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Calcifications of the basal ganglia are frequently seen on the cerebral CT scans and particularly in the globus pallidus. Their frequency increases physiologically with age after 50 years old. However, pathological processes can also be associated with calcium deposits in the gray nuclei, posterior fossa or white matter. Unilateral calcification is often related to an acquired origin whereas bilateral ones are mostly linked to an acquired or genetic origin that will be sought after eliminating a perturbation of phosphocalcic metabolism. In pathological contexts, these calcifications may be accompanied by neurological symptoms related to the underlying disease: Parkinson's syndrome, psychiatric and cognitive disorders, epilepsy or headache. The purpose of this article is to provide a diagnostic aid, in addition to clinical and biology, through the analysis of calcification topography and the study of different MRI sequences.

This work is ascribed within the framework of the development of osteoinductive biomaterials for the repair large bone defects. It is a contribution to the understanding of the physical and chemical interactions between phosphocalcic ceramics and two proteins of interest: fibronectin (Fn), a cell adhesion protein, and Vascular Endothelial Growth Factor (VEGF) which is involved in vascularisation and improvement of bone formation.Fibronectin/bioceramic physical interactions were studied by force spectroscopy to evaluate the influence of the topography and the chemical composition of phosphocalcic ceramics made of hydroxyapatite (HA), silicated hydroxyapatite (SiHA) and carbonated hydroxyapatite (CHA) on fibronectin adhesion. The results obtained in terms of force cartography do not indicate any impact of the polished ceramics chemistry on the surface distribution and intensity of adhesion forces. However, these forces are more intense at the level of the grain boundaries of unpolished ceramics, highlighting an influence of the topography modulated by the chemical composition.The protocol for functionalisation by VEGF consists of three steps: silanisation, addition of SM(PEG)6 and immobilisation of VEGF. VEGF/bioceramic chemical interactions were studied mainly by Raman imaging in order to follow the successive steps of the functionalisation by VEGF of the polished surface of ceramics made of hydroxyapatite (HA) and carbonated hydroxyapatite (CHA). This approach allowed to map the surface chemical changes and to point out the spatial distribution as well as the preferential reactions between the intermediate molecules and VEGF depending of the substrate.; Ce travail s’inscrit dans le cadre général du développement de biomatériaux ostéoinducteurs pour la réparation de grands défauts osseux. L’étude est une contribution à la compréhension des interactions physiques et chimiques entre des céramiques phosphocalciques et deux protéines d’intérêt : la fibronectine, protéine d’adhésion cellulaire, et le VEGF (pour Vascular Endothelial Growth factor) qui est impliqué dans la vascularisation et l’amélioration de la formation osseuse.Les interactions physiques fibronectine/biocéramique ont été étudiées par spectroscopie de force afin d’évaluer l’influence de la topographie et de la composition chimique de céramiques phosphocalciques en hydroxyapatite (HA), hydroxyapatite silicatée (SiHA) et hydroxyapatite carbonatée (CHA) sur l’adhésion de la fibronectine. Les résultats obtenus par cartographie de forces mettent en évidence une absence d’incidence de la chimie des céramiques polies sur la répartition en surface et l’intensité des forces d’adhésion. En revanche ces dernières sont plus fortes au niveau des joints de grains des céramiques non polies mettant en avant une influence de la topographie de surface des matériaux modulée par la chimie.Le protocole de fonctionnalisation par le VEGF consiste en trois étapes : silanisation, addition du SM(PEG)6 et immobilisation du VEGF. Les interactions chimiques VEGF/biocéramique ont été étudiées principalement par imagerie Raman pour suivre ces étapes successives de la fonctionnalisation par le VEGF de céramiques polies en hydroxyapatite (HA) et hydroxyapatite carbonatée (CHA). Cette approche a permis de cartographier l’évolution chimique de la surface des matériaux et de mettre en évidence la distribution spatiale ainsi que les réactions préférentielles entre les molécules intermédiaires et le VEGF en fonction de la nature du substrat.

Incidence of urolithiasis is increasing in industrialized countries. Amendments can be explained among others by dietary changes. More and more young patients have urolithiasis. The objective of this study was to analyze and update the epidemiology of stones in south of France about age and gender.A retrospective single-center study from 2009 to June 2015 included all urolithiasis analyzed by infrared spectroscopy. Groups were composed according to the mineral content (oxalocalcic with whewellite and weddelite, calcium phosphate stones, uric acid stones…).A total of 749 stones were analyzed. The sex ratio was 1.96 all aged confused. The most common stones were oxalocalcic (51.3 %), followed mixed stones (21.2 %) and calcium phosphate stones (11.9 %). The calcium oxalate stones are mainly composed of whewellite (42 %) and calcium phosphate stones of carbapatite (18.6 %). The stones of whewellite were more frequent in men (P=0.0009), as well as uric acid stones (P=0.01) and mixed stones in women (P=0.00003), as well as calcium phosphate (P=0.0005).Epidemiology of stones has changed with an increased incidence in women, and nephrolithiasis patients getting older. A change in the type of stones is observed with increasing the proportion of mixed stones especially among women. Nutritional and metabolic studies are needed to find the etiology of the change in the epidemiology of urolithiasis.4.

This work is focused on the synthesis of a novel hybrid biomaterial made of carbon fibers cloth (CFC)/ calcium phosphates (CaP) using the sono-electrochemical technique and the study of the influence of experimental parameters on the chemical composition, microtexture and structure of CaP deposits and on in vitro biocompatibility. Current density is shown to be a crucial parameter. Specifically, at high current densities ((≥ 100 mA/g), the fast water electrolysis rate leads to a needle-like deposit consisting in a major phase of carbonated calcium deficient hydroxyapatite (CaD-HAP) mixed with a calcium carbonate phase. At low current densities (≤ 50 mA/g), the slow water electrolysis rate generates a plate-like carbonated CaD-HAP phase, coming from the in situ hydrolysis of a former octacalcium phosphate phase. Whatever the experimental conditions, particles of the deposits consists in a carbonated CaD-HAP core showing an ordered structure, surrounded by a hydrated and disordered carbonated CaD-HAP surface layer which results of the formation of oversaturated domains during CaP precipitation. Sono-electrodeposition is shown to be a versatile process able to control the nature of CaP phases. Especially, at low current density a biomimetic CaP deposit is obtained, similar to the mineral part of bones produced during natural osteogenesis. In vitro biologic tests using primary human osteoblasts showed that the nano-porosity and hydrophilicity of the carbon fibers do not affect the biocompatibility and that fiber precursor, sizing and lobe shaped fibers seems to favor adhesion and proliferation of human cells., Ce travail a consisté à élaborer un biomatériau hybride constitué d’un tissu de fibres de carbone (TFC) revêtu de phosphates de calcium (CaP) déposés par un procédé de sono-électrodéposition et à étudier l’influence des paramètres expérimentaux sur la composition chimique, la microtexture et la structure des revêtements phosphocalciques, ainsi que la biocompatibilité in vitro du biomatériau hybride. La densité de courant s’est avérée être un paramètre important. Pour de fortes densités de courant (≥ 100 mA/g), un régime d’électrolyse rapide de l’eau entraîne la formation d’un dépôt aciculaire d’hydroxyapatite déficitaire en calcium (CaD-HAP) carbonatée avec la présence éventuelle d’une phase de calcite. Pour de faibles densités de courant (≤ 50 mA/g), un régime d’électrolyse lent de l’eau entraîne la formation d’un dépôt plaquettaire de CaD-HAP carbonatée issu de l’hydrolyse in situ du phosphate octocalcique plaquettaire préalablement précipité. Pour l’ensemble des dépôts, les particules sont constituées d’un coeur de CaD-HAP carbonatée de structure ordonnée et d’une surface hydratée de CaD-HAP carbonatée de structure désordonnée qui résulte de l’existence d’une zone de sursaturation lors de la précipitation des CaP. La sono-électrodéposition se révèle être un procédé versatile capable d’orienter la synthèse des phases de CaP, avec pour une faible densité de courant appliquée l’obtention d’un dépôt biomimétique comparable à la partie minérale du tissu osseux obtenue par le processus d’ostéogénèse naturelle. Des tests de viabilité in vitro réalisés avec des ostéoblastes humains primaires ont montré que la nanoporosité et le caractère hydrophile des TFC n’impactent pas la biocompatibilité et que les paramètres tels que le précurseur des fibres, l’ensimage et/ou la forme lobée des fibres semblent favoriser l’adhésion et la prolifération des cellules.

Nephrolithiasis is a frequent disease observed in 1 to 20 % of the general population. This disease predominates in male patients (2:1) and is characterized by a high rate of recurrences (about 50 %).We report the case of a 45-year old male patient who experienced during about ten years recurrent bilateral renal colic episodes due to brushite lithiasis. These stones were treated with multiple extracorporeal shock wave lithotripsy sessions. A pyeloureteral junction syndrome predisposing to bulky stones formation has been put in evidence and required a pyeloplasty. After more than ten years of disease activity, a biochemical screening diagnosed primary hyperparathyroidism (PHPT). Radiological assessment identified a parathyroid gland adenoma. Successful surgical removal of this lesion was followed by resolution of the symptomatic kidney stones formation.PHPT is associated with kidney stones in about 20 % of the patients. Hypercalciuria is the main risk factor of stones formation but other predisposing factors are also probably involved. Patients carrying a polymorphism located in the coding sequence of the calcium-sensing receptor gene or in the regulatory region of this gene seem to experience an increased occurrence of urinary lithiasis.The present case stresses the importance of a metabolic assessment in all patients with recurrent nephrolithiasis, especially in case of bilateral episodes.

The aim of reconstructing a calvarial donor site with biomaterial is to reconstruct the skull vault. The aim of this retrospective study was to assess the quality of reconstruction of calvarial bone with Hydroset™ (Stryker™) in patients having undergone monocortical parietal bone graft harvesting.The donor sites of patients having undergone calvarial bone harvesting had been reconstructed with Hydroset™ cement over a period of four years. Calvarial bone reconstruction and the thickness of the parietal bone were evaluated by CT scan.Twenty-six patients had undergone reconstruction. The CT scan revealed a good integration of Hydroset™ with maintained thickness of the biomaterial. The parietal bone thickness was increased by 0.67 mm on average (P=0.002).The reconstruction of calvarial donor site bone defect with Hydroset™, after a monocortical harvesting, demonstrates parietal osseous thickness maintained in time.

The development of biocompatible materials allowing the local delivery of specific drugs is of high interest to repair pathological bone defects. The first part of this manuscript describes the synthesis and the characterisation of calcium phosphates glasses doped with gallium, which is a bone resorption inhibitor. The nature of the phosphate network is probed by 31P NMR and the Ga3+ local environments are studied 71Ga NMR at very high magnetic field (20T) and ultra-fast spinning frequency. The leaching behaviour of these glasses is investigated by NMR and ICP-AES. The obtained results indicate that the glass dissolution is nearly congruent and that Ga3+ doping improves the chemical durability. The second part of this work is dedicated to the study of the Bioglass® 45S5 which is a bioactive glass (SiO2-CaO-Na2O-P2O5 glassy system) used in bone repair surgery. Double-resonance NMR experiments are used to obtain information about the association between the phosphate units and the silicate network. NMR analyses are also used to characterize quantitatively the various species formed at the glass surface after immersion into a simulated body fluid for varying periods. Results obtained from NMR and other characterization methods revealed that the carbonated hydroxyapatite formed at glass surface shows strong similarities with biological apatites., Le développement de matériaux biocompatibles permettant la vectorisation de principes actifs est particulièrement souhaitable dans le cadre de la réparation osseuse liée à certaines pathologies. Dans la première partie de ce mémoire, nous décrivons la synthèse et la caractérisation de verres de phosphates de calcium dopés avec du gallium qui est un agent inhibiteur de la résorption osseuse. Les modifications du réseau phosphate sont étudiées par RMN du 31P et les différents environnements locaux du Ga3+ sont mis en évidence par RMN du 71Ga en utilisant des conditions expérimentales spécifiques (très haut champ magnétique de 20T et rotation de l’échantillon ultra-rapide). Le comportement en solution de ces verres a été étudié par RMN et par ICP-AES. Les résultats obtenus indiquent qu’ils sont soumis à une dissolution quasi-congruente et que l’ajout de Ga3+ augmente leur durabilité chimique. La seconde partie de ce travail est dédiée à l’étude d’un verre bioactif utilisé en chirurgie réparatrice osseuse : le Bioglass® 45S5 (système SiO2-CaO-Na2O-P2O5). L’utilisation d’expériences RMN de double résonance a permis d’apporter des éléments de réponse sur le type d’association entre les groupements phosphates et le réseau silicate. Après immersion de ce verre dans un fluide physiologique simulé (SBF), un suivi quantitatif des espèces, initiales et formées à la surface du verre, a été réalisé par RMN. Les résultats obtenus par RMN et par d’autres techniques de caractérisation montrent que l’hydroxyapatite carbonatée se formant en surface du verre présente de grandes similitudes avec les apatites biologiques.

The development of biocompatible materials allowing the local delivery of specific drugs is of high interest to repair pathological bone defects. The first part of this manuscript describes the synthesis and the characterisation of calcium phosphates glasses doped with gallium, which is a bone resorption inhibitor. The nature of the phosphate network is probed by 31P NMR and the Ga3+ local environments are studied 71Ga NMR at very high magnetic field (20T) and ultra-fast spinning frequency. The leaching behaviour of these glasses is investigated by NMR and ICP-AES. The obtained results indicate that the glass dissolution is nearly congruent and that Ga3+ doping improves the chemical durability. The second part of this work is dedicated to the study of the Bioglass® 45S5 which is a bioactive glass (SiO2-CaO-Na2O-P2O5 glassy system) used in bone repair surgery. Double-resonance NMR experiments are used to obtain information about the association between the phosphate units and the silicate network. NMR analyses are also used to characterize quantitatively the various species formed at the glass surface after immersion into a simulated body fluid for varying periods. Results obtained from NMR and other characterization methods revealed that the carbonated hydroxyapatite formed at glass surface shows strong similarities with biological apatites.; Le développement de matériaux biocompatibles permettant la vectorisation de principes actifs est particulièrement souhaitable dans le cadre de la réparation osseuse liée à certaines pathologies. Dans la première partie de ce mémoire, nous décrivons la synthèse et la caractérisation de verres de phosphates de calcium dopés avec du gallium qui est un agent inhibiteur de la résorption osseuse. Les modifications du réseau phosphate sont étudiées par RMN du 31P et les différents environnements locaux du Ga3+ sont mis en évidence par RMN du 71Ga en utilisant des conditions expérimentales spécifiques (très haut champ magnétique de 20T et rotation de l’échantillon ultra-rapide). Le comportement en solution de ces verres a été étudié par RMN et par ICP-AES. Les résultats obtenus indiquent qu’ils sont soumis à une dissolution quasi-congruente et que l’ajout de Ga3+ augmente leur durabilité chimique. La seconde partie de ce travail est dédiée à l’étude d’un verre bioactif utilisé en chirurgie réparatrice osseuse : le Bioglass® 45S5 (système SiO2-CaO-Na2O-P2O5). L’utilisation d’expériences RMN de double résonance a permis d’apporter des éléments de réponse sur le type d’association entre les groupements phosphates et le réseau silicate. Après immersion de ce verre dans un fluide physiologique simulé (SBF), un suivi quantitatif des espèces, initiales et formées à la surface du verre, a été réalisé par RMN. Les résultats obtenus par RMN et par d’autres techniques de caractérisation montrent que l’hydroxyapatite carbonatée se formant en surface du verre présente de grandes similitudes avec les apatites biologiques.

International audience; INTRODUCTION: Calcium-containing (CaC) crystals, including basic calcium phosphate (BCP) and calcium pyrophosphate dihydrate (CPP), are associated with destructive forms of osteoarthritis (OA). We assessed their distribution and biochemical and morphologic features in human knee OA cartilage. METHODS: We prospectively included 20 patients who underwent total knee replacement (TKR) for primary OA. CaC crystal characterization and identification involved Fourier-transform infra-red spectrometry and scanning electron microscopy of 8 to 10 cartilage zones of each knee, including medial and lateral femoral condyles and tibial plateaux and the intercondyle zone. Differential expression of genes involved in the mineralization process between cartilage with and without calcification was assessed in samples from 8 different patients by RT-PCR. Immunohistochemistry and histology studies were performed in 6 different patients. RESULTS: Mean (SEM) age and body mass index of patients at the time of TKR was 74.6 (1.7) years and 28.1 (1.6) kg/m², respectively. Preoperative X-rays showed joint calcifications (chondrocalcinosis) in 4 cases only. The medial femoro-tibial compartment was the most severely affected in all cases, and mean (SEM) Kellgren-Lawrence score was 3.8 (0.1). All 20 OA cartilages showed CaC crystals. The mineral content represented 7.7% (8.1%) of the cartilage weight. All patients showed BCP crystals, which were associated with CPP crystals for 8 joints. CaC crystals were present in all knee joint compartments and in a mean of 4.6 (1.7) of the 8 studied areas. Crystal content was similar between superficial and deep layers and between medial and femoral compartments. BCP samples showed spherical structures, typical of biological apatite, and CPP samples showed rod-shaped or cubic structures. The expression of several genes involved in mineralization, including human homolog of progressive ankylosis, plasma-cell-membrane glycoprotein 1 and tissue-nonspecific alkaline phosphatase, was upregulated in OA chondrocytes isolated from CaC crystal-containing cartilages. CONCLUSIONS: CaC crystal deposition is a widespread phenomenon in human OA articular cartilage involving the entire knee cartilage including macroscopically normal and less weight-bearing zones. Cartilage calcification is associated with altered expression of genes involved in the mineralisation process.

This thesis deals with synthesis, densification, mechanical characterization and functionalization of mono- and biphasic calcium phosphate bioceramics. Calcium phosphate powders were synthesized by aqueous precipitation technique by mixing salts of calcium and phosphate. The Ca/P ratio of reactants was adjusted to obtain powders of β-tricalcium phosphate (TCP), hydroxyapatite (HA) and biphasic calcium phosphates containing 20 to 80% of HA (BCP). After calcination, grinding and shaping by slip casting of these powders, materials thus obtained were densified by two techniques: natural sintering and post-sintering by hot isostatic pressing (HIP). The natural sintering of all of these ceramics has led to the achievement of high densification equal or above 98%. The HIP has, in turn, allowed a densification ration close to 100% and made transparent samples, indicating the absence of porosity. Then these sintered materials were mechanically characterized by different techniques allowing determination of Young's modulus, bending strength, hardness and toughness values as a function of HA content. Densification of stoichiometric calcium phosphates to nearly 100% leads to the intrinsic properties of these biomaterials. Biological assays, functionalization by phage and an antibiotic have finally been realized on these materials.; Ce mémoire de thèse traite de la synthèse, de la densification, de la caractérisation mécanique et de la fonctionnalisation de biocéramiques de phosphates de calcium mono et biphasées. Les poudres phosphocalciques ont été synthétisées par la technique de précipitation en phase aqueuse par mélange de sels de calcium et de phosphate. Le rapport Ca/P des réactifs a été ajusté de manière à obtenir des poudres de phosphate tricalcique β (TCP), d'hydroxyapatite (HA) et de phosphates de calcium biphasiques contenant de 20 à 80% d'HA (BCP). Après calcination, broyage et mise en forme par coulage en moule de plâtre de suspensions issues des poudres synthétisées, les matériaux ainsi obtenus ont été densifiés par deux techniques : le frittage naturel et le post-frittage par pressage isostatique à chaud (HIP). Le frittage naturel de l'ensemble de ces céramiques a conduit à l'obtention de taux de densification supérieurs ou égaux à 98%. Le HIP a, quant à lui, permis une densification proche de 100% et rendu les échantillons transparents, signe de l'absence de porosités. Ces matériaux ainsi densifiés ont, ensuite, été caractérisés mécaniquement par différentes techniques permettant la détermination du module d'Young, de la résistance à la flexion, de la dureté et de la ténacité en fonction de la teneur en HA. La densification des phosphates de calcium stœchiométriques à près de 100% donne accès aux propriétés intrinsèques de ces biomatériaux. Des essais biologiques, une fonctionnalisation par des phages et un antibiotique ont été mis en œuvre sur ces divers matériaux.

Autograft is considered as the "gold standard" for bone reconstruction. It provides osteoinductive factors, osteogenic cells, and appropriate osteoconductive scaffold. Donor site morbidity is the main limitation of autograft. Donor disease transmission limits the use of allograft. Synthetic bone substitutes still lack osteoinductive or osteogenic properties. Composite bone substitutes combining synthetic scaffold and biochemical substances initiating proliferation and cell differentiation, and possibly osteogenesis. Bone substitutes and grafts intended for clinical use are listed.

Crystal-induced arthritis (CIA) is easy to diagnose as soon as the physician might suspect the diagnosis. Indeed, CIA can be readily ascertained since one single gold standard is available: identification of microcrystals in synovial fluid or in other materials (tophus, synovial tissue biopsy, periarticular tissues). It is therefore mandatory to perform joint aspiration and to get synovial fluid sample for microscopic examination. Monosodium urate crystals are the key feature of gout, and calcium pyrophosphate (CPP) crystals are associated with CPP disease, also called "chondrocalcinosis" in France. Diagnosis of gout can be readily suspected when considering typical clinical presentations such as podagra, presence of tophi, cardiovascular comorbidities, and diuretics use. Plain radiographs, as long as technical quality is present, are an easy way to suspect and eventually to diagnose CPP disease or apatite deposits in any articular or periarticular site. Joint ultrasonography when performed by skilled physicians can easily help in displaying crystal deposits at the cartilage surface (gout) or within the cartilage (CPP), along with peri-tophaceous inflammatory reaction as evidenced by power Doppler.

Bone substitutes are rarely used in the reconstruction of cleft lip and palate. The graft material of choice is cancellous bone, harvested in the hip or tibia. Tibial harvesting may lead to postoperative morbidity, or even complications. This has lead surgeons to develop alternative solution. We present a secondary alveolar bone grafting technique using synthetic calcium phosphate ceramics.A patient presenting with a complete unilateral cleft lip and palate was treated by alveolar bone grafting at the age of nine years, using a mixture of autologous bone, harvested on the operative field, and particles of biphasic calcium phosphate (BCP); the graft was included in a platelet rich plasma (PRP) gel. The patient was followed up for eight years after the procedure. No sign of early or late infection was observed. At the end of facial growth, the cuspid had erupted correctly in a safe periodontal environment. Sequential X-rays showed complete filling of the initial bone defect, progressive resorption of ceramics, and spontaneous eruption of the cuspid.In this long-term follow-up report, the use of BCP mixed with autologous bone did not interfere with dental eruption or maxilla growth. A second bone-harvesting site was thus avoided. BCP could be a suitable alternative to autologous bone graft for secondary alveoloplasty.

Revisiting the chemical diversity of the crystalline phases of prostatic calculi by means of SEM and FT-IR analysis.A set of 32 prostatic calculi has been studied by FT-IR and SEM.FT-IR analysis has determined the chemical composition of each prostatic calculus and the SEM observation has described the morphology of the calculi surfaces and layers. Infrared analysis revealed that 90.7% of the stones were mainly composed of calcium phosphates. However, several mineral phases previously not reported in prostatic calculi were observed, as brushite or octocalcium phosphate pentahydrate.Prostatic calculi exhibited a diversity of crystalline composition and morphology. As previously reported for urinary calculi, relationships between composition and morphology of prostatic stones and étiopathogenic conditions could be of interest in clinical practice.

Hydroxyapatite crystals are a common cause of periarticular disease. Virtually, any joint can be involved, but the shoulder is by far most commonly involved. These calcifications, often asymptomatic, can lead to an acute microcrystalline tendinitis or bursitis, which may simulate infection. The diagnosis of periarticular calcifications relies on imaging techniques using X-rays or ultrasounds. Treatment of acute tendinitis or bursitis includes icing, rest, analgesics or non steroidal anti-inflammatory drug and oral steroids or local steroids injection. Removal of the deposit can be considered in patients with chronic pain, particularly at the shoulder.

Secondary hyperparathyroidism is associated with an increased risk of skeletal fractures and mortality in dialysis patients. Classical treatments such as active vitamin D derivatives and surgical parathyroidectomy are efficient but have some limitations. Second generation calcimimetics allow to control serum PTH levels without increasing serum calcium phosphorus product. This article reviews the physiological bases of PTH regulation, the mode of action of calcimimetics and the results of preclinical and clinical studies evaluating the effect of calcimimetics on different biochemical, clinical and histological parameters.

The main cause of resistance to erythropoiesis-stimulating agents (ESA) used for treatment of anemia in chronic hemodialysed patients (CHP) is the iron deficiency, absolute or functional. Secondary hyperparathyroidism (SHPT) is a secondary factor of resistance. Indeed, it has been reported in the literature an improvement of anemia parameters after surgical parathyroidectomy (PTX). The objective of this study is to assess in CHP, the impact of the correction of SHPT by a calcimimetic, cinacalcet (CI), (which is considered as a pharmacological PTX) on the response to ESA, measured by the erythropoietin resistance index (ERI). Twenty-two CHP with severe SHPT documented by an intact parathyroid hormone (iPTH) above 800pg/mL were included in this prospective pilot study. Mineral bone metabolism, anemia and nutritional parameters were measured baseline and after 6 months of treatment by CI. The effect on anemia was assessed at the end of study by the ERI, the change in Hb concentration, and the proportion of patients with Hb levels above 11g/dL.At the end of study there was a significant decrease (M6 vs M0) in iPTH (1302 vs 674pg/mL or -48%, p=0.006), serum calcium (2.39 vs 2.15mmol/L or -10%), serum phosphate (2 vs 1.7mmol/L or -15%), serum calcium-phosphorus product (CaxP) (4.8 vs 3.8mmol(2)/L(2) or - 20% (p0.05), and the number of patients with CaxP4.4mmol(2)/L(2) (64 vs 32%, p0.05). The level of bone alkaline phosphatase remained stable during the study (28 vs 27 IU/L). The Hb levels increased from 11 to 11.4g/dL, as did the proportion of patients whose Hb concentration reached 11g/dL or higher (50 vs 70%, p0.05) without important change of the median weekly ESA dosis in the majority of patients, 18 cases (81%) vs four (19%). Two subgroups were identified from the median decreases in iPTH (delta iPTH) between M0 and M6, Group 1 (delta iPTH≥400pg/mL, n=10) and group 2 (delta iPTH400pg/mL, n=12): in group 1, we found a correlation between the decrease in iPTH by CI and the stability or decrease in ERI (group 1), at comparable dose of dialysis, nutritional and iron intakes and inflammatory profiles; in group 2 without a significant effect of CI on PTH reduction the levels of ERI and ESA dosis were more elevated.A treatment by calcimimetic improves the control of anemia by ESA in CHP and interferes positively on a cause of secondary resistance to ESA represented by SHPT. The mechanism of these effects could be linked to the decreased of bone marrow fibrosis and inflammation and to the triptych formed by the reduction in iPTH, CaxP and phosphate.

The use of bone substitutes in massive sinus-lift pre-implant procedures remains controversial. The aim of our study was to evaluate the long-term reliability of pure-phase beta-tricalcium phosphate (betaTCP, Cerasorb, Curasan, Kleinostheim, Germany) used in this particular indication.Twenty patients (33sinus) presenting with severe sinus floor atrophy (class 4 to 6 according to Cawood) and having undergone a sinus lift procedure by mean of betaTCP were followed in a prospective study between January 2002 and May 2008. The surgical approach was classical (under local anesthesia in eight patients) and the sinuses were filled with betaTCP (6 cm3 on average per sinus) and autologous growth factors (platelet rich plasma PRP and platelet rich fibrin PRF, according to the technique described by Dohan and Weibrich). One hundred and twenty-three dental implants were inserted in the grafted sinuses between the fourth and the eighth postoperative month (Nobel Biocare MK III and MK IV-mean length: 12.44 mm) using a 2-step buried technique and loaded between the fourth and the sixth month. Follow-up included regular clinical examination and panoramic X-rays to screen for possible sinus and implant complications. The control X-rays also allowed measuring the biomaterial resorption rate.The mean postoperative follow-up was 4.5 years for the sinus lift procedures and 4 years for the implants. We noted one case of local infection at the 15th postoperative day (3%). The implant success rate was 97.6% (lack of osteo-integration for two implants in the same patient, one failure after loading). The prosthetic success rate was 100%. The mean resorption rate of the material was 20.3% and the mean gain of height was 16.9 mm.The use of betaTCP associated to growth factors (PRP ou PRF) without bone graft, in massive sinus-lift procedures induces few complications. The implant success rate is comparable to the one obtained by using autologous bone grafts. The resorption rate of the material is comparable to that of autologous bone.

Based on a new concept, a procedure combining induced membranes and cancellous autografts allows the reconstruction of wide diaphyseal defects. To date, this procedure is limited by the amount of cancellous bone available from the patient and by the related morbidity at the donor site. The aim of this study was to evaluate the biological effect of induced membranes on a cylindrical-shaped ceramic implants loaded with OP-1 in heterotopic site.Sixty hydroxyapatite tricalcium phosphate (HA-TCP) implants, 20 of which being loaded with a bone growth factor (rhOP-1) were inserted either in a subcutaneous tunnel or within a previously induced membrane on the back of rabbits. There were two time-points at four and 16 weeks. Implants were investigated at three different levels (extremities and middle).None of the untreated implants showed any evidence of bone formation. Implants inserted in an induced membrane presented with less resorption. Bone ingrowth within the pores of the materials was significantly higher when the implants were inserted into the induced membrane whatever the time-point considered.The membrane seems to play the role it was assigned, i.e. to protect and revascularize the implant, thus favouring osteogenesis that occurs in 80% of the implants after four months.

Parenteral nutrition is actually a known method of administration of nutriments but not without risk. During the compounding of parenteral nutrition (PN) mixtures, the most pharmaceutical problem is the addition of calcium and phosphates. Since this two minerals can form insoluble precipitate that will lead to catheter occlusions and/or pulmonary emboli. Several reports has been related about suspect deaths following a PN infusion contaminated by precipitates or particles, this situation led the Food and Drug Administration (FDA) to recommend the use of filters. The precipitation of calcium phosphate is not easily predictable when the concentrations of these two salts are high and this situation constitute one of the major danger that can destabilise the parenteral nutrition admixture. Although such events still appear to be rare, it should be possible to eliminate them with improved pharmaceutical practice.

The goal of this prospective study was to characterize ureteral stents encrustation in stone formers.We report the results of a study based on 658 double-J stents (412 men and 246 women) collected from patients with in situ urinary calculi. The mean age was 48.2+/-16.0 years without differences between genders. Ureteral stent encrustation was analysed by infrared spectroscopy. Results are expressed according to the main component.The mean indwelling time was 73.5+/-73.2 days. The main component in stent encrustations was calcium oxalate (43.8%), essentially the monohydrate form (27.1%), followed by proteins (27.4%), calcium phosphates (16.4% with 8.4% brushite), and uric acid (5.2%). Struvite, detected on 49 stents, was the main component in 2.4% of cases. Significant differences according to gender and age were found: calcium oxalate monohydrate, which represented 24.5% in 20 to 29 years old men class increased to 37.0% in 50 to 59 years class and then decreased in older patients. Calcium oxalate dihydrate increased with age up to 70 years in women while it felt dramatically in man beyond 50 years old. Brushite was more abundant in young men (20.4% in patients aged 20-29 years) and was decreasing beyond this age while it remained in stable proportion for all age classes in women. Increasing prevalence of uric acid encrustations with age was observed, especially in men beyond the age of 70 years. Mineral encrustations increased with the indwelling time, the part of mineral being preponderant after 15 days: 7,3% of the stents had become massively encrusted within 113 days mean period. The comparison between biomaterials showed that silicone stents were significantly less encrusted than polyurethane stents.Stent encrustation constitutes a serious complication of ureteral stent use in stone formers. Lithogenic factors should be considered for the prevention of stent encrustation in these patients.

Management of bone stock loss remains one of the most challenging problems for revision hip surgery. The aim of this retrospective study was to report the preliminary results of peri-prosthetic femoral defect reconstruction with impacted granules of calcium phosphate ceramic.Fourteen hips in 13 patients (3 men and 10 women) were evaluated. Age at surgery ranged from 30 to 79 years (mean 66.1 years). All revised devices had been cemented. Femoral revision was indicated for loosening in eleven hips (including six septic cases), femoral osteolysis (one hip), persistent pain (one hip), and recurrent dislocation (one hip). On the preoperative radiological evaluation, bone defects were assessed as SOFCOT grade II in seven case, and grade III in fourteen. None was rated grade IV. Once the loose prosthesis had been removed, bone graft or ceramic granules (14 cases) were firmly impacted in the femoral canal. The stem was standard and always cemented using modern cementing technique.At a mean follow-up of 34 +/- 15 months (range 14-76 months), eleven of fourteen hips were rated good or very good according to the Postel-Merle-d'Aubigné score. One diaphyseal femoral fracture occurred and later united. Two hips required re-revision (one aseptic femoral loosening, one septic recurrence). Direct bonding between synthetic graft and bone was observed on standard radiographs in eleven cases. Stem subsidence occurred in two cases and was limited (mean 4.5 mm).Femoral bone reconstruction using impacted calcium phosphate ceramic in revision hip arthroplasty provided encouraging results in the short to mid term. Femoral stock restoration was achieved in the great majority. No adverse effect related to the use of a synthetic graft was noted. Further long-term evaluation is required before wider application.

Synovial fluid analysis is a very important diagnostic procedure in rheumatology. Cell count allows the differentiation ting between inflammatory arthritis, in which cell count exceeds 2000 cells/mm3, and non inflammatory arthropathy, in which cell count is less than 1000 cells/mm3. Demonstration of crystals in synovial fluid is a rapid and inexpensive way to diagnose microcrystalline arthritis. Synovial fluid must be examined under normal and polarized light. Monosodium urate crystals are negatively birefringent, whereas calcium pyrophosphate dihydrate crystals are positively birefringent. Other crystals (cholesterol, oxalate, corticosteroids....) can also be identified in synovial fluid. Various artefacts must be avoided including anticoagulant crystals and synovial fluid must be anticoagulated with sodium heparin or citrate.

We report our experience with a B tricalcium phosphate ceramic to fill open-wedge tibial osteotomy gaps.Seventy high tibial open-wedge osteotomies were performed in 70 patients (47 men and 23 women). Ostotomy was performed for osteoarthritis in 56 knees, Ahlback classification stage I (n = 18), stage II (n = 32), stage III (n = 6) and for congenital varus in 14. Mean patient age was 45.2 years (16-69). We used a wedge-shaped piece of ceramic with an appropriate angle, which was associated with granulated material to complete the gap filling for the last 20 cases. One or two staples were used for fixation. Clinical and radiological outcome was assessed at 6 weeks, 3 months, 6 months, and at last follow-up. Mean follow-up was 18 months.There were no biological or clinical complications related to biomaterial intolerance. Tolerance to the osteosynthesis material was mediocre since we observed one infection and 12 cases of pain related to the staples which required material removal in 8 patients. Bone healing was achieved in 98.5%. Final correction was between 3 degrees and 6 degrees valgus in 80.5%. There was a loss of correction angle between the postoperative film and the bone healing film. Factors related to sustained correction were: non-fractured wedge, intact lateral tibial cortical, osteosynthesis with two staples. Osteointegration was good and rapid in 96%. We found two complete lucent lines at last follow-up but with variable resorption depending on the shape of the bone substitute.Use of a ceramic wedge to fill high tibial medial open-wedge osteotomy gap is a reliable reproducible technique providing correction without formation of a malalignment callus. Bone healing is achieved in 98.5% of the cases at about three months. Osteointegration is good in 96%. Resorption is complete and rapid when the substitute is implanted in granular form in a cancellous zone and is partial and slow when implanted as a massive wedge.

The authors have made an histological study of the evolution, after 120 days, of coral implant and tricalcic phosphate ceramic implant in each femur of 12 rabbits. The results have shown on the one hand that ceramic is resorbed faster than coral, on the other hand that for both types of biomaterials the resorption was much faster for the implants in contact with the bone-marrow than for those which were not.

Comminution is often neglected in patients presenting fractures of the distal radius. Use of injectable bone substitutes can fill the gap left by comminution, avoiding radial shortening and loss of prono-supination.Forty-eight patients with a distal fracture of the radius were treated by osteosynthesis and injectable cement between 1998 and 2001. These patients were reviewed at mean follow-up of 46 months (36-56). Dorsal displacement was present in all cases and the AO classification was A (n=26), B (n=15), C (n=7). Fixation was achieved with pins (n=32), posterior plate (n=14), and external fixator (n=2) before injection of the bone substitute. Outcome was evaluated with the Herzberg score, the Gartland and Werley score and DASH by an independent operator.Four patients were lost to follow-up and five who developed a deformed callus after the initial osteosynthesis were excluded from the analysis. The Herzberg functional score reached 84 (range 54-100) and the Gartland and Werley radioclinical score was 4.6 (0-11) with 89% excellent and good outcomes. DASH was 23.6 (5.8-62.7). Ulnar variance was unchanged or changed less than 2 mm between the immediate postoperative period and last follow-up in 88% of patients. There was one carpal tunnel syndrome related to anterior cement leakage. Three biopsies were performed and revealed a "humid sand" aspect six months after injection as well as presence of osteoblasts within the bone substitute. There was no or very little resorption.Several authors have demonstrated the biomechanical and functional effects of filling the comminution gap to avoid radial shortening. The first reported cases, then later prospective series, favored the use of injectable cements for patients with comminution. Cement used in our patients allowed preservation enables preservation of normal ulnar variance in addition to filling the gap. Like any bone substitute, it is an attractive alternative to other filling methods (ceramic graft) offering two advantages: adaptation to the bone defect and primary stability. This easy-to-use cement is resorbed slowly. Because of high cost, it may be reserved for patients with important functional needs.

We report a case of a 33 years old female with a history of paroxystic hemidystonia treated by acetazolamide, a carbonic anhydrase inhibitor (CAI), and who developed two years after the initiation of this treatment bilateral radio-opaque stones. Laboratory tests revealed a hyperchloremic acidosis, an elevated urinary pH, a hypercalciuria, a severe hypocitraturia and numerous granulations of amorphous carbonated calcium phosphates and brushite crystals on urinary microscopic examination, the whole suggests a diagnosis of acetazolamide-induced nephrolithiasis. We discuss in this article the lithogenetic process and the usual composition of the stones induced by CAI, and specific risk factors for developing drug-induced lithiasis which should be taken into consideration when prescribing long-term drug regimens.

Crystalluria is a marker of urine supersaturation present in both normal and pathological conditions. Indeed, nature and characteristics of the spontaneous crystalluria are of clinical interest for detecting and following biological disorders involved in renal diseases. Method. Crystalluria examination should preferably be performed on first morning urine or fresh fasting voiding samples by polarised microscopy in a Malassez cell. Urine samples must be stored at 37 degrees C or at room temperature and examined within two hours following voiding. Results and discussion. Crystalluria should be interpreted according to various criteria: 1) chemical nature of crystals for abnormal crystals such as struvite, ammonium urate, cystine, dihydroxyadenine, xanthine or drugs; 2) crystalline phase of common chemical species as calcium oxalates, calcium phosphates and uric acids; 3) crystal morphology (calcium oxalates); 4) crystal size (calcium oxalates); 5) crystal abundance (calcium oxalates, calcium phosphates, uric acids, cystine); 6) crystal aggregation (calcium oxalates); 7) frequency of crystalluria assessed on serial first morning urine samples, a very useful tool for long-term surveillance of patients. Within calcium oxalate crystalluria, presence of whewellite is a marker of elevated oxalate concentration (urine oxalate0.3 mmol/L); a crystal number200/mm 3 is highly suggestive of heavy hyperoxaluria of genetic or absorptive origin. Predominant weddellite crystalluria is most often indicative of an excessive urine calcium concentration (3.8 mmol/L); a dodecahedric aspect of the crystals is a marker for heavy hypercalciuria (6 mmol/L) while an increased crystal size (or= 35 microm) is indicative of simultaneous hypercalciuria and hyperoxaluria. Calculation of the global crystal volume, especially when applied to calcium oxalates or cystine, is a clinically useful tool for the monitoring of patients suffering from primary hyperoxaluria or cystinuria. Lastly, presence of crystalluria in more than 50% of serial first voided morning urine samples is in our experience the most reliable biological marker for detecting the risk of stone recurrence in lithiasic patients. Conclusion. Crystalluria examination is an essential laboratory test for detecting and following pathological conditions, which may induce renal stone disease or alter kidney function due to urine crystals.

Diagnosis and treatment of osteoporosis are focused on demineralisation but bone mineral density is not directly correlated with bone strength. As with every material, the mechanical strength of bone depends upon its Young's modulus and its cross-sectional moment of inertia. In the clinical situation, bone strength can be quantified using peripheral quantitative computed tomography imaging (pQCT), a non-invasive imaging method, which allows calculation of a strength index. In this study, we tried to increase the fracture threshold of the distal radius by directly increasing bone strength rather than density. Twenty wrists in 10 cadavers were filled percutaneously with a calcium phosphate cement. Fluoroscopy and pQCT were performed twice, once before cementing and again 24 h after cement crystallisation to hydroxyapatite. We obtained measurements of trabecular and total bone density, and also stress strain index (SSI). Our results showed that trabecular bone density increased by a factor of 2.85, whereas total bone density increased by 1.61 and SSI by 1.99. Fluoroscopy showed two small leaks of cement at the point of injection. This study demonstrated that percutaneous injection of calcium phosphate cement increased distal radius strength, and consequently its fracture threshold. This technique could be employed in the future to prevent the occurrence of fractures in osteoporotic patients.

We report successful use of calcium-phosphate cement for the treatment of benign polyostotic fibrous dysplasia in a patient who had undergone several unsuccessful surgical procedures. As no autologous bone was available for further grafting, we used a bone substitute to fill two defects, one in the upper part of the humerus and the other in the radial shaft. The curettage cavity was filled with calcium-phosphate hydroxyapatite cement. The type of bone substitute was chosen for its specific properties: mineral structure similar to bone, microporosity, resistance to compression between cancellous and cortical bone, composition favorable to exchange between the crystals and the interstitial medium. Outcome was favorable early for the shoulder and later for the forearm after surgery for recurrence. Due to progress in the development of diphosphonates, indications for surgery for fibrous dysplasia have been reduced. There remains a risk of recurrence and incomplete results but bone substitute filling can be a useful alternative to autografts and complementary fixation. Calcium-phosphate cement is an easy-to-use paste-like product with interesting physicochemical and biological properties making it a leading choice for bone substitution.

Calcium phosphate ceramics are synthetic bone substitutes able to fill in bone destruction as a support of the bone growth. This work consisted in an in vitro assessment of osteoblasts and fibroblasts cultures on macroporous calcium-phosphate bone substitutes to analyze the interaction between cells and bone substitute.The macroporous ceramic was composed of 70% hydroxyapatite and 30% tri-calcium phosphate with known mechanical and physico-chemical properties. Three compounds were processed with different size of macropore and with or without microporosity on their surface. Cells were seeded on discs measuring 10 mm in diameter and 2 mm in thickness. Cellular viability was evaluated by the MTT test for every stage of observation. An histological study to observe the invasion in the depth of discs was performed. Scanning electron microscopy was used to analyze the cellular comportment in contact with the surface of substitutes.An exponential cellular growth was effective on each substitute with the two cellular types. Cells spread on the surface of the compounds covering macropores and colonized the depth of the discs. A size of macropore of 300 microm or more seemed to support this invasion. 15 microm sized interconnections appeared to be effective to allow cell migration between macropores. The cell proliferation was similar on substitutes with or without microporosity.Biomaterials currently used as bone substitute are more or less osteoconductive but they have no osteoinductive property. A hybrid association of calcium-phosphate ceramic with osteogenic cells should promote the development of a calcium phosphate compound with osteoinductive capacity.

We present a minimally invasive technique for tibial valgus osteotomy using a medial wedge composed of tricalcium phosphate.The bone substitute is composed of slowly resorbable tricalcium phosphate material shaped to the desired form and having mechanical properties allowing stable osteotomy via a short incision and staple fixation. Intraoperative fluoroscopy enables a reliable and reproducible technique. A lateral fixation staple is required because there is a risk the lateral hinge could break. This technique was used for 58 knees in 55 patients (mean age 47 years). According to the Ahlback classification of femorotibial degeneration, there were 43 grade I knees, 12 grade II, and 3 grade III.The implant was well tolerated in all cases. Bone healing was achieved in most cases without loss of the osteotomy angle. Complications were: rupture of the lateral hinge in four cases leading to nonunion in one, one low-grade infection. Implant resorption at mid term was significant: among the 22 patients with a follow-up of more than 5 years, the implant was barely visible in 18.This technique provides an easy way to achieve tibial valgus osteotomy without compromising future intervention. The technique can be considered to be minimally invasive because of the size of the incision, the minimal fixation required, and the bone sparing effect of the bone substitute.

Different kinds of calcium phosphate biomaterials can be used as bone substitutes. Ceramics are constituted by HA or TCP grains linked by grain boundaries. Their porosity depends on the powder characteristics and the sintering temperature. It can be very low with a pore size inferior to one micron. The setting of calcium phosphate hydraulic cements results from the precipitation of a calcium phosphate phase different from the one in suspension in the paste. The strength of the cement is given by the entanglement of the growing mineral crystals. Calcium phosphate hydraulic cements and ceramics have very different physico-chemical characteristics. We have studied the histological integration of both kinds of material. The first material was constituted by macroporous ceramics composed of 75% HA and 25% beta-TCP, the cement was made of beta-TCP grains dispersed in a DCPD matrix. The sequence of events which leads to the ceramic integration is always the same: a/ ingrowth of a loose connective tissue; b/ osteoblast differentiation from fibroblast-like cells of the connective tissue in close proximity to the implant surface; c/ osteoid synthesis at the ceramic surface toward the pore center; d/ remodeling of the immature bone and the ceramic itself. The cement is differently integrated. The osteoblasts differentiate at some distance from the implant and there is a trabeculae ingrowth toward the material.The early stages of both materials osteointegration are different. The integration is centrifugal for ceramics and centripetal for the cement.

MRI is becoming an important tool of examination of the head and neck. However, certain dental alloys cause artifacts characterized by a loss of signal surrounded by bright line and sometimes distortions. In our work, we studied artifacts caused by Titanium, metallic biomaterial used for oral implantology. Therefore, 2 experimental were investigated in a 1.5 T MR unit, with 2 sequences commonly used (SE, GRE). The investigation showed minor artefacts, without distortions. In order to minimize these "ghost images", the Titanium and its alloys should be an alternative.

Synthetic bone substitutes like calcium phosphate ceramics have been used in orthopaedic surgery for several years. The aim of this study was to assess the results of the use of tricalcium phosphate beta for filling bone defects in trauma cases.beta tricalcium phosphate was used in 24 trauma cases. The GESTO classification (Association pour l'étude des Greffes et Substituts Tissulaires en Orthopédie) and a qualitative scale were used to estimate the integration.With a mean follow-up of 20 months, integration was excellent in 41.2%, good in 29.2% and moderate in 17.4%. No fibrous encapsulation was observed around the implants in any case. Sepsis occurred in 3 cases with open fractures.beta-Tricalcium phosphate seems in our experience to be an excellent bone substitute for filling bone defects in trauma cases.

The effectiveness of a macroporous biphasic calcium phosphate ceramic was studied after laterovertebral arthrodesis in sheep. A ceramic with a TCP/HAP ratio of 35/65 was compared with autologous bone graft in an histomorphometric and biomechanical point of view. Quantitative analysis of the results indicated that the biphasic ceramic allows an arthrodesis after 12 months, although control graft is effective after six months. A large decrease of flexibility in all directions was obtained with the ceramic, similarly to autologous graft. No nonfusion case was observed. In conditions very close to the human surgery, a posterolateral fusion can be obtained using biphasic phosphate ceramic as bone substitute.