Search PubMed⌕ Search

Biomedical subjects

P Fratzl

Publications and source records attributed to P Fratzl.

At least 55 records · Page 3Linked to original sources

Effects of sodium fluoride and alendronate on the bone mineral in minipigs: a small-angle X-ray scattering and backscattered electron imaging study.

Sodium fluoride (NaF), which stimulates bone formation, and bisphosphonates, which reduce bone resorption, are both used in the treatment of osteoporosis, and are binding to bone mineral. In this study, using small-angle X-ray scattering and backscattered electron imaging, we analyzed the bone mineral in the vertebrae of minipigs treated with fluoride, with the bisphosphonate alendronate (ALN), or with vehicle. All specimens were investigated blindly. A slight increase in the average thickness of the mineral crystals as well as changes in the structure of the mineral/collagen composite were found in the case of fluoride-treated animals. No differences were found between ALN-treated animals and controls. The changes produced by fluoride are in the same direction as seen in bones from patients treated with NaF, albeit much smaller. They also correlate quantitatively with the reduction in biomechanical properties of bone in fluoride-treated minipigs found in an earlier study with the same animals. These findings suggest that small changes in the structure of the mineral/collagen composite in bone may considerably affect its biomechanical properties. It also emphasizes the delicate balance between the increase of bone mass and deterioration of bone material properties for the effect of fluoride on the biomechanical properties of bone.

Alendronate↗

Characterization of bone mineral crystals in horse radius by small-angle X-ray scattering.

The size and the orientation of the bone salt (mineral) crystals in the cranial and caudal zones in the transverse midshaft section of the equine radius were investigated by small-angle X-ray scattering (SAXS). The results are interpreted as indicating that the crystals had an elongated shape with an average thickness of T = 3.17 +/- 0. 15 nm in the caudal region and T = 3.79 +/- 0.20 nm in the cranial region. Their orientation was predominantly in the longitudinal direction of the bone. There was no preferential orientation within the transverse plane. The distribution of tilt angles with respect to the longitudinal direction was determined directly from the SAXS data: the average angle was about 30 degrees for the cranial region and 45 degrees for the caudal region. Assuming that the needle-like crystals are parallel with the collagen fibrils, the angular distribution of the crystals is in good agreement with previous measurements of collagen orientation using circularly polarized light microscopy.

Animals↗

Bone mineralization as studied by small-angle x-ray scattering.

Small-angle x-ray scattering (SAXS) can provide information on mean size, predominant orientation and typical shape of mineral crystals in bone. In this paper, recent developments of this technique for application in bone research are reviewed. Then the structure of the collagen/mineral composite in bone, as determined by SAXS, is compared for a number of species. The thickness of the mineral crystals was found to increase with age up to a value around 3 to 4 nanometers in adult animals, depending on the species. The SAXS results also suggest the existence of needle-shaped mineral crystals in mouse or rat bone and more plate-shaped crystals in other tissues like adult human bone or mineralized turkey leg tendon.

Animals↗

Radial packing, order, and disorder in collagen fibrils.

Collagen fibrils resemble smectic, liquid crystals in being highly ordered axially but relatively disordered laterally. In some connective tissues, x-ray diffraction reveals three-dimensional crystallinity in the molecular packing within fibrils, although the continued presence of diffuse scatter indicates significant underlying disorder. In addition, several observations from electron microscopy suggest that the molecular packing is organized concentrically about the fibril core. In the present work, theoretical equatorial x-ray diffraction patterns for a number of models for collagen molecular packing are calculated and compared with the experimental data from tendon fibrils. None of the models suggested previously can account for both the crystalline Bragg peaks and the underlying diffuse scatter. In addition, models in which any of the nearest-neighbor, intermolecular vectors are perpendicular to the radial direction are inconsistent with the observed radial orientation of the principal approximately 4 nm Bragg spacing. Both multiple-start spiral and concentric ring models are devised in which one of the nearest-neighbor vectors is along the radial direction. These models are consistent with the radial orientation of the approximately 4 nm spacing, and energy minimization results in radially oriented crystalline domains separated by disordered grain boundaries. Theoretical x-ray diffraction patterns show a combination of sharp Bragg peaks and underlying diffuse scatter. Close agreement with the observed equatorial diffraction pattern is obtained. The concentric ring model is consistent with the observation that the diameters of collagen fibrils are restricted to discrete values.

Animals↗

Abnormal bone mineralization after fluoride treatment in osteoporosis: a small-angle x-ray-scattering study.

Sodium fluoride treatment of osteoporosis is known to stimulate bone formation and to increase bone mass, but recent clinical trials failed to prove its antifracture effectiveness. The formation of bone with abnormal structure and, therefore, increased fragility is discussed as a possible explanation. Until now, however, exact information on the mineral structure of osteoporotic bone after fluoride treatment has been lacking. Bone biopsies were taken from three patients with postmenopausal osteoporosis before and after fluoride treatment (60 mg NaF/day for 1-2 years), from one patient with iatrogenic fluorosis, as well as from three normal controls. The mineral in these samples was investigated by a combination of backscattered electron imaging and small-angle x-ray scattering. Depending on the total dose of fluoride, an increasing amount of new bone is laid down on the surface of preexisting trabeculae. Its mineral structure is identical to that of heavy fluorosis and is characterized by the presence of additional large crystals, presumably located outside the collagen fibrils. These large crystals, which are not present in the controls or in osteoporotic bone before fluoride treatment, contribute to increase the mineral density without significantly improving the biomechanical properties of the bone. The possible success of fluoride treatment depends not only on the amount of newly formed bone but also on the rate of bone turnover. Indeed, as soon as significant amounts of fluoride are present, bone turnover leads to the replacement of old (normal) bone by new (pathologically mineralized) bone.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Collagen packing and mineralization. An x-ray scattering investigation of turkey leg tendon.

Several recent results are suggesting that the collagen packing in mineralized tissues is much less regular than in the case of other nonmineralizing collagen, e.g., rat tail tendon. To clarify this question we have investigated the molecular arrangement in mineralized and unmineralized turkey leg tendon as a model for the collagen of mineralized tissues. Using a combination of diffuse x-ray scattering and computer simulation, it could be shown quantitatively that, although the collagen fibril structure is periodic in the axial direction, it is similar to a two-dimensional fluid in the lateral plane. This has important consequences for the understanding of the mineralization process, which is also discussed.

Animals↗

Structural transformation of collagen fibrils in corneal stroma during drying. An x-ray scattering study.

X-ray scattering experiments were performed on human corneas during drying. In a first stage the collagen interfibrillar distance decreased considerably. Then, at a critical point of dehydration, a structural transformation of the collagen fibrils was observed. This finding leads to a two-stage drying model, which explains the discrepancy between the collagen fibril diameters determined by x-ray scattering and by electron microscopy. Our results strongly suggest that the collagen fibrils in the corneal stroma are surrounded by a cylindrical coating made mainly of proteoglycans. The coating appears as a three-dimensional fractal network with fractal dimension of 2.7 +/- 0.1.

Biophysical Phenomena↗

Mineral crystals in calcified tissues: a comparative study by SAXS.

The shape, the typical orientation, and the average size of mineral crystals in different types of mineralized tissues were investigated by means of small-angle x-ray scattering (SAXS). To rule out eventual artifacts due to sample preparation, four different standard preparation techniques were used and a comparison showed that the SAXS results were identical for all four methods. In mineralized turkey leg tendon, a frequently used model system for bone, the crystals were found to be typically plate-like with a thickness of the order of 2 nm. This stands in contrast to the case of bone (calvaria, femur, and iliac crest) from mouse, rat, and dog, where mainly needle-like crystals were found. The thickness of these crystals ranged from 3 to 4 nm but was remarkably constant for different bones of a given animal. The preferred orientation of the needle-like crystals was along the main axis of the femur and within the surface of the calvaria (for mouse, rat, and dog). The mineral plates in turkey leg tendon were located inside the hole zone and oriented along the fibril axis. Finally, no periodic arrangement of the crystals inside the hole zone of the collagen could be found.

Animals↗

Nucleation and growth of mineral crystals in bone studied by small-angle X-ray scattering.

The mechanism of calcification in bone and related tissues is a matter of current interest. The mean size and the arrangement of the mineral crystals are important parameters difficult to obtain by electron microscopy. Furthermore, most studies have been carried out on poorly calcified model systems or chemically treated samples. In the work presented here, native bone was studied as a function of age by a quantitative small-angle X-ray scattering method (SAXS). Bone samples (calvariae and ulnae) from rats and mice were investigated. Measurements were performed on native bone immediately after dissection for samples up to 1 mm thick. The size, shape, and predominant orientation of the mineral crystals in bone were obtained for embryonal, young, and adult animals. The results indicate that the mineral nucleates as thin layers of calcium phosphate within the hole zone of the collagen fibrils. The mineral nuclei subsequently grow in thickness to about 3 nm, which corresponds to maximum space available in these holes.

Animals↗