for >3 yr. MATERIALS AND METHODS: We measured microcrack frequency and histomorphometry parameters on transiliac bone biopsies in 50 postmenopausal osteoporotic women (mean age = 68 yr) who had received BP therapy (3 on intravenous pamidronate, 37 on oral alendronate, and 10 on oral risedronate) for at least 3 yr (mean treatment duration = 6.5 yr). We compared these results with transiliac bone biopsies obtained from 12 cadavers. We used bulk staining with green calcein as a fluorochrome. The microcracks were quantified in three 100-microm-thick sections using optic microscopy and were confirmed by laser confocal microscopy. Microcrack frequency (number of microcracks/mm2 of bone tissue) was compared between treated women and controls using nonparametric tests. We also explored predictors of microcrack frequency, including age, duration of BP therapy, and activation frequency. RESULTS: Among treated women, cancellous bone microcrack frequency was low (mean, 0.13 microcracks/mm2) and did not differ significantly from that observed in controls (0.05 microcracks/mm2; p = 0.59). Of note, 54% of the treated women and 58% of the controls had no observable microcracks. There was no association between microcrack frequency and the duration of BP therapy (for microcracks/mm2 and duration, Spearman r = 0.04, p = 0.80) and between patients' ages and the number of microcracks (Spearman r = -0.09, p = 0.61). Although bone remodeling parameters were suppressed in treated women, we found no relationship between microcrack density and activation frequency (Spearman r = -0.003, p = 0.99). Also, microcrack frequency was not increased in women with prevalent vertebral fracture compared with those without fractures. CONCLUSIONS: Among postmenopausal osteoporotic women on long-term BPs, microcrack frequency in the iliac bone is low, despite a marked reduction of bone turnover.


Assuntos
Remodelação Óssea/efeitos dos fármacos , Difosfonatos/uso terapêutico , Fraturas Ósseas/tratamento farmacológico , Fraturas Ósseas/patologia , Osteoporose Pós-Menopausa/tratamento farmacológico , Osteoporose Pós-Menopausa/patologia , Distribuição por Idade , Idoso , Idoso de 80 Anos ou mais , Biópsia , Cadáver , Estudos Transversais , Feminino , Fraturas Ósseas/cirurgia , Humanos , Pessoa de Meia-Idade , Osteoporose Pós-Menopausa/cirurgia , Fatores de Tempo
3.
J Bone Miner Res ; 21(2): 300-6, 2006 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-16418786

RESUMO

UNLABELLED: A 3-year, randomized, double-blind, placebo-controlled trial evaluated the effect of oral alendronate on the BMD of 64 adult patients with osteogenesis imperfecta. The mean increases in the lumbar spine BMD were 10.1 +/- 9.8% (p < 0.001) and 0.7 +/- 5.7% in the alendronate and placebo groups, respectively. Oral alendronate increases BMD in adult patients with osteogenesis imperfecta. INTRODUCTION: This study evaluated the effect of oral alendronate on the BMD of adult patients with osteogenesis imperfecta. MATERIALS AND METHODS: We carried out a 3-year, randomized, double-blind, placebo-controlled trial of oral alendronate in 64 adult patients with osteogenesis imperfecta. The primary endpoint was the difference between the groups in the mean percent change in lumbar spine BMD at 3 years. Secondary outcomes included changes in BMD of total hip, vertebral and peripheral fracture incidence, pain, hearing loss, and bone turnover biochemical markers. Patients were treated daily with either placebo or 10 mg alendronate. All received 1 g of calcium and 800 IU of vitamin D daily. RESULTS: The mean +/- SD increases in the lumbar spine BMD were 10.1 +/- 9.8% (p < 0.001) and 0.7 +/- 5.7% in the alendronate and placebo groups, respectively. Hip BMD increased in the alendronate group by 3.3 +/- 0.5% (p = 0.001) and decreased in the placebo group by 0.3 +/- 0.6%. The sample size was not sufficient to determine an effect of alendronate on fracture rate. A significant increase of the pain score was noted in the alendronate group (p = 0.04) in the intent-to-treat analysis but not in the per protocol analysis. There was no change in hearing in either group. Bone resorption and formation biochemical markers were significantly decreased in the alendronate group (p < 0.001). There were no differences in severe adverse effects between the groups, but there was an increase in nonsevere upper gastrointestinal effects in the alendronate group (p = 0.003). CONCLUSIONS: Oral alendronate increases BMD and increase nonsevere gastrointestinal adverse effects but does not modify the hearing loss in adult patients with osteogenesis imperfecta. More studies are needed to evaluate an effect on the fracture rate.


Assuntos
Alendronato/administração & dosagem , Conservadores da Densidade Óssea/administração & dosagem , Densidade Óssea/efeitos dos fármacos , Osteogênese Imperfeita/tratamento farmacológico , Absorciometria de Fóton , Administração Oral , Adulto , Alendronato/efeitos adversos , Biomarcadores/sangue , Biomarcadores/urina , Conservadores da Densidade Óssea/efeitos adversos , Remodelação Óssea , Colágeno/sangue , Colágeno/urina , Colágeno Tipo I , Feminino , Fraturas Ósseas/diagnóstico por imagem , Perda Auditiva/diagnóstico , Quadril/diagnóstico por imagem , Humanos , Vértebras Lombares/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade , Dor/diagnóstico , Peptídeos/sangue , Peptídeos/urina , Placebos , Fraturas da Coluna Vertebral/diagnóstico por imagem , Resultado do Tratamento
4.
J Bone Miner Res ; 20(7): 1244-53, 2005 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-15940379

RESUMO

UNLABELLED: An 18-month randomized double-blind study was conducted in postmenopausal women with osteoporosis to compare the effects of once-daily teriparatide 20 microg with alendronate 10 mg on bone histomorphometry. Biopsies were obtained from 42 patients. Indices of bone formation were significantly higher after 6 or 18 months of teriparatide compared with alendronate treatment. INTRODUCTION: Alendronate and teriparatide increased BMD, assessed by DXA, by different mechanisms of action, supported by changes in biochemical markers of bone turnover. The purpose of this cross-sectional study was to explore the differential effects of these two osteoporosis treatments at the bone tissue level by examining bone histomorphometric parameters of bone turnover after either 6 or 18 months of treatment. MATERIALS AND METHODS: Patients were a cohort from a randomized parallel double-blind study conducted to compare the effects of once-daily teriparatide 20 microg and alendronate 10 mg in postmenopausal women with osteoporosis. Transiliac crest bone biopsies were obtained after tetracycline double labeling from 42 patients treated for 6 months (n = 23) or 18 months (n = 14); 5 additional patients were biopsied from contralateral sides at 6 and 18 months. Biopsy specimens adequate for quantitative analysis were analyzed by 2D histomorphometry from 17 patients at 6 months (teriparatide, n = 8; alendronate, n = 9) and 15 patients at 18 months (teriparatide, n = 8; alendronate, n = 7). Data were analyzed by two-sample tests. RESULTS: Histomorphometric indices of bone formation were significantly and markedly greater in the teriparatide group than in the alendronate group at 6 and 18 months, whereas indices of bone resorption were only significantly greater in the teriparatide group than in the alendronate group at 6 months. Bone formation and activation frequency were significantly lower at 18 months compared with 6 months in the teriparatide group, returning to levels comparable with untreated postmenopausal women. In the teriparatide group, the peak in histomorphometric bone formation indices coincided with peak levels for N-terminal propeptide of type I collagen, a biochemical marker of bone formation. The degree of mineralization was lower at 18 months than at 6 months with treatment in both groups but was not different between groups. CONCLUSIONS: These results confirm the opposite mechanisms of action of teriparatide and alendronate on bone remodeling and confirm the bone formation effect of teriparatide.


Assuntos
Alendronato/uso terapêutico , Remodelação Óssea/efeitos dos fármacos , Osteoporose Pós-Menopausa/tratamento farmacológico , Teriparatida/uso terapêutico , Absorciometria de Fóton , Idoso , Biomarcadores/análise , Densidade Óssea/efeitos dos fármacos , Calcificação Fisiológica/efeitos dos fármacos , Feminino , Humanos , Ílio/patologia , Pessoa de Meia-Idade , Pós-Menopausa/efeitos dos fármacos , Pós-Menopausa/metabolismo
5.
Maturitas ; 44(4): 299-305, 2003 Apr 25.
Artigo em Inglês | MEDLINE | ID: mdl-12697371

RESUMO

OBJECTIVE: To assess the cost implications for a preventive treatment strategy for institutionalised elderly women with a combined 1200 mg/day calcium and 800 IU/day vitamin D(3) supplementation in seven European countries. DESIGN: Retrospective cost effectiveness analysis based on a prospective placebo-controlled randomised clinical trial. DATA SOURCES: Recently published cost studies in seven European countries. Clinical results from Decalyos, a 3-year placebo-controlled study in elderly institutionalised women. TRIALS: Decalyos study, with 36 months follow-up of 3270 mobile elderly women living in 180 nursing homes, allocated to two groups. One group received 1200 mg/day elemental calcium in the form of tricalcium phosphate together with 800 IU/day (20 microg) of cholecalciferol (vitamin D(3)), the other placebo. RESULTS: In the 36 months analysis of the Decalyos study, 138 hip fractures occurred in the group of 1176 women, receiving supplementation and 184 hip fractures in the placebo group of 1127 women. The mean duration of treatment was 625.4 days. Adjusted to 1000 women, 46 hip fractures were avoided by the calcium and vitamin D(3) supplementation. For all countries, the total costs in the placebo group were higher than in the group receiving supplementation, resulting in a net benefit of 79000-711000 per 1000 women. CONCLUSION: This analysis suggests that the supplementation strategy is cost saving. The results may underestimate the net benefits, as this treatment has also shown to be effective in decreasing the incidence of other non-vertebral fractures in elderly institutionalised women.


Assuntos
Fosfatos de Cálcio/administração & dosagem , Colecalciferol/administração & dosagem , Fraturas do Quadril/prevenção & controle , Osteoporose Pós-Menopausa/complicações , Idoso , Fosfatos de Cálcio/economia , Colecalciferol/economia , Análise Custo-Benefício , Custos de Medicamentos , Quimioterapia Combinada , Europa (Continente) , Feminino , Custos de Cuidados de Saúde , Fraturas do Quadril/economia , Fraturas do Quadril/etiologia , Humanos , Osteoporose Pós-Menopausa/economia
6.
J Bone Miner Res ; 26(4): 739-46, 2011 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-20928886

RESUMO

The ability of a vertebra to carry load after an initial deformation and the determinants of this postfracture load-bearing capacity are critical but poorly understood. This study aimed to determine the mechanical behavior of vertebrae after simulated mild fracture and to identify the determinants of this postfracture behavior. Twenty-one human L(3) vertebrae were analyzed for bone mineral density (BMD) by dual-energy X-ray absorptiometry (DXA) and for microarchitecture by micro-computed tomography (µCT). Mechanical testing was performed in two phases: initial compression of vertebra to 25% deformity, followed, after 30 minutes of relaxation, by a similar test to failure to determine postfracture behavior. We assessed (1) initial and postfracture mechanical parameters, (2) changes in mechanical parameters, (3) postfracture elastic behavior by recovery of vertebral height after relaxation, and (4) postfracture plastic behavior by residual strength and stiffness. Postfracture failure load and stiffness were 11% ± 19% and 53% ± 18% lower than initial values (p = .021 and p < .0001, respectively), with 29% to 69% of the variation in the postfracture mechanical behavior explained by the initial values. Both initial and postfracture mechanical behaviors were significantly correlated with bone mass and microarchitecture. Vertebral deformation recovery averaged 31% ± 7% and was associated with trabecular and cortical thickness (r = 0.47 and r = 0.64; p = .03 and p = .002, respectively). Residual strength and stiffness were independent of bone mass and initial mechanical behavior but were related to trabecular and cortical microarchitecture (|r| = 0.50 to 0.58; p = .02 to .006). In summary, we found marked variation in the postfracture load-bearing capacity following simulated mild vertebral fractures. Bone microarchitecture, but not bone mass, was associated with postfracture mechanical behavior of vertebrae.


Assuntos
Fraturas por Compressão , Vértebras Lombares/anatomia & histologia , Vértebras Lombares/química , Fenômenos Mecânicos , Absorciometria de Fóton , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Fenômenos Biomecânicos , Densidade Óssea , Força Compressiva , Elasticidade , Feminino , Dureza , Humanos , Masculino , Pessoa de Meia-Idade , Caracteres Sexuais , Microtomografia por Raio-X
7.
J Orthop Res ; 29(4): 481-8, 2011 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-20957742

RESUMO

Previous studies have shown that the mechanical properties of trabecular bone are determined by bone volume fraction (BV/TV) and microarchitecture. The purpose of this study was to explore other possible determinants of the mechanical properties of vertebral trabecular bone, namely collagen cross-link content, microdamage, and mineralization. Trabecular bone cores were collected from human L2 vertebrae (n = 49) from recently deceased donors 54-95 years of age (21 men and 27 women). Two trabecular cores were obtained from each vertebra, one for preexisting microdamage and mineralization measurements, and one for BV/TV and quasi-static compression tests. Collagen cross-link content (PYD, DPD, and PEN) was measured on surrounding trabecular bone. Advancing age was associated with impaired mechanical properties, and with increased microdamage, even after adjustment by BV/TV. BV/TV was the strongest determinant of elastic modulus and ultimate strength (r² = 0.44 and 0.55, respectively). Microdamage, mineralization parameters, and collagen cross-link content were not associated with mechanical properties. These data indicate that the compressive strength of human vertebral trabecular bone is primarily determined by the amount of trabecular bone, and notably unaffected by normal variation in other factors, such as cross-link profile, microdamage and mineralization.


Assuntos
Calcificação Fisiológica/fisiologia , Colágeno/metabolismo , Reagentes de Ligações Cruzadas/metabolismo , Vértebras Lombares/patologia , Idoso , Idoso de 80 Anos ou mais , Aminoácidos/metabolismo , Arginina/análogos & derivados , Arginina/metabolismo , Biomarcadores/metabolismo , Força Compressiva , Feminino , Humanos , Vértebras Lombares/metabolismo , Lisina/análogos & derivados , Lisina/metabolismo , Masculino , Pessoa de Meia-Idade , Estresse Mecânico , Suporte de Carga
8.
Arthritis Care Res (Hoboken) ; 62(12): 1699-705, 2010 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-20665746

RESUMO

OBJECTIVE: To investigate whether knowledge of the sequence of radiographs impacts inter- and intraobserver reproducibility and sensitivity to change for measuring joint space width (JSW) in patients with knee osteoarthritis (OA). METHODS: A cohort of 70 postmenopausal women with radiologic knee OA was assessed through the measurement of knee radiographs acquired in the semiflexed posteroanterior view, using a positioning frame and fluoroscopy, at baseline and 48 months later. Paired readings of radiographs were made using landmarks at baseline by 2 independent observers unblinded to sequence and blinded to sequence. Intra- and interobserver reproducibility was assessed on JSW measurements at baseline and 4 years later and on the longitudinal difference (joint space narrowing [JSN]), using intraclass correlation coefficient (ICC) and Bland and Altman methods. The sensitivity to change was assessed through standardized response means (SRMs). RESULTS: For JSW and JSN and with both methods, ICCs were high for the intra- and interobserver reproducibility (0.90-0.99 for JSW and 0.77-0.89 for JSN). For the Bland-Altman method, the mean difference was close to 0, with no bias for both observers and methods. The SRMs ranged from 0.38 to 0.48. All of the results were numerically in favor of measuring with knowledge of time sequence, but without a statistically significant difference between the methods. CONCLUSION: Intra- and interobserver reproducibility was high with or without blinding of the radiograph sequence. Reading with knowledge of time sequence using baseline landmarks tended to improve sensitivity. Therefore, in longitudinal studies of OA radiographs can be read unblinded to sequence.


Assuntos
Articulação do Joelho/diagnóstico por imagem , Osteoartrite do Joelho/diagnóstico por imagem , Tomografia Computadorizada por Raios X/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Seguimentos , Humanos , Pessoa de Meia-Idade , Curva ROC , Reprodutibilidade dos Testes , Estudos Retrospectivos , Sensibilidade e Especificidade
9.
J Bone Miner Res ; 25(2): 356-61, 2010 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-19653808

RESUMO

Whereas there is clear evidence for a strong influence of bone quantity (i.e., bone mass or bone mineral density) on vertebral mechanical behavior, there are fewer data addressing the relative influence of cortical and trabecular bone microarchitecture. The aim of this study was to determine the relative contributions of bone mass, trabecular microarchitecture, and cortical thickness and curvature to the mechanical behavior of human lumbar vertebrae. Thirty-one L3 vertebrae (16 men, 15 women, aged 75 +/- 10 years and 76 +/- 10 years, respectively) were obtained. Bone mineral density (BMD) of the vertebral body was assessed by lateral dual energy X-ray absorptiometry (DXA), and 3D trabecular microarchitecture and anterior cortical thickness and curvature was assessed by micro-computed tomography (microCT). Then compressive stiffness, work to failure, and failure load were measured on the whole vertebral body. BMD was correlated with compressive stiffness (r = 0.60), failure load (r = 0.70), and work to failure (r = 0.55). Except for the degree of anisotropy, all trabecular and cortical parameters were correlated with mechanical behavior (r = 0.36 to 0.58, p = .05 to .001, and r = 0.36 to 0.61, p = .05 to .0001, respectively). Stepwise and multiple regression analyses indicated that the best predictor of (1) failure load was the combination of BMD, structural model index (SMI), and trabecular thickness (Tb.Th) (R = 0.80), (2) stiffness was the combination of BMD, Tb.Th, and curvature of the anterior cortex (R = 0.82), and (3) work to failure was the combination of anterior cortical thickness and BMD (R = 0.68). Our data imply that measurements of cortical thickness and curvature may enhance prediction of vertebral fragility and that therapies that improve both vertebral cortical and trabecular bone properties may provide a greater reduction in fracture risk.


Assuntos
Densidade Óssea , Vértebras Lombares/diagnóstico por imagem , Absorciometria de Fóton , Idoso , Idoso de 80 Anos ou mais , Fenômenos Biomecânicos , Células Cultivadas , Feminino , Humanos , Vértebras Lombares/fisiologia , Masculino , Análise de Regressão
10.
J Bone Miner Res ; 25(11): 2324-31, 2010 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-20564249

RESUMO

Low bone mineral density (BMD) is a strong risk factor for vertebral fracture risk in osteoporosis. However, many fractures occur in people with moderately decreased or normal BMD. Our aim was to assess the contributions of trabecular microarchitecture and its heterogeneity to the mechanical behavior of human lumbar vertebrae. Twenty-one human L(3) vertebrae were analyzed for BMD by dual-energy X-ray absorptiometry (DXA) and microarchitecture by high-resolution peripheral quantitative computed tomography (HR-pQCT) and then tested in axial compression. Microarchitecture heterogeneity was assessed using two vertically oriented virtual biopsies--one anterior (Ant) and one posterior (Post)--each divided into three zones (superior, middle, and inferior) and using the whole vertebral trabecular volume for the intraindividual distribution of trabecular separation (Tb.Sp*SD). Heterogeneity parameters were defined as (1) ratios of anterior to posterior microarchitectural parameters and (2) the coefficient of variation of microarchitectural parameters from the superior, middle, and inferior zones. BMD alone explained up to 44% of the variability in vertebral mechanical behavior, bone volume fraction (BV/TV) up to 53%, and trabecular architecture up to 66%. Importantly, bone mass (BMD or BV/TV) in combination with microarchitecture and its heterogeneity improved the prediction of vertebral mechanical behavior, together explaining up to 86% of the variability in vertebral failure load. In conclusion, our data indicate that regional variation of microarchitecture assessment expressed by heterogeneity parameters may enhance prediction of vertebral fracture risk.


Assuntos
Vértebras Lombares/anatomia & histologia , Vértebras Lombares/fisiologia , Idoso , Idoso de 80 Anos ou mais , Fenômenos Biomecânicos/fisiologia , Feminino , Humanos , Vértebras Lombares/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade , Modelos Biológicos , Tamanho do Órgão , Análise de Regressão , Tomografia Computadorizada por Raios X
11.
Arthritis Rheum ; 61(3): 336-43, 2009 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-19248124

RESUMO

OBJECTIVE: To analyze a population-based cohort of women in order to establish normal values of joint space width (JSW) and to evaluate the existence of age-related joint space loss (JSL). METHODS: Knee radiographs were performed 4 years apart in women from the OFELY (Os des Femmes de Lyon) Cohort. Posteroanterior radiographs of both knees were taken in semiflexion with a standardized fluoroscopically assisted protocol. Radiographs were qualitatively evaluated using a scoring system based on the Altman score that assessed joint space narrowing, osteophytes, and sclerosis for each tibiofemoral compartment and each side. For quantitative assessment, radiographs were digitized using a video camera, and specific software was used to measure JSW in every compartment. RESULTS: We evaluated the radiographs of 606 women (ages 39-90 years, mean 62 years) and found that in all subjects, JSW significantly decreased with age in every compartment (r = -0.12 to -0.16, P < 0.001), including in 358 subjects without any radiographic abnormality related to osteoarthritis (OA) at baseline. The longitudinal analysis confirmed a significant loss over 4 years of approximately 0.30 mm (6%) for the medial compartment. Multiple regression analysis did not identify significant predictors of JSL among clinical risk factors and biochemical markers of bone and cartilage turnover. CONCLUSION: In this first longitudinal study of a population-based cohort of women, we have established normal values of JSW and shown that JSW decreases with aging, especially at the medial compartment, even in subjects without any radiographic abnormalities related to OA.


Assuntos
Envelhecimento/fisiologia , Articulação do Joelho/diagnóstico por imagem , Articulação do Joelho/fisiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Interpretação de Imagem Assistida por Computador , Articulação do Joelho/anatomia & histologia , Estudos Longitudinais , Pessoa de Meia-Idade , Osteoartrite do Joelho/diagnóstico por imagem , Radiografia , Valores de Referência
12.
J Bone Miner Res ; 23(10): 1613-8, 2008 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-18518771

RESUMO

It has been suggested that accumulation of microdamage with age contributes to skeletal fragility. However, data on the age-related increase in microdamage and the association between microdamage and trabecular microarchitecture in human vertebral cancellous bone are limited. We quantified microdamage in cancellous bone from human lumbar (L(2)) vertebral bodies obtained from 23 donors 54-93 yr of age (8 men and 15 women). Damage was measured using histologic techniques of sequential labeling with chelating agents and was related to 3D microarchitecture, as assessed by high-resolution microCT. There were no significant differences between sexes, although women tended to have a higher microcrack density (Cr.Dn) than men. Cr.Dn increased exponentially with age (r = 0.65, p < 0.001) and was correlated with bone volume fraction (BV/TV; r = -0.55; p < 0.01), trabecular number (Tb.N; r = -0.56 p = 0.008), structure model index (SMI; r = 0.59; p = 0.005), and trabecular separation (Tb.Sp; r = 0.59; p < 0.009). All architecture parameters were strongly correlated with each other and with BV/TV. Stepwise regression showed that SMI was the best predictor of microdamage, explaining 35% of the variance in Cr.Dn and 20% of the variance in diffuse damage accumulation. In addition, microcrack length was significantly greater in the highest versus lowest tertiles of SMI. In conclusion, in human vertebral cancellous bone, microdamage increases with age and is associated with low BV/TV and a rod-like trabecular architecture.


Assuntos
Coluna Vertebral/ultraestrutura , Idoso , Idoso de 80 Anos ou mais , Densidade Óssea , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Reprodutibilidade dos Testes
13.
J Bone Miner Res ; 23(2): 215-22, 2008 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-17922612

RESUMO

UNLABELLED: Strontium ranelate is a new anti-osteoporotic treatment. On bone biopsies collected from humans receiving long-term treatment over 5 yr, it has been shown that strontium ranelate has good bone safety and better results than placebo on 3D microarchitecture. Hence, these effects may explain the decreased fracture rate. INTRODUCTION: Strontium ranelate's mode of action involving dissociation of bone formation and resorption was shown in preclinical studies and could explain its antifracture efficacy in humans. MATERIALS AND METHODS: One hundred forty-one transiliac bone biopsies were obtained from 133 postmenopausal osteoporotic women: 49 biopsies after 1-5 yr of 2 g/d strontium ranelate and 92 biopsies at baseline or after 1-5 yr of placebo. RESULTS AND CONCLUSIONS: Histomorphometry provided a 2D demonstration of the bone safety of strontium ranelate, with significantly higher mineral apposition rate (MAR) in cancellous bone (+9% versus control, p = 0.019) and borderline higher in cortical bone (+10%, p = 0.056). Osteoblast surfaces were significantly higher (+38% versus control, p = 0.047). 3D analysis of 3-yr biopsies with treatment (20 biopsies) and placebo (21 biopsies) using microCT showed significant changes in microarchitecture with, in the strontium ranelate group, higher cortical thickness (+18%, p = 0.008) and trabecular number (+14%, p = 0.05), and lower structure model index (-22%, p = 0.01) and trabecular separation (-16%, p = 0.04), with no change in cortical porosity. The changes in 3D microarchitecture may enhance bone biomechanical competence and explain the decreased fracture rate with strontium ranelate.


Assuntos
Ílio/efeitos dos fármacos , Compostos Organometálicos/uso terapêutico , Osteoporose Pós-Menopausa/tratamento farmacológico , Tiofenos/uso terapêutico , Idoso , Biópsia , Remodelação Óssea/efeitos dos fármacos , Método Duplo-Cego , Feminino , Histocitoquímica , Humanos , Ílio/patologia , Pessoa de Meia-Idade , Compostos Organometálicos/efeitos adversos , Osteoblastos/efeitos dos fármacos , Osteoblastos/patologia , Osteogênese/efeitos dos fármacos , Osteoporose Pós-Menopausa/diagnóstico por imagem , Pós-Menopausa , Tiofenos/efeitos adversos , Tempo , Tomografia Computadorizada por Raios X/instrumentação , Tomografia Computadorizada por Raios X/métodos
14.
Calcif Tissue Int ; 77(4): 195-204, 2005 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-16193237

RESUMO

In osteoporosis, bone fragility results from both bone loss and changes in trabecular microarchitecture, which can be quantified by bone histomorphometric parameters. Twenty human calcaneum were collected after necropsy. All measurements were performed at the same anatomical location. Bone histomorphometric parameters were measured on histological slides with an automatic image analyzer. The aims of our study were (1) to develop automatic measurements of four additional parameters reflecting trabecular network connectivity and complexity, i.e., trabecular bone pattern factor (TBPf), Euler number/tissue volume (Euler) according to the three definitions previously reported and to a fourth one established in the laboratory (Euler(strut.cavity)), marrow star volume, and interconnectivity index, and to determine their usefulness in microarchitecture characterization; and (2) to validate these parameters by evaluating their relationship with dual-energy X-ray absorptiometry and quantitative ultrasound (QUS) measurements performed on the same samples. The statistical analysis showed that TBPf and Euler(strut.cavity) appeared to be the most significant connectivity parameters, independently of bone quantity (bone mineral density, apparent density, cancellous bone volume). For QUS, after adjustment for bone quantity, only speed of sound (SOS) was significantly and negatively correlated to Euler(strut.cavity). Broadband ultrasound attenuation depends only on bone quantity. In conclusion, TBPf (a strut analysis parameter extrapolable in three dimensions) and Euler(strut.cavity) (the only bone connectivity parameter reflecting SOS) are two valid bone microarchitecture parameters. These new parameters were significantly correlated to the established trabecular structure parameters: trabecular thickness or trabecular spacing, being weakly correlated with SOS.


Assuntos
Absorciometria de Fóton/métodos , Densidade Óssea , Crânio , Ultrassonografia/métodos , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Processamento de Imagem Assistida por Computador , Masculino , Pessoa de Meia-Idade , Reprodutibilidade dos Testes , Crânio/anatomia & histologia , Crânio/diagnóstico por imagem
15.
Rev Med Suisse Romande ; 124(2): 91-2, 2004 Feb.
Artigo em Francês | MEDLINE | ID: mdl-15095621

RESUMO

Alendronate and teparatide, recombinant human PTH (1-34) are available treatment for osteoporosis in postmenopausal women. They act through opposite mechanisms of action. Alendronate reduces the remodeling of bone and thus increases secondary mineralization without any change in the amount of bone. Teriparatide, 20 micrograms/day, a bone forming agent would increase the amount of bone through two mechanisms, modeling--formation without resorption, and remodeling--resorption then formation with formation higher than resorption. Theses effects are present at the sixth month.


Assuntos
Alendronato/uso terapêutico , Osteoporose/tratamento farmacológico , Osteoporose/patologia , Hormônio Paratireóideo/uso terapêutico , Feminino , Humanos , Teriparatida/uso terapêutico
16.
Arthritis Rheum ; 50(10): 3137-44, 2004 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-15476251

RESUMO

OBJECTIVE: To investigate whether radiologic spine disc degeneration is associated with increased type II collagen (CII) degradation products in the urine of postmenopausal women, independently of radiologic knee osteoarthritis (OA) and clinical hand OA. METHODS: The study group comprised 324 postmenopausal women ages 58-94 years who had no treatment or disease that could alter bone metabolism. Lateral radiographs of the thoracic and lumbar spine were obtained in each woman and scored for disc space narrowing (DSN) and osteophytes. Fixed-flexion posteroanterior radiographs of the knee were obtained to assess femorotibial knee OA. In all women, hand OA was assessed by clinical examination, and the level of urinary C-terminal crosslinking telopeptide of CII (CTX-II), a biologic marker of CII degradation, was measured. RESULTS: The prevalences of radiographic lumbar and thoracic spine disc degeneration, knee OA, and clinical hand OA were 84%, 88%, 35%, and 58%, respectively. After adjustment for age and body mass index (BMI), patients with lumbar spine DSN grade > or = 1 had, on average, 34% higher CTX-II levels compared with the other women (P = 0.0005), whereas no association was observed with lumbar spine osteophytes. No significant association between thoracic spine DSN or osteophytes and urinary CTX-II levels was observed. Multivariate analysis of variance showed that, after adjustment for age and BMI, lumbar spine DSN (P = 0.0049), knee OA (P = 0.0055), and clinical hand OA (P = 0.0060) were, independently of each other, associated with CTX-II levels. Thus, patients with lumbar spine DSN, knee OA, and clinical hand OA had CTX-II levels 80% higher (P < 0.0001 after adjustment for age and BMI) than those of patients with no lumbar spine DSN, no radiologic knee OA, and no clinical hand OA. CONCLUSION: Postmenopausal women with lumbar spine disc degeneration are characterized by increased CII degradation. The contribution of lumbar spine DSN to CII degradation was similar to, and independent of, the contribution of radiologic knee OA or clinical hand OA. Lumbar spine disc degeneration in elderly patients should be assessed when analyzing levels of CTX-II in studies of knee, hip, and hand OA.


Assuntos
Colágeno Tipo II/metabolismo , Pós-Menopausa/fisiologia , Doenças da Coluna Vertebral/urina , Adulto , Idoso , Colágeno Tipo II/urina , Feminino , Mãos/diagnóstico por imagem , Humanos , Disco Intervertebral , Articulação do Joelho/diagnóstico por imagem , Vértebras Lombares/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade , Osteoartrite/diagnóstico por imagem , Fragmentos de Peptídeos/urina , Radiografia , Doenças da Coluna Vertebral/diagnóstico por imagem , Osteofitose Vertebral/patologia , Estenose Espinal/diagnóstico por imagem , Vértebras Torácicas/diagnóstico por imagem
17.
Rev Med Suisse Romande ; 124(2): 71-2, 2004 Feb.
Artigo em Francês | MEDLINE | ID: mdl-15095615

RESUMO

Bone quality can be defined by the ability to resist fracture. Biomechanical testing represents a direct approach to evaluate bone quality. This quality is dependent of several determinants: intrinsic properties of bone including mineral and organic phases, amount of bone, bone architecture and bone size. These determinants are more or less linked to bone turnover, an absence or excessive one increasing bone fragility. Consequently, a minimum but not excessive level of bone turnover must be preserved in osteoporosis treatment.


Assuntos
Absorciometria de Fóton/métodos , Densidade Óssea , Humanos
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