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1.
Gerontology ; 65(6): 699-706, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31505504

RESUMO

The Tyrolean Iceman, commonly known as Ötzi, is the world's oldest glacier mummy and one of the best investigated ancient human remains in the world. Since the discovery of the 5,300-year-old Copper Age individual in 1991, in a glacier in the Eastern Italian Alps, a variety of morphological, biochemical, and molecular analyses have been performed that revealed important insights into his origin, his life habits, and the circumstances surrounding his demise. In more recent research, the mummy was subjected to cutting-edge modern research methodologies currently focusing on high-throughput sequence analysis of ancient biomolecules (DNA, proteins, lipids) that are still preserved in the mummified tissues. This application of innovative "-omics" technologies revealed novel insights on the ancestry, disease predisposition, diet, and the presence of pathogens in the glacier mummy. In this review, the most important and actual results of the molecular studies will be highlighted.


Assuntos
Múmias , Cromossomos Humanos Y , Grupos de Populações Continentais/genética , DNA/isolamento & purificação , Dieta , Conteúdo Gastrointestinal , Genoma Humano , Helicobacter pylori/genética , Helicobacter pylori/isolamento & purificação , História Antiga , Humanos , Camada de Gelo , Ílio/química , Múmias/história , Fibras Musculares Esqueléticas/patologia , Estômago/microbiologia , Estômago/patologia , Sequenciamento Completo do Genoma
2.
J Clin Endocrinol Metab ; 100(12): 4662-8, 2015 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-26505821

RESUMO

CONTEXT: The levels of bone formation and resorption can be assessed at the tissue level by bone histomorphometry on transiliac bone biopsies. Systemic biochemical markers of bone turnover reflect the overall bone formation and resorption at the level of the entire skeleton but cannot discriminate the different skeletal compartments. OBJECTIVE: Our aim was to investigate the correlations between the serum biochemical markers of formation and resorption with histomorphometric parameters. DESIGN: We performed post hoc analysis of a previous clinical study. SETTING: Patients were selected from the general population. PATIENTS: A total of 371 untreated postmenopausal osteoporotic women aged 50 to 84 years with a lumbar T-score ≤ -2.5 SD or ≤ -1 SD with at least one osteoporotic fracture. INTERVENTIONS: Transiliac bone biopsies were obtained after a double tetracycline labeling, and blood samples were collected. MAIN OUTCOME MEASURES: The static and dynamic parameters of formation and bone resorption were measured by histomorphometry. Serum biochemical markers of formation (bone alkaline phosphatase [ALP]; procollagen type I N-terminal propeptide [PINP]) and resorption (C-terminal crosslinking telopeptide of collagen type 1 [sCTX]) were assessed. RESULTS: The mean values of biochemical markers were: bone ALP, 15.0 ± 5.2 ng/mL; PINP, 56.2 ± 21.9 µg/mL; and sCTX, 0.58 ± 0.26 ng/mL. Bone ALP and PINP were significantly correlated with both the static and dynamic parameters of formation (0.21 ≤ r' ≤ 0.36; 0.01 ≥ P ≥ .0001). sCTX was significantly correlated with all resorption parameters (0.18 ≤ r' ≤ 0.24; 0.02 ≥ P ≥ .0001). CONCLUSION: Bone turnover markers were significantly but modestly associated with bone turnover parameters measured in iliac cancellous bone. The iliac crest bone may not represent perfectly the whole bone turnover.


Assuntos
Biomarcadores/metabolismo , Remodelação Óssea , Osso e Ossos/patologia , Pós-Menopausa/metabolismo , Idoso , Idoso de 80 Anos ou mais , Fosfatase Alcalina/genética , Fosfatase Alcalina/metabolismo , Reabsorção Óssea/genética , Colágeno Tipo II/genética , Colágeno Tipo II/metabolismo , Feminino , Humanos , Ílio/química , Ílio/metabolismo , Testes de Função Renal , Pessoa de Meia-Idade , Osteogênese/genética , Osteoporose/metabolismo , Osteoporose/patologia , Fraturas por Osteoporose/metabolismo , Fraturas por Osteoporose/patologia , Fragmentos de Peptídeos/genética , Fragmentos de Peptídeos/metabolismo , Pró-Colágeno/genética , Pró-Colágeno/metabolismo
3.
Bone ; 81: 161-167, 2015 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-26164477

RESUMO

Deposition of calcium oxalate crystals in the kidney and bone is a hallmark of systemic oxalosis. Since the bone compartment can store massive amounts of oxalate, patients present with recurrent low-trauma fractures, bone deformations, severe bone pains and specific oxalate osteopathy on plain X-ray. Bone biopsy from the iliac crest displays specific features such as oxalate crystals surrounded by a granulomatous reaction due to an invasion of bone surface by macrophages. We present data obtained in 10 samples from 8 patients with oxalosis (16-68 years) who underwent iliac crest bone biopsy and bone quality analysis using modern methods (microradiography, microindentation, Fourier Transform InfraRed Microspectroscopy, transmission electron microscopy) in addition to histomorphometry. Disseminated calcium oxalate deposits (whewellite) were found in the bone marrow space (with a granulomatous reaction) but not in the bone matrix. Calcium oxalate deposits were totally surrounded by macrophages and multinucleated giant cells, and a phagocytosis activity was sometimes observed. Very few calcium oxalate crystals were directly in close contact with the mineral substance of the bone. Bone mineralization was not modified by the presence of calcium oxalate even in close vicinity. Bone quality analysis also revealed a harder bone than normal, perhaps in relationship with decreased carbonate content in the mineral. This increase in bone hardness could explain a more "brittle" bone. In patients with oxalosis, the formation and growth of calcium oxalate crystals in the bone appeared independent of apatite. The mechanisms leading to nucleation and growth of oxalate deposits are still unclear and deserve further studies.


Assuntos
Calcificação Fisiológica/fisiologia , Hiperoxalúria/diagnóstico , Hiperoxalúria/metabolismo , Ílio/metabolismo , Ílio/ultraestrutura , Adolescente , Adulto , Idoso , Oxalato de Cálcio/análise , Oxalato de Cálcio/metabolismo , Feminino , Humanos , Ílio/química , Falência Renal Crônica/diagnóstico , Falência Renal Crônica/metabolismo , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Adulto Jovem
4.
J Periodontal Res ; 50(4): 468-78, 2015 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-25225160

RESUMO

BACKGROUND AND OBJECTIVE: The jaw bone, unlike most other bones, is derived from neural crest stem cells, so we hypothesized that it may have different characteristics to bones from other parts of the body, especially in the nature of its periosteum. The periosteum exhibits osteogenic potential and has received considerable attention as a grafting material for the repair of bone and joint defects. MATERIAL AND METHODS: Gene expression profiles of jaw bone and periosteum were evaluated by DNA microarray and real-time polymerase chain reaction. Furthermore, we perforated an area 2 mm in diameter on mouse frontal and parietal bones. Bone regeneration of these calvarial defects was evaluated using microcomputed tomography and histological analysis. RESULTS: The DNA microarray data revealed close homology between the gene expression profiles within the ilium and femur. The gene expression of Wnt-1, SOX10, nestin, and musashi-1 were significantly higher in the jaw bone than in other locations. Microcomputed tomography and histological analysis revealed that the jaw bone had superior bone regenerative abilities than other bones. CONCLUSION: Jaw bone periosteum exhibits a unique gene expression profile that is associated with neural crest cells and has a positive influence on bone regeneration when used as a graft material to repair bone defects. A full investigation of the biological and mechanical properties of jaw bone as an alternative graft material for jaw reconstructive surgery is recommended.


Assuntos
Mandíbula/crescimento & desenvolvimento , Maxila/crescimento & desenvolvimento , Periósteo/crescimento & desenvolvimento , Animais , Desenvolvimento Ósseo/genética , Doenças Ósseas/cirurgia , Regeneração Óssea/genética , Transplante Ósseo/métodos , Fêmur/química , Osso Frontal/patologia , Osso Frontal/cirurgia , Perfilação da Expressão Gênica , Ílio/química , Masculino , Mandíbula/química , Maxila/química , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Endogâmicos , Proteínas do Tecido Nervoso/análise , Nestina/análise , Análise de Sequência com Séries de Oligonucleotídeos , Osteogênese/genética , Osso Parietal/patologia , Osso Parietal/cirurgia , Periósteo/química , Periósteo/transplante , Proteínas de Ligação a RNA/análise , Distribuição Aleatória , Reação em Cadeia da Polimerase em Tempo Real , Fatores de Transcrição SOXE/análise , Proteína Wnt1/análise , Microtomografia por Raio-X/métodos
5.
Clin J Am Soc Nephrol ; 9(7): 1263-70, 2014 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-24763863

RESUMO

BACKGROUND AND OBJECTIVES: Increased bone resorption, low bone formation, and abnormal mineralization have been described in stone formers with idiopathic hypercalciuria. It has been previously shown that the receptor activator of NF-κB ligand mediates bone resorption in idiopathic hypercalciuria (IH). The present study aimed to determine the expression of fibroblast growth factor 23 (FGF-23), vitamin D receptor (VDR), and sclerostin in bone tissue from IH stone formers. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Immunohistochemical analysis was performed in undecalcified bone samples previously obtained for histomorphometry from 30 transiliac bone biopsies of idiopathic hypercalciuria stone-forming patients between 1992 and 2002 and 33 healthy individuals (controls). Serum parameters were obtained from their medical records. RESULTS: Histomorphometry disclosed 21 IH patients with high and 9 IH patients with normal bone resorption. Importantly, eroded surfaces (ES/BS) from IH patients but not controls were significantly correlated with VDR immunostaining in osteoblasts (r=0.51; P=0.004), sclerostin immunostaining in osteocytes (r=0.41; P=0.02), and serum 1,25-dihydroxyvitamin D (r=0.55; P<0.01). Of note, both VDR and sclerostin immunostaining were significantly correlated with serum 1,25-dihydroxyvitamin D in IH patients (r=0.52; P=0.01 and r=0.53; P=0.02, respectively), although VDR and sclerostin expression did not differ between IH and controls. IH patients with high bone resorption exhibited a significantly stronger sclerostin immunostaining than IH patients with normal bone resorption. FGF-23 expression in osteocytes from IH patients did not differ from controls and was not correlated with any histomorphometric parameter. CONCLUSIONS: These findings suggest the contribution of VDR and sclerostin, as well as 1,25-dihydroxyvitamin D, to increase bone resorption in idiopathic hypercalciuria but do not implicate FGF-23 in the bone alterations seen in these patients.


Assuntos
Proteínas Morfogenéticas Ósseas/análise , Fatores de Crescimento de Fibroblastos/análise , Hipercalciúria/metabolismo , Ílio/química , Receptores de Calcitriol/análise , Urolitíase/metabolismo , Adulto , Reabsorção Óssea/metabolismo , Reabsorção Óssea/fisiopatologia , Feminino , Marcadores Genéticos , Humanos , Hipercalciúria/diagnóstico , Hipercalciúria/fisiopatologia , Ílio/fisiopatologia , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Osteoblastos/química , Osteócitos/química , Estudos Retrospectivos , Urolitíase/diagnóstico , Urolitíase/fisiopatologia , Vitamina D/análogos & derivados , Vitamina D/sangue
6.
Int J Clin Exp Pathol ; 7(12): 9099-103, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25674295

RESUMO

Bone epithelioid angiosarcoma (EA) is rare and characterized by large, mildly to moderately pleomorphic epithelioid cells, with abundant eosinophilic cytoplasm, vesicular nuclei, and prominent nucleoli. The tumors may arise in various locations in bone and the patients may present with unifocal or multifocal osseous disease. We present a unifocal lesion case of EA of the ilium in a 62-year-old woman. A needle biopsy of the ilium was performed and first diagnosed poorly differentiated adenocarcinoma based on CKpan and CK18 immunopositivity. The tumor was treated initially with curettage followed by chemotherapy. The final diagnosis on the surgical specimen was epithelioid angiosarcoma.


Assuntos
Adenocarcinoma/patologia , Neoplasias Ósseas/patologia , Células Epitelioides/patologia , Hemangiossarcoma/patologia , Ílio/patologia , Adenocarcinoma/química , Biomarcadores Tumorais/análise , Biópsia , Neoplasias Ósseas/química , Neoplasias Ósseas/terapia , Quimioterapia Adjuvante , Curetagem , Erros de Diagnóstico , Células Epitelioides/química , Células Epitelioides/efeitos dos fármacos , Feminino , Hemangiossarcoma/química , Hemangiossarcoma/terapia , Humanos , Ílio/química , Ílio/efeitos dos fármacos , Ílio/cirurgia , Imuno-Histoquímica , Imagem por Ressonância Magnética , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Tomografia Computadorizada por Raios X , Resultado do Tratamento
7.
J Orthop Res ; 30(5): 700-6, 2012 May.
Artigo em Inglês | MEDLINE | ID: mdl-22034199

RESUMO

The extent to which bone tissue composition varies across anatomic sites in normal or pathologic tissue is largely unknown, although pathologic changes in bone tissue composition are typically assumed to occur throughout the skeleton. Our objective was to compare the composition of normal cortical and trabecular bone tissue across multiple anatomic sites. The composition of cadaveric bone tissue from three anatomic sites was analyzed using Fourier transform infrared imaging: iliac crest (IC), greater trochanter (GT), and subtrochanteric femur (ST). The mean mineral:matrix ratio was 20% greater in the subtrochanteric cortex than in the cortices of the iliac crest (p = 0.004) and the greater trochanter (p = 0.02). There were also trends toward 30% narrower crystallinity distributions in the subtrochanteric cortex than in the greater trochanter (p = 0.10) and 30% wider crystallinity distributions in the subtrochanteric trabeculae than in the greater trochanter (p = 0.054) and the iliac crest (p = 0.11). Thus, the average cortical tissue mineral content and the widths of the distributions of cortical crystal size/perfection differ at the subtrochanteric femur relative to the greater trochanter and the iliac crest. In particular, the cortex of the iliac crest has lower mineral content relative to that of the subtrochanteric femur and may have limited utility as a surrogate for subtrochanteric bone.


Assuntos
Fêmur/química , Ílio/química , Idoso , Idoso de 80 Anos ou mais , Feminino , Fêmur/anatomia & histologia , Humanos , Ílio/anatomia & histologia , Masculino , Pessoa de Meia-Idade , Espectroscopia de Infravermelho com Transformada de Fourier
8.
Clin Biomech (Bristol, Avon) ; 26(6): 556-61, 2011 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-21345556

RESUMO

BACKGROUND: Iliac screw loosening has been a clinical problem in the lumbo-pelvic reconstruction. Although iliac screws are commonly inserted into either upper or lower iliac column, the biomechanical effects of the two fixations and their revision techniques with bone cement remain undetermined. The purpose of this study was to compare the anchoring strengths of the upper and lower iliac screws with and without cement augmentation. METHODS: 5 pairs of formalin fixed cadaveric ilia with the bone mineral density values ranged from 0.82 to 0.97 g/cm(2) were adopted in this study. Using screws with 70-mm length and 7.5-mm diameter, 2 conventional iliac screw fixations and their revision techniques with cement augmentation were sequentially established and tested on the same ilium as follows: upper screw, upper cement screw, lower screw, and lower cement screw. Following 2000 cyclic compressive loading of -300 N to -100 N to the screw on a material testing machine, the maximum pull-out strengths were measured and analyzed. FINDINGS: The average pull-out strengths of upper, upper cement, lower, and lower cement screws were 964 N, 1462 N, 1537 N, and 1964 N, respectively. The lower screw showed significantly higher pull-out strength than the upper one (P=0.008). The cement augmentation notably increased the pull-out strengths of both upper and lower screws. The positive correlation between pull-out strength and bone mineral density value was obtained for the 4 fixations. INTERPRETATION: The lower iliac screw technique should be the preferred choice in lumbo-pelvic stabilization surgery; cement augmentation may serve as a useful salvage technique for iliac screw loosening; preoperative evaluation of bone quality is crucial for predicting fixation strength of iliac screw.


Assuntos
Cimentos para Ossos/química , Parafusos Ósseos , Idoso , Fenômenos Biomecânicos , Densidade Óssea , Feminino , Humanos , Ílio/química , Masculino , Pessoa de Meia-Idade , Ossos Pélvicos/patologia , Pelve/patologia , Estresse Mecânico
9.
J Bone Miner Res ; 25(4): 891-900, 2010 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-20437609

RESUMO

Strontium ranelate (SrR) is a relatively new treatment for osteoporosis. In this study we investigated its potential impact on human bone material quality in transiliac bone biopsies from postmenopausal osteoporotic women treated 3 years with calcium and vitamin D plus either 2 g SrR per day or placebo. Bone mineralization density distribution (BMDD), strontium (Sr) concentration, collagen cross-link ratio, and indentation modulus were analyzed by quantitative backscattered electron imaging, electron-induced X-ray fluorescence analysis, synchrotron radiation induced micro X-ray fluorescence elemental mapping, Fourier transform infrared imaging, and nanoindentation, respectively. The BMDD of SrR-treated patients was shifted to higher atomic numbers (Z(mean) +1.5%, p < .05 versus placebo). We observed Sr being preferentially incorporated in bone packets formed during SrR treatment up to 6% atom fraction [Sr/(Sr + Ca)] depending on the SrR serum levels of the individuals (correlation r = 0.84, p = .018). Collagen cross-link ratio was preserved in SR-treated bone. The indentation modulus was significantly decreased in younger versus older bone packets for both placebo- (-20.5%, p < .0001) and SrR-treated individuals (-24.3%, p < .001), whereas no differences were found between the treatment groups. In conclusion, our findings indicate that after SrR treatment, Sr is heterogeneously distributed in bone and preferentially present in bone packets formed during treatment. The effect of SrR on BMDD seems to be due mainly to the uptake of Sr and not to changes in bone calcium content. Taken together, these data provide evidence that the investigated bone quality determinants at tissue level were preserved in postmenopausal osteoporotic women after 3-year treatment with 2 g SrR per day plus calcium and vitamin D.


Assuntos
Conservadores da Densidade Óssea/uso terapêutico , Densidade Óssea/efeitos dos fármacos , Ílio/patologia , Compostos Organometálicos/uso terapêutico , Osteoporose Pós-Menopausa/tratamento farmacológico , Tiofenos/uso terapêutico , Cálcio/uso terapêutico , Colágeno/química , Módulo de Elasticidade , Feminino , Humanos , Ílio/química , Compostos Organometálicos/análise , Osteoporose Pós-Menopausa/patologia , Tiofenos/análise , Vitamina D/uso terapêutico
10.
J Trace Elem Med Biol ; 24(1): 1-6, 2010 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-20122572

RESUMO

PROJECT: To understand the role of major, minor, and trace elements in the etiology of bone diseases including osteoporosis, it is necessary to determine the normal levels and age-related changes of bone chemical elements. PROCEDURE: The effect of age and gender on 38 chemical element contents in intact iliac crest of 84 apparently healthy 15-55 years old women (n=38) and men (n=46) was investigated by neutron activation analysis. RESULTS: Mean values (M+/-SEM) for mass fraction (on dry weight basis) of Ca, Cl, Co, Fe, K, Mg, Mn, Na, P, Rb, Sr, and Zn for both female and male taken together were Ca - 169+/-3g/kg, Cl - 1490+/-43 mg/kg, Co - 0.0073+/-0.0024 mg/kg, Fe - 177+/-24 mg/kg, K - 1820+/-79 mg/kg, Mg - 1840+/-48 mg/kg, Mn - 0.316+/-0.013 mg/kg, Na - 4970+/-87 mg/kg, P - 79.7+/-1.5 g/kg, Rb - 1.89+/-0.22 mg/kg, Sr - 312+/-15 mg/kg, and Zn - 65.9+/-3.4 mg/kg, respectively. The upper limit of mean contents of Cs, Eu, Hg, Sb, Sc, and Se were Cs < or = 0.09 mg/kg, Eu < or = 0.005 mg/kg, Hg < or = 0.005 mg/kg, Sb < or = 0.004 mg/kg, Sc < or = 0.001 mg/kg, and Se < or = 0.1mg/kg, respectively. In all bone samples the contents of Ag, As, Au, Ba, Br, Cd, Ce, Cr, Gd, Hf, La, Lu, Nd, Sm, Ta, Tb, Th, U, Yb, and Zr were under detection limits. CONCLUSIONS: The Ca, Mg, and P contents decrease with age, regardless of gender. Higher Ca, Mg, P, and Sr mass fractions as well as lower Fe content are typical of female iliac crest as compared to those in male bone.


Assuntos
Ílio/química , Oligoelementos/análise , Adolescente , Adulto , Fatores Etários , Doenças Ósseas/etiologia , Feminino , Humanos , Limite de Detecção , Masculino , Pessoa de Meia-Idade , Análise de Ativação de Nêutrons/métodos , Fatores Sexuais
11.
Ann Vasc Surg ; 24(3): 367-72, 2010 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-19896796

RESUMO

INTRODUCTION: In a prospective trial we tested whether adjunctive intraoperative stem cell treatment in patients with critical limb ischemia (CLI) can be performed safely in combination with bypass surgery and/or interventional treatment. The end point of our study was the safety and integrity of a novel point-of-care system used in patients with CLI. METHODS: We included only patients with CLI and tissue loss according to Rutherford categories 4-6. The Harvest Bone Marrow Aspirate Concentrate System consists of an automated, microprocessor-controlled dedicated centrifuge with decanting capability and the accessory BMAC Pack for processing a patient's bone marrow aspirate (BMA). The centrifuge is portable and enables BMA to be rapidly processed in the operating room to provide an autologous concentrate of nucleated cells for immediate injection. The surgeon aspirated 120 ml BMA from the iliac crest. RESULTS: Eight consecutive patients were treated according to the study protocol. The mean follow-up period was 9.2 months (range 2-18). Stem cells were always injected during the final revascularization attempt. One minor amputation and two major amputations were required. In five of eight patients there was a discrete increase in the ankle-brachial index post-stem cell treatment. The dose of stem cells after centrifugation was 17.2 (range 13.8-54.2)x10E6 CD34-positive cells and 7.8 (range 1.8-35.9)x10E6 CD133-positive cells. The injected dose of VEGFR-2-coexpressing stem cells was 0.5-5.7x10E4. CONCLUSION: We were able to show that the buffy coat preparation using a point-of-care system is a simple and fast method to enrich stem cells from BMAs. This automated system gives high recovery rates and good reproducibility.


Assuntos
Transplante de Medula Óssea/instrumentação , Isquemia/cirurgia , Extremidade Inferior/irrigação sanguínea , Sistemas Automatizados de Assistência Junto ao Leito , Transplante de Células-Tronco/instrumentação , Procedimentos Cirúrgicos Vasculares , Antígeno AC133 , Adulto , Idoso , Idoso de 80 Anos ou mais , Amputação , Antígenos CD/análise , Antígenos CD34/análise , Transplante de Medula Óssea/efeitos adversos , Separação Celular/instrumentação , Sobrevivência Celular , Centrifugação/instrumentação , Estado Terminal , Desenho de Equipamento , Glicoproteínas/análise , Humanos , Ílio/química , Ílio/citologia , Ílio/imunologia , Período Intraoperatório , Salvamento de Membro , Pessoa de Meia-Idade , Peptídeos/análise , Estudos Prospectivos , Reoperação , Transplante de Células-Tronco/efeitos adversos , Fatores de Tempo , Resultado do Tratamento , Receptor 2 de Fatores de Crescimento do Endotélio Vascular/análise , Procedimentos Cirúrgicos Vasculares/efeitos adversos
12.
J Bone Miner Res ; 25(5): 968-75, 2010 May.
Artigo em Inglês | MEDLINE | ID: mdl-19874195

RESUMO

Strontium ranelate has been shown to increase bone mass in postmenopausal osteoporosis patients and to reduce fracture risk. The aim of this study was to investigate the potential influence of strontium ranelate (Protelos) treatment on human bone tissue characteristics and quality at the micro- and nanostructural levels. We investigated transiliac biopsies from patients treated for 36 months with strontium ranelate or placebo (n = 5 per group) using synchrotron radiation with a microbeam combining scanning small-angle scattering, X-ray diffraction, and fluorescence spectroscopy (SAXS/XRD/XRF) for a detailed characterization of the mineral crystals within the collagenous bone matrix. A scanning procedure allowed the simultaneous determination of maps of the chemical composition together with thickness, length, and lattice spacing of these mineral crystals within each of the 15- or 25-microm-wide pixels in a thin bone section. The fluorescence results show that only bone packets or osteons formed during the strontium ranelate treatment contain significant amounts of strontium and that up to 0.5 of 10 calcium atoms in the mineral crystals are replaced by strontium, as revealed by a corresponding shift in apatite lattice spacing. The thickness and length of the plate-shaped bone mineral crystals were not affected by the strontium ranelate treatment. As a consequence, there was no indication for a change in human bone tissue quality at the nanoscale after a 36-month treatment of postmenopausal osteoporotic women with strontium ranelate, except for a partial replacement of calcium by strontium ions in the hydroxyapatite crystals, only in newly formed bone.


Assuntos
Conservadores da Densidade Óssea/uso terapêutico , Osso e Ossos/metabolismo , Compostos Organometálicos/uso terapêutico , Osteoporose Pós-Menopausa/tratamento farmacológico , Estrôncio/metabolismo , Tiofenos/uso terapêutico , Biópsia , Durapatita/química , Feminino , Humanos , Ílio/química , Espalhamento a Baixo Ângulo , Espectrometria por Raios X , Difração de Raios X
13.
Tissue Eng Part A ; 15(11): 3547-58, 2009 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-19459781

RESUMO

Autologous bone graft, the standard of bone grafting in achieving spinal fusion, is associated with several limitations and complications. The use of bone marrow cells (BMCs) as a potential cell source for spinal fusion, combined with a suitable scaffold to promote bone formation, may be a better choice. The aims of this study were to evaluate the efficacy of natural bone collagen scaffold (NBCS) combined with autologous-enriched BMCs for induction of osteogenesis in vitro and in vivo. Ovine-enriched BMCs were co-cultured with NBCS for 1, 2, 3, and 4 weeks to investigate whether NBCS would support the population expansion and differentiation of enriched BMCs. Using an ovine interbody fusion model, NBCS seeded with autologous enriched BMCs was implanted into the lumbar disc space. Fusion outcomes were compared with the use of the autograft, NBCS without BMCs, and BMCs without NBCS. In vitro results demonstrated that NBCS facilitated the population expansion and differentiation of ovine-enriched BMCs, promoting the expression of collagen type I and the formation of a mineralized matrix. The use of NBCS combined with enriched BMCs in vivo enhanced the spinal fusion rate (6 of 6 at 10 week) (p < 0.05), the biomechanical stiffness of fusion masses, and bone volume at the fusion site (p < 0.05). Histological findings also revealed that a combination of NBCS and BMCs induced new bone formation that integrated well with host bone tissue. In conclusion, NBCS is an effective scaffold that supports ovine-enriched BMCs. The combination of NBCS and BMCs may be a useful alternative for autograft in induction of spinal fusion.


Assuntos
Transplante de Medula Óssea/instrumentação , Transplante Ósseo/instrumentação , Transplante Ósseo/métodos , Colágeno/química , Regeneração Tecidual Guiada/instrumentação , Ílio/química , Ílio/citologia , Osteogênese/fisiologia , Fusão Vertebral/instrumentação , Animais , Transplante de Medula Óssea/métodos , Células Cultivadas , Regeneração Tecidual Guiada/métodos , Ovinos , Fusão Vertebral/métodos , Resultado do Tratamento
14.
Clin J Am Soc Nephrol ; 3(5): 1446-52, 2008 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-18480302

RESUMO

BACKGROUND AND OBJECTIVES: This study aimed to determine the expression of osteoprotegerin, receptor activator of nuclear factor kappaB ligand, interleukin-1alpha, transforming growth factor-beta, and basic fibroblast growth factor in stone-forming patients with idiopathic hypercalciuria. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Immunohistochemical analysis was performed in undecalcified bone samples previously obtained from 36 transiliac bone biopsies of patients who had idiopathic hypercalciuria and whose histomorphometry had shown lower bone volume, increased bone resorption, and prolonged mineralization lag time. RESULTS: Bone expression of receptor activator of nuclear factor kappaB ligand and osteoprotegerin was significantly higher in patients with idiopathic hypercalciuria versus control subjects. Transforming growth factor-beta immunostaining was lower in patients with idiopathic hypercalciuria than in control subjects and correlated directly with mineralization surface. Interleukin-1alpha and basic fibroblast growth factor staining did not differ between groups. Receptor activator of nuclear factor kappaB ligand bone expression was significantly higher in patients who had idiopathic hypercalciuria and exhibited higher versus normal bone resorption. CONCLUSION: A higher expression of receptor activator of nuclear factor kappaB ligand in bone tissue suggests that increased bone resorption in patients with idiopathic hypercalciuria is mediated by receptor activator of nuclear factor kappaB ligand. Osteoprotegerin bone expression might have been secondarily increased in an attempt to counteract the actions of receptor activator of nuclear factor kappaB ligand. The low bone expression of transforming growth factor-beta could contribute to the delayed mineralization found in such patients.


Assuntos
Reabsorção Óssea/etiologia , Hipercalciúria/metabolismo , Ílio/química , Ligante RANK/análise , Adulto , Densidade Óssea , Reabsorção Óssea/metabolismo , Reabsorção Óssea/patologia , Estudos de Casos e Controles , Feminino , Fator 2 de Crescimento de Fibroblastos/análise , Humanos , Hipercalciúria/complicações , Hipercalciúria/patologia , Ílio/patologia , Imuno-Histoquímica , Interleucina-1alfa/análise , Masculino , Pessoa de Meia-Idade , Osteoprotegerina/análise , Fator de Crescimento Transformador beta/análise , Regulação para Cima
15.
Bone ; 39(6): 1190-5, 2006 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-16901772

RESUMO

It is generally accepted that the hallmark of osteoporosis is a reduction in bone mass. There is significant overlap, however, in bone mineral density between osteoporotic and normal individuals. This study examined the chemical composition of bone tissue obtained from women who had sustained a fracture and women without fracture to determine if there are differences between the two groups. Nineteen fractured and eleven non-fractured proximal femurs were obtained, matched for age and bone volume fraction obtained from micro-computed tomography. Trabecular bone specimens were examined by Raman spectroscopy to determine measures of chemical composition. A subset of the specimens was utilized to compare locations at the fracture and regions at least 2 mm away from apparent tissue damage using Raman spectroscopy. In addition, fifteen iliac crest biopsies each were obtained from women who had sustained a fracture and from normal controls. Raman spectroscopy was used to determine measures of chemical composition of trabecular and cortical bone. The results demonstrated that femoral bone tissue in the region of visible damage had a trend towards differences compared to regions at least 2 mm from visible damage. Femoral trabecular bone in fractured women had a higher carbonate/amide I area ratio than in unfractured women. Iliac crest biopsies revealed a higher carbonate/phosphate ratio in cortical bone from women who had sustained a fracture. Results suggest that the chemical composition of bone tissue may be an additional risk factor for osteoporotic fracture.


Assuntos
Osso e Ossos/química , Fraturas Ósseas/etiologia , Fraturas Ósseas/metabolismo , Osteoporose Pós-Menopausa/complicações , Osteoporose Pós-Menopausa/metabolismo , Idoso , Densidade Óssea , Estudos de Casos e Controles , Feminino , Cabeça do Fêmur/química , Humanos , Ílio/química , Pessoa de Meia-Idade , Fatores de Risco , Análise Espectral Raman
16.
Bone ; 39(5): 1156-1163, 2006 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-16863704

RESUMO

Large bony defects and non-unions are still a complication in trauma and orthopedic surgery. Treatment strategies include the use of autogenous materials (iliac crest), allogenic bone, bone substitutes, and currently stimulation with growth factors such as BMP-2, BMP-7 or the growth factors containing platelet-rich plasma (PRP). Another source of bone graft material might be the cuttings produced during intramedullary reaming. The aim of this study was to compare the quantity of various growth factors found within iliac crest, bony reaming debris, reaming irrigation fluid, and platelet-rich plasma. Iliac crest and reaming debris and irrigation samples were harvested during surgery. PRP was prepared from blood. The growth factors in the bony materials (iliac crest or reaming debris) and of the liquid materials (platelet-poor plasma (PPP), platelet-rich plasma (PRP) or reaming irrigation) were compared. Elevated levels of FGFa, PDGF, IGF-I, TGF-beta1 and BMP-2 were measured in the reaming debris as compared to iliac crest curettings. However, VEGF and FGFb were significantly lower in the reaming debris than from iliac crest samples. In comparing PRP and PPP all detectable growth factors, except IGF-I, were enhanced in the platelet-rich plasma. In the reaming irrigation FGFa (no measurable value in the PRP) and FGFb were higher, but VEGF, PDGF, IGF-I, TGF-beta1 and BMP-2 were lower compared to PRP. BMP-4 was not measurable in any sample. The bony reaming debris is a rich source of growth factors with a content comparable to that from iliac crest. The irrigation fluid from the reaming also contains growth factors.


Assuntos
Substitutos Ósseos/análise , Ílio/química , Peptídeos e Proteínas de Sinalização Intercelular/análise , Plasma Rico em Plaquetas/química , Adulto , Proteína Morfogenética Óssea 2 , Proteína Morfogenética Óssea 7 , Proteínas Morfogenéticas Ósseas/análise , Substitutos Ósseos/química , Transplante Ósseo/instrumentação , Feminino , Humanos , Ílio/cirurgia , Fator de Crescimento Insulin-Like I/análise , Masculino , Pessoa de Meia-Idade , Fator de Crescimento Derivado de Plaquetas/análise , Fator de Crescimento Transformador beta/análise , Fator de Crescimento Transformador beta1/análise , Fator A de Crescimento do Endotélio Vascular/análise
17.
Nephrol Dial Transplant ; 21(8): 2217-24, 2006 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-16595583

RESUMO

BACKGROUND: Lanthanum carbonate (LC) has been proposed as a new phosphate binder. Presented here are the results from one centre that participated in a multicentre trial to assess the effect of treatment with LC and calcium carbonate (CC) on the evolution of renal osteodystrophy in dialysis patients. Bone biopsies were performed at baseline, after 1 year of treatment and after a further 2-year follow-up period to assess the lanthanum concentration in bone and plasma. METHODS: Twenty new dialysis patients were randomized to receive LC (median dose 1250 mg) for 1 year (n = 10), followed by 2 years of CC treatment or CC (n = 10) during the whole study period (3 years). RESULTS: After 36 weeks of treatment, steady state was reached with plasma lanthanum levels varying around 0.6 ng/ml. Six weeks after cessation of 1 year of treatment, the plasma lanthanum levels declined to a value of 0.17 +/- 0.12 ng/ml (P < 0.05) and after 2 years to 0.09 +/- 0.03 ng/ml. Plasma and bone lanthanum levels did not correlate with the average lanthanum dose at any time point. The mean bone concentration in patients receiving LC increased from 0.05 +/- 0.03 to 2.3 +/- 1.6 microg/g (P < 0.05) after 1 year and slightly decreased at the end of the study to 1.9 +/- 1.6 microg/g (P < 0.05). CONCLUSIONS: Bone deposition after 1 year of treatment with LC is low (highest concentration: 5.5 microg/g). There is a slow release of lanthanum from its bone deposits 2 years after the discontinuation of the treatment and no association with aluminium-like bone toxicity.


Assuntos
Distúrbio Mineral e Ósseo na Doença Renal Crônica/tratamento farmacológico , Ílio/química , Falência Renal Crônica/complicações , Lantânio/análise , Diálise Renal/efeitos adversos , Idoso , Fosfatase Alcalina/sangue , Biomarcadores , Calcifediol/sangue , Calcitriol/sangue , Cálcio/sangue , Distúrbio Mineral e Ósseo na Doença Renal Crônica/sangue , Distúrbio Mineral e Ósseo na Doença Renal Crônica/etiologia , Feminino , Seguimentos , Humanos , Falência Renal Crônica/metabolismo , Falência Renal Crônica/terapia , Lantânio/efeitos adversos , Lantânio/sangue , Lantânio/farmacocinética , Lantânio/uso terapêutico , Masculino , Pessoa de Meia-Idade , Hormônio Paratireóideo/sangue , Fosfatos/metabolismo , Fósforo/sangue , Resultado do Tratamento
18.
Osteoporos Int ; 16(12): 2031-8, 2005 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-16088360

RESUMO

Fourier-transform infrared microspectroscopy (FTIRM) allows analysis of mineral content, mineral crystal maturity and mineral composition at approximately 10-micron spatial resolution. Previous FTIRM analyses comparing 4-micron thick sections from non-decalcified iliac crest biopsies from women with post-menopausal osteoporosis, as contrasted with iliac crest tissue from individuals without evidence of metabolic bone disease, demonstrated significant differences in average mineral content (decreased in osteoporosis) and mineral crystal size/perfection (increased in osteoporosis). More importantly, these parameters, which vary throughout the tissue in relation to the tissue age in healthy bone, showed no such variation in bone biopsies from patients with osteoporosis. The present study compares the spatial and temporal variation in mineral quantity and properties in trabecular bone in high- and low-turnover osteoporosis. Specifically, six biopsies from women (n=5) and one man with high-turnover osteoporosis (age range 39-77) and four women and two men with low turnover osteoporosis (age range 37-63) were compared to ten "normal" biopsies from three men and seven woman (age range: 27-69). "High turnover" was defined as the presence of increased resorptive surface, higher than normal numbers of osteoclasts and greater than or equal to normal osteoblastic activity. "Low turnover" was defined as lower than normal resorptive surface, decreased osteoclast number and less than normal osteoblastic activity. Comparing variations in FTIR-derived values for each of the parameters measured at the surfaces of the trabecular bone to the maximum value observed in multiple trabeculae from each person, the high-turnover samples showed little change in the mineral: matrix ratio, carbonate: amide I ratio, crystallinity and acid phosphate content. The low-turnover samples also showed little change in these parameters, but in contrast to the high-turnover samples, the low-turnover samples showed a slight increase in these parameters, indicative of retarded, but existent resorption and formation. These data indicate that FTIR microspectroscopy can provide quantitative information on mineral changes in osteoporosis that are consistent with proposed mechanisms of bone loss.


Assuntos
Densidade Óssea/fisiologia , Ílio/química , Osteoporose/fisiopatologia , Adulto , Idoso , Amidas/análise , Biópsia/métodos , Reabsorção Óssea/fisiopatologia , Carbonatos/análise , Contagem de Células , Cristalização , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Osteoblastos/fisiologia , Osteoclastos , Fosfatos/análise , Espectroscopia de Infravermelho com Transformada de Fourier/métodos
19.
Calcif Tissue Int ; 73(5): 446-54, 2003 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-12958694

RESUMO

Although osteotropic growth factors are known to play an important role in bone metabolism, knowledge about their expression in relation to age, sex and smoking remains limited. In this study we report mRNA levels of the recently discovered Lim mineralization protein splice variants (LMP-1, LMP-2, LMP-3) and the established osteotropic growth factors BMP-2, BMP-6, BMP-7, TGF-beta, IGF-I, IGF-II and b-FGF in human iliac crest bone. Standardized bone biopsy specimens were obtained from the iliac crest during graft harvesting in 62 patients (38 males, 24 females, mean age 44.7 years, range 13-78 years) undergoing spinal surgery. Samples were immediately stored in liquid nitrogen for PCR analysis. Semi-quantitative RT-PCR was performed for TGF-beta, IGF-I, IGF-II, BMP2, BMP-6, BMP7, bFGF, LMP-1, LMP-2 and LMP-3 using beta-actin as internal standard. Triplicate measurements were made of each growth factor and beta-actin. mRNA for all examined growth factors was detected in 69% of the specimens. The lowest degree of detection was present for b-FGF and BMP-2, both of which were found in 85% of the specimens. LMP-1 was detected in 98% of the specimens. LMP-2 in 94% and LMP-3 in 27%, respectively. LMP-1 was generally expressed in higher amounts than LMP-2 and LMP-3. Nondetectable levels of the growth factors were more frequent in the >60-year-old males compared with >60-year-old females ( P < 0.05) and <60-year-old males ( P < 0.01). LMP-1 expression was more variable among young individuals, but mean values were similar between age groups. TGF-beta, BMP-2 and BMP-7 values did not differ between age groups, but generally a higher variation was found among older patients. IGF-I values were significantly higher ( P < 0.05) in males over 60 years, whereas the highest level of bFGF mRNA was present in males younger than 20 years ( P < 0.05). In addition, regression analysis revealed correlation between BMP-2 and BMP-7 (R2 = 0.74, P < 0.0005), LMP-2 and BMP-2 (R2 = 0.27, P < 0.0005) and LMP-2 and bFGF (R2 = 0.40, P < 0.0005). In conclusion, we have demonstrated expression of LMP-1 and LMP-2 in human bone. LMP-1 was expressed in higher amounts and showed a higher degree of variation among young individuals. LMP-2 was correlated to a number of other growth factors, suggesting that LMPs may also play a role in human bone metabolism. Higher variation in the expression of TGF-beta, BMP-2 and BMP-7 was found in the older age groups, but whether or not this can be correlated to age-related changes in bone turnover requires further studies.


Assuntos
Processamento Alternativo , Proteínas Morfogenéticas Ósseas/genética , Proteínas de Transporte/genética , Ílio/metabolismo , RNA Mensageiro/análise , Adolescente , Adulto , Idoso , Biópsia , Proteínas Morfogenéticas Ósseas/análise , Proteínas Morfogenéticas Ósseas/biossíntese , Proteínas de Transporte/análise , Proteínas de Transporte/biossíntese , Estudos Transversais , Primers do DNA/química , Feminino , Regulação da Expressão Gênica , Humanos , Ílio/química , Masculino , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase Via Transcriptase Reversa
20.
Nefrologia ; 23 Suppl 2: 52-6, 2003.
Artigo em Espanhol | MEDLINE | ID: mdl-12778855

RESUMO

The objective of this study was to assess the relationship between the bone strontium content and bone histomorphometric parameters in bone biopsies from patients with chronic renal failure undergoing hemodialysis. The study was carried out in 74 illiac crest bone biopsies from patients with renal osteodystrophy from different worldwide regions (Argentina, Portugal and Spain). They were underwent to histological and histomorphometric evaluation. The bone strontium/calcium ratio was measured by quadrupole inductively coupled plasma-mass spectrometry. The samples were classified into groups according to histological criteria: hyperparathyroidism (HP), mixed (MX), osteomalacia (OM) and adynamic bone disease (ABD). Serum PTH and alkaline phosphatase before biopsy were available in most of the patients. No correlation was found between the different histomorphometric parameters and the Sr/Ca ratio. The one way ANOVA test showed statistical differences in the Sr/Ca ratio of the different histological forms (HP: 0.58 +/- 0.39; MX: 1.16 +/- 0.74; OM: 1.10 +/- 0.46; ABD: 0.91 +/- 0.40 microgram Sr/mg Ca; p < 0.003). The post-Hoc analysis showed differences between HP and MX. The biopsies having greater or equal values than 1.4 micrograms Sr/mg Ca showed higher levels of bone formation histomorphometric parameters and serum alkaline phosphatase (395 +/- 519 vs 1,022 +/- 989 UI/L, p < 0.05). Although it has been found that the biopsies with higher bone strontium had higher levels of osteoid tissue (characteristic of osteomalacia), the hypothesis of strontium-induced osteomalacia could not be demonstrated.


Assuntos
Osso e Ossos/metabolismo , Distúrbio Mineral e Ósseo na Doença Renal Crônica/metabolismo , Soluções para Hemodiálise/efeitos adversos , Falência Renal Crônica/metabolismo , Osteomalacia/induzido quimicamente , Diálise Renal , Estrôncio/efeitos adversos , Fosfatase Alcalina/sangue , Argentina/epidemiologia , Biópsia , Osso e Ossos/química , Cálcio/análise , Distúrbio Mineral e Ósseo na Doença Renal Crônica/epidemiologia , Distúrbio Mineral e Ósseo na Doença Renal Crônica/etiologia , Soluções para Hemodiálise/química , Humanos , Hiperparatireoidismo Secundário/etiologia , Ílio/química , Ílio/patologia , Falência Renal Crônica/complicações , Falência Renal Crônica/terapia , Osteomalacia/epidemiologia , Osteomalacia/etiologia , Hormônio Paratireóideo/sangue , Portugal/epidemiologia , Diálise Renal/efeitos adversos , Espanha/epidemiologia , Estrôncio/análise
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