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PubMed2007

Gamma-radiation-induced changes in structure and properties of tetracalcium phosphate and its derived calcium phosphate cement.

The purpose of the present study was to investigate the gamma-radiation effect on the structure and properties of the single-phase tetracalcium phosphate (TTCP) powder and its derived calcium phosphate cement (CPC). Experimental results show that low-dosed (0-30 kGy) CPC has a setting time of 10-12 min, while high-dosed (40-120 kGy) CPC has a setting time of 8-10 min. The low dose gamma-radiation does not significantly change porosity volume fraction or compressive strength of the CPC. The pH values of all CPC samples fell in a relatively narrow band, with a band width of 8.5-9.1 (in terms of pH value). With a dose of 10 or 20 kGy gamma-radiation, the TTCP-apatite conversion ratio does not change much. With 30 kGy the conversion ratio significantly increases and reaches a maximum value. With further increases in dose, the conversion ratio quickly declines. With increasing gamma-ray dose, the CPC morphology becomes more porous/loose and apatite particles become larger in size. When exposed to a high dose (120 kGy) of gamma-radiation, TTCP structure is radiation-damaged, and gamma-ray-induced formation of apatite is confirmed by transmission electron microscopic/selected-area diffraction/lattice imaging analyses.

Bone Cements↗

PubMed1986

The solid, calcium-phosphate mineral phases in embryonic chick bone characterized by high-voltage electron diffraction.

The solid mineral phases of calcium-phosphate (Ca-P) in the long bones from embryonic chicks between the ages of 9 and 13 days have been examined by high voltage (1.0 MV) electron microscopy and electron microdiffraction. The study was undertaken to identify the chemical and crystallographic nature of the inorganic mineral phase(s) prepared under conditions which significantly reduce artifacts of specimen preparation and microscopic examination of the tissues. Electron microdiffraction patterns of solid mineral phase particles in the osteoid matrices of the subperiosteal region of tibiae were principally those of poorly crystalline hydroxyapatite. In rare instances (less than 1% of the estimated volume of the mineral phase present in the zone of early mineralization), relatively large single crystals were observed within clusters of hydroxyapatite. From calculations of both interplanar spacings and measurements of angular displacement of diffraction reflections from single crystal microdiffraction patterns, two distinct phases other than hydroxyapatite were identified: brushite and beta-tricalcium phosphate. A third phase, resembling an apatite, remains unidentified. The results suggest that very small amounts of nonapatitic phases of Ca-P exist in chicken bone tissue. No temporal relationship could be established between the nonapatitic and apatitic phases. There is at present no evidence from this study to support the concept that nonapatitic phases are precursors of a final apatitic phase in bone.

Animals↗

PubMed1993

Collagen crosslinks and mineral crystallinity in bone of patients with osteogenesis imperfecta.

In cortical bone samples from patients with osteogenesis imperfecta (OI), the concentrations of hydroxypyridinium cross-linking amino acids in collagen were measured by reversed-phase HPLC and the x-axis crystallinity of the apatite mineral phase was determined by x-ray diffraction. Bone samples from three patients with type I, nine patients with type III, and eight patients with type IV OI were analyzed and compared with human bone from nine controls. The concentration of the two chemical forms of the mature collagen crosslinking amino acids, hydroxylysylpyridinoline (HP) and lysylpyridinoline (LP), and the ratio HP/LP were found to be alike in bone collagen of OI patients and healthy controls. However, the c-axis crystallinity of the apatite was found to be reduced in the type III and IV OI patients compared with controls. Regression analysis of crosslink concentrations and c-axis crystallinity in OI bones did not show any correlation. Therefore, collagen molecules deposited in the extracellular matrix of OI bone appear to fulfill the structural requirements for the action of the enzyme lysyl oxidase, such that a normal concentration of intermolecular crosslinks is formed compared with healthy bone. Consequently, crosslink formation and apatite crystal growth seem to be regulated independently in OI bone.

Adolescent↗

PubMed1994

Comparison of dosage-dependent effects of beta-aminopropionitrile, sodium fluoride, and hydrocortisone on selected physical properties of cortical bone.

BAPN, sodium fluoride, and hydrocortisone are reported to induce altered mineralization states. Three separate sets of experiments, one set for each agent, were performed using male New Zealand white rabbits. In each experiment the rabbits were segregated into groups, each fed a specified weight-determined dose for 13 weeks and then sacrificed. Compact bone from the left femur and tibia were tested for density, composition, sonic velocity, longitudinal elastic modulus, equatorial diffraction spacing of mineralized collagen, diaphyseal cross-sectional area, and relative load stress. beta-Aminopropionitrile (BAPN) induced monotonic degradation of all properties at all dose levels, corresponding to the decreasing density with dosage level. The elastic moduli show a decrease; the equatorial diffraction spacing of the collagen increases. The cross-sectioned diaphysis resembled woven bone. The variability in properties increased with dosage. The total cross-sectional area for a given weight increased, implying that the decreased elastic properties were compensated for by a larger area to support the weight. There was a slight increase in average density and other properties for fluoride-treated rabbits, peaking at 20 mg/kg BW/day. For higher dosages the properties are degraded and the values were much lower at high fluoride dosages than for BAPN. There was no peak for the equatorial diffraction spacing, which increased with dosage. It is inferred that the fluorosed apatite is denser than normal apatitic mineral and therefore has a smaller specific volume. A greater weight fraction of fluorosed mineral has a smaller volume fraction than the equivalent normal apatitic mineral. The bone sections look more normal, except for the porosis. The total cross-sectional area decreases when the bone density increases and then increases as the density falls, again implying that the area required to support body weight depends on the magnitude of the elastic moduli. There was a small change in some of the properties of the bones of the hydrocortisone-treated rabbits, but the effects on others were undetectable within the uncertainty of the procedures. There was no change in the cross-sectional areas of the diaphyses.

Aminopropionitrile↗

PubMed1995

Age and temperature related changes to the ultrastructure and composition of human bone mineral.

This X-ray diffraction (XRD) investigation of heat-treated human femoral bone showed that the main mineral phase of both unheated bone and bone heated to 600 degrees C resembled that of a poorly crystalline form of hydroxyapatite. The rod-shaped apatite crystals in unheated bone persisted in bone heated up to 400 degrees C. Recrystallization at approximately 600 degrees C, produced larger crystals, which either retained their original morphology or changed to tabular or equidimensional shapes. The size of the apatite crystals in unheated and heated bone specimens was dependent on both temperature and age. When heated above 600 degrees C the crystallinity of the bone mineral increased, and the XRD pattern more closely resembled that of hydroxyapatite. Partial decomposition of the hydroxyapatite phase to calcium oxide above 1000 degrees C, and beta-tricalcium phosphate, alpha-tricalcium phosphate, and calcium oxide phosphate between 1200 degrees C and 1400 degrees C, indicated that the original apatite phase was both calcium deficient and contained carbonate. The relative peak intensities of the thermal decomposition products were related to some extent to the age of the deceased person and reflected the compositional changes that occur during bone aging. Because the thermally induced changes to the composition and ultrastructure of bone mineral were influenced by the age of the individual, this investigation proposed that the heat treatment of bone tissue may offer an alternative way of studying bone aging.

Adolescent↗

PubMed1995

Structural and chemical characteristics and maturation of the calcium-phosphate crystals formed during the calcification of the organic matrix synthesized by chicken osteoblasts in cell culture.

The calcium-phosphate (CA-P) crystals formed in the extracellular organic matrix synthesized by chicken osteoblasts in cell culture were examined after 30, 40, and 60 days of culture by a number of physical and chemical techniques including chemical analyses, X-ray diffraction, transmission electron microscopy of isolated crystals, and resolution-enhanced Fourier transform infrared spectroscopy. The data reveal that the solid inorganic calcium-phosphate phase consists of a very poorly crystalline apatite, having a low carbonate content and containing acid phosphate groups. The chemical and structural characteristics are generally similar to the apatite crystals found in young newly synthesized bone but there were small but significant differences found. The major significant differences noted were the rate at which maturational changes occurred in the crystals formed in cell culture compared with those noted in vivo and in synthetic carbonate apatite crystals equilibrated with the same cell culture medium, and the persistence of labile groups, especially HPO4(-2) ions during a relatively long period of incubation. Despite extensive chemical efforts to degrade the organic constituents and to disperse the individual crystals isolated from the organic matrix constituents, a large proportion of the crystals were found to be organized in both loosely and densely packed relatively large roughly spherical aggregates. A few of the aggregates were organized in the form of fibrils with the crystals oriented with their c-axes roughly parallel to the long axes of the crystal aggregate. With briefer periods of chemical treatment, larger aggregates of crystals were occasionally observed in which there was a distinct axial periodicity of approximately 70 nm. In such collagen-crystal fragments, the crystals were well-oriented with their c-axis roughly parallel to the long axes of the aggregate similar to the organization and relationships between crystals and collagen fibrils in native bone. Isolated crystals were in the shape of thin plates. At the end of 30 days of culture, many of the crystals were clearly larger than those observed in native chick bone, except for those in the very youngest (7- to 8-day-old) embryos. At the end of 40 and 60 days of culture, the crystal habit remained as thin plates but the crystals were predominantly smaller, similar to those found in older embryo and postnatal chicken bone. The marked tendency of the crystals to form relatively large aggregates that resist dispersion by techniques that readily disperse the crystals of bone, and the presence of a significant number of larger crystals has also been observed in studies of calcified cartilage. Resolution enhanced FTIR spectroscopy revealed the presence of a high concentration of labile phosphate groups, especially after 30 days of culture and just after the plateau of mineralization is reached.

Animals↗

PubMed1991

Image analysis of mineralized and non-mineralized type I collagen fibrils.

Turkey leg tendons at an early stage of mineralization have been thin sectioned and imaged by electron microscopy. At this stage collagen-associated mineral apatite was found to be present within both the gap and overlap zones. The earliest apatite occurs in a microcrystalline form which gives a rather generalized and characteristic density to both the gap and overlap zones; with subsequent development larger defined apatite crystals arise which span gap/overlap zones. Fourier transformation of such images revealed the major 67 nm axial repeat of the gap/overlap zone plus four other maxima corresponding to repeat spacings of 22, 16, 13, and 11 nm respectively. Computer imaging techniques were used to reconstruct images by using selected spatial frequencies from such transforms. In this manner the subperiodic distributions of mineral were visually enhanced. These subperiodicities are positioned in an asymmetric fashion over the entire D unit repeat aligning with the molecular orientation of the fibril. Analyses of both negatively stained collagen and computer-generated maps of collagen hydrophobicity were compared to the mineral distribution of collagen. Densitometric comparisons showed a positional correlation between the axial banding patterns of mineralized fibrils and those of negatively stained non-mineralized fibrils. Comparable spatial frequencies were also present in transforms between hydrophobic maps and mineral distribution of collagen. These results suggest that the lateral clusterings of hydrophobic residues which span the fibril at specific sites in both the gap and overlap zones serve to prohibit early mineral deposition. This observed hydrophobic influence in combination with the gap space appear as contributing factors in the observed axial distribution of mineral within collagen.

Amino Acids↗

PubMed1997

Interaction of ortho-Phospho-l-serine with Hydroxyapatite: Formation of a Surface Complex

ortho-Phospho-l-serine (H2Psi, where Psi represents the serinephosphato ion), a constituent of salivary proteins, seems to play an important role in the mineralization of teeth. To understand the basic mechanism of this interaction, the uptake of o-phospho-l-serine from relatively concentrated aqueous solutions (up to 100 mmol/L) onto synthetic hydroxyapatite was studied. Previous studies have shown that in the dilute concentration range (<12.5 mmol/L) the uptake followed a regular Langmuirian adsorption plot. At higher concentrations the uptake curve increased steeply, but no formation of a separate phase in the reacted apatite was discernible, either by optical or by scanning electron microscopy. The dissolution of apatite released phosphate and calcium ions into the solution in amounts linearly related to the uptake of serine with P/Psi = 1 and Ca/Psi = 2. The charge and mass balance of the reaction can be reconciled with the formation of the surface complex (shown within brackets):Ca10(OH)2(PO4)6 + 6H2Psi --> [Ca6(HPsi)2(HPO4)2(PO4)2] + 4Ca2+ + 2HPsi1- + 2Psi2- + 2H2PO1-4 + 2H2O.The formation of two other surface complexes is possible; however, the complex shown above probably disrupts the apatite lattice the least. Traces of CaPsi·H2O precipitate out from the filtrates of highly concentrated solutions after 6 days. Copyright 1997 Academic Press. Copyright 1997Academic Press

Journal Article↗

PubMed1999

Peritubular dentin formation: crystal organization and the macromolecular constituents in human teeth.

Peritubular dentin (PTD) is a relatively dense mineralized tissue that surrounds the tubules of coronal tooth dentin. It is composed mainly of crystals of carbonated apatite together with a small amount of collagen. Its mode of formation has been investigated by studying the relatively dense particles isolated from a powdered preparation. Electron microscopic examination of the PTD particles, including 3-dimensional image reconstruction and electron diffraction, shows that the organization of the crystals of PTD is very similar to that of the adjacent intertubular dentin (ITD). The latter contains relatively large amounts of collagen and the carbonated apatite crystals are closely associated with the collagen matrix. The proteins present in the PTD particles are soluble after decalcification and stain with Stains All. The principal protein has higher molecular weight and a quite different amino acid composition than the phosphophoryns of the intertubular dentin. The interface between the PTD and the ITD shows structural continuity. These data show how two distinct carbonated apatite-based mineralized tissues can be organized and formed contiguously within the same organ by utilizing different sets of matrix proteins.

Adult↗

PubMed2001

Twisted plywood pattern of collagen fibrils in teleost scales: an X-ray diffraction investigation.

The distribution and orientation of collagen fibrils, and apatite crystals, in the scales of a bony fish (Leuciscus cephalus) were investigated by X-ray diffraction. The small-angle diffraction patterns obtained with a microfocus scanning setup from most of the examined areas exhibit a distribution of intensity of the collagen reflections according to five preferential orientations, at 36 degrees from one another. It is suggested that the peculiar small-angle X-ray diffraction pattern is due to a plywood arrangement of collagen fibrils in successive layers parallel to the surface of the scale. The fibrils are strictly aligned in each layer and the alignment rotates by 36 degrees in successive layers, according to a discontinuous twist that generates a symmetric plywood pattern. The large spread of the wide-angle reflections does not allow one to distinguish the five directions of orientation in the intensity distribution of the 002 reflection of apatite. However, the patterns recorded from the less ordered regions of the scales display two different orientations of the 002 reflection and allow one to infer a preferential distribution of the apatite crystals with their c-axes parallel to the collagen fibrils. Although much electron microscopic evidence of plywood arrangements in calcified, as well as uncalcified, tissues has been reported, these are the very first diffraction data which unambiguously confirm the presence of these peculiar structures and suggest that this kind of investigation represents a powerful tool with which to study plywood arrangements in biological tissues.

Animals↗

PubMed1995

Bone-bonding behavior of three heat-treated silica gels implanted in mature rabbit bone.

Silica gel has been reported to induce apatite nucleation on its surface in vitro and it can act as a stimulant that induces formation of chemical apatite (Ca-P) layers on the surfaces of bioactive glass-ceramics. In this study, apatite formation in response to and the bone-bonding behavior of silica gels implanted in the tibiae of mature rabbits were studied. Implants were made from three silica gels treated at 400, 800, and 1000 degrees C, and the effects of such heat treatment on the above parameters were investigated. The silica gel was made by hydrolysis and polycondensation of tetraethoxysilane in aqueous solution containing polyethylene glycol. Rectangular implants (15 mm x 10 mm x 2 mm) of each heat-treated silica gel were implanted into both tibial bones of mature male rabbits, which were killed 4 or 8 weeks after implantation, and the tibiae containing the implants were dissected out. The bone-implant interfaces were investigated using Giemsa surface staining, contact microradiography, scanning electron microscopy-electron probe microanalysis, and X-ray diffraction. Histologically, no bonding of bone to any of the silica gels was observed at any time postimplantation. Soft tissue was observed at the bone-silica gel interface, but there were no giant foreign body or inflammatory cells. A Ca-P-rich layer was observed only on small areas of the surfaces of the silica gels treated at 400 and 800 degrees C 4 and 8 weeks after implantation. X-ray diffraction analysis confirmed the presence of hydroxyapatite in these Ca-P-rich layers.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1993

Influence of humate on calcium hydroxyapatite implants.

Implanted bovine apatite is highly osteoconductive, since it serves the host tissue as a "guide-line" for the deposition of newly developing bone tissue. It is well tolerated, but it showed no signs of being resorbed during the course of the experiment. Previous impregnation of the bovine hydroxyapatite with a low molecular humate substance obviously encourages its resorption. This is most easily explained by the known ability of humate to induce the activation of leucocytes. The occasional over-resorption of the apatite is dependent (1) upon the preparation of the implant (granulate) and (2) the local concentration of the humate. Future research is being directed towards the production of a satisfactorily usable form of humate and apatite and the investigation of its HIV blocking action on heterologous cancellous bone.

Animals↗

PubMed1984

Tissue compatibility of different intracranial implant materials: in-vivo and in-vitro studies.

Tissue compatibility of different intracranial implant materials was studied by a tissue culture method using fibroblasts. The same materials were implanted in the crania of rabbits for two months. Undecalcified sections of rabbit crania, including the materials, were stained with Fuchsin and Methylene Blue and Masson-Goldner methods. Soft X-ray was used to detect new bone formation. The materials used were alumina ceramics, hydroxy apatite ceramics, titanium, methylmethacrylate, Sugita aneurysm clip, silicon shunt tube and lyophilized human dura mater (Lyo-dura). Both alumina ceramics and hydroxy apatite ceramics showed an excellent tissue compatibility in-vivo experiments. Although alumina ceramics showed an excellent tissue compatability in in-vitro experiments, hydroxy apatite ceramics showed less compatibility. Methylmethacrylate prepared one week before the experiment showed excellent compatibility, but the same material prepared at the time of experiment showed only fair compatibility. The titanium and silicon shunt tube showed excellent compatibility. The Sugita aneurysm clip, made from elgiloy, showed fair compatibility, while Lyo-dura showed excellent compatibility in in-vitro experiments, but less compatibility in in-vivo experiments. The reasons for the differences between the results of in-vivo and in-vitro experiments are discussed.

Animals↗

PubMed1981

Formation and structure of Ca-deficient hydroxyapatite.

When amorphous calcium phosphate (ACP) was transformed to crystalline hydroxyapatite (HA) in a series of aqueous slurry concentrations ranging from low to high, the higher slurry concentrations produced more Ca-deficient HA as measured by Ca/P ratio and heat-produced pyrophosphate. We feel that the excess solution phosphate produced in the higher slurry transformations results in lower Ca/P ratio HA. It has been suggested that an ACP is the precursor to bone apatite. Regulation of the in vivo ACP slurry concentration could then control the stoichiometry and, therefore, the metabolic activity of bone apatite. X-ray radial distribution function (RDF) analyses showed that CO3(2-) substitution in HA creates far greater structural distortions than do Ca deficiencies. The latter, however, do produce small, but observable, structural distortions when compared to stoichiometric HA. It now seems clear that the RDF of bone apatite can be modeled by a synthetic, Ca-deficient, CO3(2-)-containing HA.

Calcium↗

PubMed1991

Comparative solubility study of human dental enamel, dentin, and hydroxyapatite.

The solubility properties of hydroxyapatite (HA) are compared with those of human dental enamel and dentin. The apatites used in this study were equilibrated with dilute phosphoric acid solutions in CO2-containing atmospheres. The experimental results are interpreted in terms of solubility models which consider the biological materials as either HA or carbonatoapatites. Both in the HA and the dental mineral systems, the results are consistent with the precipitation of another carbonate-containing apatitic phase during equilibration. However, although the chemical behavior of the HA systems is in very good agreement with predictions based on the solubility models, the results with the bioapatites are not; this inconsistency is more marked for dentin than for enamel but in both cases the results clearly indicate the inadequacy of assuming for these dental apatites the stoichiometry of HA. The models and the experimental results show that, in principle, it is possible to define the two dental minerals in terms of respective solubility product constants, if independent information is attained on the stoichiometry of these bioapatites.

Bicuspid↗

PubMed1986

Changes in heated and in laser-irradiated human tooth enamel and their probable effects on solubility.

Enamel of intact human teeth laser irradiated in vitro under certain conditions is known to have less subsurface demineralization than unirradiated enamel on exposure to acid; consequently, the potential use of laser irradiance to reduce caries is apparent. The laser-induced physical and/or chemical changes that cause this reduced subsurface demineralization are not known. A laser-irradiated tooth enamel surface will have a temperature gradient that decreases towards the dentin junction. Dependent on irradiant conditions, the temperature may range from greater than 1400 degrees C at the surface to near normal at the dentin-pulp junction. Along this steep temperature gradient, different compositional, structural, and phase changes in the tooth enamel are to be expected. Identification of changes occurring along this gradient has bearing on understanding the dissolution reduction mechanism and, in turn, optimizing its effect. Changes in laser-irradiated material from the highest temperature region have been characterized, but those occurring in sequential layers of decreasing temperatures have not. Since the laser-induced changes are expected to primarily arise from localized heating, previously reported thermally induced changes in tooth enamel on heating in conventional furnaces were utilized to infer corollary changes along the gradient in laser-irradiated tooth enamel. These thermally inferred changes which resulted in modifications in the tooth enamel apatite and/or newly formed phases were correlated with their probable effects on altering solubility. A temperature gradient range from 100-1600 degrees C was considered with subdivisions as follows: I, 100-650 degrees C; II, 650-1100 degrees C; and III, greater than 1100 degrees C. Two of the products formed in range III, alpha-Ca3(PO4)2 and Ca4(PO4)2O, and also identified in the fused-melted material from laser-irradiated tooth enamel, are expected to markedly increase solubility in those regions that contain considerable amounts of these compounds. Products and changes occurring in range II, separate phases of alpha- and/or beta-Ca3(PO4)2 and a modified phase of apatite, may increase or decrease the solubility depending on the Ca/P ratio and the resultant amounts of alpha-, beta-Ca3(PO4)2 formed. Modifications in tooth enamel apatite effected in range I are expected to decrease its solubility; the formation of pyrophosphate in this range may have a substantial effect on reducing the solubility rate.(ABSTRACT TRUNCATED AT 400 WORDS)

Biological Transport, Active↗

PubMed1987

[Animal experiment studies of callus formation by hydroxyapatite injection].

Hydroxy-apatite may be suspended well in liquid high-molecular gelatine. This renders possible an application by local injection. By means of experimental animal investigations in 64 rabbits it could be proved, that hydroxy-apatite stimulates osteogenesis and local callus formation when being injected at artificial bone defects. Gelatine on its own without any HA-grains only leads to a callus-free bridging of the bone defect. In case of an injection of the HA-suspensions to muscular soft tissue, no stimulation of the osteogenesis could be proved. It has to be concluded, that hydroxy-apatite stimulates osteogenesis. To achieve this effect, a direct contact to osteogenetic cells is necessary.

Animals↗

PubMed2003

The mineralization of bone tissue: a forgotten dimension in osteoporosis research.

Osteoporosis treatment should not only prevent the loss of bone tissue, not interfere with apatite and avoid bone mineral changes at the crystal level, but should also increase the mechanical resistance of bone and thus protect the skeleton against new fractures. Mineral substance is crystallized as nonstoichiometric carbonated apatite ionic crystals of small size and extended specific surface. Consequently, they have a very large interface with extracellular fluids, and numerous interactions between ions from the extracellular fluid and ions constituting apatite crystals are thus possible. It is generally agreed that bone strength depends on the bone matrix volume and the microarchitectural distribution of this volume, while the degree of mineralization of bone tissue is almost never mentioned as a determinant of bone strength. We now have evidence that the degree of mineralization of bone tissue strongly influences not only the mechanical resistance of bones but also the bone mineral density. In adult bone, our model is based on the impact of changes in the bone remodeling rate on the degree of mineralization of bone tissue. The purpose of this paper is to report the main results concerning the interactions of strontium (Sr) with bone mineral in animals and in osteoporotic women treated with strontium ranelate (SR). These studies aimed to evaluate using X-ray microanalysis, X-ray diffraction and computerized quantitative contact microradiography: (1) the relative calcium and Sr bone content, (2) the distribution of Sr in compact and cancellous bone, (3) the dose dependence of the deposition of Sr in bone, (4) the interactions between Sr and mineral at the crystal level (in monkeys), (5) the influence of Sr on the mean degree of mineralization of bone tissue and on the distribution of the degree of mineralization of bone tissue, and (6) the bone clearance of Sr over short periods of time (6 and 10 weeks) after cessation of SR administration (monkeys treated for 13 and 52 weeks, respectively). In monkeys killed at the end of exposure (13 or 52 weeks), Sr was taken up in a dose-dependent manner into compact and cancellous bone, with a higher content in new bone than in old bone. The Sr content greatly decreased (about 2-fold) in animals killed 6 or 10 weeks after the end of treatment but this affected new bone almost exclusively. After SR treatment, there were no significant changes in crystal characteristics. Easily exchangeable in bone mineral, Sr was slightly linked to crystals by ionic substitution (generally 1 calcium ion substituted by 1 Sr ion in each unit cell). The degree of bone mineralization was not significantly different in the various groups of monkeys. Thus, at the end of long-term SR treatment and after a period of withdrawal, Sr was taken up in a dose-dependent manner into new bone without alteration of the degree of bone mineralization and with no major modification of bone mineral at the crystal level. In postmenopausal osteoporotic women treated with SR (0.5, 1 and 2 g/day) for 2 years, Sr was dose-dependently deposited into new bone without changes in the degree of mineralization of bone tissue. These findings could reflect dose-dependent stimulation of bone formation and are of potential value for the use of SR in the treatment of osteoporosis. In conclusion, the different studies performed on bone samples from monkeys and humans treated with various doses of SR showed that Sr was heterogeneously distributed between new and old bone but in a dose-dependent manner without alteration of the crystal characteristics and the degree of mineralization of bone tissue, even after long-term administration of often high doses of SR (the highest therapeutic dose used in humans is 4-fold lower than the lowest experimental dose administered to monkeys). This emphasizes the value, as antiosteoporotic treatment, of SR, which is safe at the bone mineral level.

Animals↗