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Biomedical subjects

Daniel Chappard

Publications and source records attributed to Daniel Chappard.

At least 19 recordsLinked to original sources
PubMed2006

Absence of renal lesions in C57BL/KaLwRij mice with advanced myeloma due to 5T2MM cells.

Renal failure is one of the main complications in multiple myeloma (MM) and histopathological lesions are due to light chains accumulation in the kidney. The 5T2MM mouse model closely mimics osteolytic lesions observed in clinics. We studied the occurrence of pathological changes in the kidney of mice inoculated with 5T2MM myeloma cells. No renal lesions due to light chain deposition were observed after histological, immunological staining and dosage of creatinine in serum and urine. PTH levels decreased in 5T2MM mice, confirming the absence of secondary hyperparathyroidism. Osteolytic lesions appear to be the unique consequence of 5T2MM cells inoculation.

Animals↗
PubMed2006

Rat models of bone metastases.

Bone metastases occur frequently in patients with advanced breast or prostate cancer. Bone metastases can be predominantly osteolytic, osteoblastic or mixed. Studies with animal models allow advances in understanding the molecular basis for bone metastases and provide new targets for therapy. Several animal models have been developed in rat with different pathophysiologies; they required injection or implantation of neoplastic cells into orthotopic locations, bones or the left ventricle of the heart. Several specific strains of rat have an increased incidence of spontaneous tumors. Carcinomas can be induced by either chemicals or physical agents. However, the most used and convenient way to induce bone metastases is a syngeneic transmission. MAT-Ly-Lu cells have been used in several models using Copenhagen rats to induce osteoblastic bone lesions. PA-III cells derived from Pollard tumors can also produce a combination of osteolytic and osteoblastic reactions at the site of transplantation. Osteolytic bone lesions can be obtained with an injection of Walker cells. The use of 13762 or c-SST2 cells allows also leads to osteolysis. Human xenografts can only be used in nude animals. It is essential to validate and correctly interpret the lesions in several models of bone metastasis. No animal model is sufficient by itself to represent the clinical findings observed in humans. The use of models developed in different species should be more predictive and bring a beam of arguments for a better knowledge of pathophysiological and therapeutic mechanisms.

Animals↗
PubMed2006

The influence of processes for the purification of human bone allografts on the matrix surface and cytocompatibility.

Different industrial processes exist to purify allogenic bone, providing safe and cleaned blocks for bone allografting. However, they often make use of chemical reagents that can be aggressive for the bone matrix. Bone samples were processed with several soaking techniques used in industry: NaHCO3, H2O2, NaOH and H2O2+NaOH combined; the consequences on the bone matrix and cytocompoatibility were evaluated on femoral heads from osteoarthritic patients. Alterations of matrix were searched by histochemistry, atomic force microscopy (AFM), scanning electron microscopy (SEM) and transmission electron microscopy (TEM). Cytocompatibility was evaluated by coculturing human osteoblast-like cells (SaOS-2) on bone slices. Collagen fibers were dramatically altered at the surface of bone treated with H2O2, NaOH (and their association), but not with NaHCO3. A marked reduction in the number of hydroxyapatite crystals was observed on the trabecular surfaces by TEM and morphological changes were evidenced in SEM and AFM. Argyrophilic proteins of the bone matrix were removed by H2O2 and NaOH (and their association), but not by NaHCO3. As a consequence, attachment, spreading, proliferation and alkaline phosphatase activity of SaOS-2 were reduced by H2O2 and NaOH treatments. Strong oxidizing reagents altered matrix integrity by modifying collagenous and non-collagenous proteins. Whether these changes have clinical consequences on the bone bonding and osseointegration in human necessitate further investigations.

Bone Transplantation↗
PubMed2006

Medullar fat influences texture analysis of trabecular microarchitecture on X-ray radiographs.

Alteration of trabecular architecture is a predictor of fracture risk in osteoporosis. Until now, microarchitecture analysis is difficult to evaluate in routine clinical practice for osteoporosis. Texture analysis on X-ray images has been advocated to be a suitable method to assess microarchitecture in bone diseases. The X-ray acquisition conditions have been often taken into consideration; however, the influence of anatomical conditions on texture parameters has received little interest. Because fat is a well-known problem with computed tomography and densitometry, we have designed a cadaver study to compare the influence of marrow lipids on numerous texture parameters. Twenty-one human distal radii were obtained, radiographed, and analyzed using a software that measures: heterogeneity, skeletonized parameters, run-lengths and fractal dimensions. Texture parameters were measured before, and after an extensive delipidation period lasting 3 weeks. Quality of the radiographs was improved after defatting. Delipidation had a very significant effect on measurements: afterwards defatting, the images were less blurred, and a better delineation of trabeculae and marrow cavities was obtained. This provoked an increase of parameters based on the grey level distribution but had no influence on parameters describing the reticulated honeycomb microarchitecture of the trabeculae (i.e., fractal dimension). Some parameters appeared anisotropy-sensitive, due to the different constitution and size of the trabeculae. The fat content of bone marrow induces noise that can modify some texture parameters. One should take into account the fat content of the marrow when using texture analysis to compare patients with osteoporosis due to various etiologies.

Adipose Tissue↗
PubMed2005

Comparison insight bone measurements by histomorphometry and microCT.

UNLABELLED: Morphometric analysis of 70 bone biopsies was done in parallel by microCT and histomorphometry. microCT provided higher results for trabecular thickness and separation because of the 3D shape of these anatomical objects. INTRODUCTION: Bone histomorphometry is used to explore the various metabolic bone diseases. The technique is done on microscopic 2D sections, and several methods have been proposed to extrapolate 2D measurements to the 3D dimension. X-ray microCT is a recently developed imaging tool to appreciate 3D architecture. Recently the use of 2D histomorphometric measurements have been shown to provide discordant results compared with 3D values obtained directly. MATERIAL AND METHODS: Seventy human bone biopsies were removed from patients presenting with metabolic bone diseases. Complete bone biopsies were examined by microCT. Bone volume (BV/TV), Tb.Th, and Tb.Sp were measured on the 3D models. Tb.Th and Tb.Sp were measured by a method based on the sphere algorithm. In addition, six images were resliced and transferred to an image analyzer: bone volume and trabecular characteristics were measured after thresholding of the images. Bone cores were embedded undecalcified; histological sections were prepared and measured by routine histomorphometric methods providing another set of values for bone volume and trabecular characteristics. Comparison between the different methods was done by using regression analysis, Bland-Altman, Passing-Bablock, and Mountain plots. RESULTS: Correlations between all parameters were highly significant, but microCT overestimated bone volume. The osteoid volume had no influence in this series. Overestimation may have been caused by a double threshold used in microCT, giving trabecular boundaries less well defined than on histological sections. Correlations between Tb.Th and Tb.Sp values obtained by 3D or 2D measurements were lower, and 3D analysis always overestimated thickness by approximately 50%. These increases could be attributed to the 3D shape of the object because the number of nodes and the size of the marrow cavities were correlated with 3D values. CONCLUSION: In clinical practice, microCT seems to be an interesting method providing reliable morphometric results in less time than conventional histomorphometry. The correlation coefficient is not sufficient to study the agreement between techniques in histomorphometry. The architectural descriptors are influenced by the algorithms used in 3D.

Biopsy↗
PubMed2005

Texture analysis of X-ray radiographs is correlated with bone histomorphometry.

Three-dimensional (3D) alteration of trabecular microarchitecture is a risk factor for vertebral fractures. Histomorphometry allows microarchitectural analysis of bone, but the necessity to perform a transiliac bone biopsy limits its use in large series of patients. X-Ray films are commonly used in routine practice and constitute a 2D projection of the trabecular architecture. In this study, blocks of trabecular dried bone were prepared from calf bone. They were selected from different parts of the femoral condyle to provide various patterns of trabecular disposition. All blocks (25 x 15 x 8 mm) were radiographed on a numeric X-ray system, with the same acquisition parameters. Texture analysis was carried out by several methods: (skeletonization, run lengths, and fractal techniques). Histological sections of the blocks were obtained and analyzed by 2D histomorphometric methods: trabecular bone volume (BV/TV), trabecular characteristics, and 2D descriptors of architecture (star volumes, strut analysis, fractal dimensions). Significant correlations were obtained for BV/TV with run length parameters measured on the X-ray image. The trabecular characteristics were found to be highly correlated with texture parameters describing the X-ray image (e.g., trabecular number [Tb.N]/axis, r = -0.82;/short run emphasis [SRE], r = -0.87; trabecular separation [Tb.Sp]/gray level nonuniformity [GLN], r = -0.82). Several histomorphometric parameters, independent of the "plate-and-rod" model, were also well correlated with texture descriptors. Although the relationships between the 2D and 3D trabecular architecture are not fully elucidated, the texture analysis of X-ray films might be a suitable approach to investigate the disorganization of bone in osteoporosis.

Animals↗
PubMed2005

Bone loss and teeth.

Loss of teeth results in irreversible alveolar bone resorption, and untreated dental disease causes alveolar bone lysis that ultimately leads to loss of teeth. In addition to anchoring the teeth in the alveolar ridge, the maxillary and mandibular bone allows dental restoration procedures, such as construction of root-supported implants, fixed dentures, or removable dentures. However, the functional and cosmetic results depend on the quantity and quality of the maxillary or mandibular bone, which can be affected by many normal and abnormal processes. The alveoli are particularly fragile and labile. Changes in alveolar bone vary considerably across individuals and depend directly on local factors. Many studies have investigated associations between alveolar bone status and bone mass at other skeletal sites. These studies focused chiefly on the course of parodontal disease, alveolar ridge resorption after tooth extraction, and density differences across various mandibular sites. They produced conflicting results, probably because of differences in measurement methods. Measurement sites and methods should be standardized to ensure that reliable and comparable data are obtained. To date, there are few reliable methods for obtaining quantitative measurements of bone mineral content in maxillary and mandibular bone.

Bone Density↗
PubMed2004

[Osteoporosis in men].

Less comon than in women, osteoporosis in men may be idiopathic, but in about 60% of patients several factors contribute to bone loss and fractures. The most prominent causes of secondary osteoporosis in males are hypogonadism, corticosteroid therapy, alcohol abuse, and gastrointestinal or hepatic disorders. Testosterone treatment is reserved to the treatment of hypogonadal men. In primary or secondary male osteoporosis, diphosphonates prevent bone loss and reduce the incidence of future fractures.

Humans↗
PubMed2004

Effects of calcitonin on subchondral trabecular bone changes and on osteoarthritic cartilage lesions after acute anterior cruciate ligament deficiency.

UNLABELLED: Because SBM may contribute to cartilage breakdown in OA, experimental OA was induced in dogs by transecting the anterior cruciate ligament of the knee and treating with either CT or a placebo. CT significantly reduced both SBM and cartilage lesions. This study supports the use of CT in the treatment of canine experimental OA. INTRODUCTION: Because subchondral bone remodeling (SBM) may contribute to cartilage breakdown in osteoarthritis (OA), we evaluated to what extend calcitonin (CT) might affect cartilage and bone changes in the early stages of canine experimental OA. MATERIALS AND METHODS: Twelve dogs underwent transection of the anterior cruciate ligament (ACLT) of the right knee. After ACLT, each animal received a daily nasal spray delivering either 400 U of CT (CT-treated group; n = 6) or a placebo (PL-treated group; n = 6). At day 84 after surgery, animals were killed, and cartilage changes were graded. BMD and volume fraction (BVF) were assessed by pQCT in different regions of interest (ROIs) of the subchondral cancellous bone of tibial plateaus (TPs). Statistics included a 2 x 2 factorial analysis with +/-CT as one factor and +/-ACLT as the other. RESULTS AND CONCLUSIONS: Nonoperated (N-OP) knees were normal in both groups. In the PL-treated group, ACLT knees all exhibited OA changes, which predominated in the medial knee compartment. Furthermore, compared with N-OP knees, the BMD and BVF of ACLT joints were both markedly reduced in medial TP but not in lateral TP. In contrast, in the CT-treated group, cartilage OA lesions of ACLT knees were significantly reduced, and there was no difference in BMD and BFV between N-OP and ACLT knees. These findings suggest that the loss of subchondral trabeculae contributes to cartilage breakdown, possibly by enhancing cartilage deformation on joint loading. By counteracting bone loss, CT reduced cartilage OA lesions, and thus, might be useful in the treatment of OA in cruciate-deficient dogs.

Animals↗
PubMed2004

Mandibular bone loss in an animal model of male osteoporosis (orchidectomized rat): a radiographic and densitometric study.

In humans, hypogonadism is associated with osteoporosis and can be studied by densitometry (DXA) on the vertebrae or long bones. There is some controversy about the relationships between bone loss in these sites and in the mandible. Osteoporosis has been suggested as a risk factor for dental problems. In the rat, orchidectomy (ORX) is associated with an increased bone resorption resulting in bone loss. We have studied the time effects of ORX on the alveolar bone in the rat. Forty-eight male Wistar rats were divided into four groups and studied over 2, 4, 8 and 16 weeks. In each group, six rats were ORX and six sham-operated (SHAM) animals were used as control. The mandible of each rat was dissected. Numeric radiographs, centered on the molar region, were obtained. Bone loss was observed qualitatively at 16 weeks in ORX animals. Quantitative modifications were confirmed by texture analysis of numeric radiographs using the run-length technique. The bone mineral content (BMC) and density (BMD) of the hemimandible and in a region centered on the molars were measured by DXA. The coefficient of variation (CV) for BMC was poor on the whole bone and no differences could be observed even at 16 weeks. For BMC of the molar region, the CV was improved and significant bone loss occurred in the ORX group at 16 weeks ( P<0.016). This study confirms that in the male rat, the reduction of sex hormones induced by ORX is associated with a decrease in bone mass in the mandible.

Absorptiometry, Photon↗
PubMed2004

Migration of polyethylene particles around nonloosened cemented femoral components from a total hip arthroplasty-an autopsy study.

Three cemented femoral components from total hip arthroplasties retrieved at autopsy were examined in regard to the migration of birefringent polyethylene particles across the fixation interfaces. They were obtained from two patients who died from unrelated causes. They had been in place, respectively, for 8 and 9 years (first patient) and for 9 years (second patient). Osteolysis was present in the acetabular side only. The femoral components were not loosened. Histologic sections were performed at four levels of the femoral components, and polyethylene particles were counted with the use of a semiautomatic image analyzer. Sections below the tip of the stem were treated by deorganification and the lysate was centrifuged in the attempt to isolate wear debris. Particles were found at both interfaces (bone-cement and metal-cement) and in the cancellous bone between the trabeculae. They were also present in the Haversian canals of the cortical bone. Particles of various sizes were found in the medullary canal beneath the tip of the stem. In scanning electron microscopy, they appeared to have irregular shapes. Wear debris can migrate across the cement-bone interface of nonloosened implants. They appear to progress through the porosity of the cancellous bone.

Aged↗
PubMed2004

Selection of a highly aggressive myeloma cell line by an altered bone microenvironment in the C57BL/KaLwRij mouse.

In multiple myeloma (MM), bone marrow microenvironment has an important role for the survival and growth of plasma cells. We previously showed that a high bone turnover, induced by ovariectomy, increased MM cells growth in the 5T2MM model. The present study characterized a new plasma cell line (5THL) which was isolated from 5T2MM mice previously ovariectomized. Cells were propagated unchanged in normal C57BL/KaLwRij mice during six generations. 5THL was compared to the original 5T2MM phenotype. Paraproteinemia was detected 6 weeks post injection in 5THL mice and after 8 weeks in 5T2MM mice. All 5THL mice developed a hind-limb paralysis after 10 weeks. 5T2MM mice were euthanized at 16 weeks, due to a more progressive development of the disease. In 5THL mice, osteolytic lesions were observed after 8 weeks and severe bone destruction was evidenced at 10 weeks. In 5T2MM mice, minimal lesions were observed only after 10 weeks. Like in 5T2MM mice, no extra osseous lesions were observed in 5THL mice. The 5THL MM model closely mimics human myeloma with higher and faster bone aggressiveness. This new aggressive cell line, with a preserved phenotype, was selected by an altered microenvironment due to an increased bone turnover.

Animals↗
PubMed2004

Bone structure of the calcaneus: analysis with magnetic resonance imaging and correlation with histomorphometric study.

The purpose of this study was to compare structural measurements obtained from MR images of the calcaneus with those obtained from conventional histomorphometry. Sagittal magnetic resonance (MR) images of the calcaneus of 24 fresh human cadaveric feet were obtained at a spatial resolution achievable in vivo. A three-dimensional gradient echo-sequence was used with a slice thickness of 700 microm and in plane resolution of 172 x 172 microm. Structural analysis (four histomorphometric parameters; seven connectivity parameters) was performed in the superior region of the calcaneus. Bone biopsy specimens were obtained in the same area and were sectioned for histomorphometric study. Most of the MR histomorphometric parameters were overestimated (by a factor ranging from 0.8 to 3), as compared with histomorphometry. However, significant ( P<0.05) correlations were found between MR imaging and histomorphometric measurements for bone volume/tissue volume, trabecular separation, trabecular number, star volume of the marrow space, node count and terminus count. MR histomorphometric parameters correlated much better with histomorphometry than connectivity parameters. This study suggests that structural parameters characterizing cancellous bone in the calcaneus can be derived from MR images in the limited spatial resolution regime applicable in vivo.

Absorptiometry, Photon↗
PubMed2004

Some biomechanical and histologic characteristics of early-loaded locking pin and expandable implants: a pilot histologic canine study.

BACKGROUND: A two-stage approach with a 3- to 6-month healing period is recommended for the "conventional" osseointegration technique with oral implants. This may induce inconvenience and discomfort for patients, and immediate early loading protocols are preferable. PURPOSE: To compare a new type of implant with two locking pins, designed to allow immediate loading, with an expandable implant design with regard to bone tissue response and implant stability. MATERIALS AND METHODS: The molars and premolars of two beagle dogs were extracted in the mandible, and two types of implants (an apically expandable implant and a locking pin implant) were immediately placed in the sockets. The dogs received at least four implants (two of each type) in each side of the mandible. Implants were loaded with gold-palladium bridges 15 days later. The loaded implants were left for 3 months, and the dogs were sacrificed. Resonance frequency analysis (RFA) was performed at placement and sacrifice. Ground sections for histomorphometry were produced for each implant. RESULTS: Implant stability as measured by RFA was similar for the two types of implants before healing. At termination of the study, stability was higher for the locking pin implants. Bone histomorphometry showed that both types of implant were anchored by the same amount of bone and that bone-titanium interfaces did not differ. CONCLUSION: The locking pin implant showed better secondary stability than did the expandable implant, probably because of a better transmission of strains to bone.

Animals↗
PubMed2003

Proliferation and differentiation of osteoblasts and adipocytes in rat bone marrow stromal cell cultures: effects of dexamethasone and calcitriol.

During bone loss, osteoblast population can be replaced by adipose tissue. This apparent reciprocal relationship between decreased bone density and increased fat formation can be explained by an imbalance in the production of bone-forming and fat-forming cells in the marrow cavity. Thus, osteoblast and adipocyte pathways seem more closely and inversely related. In the present study, we investigated the effects of dexamethasone (dex) and calcitriol [1,25(OH)(2)D(3)] on proliferation and differentiation of osteoblasts and adipocytes in rat bone marrow stromal cell cultures. Stromal cells were grown in primoculture in presence of dex and subcultivated in presence of dex and/or 1,25(OH)(2)D(3). Total cell proliferation, osteoblast and adipocyte-cells number, and -mRNA specific markers were used to study the effects of hormonal treatment on stromal cells. Total cell proliferation was stimulated by dex and inhibited by 1,25(OH)(2)D(3). Dex increased osteoblast and adipocyte cell population whereas calcitriol decreased bone-forming cell number and increased fat cell population. The presence of both hormones led to a strong decrease in osteoblastic cells and to a strong increase in adipocytic cell number. Dex induced mRNA osteoblastic markers expression like bone sialoprotein (BSP) and osteocalcin (OC) and an adipocyte marker expression, the fatty acid binding protein aP2. Calcitriol decreased the dex-induced BSP expression but stimulated slightly OC and aP2 mRNA. The effects of both hormones was to increase strongly OC and aP2 mRNA. These results support that, in rat bone marrow, adipocyte proliferation and differentiation are stimulated by glucocorticoids and calcitriol which act synergically, whereas osteoblastic cell proliferation and differentiation are increased by dex and inhibited by 1,25(OH)(2)D(3).

Adipocytes↗
PubMed2003

Respective roles of porto-septal fibrosis and centrilobular fibrosis in alcoholic liver disease.

In alcoholic liver disease, fibrosis classically begins around the centrilobular veins, while portal tract fibrosis is described as inconstant and septal fibrosis is a late event. The aim of this study was to compare the roles of centrilobular fibrosis (CLF) and portal tract/septal fibrosis (PTF) especially in alcoholic chronic liver disease. One hundred and sixty patients with alcoholic chronic liver disease and 83 controls with viral chronic hepatitis were included. The PTF score, derived from the Metavir score, CLF and the area of fibrosis, assessed by image analysis, were evaluated on liver biopsies in addition to blood markers of fibrosis. The correlation between the PTF score and the area of fibrosis was higher in alcoholic liver disease (r = 0.87, p < 10(-4)) than in viral chronic hepatitis (r = 0.66, p < 10(-4)). The PTF score correlated with the CLF score (r = 0.92, p < 10(-4)), serum hyaluronate (r = 0.76, p < 10(-4)), and the prothrombin index (r = -0.77, p < 10(-4)). Multiple regression analyses showed that the area of fibrosis was explained only by the PTF score and not by the CLF score. PTF appears more frequent than CLF in alcoholic chronic liver disease, suggesting that PTF may precede CLF. PTF is more responsible for the amount of fibrosis than CLF. The results of this study also validate the use of the Metavir fibrosis score in alcoholic chronic liver disease.

Biomarkers↗
PubMed2003

Increased bone remodeling due to ovariectomy dramatically increases tumoral growth in the 5T2 multiple myeloma mouse model.

Bone destruction is the main clinical consequence of multiple myeloma (MM). It is known that a "vicious circle" exists between bone and myeloma cells with plasma cells stimulating bone cells, which in return stimulate the neoplastic growth. We hypothesized that an accelerated bone remodeling induced by ovariectomy (OVX) could provide a more fertile environment for the myeloma cell growth. Ovariectomy performed on C57BL/KaLwRij mice resulted in reduced trabecular bone volume and increased osteoclast number. To test our hypothesis, we ovariectomized C57BL/KaLwRij mice one week before injection of 5T2MM myeloma cells. A non-OVX 5T2MM group was used as control. Ovariectomy increased the tumor growth and induced an earlier development of osteolytic lesions. OVX 5T2MM mice were euthanized at 10 weeks, instead of 16 weeks, for the non-OVX 5T2MM, mice because of the accelerated development of disease in OVX animals. Treatment of OVX 5T2MM mice with pamidronate reduced osteolysis but had little effect on the time development of the tumor. This combined model (ovariectomy + 5T2MM) confirmed the interdependence of bone and myeloma cells and could explain the some sudden burden of indolent MM into aggressive MM in humans.

Animals↗