Awa Yasmina

Faridha Sawadogo
email: faridha.sawadogo@univ-lorraine.fr

Sébastien Roux
email: sebastien.roux@univ-lorraine.fr

André Lecomte
email: andre.lecomte@univ-lorraine.fr

Bioreceptivity of Portland and Calcium Sulphoaluminate Cements in Urban Sewerage Networks

1. Introduction

Cements are essential materials for construction. Those listed in the European standard NF EN 197-1 [START_REF]NF EN 197-1 Cement part 1: Composition, specifications, and conformity criteria for common cements[END_REF] all contain Portland clinker, a significant source of CO2 from the decarbonation of limestone and cooking fuels. Calcium Sulphoaluminate cements (CSA) can however constitute a more ecological alternative to their use because their clinker is obtained by firing a powder in which the limestone is partially replaced by bauxite and calcium sulphate [2; 3] at a more moderate temperature. The major constituent of CSA clinker is ye'elimite Ca4Al6(SO4)O12 which is a variety of calcium sulphoaluminate.

Sewerage networks are made up of a set of underground structures built in stone, brick, cast iron, ceramics, PVC and, especially, concrete. Due to their physical-chemical properties, the effluents conveyed in these networks constitute favourable environments for the proliferation of numerous micro-organisms which naturally interfere with the materials that make up the structure whether submerged and/or emerged [START_REF] Tulliani | Sulfate attack of concrete building foundations induced by sewage waters[END_REF] This often results in superficial bioalterations (stains, dirt), or even deeper biodeteriorations that can affect and even improve the structural properties of the structure [START_REF] Roux | Alteration of cement pastes by bacterial colonization[END_REF]. However, these pathologies depend on the bioreceptivity of the concrete support, i.e. its capacity to be colonized by the present microorganisms [START_REF] Guillitte | Bioreceptivity: a new concept for building ecology studies[END_REF].

Many parameters condition the bioreceptivity of concretes including:

-Porosity, mainly controlled by the water dosage of the fresh mix (water/cement ratio). This conditions the pore volume (the quantity of pores whose size varies from a few nanometres to a few millimetres [START_REF] Wiktor | Accelerated weathering of cementitious matrix for the development of an accelerated laboratory test of biodeterioration[END_REF]) and also influences surface roughness. The porous network may be more or less connected and can also be the vector for the penetration of external agents such as biological elements (microorganisms, rhizoids) and metabolites [START_REF] Tulliani | Sulfate attack of concrete building foundations induced by sewage waters[END_REF][START_REF] Roux | Alteration of cement pastes by bacterial colonization[END_REF]; -Surface condition, characterized in particular by roughness, topography and pH [START_REF] Wiktor | Accelerated weathering of cementitious matrix for the development of an accelerated laboratory test of biodeterioration[END_REF][START_REF] Giannantonio | Effects of concrete properties and nutrients on fungal colonization and fouling[END_REF].

The carbonation of cementitious materials decreases the alkalinity of the surface (from a pH ≈ 13 to a pH ≈ 9.5), which favours the colonization of neutrophilic bacteria and the formation of a biofilm [START_REF] Lors | pH variations during growth of Acidithiobacillus thiooxidans in buffered media designed for an assay to evaluate concrete biodétérioration[END_REF], i.e. a group of microorganisms in which the cells stick together; -The chemistry and mineralogy of cement, including the nature and proportions of the hydrated phases that may be conducive to the development of certain microorganisms [START_REF] De Belie | Experimental research and prediction of the effect of chemical and biogenic sulfuric acid on different types of commercially produced concrete sewer pipes[END_REF]; -The physical-chemistry of the surrounding environment, including temperature, hygrometry, pH, oxygen, carbon dioxide, nutrients present, etc. [10; 11]. These parameters can promote or inhibit the development of some varieties of microorganisms depending on their neutrophilic or acidophilic character, which reflects their needs and/or metabolic intolerances [START_REF] Roux | Alteration of cement pastes by bacterial colonization[END_REF]; -Microorganisms present in contact with the material (genus, species, etc.) [START_REF] Magot | Microorganisms and metabolism, Biodeterioration of materials[END_REF]; -Etc. Moreover, in the case of concrete sewerage network, studies have shown that the most severe biological degradation is linked to the sulphur cycle controlled by the presence of hydrogen sulphide (H2S) [10; 13]. The latter comes from the metabolic activity of the Sulphate-Reducing Bacteria (SRB) that develop in anaerobic zones, when the flow of effluents is low. This is because the liquid medium is then poor in oxygen and so the SRB, by their metabolism are capable of reducing the sulphates present to hydrogen sulphide [START_REF] Barton | Characteristics and Activities of Sulfate-Reducing Bacteria[END_REF].

When the flow becomes turbulent (following a storm for example), dissolved H2S in supersaturation is released into the atmosphere of the pipe and condenses on the emergent vault (alkaline surface) in reduced form. Here it constitutes a nutritive substrate for Sulpho-Oxidizing Bacteria (SOB) [START_REF] Dyer | Biodeterioration of concrete[END_REF]. These bacteria include in their metabolism the production of sulphuric acid (H2SO4) which reacts locally with different hydrates of the cement matrix to form expansive degradation products such as gypsum and ettringite [12;15]. These expansive and not very cohesive phases then become the source of internal pressures within the material and generate the appearance of cracks that can lead to the disintegration of the concrete. These degradation products will cause swelling, cracks and crazing which can lead to the ruin of the structure [START_REF] Grandclerc | Accelerated biodeterioration test for the study of cementitious materials in sewer networks: experimental and modelling[END_REF].

The main objective of this study is to observe and compare the bioreceptivity of two varieties of Portland Cements and two varieties of Calcium Sulphoaluminate Cements placed in a real urban sewer network. The behaviour of Calcium Sulphoaluminate Cements in this type of environment is still poorly known.

The paper first presents the physico-chemical characterization of the cements and samples of the study. The colonization density of the samples and the evolution of the surface characteristics of the material over time (mineralogy, etc.) are then described and analysed. -CSA2 for a Calcium Sulphoaluminate Cement with a higher iron content, reputed to be resistant to sulphates and the marine environment (High Fe2O3 Calcium Sulphoaluminate Cement Clinker).

The composition, fineness and density of these cements and their clinker as declared in the product data sheets are given in the Tabs. I-1 and Tab. I-2. Let us briefly recall that OPC/PSC hydration gives mainly hydrated calcium silicates (C-S-H), calcium hydroxide C-H (Portlandite), and tri (primary ettringite C6A$3H32 1 ) and/or hydrated calcium mono sulphoaluminate C4A$H12 1 ). Hydrates formed from Calcium Sulphoaluminate Cements are mainly ettringite, hydrated calcium monosulpholuminate, Gibbsite (AH3 1 ) and strätlingite (C2ASH8 1 ). C-S-H, portlandite (CH) and hydrogarnet (C3ASH4 1 ) may also be present depending on their C2S content [3; 17]. Moreover, the rise in resistance of CSAs is much faster than that of OPC/PSCs [START_REF] Kleib | Ecodesign of cements: synthesis, hydration and durabolity[END_REF].

Tab. I-1: Composition of Portland Cements and their clinker, fineness and density

Hardened cement paste specimens

The materials used in this study are hardened cement pastes. Considering the various factors influencing bioreceptivity (see § 1), we decided that they all have approximately the same "initial" porosity at 28 days, which guarantees a comparable a priori physical surface state.

For this purpose, cement pastes with different water/cement mass ratios (w/c) were first poured into plastic tubes 16 cm long and 4 cm in diameter with plugs. These pastes were made with a mixer standardized to NF EN 196-1 [START_REF]NF EN 196-1 Cement testing methods. Part 1: Determination of mechanical resistance[END_REF]. The w/c ratios were chosen in order to obtain a range of consistency from firm to very fluid. The firmest pastes were poured progressively under vibration (evacuation of the occluded air). The paste specimens of normal and more fluid consistency were subjected to a slow rotation for 24 hours after vibration to avoid segregation before setting. The specimens were removed from the moulds after 24 hours and stored for 28 days in a moist chamber (20°C ± 1°C, RH > 90%). They were then cut into several samples on which the accessible water porosity was measured according to the method described below (see § 3.2, porosity accessible to water). The results obtained are shown in Fig. 1 and meant that the same "initial" water-accessible porosity of 16% could be chosen for all the cement pastes in the study. The corresponding w/c ratios are 0.4 and 0.47 for OPC and PSC, and 0.5 and 0.41 for CSA1 and CSA2, respectively. The choice of this porosity made it possible to produce pastes of non-fluid consistency, which could be poured into static moulds without proven segregation. It should be noted, however, that the complete hydration of cementitious hydrates is not fully ensured with these w/c ratios, especially for calcium sulfoaluminate cements for which the stoichiometric ratio of ye'elimite is about 0.78 [START_REF] Trauchessec | Hydration of ordinary mixtures of portland cement and calcium sulfoaluminate cement[END_REF]. 1 Based on these results, the cement pastes for bioreceptivity tests were manufactured following the protocol described above. Their composition is given in Tab. II. They were poured under vibration into specific rectangular moulds made of "bakelized" wood with dimensions 300×45×20 mm 3 , in the middle of which two nylon wires with a diameter of 0.55 mm had previously been stretched. The specimens were removed from the moulds at 24 hours and stored for 28 days under standard curing conditions (20°C ± 1°C, RH ≥ 90%). The nylon wires were then removed and the specimens were cut with a diamond saw into 45×20×20 mm 3 plates. These plates were all polished with grade 180 sandpaper to make their surface finish uniform. The effective porosity of a few plates, measured at 28 days, completes Tab. II (average of 5 measurements). They were then grouped together in batches corresponding to one measurement date and attached separately, without contact, by two nylon wires of 0.25 mm diameter passing through the previous reservations, before being suspended on appropriate supports subsequently placed in the exhibition sites (Fig. 2).

Each batch consisted of 12 plates, i.e. three plates per cementitious grade and four cementitious grades. This gave a total of nine batches for nine measurement deadlines set at intervals of about two months, i.e. 18 months of exposure. They were placed on four sites of the urban network selected for the study (see § 4.1), plus on a control site in the laboratory (conservation in a closed tank above a tap water supply). In total, some 540 plates were produced in this way.

Fig. 2: Conditioning of samples before exposure on real sites. Case of a manhole cover.

Methods of study

The specimens described above were used to perform a bacterial count at each observation date, accompanied by microscopic and mineralogical analyses (SEM/EDS and DRX). The protocol for collecting the samples on site was as follows:

-Removal of the support of a batch of specimens (reminder: a batch is made up of 12 plates), by handling only the attachment wires;

-Individual removal of each specimen, by severing the wires, in a sterile 100 mL pot containing distilled water with 9.5 g/L NaCl added (to adjust the osmotic pressure of the fresh water).

Bacterial enumeration

The bacteria most implicated in the degradation processes encountered in wastewater systems are Sulpho-Oxidizing Bacteria (SOB) [5; 16; 17]. This is why two microbial groups were considered: the "general" flora, which considers all bacterial flora, cultivated from a culture medium composed of yeast extract and tryptone, and the sulpho-oxidizing flora (SOB) cultivated using Gübner's specific culture medium [START_REF] Gübner | Biofilms and accelerated low-water corrosion of carbon steel piling in tidal waters[END_REF]. The composition of these two media is recalled in the appendix. The cultures were carried out on a solid support agar in Petri dishes [START_REF] Dupont | Microbiology in understanding microbial corrosion phenomena: an example: a study of the inter-influence between sulphurogenic flora and cathode protection, Enabling brief to lead research[END_REF]. At each sampling time, the following protocol was applied in the laboratory, for each cement grade:

-Ultrasonic agitation (sonication -40 kHz) of one of the 100 mL pots containing one of the plates, for 5 minutes, to detach the biofilm on the surface;

-Inoculation of three to five Petri dishes with a 10 µL suspension taken from the pot using an inoculating loop;

-After 3 days of incubation at 37 °C, we counted the number of colonies on each of the Petri dishes and calculate the average in Colony Forming Units (CFU/cm 2 ). This value is defined as the average number of bacteria counted, multiplied by the ratio of the volume of the dilution to the volume collected, all in relation to the total outer surface area of the specimen.

It should be noted that bacterial enumeration was not always possible after incubation, especially for the general medium, because the cultures formed a dense cluster that prevented the distinction of individual Colony Forming Units. In this case, the corresponding measures were not considered in the analysis of the results.

Accessible porosity water

The porosity of cementitious materials is a factor that influences bioreceptivity and biodeterioration [START_REF] Guillitte | Bioreceptivity: a new concept for building ecology studies[END_REF]. It represents the voids (pores) of a material which can be filled with water under ordinary pressure and temperature conditions. It was measured using the method of "three weighings" [START_REF]NF P18-459 Concrete-hardened concrete tests-porosity and volume mass tests[END_REF] of each cementitious grade aged 28 days on 5 plates, before exposure of the samples on the different sites (initial porosity, see Tab. II). Given the presence of hydrates, the samples were dried (dry mass) at room temperature by successive immersion in two organic solvents (isopropanol, then diethyl ether) [START_REF] Berger | Stabilization of ZnCl2-containing wastes using calcium sulfoaluminate cement: Leaching behaviour of the solidified waste form, mechanisms of zinc retention[END_REF].

Analysis by Scanning Electron Microscopy (SEM)

The upper surface of one of the three cement paste plates was observed as soon as it was removed, using a Scanning Electron Microscope under controlled pressure (SEM-PC-Quanta 650 FEG from FEI) coupled with an Energy Dispersion Spectroscope (EDS from Bruker), without prior metallization of the surface. The observations were carried out under partial water vapour pressure of 100 Pa and with an acceleration voltage of 15 kV allowing the observation of microorganisms.

X-Ray Diffraction Analysis (XRD)

The upper surface mineralogical analysis of another of the three plates was carried out by DRX to detect and identify the crystalline phases present and their possible evolution over time. The apparatus used is a Bruker D8 Advance diffractometer CuKα equipped with a germanium monochromator. The sample did not undergo any preliminary preparation to avoid destabilizing the crystallized phases present on the surface. The measuring parameters used were as follows: i) angular range 5 to 90°, ii) angular measuring step of 0.021°, iii) counting time in 158 s steps. The quantification of the phases present, by the Rietveld method in particular, was not considered relevant, given the data acquisition conditions (preferential orientations, representativeness of the investigated volume, choice of relevant interpretation parameters, mineralogical complexity, etc.). However, failing this, a "relative quantification" was carried out based on the height of the main line of the mineral phases detected on the diffractograms. In concrete terms, on each diffractogram, the highest main line was normalized to 1 (100%) and the height of the other main lines was relativized with respect to this standard (Fig. 3). Thus, a relative quantification could be established of the phases present over time. Tab. III recalls the value in 2θ of the main line of the main mineral phases detected in this study.

Study environments

Exhibition sites

The exhibition of the samples in a real environment was carried out in partnership with the Greater Nancy Metropolitan Area (Meurthe-et-Moselle, France) which authorized access to different parts of its sewer network. Four sites with different environmental conditions were selected. These sites were chosen because they offer a diversity of effluent types (stormwater, hospital wastewater, domestic, etc.). They also differ in the size of the pipes and the flows that pass through them, ranging from a few litres to several cubic metres of effluent per minute. Sites supplied by rainwater are subject to strong surges during rainy or stormy episodes. Finally, the position of the samples in relation to the effluent is also a significant difference. The samples were placed in such a way that they would not come into contact with any other material, nor with the effluents. A summary description of the sites and exposure devices is given below:

-Site S1: a large lifting/pumping chamber (approximately 700 m 3 ) designed to collect and store effluents from a sector of the city (wastewater and rainwater), before their periodic discharge to the treatment plant. This site is characterized by periods without significant fluctuations in level (balanced supply and discharge flow) and sudden events (rain, storm) causing the level in the chamber to rise rapidly. This context constitutes a probable source of H2S production and release (stable period followed by a turbulent regime) which can however be disrupted by monthly maintenance cleaning. In order to keep the samples close to the surface of the liquid at all times, while following its fluctuations, a floating support surrounded by a protective air chamber was constructed (see diagram and photo Fig. 4). It was fixed in the centre of a crinoline providing access to the chamber, by means of a cable connected to a counterweight passing through two pulleys attached to a removable crossbar anchored in the top of the crinoline. In this the roofs of buildings and car parks. Both networks are connected to the same unitary network downstream (~ 500 meters) so that the odours from the sewer network are fed back into the rainwater network, but with a low intensity. The samples were placed on metal frames with feet (see Fig. 2) resting on the manhole gutters; -Site S3: this is a large collector-interceptor (Ø 1500 mm) which transports the effluents brought by several secondary networks to the treatment plant. The flows in this collector-interceptor are always abundant, and increase in rainy periods. The samples were placed on a metal frame hung on the first bar of one of the access manholes, at a distance of at least three meters from the usual liquid level; -Site S4: This is a standard unitary network in the city centre. As before, the samples were placed on metal frames resting on the manhole gutter (Fig. 2).

In addition, a series of "control" samples, prepared under the same conditions as before, were kept in the laboratory. The plates were placed in a closed tank partially filled with tap water maintained at 20°C, on a grid fixed above the water level. Similarly, a sample of each cement paste was immersed for 24 hours in 4 solutions of sulphuric acid (of chemical origin) of 200mL, with concentrations of 0.1, 0.5, 1 and 5 mol/l respectively, in order to identify (by DRX as previously) the products that appeared and were potential markers of an attack.

Environmental conditions

Owing to the lack of technical means available, the exposition sites could not be equipped with recorders allowing the punctual or continuous measurement of the prevailing environmental conditions within them (temperature, humidity, pH, H2S content, etc.).

However, these parameters did not appear to be indispensable because:

-There is a great diversity of contexts, each with its own configuration: the measurements carried out on (only) four sites would therefore not have been truly exhaustive;

-The aim was to compare the bioreceptivity of the cement grades among themselves, in different real contexts subject to numerous random fluctuations over a long period of time;

-The real interdependence between the numerous environmental parameters that can have an influence, and the bioreceptivity of materials, is not yet (well) known; -Samples are placed in the system without ever being in contact with the effluent.

However, some qualitative information could be collected, in particular concerning the presence of H2S on site S1. Indeed, the agents who regularly maintain this station are equipped with a detector for this gas, in accordance with safety regulations. They stated that there were variable levels of H2S, mainly at the bottom of the structure, without however having recording the levels. This presence thus requires the complete ventilation of the unit before entering it.

Finally, the detailed temperature and precipitation records for the city of Nancy over the study period were retrieved. The result of their processing, in terms of maximum, minimum and average daily temperature and cumulative daily rainfall, is shown in Fig. 5. These two parameters influence the study environments as a whole, since it can be assumed that there is a direct dependence between rainfall and flow rates (at least for the combined sewerage and stormwater networks) and the temperatures outside and inside the networks. The samples were exhibited at the beginning of September 2018. The following two months were characterised by very low rainfall and rather high temperatures which are characteristic parameters for the end of the summer period in Nancy. The period between the end of October and the beginning of February was marked by numerous and sometimes intense rainy episodes with temperatures generally below 10°C. The period from February to mid-May had lower rainfall, with a few (long) periods without rain and temperatures rising gradually. From mid-May to the end of August, rainfall was low, with the exception of a few thundery episodes, and the temperature reached high values that occasionally exceeded 40°C. These evolutions are typical of the overall climatological cycle of the region.

Results

Bacterial colonization

The evolution of the bacterial population density over time, for the different cements and at different sites, in Colony Forming Units per cm 2 (CFU/cm 2 ), is shown in Fig. 6 for the general microbial flora, and Fig. 7 for the SOB. These figures also include the meteorological chronicles described above (mean daily temperature, cumulative daily rainfall) in order to establish possible correlations. The enumeration of the general flora on the surface of the samples is an indicator of interest of the bioreceptivity of the support material, without necessarily leading to biodegradations. The enumeration of BSO is an indicator of possible degradations of the support material, considering their metabolism involving the production of sulphuric acid. Note that the (thin) lines connecting the various points only serve to improve the reading of the graphs. They in no way indicate the existence of any linear evolution of bacterial colonization between two consecutive observations, nor that the bacterial population could not have evolved in this period of time above or below the point values measured. Furthermore, the standard deviation associated with the measurements ( 5Petri dishes) sometimes shows a rather strong dispersion around the mean (points), indicating the difficulty of the precise characterization of this parameter (bacterial colonization). Finally, it is important to note that no bacterial colonization by SOB was detected on the samples stored in the laboratory (see § 4.1), whatever the age of storage and the cement grade. This result is logical because there is no H2S present and therefore no presence of sulphur phases necessary for the development of these bacteria. On the other hand, as the samples and the medium are non-sterile, colonization by the general medium was indeed detected as early as 6 months, but its enumeration was not always possible (dense cluster, cf. § 3.1). These two pieces of information have not been included in the graphs. analyses. Above all, they made it possible to observe bacterial colonization, which was detected very often. These colonies can be scattered or more concentrated, at the scales of observation.

Thus, before 4 months no bacteria are visible and only traces of biofilm are locally present, particularly on OPC pastes. However, the results of the bacterial cultures (Figs. 6 and7) show the presence of SOB as early as 2 months, at least on certain cement grades and on certain sites. This "contradiction" can be attributed to the complexity of the surface topography and the presence of accumulated (observed) secondary layers which can create a "masking effect" for the (rare) bacteria present at this stage.

After 4 months of exposure, the biofilm is often well developed and bacteria are observed more frequently. By way of example, for this period, Fig. 8a shows the biofilm observed on the OPC cement paste at site S1. Fig. 8b shows stick and shell bacteria observed on the CSA1 paste at site S2u. Other mineral phases are also observed. As an example, and still after 4 months of exposure at the S2u site, Fig. 9a shows orthorhombic sulphur single crystals (confirmed by EDS) appearing on the surface of the PSC paste. It should be remembered that the PSC cement initially contains a low content of sulphur contributed by the setting regulator (S2 -≤0,7% according to the data sheet), and that this sulphur is theoretically mobilised in the afm phases. The sulphur detected probably comes from the surface crystallisation of the dissolved H2S discharged into the aerial part of the pipe, following an increase in its concentration in the effluents (from 20 ppm to 50 ppm for example), caused by the action of Sulphate-Reducing Bacteria (SRB) [START_REF] Joseph | Surface neutralization and H2S oxidation at early stages of sewer corrosion: Influence of temperature, relative humidity and H2S concentration[END_REF]. EDS analyses associated with SEM analysis of other cement grades from the same site and from other sites, for all timeframes from 4 months onwards, often reveal the presence of sulphur, sometimes in significant quantities.

However, the processing of these data was not considered relevant because they are only one-off analyses that do not reflect the "reality" of the whole surface. These indications can therefore only be considered qualitative. They do however show the presence of this characteristic element of the action of SRB. Fig. 9b shows ettringite needles appearing on the surface of the CSA2 paste. As there is little work in the literature describing the products associated with the action of sulphuric acid generated by the metabolism of SOB for CSAs, a direct sulphuric acid attack at different concentrations (0.1; 0.5; 1 and 5 mol/L) was carried out on the different hardened cement pulps in the study. After 24 hours of immersion, SEM observations revealed, on all the pastes, the presence of gypsum on the surface, although in smaller quantities for OPC and CSA2, compared to PSC and CSA1. This difference therefore reflects these two cements' better resistance to sulphuric acid. It should be noted, however, that OPC presents significant dissolutions, especially at low concentrations (0.1 and 0.5 mol/L) [START_REF] Herisson | Toward an accelerated biodeterioration test to understand the behavior of Portland and 21 calcium aluminate cementitious materials in sewer networks[END_REF].

Figs. 10a andb show gypsum crystals of different sizes, associated with bacteria (b), observed on CSA2 at the S2U site at 18 months. Similar SEM analyses were performed at all other times in the study and on all samples.

Qualitatively, a fairly good correlation was observed between surface bacterial activity (biofilm, bacteria, sulphur, ettringite) and bacterial counts, i.e. more biofilms and visible bacteria in spring and autumn than in summer and winter.

Mineralogical analysis (DRX)

The upper surface of the samples was analysed by DRX at 28 days of age and then at each observation date. The diffractograms (not presented here) were interpreted according to the approach presented in § 3.4.

The initial measurements (28 days) show that calcite is (already) the predominant mineral at the surface, for all four cement grades. It shows the rapid action of carbonation, a factor that causes a decrease in surface pH favourable to the colonization of micro-organisms (neutrophilic bacteria 6 ≤ pH ≤ 8) [START_REF] Berger | Stabilization of ZnCl2-containing wastes using calcium sulfoaluminate cement: Leaching behaviour of the solidified waste form, mechanisms of zinc retention[END_REF]. For OPC and PSC, hydrated phases characteristic of these cements were also identified, notably portlandite (CH), CSH gels (composition close to that of crystallised phases such as tobermorite (C5S6H11) and jennite (C9S6H11)). For CSA1 and CSA2, anhydrous phases were also detected, notably ye'elimite (Ca3Al6O12CaSO4) and mayenite (Ca12Al14O33). Subsequently, these phases were no longer observed. Fig. 11 shows the mineralogical changes observed between 2 months and 18 months of exposure, for the four cement grades and for the five sites:

-For OPC, calcite is almost the only mineral detected at all deadlines. Gypsum, however, appears after several months of exposure, at least at some sites (12 months for S4, 16 months for S2u, Fig. 10a andb). For S3, this phase appears around 8 months and then develops until it becomes preponderant around 18 months. Its appearance is attributed to the probable reaction between the sulphuric acid produced by the bacteria (SRB) and the calcite present on the surface (eq. 1; 2; 3) or the Portlandite present below the surface (eq. 4);

CaCO3 + H2SO4 → CaSO4 + H2CO3 CaSO4 + 2H2O → CaSO4.2H2O H2CO3 → CO2 + H2O Ca(OH)2 + H2SO4 → CaSO4.2H2O
-For PSC, calcite is also the predominant mineral, except for S3 at 18 months, where, as for OPC, gypsum becomes the majority on the surface. This phase (and sometimes semihydrate or Bassanite) also appeared on the other sites, in variable and evolving proportions, except for S4 where it is absent. On site S2p, ettringite was detected after 1 year of exposure. The gypsum necessary for its formation is well present (detected) and hydrated calcium aluminate is in principle present in this type of cement (C3AH6, C4AH12). Vaterite was also detected on this cement paste and on all sites. The appearance of this unstable calcium carbonate, often associated with organic activity, is perhaps related, here too, to bacterial activity [START_REF] Herisson | Toward an accelerated biodeterioration test to understand the behavior of Portland and 21 calcium aluminate cementitious materials in sewer networks[END_REF]. Finally, katoite (3CaO.Al2O3.6H2O) appeared at around 16 months on the S2p site. It could result from the decomposition of monosulfoaluminate into katoite and ettringite (eq. 5) [START_REF] Trauchessec | Hydration of ordinary mixtures of portland cement and calcium sulfoaluminate cement[END_REF]; 3(4CaO.Al2O3.SO3.12H2O) + 8H2O → 2(3CaO.Al2O3.6H2O)+ 3CaO.Al2O3.3CaSO4.32H2O (eq. 5)

-For CSA1, calcite (and vaterite) is also the predominant mineral, except for S3 at 18 months, where gypsum is again the predominant surface mineral. Contrary to Portland cements (OPC and PSC), gypsum and other hydrated phases appear earlier and in significant (relative) quantities. These are gibbsite (Al(OH)3), ettringite, bassanite and even also strätlingite (2CaO.Al2O3.SiO2.8H2O), the origin of which is to be compared with the mineralogical composition of this belitic sulphate-aluminous cement, manufactured with a quantity of water well below the stoichiometric value. It can be assumed here that these hydrates developed on the surface over time, depending on the more or less favourable hygrometry prevailing within the networks. The presence of gypsum on the surface (resulting from the indirect action of SOB bacteria) would also participate in these reactions;

-For CSA2, a comparable scenario was found, but with a lower intensity and the absence of strätlingite.

(eq.1) (eq.2) (eq.3)

(eq.4)

Finally, it should be noted that the evolution over time does not follow a regular progression (for CSA cements in particular), but is instead cyclical, in accordance with the seasons, i.e.

with the intensity of the bacterial activity.

Here we should recall that the samples that underwent the direct sulphuric acid attack showed the abundant presence and accumulation of gypsum on their surface (confirmation of the reaction between the sulphuric acid and the carbonates and hydrates of the cement matrix). -The temperature/humidity couple:

o Temperature acts as a catalyst to accelerate reaction speeds and temperature variations influence the rhythm of bacterial development. Herisson [START_REF] Herisson | Toward an accelerated biodeterioration test to understand the behavior of Portland and 21 calcium aluminate cementitious materials in sewer networks[END_REF] reports that an increase of 10°C doubles the bacterial activity. Thus, for example, the increase in the density of colonization observed between March and May can also be attributed to the increase in average temperature over this period, from 7.5°C to around 12.5°C;

o Humidity is essential for the development of bacteria [START_REF] Roux | Alteration of cement pastes by bacterial colonization[END_REF]. Sites S1 and S3 generally have constant humidity. In the other sites, as the temperature increases and relative humidity decreases, the density of colonization also decreases. This is because the production by the bacteria and therefore the concentration of H2S is influenced by the outside temperature.

- o This then explains the presence of gypsum on CSAs. However this is also explained by the action of the sulphuric acid produced by the SOBs (a reaction verified by immersing the cementitious pastes in baths of dilute sulphuric acid). This was observed with the appearance of gypsum on OPC (50% with a colonization density of 40,000 UFC/cm 2 ) and PSC (40% with a colonization density of 25,000 UFC/cm 2 ), from the 6th month of exposure on the S3 site, and later for the other sites (consistent counting from this time onwards with a quantity of gypsum that increased concomitantly -up to 100% with a colonization density of 100,000 UFC/cm 2 for OPC).

For CSA, the quantity of gypsum was found to increase from this time onwards.

However, the samples composed of CSA2 were still found to have the lowest bacterial population density. This behaviour can be related to the higher alumina (and iron) content of this cement (Tab. II), which would lower the surface pH to low values (3 or 4), thus inhibiting the development of bacteria [START_REF] De Belie | Experimental research and prediction of the effect of chemical and biogenic sulfuric acid on different types of commercially produced concrete sewer pipes[END_REF].

-The typology of the exhibition site.

o Site S1 has a priori the most favourable conditions for the development of SRB and the production of sulphuric acid (proven presence of SO2). However, few, if any (OPC) secondary products were detected. This can be explained by the regular and intensive cleaning and dredging of the site, which probably interrupts the metabolisation of H2S by the SRB, and thus the process of SOB development (Fig. 7).

The gypsum, gibbsite and katoite detected on CSA cements (or even on PSC) then essentially come from the mineralogical evolution of the hydrates characterising this cement (eq. 1, 2, 3, 4); o The S2p site reveals strong disparities between cements. Thus, OPC is characterised only by the presence of calcite and PSC by the additional and late appearance of gypsum, ettringite, and even katoite. On the other hand, the surface of CSA1 hosts early phases in relatively large quantities that are associated with the nature of this cement (gypsum, gibbsite, ettringite, strätlingite). CSA2 shows a similar "reactivity", but with a more moderate relative intensity. The most influential parameter is therefore the environmental conditions which are not very favourable to bacterial development on this site (rainwater);

o The S2u site displayed rather similar behaviour, with a very late appearance of gypsum for Portland cements, and earlier for CSA1 and CSA2, with a higher relative quantity for CSA1. The other phases are in smaller relative quantities, indicating that the gypsum present on CSA1 is partly due to bacterial activity linked to the favourable conditions of the site (varied chemistry of the effluents, flow, temperature, H2S). The presence of gibbsite on CSA2 could lead to a decrease in the density of colonization by inhibiting or delaying the development of biofilm and the proliferation of bacteria on the surface of these materials [START_REF] Seidel | Mechanism of bioleaching of coal fly ash by Thiobacillus thiooxidans[END_REF].

o Sites S3 and S4 correspond to more regular configurations of sewer networks and displayed quite similar responses, with a rather late and progressive appearance of gypsum associated with the activity of SOB. The context at these sites is probably less favourable for the formation and development of biofilm (surface conditioning phase of the materials), and thus for the primary adhesion of the SOB, which precedes their exponential development, as shown in Fig. 12 [5; 6].

Fig. 12 Formation and evolution of biofilm over time [START_REF] Roux | Alteration of cement pastes by bacterial colonization[END_REF].

Finally, the results of these analyses show that, in sewer systems, the cementitious nature of the cement between Portland and CSA does not strongly discriminate against the bioreceptivity of the pastes made with these materials after 18 months exposure. As soon as the pastes are carbonated and the environmental conditions (rainfall, temperature) allow the SRB bacteria to produce hydrogen sulphide, the development and activity of the sulphooxidising BSO bacteria takes place. The sulphuric acid produced then combines with the carbonated or aluminous phases present to give gypsum and secondary ettringite in particular. Therefore environmental conditions control the kinetics and intensity of the reactions more than the intrinsic nature of the cements.

Nonetheless, the effect of the secondary phases formed and their accumulation over time on the physical properties of the cements and concretes (porosity, capillarity, permeability, resistance, etc.) remains to be assessed.

Conclusion

This work focuses on the bioreceptivity of cementitious materials in sewerage networks. To

  197-1 Portland Cements and two Calcium Sulphoaluminate Cements were used. They are designated as follows: -OPC for a cement CEM I 52.5 N CE CP2 NF taken as reference. It contains only clinker (K) and calcium sulphate (CS). Its normal strength class (N) is 52.5 MPa. It meets the requirements of European (CE) and French (NF) regulations and can be used for the manufacture of prestressed concrete (CP2); -PSC for a cement CEM III/A 42.5 N-LH PM-ES-CP1 containing 62% blast furnace slag (S). It is declared Low Heat of Hydration (Low Heat LH). Its strength class is 42.5 MPa with normal hardening (N). It is suitable for work at sea (PM) and in waters with high sulphate content (ES) and its sulphide content is limited (CP1); -CSA1 for a Belite based Calcium Sulphoaluminate Cement reputed to be resistant to sulphates;

Fig. 3 :

 3 Fig. 3: Diffractogram of the CSA1 at the S2u site at 10 months.

  Fig. 4: Description of the sample installation at site S1. -Site S2: It is located at the exit of a large hospital centre equipped with a separation network. The wastewater network (S2u) carries black water and domestic water with a moderate constant flow. The air circulating in this network has the characteristic smell of medical products. Although recent, the concrete, steel bars and the underside of the cast iron manholes are corroded. The rainwater network (S2p) only carries water from

Fig. 5 :

 5 Fig. 5: Daily temperature and precipitation records during the study period.

Fig. 6 :Fig. 7 :

 67 Fig. 6: Cultivatable bacterial population in Ordinary General Medium (agar medium), in CFU (Colony Forming Units), for the four cement grades and the five exposure sites.

Figure 8 :

 8 Figure 8: SEM-PC image, 4-month term. a. Dehydrated Biofilm on the OPC paste. Site S1. b. Bacteria in sticks and shells on CSA1 paste. Site S2u.

Figure 9 :

 9 Figure 9: SEM-PC image. S2u site at 4 months. a. Orthorhombic sulphur crystals observed on the PSC. b. Needles of ettringite on CSA2 paste.

Figure 10 :

 10 Figure 10: SEM-PC image. S2u site at 18 months. a. Gypsum crystals observed on CSA2. b. Bacteria in shells embedded in micrometric gypsum crystals on CSA2.

Fig. 11 :

 11 Fig. 11: Exploitation of DRX analyses of the 4 cement grades at the 5 exposure sites for 18 months.6. DiscussionThe evolution of the biocolonization (linked to bioreceptivity) of the surface of the different cement grades during the 18 months of observation, described by bacterial counts, SEM images and surface mineralogical analyses, can be compared with the evolution of the environmental and climatic conditions surrounding the selected experimental hydraulic structures, and also with the mineralogy of the supports. Over a climatic cycle of 18 months, starting with the placement of the specimens in September, relations between the action of the SRB and SOB and the mineralogical evolution of the colonized surfaces can thus be established. These observations also refer to the work mentioned earlier in the paper which described the relations between environmental conditions and bacterial colonization but in different experimental contexts. The parameters concerned are:-Flow variations within the networks, between dry periods and rainy episodes (storms, rainfall,) leading to turbulent flows following stable regimes. Their consequences would be the following: o Between September and November, a slow hydraulic regime with low rainfall. This regime is favourable to the metabolization of H2S by the SRB; o Between November and February, sustained rainfall leading to an often turbulent flow regime favourable to the release of H2S, deposition of sulphur on the support materials. This nutritive substrate of the SOB leads to an increase in colonization densities on all sites for all cement grades; o Between February and April, more scattered rainfall and dry periods, leading to a stabilization of the colonization density;

  The mineralogical composition of the carrier materials: o The cement pastes studied, formulated with w/c ratios that do not allow complete hydration, initially present on the surface the expected hydrated or even anhydrous phases: portlandite, C-S-H, etc. for Portland cements; ettringite, gibbsite, bassanite, strätlingite, ye'elimite, mayenite for CSA. The rapid carbonation of these hydrates, especially portlandite and ettringite, results in calcite (the dominant mineral from the first analyses), gypsum and gibbsite covering the surface and causing a decrease in pH. This evolution then allows colonization by neutrophilic micro-organisms. The eq. 6 recalls the reaction between ettringite and atmospheric CO2 [3; 25]: 3CaO.Al2O3.3CaSO4.32H2O +3CO2 → 3CaCO3 + 3CaSO4.2H2O + Al (OH)3 + 23H2O (eq.6)

  this end, hardened cement pastes of the same porosity, made with two Portland cements (OPC and PSC) and two Calcium Sulpho-Aluminate Cements, were placed on five different sites of a real urban network for 18 months. Bacterial counts (general environment and Sulpho-Oxidizing Bacteria), surface mineralogy and SEM observations were carried out at fairly regular intervals (about 2 months). These measurements show that these different cements are bioreceptive from two months of exposure, at levels that are fairly comparable and variable over time. The rapid carbonation of the surfaces clearly allows bacteria to establish themselves (biofilm). Subsequently, secondary mineral phases are detected/observed on the surface and these are mainly gypsum and ettringite. They probably result from the reaction between sulphuric acid generated by sulphate-oxidising bacteria and calcite and other anhydrous or hydrated cementitious phases present. Analysis of the results obtained finally shows that the quantity of phases thus formed after 18 months exposure depends more on environmental conditions (temperature, rainfall, sometimes human intervention) -which control the production of sulphur linked to the activity of the Sulphate-Reducing Bacteria living in the effluents -than on the very nature of the support cement.

Cement notation 4 0 10 20 30 40

		OPC
		PSC
	porosity (%)	CSA1 CSA2		16%
	0	0,2	0,4	0,6	0,8
			w/c
	Fig. 1: Evolution of the accessible water porosity as a function of the water/cement ratio of
	the different cement pastes.
	Tab. II: Compositions of the different cement pastes having the same accessible water
	porosity from 16% to 28 days.
	Cementitious grade	OPC	PSC	CSA1	CSA2
	Cement (g)	450	450	450		450
	Water (g)	180	211,5	225		184,5
	w/c	0,40	0,47	0,50		0,41
	Porosity at 28 days (%)	16.42	16	16.34	16

Table III :

 III Value in 2θ of the main line of the mineral phases observed in this study

	Mineral phase	2θ
	Calcite CaCO3	29.406
	Vaterite CaCO3	33.027
	Gypsum CaSO4.2H2O	20.722
	Bassanite CaSO4.0.5H2O	29.757
	Ettringite 3CaO.Al2O3.3CaSO4.32H2O	35.023
	Katoite 3CaO.Al2O3.6H2O	33.533
	Gibbsite Al(OH)3	18.266
	strätlingite 2CaO.Al2O3.SiO2H2O	21.239

Appendix


P Guggenbuhl

F Robin

JD S Cadiou

Albert

Etiology of avascular osteonecrosis of the femoral head Titre Français : Etiologies de l'ostéonécrose aseptique de la tête fémorale

Keywords: avascular osteonecrosis, osteonecrosis, corticosteroids, alcohol, avascular osteonecrosis of the femoral head

ou non, émanant des établissements d'enseignement et de recherche français ou étrangers, des laboratoires publics ou privés.

Introduction

Avascular osteonecrosis of the femoral head (ONFH) is one of the causes of hip pain that clinicians need to know about. In many cases, it is a fortuitous discovery when pelvic X-rays is performed for another reason. In the other cases, it is pain that reveals the disease. Hip pain is most commonly pain felt in the groin and anterior thigh, of sudden appearance after an effort or a change of position. Pain can be initially strong with nocturnal awakenings mimicking an inflammatory pain.

However, rapidly and typically, the pain become mechanical, occurs when the patient put his foot on the floor and disappear in discharge with a functional impotence and variable joint limitation amplitudes, notably internal rotation. It is a differential diagnosis of all hip diseases, especially arthritis or osteoarthritis but also bone diseases. The context, and above all imaging (which is covered in another chapter of this issue) make the diagnosis.

For the rheumatologist, a major part of the job is to look for a cause and in some patients, it is the opportunity to discover an unknown disease. For others it is a complication of an already known disease.

In this paper, we will review the main causes of ONFH emphasizing the most frequent ones and those for which an etiological treatment can be considered.

The term "avascular" osteonecrosis suggests an interruption of the physiological vascularization. The femoral head vasculature is a terminal one and as in heart or brain, an arterial obstruction or interruption leads to organ necrosis, in this case osteonecrosis [START_REF] Lafforgue | Pathophysiology and natural history of avascular necrosis of bone[END_REF]. However, ONFH physiopathology is more complex and it is admitted that it is the result of an interaction between vessels damages, alteration of bone cells, especially osteocytes which are mechanosensory cells and some non-wellknown genetic factors [START_REF] Petek | Osteonecrosis of the femoral head: pathophysiology and current concepts of treatment[END_REF].

Two kinds of mechanisms can result in ONFH: traumatisms, which constitute local causes or systemic conditions. In the first case, ischemia is secondary to generally a huge traumatism followed by a fracture or a luxation and vasculature damages. It can be sometimes secondary to micro traumatisms.

In the second case, the vascular lesions can come from pathologic intravascular obstruction (lipids or gaseous microemboli; hypercoagulability state), extravascular compression (medullary adipocytes hypertrophy, intra-medullary edema, intra-medullary proliferation) or bone damages especially of osteocytes (drugs or alcohol cytotoxicity) [START_REF] Pijnenburg | A review of avascular necrosis, of the hip and beyond][END_REF].

Femoral head is the more frequent location of osteonecrosis. It may be due to its particular vascularization. The majority of the blood supply originates from the retinacula arteries supplying the superolateral weight-bearing portion of the femoral head [START_REF] Petek | Osteonecrosis of the femoral head: pathophysiology and current concepts of treatment[END_REF][START_REF] Rego | Arterial Topographic Anatomy Near the Femoral Head-Neck Perforation with Surgical Relevance[END_REF].

Avascular osteonecrosis of the femoral head risk factors

Clinicians have to check for risk factors, especially those, few, which can be modified or treated. It must be said that many mechanisms are common to all causes, most often intricate. In a few cases, not very well estimated (approximately 15 to 30%), no cause is identified and no cause is found [START_REF] Pijnenburg | A review of avascular necrosis, of the hip and beyond][END_REF][START_REF] Jergesen | The natural history of untreated asymptomatic hips in patients who have non-traumatic osteonecrosis[END_REF][START_REF] Moya-Angeler | Current concepts on osteonecrosis of the femoral head[END_REF] (Fig. 1).

a. The most frequents risk factors

Corticosteroids and alcohol are the causal agents in more than 80% of the cases [START_REF] Mont | Nontraumatic Osteonecrosis of the Femoral Head: Where Do We Stand Today?: A 5-Year Update[END_REF].

i. Corticosteroids

This is the most frequent cause of non-traumatic ONFH. In a series of 3000 cases of non-traumatic osteonecrosis, corticosteroids were in question in 30% of the cases, followed by alcohol, in 20%.

Corticosteroids seemed to be more deleterious in case of systemic lupus erythematosus (SLE), another potential cause of ONFH [START_REF] Chang | The pathogenesis, diagnosis and clinical manifestations of steroid-induced osteonecrosis[END_REF]. If the risk increases with the increasing doses and the treatment duration, it is not possible to found thresholds in the literature. In a meta-analysis of Fifty-seven studies including 23,561 patients, Mont et al found that ONFH incidence was 6.7% if corticosteroid treatment exceeded 2 g prednisone-equivalent with a 3.6% increase with each 10 mg/d increase. A threshold superior to 20 mg/d increased the risk, which was lower if < 15 mg/d [START_REF] Mont | High-Dose Corticosteroid Use and Risk of Hip Osteonecrosis: Meta-Analysis and Systematic Literature Review[END_REF]. Even short periods of treatment with relatively low doses increase the risk. Dilisio found in a huge US cohort that patients who received one 21-tablet, 4-mg methylprednisolone taper pack taken over 6 days had an increased risk of 1.6 compared to patients who did not had this treatment [START_REF] Dilisio | Osteonecrosis following short-term, low-dose oral corticosteroids: a population-based study of 24 million patients[END_REF].

Many mechanisms have been evoked to explain the occurrence of a steroid induced ONFH. At the bone remodeling level, osteocytes apoptosis and/or increase of osteoblast autophagy have been described.

Adipocytes differentiation increase at the detriment of osteoblasts differentiation, which is similar in case of alcohol toxicity. This increase of adipocytes number and size with intracellular accumulation of lipids cause an increase in bone pressure and disruption in interosseous microcirculation and bone structural changes in the femoral head. Steroids induce vascular endothelial cells damages and a complex coagulopathy leading to vessels thrombosis. There is also a potential role for the microbiome, oxidative stress, genetic and epigenetic and mi-RNAs, which regulate the differentiation of mesenchymal stem cells into adipogenic or osteogenic progenitor cells. Finally the concept of "multi-hit hypothesis" as emerged from Kenzora and Glimcher [START_REF] Kenzora | Accumulative cell stress: the multifactorial etiology of idiopathic osteonecrosis[END_REF], suggesting that a single mechanism is not sufficient to induce osteonecrosis; for example corticosteroids induced ONFH is more frequent in patients with SLE than in healthy people or patients with other pathological conditions [START_REF] Chang | The pathogenesis, diagnosis and clinical manifestations of steroid-induced osteonecrosis[END_REF].

ii. Alcohol abuse Overuse of alcohol has been associated to approximatively 20-30% of the patients who developed a hip osteonecrosis. As for steroid induced ONFH, several mechanisms have been suggested such as decreased bone formation, osteocyte apoptosis or excess lipid deposition; many of them seem likely to be shared. In an original way, it has recently be described that mi-RNAS could be aberrantly expressed in alcohol-induced osteonecrosis of femoral head, with bone or vessel genes targets including IGF2, PDGFA, RUNX2, PTEN, and VEGF. These observations could be of physiopathological and diagnosis interest [START_REF] Hong | Analysis of circulating microRNAs aberrantly expressed in alcohol-induced osteonecrosis of femoral head[END_REF].

b. The other classic risk factors i. Gaucher disease

Gaucher disease is a classic etiology of ONFH, very often in a context of multiple osteonecrosis. It is due to a deficiency in the lysosomal enzyme β-glucocerebrosidase, which leads to accumulation of glucocerebroside in the lysosomes of mononuclear phagocytes, predominantly in the liver, spleen, and bone marrow. Osteoarticular manifestations are often inaugural and contribute significantly to the morbidity and disability associated with Gaucher disease [13] [14].

ii. Systemic lupus erythematosus

Osteonecrosis in Lupus has been reported in 3-30% of the cases [START_REF] Lespasio | Osteonecrosis of the Hip: A Primer[END_REF] and as said before, corticosteroids seemed to be a major risk factor. However, the susceptibility to steroids induced osteonecrosis seems to be stronger than for other diseases [START_REF] Chang | The pathogenesis, diagnosis and clinical manifestations of steroid-induced osteonecrosis[END_REF]. Very recently a genetic predisposition has been suggested

with some Single Nucleotide Variations (SNVs) in NOS3, COL2A1, and CR2 genes, respectively involved in bone or cartilage formation and for CR2 in autoimmunity [START_REF] Sun | Gene testing for osteonecrosis of the femoral head in systemic lupus erythematosus using targeted next-generation sequencing: A pilot study[END_REF].

iii. Dysbaric osteonecrosis (Caisson disease) [START_REF] White | Dysbaric Osteonecrosis. StatPearls. Treasure Island[END_REF] It is another very classic, but rare etiology of ONFH, outside of undersea divers and workers breathing compressed air or gas. The most accepted theory is that it is due to a long-term manifestation of subclinical decompression sickness (DCS). Decompression lead to dissolution of gas in blood with gas bubble formation and emboli in bone microcirculation with activation of coagulation process. The consequence is an increase in intraosseous pressure and osteonecrosis. Diaphysis osteonecrosis of the femur and the tibia can occur sometimes, with pain under load, sometimes very intense with a significant risk of fracture.

iv. Organ transplantation and Chronic renal failure/hemodialysis

The prevalence of ONFH in organs transplantation has been estimated between 3 to 41%. Patients with renal transplant have been the most studied. Most of the studies are retrospective, with different steroids and immunosuppressive therapies regimen and imaging modalities. In a prospective study, the incidence was lower with an osteonecrosis of the femoral head in 11% of the hips [START_REF] Marston | Osteonecrosis of the femoral head after solid organ transplantation: a prospective study[END_REF]. The total dose of steroid received by the patients in the 2 weeks following renal transplantation is related to osteonecrosis development [START_REF] Saito | Corticosteroid administration within 2 weeks after renal transplantation affects the incidence of femoral head osteonecrosis[END_REF]. In a recent retrospective study, the decrease of the incidence of ONFH in kidney transplant recipients (4.1% at ten years after the transplantation) was attributed to the replacement of cyclosporine by tacrolimus over the last decade. Males were independently associated to osteonecrosis. The hypothesis of an ischemic steal syndrome due to the allograft kidney leading to an early osteonecrosis at the allograft side has been proposed [START_REF] Schachtner | Cyclosporine use and male gender are independent determinants of avascular necrosis after kidney transplantation: a cohort study[END_REF]. It is probable that the decrease of steroids doses in the modern management of kidney transplantation is also implicated in the decrease of ONFH in kidney transplant recipients.

v. Hyperlipidemia

Hyperlipidemia is a classic cause of osteonecrosis. However, few studies have addressed this topic. In 112 patients (children and young adults) with acute lymphoblastic leukemia, 22 experienced symptomatic osteonecrosis. In this population, hyperlipidemia was associated with an increased risk of developing osteonecrosis with increased triglycerides and cholesterol levels. There was a tendency of an inverse relationship between higher HDL cholesterol and osteonecrosis. However, prolonged increase of LDL cholesterol was not associated with osteonecrosis [START_REF] Mogensen | Hyperlipidemia is a risk factor for osteonecrosis in children and young adults with acute lymphoblastic leukemia[END_REF]. High serum triglyceride level seems also to be a risk factor for ONFH in systemic lupus erythematosus [START_REF] Kuroda | High triglyceride is a risk factor for silent osteonecrosis of the femoral head in systemic lupus erythematosus[END_REF].

c. Hematological disorders i. Sickle cell disease

A chapter of this review is specifically dedicated to this etiology. The ONFH is frequent in this context due to the intravascular obstruction linked to the red globules shape. The clinical context generally help in the diagnosis.

ii. Leukemia and lymphoma

In acute lymphoblastic leukemia, chronic myeloid leukemia and acute myeloid lymphoma there is an increased risk of osteonecrosis. Steroids seems to be the major risk factor [START_REF] Lespasio | Osteonecrosis of the Hip: A Primer[END_REF][START_REF] Kunstreich | Osteonecrosis in children with acute lymphoblastic leukemia[END_REF]. High doses of corticosteroids are the main explanation. Osteonecrosis is also a complication of bone marrow transplantation and graft versus host reaction in adults and children. The frequency has been estimated between 6% and 19%, 3 years after transplantation. ONFH is the most common localization.

Steroids and immunosuppressants are the major risk factors [START_REF] Hautmann | Metabolic bone diseases in patients after allogeneic hematopoietic stem cell transplantation: report from the Consensus Conference on Clinical Practice in chronic graft-versus-host disease[END_REF].

d. Less frequently [3]

A great number of other causes have been described or published in smaller series, potentially related to osteonecrosis mechanisms described before: diabetes [START_REF] Lai | Real-World Database Examining the Association Between Avascular Necrosis of the Femoral Head and Diabetes in Taiwan[END_REF], Cushing disease [START_REF] Koch | Cushing's disease presenting with avascular necrosis of the hip: an orthopedic emergency[END_REF], pancreatitis, intravascular coagulation [START_REF] Lafforgue | Pathophysiology and natural history of avascular necrosis of bone[END_REF], hyperuricemia/gout, HIV [START_REF] Green | Avascular necrosis: a growing concern for the HIV population[END_REF], hemochromatosis [START_REF] Jandl | Impaired Bone Microarchitecture in Patients with Hereditary Hemochromatosis and Skeletal Complications[END_REF], radiation [29], smoking…

Conclusion

A cause to ONFH can be found in a large number of cases. Some of them are evident and the context give the diagnosis (corticosteroids, alcohol abuse…). However, in many cases, additional tests to imaging are required to make the causal diagnosis. We propose a pragmatic approach beginning by the most frequent causes. Extra-articular symptoms and anamnesis are very important to consider (Fig. 1).

In some cases, the treatment of the cause can prevent the recurrence of the disease.

Fig. 1 .

 1 Fig. 1. Progressive diagnosis diagram to determine the main causes of osteonecrosis of the femoral head from the most frequent causes (1) to the rarest causes (3).

Conflict of interest: none